Sub-100 micron fast dissolving nanocomposite drug powders

• Geldart group C carrier particles were silica dry-coated to enable fluidization.
• Stabilized fenofibrate (drug) nanosuspensions were produced via wet media milling.
• Fluid bed coating of suspensions onto the carrier led to sub-100 μm nanocomposites.
• The nanocomposite powder is free-flowing and exhibits very fast drug dissolution.
• Formulation and water solubility of the carrier affected redispersion/dissolution.

This study focuses on the preparation of sub-100 μm 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-50 μm). This is in contrast to conventional FB coating processes that utilize carrier particles as large as 850 μm resulting in much larger final nanocomposites. Fluidization and subsequent FB processing of sub-50 μm, 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 100 μm, 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.

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