Formulation and Quality – Chemical
2019 PharmSci 360
The compendial dissolution testing, due its closed-compartmental setup and lack of absorptive sink conditions, has poor discriminatory power to assess complex formulations, such as supersaturated drug delivery systems. We have recently developed a novel high surface area, flow-through apparatus that integrates dissolution and absorption measurements, providing in vivo relevant information in biorelevant timeframes. The apparatus was utilized to evaluate the performance of amorphous formulations containing residual crystallinity. Residual crystalline content may diminish the oral bioavailability advantage offered by the amorphous formulations due to crystallization of the supersaturated solution. The dissolution-absorption measurements were carried out for formulations with varying % crystallinity and at different dissolution volumes. This is the first in vitro study demonstrating how the residual crystallinity may impact the absorption profiles at different extent of dissolution sink and how drug removal due to absorption may reduce the risk of crystallization, providing a more accurate prediction of formulation performance.