Studies on semi-solid dosage forms of terbinafine

Terbinafin HCL is widely used in the treatment of fungal infections, and the cream form of terbinafin HCL is commercially available under the name of Lamisil®. Therefore, we aimed at developing gel formulations, which are semi-solid dosage forms of 1% terbinafin HCL, as an alternative to the commercially available product (Lamisil®). According to the objective of our study, three different hydrogel formulations using chitosan, Carbopol®974P and Natrosol®250 polymers were prepared, and creating a triangular phase diagram and starting from microemulsion formulation, a microemulsion gel form containing 1% Carbopol®974P was prepared. Characteristic properties of the prepared formulations were also examined. The physical stability of hydrogel formulations and microemulsion gel were determined under different storage conditions (4ºC, 25ºC, 40ºC) during six months. The in vitro release of terbinafine HCL from the formulations prepared and the commercial product (Lamisil®) were performed by using two different methods, Franz difusion and dialysis methods, in a pH 5,2 phosphate buffer at 32ºC. Transcutol was used as a penetration enhancer with the purpose of improving the in vitro release of terbinafin HCL from the formulations prepared. The release kinetics were evaluated. In vitro MIC (minimum inhibition concentration) values on C.albicans, C.parapisilosis, C.krusei, Aspergillus niger, Penicillium, Microsporum and Trycophton rubrum of the formulations prepared were examined by comparison with the commercial preparation in the final stage of the study. According to the results of our study, physical properties (pH, appearance, viscosity) of the gel formulations which were prepared were examined, and it was observed that they were stable for 3 months. It was found that in vitro release of terbinafine HCL from chitosan, Carbopol and Natrosol gel formulations paralleled the commercial product (Lamisil®). It was observed that Transcutol increased the release of terbinafine HCL from Natrosol and microemulsion gel. On the other hand, Transcutol did not change the release of terbinafine HCL from chitosan and Carbopol gel. It was found according to the kinetic evaluation of in vitro release of terbinafine HCL that chitosan gel and the commercial product (Lamisil®) were consistent with Higuchi kinetics, Carbopol gel, microemulsion gel, and microemulsion were consistent with zero order kinetics and Natrosol gel with the Peppas kinetic model. According to the in vitro examination of antifungal activity, it has been found that all the formulations prepared and the commercial product (Lamisil®) were effective against the yeast species C.parapsilosis, moulds (Penicillium, Aspergillus niger) and the dermatophyte Microsporum. Natrosol gel was found to the most effective formulation against the dermatophyte Trichophyton rubrum. It was seen that chitosan gel was more effective against the yeasts, C.krusei and C.albicans as compared to other formulations. As a result, it can be said that chitosan, Carbopol and Natrosol gel formulations which have been prepared had the same activity with the commercial preparation (Lamisil®), where as the microemulsion gel formulation had a similar effect with the commercial preparation (Lamisil®). Keywords: Terbinafine, hydrogels, microemulsion gel, in vitro release, minimum inhibition concentration (MIC).