Correlated evaluations of in vitro release profiles and structural parameters for topical semisolid dosage forms containing metronidazole

摘要

The in-vivo performance of topical semisolid dosage forms is determined by a series of factors, related to the thermodynamic activity of the active pharmaceutical ingredient, the history of the formulation, as well as the complexity of interaction between various components of the vehicle and the complex biological barrier. The paper presents the role of correlated in vitro release (IVR) tests and structural analysis in the comparative quality assessment of topical formulations containing metronidazole in various concentrations. A simple in vitro evaluation protocol was implemented, based on previous reports relating the release rate with in vivo dermatopharmacokinetics. The similarity was assessed using a compendial nonparametric statistical method for log slopes (Wilcoxon Rank Sum/Mann Whitney rank test). The experimental data confirmed that IVR tests were discriminatory for the composition and manufacturing factors. In some cases, scaling the value of the diffusion rate with the label claimed dose strength led to similarity. The results of hysteresis loop test revealed a significant impact of structural parameters on the IVR, induced by composition variables.