Lipid-based coating of supersaturated amorphous solid dispersions: could it represent an approach to improving their physical stability or oral bioavailability?

ABSTRACT Amorphous solid dispersions (ASDs) are widely recognized as an effective formulation strategy to enhance the in vivo performance of poorly water-soluble drugs; however, their broader application is often limited by insufficient long-term physical stability especially if the drug load is higher than the saturation concentration of the drug in the polymer under standard storage temperature conditions. In this study, the objective was to investigate the functional role of a lipid coating in modulating physical stability and in vitro release and bioaccessibility of a supersaturated praziquantel amorphous solid dispersions (ASD-PZQ). ASD-PZQ systems composed of praziquantel and a vinylpyrrolidone–vinyl acetate copolymer was coated using two lipid-based formulations predominantly composed of either beeswax or tristearin. These lipid systems differ in chemical composition, physicochemical characteristics, and biopharmaceutical behavior, particularly with respect to lipid digestibility. Selected additives (surfactants) were incorporated to tailor manufacturability, stability, and coating functionality. As amorphous systems are particularly sensitive to moisture-induced recrystallization, the coated ASDs were deliberately directly exposed to harsh storage conditions, namely excessive humidity (60% RH) and their physical stability was monitored over a six-month period. To better capture the complexity of gastrointestinal processes, the bioperformance of the lipid coating was assessed using an in vitro multicompartmental digestion model. From a stability standpoint, the lipid coating reduced moisture-induced plasticization during storage. In terms of biopharmaceutical performance, ASD-PZQ coated with beeswax-based formulations exhibited enhanced bioaccessibility compared with uncoated ASD-PZQ, whereas tristearin-based coatings resulted in a prolonged drug release profile. Overall, this work demonstrates that a lipid coating on supersaturated amorphous solid dispersions would mitigate key stability challenges associated with ASD development but also enables the introduction of new functional attributes. These findings position lipid-coated ASDs as advanced, multifunctional drug delivery systems for poorly water-soluble compounds and reinforce their relevance as high-value platforms in pharmaceutical research.