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

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.

THE PCCA BLOG

SubMagna™ SL HMW: Delivery of APIs — Sublingually

Drug Delivery Systems

Sublingual Dosage Forms

Final Formulation & Testing