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by Christine Vu, BS, PCCA Senior Scientist/R&D Product Analyst
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.
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.2 Due 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 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 liposomes 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 liposome.
Figure 2. Structure of a liposome. The phospholipids with hydrophilic heads and hydrophobic tails will self-assemble into this spherical shape when thermodynamic conditions are favorable.7
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 a liposome 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 liposomes (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 formation of one liposome.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
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.