Efficient development of high drug loaded posaconazole tablets enabled by amorphous solid dispersion

Abstract

Determining the upper limits of drug loading in amorphous solid dispersion (ASD) with sufficient physical stability and release performance is critical for developing ASD-enabled tablets for poorly soluble drugs. Recent studies have highlighted the utility of the polymer overlap concentration, c*, in maintaining the physical stability of ASD formulations. The present work demonstrates the feasibility of effectively developing high drug loaded ASD tablets using the c* concept as a guide, with posaconazole as the model drug. By incorporating various material sparing formulation technologies, a record high 50% POS loaded tablet with adequate manufacturability and satisfactory dissolution performance was developed using 1.5 g of POS within 14 days. Physical stabilities of the ASD and tablet were maintained for at least 6 months under ambient conditions and 1 month at 40 °C.