title: Development of Sustained Release "NanoFDC (Fixed Dose Combination)" for Hypertension - An Experimental Study.
abstract: OBJECTIVE
  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).
  
  
  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].
  
  
  CONCLUSIONS
  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.
authors.affiliation: Dept. of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Anjuman
authors.initials: A
authors.lastname: Arora
authors.affiliation: Dept. of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Nusrat
authors.initials: N
authors.lastname: Shafiq
authors.affiliation: Dept. of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Jain
authors.affiliation: Dept. of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: G K
authors.initials: GK
authors.lastname: Khuller
authors.affiliation: Dept. of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Sadhana
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Dept. of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Samir
authors.initials: S
authors.lastname: Malhotra
mesh_terms: D017311:Amlodipine / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry; D001562:Benzimidazoles / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D001713:Biphenyl Compounds; D002121:Calcium Channel Blockers / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D006207:Half-Life; D006852:Hydrochlorothiazide / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry; D006973:Hypertension / Q000188:drug therapy*; D019344:Lactic Acid / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017208:Rats, Wistar; D017550:Spectroscopy, Fourier Transform Infrared; D013777:Tetrazoles / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D002121:Calcium Channel Blockers; D004337:Drug Carriers; D013777:Tetrazoles; D006852:Hydrochlorothiazide; D017311:Amlodipine; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C081643:candesartan