One-step preparation of sustained-release ASDs using mesoporous spherical silica

Abstract

Preparing amorphous solid dispersions (ASDs) is one of the most important approaches in formulation studies to improve the oral bioavailability of poorly water-soluble drugs. Although a large number of studies have reported the validity of ASDs, most are focused on immediate-release formulations. Therefore, the principal aim of the present study is to establish a practical approach for preparing a sustained-release ASD pellet using mesoporous spherical silica by a Wurster-type fluidized bed granulator. The mesoporous spherical silica used in the present study has a porous structure with silica of different pore sizes. As a model drug, indomethacin (IND) was layered onto the mesoporous spherical silica in an amorphous state, but a clear difference was found in the degree of amorphization and drug release rate of each kind of silica. Moreover, the dissolution profiles of IND after layering with a pH-independent sustained-release polymer on spherical silicate using a Wurster-type fluidized bed granulator were evaluated. Mesoporous silica, with small pore size, showed an ideal sustained-release profile with much smaller polymer amounts compared with larger-pore-size silica. In this approach, the pore size of mesoporous spherical silica was a very important factor to prepare sustained-release ASDs efficiently and stably.