Azad Mohammad, Moreno Jacqueline, Bilgili Ecevit, Davé Rajesh
Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA.
Otto H. York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA.
Int J Pharm. 2016 Nov 20;513(1-2):319-331. doi: 10.1016/j.ijpharm.2016.09.046. Epub 2016 Sep 14.
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-50μm) as opposed to the traditional large carrier particles (>300μm) 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-50μm 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-50μm lactose (GranuLac 200) carrier particles or larger carrier particles of median size >300μm (PrismaLac40). The resulting finer composite powders (sub-100μm) 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.
研究了通过流化床（FB）包衣法制备非诺贝特和伊曲康唑（两种难溶性药物模型）的核壳纳米复合材料，该方法是将稳定良好且载药量高的纳米混悬液进行包衣。具体而言，研究了使用细载体颗粒（小于50μm）与传统大载体颗粒（大于300μm）相比时，溶出度提高的程度。这使得可以验证以下假设：当喷雾包衣的纳米混悬液稳定良好时，在相同载药量下，细载体的载体表面积大幅增加，更重要的是壳层更薄，可显著提高溶出速率。通过用纳米二氧化硅进行干包衣，使小于50μm的乳糖（GranuLac 200）细载体颗粒具有流化性能，从而降低内聚力、实现流化并随后进行纳米混悬液包衣。对于这两种药物，均使用羟丙基甲基纤维素和十二烷基硫酸钠作为稳定剂，通过湿搅拌介质研磨制备30%载药的混悬液。改变稳定剂浓度以影响研磨后的粒径并制备稳定的纳米混悬液。将混悬液通过流化床包衣到亲水性纳米二氧化硅（M-5P）干包衣的小于50μm乳糖（GranuLac 200）载体颗粒或中值粒径大于300μm的较大载体颗粒（PrismaLac40）上。基于GranuLac 200得到的更细的复合粉末（小于100μm）具有良好的流动性、高堆密度，且难溶性药物的溶出速度更快、可立即溶出，尤其是伊曲康唑。这归因于细载体与大载体颗粒相比具有更高的比表面积和相应更薄的包衣层。
