EVALUATION OF EFFECT OF PRESSURE AND TEMPERATURE ON THE BIOAVAILABILITY OF MARKETED FORMULATION OF DICLOFENAC GEL

This study involves research to assess the pharmacokinetics of Diclofenac Sodium Marketed formulations as well as the effect of pressure and temperature on its bioavailability by Dermatopharmacokinetic method. This drug is used for the treatment of Local pain. This was a singledose-one arm, open label pharmacokinetic study of marketed formulations of Diclofenac Sodium using 12 healthy Indian male subjects. A marketed Diclofenac Sodium topical formulation was applied on the pre-marked forearms of the subjects as per the dosing schedule. Subjects received treatment on one arm & same treatment on another with the application of sufficient pressure in the first period & sufficient heat in the second period of the study. The study was conducted following open label three way parallel design. A washout period of two days was kept between the two periods of the study. Skin Stratum Corneum samples were collected in sterile glass test tubes during each period. The samples were collected pre-dose and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, & 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. A total of 12 subjects were enrolled in this study. The bioequivalence values of the test drug A were Cmax of 25.108 ± 2.398 μg/mL, tmax of 1.75 ± 0.261 h, AUC0-t of 99.87 ± 10.455 h. μg/mL, AUC0-∞ of 178.86± 22.859 h. μg/mL; after applying pressure, Cmax of 31.1 ± 2.742 μg/mL, tmax of 1.45 ± 0.342 h, AUC0-t of 100.25 ± 10.072 h. μg/mL, AUC0-∞ of 179.421 ± 47.627 h. μg/mL; and after using heat belt Cmax of 28.084 ± 2.216 μg/mL, tmax of 1.62 ± 0.261 h, AUC0-t of 100.496 ± 11.15 h. μg/mL, AUC0-∞ of 179.706 ± 21.553 h. μg/mL. This study demonstrated that the bioavailability of the topical formulations increased with the help of pressure and temperature.