Sub-100 micron fast dissolving nanocomposite drug powders

Abstract

This study focuses on the preparation of sub-100μm freely flowing yet fast dissolving core–shell nanocomposite powders via fluidized bed (FB) coating of poorly water-soluble drug nanosuspensions onto fine carrier particles (sub-50μm). This is in contrast to conventional FB coating processes that utilize carrier particles as large as 850μm resulting in much larger final nanocomposites. Fluidization and subsequent FB processing of sub-50μm, Geldart group C powders, is a major technological barrier, which can be overcome by either increasing the body weight of the powders, or decreasing their cohesion. Here, the latter is considered as a practical way to enhance fluidization, accomplished through applying a discrete, fairly uniform layer of nano-sized silica particles onto the surface of the cohesive host particles dry coating. Fenofibrate was considered as a model poorly water-soluble drug, and was wet-milled in a stirred media mill and stabilized via an optimized polymer and surfactant combination. The nanoparticle suspensions were then coated onto hydrophilic nano-silica (M5P) coated sub-50 micron lactose (Granulac® 200) or potato starch carrier particles in a FB process. Their coating with drug particle nanosuspensions was achieved without appreciable agglomeration, which is a major novelty of this work. In spite of having a median particle size well under 100μm, the resulting final composite powders were freely flowing, had high bulk density, and allowed for fast dissolution of a poorly water-soluble drug in comparison to either micronized or nano-milled drug along with the same excipients in physical mixtures.