Fast dissolution of poorly water soluble drugs from fluidized bed coated nanocomposites: Impact of carrier size

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• 作者：Mohammad Azad¹ ; Jacqueline Moreno ; Ecevit Bilgili ; Rajesh Davé ; ; ^{dave@njit.edu" class="auth_mail" title="E-mail the corresponding author} ; ^{rajndave@gmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Poorly water soluble drug ; Wet-stirred media milling ; Fluidized bed coating ; Fine vs large carrier particles ; Thick vs thin polymer coating ; Fast dissolving nanocomposite powders
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：20 November 2016
• 年：2016
• 卷：513
• 期：1-2
• 页码：319-331
• 全文大小：7011 K

文摘

Formation of core-shell nanocomposites of Fenofibrate and Itraconazole, model poorly water soluble drugs, via fluidized bed (FB) coating of their well-stabilized high drug loaded nanosuspensions is investigated. Specifically, the extent of dissolution enhancement, when fine carrier particles (sub–50 μm) as opposed to the traditional large carrier particles (>300 μm) are used, is examined. This allows testing the hypothesis that greatly increased carrier surface area and more importantly, thinner shell for finer carriers at the same drug loading can significantly increase the dissolution rate when spray-coated nanosuspensions are well-stabilized. Fine sub–50 μm lactose (GranuLac^® 200) carrier particles were made fluidizable via dry coating with nano-silica, enabling decreased cohesion, fluidization and subsequent nanosuspension coating. For both drugs, 30% drug loaded suspensions were prepared via wet-stirred media milling using hydroxypropyl methyl cellulose and sodium dodecyl sulfate as stabilizers. The stabilizer concentrations were varied to affect the milled particle size and prepare a stable nanosuspension. The suspensions were FB coated onto hydrophilic nano-silica (M-5P) dry coated sub-50 μm lactose (GranuLac^® 200) carrier particles or larger carrier particles of median size >300 μm (PrismaLac^®40). The resulting finer composite powders (sub-100 μm) based on GranuLac^® 200 were freely flowing, had high bulk density, and had much faster, immediate dissolution of the poorly water-soluble drugs, in particular for Itraconazole. This is attributed to a much higher specific surface area of the carrier and corresponding thinner coating layer for fine carriers as opposed to those for large carrier particles.