Formulation and Evaluation of Itraconazole Topical Spray

1. Objective: Itraconazole is a broad spectrum antifungal drug which inhibits fungal Cytochrome P450 and hence inhibits fungal growth. This drug is preferable over other antifungal agents in many aspects to treat topical fungal infection but only oral and I.V preparations are approved for administration of this drug and topical route for delivery of this drug is highly desirable and is under investigation. The present study is aimed to formulate and evaluate Itraconazole topical spray for obtaining effective therapeutic action in superficial fungal infection using co-solvent as solubilizer and volatile solvent system.

2. Experimental work: Nine formulations of Itraconazole topical spray were prepared using 32 full factorial designs where propylene glycol (X1) and Propellant (X2) were selected as independent variables and % skin retention (Y1) and spray pattern (Y2) were selected as dependent variables. LPG was used as propellant for the formulation. All ingredients of the spray were packaged in an aluminum container fitted with continuous-spray valves. Itraconazole topical spray was evaluated for delivery rate, pressure, minimum fill, flammability, spray patterns, particle image, unit content per spray and plume angle, leakage test, skin irritation, ex vivo diffusion studies, in vitro antifungal activity.

3. Results and discussion: Preformulation studies of Itraconazole pure drug satisfy the official compendial requirement. Formulation components of Itraconazole topical spray were found compatible to each other and showed no sign of precipitation, deformation and discoloration. The optimized batch containing 50% propellant and 15% propylene glycol retained highest concentration of Itraconazole 33.6% skin retention after 5 hours. The flame extension, flame flash back, pressure, density, pH, delivery rate, spray angle, minimum fill, unit drug content per spray and leakage rate were found to be 63.29cm, 8cm, 1.64 kg/cm2, 0.904 g/ml, 7.0, 2.15 g/sec, 21°, 100 %, 10.2 mg and 0.11 %/year respectively. Spray pattern was uniform and uniform. Particle size distribution was optimum. Diffusion studies of the optimized formulation through the rats' skin showed the average release of drug 21.97 %. Maximum zone of inhibition was 3.76 mm. Skin irritation studies were performed using wistar rat as an animal model. Short-term stability study demonstrated insignificant changes in performance characteristics.

4. Conclusions: The results of optimized Itraconazole topical spray formulation has been satisfactorily formulated which showed comparatively better performance in superficial antifungal treatment.