Topical fixed-dose combinations: Current in vitro methodologies for pre-clinical development

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.

Automated summary

The combination of multiple active pharmaceutical ingredients in a fixed-dose combination product for topical administration shows potential in treating various pathologies, including pain. This study presents information on accepted in vitro tests for assessing the safety of topical products and the commonly used methods for evaluating anti-inflammatory activity. Additionally, a new approach for selecting fixed-dose combination products to enhance therapeutic effects is rationalized.