Dermatopharmacokinetic Approach to Evaluate and Compare the Pharmacokinetic Profile of Marketed Preparations of Diclofenac Sodium

Abstract

In this single-dose-one arm, open label three way parallel design, pharmacokinetic study of three marketed formulations of Diclofenac Sodium using 12 healthy Indian male subjects the pharmacokinetic parameters of three marketed Diclofenac Sodium topical formulations were compared . Marketed Diclofenac Sodium topical formulations (A, B and C) were applied on the pre-marked forearms of the subjects as per the dosing schedule. Treatment sample C was used as a reference sample. Subjects received treatment A, treatment B and treatment C on both the arms simultaneously, following open label three way parallel design. Skin Stratum Corneum samples were collected in sterile glass test tubes during the study period. The samples were collected pre-dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, and 6.0 hours post-dose application. The Stratum Corneum samples were analysed for Diclofenac Sodium concentrations only. Pharmacokinetic parameters of Diclofenac sodium were calculated as Cmax, tmax, AUC (0-t) and AUC (0-∞) Diclofenac Sodium was estimated in Stratum Corneum using a validated Spectroscopic method. If the point estimate of the geometric mean ratio and the confidence intervals for the entire log transformed pharmacokinetic parameters [Cmax, AUC (0-t) and AUC (0-∞)] were entirely included in the range of 80-125%, then the treatments were claimed to be bio-equivalent. A total of 12 subjects were enrolled in this study. The bioequivalence values of the test drug A were Cmax of 23.767±2.398 μg/mL, tmax of 1.75 ±0.261 h, AUC0-t of 100.507± 10.455 h. μg/mL, AUC0-∞ of 178.286± 22.859 h. μg/mL; of the test drug B Cmax of 31.1± 2.742 μg/mL, tmax of 1.75 ±0.261 h, AUC0-t of 103.555± 10.072 h. μg/mL, AUC0-∞ of 166.971± 47.627 h. μg/mL; and of test drug C Cmax of 24.084± 2.216 μg/mL, tmax of 1.75 ±0.261 h, AUC0-t of 100.586±11.15 h. μg/mL, AUC0-∞ of 179.887± 21.553 h. μg/mL.