Preformulation study of the inclusion complex irbesartan-beta-cyclodextrin.
The aim of the present work was to improve the solubility and dissolution profile of irbesartan (IRB), a poorly water-soluble drug by formation of inclusion complex with beta-cyclodextrin (betaCD). Phase solubility studies revealed increase in solubility of the drug upon cyclodextrin addition, showing A(L)-type of graph with slope less than one indicating formation of 1:1 stoichiometry inclusion complex. The stability constant (K(s)) was found to be 104.39 M(-1). IRB-betaCD binary systems were prepared by cogrinding, kneading using alcohol, kneading using aqueous alcohol, and coevaporation methods. Characterization of the binary systems were carried out by differential scanning calorimetry, Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction, and proton nuclear magnetic resonance. The dissolution profiles of inclusion complexes were determined and compared with those of IRB alone and physical mixture. Among the various methods, coevaporation was the best in which the solubility was increased and dissolution rate of the drug was the highest. The study indicated the usefulness of cyclodextrin technology to overcome the solubility problem of IRB.
Hirlekar
Rajashree
R
Department of Pharmaceutics, Bharati Vidyapeeth's College of Pharmacy,CBD Belapur, Navi Mumbai, Maharashtra, India. rshirlekar@rediffmail.com
Kadam
Vilasrao
V
D047228:Angiotensin II Type 1 Receptor Blockers / Q000737:chemistry*; D001713:Biphenyl Compounds / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D018360:Crystallography, X-Ray; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D000077405:Irbesartan; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008855:Microscopy, Electron, Scanning; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D013777:Tetrazoles / Q000737:chemistry*; D047392:beta-Cyclodextrins / Q000737:chemistry*
D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D004337:Drug Carriers; D013777:Tetrazoles; D047392:beta-Cyclodextrins; D000077405:Irbesartan