Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal; Coimbra Chemistry Center, Department of Chemistry, University of Coimbra, Rua Larga, 3004-535 Coimbra, Portugal.
REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, R. Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal.
Int J Pharm. 2022 Apr 5;617:121621. doi: 10.1016/j.ijpharm.2022.121621. Epub 2022 Feb 24.
The combination of two or more active pharmaceutical ingredients in the same dosage form - fixed-dose combination products - for topical administration represents a promising therapeutic approach for treating several pathologies, including pain. The pre-clinical development of fixed-dose combination products aims to characterize the interactions between the different APIs and ensure that the final medicinal product has the required safety characteristics. To this end, there are several regulatory accepted in vitro tests to assess the safety of medicinal products intended for cutaneous administration. In turn, the evaluation of anti-inflammatory activity should be based on models described in the scientific literature, as there are no models fully validated by competent entities. Therefore, this work presents the information regarding accepted in vitro tests to assess the safety of topical products and the most used methods to assess anti-inflammatory activity. Additionally, a new approach to select a fixed-dose combination product with the potential to enhance the therapeutic effects of the individual active pharmaceutical ingredients is rationalized by integrating the overall effects on several targets relevant for inflammation and pain management in one numeric index.
将两种或多种活性药物成分组合在同一剂型中（固定剂量组合产品），用于局部给药，代表了一种有前途的治疗多种疾病的方法，包括疼痛。固定剂量组合产品的临床前开发旨在描述不同 API 之间的相互作用，并确保最终药物具有所需的安全性特征。为此，有几种已被监管机构接受的体外试验可用于评估用于皮肤给药的药物的安全性。相反，抗炎活性的评估应基于科学文献中描述的模型，因为没有完全由主管机构验证的模型。因此，这项工作提供了有关评估局部产品安全性的已接受体外试验的信息，以及评估抗炎活性的最常用方法。此外，通过将与炎症和疼痛管理相关的几个目标的综合效果整合到一个数字指数中，提出了一种选择具有增强单个活性药物成分治疗效果潜力的固定剂量组合产品的新方法。
