Development of Sustained Release "NanoFDC (Fixed Dose Combination)" for Hypertension - An Experimental Study

Area of Science:

• Nanotechnology in Pharmaceutical Sciences
• Drug Delivery Systems
• Pharmacokinetics and Drug Metabolism

Background:

• Hypertension management often involves multiple medications, leading to challenges with patient adherence.
• Fixed-dose combinations (FDCs) aim to simplify treatment regimens.
• Developing advanced drug delivery systems can enhance the efficacy and reduce the side effects of antihypertensive drugs.

Purpose of the Study:

• To formulate, characterize, and evaluate the pharmacokinetics of a novel nano-formulation containing hydrochlorothiazide, candesartan, and amlodipine.
• To create a single nano-formulation (NanoFDC) of three common antihypertensive drugs.
• To assess the feasibility of reducing pill burden through a nanotechnology-based FDC.

Main Methods:

• Poly (DL-lactide-co-gycolide) (PLGA) nanoparticles were prepared using an emulsion-diffusion-evaporation method.
• Formulations were evaluated for size, morphology, drug loading, and in vitro drug release.
• Single-dose pharmacokinetic profiles of the nanoformulations and the NanoFDC were assessed in Wistar rats.

Main Results:

• Nanoparticles ranged from 110-180 nm with entrapment efficiencies of 30-33.5%.
• In vitro release showed 100% drug release by day 6 in physiological conditions.
• Pharmacokinetic analysis revealed a sustained-release for 6 days and significantly increased mean residence time (MRT) for all three drugs compared to their free forms.

Conclusions:

• Encapsulating amlodipine, hydrochlorothiazide, and candesartan into a single nanoformulation (NanoFDC) is a feasible strategy.
• This NanoFDC approach offers a promising method to decrease pill burden for hypertensive patients.
• The developed NanoFDC demonstrates potential for improved therapeutic outcomes in hypertension management.