In vitro and in vivo studies on chitosan beads of losartan Duolite AP143 complex, optimized by using statistical experimental design.
The aim of the present research work was to develop release modulated beads of losartan potassium complexed with anion exchange resin, Duolite AP143 (cholestyramine). Chitosan was selected as a hydrophilic polymer for the formation of beads which could sustain the release of the drug up to 12 h, along with drug resin complex (DRC). Chitosan beads were prepared using an in-liquid curing method by ionotropic cross-linking or interpolymer linkage with sodium tripolyphosphate (TPP). The formulation of the beads was optimized for entrapment efficiency and drug release using 3(2) full factorial design. The independent variables selected were DRC/chitosan and percent of TPP. The optimization model was validated for its performance characteristics. Studies revealed that as the concentration of chitosan and TPP was increased, entrapment efficiency and the drug release were found to increase and decrease, respectively. The swelling capacity of chitosan-TPP beads decreased with increasing concentration of TPP. The effect of chitosan concentration and percentage of TPP solution used for cross-linking on entrapment efficiency and drug release rate was extensively investigated. Optimized beads were subjected to in vivo studies in Wistar albino rats to determine the mean arterial blood pressure and compared with marketed formulation. The pharmacodynamic study demonstrates steady blood pressure control for optimized formulation as compared to fluctuated blood pressure for the marketed formulation.
Madgulkar
Ashwini
A
AISSMS College of Pharmacy, Shivajinagar, Pune 411001, India. ashwini.madgulkar@indiatimes.com
Bhalekar
Mangesh
M
Swami
Megha
M
D000465:Algorithms; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002151:Calorimetry; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry*; D003432:Cross-Linking Reagents; D005079:Excipients; D005260:Female; D019808:Losartan / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D008297:Male; D008855:Microscopy, Electron, Scanning; D015233:Models, Statistical; D010316:Particle Size; D011122:Polyphosphates; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012995:Solubility
D047228:Angiotensin II Type 1 Receptor Blockers; D003432:Cross-Linking Reagents; D005079:Excipients; D011122:Polyphosphates; D048271:Chitosan; D019808:Losartan; C005692:triphosphoric acid