THE PCCA BLOG

Know Pain, Know Gain

Wed, 03 Sep 2025 13:26:00 GMT

I’m honored to be speaking at ThinkNext 2025, where I’ll deliver a lecture on the Neuroscience of Pain. This presentation will explore how modern pain science is revolutionizing our understanding of pain and unlocking powerful, non-pharmacologic strategies to improve patient care.

The Pain Crisis: Time for a Paradigm Shift

The pain epidemic and its devastating link to the opioid crisis is well-documented. As a health care community, we must do better. Our patients deserve it. Fortunately, the last two to three decades have ushered in a “pain revolution,” dramatically expanding our understanding of the human pain experience. Gone are the days when pain was simply equated with tissue damage. The outdated formula of “injury = pain” no longer holds. We now recognize pain as a complex, multifactorial experience involving:

Sensitization of peripheral and central nervous systems
Functional and structural changes in the brain
Psychosocial influences
Neuroplasticity and bioplasticity
Immune system alterations
And much more

Part I: The Latest in Pain Neuroscience

At ThinkNext, I'll introduce an overview of cutting-edge pain neuroscience and its implications for clinical practice. We’ll explore pain phenotyping, outline a precision medicine approach and examine the mechanisms behind:

Nociceptive-driven pain
Peripheral neuropathic pain
Central sensitization (nociplastic pain)

This research will challenge outdated models and highlight how evolving science can reshape our response to pain and the opioid epidemic.

Part II: Translating Science into Non-Pharmacologic Care

In light of the opioid crisis and in alignment with global guidelines, pharmacologic interventions must no longer be the default approach to chronic pain. At ThinkNext, I’ll also delve into how advances in neuroscience now support a range of evidence-based, non-pharmacologic treatments that activate endogenous pain-relief mechanisms and reduce reliance on medication.

You’ll learn about the three key domains that we must address to truly transform lives affected by persistent pain:

Cognitive: Therapeutic cognitive strategies can reduce fear-avoidance, catastrophizing, depression and anxiety. Changing pain behavior begins with changing beliefs.
Movement: Once fear is addressed, movement becomes one of the most potent tools for pain relief, whether through aerobic exercise, resistance training or recreational activity.
Nervous System Down-Regulation: Persistent pain often stems from a hypervigilant nervous system. Calming it, preferably through non-pharmacologic means, is essential. Techniques include relaxation, sleep hygiene, nutrition, breathing exercises and more.

The Power of Words

Pain is a normal, necessary human experience. Chronic pain is not. Pain that is understood is pain that need not be feared. Every health care provider communicates with patients and as Rudyard Kipling once said in a 1923 address to the Royal College of Surgeons: “Words are, of course, the most powerful drug used by mankind.”

This October, join me as we journey from tissues through C-fibers, into the dorsal horn, second-order neurons and the brain’s distributed neuromatrix. Let’s deepen our understanding of pain and use this knowledge to engage meaningfully with every patient we meet, transforming their experience of pain and suffering.

Sublingual Semaglutide: Dosing Considerations, Patient Care and Regulatory Insights

Tue, 22 Apr 2025 13:00:00 GMT

Sublingual Semaglutide: Dosing Considerations, Patient Care and Regulatory Insights

In the world of GLP-1 receptor agonists, semaglutide has become a key player for several health conditions. But with growing patient demand and evolving regulations, healthcare providers are looking beyond traditional injections to explore new ways to deliver this powerful therapy.

One of the most promising alternatives? Sublingual administration.

In this article, we’ll discuss several considerations for sublingual semaglutide, including patient care and regulatory compliance.

Why Sublingual Semaglutide?

Peptide drugs like semaglutide are notoriously difficult to deliver orally; when taken by mouth, up to 1% of the drug is absorbed under ideal conditions.

Sublingual dosing offers an alternative route of administration by allowing absorption directly into the bloodstream through the mucosal tissue, bypassing the gastrointestinal system and first-pass metabolism. This may improve bioavailability and make therapy more accessible for patients who struggle with injections.

Best Practices for Sublingual Administration

Sublingual therapy isn’t as simple as “place and swallow.” For improved absorption, the medication should stay in contact with the sublingual or buccal tissue for as long as possible.

The minimum hold time is 30 seconds, but ideally, patients should aim for 5 to 15 minutes. Increased contact time with the sublingual tissue may help with sublingual absorption. Swallowing the compounded preparation would likely result in very limited absorption.

Pro Tips for Better Absorption:

Take the dose on an empty stomach or away from meals to minimize salivation and swallowing.
Avoid eating or drinking for at least 15–30 minutes after dosing.
Try holding the dose while reading, watching TV or during quiet moments to extend the hold time.

Dosing Strategies: Start Low, Go Slow

Sublingual semaglutide should follow a titration approach, with typical starting doses of 0.5 mg to 1 mg daily for new patients. Increase the dose every 4 weeks, if needed, based on patient response.

Beyond Weight Management

While GLP-1 medications like semaglutide are best known for their role in weight management and diabetes, emerging research is pointing to broader therapeutic potential, including:

Cardiovascular risk reduction
Neuroprotection
Anti-inflammatory effects
Support for conditions like depression and alcohol use disorder

Patient Considerations and Monitoring

As with any GLP-1 therapy, thoughtful patient selection and regular monitoring are essential, with special attention paid to:

GI Side Effects: Nausea is common, especially during titration. Starting low and increasing gradually helps manage this.
Hormonal Health: Check thyroid, sex hormones and metabolic labs — hormonal imbalances can blunt the effectiveness of GLP-1 therapies.
Pregnancy: Avoid use during pregnancy or for women planning conception within 2 months.
Supplementation: Support patients with vitamin D, magnesium, zinc and sufficient protein to prevent muscle loss during weight reduction.

Regulatory Insights: Staying Compliant

Compounded semaglutide, whether sublingual or injectable, sits under a shifting regulatory microscope. Shortages of commercial GLP-1 drugs initially opened the door for compounding, but as supply chains recover, the rules are tightening.

Key points for pharmacies:

Be cautious with marketing: Avoid calling compounded semaglutide “safe and effective” or comparing it directly to FDA-approved products.
Stay up to date: Legal cases and FDA guidance are still evolving.
Consult legal experts: If you’re unsure about what’s allowed, a healthcare attorney with FDA experience is an important ally.

Individualized Care is Essential

An important takeaway from the latest research and clinical experience is that patient care must remain personalized. Flexibility and close monitoring are essential.

Final Thoughts

Sublingual semaglutide is more than just an alternative to injections — it represents a significant opportunity to improve access, adherence and possibly unlock new therapeutic applications.

As with any evolving treatment landscape, the best results come from careful dosing, ongoing education and staying current on regulatory developments.

Whether you’re a prescriber, pharmacist or patient, the message is clear: Personalized care, open communication and compliance are the keys to success.

PCCA members with clinical services access may contact our Clinical Services team for help with sublingual semaglutide and other compounding concerns.

Illuminating Stealth Syndromes

Wed, 29 Jan 2025 17:08:00 GMT

A forthcoming documentary from the LDN Research Trust gives compounding pharmacists, physicians and prescribers an opportunity to learn about a group of complex and debilitating syndromes that affect one in six Americans — syndromes that occur in almost every part of the body, often accompany each other and collectively exacerbate the patient’s pain and other symptoms. This article briefly summarizes these syndromes and their overlapping symptoms and discusses how you can help educate providers in your community — as well as your staff and patients — about their effects, along with the potential use of low-dose naltrexone (LDN) in compounding preparations.

Summary of Syndromes

Stealth syndromes include mast cell activation syndrome (MCAS), postural orthostatic tachycardia syndrome (POTS) and Ehlers-Danlos syndrome (EDS), each of which is discussed below.

MCAS (Mast Cell Activation Syndrome)

Found in most organs of the body, mast cells are part of the immune system and are responsible for immediate allergic reactions that are triggered by allergic substances such as medications, infections, chemicals and insect bites. Mediators stored in or created by mast cells are released and create allergic reactions. A trigger from an allergen is called activation and the release of mediators is called degranulation.

MCAS is caused by dysfunction of mast cells; patients afflicted by MCAS experience repeated episodes of allergic reactions with accompanying symptoms:

Fatigue, headache, tingling, chills
Rapid pulse (tachycardia), low blood pressure (hypotension) and fainting
Itching (pruritus), hives (urticaria), swelling (angioedema) and skin flushing
Wheezing, shortness of breath and harsh noise when breathing (stridor) due to throat swelling
Diarrhea, nausea with vomiting and cramping abdominal pain^1,2

POTS (Postural Orthostatic Tachycardia Syndrome)

POTS (also referred to as dysautonomia) is caused by a malfunction in part of the autonomic nervous system, which controls involuntary body functions such as breathing and heart rate. The syndrome is considered one of a group of disorders that present symptoms of orthostatic intolerance (OI). OI is a condition where an excessively reduced volume of blood returns to the heart after an individual stands up after laying down.

Patients afflicted with POTS often experience:

Lightheadedness or fainting when standing
A rapid increase in heartbeat (more than 30 beats per minute or exceeds 120 beats per minute)
Low blood pressure
Digestive and bladder problems
Temperature and sweating dysregulation
The syndrome often prevents individuals from exercising due to onset of fainting spells or dizziness. POTS is often associated with EDS.³

EDS (Ehlers-Danlos Syndrome)

EDS is a group of disorders that affect connective tissues that support the skin, tendons, ligaments, bone, blood vessels and many organs and tissues. An unusually large range of joint movement (hypermobility) occurs in most forms and is the hallmark feature of the hypermobile type.

Patients afflicted with hypermobile EDS (hEDS) may present some or all of the following symptoms:

Joint hypermobility
Loose, unstable joints that easily dislocate
Joint pain and clicking joints
Extreme fatigue
Skin that bruises easily
Digestive problems, such as heartburn and constipation
Dizziness and an increased heart rate after standing up
Problems with internal organs, such as mitral value issues or organ prolapse (types include bladder, pelvic and rectal prolapse)
Urinary incontinence (bladder control)⁴

Compassion and Concern: The LDN Research Trust

Linda Elsegood, Chief Executive Officer and founder of the LDN Research Trust, refers to the collection of MCAS, POTS and EDS as “Stealth Syndromes.” Keenly aware of the debilitating impacts and empathetic for patients who suffer from these syndromes, Linda shared her concerns during The Mortar & Pestle podcast. “Patients with MCAS are also susceptible to having EDS and POTS; they tend to go hand-in-hand,” Linda said. “Some of these patients come into the doctor’s office with 40 different symptoms and practitioners have no idea where to start. Some physicians just throw up their hands and walk away. Others just treat one or two individual issues. But until you get down to the root cause — it’s nothing more than a Band-Aid.”

Adding insult to injury, many conventionally prescribed tests return with negative results, which add to the growing pile of doubts among family and friends.

“A lot of the tests, they do come back negative, which leads family and friends to thinking, ‘Well, if the doctors can't find anything wrong with you, there is nothing really wrong with you!’” Linda said. “I know one lady whose parents wouldn't talk to her anymore because they thought she was just a hypochondriac, that there was nothing really wrong with her. And that is so isolating for the patient.” Although considered a rare disease, Dr. Leonard Weinstock, a gastroenterologist and leading expert on MCAS, estimates one-in-six people are afflicted with the syndrome in the Northern Hemisphere; most are unaware.

During the podcast, Linda likened the lack of awareness to Lyme disease. “There were no reported cases of Lyme disease anywhere in the United States because there was no true diagnosis. And so they couldn't gather the data. And then very quickly, they said Lyme disease existed in the United States.”

Help Spread Awareness

Linda is calling on compounding pharmacists — notably PCCA members — to raise awareness of Stealth Syndromes and the potential use of low-dose naltrexone (LDN) in preparations.

The LDN Research Trust developed a documentary, “Understanding Stealth Syndromes,” that sheds light on these esoteric conditions. The documentary, which airs for 24 hours on February 27 (to accommodate global time zones), explains the underlying root causes, why most doctors miss these conditions, potential treatments and more.

Compounding pharmacies are urged to help raise awareness by:

Purchasing a documentary license — $100 for up to 50 individuals
Hosting an event at their pharmacy or a local venue
Inviting community physicians, prescribers and patients to view the documentary

“We’re aiming to raise awareness and connect individuals suffering from undiagnosed Stealth Syndromes with knowledgeable local providers,” Linda said. “Compounding pharmacists, technicians and staff are compassionate — many are aware of the benefits of LDN — and are adept at providing personalized preparations to these patients.

“They are positioned to develop awareness in their communities and can purchase as many licenses to the documentary as needed. Once we have sold the license, they can do whatever they like.”

This includes selling tickets to and/or publicizing the event on their respective pharmacy websites.

“We are happy to help them publicize or advertise the event,” Linda said. “On our website and throughout our social media platforms, we list all pharmacies who purchased licenses for the documentary, as well as their locations, so people know who to contact to attend viewings. We also hope to invite local media to these events; if an event is sold out, many become really interested and will send reporters who will broadcast or write about it.”

Watch the compelling trailer for “Understanding Stealth Syndromes”. Click Here.

To purchase one or more licenses for the documentary, Click Here.

For additional information, email contact@ldnresearchtrust.org.

Listen as Linda shares her personal struggles and the impetus for creating the LDN Research Trust, as well as the need for public awareness of Stealth Syndromes, in The Mortar & Pestle Podcast.

PCCA is recognized as the leader of quality products, education and advocacy in the compounding industry. Find out how a PCCA membership can benefit your compounding practice.

