Abstract
Bioequivalence studies of topical formulations have attracted increased interest as the European Medicines Agencies "Guideline on quality and equivalence on locally applied, locally acting cutaneous products" describes them in the context of the approval of generics. Since the guideline only proposes tape stripping as a destructive method for bioequivalence testing in in vitro skin penetration, the aim of this study was to investigate the suitability of confocal Raman spectroscopy (CRS) as a non-destructive alternative. To validate the CRS results, tape stripping and CRS experiments using ketoprofen as a model API were performed consecutively on the same samples of ex vivo porcine skin after frozen storage and compared. All experiments were also carried out on two different animal test subjects to investigate a possible influence of inter-individual variations. Furthermore, the influence of the chosen incubation times inside and outside of the steady state was determined. We were able to show that CRS and tape stripping results were very similar both in overall detected API amounts as well as in the results of bioequivalence testing, proving CRS is not only suitable for quantitative skin penetration experiments but also for bioequivalence testing. Inter-individual variations were found to be relevant when comparing formulations measured on different subjects. Bioequivalence testing however reached the same results on both subjects. Finally, the chosen incubation time was limited by skin disintegration, the reaching of steady state however did not influence the results of bioequivalence testing.
Published Version
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