Crosslinked gelatin pastilles prepared via maillard reaction as oral dosage form of ionic liquid pharmaceuticals

Ionic liquid pharmaceuticals (ILP) represent a new class of pharmaceuticals that can circumvent the issues of low aqueous solubility and polymorphism prevalent in pharmaceutical crystals. Due to their highly viscous and hygroscopic nature, ILPs must be formulated into solid dosage forms to ensure their shelf-life stability and dosing accuracy. Gelatin is widely used as carrier matrix for ILPs owed to its high compatibility with various ILPs. Gelatin-based dosage forms, however, exhibit poor storage stability, thereby necessitating reinforcement of the gelatin matrix. The present work investigated the feasibility of employing Maillard reaction (MR)-mediated crosslinking of gelatin with sugars to enhance the storage stability of chewable ILP-loaded gelatin pastilles, while simultaneously conferring taste-masking properties to them. Ionic-liquid pair of poorly-soluble drug ibuprofen (IBU) and 1-butyl-3-methylimidazolium (BMIM) was used as the model ILP. The effects of the degree of gelatin crosslinking, which was modulated by stevia: glucose ratio, on the quality attributes (e.g., dosage uniformity, IBU-BMIM release) and storage stability of the pastilles were evaluated. The results showed MR-mediated crosslinking preserved the liquid-like form of IBU-BMIM in the pastilles, without adverse effect on IBU-BMIM content (≈30 wt%) and its entrapment efficiency (>95 wt%). The pastilles prepared at stevia: glucose = 75:25 (w/w) exhibited 80 wt% IBU-BMIM release after 120 min (intact dosage), high dosage uniformity, and comparable texture/taste profiles as commercial chewable drug tablets. Importantly, the pastilles exhibited good stability after one-month accelerated storage (40°C and 75% relative humidity), as reflected by minimal changes in their quality attributes and high microbiological safety.