Microemulsion-Based Gel of Terbinafine for the Treatment of Onychomycosis: Optimization of Formulation Using D-Optimal Design

Abstract

Abstract. The aim of the present investigation was to evaluate microemulsion as a vehicle for dermal drug delivery and to develop microemulsion-based gel of terbinafine for the treatment of onychomycosis. Doptimal mixture experimental design was adopted to optimize the amount of oil (X 1 ), Smix (mixture of surfactant and cosurfactant; X 2 ) and water (X 3 ) in the microemulsion. The formulations were assessed for globule size (in nanometers; Y 1 ) and solubility of drug in microemulsion (in milligrams per milliliter; Y 2 ). The microemulsion containing 5.75% oil, 53.75% surfactant-cosurfactant mixture and 40.5% water was selected as the optimized batch. The globule size and solubility of the optimized batch were 18.14 nm and 43.71 mg/ml, respectively. Transmission electron microscopy showed that globules were spherical in shape. Drug containing microemulsion was converted into gel employing 0.75% w/w carbopol 934P. The optimized gel showed better penetration and retention in the human cadaver skin as compared to the commercial cream. The cumulative amount of terbinafine permeated after 12 h was 244.65±18.43 μg cm −2 which was three times more than the selected commercial cream. Terbinafine microemulsion in the gel form showed better activity against Candida albicans and Trichophyton rubrum than the commercial cream. It was concluded that drug-loaded gel could be a promising formulation for effective treatment of onychomycosis.

D-optimal Design and Development of Microemulsion Based Transungual Drug Delivery Formulation of Ciclopirox Olamine for Treatment of Onychomycosis

“…Therefore, different models, viz., linear, quadratic, cubic, and special cubic, were first analyzed for the response variables (Y 1 to Y 3 ) by the predicted residual sum of square (PRESS) statistic for determination of suitability of model fitting. The PRESS statistic basically analyzes the prediction ability of the fitted models and the model with minimum value of PRESS statistic is usually considered as the most predictive model for the given set of data [16] . The quadratic model was selected for all three response variables as they observed the smallest value of PRESS statistic as compared to other three models (Table 6).…”

“…An o/w microemulsion containing an experimental drug (NB-002) effectively delivered across the skin present nearby nail plate [14] . In another attempt itraconazole could be delivered in nail plate through a o/w microemulsion formulation applied on nail plate in an in vitro drug loading study [15] , other than this, microemulsion based gel of terbinafine showed better in vitro transdermal permeation compared to marketed formulation [16] .…”

Novel nail penetration enhancer containing vesicles “nPEVs” for treatment of onychomycosis

“…Three wells were made in the middle of the plates with the help of sterile cork-borer, each well (6 mm internal diameter) was accurately filled with either 0.1 ml of the nPEVs formula, 0.1 ml of the control formula or an amount of Dermofix Õ cream equivalent to the sertaconazole dose in the 0.1 ml nPEVs formula. The plates were then incubated at 25 C for three days in the incubator to allow fungal growth (Barot et al, 2012;Sahoo et al, 2014).…”

“…It is a fungal infection that causes thickening, discoloration of the nail (Hall et al, 1997;Sigurgeirsson & Ghannoum, 2012;Barot et al, 2012). As infection progresses, the nail becomes brittle and starts to break or totally comes out of the toe or finger.…”

Progressive development in experimental models of transungual drug delivery of anti‐fungal agents

“…Three wells in Petri dishes containing different strains were bored, and 0.1 g of each formulation containing drug was filled. After the incubation period, anti-fungal activity was analysed by comparing the zone of inhibition [66]. Flores et al (2013) have evaluated anti-fungal efficacy of nanocapsules and nanoemulsions containing Melaleuca alternifolia (tea tree oil) using two different in vitro models of dermatophyte nail infection.…”