References

American Academy of Allergy, Asthma & Immunology. Mast Cell Activation Syndrome (MCAS). August 2024. Accessed January 2025 at https://www.aaaai.org/conditions-treatments/related-conditions/mcas#:~:text=Idiopathic%20Mast%20Cell%20Activation%20Syndrome,are%20released%20during%20those%20episodes
POTS UK. Mast Cell Activation Syndrome. Version 3. Last reviewed July 2024. Accessed January 2025 at https://www.potsuk.org/about-pots/associated-conditions/mcas/
National Institute of Neurological Disorders and Stroke. Postural Tachycardia Syndrome (POTS). Last reviewed July 2024. Accessed January 2025 at https://www.ninds.nih.gov/health-information/disorders/postural-tachycardia-syndrome-pots
National Health Service UK. Ehlers-Danlos Syndromes. Last reviewed October 2022. Accessed January 2025 at https://www.nhs.uk/conditions/ehlers-danlos-syndromes/#:~:text=types%20of%20EDS-,Hypermobile%20EDS,with%20bladder%20control%20(urinary%20incontinence)

These statements are provided for educational purposes only. They have not been evaluated by the Food and Drug Administration, and are not to be interpreted as a promise, guarantee or claim of therapeutic efficacy or safety. The information contained herein is not intended to replace or substitute for conventional medical care or encourage its abandonment.

Bacterial Vaginosis: A Persistent Challenge

Thu, 16 Jan 2025 16:42:55 GMT

by Deborah H. Clark, RPh, FACVP, PCCA Clinical Compounding Pharmacist

Bacterial vaginosis (BV) is the most common vaginal infection that affects women around the globe. In addition to its effects on total health, BV can significantly impact reproductive wellness. The condition is thought to originate from a decrease of Lactobacilli in the vagina, resulting in an imbalance in the natural vaginal microbiome.¹ In the following article, we explore the pathogens associated with BV and challenges with commercial treatments, as well as compounding options and an innovative base that may potentially improve patient compliance.

Common and Uncommon Pathogens

One of the more common pathogens associated with BV is Gardnerella; however, other pathogens can be present. According to researchers, many studies have demonstrated the relation of Gardnerella vaginalis with other bacteria in causing BV, such as Lactobacillus, Prevotella and anaerobes. In addition, patients with BV may be infected with Mobiluncus, Bacteroides, Peptostreptococcus, Fusobacterium, Veillonella, Eubacterium, Mycoplasma hominis, Ureaplasma urealyticum, Streptococcus viridans and Atopobium vaginae. In many cases, the infecting pathogen will form a biofilm that makes the infection persistent and treatment challenging.²

Diagnosis and Compounding Options

Most patients present with a complaint of a malodorous discharge; a diagnosis of BV is then made through physical exam and testing. In some cases, physicians will treat empirically, using commercially available antibiotic vaginal suppositories, gels or creams. Clindamycin and metronidazole are two agents that are commonly selected and administered in these patients. When these agents fail to resolve the infection, many practitioners will consult a compounding pharmacist to discuss test results; the compounding pharmacist may then suggest more culture and sensitivity testing for specific bacterial strains.

Additional culture and sensitivity testing will confirm what organisms are present to employ a more targeted approach when choosing active pharmaceutical ingredients (APIs). As stated earlier, a biofilm is normally present, so the addition of a biofilm disrupting agent, such as edetate disodium in a 0.5% concentration, would be a smart addition to the formulation.³

Ellage^® Anhydrous Vaginal: The Base of Choice

Using the right base vehicle is important when compounding preparations for BV patients. Ellage Anhydrous Vaginal is an excellent option due to its consistent delivery of APIs and potential improvement of compliance.

Ellage contains a self-emulsifying drug delivery system that creates a microemulsion when it contacts vaginal fluid. This emulsion releases APIs from the base into the mucosa. Once the APIs are released, the emulsification system holds the APIs to the surface, prolonging contact time. The combination of excellent release properties and prolonged contact time helps facilitate the action of the antimicrobials used in treating BV patients.

Leakage is a common complaint from patients using vaginal preparations and may affect compliance. In vitro testing (PCCA Document #99816) showed Ellage is likely to adhere to vaginal tissue for a long period of time without leakage or messiness, despite vaginal secretions. In vitro testing (PCCA Documents #99817 and #99818) also showed safety with minimal irritation on the vaginal mucosal tissue and no effect on vaginal pH (PCCA Document #99815). Ellage is an anhydrous vehicle, offering the option of longer beyond-use dates (BUDs*).

Commonly requested formulas for patients with BV include PCCA Formula #13836, PCCA Formula #13858, PCCA Formula #14396 and PCCA Formula #14584.

PCCA members with clinical services access may view and/or download PCCA Ellage formulations — including formulas with FormulaPlus™ BUD and stability studies — after logging on to our Members-Only Website. Clinical services access also allows members to contact our Clinical Services team for additional information on compounding Ellage preparations for patients with BV and other compounding concerns.

*USP 795 establishes BUD limits by type of preparation in the absence of a USP−NF Compounded Preparation Monograph or CNSP-specific stability information.

PCCA is recognized as the leader of quality products, education and advocacy in the compounding industry. Find out how a PCCA membership can benefit your compounding practice.

References

Kairys N, Carlson K, Garg M. Bacterial Vaginosis. [Updated 2024 May 6]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Accessed December 2024at https://www.ncbi.nlm.nih.gov/books/NBK459216/
Girerd P and Riven M, Price TM, et al. Bacterial Vaginosis. Medscape > Drugs & Diseases > Obstetrics & Gynecology. Accessed December 2024 at https://emedicine.medscape.com/article/254342-overview
Finnegan S, Percival SL. EDTA: An Antimicrobial and Antibiofilm Agent for Use in Wound Care. Adv Wound Care (New Rochelle). 2015 Jul 1;4(7):415-421. Accessed December 2024 at https://pubmed.ncbi.nlm.nih.gov/26155384

Importance of Content Uniformity in Suspensions

Wed, 08 Jan 2025 19:14:53 GMT

by Maria Carvalho, PharmD, MRPharmS, PhD, PCCA Manager of PCCA Science

Suspensions are pharmaceutical dosage forms consisting of insoluble active ingredients dispersed in a base vehicle. An ideal suspension should be uniform in content so each dose contains an equivalent amount of one or more — most likely one — active pharmaceutical ingredients (APIs). We briefly review oral suspensions and why content uniformity is vital in compounded preparations, as well as showcase the most studied oral suspension, in the following article.

Liquid Suspensions and Content Uniformity

The type of suspension used to compound preparations depends on the route of administration: oral, topical or injectable. Oral liquid suspensions are advantageous in their ability to provide an easy-to-swallow medication for pediatric, geriatric and patients challenged by other dosage forms such as tablets and capsules. However, due to the heterogeneous nature of liquid suspensions, insoluble APIs tend to settle at the bottom of containers when standing. For this reason, if patients or caregivers forget to agitate — or shake — the preparation or do not agitate it adequately before administration, the content uniformity and dosing accuracy of the APIs may be compromised.

Content uniformity, defined as the consistency in the amount of APIs among dosage units, is determined by performing a series of tests using APIs and the suspension vehicle. An ideal suspension should retain content uniformity so that each dose contains an equivalent amount of APIs. As such, content uniformity is highly dependent on the characteristics of the suspension. If a suspending vehicle is too viscous — or has a thick and sticky consistency — APIs are not easily dispersed. In contrast, if the suspending vehicle is too thin, the APIs will settle at the bottom of the container.¹

The Superior Liquid Vehicle

PCCA SuspendIt® (PCCA #30-4825) is our “all-in-one” aqueous (water activity [aw] > 0.6) oral suspension vehicle. It contains a synergistic polymer complex that offers a unique thixotropic flow — which means it thins when shaken and thickens upon standing — that allows rapid redispersion of APIs and minimizes sedimentation. Made with an all-natural sweetener derived from monk fruit, SuspendIt is an ideal choice for patients requiring formulations without sugar, casein or gluten.

As an aqueous oral suspension, SuspendIt uses potassium sorbate and sodium benzoate as preservatives. The November 2023 revisions to the United States Pharmacopeia (USP) 795 offer beyond-use dates (BUDs) of up to 35 days for an aqueous, preserved preparation.

Although SuspendIt may be used in veterinary preparations, it’s important to recognize that in felines, sodium benzoate can be a potential toxin when chronically administered and use should be limited to two weeks.

Suspendit is featured in a number of USP compounded preparation monographs and is currently one of the most studied oral vehicles in the compounding industry. SuspendIt studies, including scientific journal abstracts, scientific posters and a technical report summarizing the content uniformity of eight SuspendIt formulations, are available in SuspendIt Scientific Publications.

Competitor Suspension vs. SuspendIt

Within one minute, this timelapse video shows the content uniformity between SuspendIt and a competitor’s suspension base over the course of five days.

PCCA members with clinical services access may view and/or download PCCA SuspendIt formulations — including formulas with FormulaPlus™ BUD Studies — after logging on to our Members-Only Website. Clinical services access also allows members to contact our Clinical Services team for additional information on compounding SuspendIt preparations and other compounding concerns.

PCCA is recognized as the leader of quality products, education and advocacy in the compounding industry. Find out how a PCCA membership can benefit your compounding practice.

References

PCCA Science Technical Report. Evaluation of the Content Uniformity of 8 SuspendIt® Formulations. 2015. Accessed January 2025 at https://beta.pccarx.com/pdf_files/98962_TR_SuspendIt_ContentUnif.pdf

Balance Hormones and Grow Your Practice

Thu, 19 Dec 2024 23:31:00 GMT

The numbers are in — forecasters predict 1.1 billion women worldwide will experience menopause in 2025.¹ In the U.S., more than 1 million women reach menopause each year, and more than 75 percent of these women work during menopause transition years. Research conducted by the National Institute on Aging indicates menopausal hormone therapy (MHT) reduced the severity of menopause symptoms while elevating mood, sexual function, cardiovascular and brain health.²

With all of these studies and reports, it’s no wonder that hormone replacement therapy (HRT) currently leads all compounding therapeutic areas in the U.S. — or that the U.S. HRT market value is forecasted to reach $12.6 billion within the next five years.³Maintaining up-to-date HRT knowledge is now a top priority for compounding pharmacists who support patients that experience the many side effects of perimenopause or menopause.

Introducing PCCA Master Courses: HRT

PCCA Master Courses: Hormone Replacement Therapy (HRT), a new education tool, will prepare compounding pharmacists to meet the needs of this expanding female patient segment. The dynamic platform delivers specialty education using:

Online, self-paced HRT education available on demand
Engaging, multimedia formats for interactive learning
Continuing education (CE) courses with 25 hours of CE applied for

“We understand the many nuances of compounding and recognize the varied responsibilities of compounding pharmacy owners and pharmacists,” said PCCA Director of Online Education Jerra Banwarth, RPh, FAPC. “This is why we wanted to develop a flexible program that accommodates their busy schedules. We also wanted to make it a dynamic experience to captivate and retain their interest — regardless of time or day. And we recognize the importance of specialty education — it’s an advantage that a compounding pharmacist can use to distinguish their practice from competitors.”

PCCA Master Courses: HRT was developed to be easy to follow and provides a true multimedia experience. Education is delivered through impactful audio, visual and animations, which helps learners better understand the physiological concepts of perimenopause through post-menopause.

Master Courses: HRT is composed of five courses:

Introduction to Hormones
Reviews foundational anatomy and physiology; explores the goals of HRT.
Testing and Therapy Options
Takes an in-depth look at different testing options and applications for utilization.
Clinical Evidence for HRT Patient-Centered Care
Provides insights into patient specific therapies, including dosing, routes of administration and formulations.
Bases for HRT Application
Explores appropriate bases, devices and compounding considerations for HRT formulations.
Building a Thriving HRT Compounding Practice
Provides a foundation for marketing your expertise and knowledge; offers professional recommendations on how to implement a hormone consultation practice.

Earn Your Certified Master Designation in HRT

Upon successfully completing the Master Course, learners can take their expertise further with the PCCA Certified Master* designation. The designation is achieved in two steps:

Successfully complete all courses in PCCA Master Courses: HRT by February 7, 2025.
Attend a PCCA HRT Symposium within 12 months: in-person or virtually at the Las Vegas HRT Symposium, February 20-22, or at the virtual HRT Symposium on July 24-25, 2025.

The HRT Symposium and Master Courses: HRT are complimentary educational achievements designed to help shorten the learning curve and create a powerful experience for pharmacists. In addition to increasing their knowledge, those who achieve the PCCA Certified Master designation can use it to market their practice to prescribers and patients.

“We work to ensure our education programs and symposiums benefit all attendees — from pharmacists to pharmacy technicians and medical practitioners,” said PCCA Senior Director of Education Renee Prescott. “We hire industry-expert speakers who share cutting-edge clinical research, provide ample time for participants to network and we apply for CEs, yet another benefit. More than 98 percent of participants give us an ‘A’ grade.”

Participants who achieve their initial Certified Master designation have the option to recertify by attending the PCCA HRT Symposium every two years.

“There’s always something new to learn,” said Jerra. “Serving this population not only helps women, it also benefits their families, friends, workplace and communities.”

Prepare to meet the needs of a growing market. Register today for PCCA Master Courses: HRT.

PCCA members with clinical service access may contact our Clinical Services team for additional information on compounding for HRT and other compounding concerns.

PCCA is recognized as the leader of quality products, education and advocacy in the compounding industry. Find out how a PCCA membership can benefit your compounding practice.

