Development and Characterization of Liposome-Based Formulation of Amiloride Hydrochloride.

Amiloride hydrochloride, a generally used diuretic recently has been found effective in the treatment of epilepsy. The side effects of the drug, such as hyperkalemia, hypertension, and hyperaldosteronism were controlled by reducing the dose and targeting the drug to the brain. The objective of this study was to determine the factors influencing encapsulation of amiloride hydrochloride in liposomes and to demonstrate the anti-epileptic potential of liposomal drug. A series of liposomal formulations of amiloride hydrochloride were prepared by varying the compositions of the formulations. The optimized formulation consisted of 10 mg/mL of amiloride hydrochloride, L-phosphatidyl choline, lecithin, cholesterol, and butylated hydroxy toulene. The percentage entrapment efficiency in the optimized formulation was 44%. The drug to lipids ratio and L-phosphatidyl choline: lecithin: cholesterol: butylated hydroxy toulene ratios were 2.0:3.0 and 5:5:5:2, respectively. The formulation showed an in vitro release of 98.17% in 8 hours, and the best fit kinetic model was Peppas model. Treatment with amiloride hydrochloride liposomes resulted in a significant increase in seizure threshold as compared to free drug in increasing current electroshock seizures in mice, which indicated an increase in CNS uptake of drug in liposome formulation. [ABSTRACT FROM AUTHOR]