Amorphous solid systems of poorly water-soluble drugs

Abstract

Most of active pharmaceutical ingredients (API) are poorly water-soluble and shows limited dissolution rate which consequently affects drug absorption rate and bioavailability. This leads to a challenging in product development in pharmaceutical industry. Regarding solid state properties, API can be classified as crystalline and amorphous solids. Most marketed pharmaceutical products consist of crystalline API because of their greater chemical stability as compared to amorphous API. Amorphous solids exhibits a higher dissolution rate which is a desirable pharmaceutical property, however, it will be eventually revert to the most stable crystalline solids because of the higher molecular mobility and thermodynamic activity which can be accelerated by moisture and temperature. Amorphous solid systems with improved dissolution and good stability are desirable for product development. In this study, spray drying, a common manufacturing process, was used to prepare the amorphous systems for poorly water-soluble drugs by two approaches; molecular inclusion complexation using β- cyclodextrin (β-CD) Molecular inclusion complex between dihydroartemisinin (DHA) and β-CD was formed at 1:2 molar ratio and its spray-dried powder showed an amorphous system with dramatically enhanced dissolution rate. It was chemically and physically stable with remained antimalarial activity at 30 °C after 3 months storage. In conclusion, the amorphous systems for poorly water-soluble drugs with improved dissolution rate and good stability were successfully obtained by spray drying process. *