Differential penetration of skin by topical metronidazole formulations

This in vitro study compared the release and penetration of various metronidazole formulations: 0.75% gel, 0.75% cream, and a new 1% cream. Six skin samples from each of six women (28 to 58 years of age) were used to test the three formulations, for a total of 12 samples per formulation. A 10-mg target dose of each metronidazole formulation (75 micrograms of 0.75% gel and 0.75% cream, 100 micrograms of 1% cream) was applied to a skin surface of 1 cm2 per cell. The randomized application schedule controlled for variability in skin origin, individual cell thickness, and formulations. Seven fluid samples were collected over a 15-hour period. Metronidazole concentrations were measured in both the skin samples and through the fluid from a dynamic diffusion system with the use of high-performance liquid chromatography method with ultraviolet detection. Cutaneous penetration of metronidazole was significantly greater with the 0.75% gel and cream formulations than with the 1% cream. These results suggest that the delivery vehicle may be more important than the active drug concentration in cutaneous delivery of metronidazole.