Development of low strength diclofenac sodium dermatological formulations with enhanced drug release profiles

This study was undertaken to screen various formulations for the in-vitro release of Diclofenac Sodium from various topical bases including Hydrophilic Ointment base, Carbopol Gel and HPMC gel bases. Various ingredients known to enhance the drug release from the topical bases were also evaluated at various concentration levels. These included Ethanol, Propylene Glycol and Diethylene Glycol Monoethyl ether. The formulations containing 1% of Diclofenac Sodium and penetration enhancing ingredients at various levels (2.5%, 5% and 10%) were prepared and evaluated for their in-vitro drug release profiles. For comparison purposes commercial products Voltaren Gel (1%) and Solaraze Gel (3%) were included as a control. One gram sample of each formulation was placed in the donor compartment, and the in-vitro drug was determined by using Franz diffusion cells through the cellulose membrane for up to 2 hour period. The general rank order for the drug release was observed to be: HPMC Gel > Hydrophillic Ointment Base > Carbopol Gel.;Among all the formulations evaluated, the sample prepared with HPMC gel without any enhancer gave the double amount of drug release through cellulose membrane as compared with Voltaren gel (1%). Then four samples were prepared containing 0.5%, 1.5%, 2.0% and 1.75% drug with HPMC gel. Samples with 0.5% and 1.75% were found comparable with Voltaren gel (1%) and Solaraze Gel (3%) respectively through cellulose membrane. These two optimum formulations and both the commercial products were further evaluated for drug release profile up to 12 hours through cellulose membrane as well as through Human Cadaver Skin. Here again the optimum formulation exhibited the maximum drug release and the data correlated well with the in-vitro results obtained through cellulose membrane up to 2 hours release profiles.;The in-vitro release data were treated with various kinetic principles to determine relevant parameters, such as steady-state flux, diffusion, and permeability coefficient values and these correlated well with amount of drug release.;This study supports the fact that with a proper selection of base and vehicle, it is possible to develop dermatological formulation of such clinically important drug with significantly reduced drug concentration.