Solidified ionic liquid-based formulations of metformin with enhanced GI epithelial permeability

Active Pharmaceutical Ingredient-Ionic Liquids (API-ILs) can enhance intestinal epithelial membrane permeability of poorly bioavailable APIs, improving bioavailability. However, clinical and commercial application is to date limited due to challenging physical handling properties. Lipid-based formulations (LBFs) are commonly used to enhance intestinal drug absorption but face challenges including low drug-loading capacity and limited stability. To address these issues, a method for transforming liquid API-ILs and LBFs into high-loading solid forms via spray-encapsulation with polymers was developed. Here the method was applied to a lipophilic API-IL of BCS Class III, namely metformin, and multi-component API-IL solutions containing known intestinal permeation enhancers (Labrasol®, docusate). The spray-encapsulated solid formulations exhibited improved handling, self-emulsified in both phosphate buffer (pH 6.8) and fasted state simulated intestinal fluid (FaSSIF), while exhibiting superior in vitro release profiles compared to the liquid formulations. Ex vivo permeability studies on metformin docusate formulations using rat intestinal mucosae in Ussing chambers demonstrated a 2.3- to 6.3-fold increase in permeability (P_app) for solidified formulations, with metformin hydrochloride as the control. Further studies revealed a correlation between docusate concentration and permeability enhancement. These findings highlight the potential of solidified docusate-based lipophilic API-IL formulations to improve membrane permeability of poorly bioavailable APIs.