1: Eur J Pharm Sci. 2009 Feb 15;36(2-3):219-25. Epub 2008 Sep 20.

Application of dermal microdialysis for the evaluation of bioequivalence of a
ketoprofen topical gel.

Tettey-Amlalo RN, Kanfer I, Skinner MF, Benfeldt E, Verbeeck RK.

Faculty of Pharmacy, Rhodes University, P.O. Box 94, Grahamstown 6140, South
Africa.

The purpose was to investigate dermal microdialysis (DMD) for the assessment of
the bioavailability of a ketoprofen topical gel formulation and to evaluate this 
technique as a tool for the determination of bioequivalence. Four microdialysis
probes were inserted into the dermis on the volar aspect of the forearms of 18
human subjects and the probes were perfused with normal saline for 60 min. A
ketoprofen (2.5%, m/m) gel formulation (50mg) was applied to the skin directly
overlying the probes and samples were collected at 30 min intervals for 5h. With 
the probes still in place in the dermis each site was scanned by ultrasound to
determine the implantation depth of these probes. Ketoprofen concentration in
dialysates was determined by LC-MS/MS. The area under the curve obtained from the
concentration-time profiles from pairs of application sites in each subject was
evaluated in order to assess bioequivalence. Ninety percent confidence intervals 
were calculated using the two one-sided test procedure and limits of 80-125%
based on log-transformed data were used as acceptance criteria to declare
bioequivalence. The intra-subject variability was 10% between probes whereas
inter-subject variability was 68% (n=18). Bioequivalence was confirmed with a
power greater than 90%.


PMID: 18848881 [PubMed - indexed for MEDLINE]

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