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.
Wagner
N
N
Pharmacokinetics-Bioanalysis Department, International Center for Dermatological Research, Sophia Antipolis, France.
Berthaud
C
C
Laffet
G
G
Caron
J C
JC
D000279:Administration, Cutaneous; D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008795:Metronidazole / Q000008:administration & dosage*; D008875:Middle Aged; D011897:Random Allocation; D012867:Skin / Q000378:metabolism*
D000890:Anti-Infective Agents; D008795:Metronidazole