Preparation of self-nano emulsifying drug delivery system (SNEDDs) of flutamide and evaluation of its intestinal permeability

Abstract

Introduction: Flutamide is a non-steroidal anti-androgen drug that is used to treat prostate hypertrophy and androgen-dependent prostate cancer. This drug has low solubility and high permeability and belongs to class II of Biopharmaceutical classification system.Aim: The aim of the presents study was to prepare flutamid loaded self nanoemulsifying drug delivery system (SNEDDS) and to determine and compare the intestinal permeability of flutamide loaded SNEDDS formulation and flutamide solution using the single pass intestinal perfusion (SPIP) method .Methods and Materials: SNEDDS formulations were designed and prepared using different percentages of oil, surfactant and cosurfactant. Physicochemical characteristics of SNEDDS formulations including droplet size, poly dispersity index and zeta potential were evaluated.SPIP technique was applied to determine intestinal permeability. A jejunal segment of 10 cm was isolated and cannulated in both ends. Either flutamide solution or flutamide SNEDDS dispersion was perfused through the cannulated segment. Outlet perfusates were collected every 10 min to 90 min and were analyzed by HPLC. Permeability coefficients (Peff) were calculated and compared.Results: The composition of optimized SNEDDS was Mygliol 812 10%, Transcutol P 30% and Tween 20 60% The mean droplet diameter, polydispersity index and zeta potential of optimized SNEDDS formulation were 120.5 nm, 0.168 and -15.5 mV. The mean effective permeability coefficients of flutamide solution was found to be 0.0177 ± 0.0025 cm/min and the mean effective permeability of flutamide loaded SNEDDS dispersion was found to be 0.02523 ± 0.0029 cm/min. statistical evaluation using t-test showed that the intestinal permeability of flutamide in SNEDDS formulation is significantly increased in comparison with its solution (P < 0.05).Conclusion: SNEDDS is suitable for the delivery of Flutamide according to observed increase in intestinal permeability and solubility of the drug, which could consequently enhance the oral bioavaibility.