Development and Ex vivo evaluation of Rasagiline Mesylate mucoadhesive microemulsion for intranasal delivery using Box-Behnken design

Abstract

Rasagiline mesylate (RM), an irreversible, selective inhibitor of MAO-B enzyme, is used in the treatment of Parkinson’s disease as oral tablets. It has low oral bioavailability (36%) due to hepatic first pass metabolism. Oral route of administration is associated with nausea and vomiting. Hence present research work was aimed to develop intranasal RM- loaded mucoadhesive microemulsions for brain targeting via olfactory pathway. The microemulsions were developed using Box Behnken design and evaluated for globule size, PDI, Zeta potential, pH, viscosity and ex vivo permeation on excised porcine nasal mucosa. Based on drug solubility, Capmul MCM, Tween 20 and Transcutol P were selected as oil, surfactant and cosurfactant respectively. Microemulsions were prepared by water titration method. Pseudoternary phase diagrams were constructed and the levels of surfactants, oil were selected. The influence of independent variables such as oil, Smix and water on responses size, zeta potential and flux were studied with the help of polynomial equations, contour plots and 3D response surface plots generated by design expert software. Optimized microemulsion formulation (ME18) was composed of oil (Capmul MCM), Smix (Tween 20: Transcutol P; 1:1), water and drug in the ratio 5:42:65:5.The globule size, zeta potential and flux of the optimized microemulsion was 150 nm, -29.6 mV and 291.7 μg/cm2/h respectively. Mucoadhesive agent (Chitosan) was added at 0.5% concentration to optimized microemulsion formulation (MME18). The size, zeta potential and flux of the MME18 was 176.4 nm, 12.1 mV and 323.1 μg/cm2/h respectively. The flux of ME18 and MME 18 was significantly higher than drug solution. The enhancement ratio of MME 18 was 4.2 times to that of drug solution, indicating potential advantage of microemulsion formulation.