New Approach to Hypertension Treatment: Carvediol-Loaded PLGA Nanoparticles, Preparation, In Vitro Characterization and Gastrointestinal Stability

Abstract

Carvedilol (CVL) has advantages over the first generation of beta-blockers in patients with heart failure due to its properties of reducing cardiovascular morbidity and mortality. On the other hand, CVL has a short half-life leading to administration of high dosage and frequent dosing range. The need of design and producing a new prolonged-release dosage form containing CVL is the major aim of the study with low active ingredient and low side effects. In the present study, CVL loaded poly(lactic-co-glycolic acid)[PLGA] nanoparticles (NPs) were produced by nanoprecipitation method for oral drug delivery. The formulations were developed and characterized including the gastrointestinal stability. Structures of NPs were elucidated by particle size, zeta potential, DSC and FTIR. In vitro release of CVL loaded NPs were examined in phosphate buffer (pH 6.8). CVL-loaded NPs demonstrated nanostructures while in vitro relase studies showed extended release. High encapsulation efficiency was obtained (68-79%) for the prepared formulations in spite of poor aqueous solubility of CVL. Peppas-Sahlin kinetic model was found to fit best to CVL release from NPs. CVL-loaded NPs were set up by economic nanoprecipitation method owing to the advantages of PLGA polymer accepted as the gold standard. This study aims to treat hypertension effectively by low dose of CVL in a prolonged release pattern. According to the proposed method it can be successfully applicable to the nanoparticle preparation containing CVL and it could be concluded that CVL loaded NPs seem to be a promising extended release drug delivery system for oral administration.