Formulation and evaluation of thermosensitive hydrogel of terbinafine hydrochloride for topical drug delivery

Stimuli-sensitive hydrogels change their swelling behavior and drug release by sensing changes in the surrounding environment. One example is temperature-sensitive hydrogels which change their swelling behavior in response to a change in the environmental temperature. Poloxamers are tri-block copolymers that exhibit thermoreversibleproperties by transforming from a liquid-like behavior to gel-like behavior above acertain temperature called sol-gel transition temperature. By varying the concentration of poloxamer and other excipients, hydrogels with sol-gel transition point close to bodytemperature can be achieved. The aim of the present study was to develop poloxamerhydrogels as in situ gelling formulation for topical drug delivery. The anti-fungal drug Terbinafine was used as a model drug substance. First, pre-formulation work on the solubility of Terbinafine in different co-solvents was performed. Then, eight different formulations containing 1% Terbinafine in poloxamer and a particular co-solvent (propyleneivglycol or Transcutol®-P) of various concentrations were prepared. The formulations were characterized for transition temperatures, rheological, mechanical, and mucoadhesiveproperties.
Terbinafine permeability and antifungal effect of the systems were evaluated. Except for one formulation, all hydrogels exhibited thermo sensitive property, i.e. changing from Newtonian (liquid-like) behavior at 20°C to non-Newtonian (gel-like) behavior at 37°C. Transcutol increased the transition temperature of the formulations, while the opposite effect was observed for propylene glycol. At body temperature, formulations with high poloxamer concentrations (17%) rendered gels with higher valuesin viscosity, compressibility and hardness. Formulations containing 17% poloxamer and20% Transcutol-P and 10% propylene glycol, respectively, exhibited high values in both adhesiveness and work of adhesion. No significant differences in the permeability and antifungal activity of Terbinafine were observed between the formulations. The latter suggests no influence of the gel vehicles on the biological effect of Terbinafine. Based on the results, formulations containing 17% poloxamer and 20% Transcutol-P and 10%propylene glycol, respectively, seemed to be promising thermosensitive systems for topical drug delivery.