Formulation development, Ex vivo evaluation and In vivo antihypertensive study of losartan potassium loaded nanoproniosomal gel: A novel vesicular approach for transdermal delivery

Abstract

The transdermal nanoproniosomal gel of Losartan potassium was prepared to treat hypertension that is efficient to deliver the encapsulated drug over extended periods and to provide better bioavailability. In the present study, the nanoproniosomal gel of Losartan potassium was formulated by Lecithin, Cholesterol, Non-ionic surfactants using the Coacervation-phase separation method. The physical mixture of drug, lecithin, and cholesterol were subjected to compatibility study using FTIR spectroscopy. The prepared nanoproniosomal gels were subjected to various evaluation parameters like the determination of pH and viscosity, vesicle size analysis, rate of spontaneity, entrapment efficiency, zeta potential, ex vivo skin permeation studies, skin irritation test, stability studies and in vivo antihypertensive studies. The physical characterization of nanoproniosomal gels was found to be within the acceptable limits. The ex vivo skin permeation studies showed the cumulative permeation of 47.25% to 82.49% through the albino rat skin in 24 hrs for all the formulations which indicate the zero-order drug permeation with diffusion, non-fickian release as the possible mechanisms of drug release. Among all formulations, NLPG2 was selected as best formulation because it showed better characteristics than other formulations in several aspects like entrapment efficiency, vesicle size, ex vivo permeation studies, zeta potential, stability studies, and other evaluation parameters. The selected formulation NLPG2 showed the highest transdermal flux (28.67μg/cm2/h), with an enhancement ratio of 2.87 when compared to other formulations. In vivo antihypertensive study revealed that the formulation NLPG2 was successful to regress the rat BP to normal values in experimental hypertensive rats. Finally, it could be concluded that the formulation NLPG2 accentuates the flux of Losartan potassium and is an efficient transdermal therapeutic system for the delivery of a drug. The nanoproniosomal gels are suitable for once a day controlled release formulation.