A comparative assessment of solubility advantage from glassy and crystalline forms of a water-insoluble drug.
The objective of the present study was to generate and characterize the glassy state of Irbesartan (IBS), with a view to exploit the solubility advantage from disordered high energy system. The major reason for limited solubility benefit from amorphous systems is their devitrification, on exposure to primarily aqueous dissolution medium. IBS is a lipophilic molecule and exhibits poor aqueous solubility and incomplete dissolution. IBS was found to be a good glass former (with glass transition/melting temperature >0.7), non-hygroscopic in nature and showed reasonable solid-state stability. The present work places particular emphasis on studying the influence of various dissolution environments on the devitrification of amorphous system. It was noted that IBS forms a relatively 'stable' glassy system with a 2.5-fold increase in aqueous solubility and a higher intrinsic dissolution rate (IDR). The dissolution behavior showed pH dependency and about eight-fold solubility advantage was obtained from amorphous system at pH 3. Both the crystalline and amorphous forms exhibited appreciably high solubility in HCl and HCl strength was found to significantly influence the solubility of crystalline form. Amorphous IBS showed reduced devitrification in HCl, as against water, thus highlighting the effect of dissolution environment on devitrification kinetics. Statistical and mathematical analyses were performed to compare the solubility advantage obtained using amorphous IBS vis-à-vis the crystalline counterpart.
Chawla
Garima
G
Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, Phase X, S.A.S. Nagar, Punjab 160062, India.
Bansal
Arvind K
AK
D000465:Algorithms; D000959:Antihypertensive Agents / Q000737:chemistry; D001713:Biphenyl Compounds / Q000737:chemistry*; D002021:Buffers; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004355:Drug Stability; D006851:Hydrochloric Acid / Q000737:chemistry; D000077405:Irbesartan; D044367:Phase Transition; D012995:Solubility; D013777:Tetrazoles / Q000737:chemistry*; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D002021:Buffers; D013777:Tetrazoles; D014867:Water; D000077405:Irbesartan; D006851:Hydrochloric Acid