Improving dissolution kinetics of pharmaceuticals by fluidized bed impregnation of active pharmaceutical ingredients

摘要

Investigational drugs are increasingly becoming less soluble in aqueous media, thus, presenting real challenges during development. Previous work has successfully demonstrated the manufacturing of pharmaceuticals using fluidized bed (FB) impregnation of APIs onto porous carriers. This study demonstrates the usefulness of FB impregnation in formulating poorly soluble drugs. We show that dissolution of Fenofibrate is greatly improved by FB impregnation onto Neusilin((R)) (Fuji Health Science Inc, Burlington, NJ USA), a synthetic amorphous form of magnesium alumino-metasilicate. We impregnate Neusilin((R)) for range of loadings and examine Fenofibrate's physical state. Dissolution of impregnated formulations is drug loading dependent and loadings below 40% show great improvement (decrease) in release time compared to physical blend. Release times are further improved by milling. We also examine feasibility of coimpregnating Fenofibrate with additives and observe stability (1.5 years) of the amorphous form of Fenofibrate inside Neusilin((R)). This stabilization significantly improves Fenofibrate's dissolution kinetics, making our formulation comparable to one of the current market formulations, TriCor((R)) tablets (AbbVie Inc, North Chicago, IL USA). (c) 2016 American Institute of Chemical Engineers AIChE J, 62: 4201-4214, 2016