systematically optimized topical delivery system for loperamide hydrochloride: formulation design, in vitro and in vivo biopharmaceutical evaluation

This study aimed to develop a suitable topical delivery system containing diethylene glycol monoethyl ether (DGME) for Loperamide hydrochloride (Lop). Two factors, three levels Central-Composite design were applied by generating a quadratic polynomial equation to form contour plots and response surface for prediction of responses as two selected independent variables with EtOH-DGME ratio and EtOH concentration. The response variables flux and skin retention were determined in in vitro hairless mouse skin model. The selected optimum formulation was evaluated for the skin transport characteristics by developing dermatokinetic analysis model and the results demonstrated DGME improved the delivery of Lop into skin deep layers, which was further confirmed by confocal laser scanning microscopy (CLSM) study. In vitro skin permeation was found to have triphasic correlation with plasma AUC in the in vivo pharmacokinetic study. The in vitro–in vivo correlation enabled the prediction of pharmacokinetic profile of Lop from in vitro permeation results. Therefore, the optimum formulation capable of enhancing Lop intracutaneous depot could be a candidate for topical delivery of Lop as analgesics. Keywords: Loperamide hydrochloride, Topical delivery, Skin retention, In vitro–in vivo correlation