engleski

Dermatopharmacokinetic properties of different topical diclofenac formulations

Purpose of the work: Standard pharmacokinetic testing of drugs applied topically on the skin is usually focused on potential systemic absorption and involves measuring drug concentration in blood followed by calculation of its systemic bioavailability. However, skin itself is a pharmacokinetic compartment that requires further attention and the importance of dermatopharmacokinetic testing of different topical formulations has been often underlined. The aim of this study was to determine dermatopharmacokinetic properties of different topical diclofenac formulations, by combining experiments with human participants and in vitro laboratory testing. Materials and methods: Two diclofenac gels with considerably different constituents (product A and product B) were applied to volar forearms of the participants (n=5) in amount of io mg of formulation per cm2 of the skin. Test sites were stripped, using sampling discs, 3, 6 and 23 hours after application. First disc on each site was discarded after stripping while next 15 consecutive discs were analysed for the protein content. Diclofenac was extracted from the discs with methanol and its content was measured using HPLC instrumentation. The measured diclofenac level was standardised to the mass of stratum corneum proteins removed by stripping. Two formulations were also tested in vitro, by using Franz cell for permeation test study. Results: The level of diclofenac after application of product A was higher in comparison to product B after 3, 6 and 23 hours (0.67±0.13 vs. 0.51±0.10, 0.50±0.12 vs. 0.37±0.46, 0.20±0.03 vs. 0.15±0.02 ug/ug/cm2, respectively, data are presented as mean±SEM). Area under curve T3-23 h was similarly higher for product A (7.67±1.6 vs. 5.75±0.44 ug*h/ug/cm2), and the flux was different as well (0.0046±0.0015 vs. 0.0034±0.0008 hr-1). However, some of this observed differences lacked reaching statistical significance. Similar results were obtained by in vitro permeation test study. Conclusions: Results of the pilot study suggest the difference in dermatopharmacokinetic properties of the two tested diclofenac formulations might exist. Further studies with higher number of participants are warranted to confirm this difference.

diclofenac ; dermatopharmacokinetic properties ; in vitro permeation

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