Formulation of Herbal Topical Dermatological Dosage Form by Quality by Design Approach

Abstract

Objective: The study developed an optimized dosage form by quality by design (QbD) approach containing Azadirachta indica (Neem) leaf extract and a combination of selected herbal oils viz. A. indica oil, Eucalyptus citriodora oil and Cymbopogon martini oil and assessed for its antifungal efficacy, stability and dermal safety. Methods: Ointment was prepared using the fusion method from an extract of neem leaves with a combination of herbal oils viz. A. indica, E. citriodora, C. martini, bees wax and soft-paraffin. Utilizing the Box-Behnken Design (BBD), the variables such as the percentage of soft paraffin, beeswax and melting temperature were optimized in relation to the output variables such as viscosity, spreadability, and finally the antifungal efficacy, which was further quantified. Wistar albino rats were used (n = 5/test, positive and negative control) to evaluate the acute dermal toxicity test of the formulated ointment. Stability studies were assessed at 25 ± 2℃/ 60 ± 5% RH and 40 ± 2℃/ 75 ± 5% RH. Results: Melting point and percentage of beeswax significantly affect viscosity and spreadability. Optimal viscosity was obtained at 5.4% beeswax and 89.6% soft-paraffin when melted at 58℃. No dermal toxicity was observed by the ointment when comparable to petroleum jelly, both differed significantly with negative control. The absence of new spots on chromatograms, a prominent zone on agar plates, and negligible changes in spreadability (p = 0.112) all suggested physical stability, chemical stability, and antifungal efficacy, respectively. Conclusion: Neem leaf extract and a blend of selected herbal oils; A. indica, E. citrodora, and C. martini, when combined to formulate ointment, proved reliable and stable dosage form with significant anti-fungal efficacy. The formulated ointment might be helpful tool for dermatophytes management.