Microemulsion and microemulsion based gel of zaleplon for transdermal delivery: Preparation, optimization, and evaluation

Abstract

In this work solubility and permeability of BCS II drug Zaleplon was increased by loading it into microemulsion which in turns enhance bioavailability. Carbomer 940 was incorporated to fabricate microemulsion based gel (MEBG) which sustained transdermal delivery. Solubility studies screened Castor oil, Tween 80 (surfactant), and Polyethylene glycol 200 (co-surfactant) for preparing Microemulsion. Pseudoternary phase diagrams were constructed to determine the microemulsion region. Box Behnken Design (BBD) was employed for optimizing microemulsions which were initially investigation for physicochemical characteristics. Oil, Smixand water; Q24, Flux and lag time were selected as independent and dependent variables, respectively. Franz diffusion cell was employed to compare in vitro permeability for optimized microemulsions across Rabbit skin. Variables were related using mathematical equations and response surface plots. MEBG was distinguished for stability, in-vitro Zaleplon permeation, anti-inflammatory studies and skin irritation than control gel and in-vivo studies for oral tablet. Microemulsions showed pH of 5.36-5.98 (physiological), conductivity of 140-186 µS/cm, isotropic value of 1.340-1.417, average droplet size of 63-89 nm, homogeneity, droplet size of 53ñ61 cP and spherical shape. Predicted values of optimized microemulsions were found in reasonable agreement for experimental values. Preparations were stable and found to be skin non-irritant. When comparing edema percent inhibition of MEBG (85%) and control gel (42%) than standard, a significant difference was estimated. MEBG pattern differed significantly than oral tablet formulation for in vivo studies. This BBD based evaluation will decrease cost and time for designing drug, delivery and targeting.