Formulation and Characterization of Transethosomes for Enhanced Transdermal Delivery of Propranolol Hydrochloride

Abstract

Objective: The objective of the present work was to develop transethosomes loaded with propranolol hydrochloride using Lipoid S100 as phospholipid, and oleic acid as permeation enhancer and evaluate them for prolonged release effect, in-vitro skin permeation, and in-vivo plasma concentration. Methods: Transethosomes loaded with propranolol hydrochloride were prepared by homogenization method. Furthermore, they were characterized by using Transmission Electron Microscopy (TEM), zeta sizer, Differential Scanning Calorimetry (DSC), and Confocal Laser Scanning Microscopy (CLSM) for in-vitro skin permeation. Plasma concentration profile of transethosomal gel was determined using Sprague Dawley rats and compared with a marketed oral tablet of propranolol hydrochloride. Results: Developed transethosomes loaded with propranolol hydrochloride showed acceptable size (182.7 ± 5.4 nm), high drug entrapment (81.98 ± 2.9%) and good colloidal characteristics [polydispersity index (PDI) = 0.234 ± 0.039, zeta potential = -21.91 ± 0.65 mV]. Transethosomes showed prolonged in-vitro release of propranolol hydrochloride for 24 h. Results of in-vitro skin permeation studies of transethosomal gel showed 74.34 ± 2.33% permeation of propranolol hydrochloride after 24 h and confocal microscopy revealed accumulation of transethosomes in the stratum basale layer of the skin. Transethosomal gel was capable to prolong the in-vivo release of propranolol hydrochloride upto 24 h. The value of peak plasma concentration (Cmax) of propranolol hydrochloride was found to be 93.8 ± 3.6 ng/mL which was very high compared to the marketed oral tablet of propranolol hydrochloride (45.6 ± 3.1 ng/mL). Conclusion: The results suggested that transethosomal gel of propranolol hydrochloride could be a better alternative to oral propranolol hydrochloride as it can avoid various disadvantages of oral propranolol hydrochloride like high dosing frequency, first pass effect, and organ toxicity.