Krull Scott M, Ammirata Jennifer, Bawa Sonia, Li Meng, Bilgili Ecevit, Davé Rajesh N
Otto H. York Department of Chemical, Biological, and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, New Jersey 07102.
Otto H. York Department of Chemical, Biological, and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, New Jersey 07102.
J Pharm Sci. 2017 Feb;106(2):619-628. doi: 10.1016/j.xphs.2016.10.009. Epub 2016 Nov 18.
Recent work established polymer strip films as a robust platform for delivery of poorly water-soluble drug particles. However, a simple means of manipulating rate of drug release from films with minimal impact on film mechanical properties has yet to be demonstrated. This study explores the impact of film-forming polymer molecular weight (MW) and concentration on properties of polymer films loaded with poorly water-soluble drug nanoparticles. Nanoparticles of griseofulvin, a model Biopharmaceutics Classification System class II drug, were prepared in aqueous suspension via wet stirred media milling. Aqueous solutions of 3 viscosity grades of hydroxypropyl methylcellulose (14, 21, and 88 kDa) at 3 viscosity levels (∼9500, ∼12,000, and ∼22,000 cP) were mixed with drug suspension, cast, and dried to produce films containing griseofulvin nanoparticles. Few differences in film tensile strength or elongation at break were observed between films within each viscosity level regardless of polymer MW despite requiring up to double the time to achieve 100% drug release. This suggests film-forming polymer MW can be used to manipulate drug release with little impact on film mechanical properties by matching polymer solution viscosity. In addition, changing polymer MW and concentration had no negative impact on drug content uniformity or nanoparticle redispersibility.
最近的研究表明,聚合物条带薄膜是一种用于递送难溶性药物颗粒的强大平台。然而,尚未证明一种能以最小程度影响薄膜机械性能来控制药物从薄膜中释放速率的简单方法。本研究探讨了成膜聚合物分子量(MW)和浓度对负载难溶性药物纳米颗粒的聚合物薄膜性能的影响。通过湿式搅拌介质研磨在水悬浮液中制备了灰黄霉素(一种生物药剂学分类系统II类药物模型)的纳米颗粒。将3种粘度等级(14 kDa、21 kDa和88 kDa)的羟丙基甲基纤维素在3种粘度水平(约9500 cP、约12000 cP和约22000 cP)的水溶液与药物悬浮液混合、浇铸并干燥,以制备含有灰黄霉素纳米颗粒的薄膜。尽管达到100%药物释放所需时间最多翻倍,但在每个粘度水平内,无论聚合物MW如何,薄膜之间的拉伸强度或断裂伸长率几乎没有差异。这表明,通过匹配聚合物溶液粘度,成膜聚合物MW可用于控制药物释放,而对薄膜机械性能影响很小。此外,改变聚合物MW和浓度对药物含量均匀性或纳米颗粒再分散性没有负面影响。