Recovery of BCS Class II drugs during aqueous redispersion of core-shell type nanocomposite particles produced via fluidized bed coating
Recovery of BCS Class II drugs during aqueous redispersion of core-shell type nanocomposite particles produced via fluidized bed coating
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DOI：
10.1016/j.powtec.2011.12.066
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发表时间：
2013-02-01
影响因子：
5.2
通讯作者：
Bilgili, Ecevit
中科院分区：
文献类型：
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作者：
Bhakay, Anagha;Dave, Rajesh;Bilgili, Ecevit
将BCS II类药物纳米颗粒掺入固体剂型中需要干燥纳米混悬液作为中间步骤，这可能不幸地导致通过尺寸增长和/或团聚损失其大表面积。在固体剂型的溶解过程中，随后的不完全纳米颗粒回收和再分散可能导致生物利用度差。在这项研究中，从纳米复合材料微粒再分散在水或表面活性剂水溶液中的纳米颗粒回收率作为各种赋形剂的函数进行了研究。灰黄霉素（GF）（被认为是BCS II类药物的模型）的纳米悬浮液通过湿介质研磨制备，随后通过在流化床处理器中涂覆在载体颗粒上干燥。聚合物（羟丙基纤维素，HPC），表面活性剂（十二烷基硫酸钠，SDS），以及它们的组合在各种浓度下被用作稳定剂在研磨过程中，甘露醇被用作分散剂在一个配方。使用各种搅拌方法将从流化床涂布获得的核-壳型纳米复合材料微粒再分散在水中以回收GF纳米颗粒。使用粒度分析、SEM成像和溶出测试来阐明再分散现象及其与溶出的相关性。发现SDS的存在对于纳米颗粒的完全回收及其溶解是关键的，而HPC似乎具有积极但复杂的效果。当SOS存在于制剂或再分散介质（水）中时，研究的再分散方法对纳米颗粒的回收率有轻微影响。纳米颗粒的不完全回收导致相对较差的药物溶出度，表明完全再分散的重要性。HPC-SDS组合导致在形成更细的纳米颗粒以及GF纳米颗粒从纳米复合材料微粒的快速再分散中的协同效应。另一种BCS II类药物保泰松（PHB）也观察到类似的再分散反应。(C)2012 Elsevier B. V.保留所有权利。
Incorporation of BCS Class II drug nanoparticles into solid dosage forms entails drying of nanosuspensions as an intermediate step, which can unfortunately lead to loss of their large surface area through size growth and/or agglomeration. Ensuing incomplete nanoparticle recovery and redispersion during dissolution of the solid dosage forms may lead to poor bioavailability. In this study, nanoparticle recovery from nanocomposite microparticles redispersed in water or an aqueous surfactant solution was investigated as a function of various excipients. Nanosuspensions of griseofulvin (GF), considered as a model BCS Class II drug, were prepared by wet media milling and subsequently dried through coating on Pharmatose (R) carrier particles in a fluidized bed processor. A polymer (hydroxypropyl cellulose, HPC), a surfactant (sodium dodecyl sulfate, SDS), and their combinations at various concentrations were used as stabilizers during milling; mannitol was used as dispersant in one formulation. The core-shell type nanocomposite microparticles obtained from the fluidized bed coating were redispersed in water using various methods of agitation to recover the GF nanoparticles. Particle size analysis, SEM imaging, and dissolution testing were used to elucidate the redispersion phenomenon and its relevance to dissolution. It was found that the presence of SDS was critical to the full recovery of nanoparticles and their dissolution, whereas HPC appeared to have positive yet convoluted effects. The redispersion methods studied had a slight impact on the recovery of nanoparticles when SOS was present either in the formulation or in the redispersion medium (water). Incomplete recovery of the nanoparticles caused relatively poor drug dissolution, signifying the importance of complete redispersion. The HPC-SDS combination resulted in a synergistic effect in the formation of finer nanoparticles as well as in fast redispersion of GF nanoparticles from the nanocomposite microparticles. A similar redispersion response was observed with another BCS Class II drug, phenylbutazone (PHB). (C) 2012 Elsevier B.V. All rights reserved.