*The Certified Master award is an internal designation provided by PCCA. It does not denote a board certification or certification by a licensed health care body. Pharmacists and practitioners are eligible for the Certified Master designation.

References

Zhang L, Ruan X, Cui Y, Gu M, Mueck AO. Menopausal Symptoms and Associated Social and Environmental Factors in Midlife Chinese Women. Clin Interv Aging. 2020;15:2195-2208. Published 2020 Nov 16. doi:10.2147/CIA.S278976
National Institute on Aging. News. Research explores the impact of menopause on women’s health and aging. Research Highlights. 2022. Accessed December 2024 at https://www.nia.nih.gov/news/research-explores-impact-menopause-womens-health-and-aging#hormone
Grand View Research. Hormone Replacement Therapy Market Size, Share & Trend Analysis By Product (Estrogen & Progesterone Replacement Therapy), By Route of Administration, By Disease Type, By Region, And Segment Forecasts, 2023 – 2030. Accessed October 2024 at https://www.grandviewresearch.com/industry-analysis/hormone-replacement-therapy-market

Penetrating the Nail Fungus Market with EctoSeal P2G™

Wed, 04 Dec 2024 18:13:00 GMT

by Sam Hamburger, PharmD Candidate, PCCA Clinical Services Intern, and Mark Gonzalez, PharmD, PCCA Clinical Compounding Pharmacist

One of the most valuable benefits of PCCA membership is access to our knowledgeable Research & Development department and their compounding base innovations. Their creativity has led the industry and provided resources that benefit thousands of patients every day. This post focuses on a powerful base launched in 2023, EctoSeal P2G, and its application in one of the most common dermatological conditions — nail fungus (onychomycosis).

Beyond Basic: EctoSeal P2G

EctoSeal P2G (powder to gel) was developed by the PCCA R&D department and released in 2023. It is one of the most innovative and clinically versatile bases in the compounding industry, with seemingly limitless potential. The base itself is available as a powder that can be compounded with a wide variety of active pharmaceutical ingredients (APIs) and dispensed in one of three unique dosage forms: a powder, a powder for reconstitution or a hydrogel. Each dosage form has unique and versatile therapeutic possibilities. Regardless, the end goal of this base is to form a protective film over the affected area, delivering the API while simultaneously shielding the area and enhancing the skin’s local microbiome. It is also easily removed by simply rinsing with water, which causes the film to revert to a liquid gel that will simply wash off.

As a compounder, you are by definition a creative individual. Imagine the possibilities of compounding a preparation that creates a microbiome-enhancing protective film — one that easily washes off with water, easing the discomfort experienced by wound patients during dressing changes or Polyox bandage removal. Coupled with the imagination and ingenuity of PCCA members, we have seen incredible advances beyond wound care in conditions such as acne, diaper rash, excoriated eczema, veterinary infections, vaginal/rectal lesions and most recently, nail fungus (onychomycosis).

Onychomycosis

For decades, compounders have formulated prescriptions for use on patients with onychomycosis. The condition occurs in 10 percent of the general population, 20 percent of persons older than 60 years and 50 percent of those older than 70 years. Although caused by a variety of organisms, most cases are created by dermatophytes, a pathogenic fungus that causes ringworms and other diseases.¹ Topical preparations have often been preferred over oral therapies due to a lower side effect profile.

The vehicle of choice to deliver compounded antifungal agents has traditionally been dimethyl sulfoxide (DMSO) because of its ability to solubilize many APIs and penetrate various tissues. For antifungal preparations to be effective, transungal (through the nail) penetration is crucial to eliminate an infection that resides in the nail and nail bed.

EctoSeal P2G Study

Recognizing EctoSeal P2G’s excellent film-forming property, the PCCA Science team tested and measured the vehicle’s drug delivery potential in the nail using two PCCA formulas containing EctoSeal P2G, then compared those formulations with a standard formula involving APIs and DMSO alone. Five volunteers who met study eligibility criteria provided nail clippings, which were coated with one of the following compounded formulations:

Fluconazole 2%/Ibuprofen 2% Topical Nail Hydrogel (EctoSeal P2G)
Fluconazole 2% Topical Nail Hydrogel (EctoSeal P2G)
Fluconazole 2%/Ibuprofen 2%/Dimethyl Sulfoxide (DMSO) Nail Solution

After the compounds were applied to the nail clippings and allowed to dry for 48 hours, the clippings were washed to remove any drug residue. Ultra-Performance Liquid Chromatography (UPLC), a liquid chromatography technique that uses high pressure and new column technologies to separate compounds in complex mixtures, was used to measure the amount of drug in the pulverized nail clippings. When compared to the DMSO solution delivery, both EctoSeal P2G formulations resulted in much higher concentrations of drug (approximately 50 percent more) within the nail plate. This proves that an EctoSeal P2G/DMSO mixture is more effective at delivering drugs into the nail than DMSO alone.²

Compounders now have reliable data to present to dermatologists, podiatrists and general practitioners who have not found success with commercially available options for onychomycosis. Marketing this study may also broaden the practitioner’s imagination regarding the use of the film-forming possibilities of EctoSeal P2G. As compounders, we can take advantage of this data and innovative base vehicle to promote the endless opportunities that compounding can provide to solve medication problems and potentially improve patient outcomes.

Build and market your practice by promoting EctoSeal P2G:

As part of your next marketing campaign, take in or mail a sample of non-medicated EctoSeal P2G to your practitioners so they can experience its film-forming properties for themselves.
Provide copies of this study and other EctoSeal P2G studies to your practitioners and patients.
Compound with confidence knowing PCCA bases are backed by science and research.

PCCA members may learn more about EctoSeal P2G by watching a free webinar. PCCA members with clinical service access may contact our Clinical Services team for additional information on EctoSeal P2G and other compounding concerns.

PCCA is recognized as the leader of quality products, education and advocacy in the compounding industry. Find out how a PCCA membership can benefit your compounding practice.

References

Westerberg DP, Voyack MJ. Onychomycosis: Current trends in diagnosis and treatment. Am Fam Physician. 2013;88(11):762-770. Accessed November 2024 at https://pubmed.ncbi.nlm.nih.gov/24364524/
PCCA Research & Development. EctoSeal P2G (#30-5217) Science Manual. 2024; 8-9.

Microdosing GLP-1 RAs: Fad or Forever?

Fri, 22 Nov 2024 15:58:06 GMT

by Jennifer Lines, PharmD Candidate, PCCA Clinical Services Intern, and Catherine Henderson, PharmD, PCCA Clinical Compounding Pharmacist

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have revolutionized metabolic health and weight management, leading to a host of new weight loss wonder drugs. But did you know that recent evidence shows these new drugs may do more than just help with weight loss and diabetes? And at a fraction of the standard dose?

Looking Back on GLP-1 RAs

Originally discovered in the saliva of the Gila monster, exenatide — a GLP-1 RA— was approved as a twice-daily injection by the FDA in 2005 for adults with type 2 diabetes.¹ Within the past decade, longer-acting GLP-1 RA formulations entered the market as once-weekly, self-administered injectable pens — most notably, semaglutide.

Recent FDA approvals and indications for products containing semaglutide include the reduction of cardiovascular risk in patients with type 2 diabetes and body weight reduction for obesity. New research, however, reveals the potential for additional benefits of the drugs.

Potential Benefits of GLP-1 RAs

Known for their metabolic benefits, emerging studies suggest GLP-1 RAs may help improve kidney function, cardiovascular health, non-alcoholic fatty liver disease, Alzheimer's disease and Parkinson’s disease.²

GLP-1 RAs, such as semaglutide, also show potential anti-inflammatory properties. Although the specific mechanisms are not understood, reports indicate that semaglutide can modulate inflammatory processes by reducing levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and high-sensitivity C-reactive protein (hsCRP).

In an animal model, semaglutide demonstrated neuroprotective effects and improved cognitive function by inhibiting the release of inflammatory cytokines mediated by the NLRP3 inflammasome, a protein involved in regulating the innate immune system and inflammatory responses.

GLP-1 receptors are also found on different immune cells, such as neutrophils and eosinophils, and their activation has modulatory effects on immune responses and inflammatory processes associated with these types of cells.³

What Is Microdosing?

Microdosing is not an official medical term; it refers to taking less than the standard dose of a medication to achieve benefits while potentially minimizing undesirable side effects.

The term microdosing has risen in popularity in recent years. Initially, it referred to taking small doses of psychedelic drugs to alleviate symptoms of depression and anxiety, or boost mood and creativity. Interest in microdosing GLP-1 RAs is growing among many holistic physicians.⁴

Endogenous GLP-1 vs. Exogenous GLP-1 RAs

At normal physiological levels, active GLP-1 levels peak around 30-60 minutes after ingesting a meal before being rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4). During DPP-4 inhibition, levels of active GLP-1 increase up to 2-3 times. However, with exogenous GLP-1 RAs, active levels of GLP-1 RAs can rise to 10-30 times the normal physiological levels (depending on the agent used) and maintain steadily high levels independent of meal ingestion. One of the most common reasons patients discontinue GLP-1 RA treatment is due to gastrointestinal side effects, which could be attributed to the markedly high GLP-1 RA levels.⁵

Microdosing GLP-1 RAs

Anecdotal discussions between holistic practitioners suggest microdosing semaglutide may help people lose weight while limiting side effects. Naturopathic physician Dr. Tyna Moore, for example, suggests people with reduced GLP-1 levels may benefit from lower dosing and slowly increasing to the patient’s normal physiological levels. Dr. Moore also believes that slower, more sustainable weight loss allows the body more time to adjust to changes in weight, reducing the side-effect profile and potentially leading to better long-term success.⁶

While there are no clinical studies exploring the concept of microdosing GLP-1 RAs, it may be a useful tool for a holistic metabolic health strategy. It is important to remember that GLP-1 RAs are only one piece of the puzzle and should always be recommended in conjunction with diet, exercise and lifestyle modifications.

Smaller doses of GLP-1 RAs may not benefit those with severe metabolic dysfunction or those needing substantial weight loss. However, it may be helpful to those seeking a more gradual approach to weight loss while potentially providing overall health benefits like anti-inflammatory and neuroprotective effects.

While the safety of GLP-1 RAs is well established, current scientific evidence on the efficacy of microdosing GLP-1 RAs is lacking and further research is required to assess its benefits at lower doses.⁷

PCCA members with clinical services access may contact our Clinical Services team for help with microdosing GLP-1 RAs and other compounding concerns.

References

Paternoster S, Falasca M. Dissecting the Physiology and Pathophysiology of Glucagon-Like Peptide-1. Front Endocrinol (Lausanne). 2018;9:584. Published 2018 Oct 11. doi:10.3389/fendo.2018.00584
Laurindo LF, Barbalho SM, Guiguer EL, et al. GLP-1a: Going beyond Traditional Use. Int J Mol Sci. 2022;23(2):739. Published 2022 Jan 10. doi:10.3390/ijms23020739
Yaribeygi H, Maleki M, Jamialahmadi T, et al. Anti-inflammatory benefits of semaglutide: State of the art. J Clin Transl Endocrinol. 2024;36:100340. Published 2024 Mar 28. doi:10.1016/j.jcte.2024.100340
Mammoser G. (fact checked by Seladi-Shulman J.) Ozempic Microdosing Is Gaining Popularity. Does It Work for Weight Loss? Healthline. Published 2024 Oct 17. https://www.healthline.com/health-news/ozempic-microdosing-weight-loss
Smits MM, Holst JJ. Endogenous glucagon-like peptide (GLP)-1 as alternative for GLP-1 receptor agonists: Could this work and how?. Diabetes Metab Res Rev. 2023;39(8):e3699. doi:10.1002/dmrr.3699
Fitzgerald, J. (Host). (2023, October 12). Is Ozempic a miracle medicine? Heal Thy Self w/ Dr. G #283 [Video]. YouTube. https://www.youtube.com/watch?v=xI37HDVEMjo
Smits MM, Van Raalte DH. Safety of Semaglutide [published correction appears in Front Endocrinol (Lausanne). 2021 Nov 10;12:786732. doi: 10.3389/fendo.2021.786732]. Front Endocrinol (Lausanne). 2021;12:645563. Published 2021 Jul 7. doi:10.3389/fendo.2021.645563

What’s in Store at the LDN Virtual Conference

Fri, 15 Nov 2024 03:53:03 GMT

Individuals who suffer from symptoms of gastrointestinal, autoimmune, dermatological and pain conditions make up 80% of the patient population. But here’s the good news: multiple studies indicate that low-dose naltrexone (LDN) may potentially help many of these conditions. Take a sneak peek at topics our Clinical Services team will discuss during the Low-Dose Naltrexone One-Day Virtual Conference on Thursday, November 21, 2024.

The Immune System — Autoimmune Conditions and the Benefits of LDN

by Catherine Henderson, PharmD, PCCA Clinical Compounding Pharmacist

LDN has long been touted for its effects in autoimmune disorders. Understanding the mechanisms of LDN action involves diving deeper into immune system function and the irregularities that occur in autoimmune disorders. We’ll explore the data related to LDN’s various mechanisms for improving disease symptomatology and quality of life, as well as review real world published studies and cases of LDN use in various autoimmune disorders.

Dermatological Inflammatory Diseases and LDN

by Nat Jones, RPh, FAPC, PCCA Clinical Compounding Pharmacist

LDN is growing in popularity in the dermatology world. It has proven to be beneficial for pruritus and inflammation due to its ability to attenuate toll-like receptors found in the skin. We’ll discuss two cases: one of a tattoo allergic reaction and one of hidradenitis suppurativa (HS). Tattoo reactions to the coloring agents can be intense and difficult to treat. HS is a chronic inflammatory, potentially scarring, skin disease primarily affecting apocrine gland-rich areas of the body (axillary, groin, perianal, perineal regions and abdominal folds), often mediating pain and considerable morbidity, both physical and psychological.

