Characterization of Critical Quality Attributes for Semisolid Topical Drug Products

摘要 迫切需要为外用药物建立质量目标产品简介(QTPP) 并确定关键质量属性(CQA)以开发有意义的产品 以临床表现为基础的药品规格并确保等效性 大多数半固体制剂中参考上市药物(RLD)的安全性和有效性 例如药物/化妆品乳膏、软膏、乳液等展示复合体 流动行为，包括应用高剪切、触变性和 粘弹性可以用测量的方法来描述 这些参数。 大多数半固体系统，如软膏、乳膏、糊剂和凝胶，都是 粘弹性的性质，因为它们在相同的 材料。在这个项目中，我们的目标是改变关键配方和制造 用于识别和定义影响产品的潜在故障模式的参数 性能。 我们将使用有限(使用中)和无限剂量和使用来比较生物利用度 原子力显微镜(AFM)、共焦拉曼和多光子等工具 赋形剂及其制剂对体内外影响的显微镜研究 皮肤。除了BE，我们的目标是定义化妆品等价性(CE)。感官 相似性/外观等效性将通过以下方式定义为关键质量属性 这一过程。

Abstract There is an urgent need to establish Quality target product profile (QTPP) for topical products and identify the Critical Quality Attributes (CQAs) to develop meaningful drug product specifications based on clinical performance and to ensure equivalent safety and efficacy to the Reference Listed Drug (RLD). Most semisolid preparations such as pharmaceutical/ cosmetic creams, ointments, lotions etc. display complex flow behaviour including breakdown on application of high shear, thixotropy and viscoelasticity which can be described by the methods used in measurement of these parameters. Most of the semisolid systems such as ointments, creams, pastes, and gels are viscoelastic in nature as they display both liquid and solid properties within the same material. In this project we aim to vary key formulation and manufacturing parameters to identify and define potential failure mode that effect a products performance. We will compare bioavailability using both finite (in use) and infinite dosing and use tools such as Atomic Force Microscopy (AFM), Confocal Raman and multiphoton microscopy to study the effects of excipients and formulation on in vitro and in vivo skin. Apart from BE we aim to define cosmetic equivalence (CE). Sensorial similarity/cosmetic equivalence will be defined as a critical quality attribute through this process.