Comparison between Marketed Formulations of Diclofenac Gel, Emugel and Spray for the Evaluation of Effect of Pressure and Temperature on Their Bioavailability

Abstract

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 single-dose-three 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. Gel and Emugel formulation was applied on one forearm whereas the spray was applied on the other arm. Subjects received treatment on both arms in normal conditions of temperature and pressure and same treatment with the application of sufficient pressure in the second period and heat in the third 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 three 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, 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. A total of 12 subjects were enrolled in this study. The bioequivalence values of the test drug are mentioned in the Tables 1-4 and the graphical representation is shown in the Fig. 1-16. This study demonstrated that the bioavailability of the topical formulations increased with the help of pressure and temperature in case of the Gel and Emugel formulations whereas there was negligible effect of temperature and pressure on the Spray formulation of Diclofenac.