The Use of LDN in Veterinary Patients

by Katy Hecker, PharmD, PCCA Clinical Compounding Pharmacist

As pet owners, we lovingly share many things with our pets including treats, affection and half of the bed. Research suggests we also share similarities in physiological function, disease state manifestation and treatment modalities utilized. Join in the discussion and learn more about the science behind LDN for veterinary clinical indications including behavioral disorders, atopic dermatitis, osteoarthritis, cancer, inflammatory bowel disease (IBD) and more!

Perimenopause and Menopause Are Inflammatory Conditions: The Use of LDN for Hormones and Weight Loss

by Sara Hover, RPh, FAARM, PCCA Director of Clinical Services

Understanding the inflammatory processes that characterize perimenopause and menopause will shed light on how the hormonal changes contribute to weight gain and obesity. Central to this discussion is the shift in estrogen profiles — from estradiol, which possesses anti-inflammatory properties, to estrone, a pro-inflammatory estrogen that becomes predominant during menopause. This hormonal transition fosters an inflammatory state that can disrupt metabolism and promote adiposity. Additionally, the presentation will explore various options aimed at reducing inflammation and managing weight effectively. Key strategies include optimizing sleep quality, utilizing probiotics to support gut health and implementing LDN as an innovative therapeutic approach. Attendees will gain a comprehensive understanding of the biological mechanisms linking menopause to inflammation and weight gain, along with practical interventions to enhance health and well-being during this pivotal life stage.

Using LDN for Chronic Pain Conditions

by Tricia Heitman, PharmD, PCCA Clinical Compounding Pharmacist

LDN is gaining attention for its anti-inflammatory properties and its ability to manage pain and opioid addiction. By acting on the opioid receptors at lower doses, LDN enhances endorphin production, which can help reduce inflammation and alleviate pain associated with various conditions such as arthritis, fibromyalgia and autoimmune disorders. Many patients report significant relief from chronic pain and inflammation while taking LDN. We will discuss the appropriate doses and review the literature associated with LDN and pain.

LDN for Gut Inflammatory Disorders

by Ranel A. Larsen, PharmD, PCCA Clinical Compounding Pharmacist

LDN is emerging as a promising therapeutic option for enhancing gut health, particularly in the context of IBD and irritable bowel syndrome (IBS). LDN helps to regulate immune responses, improve epithelial barrier function and reduce inflammation within the gut, all of which are critical for maintaining intestinal homeostasis. In IBD, LDN may lower disease activity and enhance quality of life, while in IBS, it can alleviate symptoms such as pain and bloating. Overall, LDN's role in improving gut health underscores its therapeutic potential to support management of complex gastrointestinal disorders.

How to Market LDN Studies

by Mark Gonzalez, PharmD, PCCA Clinical Compounding Pharmacist

Today’s compounding pharmacist wanting to effectively market LDN to practitioners and patients has access to tools that were not as available 20 years ago when LDN started to become popular. Clinical studies, therapeutic reviews and case series are now readily available to substantiate what were once only theories on the effectiveness of naltrexone in autoimmune disorders. These studies span a wide array of specialties and medical conditions. Research groups such as the LDN Research Trust, publications such as the series of three LDN books and many of the clinical presentations given on the subject of LDN all reference these studies. The pharmacist and marketer must leverage the power of this data as part of their communication to both the practitioner and the patient they are marketing to. With the additional aid of social media, positive patient stories can accompany the data from these clinical studies to make for attractive and effective marketing.

Register for the Low-Dose Naltrexone One-Day Virtual Conference today and get more details — plus more information — on the potentials of LDN. We look forward to additional discussions and answering your questions!

A Personalized Approach to HRT for Perimenopausal Women

Thu, 14 Nov 2024 04:23:17 GMT

by Sara Hover, RPh, FAARM, PCCA Director of Clinical Services

Perimenopause is a unique phase in a woman’s life, marked by fluctuating hormones and a wide range of symptoms. Hormone replacement therapy (HRT) can offer relief, but a one-size-fits-all approach may not yield the best results. A personalized approach, tailored to each woman’s unique hormonal profile, lifestyle and symptoms, can make all the difference in managing this transition effectively. Let’s explore the factors that contribute to low estrogen, the role of cortisol and progesterone, and why a customized approach to HRT is essential for perimenopausal women.¹

Understanding Estrogen Levels in Perimenopause

Estrogen is a key hormone for various bodily functions, from reproductive health to mood regulation. During perimenopause, estrogen levels fluctuate and eventually decline when menopause is reached. Several factors can contribute to low estrogen levels during perimenopause.

First, the natural abatement of ovarian function plays a major role; as women approach menopause, ovarian follicles reduce in number and function, resulting in decreased estrogen production. Genetic predisposition can also influence estrogen levels, as some women have genetic factors that may lead to an earlier or more abrupt drop. Additionally, lifestyle factors, including diet, stress and physical activity levels, significantly impact estrogen. For instance, poor nutrition or extreme physical training can suppress estrogen production.² Another crucial factor is high cortisol levels. Chronic stress increases cortisol, which may inhibit the body’s ability to produce adequate estrogen.³

By identifying these factors, healthcare providers can develop a more precise treatment plan, addressing not only hormonal imbalances but also lifestyle factors that might be exacerbating symptoms. During perimenopause, women are still making estrogen — maybe in an erratic fashion — but identifying the cause of low estrogen is most important. We should not give estrogen until there is certainty that the patient has entered menopause. Keep in mind that the testing results are a one-time snapshot of that moment and results may vary over time.¹

The Role of Cortisol in Perimenopausal Health

Cortisol, often referred to as the “stress hormone,” is produced by the adrenal glands and plays a significant role in managing stress and regulating metabolism. For perimenopausal women, high cortisol levels can have several consequences. Elevated cortisol can lead to increased fatigue and mood swings, as it causes feelings of exhaustion, irritability and mood fluctuations. It also disrupts other hormones; high cortisol can hinder estrogen production, exacerbating symptoms like hot flashes, insomnia and night sweats.

Furthermore, cortisol impacts progesterone levels due to a phenomenon known as “pregnenolone steal.” Since cortisol production draws on the same hormonal precursor (pregnenolone) that produces progesterone, the body under stress prioritizes cortisol production over progesterone, potentially leading to imbalances.⁴ By managing cortisol levels through stress reduction techniques, exercise and lifestyle modifications, women can help balance their hormones and reduce the intensity of perimenopausal symptoms.

Progesterone: The Balancing Hormone

Progesterone plays a vital role in regulating estrogen, stabilizing mood, promoting restful sleep and reducing anxiety. During perimenopause, progesterone levels begin to decline as ovulation becomes irregular, leading to several potential challenges.

One significant issue is estrogen dominance; when progesterone is low, estrogen may dominate, resulting in symptoms such as weight gain, bloating, breast tenderness and mood swings. Progesterone also affects sleep and anxiety levels, as it has a calming effect on the brain. Low levels of progesterone may lead to sleep disturbances and heightened anxiety, making this transitional phase more challenging.⁵ In addition, progesterone supports bone health, so declining levels can impact bone density over time.⁶ Replenishing progesterone through bioidentical hormones or other supplements, as determined by a healthcare provider, can help mitigate these symptoms and maintain hormonal balance.

Benefits of a Personalized HRT Approach

A personalized HRT approach considers each woman’s unique hormonal profile, lifestyle factors and symptom severity. This approach offers several distinct advantages. First, targeted hormone support is possible by measuring hormone levels and monitoring symptoms, allowing health care providers to recommend specific combinations and dosages of estrogen, progesterone and other hormones based on individual needs.

Personalized HRT plans address underlying causes; beyond hormone therapy, they may include lifestyle and nutritional adjustments to address root causes such as high cortisol or low progesterone. Ultimately, a personalized approach enhances a woman’s quality of life by addressing a broad range of factors — from hormonal imbalances to lifestyle changes — so she can experience a smoother perimenopausal transition with improved energy, mood and sleep quality.

Perimenopause doesn’t have to be a time of discomfort and uncertainty. A personalized approach to HRT empowers women to navigate this transition with a clear, effective and safe plan. With proper guidance, perimenopausal women can regain control over their bodies, ensuring that their unique needs are met. Whether through bioidentical hormone therapy, lifestyle changes or stress management, each woman deserves an individualized strategy that supports her well-being through this important life stage.

PCCA members with clinical services access may contact our Clinical Services team to answer any questions about HRT and other compounding concerns.

References

Smith, P., What You Must Know About Women’s Hormones. 2nd. Ed. Garden City Park, NY: Square One Publishing, 2022.
Delamater L, Santoro N. Management of the Perimenopause. Clin Obstet Gynecol. 2018 Sep;61(3):419-432. doi: 10.1097/GRF.0000000000000389. Accessed 2024 at https://pubmed.ncbi.nlm.nih.gov/29952797/
Woods NF, Mitchell ES, Smith-Dijulio K. Cortisol levels during the menopausal transition and early postmenopause: observations from the Seattle Midlife Women's Health Study. Menopause. 2009 Jul-Aug;16(4):708-18. Accessed 2024 at https://pubmed.ncbi.nlm.nih.gov/19322116/
Solano ME, Arck PC. Steroids, Pregnancy and Fetal Development. Front Immunol. 2020;10:3017. Published 2020 Jan 22. Accessed 2024 at https://pmc.ncbi.nlm.nih.gov/articles/PMC6987319/
Stefaniak M, Dmoch-Gajzlerska E, Jankowska K, et al. Progesterone and Its Metabolites Play a Beneficial Role in Affect Regulation in the Female Brain. Pharmaceuticals. 2023; 16(4):520. Accessed 2024 at https://pubmed.ncbi.nlm.nih.gov/37111278/
Mills EG, Yang L, Nielsen MF, et al. The Relationship Between Bone and Reproductive Hormones Beyond Estrogens and Androgens [published correction appears in Endocr Rev. 2021 Nov 16;42(6):872. doi: 10.1210/endrev/bnab024]. Endocr Rev. 2021;42(6):691-719. Accessed 2024 at https://pubmed.ncbi.nlm.nih.gov/33901271/

Backed by Science: Anhydrous VersaBase® HRT

Tue, 12 Nov 2024 14:48:13 GMT

At PCCA Science, we continuously build and grow scientific support for compounding and the technologies our members use in their practices. We test our bases using various methods before, during and after the release of a new product. We regularly submit results of these studies for publication in peer-reviewed journals and make them available to our members, who in turn can share them with prescribers, physicians and patients.

In Vitro Evaluation of the Percutaneous Absorption of Progesterone in Anhydrous Permeation-Enhancing Base Using the Franz Skin Finite Dose Model and Mass Spectrometry

What does the study say?

This study, published in the Archives of Dermatological Research, compares how well progesterone penetrates the skin in two topical formulations: one using Anhydrous VersaBase HRT and the second using a non-ionic cream. Results of the study showed that Anhydrous VersaBase HRT had a 3.2-fold increase in skin penetration over the non-ionic cream base, indicating it may be a good base to use in topical progesterone formulations.

Figure 1: The Anhydrous VersaBase HRT formulation offered a 3.2-fold increase in optical density (p = 0.029) for progesterone penetrating layers of skin compared to the non-ionic cream formulation.

What do the results of the study mean to prescribers and physicians?

Progesterone in a topical preparation using Anhydrous VersaBase HRT shows exceptional delivery of the hormone through the skin compared to the standard non-ionic cream base. It also indicates that the stability and potency of progesterone in the Anhydrous VersaBase HRT formulation was consistent for more than 180 days. Consistent hormone delivery is commonly recognized as achieving optimal prescriptive therapeutic outcomes for patients.

What do the results mean to patients?

The 180 beyond-use date (BUD) means patients will make fewer trips to the pharmacy for refills. Consistent hormone delivery may potentially help patients achieve a better therapeutic outcome.

What does anhydrous mean and why is that important?

Literally, anhydrous indicates a substance that contains no water. For compounded preparations, it means the water activity (Aw) — or the amount of available water in a substance — is less than 0.6 (<0.6). This is important because compounded preparations with Aw <0.6 do not support the growth of bacteria, yeast or molds.

Get a summary of study methods, images, graphs and more here.

*USP 795 establishes BUD limits by type of preparation in the absence of a USP−NF Compounded Preparation Monograph or CNSP-specific stability information.

Progesterone: Size Matters

PCCA offers USP-grade Special Micronized Progesterone with an unparalleled particle size to promote better bioavailability:

100% <9 microns
99% <5 microns
90% <2 microns

Additional Benefits

Consistently sourced from FDA-registered and GMP-compliant facilities
Tested in PCCA formulations in a range of concentrations
Above and beyond USP standards

Low-Dose Naltrexone in the Oncology Setting

Wed, 06 Nov 2024 19:19:31 GMT

by Sebastian Denison, RPh, PCCA Clinical Compounding Pharmacist

Since 2014, there’s been an explosion of information about the potential applications of low-dose naltrexone (LDN), including use as an adjunct therapeutic in some types of cancer. The exploration of LDN in cancer treatment underscores the importance of understanding the complex interplay between immune signaling and cancer biology, which we discuss in the following article.

