| Fluoxetine Hydrochloride is a selective serotonin reuptake inhibitor, used in the treatment of major depression, obsessive-compulsive disorder (in both adult and pediatric population), bulimia nervosa and premenstrual dysphoric disorder. It is the third most prescribed antidepressant drug in United States. Fluoxetine is available as a capsule dosage form in two different strengths, 10 and 20 mg. An attempt was made to evaluate the feasibility of developing topical formulations of this drug, as a means to overcome its high first pass metabolism when administered as an oral dosage form. Various dermatological formulations of Fluoxetine Hydrochloride were formulated using bases like HPMC gel and cationic emulsion based cream and further evaluated for in vitro drug release characteristics. Using cellulose membrane (cut off Mol. Wt. 1000 Da) as a barrier model, and diffusion cells working on static Franz principle, served as an in vitro experimental model to evaluate the drug release from the developed formulations. The hierarchy of drug release was observed to be as follows: HPMC gel system > cationic emulsion based cream > non-ionic emulsion based cream. Further, the effects of various permeation enhancers like Ethanol, Dimethyl Sulfoxide (DMSO) and Diethylene glycol monoethyl ether (DGME) on drug release were evaluated. Among all formulations evaluated, the HPMC gel system (with no additive) exhibited maximum release of the drug (58.89%). This formulation was then further studied for its drug release using the human cadaver skin. Here, the drug release pattern remained similar to the cellulose membrane, but the total amount of drug released was reduced to 16.59% as expected. The release data was treated were treated to determine the physical parameters that influence drug diffusion, and the values for the steady flux and diffusion coefficient were found to be the highest with this formulation and it yielded the lowest values for the lag time and partition coefficient. |
