Compound A, a weak base molecule, is a BCS class 2 drug with highly pH dependent solubility. It's very soluble in gastric pH but has extremely low solubility in the intestinal pH causing a rapid precipitation. The significant pH solubility difference could cause an impact on pK performance during co-dosing with acid-reducing agents (ARAs). Multiple formulation strategies, such as on-site suspension, direct compressed tablets, and amorphous solid dispersion (ASD), were developed to tackle the drug delivery and enhance the its bioavailability. Various in vitro biorelevant dissolution techniques were employed to evaluate these formulations. Predictive biorelevant dissolutions guided the formulation development and selection successfully to support clinical study. Both regular two stage biorelevant dissolution (SGF-FaSSIF) and a dissolution mimicking ARA effect was utilized to assess the in-vitro release of different formulations. ASD formulations and acidified conventional formulations exhibited superior performance than other formulations of Compound A.
Learning Objectives:
Upon completion, participant will be able to describe the challenges of drug delivery and bioavailability of weak base molecules in different formulations.
Upon completion, participant will be able to conduct predictive in vitro dissolution to evaluate the performance of weak base in different formulations under normal and ARA biorelevant conditions.
Upon completion, participant will be able to compare conventional and amorphous solid dispersion formulations to support formulation development.