Understanding TLR Signaling and Inflammation

Toll-like receptors (TLRs) play a crucial role in detecting and responding to pathogens and initiating inflammation. TLR signaling culminates in the activation of key transcription factors such as nuclear factor kappa B (NF-κB) and activating protein-1 (AP-1).

These transcription factors regulate a multitude of genes, including those encoding important proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukins (IL-1, IL-6, IL-8, IL-12). Some TLRs also activate production of type 1 (alpha and beta) interferons by inducing the interferon regulatory factors (IRFs) IRF3, IRF5 and IRF7.¹

NF-κB has been implicated in the pathogenesis of a number of inflammatory diseases, such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis, atherosclerosis, systemic lupus erythematosus, type I diabetes, chronic obstructive pulmonary disease and asthma. It also links chronic inflammation to cancer.²

Ongoing inflammation can also contribute to a condition known as "inflammaging," characterized by elevated inflammatory markers in older adults, increasing their susceptibility to chronic diseases and frailty.³

LDN: A New Perspective in Oncology

Traditionally, naltrexone (NTX) was used in treating opioid and alcohol dependence. Emerging research indicates that LDN may have a significant impact on cancer progression. This is primarily mediated through its effects on the opioid growth factor receptor (OGFr) axis, which has been associated with cancer cell survival, proliferation and invasion.⁴

Mechanisms of Action

Antagonism of Receptors: LDN’s antagonistic effects extend to TLRs 7-9, which can lead to the suppression of IL-6, a cytokine often elevated in cancer. By inhibiting these receptors, LDN may help to modulate the inflammatory environment that tumors exploit for growth.
Modulation of Immune Function: LDN appears to enhance the immune response in patients, potentially leading to improved cancer control. By promoting the activity of immune cells, LDN may assist the body in recognizing and attacking cancer cells more effectively.
Inhibition of Signaling Pathways: LDN is shown to prime pro-apoptotic pathways, encouraging cancer cells to undergo programmed cell death. This mechanism is particularly advantageous in combination with other therapies such as chemotherapy and immunotherapy.⁵

Low vs. Standard Dose

The effectiveness of NTX is highly dependent on individual dosage. Standard doses (25-50 mg) exhibit a classic antagonistic effect on opioid receptors, while LDN (1-5 mg) creates a transient blockade. This low-dose administration results in a compensatory increase in the synthesis of endogenous opioid peptides, fostering a feedback mechanism that enhances the anti-cancer effects. Research led by McLaughlin emphasizes the importance of both dosage and duration of exposure to opioid receptor antagonists. LDN’s temporary blockade of the OGFr ultimately leads to an increase in the expression of various opioid receptors, which can inhibit DNA replication and limit cancer cell proliferation. Conversely, higher doses of NTX could promote cellular division, counteracting the intended therapeutic effects.⁶

Promising Preclinical Evidence

Numerous preclinical studies support the idea that LDN can positively impact cancer outcomes. These studies indicate that LDN may inhibit the OGFr-OGF signaling axis, leading to decreased cancer cell proliferation. The lack of direct cytotoxic effects, combined with its immunomodulatory properties, positions LDN as an appealing option for cancer patients, particularly when used in conjunction with conventional therapies.

As anecdotal reports and preliminary studies point towards its efficacy, there is a growing momentum for clinical trials assessing LDN in oncology. The promise of LDN lies in its unique mechanism of action, which harnesses the body’s own systems to combat cancer while potentially reducing the side effects associated with traditional chemotherapy.

PCCA Members: Are you curious to know more? Log on to the Members Only website and check out our free webinar, Low-Dose Naltrexone: What’s New?

References

McDonald D. Toll-like receptors: Roles in disease and therapy. UpToDate (2022; literature review current through May 2024). Accessed 2024 at https://medilib.ir/uptodate/show/3985
Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017;2:17023-. Accessed 2024 at https://pubmed.ncbi.nlm.nih.gov/29158945/
Ferrucci L, Fabbri E. Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nat Rev Cardiol. 2018;15(9):505-522. Accessed 2024 at https://pubmed.ncbi.nlm.nih.gov/30065258/
Belltall A, Mazzinari G, Diaz-Cambronero O, Eroles P, Argente Navarro MP. Antagonists of the Mu-Opioid Receptor in the Cancer Patient: Fact or Fiction?. Curr Oncol Rep. 2022;24(10):1337-1349. Accessed 2024 at https://pubmed.ncbi.nlm.nih.gov/35648340/
Liu WM, Dalgleish AG. Naltrexone at low doses (LDN) and its relevance to cancer therapy. Expert Review of Anticancer Therapy, 2022;(3), 269–274. Accessed 2024 at https://www.tandfonline.com/doi/citedby/10.1080/14737140.2022.2037426?scroll=top&needAccess=true
Ciwun M, Tankiewicz-Kwedlo A, Pawlak D. Low-Dose Naltrexone as an Adjuvant in Combined Anticancer Therapy. Cancers. 2024; 16(6):1240. Accessed 2024 at https://www.mdpi.com/2072-6694/16/6/1240

Subclinical Hypothyroidism: Weight, Testing and Medication Absorption

Wed, 09 Oct 2024 15:41:00 GMT

Thyroid health plays a pivotal role in regulating metabolism, energy levels and overall well-being.1 Among the spectrum of thyroid disorders, subclinical hypothyroidism often flies under the radar due to its subtle symptoms. However, its implications on weight management warrants closer attention. Taking a closer look into what subclinical hypothyroidism entails, its connection to weight loss challenges, the importance of appropriate testing, and how excipients in medications can influence thyroid hormone absorption can help many patients with this elusive condition.

What Is Subclinical Hypothyroidism?

Subclinical hypothyroidism (SCH) is a mild form of hypothyroidism where the thyroid gland doesn't produce enough thyroid hormones to meet the body's needs, but the deficiency isn't severe enough to cause overt symptoms. It's characterized primarily by elevated thyroid-stimulating hormone (TSH) levels, while free thyroxine (free T4) and free triiodothyronine (free T3) levels remain within the normal range but might not be what is considered optimal. When TSH is elevated, this indicates that the pituitary gland is sending out a stronger signal to the thyroid to produce more hormones.² It is always important to look at a complete thyroid panel to obtain the full picture, such as looking at both the free T4 and free T3. T4 is a prohormone for T3, and the body converts it to T3 as it is needed. T3 is the hormone that actually interacts with the receptor and does the work, so to speak.³

Subclinical Hypothyroidism and Weight Management

Thyroid hormones are integral to regulating metabolism — the rate at which the body converts food into energy. Even subtle imbalances can influence weight management. When thyroid levels are lower, the metabolic rate is slowed as well as the patient typically is more fatigued. A sluggish metabolism can make weight loss more challenging. And a patient with low energy has a difficult time staying committed to an exercise regimen.

However, it's essential to note that the relationship between SCH and weight is complex. While overt hypothyroidism is more directly linked to weight gain, SCH's impact can vary among individuals. Some may experience weight fluctuations, while others may not notice significant changes.²

Importance of Appropriate Testing

Accurate diagnosis is crucial for effective management of SCH, especially when addressing weight-related concerns. As previously mentioned, TSH, free T4 and free T3 are essential to be included in the thyroid panel. In addition to those components, it is also very beneficial to look at peroxidase antibodies (TPOAb). If these antibodies are elevated, it can indicate autoimmune thyroiditis, a common cause of SCH.⁴In addition to antibodies, a lipid panel is essential since thyroid hormones can influence cholesterol metabolism. For some patients, an atypical rise in lipids is a sign that there could be thyroid dysfunction.⁵

Treatment Options for Subclinical Hypothyroidism

The decision to treat SCH hinges on several factors, including TSH levels, presence of symptoms, age and underlying health conditions.²It is also key to evaluate adrenal function before beginning thyroid supplementation. Adrenal insufficiency is actually a contraindication for thyroid replacement.⁶

The Role of Excipients in Thyroid Medication Absorption

When it comes to managing SCH, thyroid hormone replacement therapy, such as levothyroxine or Thyroid USP (Porcine), is commonly prescribed. However, the efficacy of these medications isn't solely dependent on the active ingredient. Excipients play a crucial role in the drug's absorption and effectiveness. Common excipients in thyroid medications include fillers such as lactose, microcrystalline cellulose and magnesium stearate. Excipients can influence how well the active hormone is absorbed in the gastrointestinal tract.⁷ For instance, certain fillers might bind to thyroid hormones, reducing their availability, while others, such as PCCA LoxOral®, can enhance dissolution, potentially leading to improved absorption.

Subclinical hypothyroidism is a nuanced condition that, despite its subtlety, can influence various aspects of health, including weight management. Recognizing its signs, understanding the importance of appropriate testing and being aware of how excipients affect medication absorption are vital steps in effective management. If a patient suspects thyroid imbalances or is facing challenges with weight management despite a healthy lifestyle, consulting with a healthcare professional for comprehensive evaluation and personalized treatment is essential. Pharmacists should empower patients with knowledge and help them take proactive steps towards optimal thyroid health and overall well-being.

References

Liu G, Liang L, Bray GA, et al. Thyroid hormones and changes in body weight and metabolic parameters in response to weight loss diets: the POUNDS LOST trial. Int J Obes (Lond). 2017 Jun;41(6):878-886. doi: 10.1038/ijo.2017.28. Epub 2017 Jan 31. Accessed October 2024 at https://pubmed.ncbi.nlm.nih.gov/28138133/
Azim S, Nasr C. Subclinical hypothyroidism: When to treat. Cleve Clin J Med. 2019 Feb;86(2):101-110. doi: 10.3949/ccjm.86a.17053. Erratum in: Cleve Clin J Med. 2019 Jun;86:392. Accessed October 2024 at https://pubmed.ncbi.nlm.nih.gov/30742580/
Armstrong M, Asuka E, Fingeret A. Physiology, Thyroid Function. [Updated 2023 Mar 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Accessed October 2024 at https://www.ncbi.nlm.nih.gov/books/NBK537039/
Rugge B, Balshem H, Sehgal R, et al. Screening and Treatment of Subclinical Hypothyroidism or Hyperthyroidism [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2011 Oct. (Comparative Effectiveness Reviews, No. 24.) Introduction. Accessed October 2024 at https://www.ncbi.nlm.nih.gov/books/NBK83492/
Kumar M, Dheeraj D, Kant R, Kumar A. The Association Between Anti-Thyroid Peroxidase Antibody and Dyslipidemia in Subclinical Hypothyroidism Among the Rural Population of Central India. Cureus. 2022 Feb 17;14(2):e22317. doi: 10.7759/cureus.22317. Accessed October 2024 at https://pubmed.ncbi.nlm.nih.gov/35317033/
AbbVie. Highlights of Prescribing Information, Synthroid. 2024 Feb Updates. Accessed October 2024 at https://www.rxabbvie.com/pdf/synthroid.pdf Accessed 10/2/2024
Patel H, Stalcup A, Dansereau R, Sakr A. The effect of excipients on the stability of levothyroxine sodium pentahydrate tablets. Int J Pharm. 2003 Oct 2;264(1-2):35-43. doi: 10.1016/s0378-5173(03)00387-9. Accessed October 2024 at https://pubmed.ncbi.nlm.nih.gov/12972334/

Mitochondrial Health: The Key to Longevity?

Wed, 25 Sep 2024 17:34:52 GMT

In the race to unlock the secrets of longevity, one of the most exciting areas of research is mitochondrial health. These tiny organelles, often referred to as the "powerhouses" of the cell, are responsible for producing the energy (ATP) that fuels every cell in the body. As we age, mitochondrial function tends to decline, leading to reduced energy, increased oxidative stress and accelerated aging. Maximizing mitochondrial health has emerged as a key strategy for extending both lifespan and health span — how long we live and how well we live.¹

The Latest Breakthroughs in Mitochondrial Health

Recent research has identified several pathways to optimize mitochondrial function. One major discovery involves the molecule nicotinamide adenine dinucleotide (NAD+), which plays a crucial role in mitochondrial energy production.² As we age, NAD+ levels decline, leading to less efficient energy production and greater cellular damage. Boosting NAD+ through precursors like nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) has shown promise in improving mitochondrial function and extending the lifespan of various organisms in laboratory studies.³ How this translates to human longevity — that is the question!

Another fascinating area is mitophagy, the process by which cells clear out damaged or dysfunctional mitochondria. With age, the body's ability to efficiently remove these damaged mitochondria diminishes, leading to cellular dysfunction. Promoting mitophagy through intermittent fasting or caloric restriction can help maintain a population of healthy mitochondria, thereby improving metabolic efficiency and reducing oxidative stress. Compounds such as creatine and urolithin A have been shown to stimulate mitophagy, offering potential therapeutic benefits for aging populations.^4,5

Maximizing Mitochondrial Health for Longevity

Dietary Interventions: Nutrients like coenzyme Q10, alpha-lipoic acid and omega-3 fatty acids (especially from fresh fish) directly support mitochondrial energy production.⁶
Exercise: Regular physical activity, particularly high-intensity interval training (HIIT), has been shown to enhance mitochondrial biogenesis. It is interesting how FEW individuals in their 40s and older do exercises that really elevate their heart rate.⁷
Cold Exposure: Cold thermogenesis, or exposing the body to cold temperatures (e.g., ice baths or cold showers), stimulates the production of mitochondria and enhances their efficiency, offering a novel way to boost energy and longevity.⁸
Sleep and Stress Reduction: Poor sleep and chronic stress are mitochondrial toxins. Prioritizing restorative sleep and managing stress through practices like mindfulness meditation or yoga can promote mitochondrial repair and rejuvenation.⁹

Maintaining optimal hormone levels as we age plays a crucial role in supporting mitochondrial health. Hormones like estrogen, testosterone and thyroid hormones are vital regulators of mitochondrial function, helping to enhance mitochondrial biogenesis (the creation of new mitochondria) and optimize energy production. Adequate levels of these hormones, monitored through optimal testing, also promote mitochondrial repair.¹⁰

By integrating these strategies on a regular basis, we can enhance mitochondrial function, slow down the aging process and increase both lifespan and health span for a brighter, more energized future.

