Physicochemical attributes and dissolution testing of ophthalmic ointments
Physicochemical attributes and dissolution testing of ophthalmic ointments
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DOI：
10.1016/j.ijpharm.2017.03.039
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发表时间：
2017-05-15
影响因子：
5.8
通讯作者：
Burgess, Diane J.
中科院分区：
文献类型：
--
作者：
Bao, Quanying;Jog, Rajan;Burgess, Diane J.
半固体眼软膏由于其复杂的物理化学性质和人眼独特的解剖结构而具有挑战性。以Lotemax (R)为模型眼药膏，采用三种不同的生产工艺和两种辅料来源(Fisher (R) （OWP）和Fougera （R) (NWP)）制备了在各制剂中定性和定量相同的他巴酸洛替尼软膏。研究了药物的理化性质，包括药物含量和均匀性、粒径和分布，以及流变参数（起始点、交叉模量、储存模量和幂律一致性指数）。此外，利用增强细胞USP仪器2研究了该眼膏的体外释药特性。制备工艺和辅料来源对软膏的理化性质和体外释药特性均有显著影响。通过热熔法制备的软膏与没有热熔法制备的软膏相比，具有更高的流变参数和更低的药物释放率。与NWP制备的软膏相比，用OWP制备的软膏具有更高的流变学参数和更低的体外药物释放率。用对数线性回归分析表明，流变学参数与体外药物释放率有较强的相关性。这种相关性可能有助于通过测量的物理化学性质来预测体外药物释放，并在软膏配方开发过程中确定关键的质量属性。(C) 2017 Elsevier B.V.版权所有
The investigation of semisolid ophthalmic ointments is challenging due to their complex physicochemical properties and the unique anatomy of the human eye. Using Lotemax (R) as a model ophthalmic ointment, three different manufacturing processes and two excipient sources (Fisher (R) (OWP) and Fougera (R) (NWP)) were used to prepare loteprednol etabonate ointments that were qualitatively and quantitatively the same across the manufactured formulations. Physicochemical properties including drug content and uniformity, particle size and distribution, as well as rheological parameters (onset point, crossover modulus, storage modulus and Power law consistency index) were investigated. In addition, USP apparatus 2 with enhancer cells was utilized to study the in vitro drug release characteristics of the ophthalmic ointments. Both manufacturing processes and excipient sources had a significant influence on the physicochemical attributes and the in vitro drug release profiles of the prepared ointments. Ointments prepared via the hot melt processes exhibited higher rheological parameters and lower drug release rates compared to ointments prepared without hot melting. Ointments prepared with OWP demonstrated higher rheological parameters and lower in vitro drug release rates compared to ointments prepared with NWP. A strong correlation between the rheological parameters and in vitro drug release rate was shown using logarithmic linear regression. This correlation may be useful in predicting in vitro drug release from measured physicochemical properties, and identifying the critical quality attributes during the development of ointment formulations. (C) 2017 Elsevier B.V. All rights reserved.