Nanostructured lipid carriers of ivabradine hydrochloride: Optimization, characterization and in-vivo estimation for management of stable angina

Abstract

Stable angina (angina pectoris) is a type of chest pain that happens when the heart muscle needs more oxygen than usual but it's not getting it at that moment because of heart disease. The drawback of the marketed formulation is required repeated administration of the drug due to low bioavailability. A recently licenced medication called ivabradine hydrochloride (IVB) is used to treat stable angina and signs of heart failure. Technical problems in the approved IBH tablets include a two-hour half-life, erratic systemic absorption, and a high rate of first-pass metabolism (>50%). We therefore created a distinctive and cutting-edge formulation of IVB using a nano formulation approach like nanostructured lipid carriers (NLCs). The response surface method with a three-level Box–Behnken design was used for the creation and improvement of IVB. The optimized formulation was proceeded for physicochemical characterizations like particle size, zeta potential, morphology (TEM and SEM), entrapment efficiency, in-vitro release, stability studies, compatibility study (DSC, FTIR and XRD), hemocompatibility study, ex-vivo permeability, and in-vivo angina study. As results, optimized formulation was found to be 114.45 ± 5.14 nm particle size with 83.45 ± 3.23% entrapment efficiency and biphasic release. The formulation showed spherical and compatible with excipients, no interaction was observed and hemocompatible. The IBH-NLCss showed more permeability (1.85 folds) as compared to the marketed dosage form. The in-vivo pharmacological activity was established in terms of decrease in severity and duration of ST-segment depression in vasopressin-induced angina model in experimental rats.