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Rational design and in-vivoestimation of Ivabradine Hydrochloride loaded nanoparticles for management of stable angina

Authors :
Sharma, Vipin
Dewangan, Hitesh Kumar
Maurya, Lakshmi
Vats, Kanchan
Verma, Himanshu
Singh, Sanjay
Source :
Journal of Drug Delivery Science and Technology; December 2019, Vol. 54 Issue: 1
Publication Year :
2019

Abstract

Stable angina or angina pectoris is referred to as uneasiness/pain in the chest, resulting from coronary heart disease (CHD). Ivabradine Hydrochloride (IBH) is a recently approved drug to manage stable angina and heart failure symptoms. The approved IBH tablets exhibit some technical shortcomings i.e. short half-life (2 h), variable systemic absorption, and high first-pass metabolism (>50%). Therefore, utilizing a nanoformulation technique, we have designed a differentiated and innovative formulation of IBH. The IBH loaded polymeric nanoparticles (IBH-PNPs) are being developed for per-oral delivery by double emulsion method, using Poly lactic-co-glycolic acid (PLGA) as polymer, and d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) as a stabilizer. The pre-formulation studies performed are UV spectroscopy, FT-IR, and X-ray diffraction. The Box-Behnken design was exploited for formulation optimization. The optimized formulation was characterized for its particle size, zeta potential, morphology, entrapment efficiency, in-vitro release, stability studies, ex-vivo permeability, and in-vivo pharmacodynamics study. The optimized IBH-PNPs were found to be spherical (<200nm) and exhibited normal size distribution under transmission electron microscopy and atomic force microscopy respectively. The zeta potential and entrapment efficiency were found to be −43.75 mv and 60 ± 4.8% respectively. Developed IBH-PNPs analyzed for in-vitrodrug release where they exhibited biphasic release. The ex-vivodrug permeation study showed 1.85 folds increment in intestinal permeability as compared to IBH tablets. The in-vivoanti-anginal efficacy studies were performed using vasopressin-induced angina model in Wistar rats. Developed formulation was found to have a therapeutic effect for three days.

Details

Language :
English
ISSN :
17732247
Volume :
54
Issue :
1
Database :
Supplemental Index
Journal :
Journal of Drug Delivery Science and Technology
Publication Type :
Periodical
Accession number :
ejs51661811
Full Text :
https://doi.org/10.1016/j.jddst.2019.101337