AIM

To evaluate the bioequivalence of 3 marketed topical metronidazole formulations by simultaneous dermal microdialysis and stratum corneum sampling by the tape stripping methodology, and to compare the techniques as tools for the determination of bioequivalence.

METHODS

Nine microdialysis probes were inserted in the volar aspect of the left forearm of 14 healthy volunteers and, following application of the 3 metronidazole creams, microdialysis samples were collected for 5 h. On the right forearm, tape strip sampling was performed 30 and 120 min after product application. At the end of the experiment, ultrasound scanning measurements confirmed that all probes were placed inside the dermis.

RESULTS

There was no statistical difference in penetration of the 3 topicals as determined by microdialysis. However, their bioequivalence could not be determined due to intersubject variability exceeding the criteria for bioequivalence evaluation. Tape strip sampling established a bioequivalence between 2 of the creams, but rejected any bioequivalence between these 2 formulations and the third. The third formulation was a generic formulation approved despite containing a lower concentration of metronidazole (0.75%) than the innovator formulation (1.0%). The result of the bioequivalence evaluation depends on the methodology employed.

CONCLUSION

Whenever the dermis is the target tissue, microdialysis provides the most relevant information on drug bioavailability.