SubOral™ SL HMW Anhydrous Sublingual Vehicle (Cool Mint)

• Anhydrous water-soluble formulation enabling extended BUDs for a wide spectrum of prescriptions
• Employs functional ingredients for large and small molecular weight compounds to be administered sublingually
• Rapidly forms an occlusive hydrogel emulsion when exposed to saliva for improved bioavailability
• Water based hydrogels vs. oil-based vehicles offer several advantages for sublingual delivery:
  • Superior bioadhesion⁸ and hydration potential for improved bioavailability via oral mucosal tissue delivery with a wide range of molecular weight actives
  • Several oral delivery studies show water-soluble sublingual vehicles offer up to 5 times⁹ more bioavailability than oil-soluble formulations
  • Water-soluble properties allow for precise, uniform dosing without separation issues common in oil-based emulsions
  • Ability to target a precise pH to maintain stability and solubility
  • Taste, texture, and palatability are widely accepted
  • Generally hypoallergenic and less likely to cause irritation than some oil sources
•  Formulated with a unique dual NADES and NPTS system that assists with solubilization and enhances penetration, leading to improved bioavailability
• Promotes the unfolding of functional proteins and peptides, preventing aggregation more effectively than other systems for improved bioavailability
• Can be easily formulated with Salcaprozate Sodium (SNAC) due to its water-soluble properties
• Formulated to improve the solubility of poorly soluble drugs
• Ideally formulated for both HMW therapeutic biomolecules (peptides/proteins) as well as small molecular drugs (APIs)
• Can be homogenized without base degradation
• Ideal pH that mimics the natural oral mucosa pH
• Incorporates an Oral Osmotic System (OROS) with a widely used tonicity agent
• Stable suspension properties formed through a unique microgel network
• Improved protein stabilizing properties
• Sugar-free; utilizes only natural sweeteners
• For oil and water-soluble small and large molecules
• Occlusive bio-adhesive properties for prolonged absorption advantages
• Excellent suspension properties to improve drug loading capacity and increase the overall bioavailability of the medication
• Demonstrated great taste for prolonged sublingual absorption leading to improved patient compliance and satisfaction
• Allergen-free/gluten-free
• Water and oil miscible flavor ready
• Incorporates our proprietary Bitter-Bloc™ Technology for optimal palatability

Natural Deep Eutectic Solvents (NADES) and Therapeutic Deep Eutectic Systems (THEDES):

Several studies¹²³⁴ have demonstrated that certain hydrated Deep Eutectic Solvents (DESs) can interact with intercellular lipids, creating wider water channels between lipid vesicles, enhancing the paracellular-like transport of hydrophilic compounds. This can be very effective through oral mucosa, a highly vascularized thin membrane. DESs and their specialized derivatives, Therapeutic Deep Eutectic Systems (THEDES), effectively increase the permeability of biological barriers⁵ (such as the skin, intestinal wall) to various agents, including drugs, proteins, and nanoparticles. Their function leads to higher solubility and superior penetration through biological tissues. DESs enhance the systemic absorption⁶ of subcutaneously injected therapeutic proteins (such as insulin) or larger proteins/peptides by reducing interactions with the subcutaneous matrix, a mechanism that can involve modulating the transport pathways. In essence, the unique properties of a DES can be leveraged in drug delivery systems to open or widen the paracellular route temporarily and reversibly⁷, allowing for improved absorption of drugs that would otherwise struggle to cross epithelial barriers.

¹National Library of Medicine, Penetration Process of a Hydrated Deep Eutectic Solvent Through the Stratum Corneum and its Application as a Protein Penetration Enhancer. https://pmc.ncbi.nlm.nih.gov/articles/PMC7493194/

²MDPI Journal, Advancements in Therapeutic Deep Eutectic Solvents as Multifunctional Transdermal Delivery Systems. https://www.mdpi.com/1999-4923/18/3/360

³International Journal of Pharmaceutical Sciences, Deep Eutectic Solvents as Solubility Enhancers: A Systematic Review. Volume 03 | Issue 10 | Article Id IJPS/250310415

⁴International Journal of Pharmaceutical Sciences, Development and In Vitro Evaluation of a Deep Eutectic System to Improve Cefuroxime Axetil Solubility by Enhancing the Dissolution. Volume 03 | Issue 12 | Article Id IJPS/250312253

⁵MDPI Journal, Deep Eutectic Systems as Novel Vehicles for Assisting Drug Transdermal Delivery. https://www.mdpi.com/1999-4923/14/11/2265

⁶Wiley Advanced Science, Deep Eutectic Solvents for Subcutaneous Delivery of Protein Therapeutics. https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202205389

⁷ScienceDirect, Deep eutectic solvents@enteric technology for orally delivering anticoagulant macromolecule drug. https://www.sciencedirect.com/science/article/pii/S2211383525007178?via%3Dihub

⁸ScienceDirect, Mucoadhesion, hydration and rheological properties of non-aqueous delivery systems (NADS) for the oral cavity. https://www.sciencedirect.com/science/article/abs/pii/S0300571208000274?via%3Dihub

⁹True North Labs, April 24, 2024, Water-soluble or Oil-Soluble Cannabinoids: Exploring mechanisms of absorption, bioavailability, and fat solubility of cannabis products. https://www.truenorthlabs.ch/news/water-soluble-vs-oil-soluble-cannabis-products-key-differences-and-why-they-matter#:~:text=Water%2Dsoluble%20powder%20has%20been,with%20a%20high%2Dfat%20meal

¹⁰National Library of Medicine / International Journal of Nanomedicine. 2007 Dec;2(4):735–741. PEGylation of nanoparticles improves their cytoplasmic transport.  https://pmc.ncbi.nlm.nih.gov/articles/PMC2676827/