References

López-Otín C, Blasco MA, Partridge L, et al. Hallmarks of aging: An expanding universe. Cell. 2023;186(2):243-278. Accessed September 2024
Zhao Y, Zhang J, Zheng Y, et al. NAD+ improves cognitive function and reduces neuroinflammation by ameliorating mitochondrial damage and decreasing ROS production in chronic cerebral hypoperfusion models through Sirt1/PGC-1α pathway. J Neuroinflammation. 2021;18(1):207. Published 2021 Sep 16. Accessed September 2024 at https://pubmed.ncbi.nlm.nih.gov/34530866/
Lapatto HAK, Kuusela M, Heikkinen A, et al. Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study. Sci Adv. 2023;9(2):eadd5163. Accessed September 2024 at https://pubmed.ncbi.nlm.nih.gov/35276888/
Marshall RP, Droste JN, Giessing J, Kreider RB. Role of Creatine Supplementation in Conditions Involving Mitochondrial Dysfunction: A Narrative Review. Nutrients. 2022;14(3):529. Published 2022 Jan 26. Accessed September 2026 at https://pubmed.ncbi.nlm.nih.gov/35276888/
Pagano G, Pallardó FV, Lyakhovich A, et al. Aging-Related Disorders and Mitochondrial Dysfunction: A Critical Review for Prospect Mitoprotective Strategies Based on Mitochondrial Nutrient Mixtures. Int J Mol Sci. 2020;21(19):7060. Published 2020 Sep 25. Accessed September 2024 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582285/
Pagano G, Pallardó FV, Lyakhovich A, et al. Aging-Related Disorders and Mitochondrial Dysfunction: A Critical Review for Prospect Mitoprotective Strategies Based on Mitochondrial Nutrient Mixtures. Int J Mol Sci. 2020;21(19):7060. Published 2020 Sep 25. Accessed September 2024 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582285/
San-Millán I. The Key Role of Mitochondrial Function in Health and Disease. Antioxidants. 2023; 12(4):782. Accessed September 2024 at https://www.mdpi.com/2076-3921/12/4/782
Chung N, Park J, Lim K. The effects of exercise and cold exposure on mitochondrial biogenesis in skeletal muscle and white adipose tissue. J Exerc Nutrition Biochem. 2017;21(2):39-47. Accessed September 2024 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5545200/
Zielinski MR, Systrom DM, Rose NR. Fatigue, Sleep, and Autoimmune and Related Disorders. Front Immuno. 2019;10. Accessed September 2024 at https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.01827/full
Klinge CM. Estrogenic control of mitochondrial function. Redox Biol. 2020;31:101435. Accessed September 2024 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212490/

Managing Menopausal Weight Gain: The role estrogen plays with GLP-1 agonists

Wed, 11 Sep 2024 13:27:35 GMT

by Katy Hecker, PharmD, PCCA Clinical Services

In a woman’s life, the absence of menstruation for 12 months marks the official beginning of menopause. Waning ovarian function coupled with declining circulating hormone levels spark natural menopause, but menopause may also occur as result of surgical procedures such as following a hysterectomy and/or oophorectomy. Commonly reported symptoms of menopause include hot flashes, night sweats, vaginal dryness, sleep disturbances, mood swings and weight gain,¹ with an estimated 70% of menopausal women experiencing weight gain.²

Menopause and Body Composition

Menopause triggers body composition changes such as increased abdominal adipose tissue and decreased lean muscle mass. This change in body composition intensifies the risk of diabetes, cardiovascular disease, dyslipidemia (abnormal levels of lipids in the blood) and metabolic dysfunction-associated steatotic (fatty) liver disease. Heart disease is the leading cause of death in women; therefore, it is critical to address menopausal weight gain and the cardiometabolic changes that occur. Hormone replacement therapy, lifestyle modification and in some instances medication therapy may be beneficial to help combat menopausal weight gain.^2,3

GLP-1 and Weight Loss

GLP-1 is a hormone naturally produced in the central nervous system, intestine and pancreas. It is released in response to the consumption of fats and carbohydrates.^2,4GLP-1 increases insulin secretion, decreases glucagon release, slows gastric emptying and reduces food intake. Research also suggests it may reduce food reward behavior. The appetite suppressing effect of GLP-1 is due to its action in the hypothalamus and brainstem. Interestingly, this is the same region of the brain responsible for the food intake reduction effects of estrogen. Glucagon-like peptide-1 (GLP-1) receptor agonist and dual agonist therapies are FDA-approved for the treatment of obesity, weight management, type 2 diabetes mellitus and cardiovascular mortality reduction.⁴

Semaglutide and Hormone Replacement Therapy

Combining hormone replacement therapy with semaglutide, a GLP-1 receptor agonist, may lead to better outcomes for total body weight loss and subsequent improvements in cardiometabolic health. A recent retrospective review compared weight loss response and cardiometabolic changes in post-menopausal women using semaglutide in combination with and without hormone therapy. At three, six, nine and 12 months following semaglutide initiation, women using hormone therapy experienced approximately 30% greater total body weight loss than the non-hormone therapy users. Both groups showed improvements in cardiometabolic health marked by lower fasting blood glucose, blood pressure, LDL, total cholesterol and triglycerides.²

Reward Eating, GLP-1 and Estrogen

Reward eating is comprised of two categories, “wanting” and “liking.”⁵ Liking is associated with the palatability of the food and wanting is food craving triggered by a cue or stimuli which then leads to motivation to obtain a specific type of food.⁴ Research suggests women may exert a greater response to a centrally administered long acting GLP-1 agonist on food reward due to the activation of central estrogen receptor alpha. This reduction was noted with the “wanting” subtype of reward eating in women greater so than men. A reduction in the “liking” subtype of reward eating was displayed in both men and women. Administration of an estrogen receptor antagonist was sufficient to blunt the effects of the central GLP-1 agonist on food reward behavior in both men and women. This evidence suggests the activation of central estrogen receptor alpha may be critical for central GLP-1 agonist’s effect on reward eating.^4,5

Compounded Medications

There are many treatment strategies that may help menopausal women with the natural challenges and health risks associated with this phase of life. Combining therapies has yielded compelling results, and compounded medications can be personalized to meet the needs of each patient, offering a unique solution for various medication related concerns. For example, SubMagnaTM SL HMW can be used to deliver semaglutide in a sublingual dosage form. This may improve adherence in patients who have trouble swallowing or who are fearful of needles.

Members with clinical services access may contact our Clinical Services Team for help with PCCA formulas and other compounding questions.

References

World Health Organization. Menopause [Internet]. Oct 2022. Accessed August 2024 at https://www.who.int/news-room/fact-sheets/detail/menopause
Hurtado MD, Tama E, Fansa S, et al. Weight loss response to semaglutide in postmenopausal women with and without hormone therapy use. Menopause. 2024;31(4):266-274. doi:10.1097/GME.0000000000002310
Centers for Disease Control. About Women and Heart Disease [Internet]. May 15, 2024. Accessed August 2024 at https://www.cdc.gov/heart-disease/about/women-and-heart-disease.html#:~:text=Heart%20disease%20is%20the%20leading,affect%20women%20at%20any%20age
Elsevier Clinical Pharmacology. Glucagon-like Peptide-1 (GLP-1) Receptor Agonists and Dual Agonists [Internet]. Apr 9, 2024. Accessed August 2024 at https://elsevier.health/en-US/preview/glucagon-like-peptide-1-glp-1-receptor-agonists
Richard JE, Anderberg RH, Lopez-Ferreras L, et al. Sex and estrogens alter the action of glucagon-like peptide-1 on reward. Biol Sex Differ. 2016;7:6. doi:10.1186/s13293-016-0059-9

Challenges in Pediatric Compounding: Excipients and Dosage Forms

Wed, 14 Aug 2024 13:48:00 GMT

by Rudesha Sanders, PharmD Candidate, PCCA Clinical Services Intern, and Tricia Heitman, PharmD, PCCA Clinical Compounding Pharmacist

Developing pharmaceutical products for pediatric patients generally requires age appropriate, weight-based dosing or extensive formula considerations. Most commercially available drug products are not formulated with pediatric populations in mind; they are often generated using unsafe excipients or produced in inappropriate dosage forms.¹

Excipients with Known Toxicity in Neonates

We should eliminate the use of these known excipients in compounds for neonatal (birth – 28 days) patients as much as possible due to toxicities:

Benzyl alcohol
Ethyl alcohol
Propylene glycol
Parabens

Benzyl alcohol intoxication can lead to metabolic acidosis and possible respiratory depression; ethyl alcohol is known to cause neurotoxicity and cardiovascular problems in pediatric patients; and high doses of propylene glycol can affect the central nervous system.²

In addition, the above-mentioned excipients are known to accumulate more in a neonate’s system due to the baby’s premature and underdeveloped organs — exercise caution if including any of the excipients in a compounded preparation.

Caution should also be exercised with other excipients, including benzalkonium chloride; polysorbate; peanut oil or other known food-related allergens such as lactose, sorbitol, sucrose, aspartame, saccharin, artificial colors; as well as sulfites such as sodium metabisulfite and sodium bisulfite, which may cause allergy-like reactions.^1-3

Excipient Concerns for Infants and Children

As infants (ages 29 days – < 2 years) and children (ages 2 years – < 12 years) grow, so do their organ systems; however, excipients remain a concern. Ethyl alcohol should be avoided in children under 2 years of age. Children 2 to 5 years of age should receive no more than a 6 mg/kg/dose of ethyl alcohol daily, with less than 0.5% percent volume in volume (v/v). Children 6 years and older should receive no more than 75 mg/kg/dose of ethyl alcohol daily; ages 6 to 12 years should receive less than 5% (v/v) of ethyl alcohol daily; and children ages 12 and older should receive less than 10% (v/v) of ethyl alcohol per day.^1,3

Benzyl alcohol is contraindicated in children 3 years old and younger. Polyethylene glycol should be used with caution in infants. It is recommended to use propylene glycol with caution in children less than 4 years old.²

Pediatric Dosage Forms and Safety Considerations

We should always be mindful of the types of dosage forms used when compounding preparations for children. Dosage forms should always be individualized to accommodate the child’s age, specific needs and preferences, as well as always dispensed in child-resistant packaging.

Oral suspensions, for example, are generally formulated in oil bases and pose a threat for aspiration, which can lead to lipoid pneumonia.^3,4 To reduce this risk, children under 2 years of age or children at high risk for aspiration should have oral suspensions formulated with aqueous bases. SuspendIt^® Anhydrous is a great base for pediatric patients: it’s preservative free; its anhydrous property allows for the potential of extended beyond-use dates (BUDs) and convenience for a parent or caregiver; its ability to mix easily with water, juice or other flavored liquids may possibly improve patient adherence; and its self-emulsifying drug delivery system allows use in nasogastric feeding tubes without clogging.⁶

Avoid using lollipops in children younger than 5 years of age due to the potential choking hazard — where the stick dislodges from the preparation — unless the child is closely supervised by a caregiver or medical personnel. Other challenges include flavoring issues and that lollipops must remain in the mouth for an extended period before they completely dissolve.

Like lollipops, hard troches should also be avoided in children under 5 years of age. In the event other dosage forms are not available or possible, ensure the child is closely monitored and supervised by a caregiver or medical personnel. Gelatin troches may be an option for children 2 years and older who have their primary teeth and can safely chew and swallow.⁷

Suppositories are generally a safe option in pediatric patients; just ensure use of the smallest size suitable for the dosage quantity.

Topical dosage forms are often a convenient and effective way to dose a child. The volume dispensed should be accurately measured and based on the patient’s age and weight. If a child has siblings, pets or attends school, instruct the child’s parents or caregivers to avoid placing the topical medication in an area where accidental transference to another child, caregiver or pet could occur.⁸

Remaining mindful and cautious of formulations and dosage forms used to compound preparations for neonates and infants will help reduce the accumulation of harmful toxicities. Applying the right dosage form with consideration toward the child’s age, specific needs and preferences, as well as their height and weight, will help ensure the safety and efficacy of compounded medications for pediatric patients.

