Chiarentin Lucas, Cardoso Catarina, Miranda Margarida, Vitorino Carla
Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
Laboratórios Basi Indústria Farmacêutica S.A., Parque Industrial Manuel Lourenço Ferreira, lote 15, 3450-232 Mortágua, Portugal.
Pharmaceutics. 2023 Jun 24;15(7):1810. doi: 10.3390/pharmaceutics15071810.
Analytical method validation ensures that a method provides trustworthy information about a particular sample when applied in accordance with the predefined protocol. According to regulatory standards, the rheological characteristics of topically applied semisolid formulations are one of the key elements involved in microstructure equivalence documentation. Therefore, for generic drug product manufacturers, it is a dire need to take a step forward in rheology method development and validation procedures. This paper aims to apply Analytical Quality by Design (AQbD) principles towards the development and validation of rheology methods for topical creams, as complex semisolid formulations. Risk assessment was carried out through an Ishikawa diagram and an estimate failure mode, effects, and criticality analysis (FMECA). Sample application, peltier temperature control, and sample rest time were identified as critical method variables (CMVs), and a 2 full factorial design was applied to understand their impact on rotational, creep recovery and, oscillatory measurements. The development of the method was carried out as per the ICH Q8-Q10, and Q14 guidelines and validated according to ICH Q2 (R2) guideline. The method demonstrated adequate precision (RSD < 15%), as well as selectivity. AQbD provided a comprehensive framework for developing a reliable and effective rheology method for this type of formulation.
分析方法验证可确保当按照预定义方案应用某方法时，该方法能提供有关特定样品的可靠信息。根据监管标准，局部应用的半固体制剂的流变学特性是微观结构等效性文件涉及的关键要素之一。因此，对于仿制药产品制造商而言，在流变学方法开发和验证程序方面向前迈进是当务之急。本文旨在将质量源于设计（AQbD）原则应用于局部乳膏（作为复杂半固体制剂）流变学方法的开发和验证。通过石川图和估计失效模式、影响及危害性分析（FMECA）进行风险评估。样品施加、珀耳帖温度控制和样品静置时间被确定为关键方法变量（CMV），并应用2全因子设计来了解它们对旋转、蠕变恢复和振荡测量的影响。该方法的开发按照国际人用药品注册技术协调会（ICH）Q8 - Q10和Q14指南进行，并根据ICH Q2（R2）指南进行验证。该方法显示出足够的精密度（相对标准偏差<15%）以及选择性。AQbD为开发针对此类制剂的可靠且有效的流变学方法提供了一个全面的框架。
