Assessment of Topical Bioequivalence Using Dermal Microdialysis and Tape Stripping Methods
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To assess the bioequivalence of two commercial topical formulations of oxytetracycline HCl by tape stripping and microdialysis in healthy volunteers.
Tape stripping study was conducted on 12 healthy volunteers. After a 30-minute application of the formulations, adhesive tapes were used to sample stratum corneum at 0.25, 0.5, 1, 1.5, 2, 3, 4 hr. Ten of these volunteers were included in the microdialysis study with a period of 4 weeks between the experiments. Microdialysis probes were inserted into the dermis of the forearm. Following the application of the test and reference simultaneously, dialysates were collected in 30-minute sampling intervals up to 4 hr.
Pharmacokinetic evaluation by microdialysis yielded that the test could not be said to be bioequivalent to the reference at 90% CI. The intersubject variability of oxytetracycline content in stratum corneum was moderate when it was compared to the dermal levels. The test was found to be bioequivalent to reference according to the dermatopharmacokinetic evaluation by tape stripping.
No significant correlations were found between microdialysis and tape stripping methods as regarding the topical bioequivalence of oxytetracycline HCl formulations.
KEY WORDSbioequivalence microdialysis oxytetracycline tape stripping topical
area under the OTC content-time profile or area under the OTC concentration-time profile
amount of OTC at SC
maximum observed OTC content of the DPK profile or maximum observed OTC concentration in dermis
coefficient of variation
high performance liquid chromatography
absorption rate constant
elimination rate constant
limit of detection
limit of quantification
time point at which Cmax was observed
ultra performance liquid chromatography tandem mass spectroscopy
area of distribution
volume of distribution
This study was supported by the research grant (107S177) from TUBITAK (The Turkish Scientific and Technological Research Council), which is gratefully acknowledged. The authors would like to thank Düzen-Norwest Laboratory, Ankara, Turkey, for the technical assistance in providing UPLC-MS-MS analysis.
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