References

Rouaz K, Chiclana-Rodríguez B, Nardi-Ricart A, et al. Excipients in the Paediatric Population: A Review. Pharmaceutics. 2021;13(3):387. Published 2021 Mar 13. doi:10.3390/pharmaceutics13030387 Accessed July 2024 at https://pubmed.ncbi.nlm.nih.gov/33805830/
U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER). (2022). General Clinical Pharmacology Considerations for Neonatal Studies for Drugs and Biological Products: Guidance for Industry. Accessed July 2024 at https://digirepo.nlm.nih.gov/catalog/nlm:nlmuid-9918486678506676-pdf
Bobillot M, Delannoy V, Trouillard A, et al. Potentially Harmful Excipients: State of the Art for Oral Liquid Forms Used in Neonatology and Pediatrics Units. Pharmaceutics. 2024;16(1):119. Published 2024 Jan 17. Accessed July 2024 at https://pubmed.ncbi.nlm.nih.gov/38258129/
Annobil SH, el Tahir M, Kameswaran M, Morad N. Olive oil aspiration pneumonia (lipoid) in children. Trop Med Int Health. 1997;2(4):383-388. Accessed July 2024 at https://pubmed.ncbi.nlm.nih.gov/9171848/
Sias SM, Ferreira AS, Daltro PA, et al. Evolution of exogenous lipoid pneumonia in children: clinical aspects, radiological aspects and the role of bronchoalveolar lavage. J Bras Pneumol. 2009;35(9):839-845. Accessed July 2024 at https://pubmed.ncbi.nlm.nih.gov/19820809/
Banov D, Liu Y, Ip K, Shan A, Vu C, Zdoryk O, Bassani A, Carvalho M. Analysis of the Physical Characteristics of an Anhydrous Vehicle for Compounded Pediatric Oral Liquids. Pharmaceutics. 2023;15(11):2642. Published 2023 Nov 20. Accessed July 2024 at https://pubmed.ncbi.nlm.nih.gov/38004620/
CDC (Last Reviewed 2022), Nutrition, Choking Hazards. Accessed July 2024 at https://www.cdc.gov/nutrition/infantandtoddlernutrition/foods-and-drinks/choking-hazards.html
Committee for Medicinal Products for Human Use. Reflection Paper: Formulations of Choice for the Paediatric Population. European Medicines Agency. Published 2006 Jul 28. Accessed July 2024 at https://www.ema.europa.eu/en/documents/scientific-guideline/reflection-paper-formulations-choice-paediatric-population_en.pdf

Acne Patients: You’re Not Alone

Wed, 05 Jun 2024 21:20:46 GMT

Although acne commonly occurs in adolescents and some adults, it can leave lasting effects, including scarring. With June designated as Acne Awareness Month, gain clinical understanding of causes and potential treatments that may help your patients.

by Nat Jones, RPh, FAPC, PCCA Clinical Compounding Pharmacist

Acne is the most common dermatologic disease, with a cumulative prevalence approaching 100 percent in males and females as they near puberty. In most cases, acne becomes less active as adolescence ends. However, the intensity and duration can vary among individuals — 20 percent will experience severe acne that can result in scarring.

The presence of acne may profoundly limit self-esteem and self-confidence, placing individuals at risk for developing depression and anxiety. Acne may also be associated with increased risk of self-injury and suicide attempts.¹

Pathophysiology

Acne pathophysiology is multifactorial: sebum alteration, aberrant follicular keratinization and Cutibacterium acnes (C. acnes, formerly known as Propionibacterium acnes or P. acnes) combine to cause comedones that can lead to inflammation and acne lesions.

Lightbox

Acne has multiple contributing factors, including hormones and neuropeptides, sebum production, the microbiome, as well as innate and adaptive immune functions. Androgens (dihydrotestosterone) stimulate sebocyte proliferation, which ultimately increases sebum production — a substrate for C. acnes growth — as well as lipid and triglyceride formation. Collectively, these factors induce the excessive shedding of skin cells, or hyperkeratinization, of the uppermost section of the hair follicle near the opening of pores, known as the follicular infrainfundibulum.

Diets comprised of high-glycemic-index foods, dairy and whey protein contribute to acne through stimulation of insulin-like growth factor-1 (IGF-1), while omega-3-fatty acids and low-glycemic-load diets are protective because they downregulate IGF-1. This suggests that increasing the ratio of monounsaturated to saturated fatty acids in sebum is proinflammatory and may promote acne.

Lesion Types & Treatment

Targeting inflammation is an important aspect of acne treatment. C. acnes stimulate inflammation via innate toll-like receptors (TLRs) and adaptive immunity (IL-17A and IFN-γ secretion from CD4+ T cells) and promote production of matrix metalloproteinases that contribute to scarring. C. acnes also form biofilms, which create a pro-inflammatory sebum concentration via increased lipase activity and promote resistance to treatment with antimicrobial agents.² Because low-dose naltrexone (LDN) attenuates activation of TLRs in the skin, it can be used as an adjunct therapy to treat acne (and other inflammatory skin diseases) in resistant cases.³

There are different types of acne lesions: open comedones (blackheads), closed comedones (whiteheads), inflammatory lesions (where the follicular wall ruptures, releasing sebum, cells and bacteria into the surrounding tissue, causing inflammation and redness) and cystic lesions that can lead to atrophic scars (icepick and boxcar).

Lightbox

Treatment of acne depends on severity (mild, moderate or severe), type of lesion and location. Acne lesions can appear on the face, forehead, chest, upper back and shoulders, or in combination of these areas, because these areas have the highest concentration of sebaceous glands. For a successful outcome, it is recommended that acne patients have a thorough regimen addressing all aspects of the disease.

Most regimens include:

A cleansing routine (usually twice daily) with a cleanser that removes dirt but does not strip all the oils from the skin to allow for healthy barrier function, followed by a light non-comedogenic moisturizer (such as VersaBase® Cream).
An exfoliation process 1-3 times a week, depending on severity.
Active treatment of some single API or combination of an antibacterial and a keratolytic. If using nightly tretinoin, exfoliation may not be necessary.

In severe cases, isotretinoin may be considered with usual precautions for reproductive-age female patients.1 Compounding formulations (non-cosmetic), especially combinations, are very useful and often more convenient for patients who require more than one API in a single application. Compounding APIs include:

Keratolytics
- Tretinoin
- Salicylic Acid
- Benzoyl Peroxide (also antibacterial)
Antibacterial
- Clindamycin
- Erythromycin
- Minocycline
- Sulfacetamide
- Tea Tree Oil
Sebostatic
- Niacinamide
- Azelaic Acid (also antibacterial)
Miscellaneous
- Progesterone (5α-reductase inhibitor)
- Spironolactone (DHT receptor antagonist)

PCCA bases often used in acne formulations include VersaBase Cream, VersaBase Gel, Clarifying™, PracaSil®-Plus, Occlusaderm® and WO6® Anhydrous Topical Gel (sometimes with the addition of PermE8® Anhydrous Gel to modestly enhance penetration through the stratum corneum).

Therapy should always be tailored to the patients’ needs — sensitivities and exceptions are always the rule. Remember to let your patients know that you’re here to help and they are not alone combating acne! PCCA members may access formulations developed for compounded preparations on the Members-Only Website, including a new formulation that uses aminolevulinic acid* in a topical gel with PermE8 Anhydrous Gel and WO6 Anhydrous Topical Gel.

*Aminolevulinic acid (ALA) is a compound used in photodynamic therapy (PDT) to treat acne vulgaris. Although the mechanism of action of ALA with PDT is not fully understood, it is believed to reduce sebum excretion by suppression of the sebaceous gland function. ALA-PDT was shown to be effective for acne and did not exhibit severe side effects.⁴

Members with clinical services access may contact our Clinical Services team for help with acne preparations and other compounding concerns.

References

Gupta, N., & Gupta, M. (2023). The Controversies Surrounding Acne and Suicide: Essential Knowledge for Clinicians. Cureus, 15(8), e43867. Accessed May 2024 at https://doi.org/10.7759/cureus.43867
Cruz, S., Vecerek, N., & Elbuluk, N. (2023). Targeting Inflammation in Acne: Current Treatments and Future Prospects. American journal of clinical dermatology, 24(5), 681–694. Accessed May 2024 at https://doi.org/10.1007/s40257-023-00789-1
Jaros, J., & Lio, P. (2019). Low Dose Naltrexone in Dermatology. Journal of drugs in dermatology: JDD, 18(3), 235–238. Accessed May 2024 at https://jddonline.com/articles/low-dose-naltrexone-in-dermatology-S1545961619P0235X/
Asayama-Kosaka, S., Akilov, O. E., and Kawana, S. (2014). Photodynamic Therapy with 5% δ-Aminolevulinic Acid is Safe and Effective Treatment of Acne Vulgaris in Japanese Patients. Laser therapy, 23(2), 115–120. Accessed May 2024 at https://doi.org/10.5978/islsm.14-OR-09

The Vaginal Microbiome, Menopause & HRT

Thu, 09 May 2024 03:38:07 GMT

Menopause causes more than hot flashes, mood swing and changes in libido; it also impacts diseases caused by shifting changes in the vaginal microbiome. Bridget Briggs, MD, sheds light on the vaginal microbiome, its influences on a woman’s health throughout various life stages, as well as how HRT helps mediate changes — and associated diseases — in the vaginal microbiome during menopause.

by Dr. Bridget Briggs, PCCA HRT Symposium Keynote Speaker

The vaginal microbiome (VM) is a complex ecological system that includes commensal, symbiotic and pathogenic organisms that inhabit the vaginal surfaces and its cavity. These organisms include bacteria, viruses and fungi.

The composition of organisms within the VM changes throughout the various stages of a woman’s life:

Childhood: Corynebacterium spp., Escherichia coli (E. coli), and Mycoplasma spp. form the vaginal microbiome.
Puberty: At puberty, the vaginal microbial niche shifts toward other predominant colonies, including Lactobacillus spp., Atopobium and Streptococcus spp.
Reproductive Ages: During reproductive age, the vaginal microbiome houses a range of bacterial communities, including lactobacilli (L. crispatus, L. gasseri, L. jensenii and L. iners) along with anaerobic bacteria.
Menopause: Further changes in the composition of the VM include Gardnerella vaginalis, Ureaplasma urealyticum, Candida albicans and Prevotella spp., with a progressive decrease in species of lactobacillus.

VM and Lactobacillus

The composition of the vaginal microbiome can vary widely between individuals. It influences a woman’s reproductive health, immune responses and overall wellbeing. Imbalance in the microbiome is linked to bacterial vaginosis (BV), thrush (a common yeast infection), urinary tract infections (UTIs) and influences fertility.

Lactobacillus species dominate in a healthy vagina and are associated with cervicovaginal health. Disruption of the microbial status quo — notably during menopause — is associated with disease. Hormone replacement therapy (HRT), however, has shown to improve the vaginal microbiome:

Vaginal estradiol (E2) tablets resulted in substantial changes in the VM and metabolome with a lowering in pH, particularly in women with high-diversity bacterial communities at baseline.
Low pH moisturizer or placebo did not significantly impact the vaginal microbiota or metabolome despite lowering the vaginal pH.
Estradiol use may offer additional genitourinary health benefits to postmenopausal women.
A small randomized clinical trial of a vaginal probiotic in postmenopausal women found short-term decreases in proinflammatory gene pathways with increased vaginal lactobacilli.
A 2020 study conducted on 228 premenopausal women suggested that daily administration of a vaginal dose of Lactobacillus crispatus, after treatment with vaginal metronidazole, can reduce recurrence of bacterial vaginosis after 12 weeks.¹

Menopause, VM and Urinary Health

Decrease in lactobacillus results in an elevated vaginal pH and higher microbial diversity. Decreased levels may also cause vaginal epithelium atrophy (thinning of the vaginal epithelium), dyspareunia (painful intercourse), dysuria (pain when urinating) and other genitourinary symptoms of menopause (GSM), due in part from the changes in the local microenvironment.

GSM affects approximately 50% of postmenopausal women. A 2013 cross-sectional study (n = 87) showed that women with signs of mild or moderate vulvovaginal atrophy (VVA) had greater odds of having highly diverse microbiota depleted of lactobacilli than microbiota dominated by L. crispatus when compared to women with no VVA.
Use of HRT in menopause indicates the reversion of lactic acid bacteria (LAB) microbial diversity to premenopausal levels; use of HRT has also shown not to increase the prevalence of bacterial vaginosis in postmenopausal women.
Postmenopausal women have been found to display significantly lower levels of free glycogen than premenopausal women.²

Benefits of Estriol

A study on the effect of ultra-low dose estriol vaginal tablets (0.03 mg) and Lactobacillus acidophilus compared to placebo was investigated in 87 postmenopausal women. The instillation of lactobacilli and ultra-low dose estriol was found to significantly improve the vulvovaginal symptoms in these women.

A second study was conducted on 60 postmenopausal women, who were randomly assigned to receive oral isoflavone alone, isoflavone plus probiotic or hormonal replacement therapy (1 mg estradiol and 0.5 mg norethisterone acetate). After 16 weeks, the hormonal therapy group showed an increased number of lactobacilli in the vagina, similar to that seen in premenopausal state, and a decrease in vaginal pH. Conversely, no change in pH value was found in the isoflavone group and isoflavone plus probiotic group.¹

Impact of Progesterone on the VM

DMPA injection reduced total bacterial load and abundance of Gardnerella vaginalis.
Localized progesterone contraceptive also reduced lactobacillus abundance.
Progesterone inhibits vaginal epithelium proliferation. Lack of epithelial-derived glycogen in a progesterone-enriched environment may reduce lactobacillus and other bacterial abundance.
Due to increased levels of endogenous estrogen and progesterone during pregnancy, the contributions of exogenous progesterone may be obscured in pregnant women.¹

Additional Influences

The intestinal microbiota have a role in shaping the vaginal microbiota. Both are formed throughout the stages of development and are influenced by lifestyle, use of antibiotics and hormones; both produce metabolites that help guide the immune system to be tolerogenic (producing immunological tolerance) or pro-inflammatory. The use of antibiotics can have long lasting negative impacts on a person’s microbiome and promote chronic disease development. Various forms of oral, vaginal or fecal transplanted probiotics can help to influence disease states.

Interested in learning more?

Attend the July 18-19 HRT Virtual Conference, Winning with Weight Loss, Detox and the Microbiome. This highly engaging symposium features a lineup of experts shaping the field of HRT — including: Dr. Briggs; Carrie Jones, ND; Pamela Smith, MD, MPH, MS; Daniel Banov, RPh, MS; Sara Hover, RPh, FAARM; and Ranel Larson, PharmD.

