First report on QSAR modelling for chemical penetration enhancement ratio (ER) of different FDA-approved drugs in Poloxamer 407: A next step towards better skin permeability of drugs

Poloxamer 407 is a versatile excipient that enhances drug solubilization and prolongs drug release. Poloxamers are non-ionic tri-block copolymers composed of a central hydrophobic chain of polyoxypropylene flanked by two hydrophilic chains of polyoxyethylene. Various researchers have utilized Poloxamer 407 in topical and transdermal drug delivery systems, and it has also been reported to enhance skin permeability. The present investigation was conducted to predict the structural features of drugs that contribute to increased skin permeation in the presence of Poloxamer 407 as a polymer or carrier system. This was achieved using a multiple linear regression-based quantitative structure-activity relationship (QSAR) model developed with six molecular descriptors. The statistical outcomes (r² = 0.872, Q²_F1 = 0.805, Q²_F2 = 0.804, and Q²_F3 = 0.821) demonstrated the model's strong internal and external predictive capability. The model was further validated using various criteria to ensure its reliability. Additionally, an ex vivo study was performed on selected drugs (Voriconazole, Terbinafine, Ketoconazole, Pantoprazole, Sumatriptan, Sitagliptin, and Rabeprazole) to evaluate the predictive power of the developed 2D-QSAR model. The results of this study (experimental enhancement ratio, ER) were found to be highly correlated with the predicted ER values from the model. This QSAR-based prediction study highlights the potential for forecasting the skin penetration abilities of various drug classes in the presence of Poloxamer 407. It also provides a foundation for designing pharmaceutical dosage forms with improved skin permeability, which could aid in the treatment of skin-related conditions and other diseases.