Abstract

Objective: The aim of this study was to develop a formulation for lymphatic uptake with enhanced solubility of antifungal drug, terbinafine by use of self-microemulsifying drug delivery system (SMEDDS); suitable enough to be an industrially feasible and acceptable dosage form. Methods: Pseudo ternary phase diagrams were plotted using suitable oils, surfactants and co-surfactants. The optimized formulation was fabricated and characterized by various in-vitro parameters like droplet size, polydispersity index, zeta potential, cross-polarized light microscopy, thermodynamic stability, viscosity and compatibility with capsule shell. The optimized formulation was also tested in animal model for per oral conceptualization of lymphatic uptake in absence and presence of chylomicron blocker (cycloheximide) followed by the pharmacokinetic evaluation of the same. Results: The self-emulsification time, droplet size, polydispersity index of the optimized formulation remained unaffected in different media (water, 0.1N HCl and phosphate buffer pH 6.8) over the test time period. Crossed-polarized light microscopy examination of diluted SMEDDS formulation indicated that the dispersion was an isotropically stable system. The rate of dissolution for SMEDDS formulation was almost two folds than the marketed formulation (Lamisil^®). Current investigation indicates a potential for uptake of the lipid based SMEDDS formulation through lymphatic route with enhanced solubility of the candidate drug terbinafine. The terbinafine SMEDDS when orally administered to rat with and without chylomicron flow blocking agent (cycloheximide) exhibited the area under the curve (AUC_0-48 hr) as 7425.44 ng h/ml and 10168.17 ng h/ml respectively hence indicating absorption through the lymphatic route. Thus, the study reaffirms the use of SMEDDS formulation for the drug delivery by lymphatic uptake.

Keywords: Bioavailability, lymphatic uptake, SMEDDS, terbinafine, zeta potential.

Graphical Abstract