Characterization of Critical Quality Attributes for Semisolid Topical Drug Products

半固体外用药品关键质量属性的表征

• 批准号: 8857569
• 负责人: Michael Roberts
• 金额: $ 24.98万
• 依托单位: UNIVERSITY OF SOUTH AUSTRALIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-10 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8857569
• 关键词: Characterization; Critical; Quality; Attributes; Semisolid

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.

摘要 目前，迫切需要建立局部用药的质量目标产品概况（QTPP）。 产品，并确定关键质量属性（CQA），以制定有意义的 基于临床性能的制剂质量标准，并确保等效性 安全性和有效性的参考上市药物（RLD）。大多数半固体制剂 例如药物/化妆品霜剂、软膏剂、洗剂等 流动行为，包括应用高剪切、触变性和 粘弹性，其可以通过测量中使用的方法来描述， 这些参数。 大多数半固体系统如软膏、乳膏、糊剂和凝胶是可接受的。 粘弹性的性质，因为它们在相同的温度下显示出液体和固体性质。 材料在这个项目中，我们的目标是改变关键配方和制造 识别和定义影响产品的潜在失效模式的参数 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 诸如原子力显微镜（AFM）、共焦拉曼和多光子 显微镜检查，以研究辅料和制剂对体外和体内 皮肤除BE外，我们还旨在定义外观等效性（CE）。感官 相似性/外观等同性将被定义为关键质量属性， 这个过程