Bioequivalence of topical formulations in humans:evaluation by dermal microdialysis sampling and the dermatopharmacokinetic method

The aim of this study was to evaluate the relationship between dermal microdialysis (DMD) sampling and the dermatopharmacokinetic method when employed simultaneously for bioequivalence (BE) investigations of topical formulations. Topical lidocaine cream and ointment (both 5%) was investigated in eight healthy human volunteers (four male, four female). On one forearm, four microdialysis probes in two penetration areas sampled for 5hours, and on the other arm, tape stripping was performed 30 and 120minutes after product application. Lidocaine content in samples was analyzed by HPLC–mass spectrometry. The two methods were in agreement showing 3- to 5-fold higher lidocaine penetration from cream formulation than from ointment. A rank-order correlation between the two methods was demonstrated for lidocaine contents in microdialysates versus tape strip at 120minutes, significant for the ointment formulation and for both formulations analyzed together. Analysis of variance demonstrated reproducible lidocaine concentrations in microdialysates with an intrasubject variability of 19% between probes and 20% between the two penetration areas. Thus, intersubject variability accounted for 61% of the variance. DMD sampling proved effective and variability analyses demonstrated the feasibility of BE studies in as little as 18 subjects

Application of dermal microdialysis for the determination of bioavailability of clobetasol propionate applied to the skin of human subjects

Dermal microdialysis was used to assess the bioavailability of a topical corticosteroid, clobetasol propionate, following application onto the skin of human subjects. The penetration of clobetasol propionate from a 4% m/v ethanolic solution applied onto 4 sites on one forearm of healthy human volunteers was studied. A lipid emulsion, Intralipid®, was used as the perfusate and linear microdialysis probes with a 2-kDa cutoff were inserted intradermally at the designated sites. The results indicated that Intralipid could be used as a suitable perfusate for in vivo microdialysis of this lipophilic drug of interest. Furthermore, the study clearly demonstrated the application of dermal microdialysis as a valuable tool to assess the bioavailability/bioequivalence of clobetasol propionate penetration into the skin following topical application