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通过低温强制对流快速干燥载有疏水性药物纳米颗粒的生物相容性聚合物薄膜。

Fast drying of biocompatible polymer films loaded with poorly water-soluble drug nano-particles via low temperature forced convection.

机构信息

Department of Chemical, Biochemical, and Pharmaceutical Engineering, New Jersey Institute of Technology, USA.

出版信息

Int J Pharm. 2013 Oct 15;455(1-2):93-103. doi: 10.1016/j.ijpharm.2013.07.051. Epub 2013 Jul 31.

Abstract

Fast drying of nano-drug particle laden strip-films formed using water-soluble biocompatible polymers via forced convection is investigated in order to form films having uniform drug distribution and fast dissolution. Films were produced by casting and drying a mixture of poorly water soluble griseofulvin (GF) nanosuspensions produced via media milling with aqueous hydroxypropyl methylcellulose (HPMC E15LV) solutions containing glycerin as a plasticizer. The effects of convective drying parameters, temperature and air velocity, and film-precursor viscosity on film properties were investigated. Two major drying regimes, a constant rate period as a function of the drying conditions, followed by a single slower falling rate period, were observed. Films dried in an hour or less without any irreversible aggregation of GF nanoparticles with low residual water content. Near-infrared chemical imaging (NIR-CI) and the content uniformity analysis indicated a better drug particle distribution when higher viscosity film-precursors were used. Powder X-ray diffraction showed that the GF in the films retained crystallinity and the polymorphic form. USP IV dissolution tests showed immediate release (~20 min) of GF. Overall, the films fabricated from polymer-based suspensions at higher viscosity dried at different conditions exhibited similar mechanical properties, improved drug content uniformity, and achieved fast drug dissolution.

摘要

为了形成具有均匀药物分布和快速溶解特性的薄膜,研究了通过强制对流快速干燥由水溶性生物相容聚合物形成的载纳米药物颗粒的条带薄膜。通过介质研磨制备的疏水性灰黄霉素(GF)纳米混悬液与含有甘油作为增塑剂的羟丙基甲基纤维素(HPMC E15LV)水溶液混合,浇铸并干燥制备薄膜。考察了对流干燥参数(温度和空气速度)和薄膜前体粘度对薄膜性能的影响。观察到两个主要的干燥阶段,即与干燥条件相关的恒速阶段,随后是单一的较慢下降速率阶段。在一小时内干燥而不发生 GF 纳米颗粒不可逆聚集,且残留水分含量低。近红外化学成像(NIR-CI)和含量均匀度分析表明,使用更高粘度的薄膜前体时,药物颗粒分布更好。粉末 X 射线衍射表明,薄膜中的 GF 保留了结晶度和多晶型形式。USP IV 溶出度测试表明 GF 即刻释放(~20 分钟)。总体而言,在不同条件下由基于聚合物的悬浮液制备的高粘度薄膜表现出相似的机械性能、改善的药物含量均匀度,并实现了快速药物溶解。

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