Development of Sustained Release “NanoFDC (Fixed Dose Combination)” for Hypertension – An Experimental Study
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OBJECTIVES: The present study was planned to formulate, characterize and evaluate the pharmacokinetics of a novel "NanoFDC" comprising three commonly prescribed anti-hypertensive drugs, hydrochlorothiazide (a diuretic), candesartan (ARB) and amlodipine (a calcium channel blocker). BASIC METHODS: The candidate drugs were loaded in Poly (DL-lactide-co-gycolide) (PLGA) by emulsion- diffusion-evaporation method. The formulations were evaluated for their size, morphology, drug loading and in vitro release individually. Single dose pharmacokinetic profiles of the nanoformulations alone and in combination, as a NanoFDC, were evaluated in Wistar rats. RESULTS: The candidate drugs encapsulated inside PLGA showed entrapment efficiencies ranging from 30%, 33.5% and 32% for hydrochlorothiazide, candesartan and amlodipine respectively. The nanoparticles ranged in size from 110 to 180 nm. In vitro release profile of the nanoformulation showed 100% release by day 6 in the physiological pH 7.4 set up with PBS (phosphate buffer saline) and by day 4-5 in the intestinal pH 1.2 and 8.0 set up SGF (simulated gastric fluid) and SIF (simulated intestinal fluid) respectively. In pharmacokinetic analysis a sustained-release for 6 days and significant increase in the mean residence time (MRT), as compared to the respective free drugs was noted [MRT of amlodipine, hydrochlorothiazide and candesartan changed from 8.9 to 80.59 hours, 11 to 69.20 hours and 9 to 101.49 hours respectively]. CONCLUSION: We have shown for the first time that encapsulating amlodipine, hydrochlorothiazide and candesartan into a single nanoformulation, to get the "NanoFDC (Fixed Dose Combination)" is a feasible strategy which aims to decrease pill burden.
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Hydrochlorothiazide, amlodipine, and candesartan conjugated with PLGA NPs showed similar improved results.
“Similar results were also observed when other commonly used hypertensive drugs (hydrochlorothiazide, amlodipine, and candesartan) were conjugated with PLGA NPs.141”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [141]
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- Authors
- Arora, A., Shafiq, N., Jain, S., Khuller, G. K., Sharma, S., & Malhotra, S.
- Affiliations
- Post Graduate Institute of Medical Education and Research (IN)
- Corresponding author
- Malhotra, Samir
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-06-05
- Volume
- 10
- Issue
- 6
- Pages
- e0128208
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4457799
- OpenAlex
- W1105212941
- Cited by
- 22
- References
- 35
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 5 · 2020: 1 · 2019: 6 · 2018: 2 · 2017: 2 · 2016: 1
- FWCI
- 0.93
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Keywords
- fixed-dose combination, sustained drug release, nanoparticle drug delivery, hypertension, hydrochlorothiazide, candesartan, amlodipine, PLGA nanoparticles, pharmacokinetics, encapsulation efficiency, in vitro drug release, mean residence time
- MeSH terms
- Polylactic Acid-Polyglycolic Acid Copolymer, Animals, Antihypertensive Agents, Benzimidazoles, Biphenyl Compounds, Calcium Channel Blockers, Drug Carriers, Half-Life, Hydrochlorothiazide, Hypertension, Polyglycolic Acid, Tetrazoles, Rats, Wistar, Amlodipine, Spectroscopy, Fourier Transform Infrared, Lactic Acid, Microscopy, Electron, Transmission, Rats, Nanoparticles, Drug Liberation
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