References

Auriemma, R.S., Scairati, R., del Vecchio, G., et al. (2021). The Vaginal Microbiome: A Long Urogenital Colonization Throughout Woman Life. Front. Cell. Infect. Microbiol. 11. Sec. Microbiome in Health and Disease. Accessed July 2021 at https://www.frontiersin.org/articles/10.3389/fcimb.2021.686167/full
Meštrović, T., Matijašić, M., Perić, M., et al. (2020). The Role of Gut, Vaginal, and Urinary Microbiome in Urinary Tract Infections: From Bench to Bedside. Diagnostics (Basel, Switzerland), 11(1), 7. Accessed December 2020 at https://pubmed.ncbi.nlm.nih.gov/33375202/

SubMagna™ SL HMW: Delivery of APIs — Sublingually

Wed, 27 Mar 2024 17:48:08 GMT

by Christine Vu, BS, PCCA Senior Scientist/R&D Product Analyst

The PCCA Research & Development (R&D) team constantly explores innovative ways to help meet the unique needs of patients. Using a multi-disciplinary approach, we developed SubMagna SL HMW, a self-emulsifying, sublingual delivery system, to accommodate a wide range of drugs with varying molecular weights — including those with a high-molecular weight. This innovative base is another way PCCA helps to fill the unmet needs of patients, prescribers and compounding pharmacies.

Oftentimes, commercially available medications are designed as a one-size-fits-most solution; however, not all patients can tolerate commercially manufactured drugs. These patients need personalized options made available from compounding pharmacies.

Addressing the gap between available drugs and how they are delivered to patients is yet another way compounding helps solve medication challenges. Many pharmaceutical researchers are now focusing on developing high-molecular weight (HMW) therapeutics. Yet delivery methods for HMW drugs may pose additional challenges for patients and their healthcare providers. SubMagna SL HMW can help compounders provide a solution to these and other challenges.

Drug Delivery Systems

New and emerging technologies in pharmaceutical drug delivery systems (DDSs) are focused on HMW therapeutics — such as proteins and peptides — due to their high specificity and potency.¹ However, HMW substances pose several challenges. For example, peptides and proteins are susceptible to proteolytic degradation and their large, bulky structures make penetrating the skin to reach systemic circulation extremely difficult.²Due to these and other factors, parenteral injection is the most common route of administrating HMW drugs.^3,4

Recognizing the advanced technologies and the potential to meet the needs of unique patients, our PCCA R&D team spent a considerable amount of focused effort exploring new DDS options. In addition to overcoming the challenges of HMW penetration, we also sought to create an anhydrous base with the potential for longer beyond-use dates (BUDs) — which adds greater efficiencies to compounding pharmacies and may improve patient compliance by limiting trips to the pharmacy for medication refills.

After extensive exploration, we concluded that a sublingual route presented an innovative method to deliver HMW compounded medications.

Sublingual Dosage Forms

Sublingual dosage forms are administered under the tongue to deliver drugs rapidly and directly into the systemic circulation by reaching the superior vena cava through the venous drainage located in the external carotid artery (see Figure 1).⁵

Figure 1. Overview of salivary glands shows the SLG (sublingual gland), SMG (submandibular gland) and the external carotid artery.⁶

After selecting the type of base vehicle, we began researching how to facilitate molecular transport through the sublingual mucosa. We quickly realized that the distinct structure and features of micelles mimic human epithelia. As seen in Figure 2, phospholipids with hydrophilic heads and hydrophobic tails form the outer vesicle wall around an aqueous core. We hypothesized that characteristics of the drug molecule could be incorporated into different parts of the micelle.

Figure 2. The phospholipids with hydrophilic heads and hydrophobic tails will self-assemble into this spherical shape when thermodynamic conditions are favorable.⁷

Final Formulation & Testing

Due to the extensive knowledge and skillsets of our R&D team, we formulated a vehicle using carefully chosen ingredients that could self-assemble when interacting with saliva.

While selecting the proper ingredients is an important component in formulation science, developing the right type of micellar structure is even more critical, as it needs to be formulated in such a way that must consider thermodynamic conditions to encourage the formation of these artificial vesicles.

After we felt confident in the formulation, our R&D team conducted tests to verify that all formulation goals were achieved. We conducted a test using fluorescence microscopy, which confirmed that the formulation would indeed create a uniform micellar structure (see Figure 3).⁸

Figure 3. Fluorescence microscopy: GFP 0.1 mg/mL in SubMagna using blue light at 40x magnification. The white arrow indicates the formation of one uniform micelle.⁹

Our R&D team also conducted in vitro testing to understand the potential of HMW molecules penetrating through the sublingual mucosa. The study concluded that SubMagna SL HMW could deliver a peptide into and through the human gingival and oral phenotypic tissues.¹⁰

PCCA members may access the scientific technical report, which contains details of all testing performed on SubMagna SL HMW, after logging on to our Members-Only Website. PCCA members with clinical services access may contact our Clinical Services team to answer any questions about SubMagna, as well as other compounding concerns.

We also invite you to watch our free SubMagna webinar to learn more.

References

Jain K. K. (2020). An Overview of Drug Delivery Systems. Methods in molecular biology (Clifton, N.J.), 2059, 1–54. Accessed February 2024 at https://doi.org/10.1007/978-1-4939-9798-5_1
Lian, Z., & Ji, T. (2020). Functional peptide-based drug delivery systems. Journal of materials chemistry. B, 8(31), 6517–6529. Accessed February 2024 at https://doi.org/10.1039/d0tb00713g
Bajracharya, R., Song, J. G., Back, S. Y., & Han, H. K. (2019). Recent Advancements in Non-Invasive Formulations for Protein Drug Delivery. Computational and structural biotechnology journal, 17, 1290–1308. Accessed February 2024 at https://doi.org/10.1016/j.csbj.2019.09.004
U.S. Food & Drug Administration Center for Drug Evaluation and Research (CBER). 2023 Biological Approvals. Accessed February 2024 at https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber/2023-biological-approvals
Hua S. (2019). Advances in Nanoparticulate Drug Delivery Approaches for Sublingual and Buccal Administration. Frontiers in pharmacology, 10, 1328. Accessed February 2024 at https://doi.org/10.3389/fphar.2019.01328
Vining, K.H., Hoffman, M.P. (2014). Anatomy, Biogenesis and Regeneration of Salivary Glands. Monographs in Oral Science 24: 1-13. Open Access Publication. Accessed February 2024 at https://doi.org/10.1159/000358776
Cimino C., Maurel O.M., Musumeci T., et al. (2021). Essential Oils: Pharmaceutical Applications and Encapsulation Strategies into Lipid-Based Delivery Systems. Pharmaceutics 13:327. Open Access Publication. Accessed February 2024 at https://doi.org/10.3390/pharmaceutics13030327
PCCA Science Technical Report (2024). Evaluation of SubMagna™ SL HMW Micellar Formation using Florescence Microscopy. PCCA Document #100069
PCCA Science Technical Report (2024). Evaluation of SubMagna™ SL HMW Micellar Formation using Florescence Microscopy. PCCA Document #100069
PCCA Science Technical Report (2024) Evaluation of the Absorption of a Sublingual Semaglutide Compounded Formulation (SubMagna™ SL HMW) using the EpiGingival™ and EpiOral™ In Vitro Tissue Models. PCCA Document #100068

Working with Methylene Blue: Best Practices for Compounding and Cleanup

Thu, 15 Feb 2024 00:56:45 GMT

by Stacey Lemus, BS, PCCA Senior Formulation Specialist and Project Manager

Pro Tips for Compounding Methylene Blue

Preparation and focus is key to achieving positive results. Prior to compounding with methylene blue, line your hood work surface with spill mats or low-lint disposable towels to contain any spills. Work slowly and diligently.

Your containment ventilated enclosure (CVE), when certified, has a specific airflow range to meet best practice standards. If you notice excess pull of weighing paper or powders toward the back of the hood while compounding, consider having your CVE certification company check the airflow parameters. It may also be helpful to adjust the airflow to the lower end of the range of the best practices standard. This may drastically reduce the amount of powder residue that can stain your CVE and balance.

When mixing topical formulations using an electronic mortar and pestle (EMP), single-use disposable mixing blades are a great option. PCCA carries a variety of sizes to accommodate different EMP jar sizes (PCCA #35-2449, #35-2450, #35-2451). These are compatible with detachable shafts (PCCA #35-2452). The single-use blades are twisted on to the end of the shaft and are easy to remove after mixing for disposal.

Methylene blue powder requires pulverizing to make powder capsules, oil-based capsules or oil suspensions. We advise using a glass mortar and pestle. Other mortars, such as ceramic or plastic, are made of more porous materials that are prone to staining.

Pro Techniques for Cleaning After Compounding Methylene Blue

We suggest rinsing all equipment and devices immediately after use with isopropyl alcohol and cleaning it with an EPA-registered cleaning agent that is suitable for the equipment.

We also suggest following these clean-up tips after compounding powder capsules:

After properly rinsing all equipment and devices, prepare a clean surface inside the hood.
Set up a designated plastic tub in the hood containing enough isopropyl alcohol 70% to cover the plates.
Carefully submerge the capsule machine plates into the plastic basin.
Stage the bin and contents outside of the hood using proper technique.
Allow three (3) minutes of soaking.
Pour out the rinsing alcohol into an appropriate container for disposal and refill with fresh alcohol (barely cover).
Move the container gently from side to side, while on the counter, to facilitate removal of the staining inside the holes.
If necessary, repeat steps 6 and 7, allowing three (3) minutes of soaking in between.

Remember, powder capsules are not the only methylene blue formulation. Get innovative! Explore alternate formulations, such as oil capsules, to avoid tricky dosage forms. Powder capsules can be messy to compound, and compounding oil-filled capsules is a great way to avoid excess cleanup.

We’re here to assist you!

PCCA members may access PCCA Play training videos on techniques for compounding oil capsules. Members with clinical services may contact our Clinical Services team for help when compounding methylene blue and for other compounding questions.

Access the free webinar, Navigating the Lab with Methylene Blue — Compounding Techniques and Best Practices, on PCCA Play.

THE PCCA BLOG

Know Pain, Know Gain

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Part I: The Latest in Pain Neuroscience

Part II: Translating Science into Non-Pharmacologic Care

The Power of Words

Sublingual Semaglutide: Dosing Considerations, Patient Care and Regulatory Insights

Sublingual Semaglutide: Dosing Considerations, Patient Care and Regulatory Insights

Why Sublingual Semaglutide?

Best Practices for Sublingual Administration

Pro Tips for Better Absorption:

Dosing Strategies: Start Low, Go Slow

Beyond Weight Management

Patient Considerations and Monitoring

Regulatory Insights: Staying Compliant

Individualized Care is Essential

Final Thoughts

Illuminating Stealth Syndromes

Summary of Syndromes

MCAS (Mast Cell Activation Syndrome)

POTS (Postural Orthostatic Tachycardia Syndrome)

EDS (Ehlers-Danlos Syndrome)

Compassion and Concern: The LDN Research Trust

Help Spread Awareness

Watch the compelling trailer for “Understanding Stealth Syndromes”. Click Here.

To purchase one or more licenses for the documentary, Click Here.

References

Bacterial Vaginosis: A Persistent Challenge

Common and Uncommon Pathogens

Diagnosis and Compounding Options

Ellage® Anhydrous Vaginal: The Base of Choice

References

Importance of Content Uniformity in Suspensions

Liquid Suspensions and Content Uniformity

The Superior Liquid Vehicle

Competitor Suspension vs. SuspendIt

References

Balance Hormones and Grow Your Practice

Introducing PCCA Master Courses: HRT

Earn Your Certified Master Designation in HRT

References

Penetrating the Nail Fungus Market with EctoSeal P2G™

Beyond Basic: EctoSeal P2G

Onychomycosis

EctoSeal P2G Study

References

Microdosing GLP-1 RAs: Fad or Forever?

Looking Back on GLP-1 RAs

Potential Benefits of GLP-1 RAs

What Is Microdosing?

Endogenous GLP-1 vs. Exogenous GLP-1 RAs

Microdosing GLP-1 RAs

References

What’s in Store at the LDN Virtual Conference

The Immune System — Autoimmune Conditions and the Benefits of LDN

Dermatological Inflammatory Diseases and LDN

The Use of LDN in Veterinary Patients

Perimenopause and Menopause Are Inflammatory Conditions: The Use of LDN for Hormones and Weight Loss

Using LDN for Chronic Pain Conditions

LDN for Gut Inflammatory Disorders

How to Market LDN Studies

A Personalized Approach to HRT for Perimenopausal Women

Understanding Estrogen Levels in Perimenopause

The Role of Cortisol in Perimenopausal Health

Progesterone: The Balancing Hormone

Benefits of a Personalized HRT Approach

References

Backed by Science: Anhydrous VersaBase® HRT

In Vitro Evaluation of the Percutaneous Absorption of Progesterone in Anhydrous Permeation-Enhancing Base Using the Franz Skin Finite Dose Model and Mass Spectrometry

What does the study say?

What do the results of the study mean to prescribers and physicians?

What do the results mean to patients?

What does anhydrous mean and why is that important?

Progesterone: Size Matters

Low-Dose Naltrexone in the Oncology Setting

Understanding TLR Signaling and Inflammation

LDN: A New Perspective in Oncology

Mechanisms of Action

Low vs. Standard Dose

Promising Preclinical Evidence

Ellage^® Anhydrous Vaginal: The Base of Choice