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

Arora A, Shafiq N, Jain S, Khuller GK, Sharma S, Malhotra S - PLoS ONE (2015)

Bottom Line: The nanoparticles ranged in size from 110 to 180 nm.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].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.

View Article: PubMed Central - PubMed

Affiliation: Dept. of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

ABSTRACT

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.

No MeSH data available.


TEM images of (a) amlodipine (b) hydrochlorothiazide and (c) candesartan nanoparticles.
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pone.0128208.g001: TEM images of (a) amlodipine (b) hydrochlorothiazide and (c) candesartan nanoparticles.

Mentions: The developed nanoparticles showed smooth spherical surface morphology with the drugs entrapped inside the different nanoparticles when seen by the difference in the staining as observed under TEM (Fig 1).


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

Arora A, Shafiq N, Jain S, Khuller GK, Sharma S, Malhotra S - PLoS ONE (2015)

TEM images of (a) amlodipine (b) hydrochlorothiazide and (c) candesartan nanoparticles.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4457799&req=5

pone.0128208.g001: TEM images of (a) amlodipine (b) hydrochlorothiazide and (c) candesartan nanoparticles.
Mentions: The developed nanoparticles showed smooth spherical surface morphology with the drugs entrapped inside the different nanoparticles when seen by the difference in the staining as observed under TEM (Fig 1).

Bottom Line: The nanoparticles ranged in size from 110 to 180 nm.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].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.

View Article: PubMed Central - PubMed

Affiliation: Dept. of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

ABSTRACT

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.

No MeSH data available.