Chawla Garima, Bansal Arvind K
Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, Phase X, S.A.S. Nagar, Punjab 160062, India.
Eur J Pharm Sci. 2007 Sep;32(1):45-57. doi: 10.1016/j.ejps.2007.05.111. Epub 2007 Jun 2.
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.
本研究的目的是制备并表征厄贝沙坦（IBS）的玻璃态，以期利用无序高能体系的溶解度优势。非晶态体系溶解度提升有限的主要原因是其在主要为水性的溶解介质中会发生析晶。IBS是一种亲脂性分子，水溶性差且溶解不完全。研究发现IBS是一种良好的玻璃形成体（玻璃化转变温度/熔点>0.7），本质上不吸湿，且具有合理的固态稳定性。本工作特别着重研究各种溶解环境对非晶态体系析晶的影响。值得注意的是，IBS形成了一个相对“稳定”的玻璃态体系，其水溶性提高了2.5倍，固有溶解速率（IDR）更高。溶解行为显示出对pH的依赖性，在pH 3时，非晶态体系的溶解度优势约为8倍。结晶态和非晶态在HCl中均表现出相当高的溶解度，且发现HCl浓度对结晶态的溶解度有显著影响。与水相比，非晶态IBS在HCl中的析晶减少，从而突出了溶解环境对析晶动力学的影响。进行了统计和数学分析，以比较使用非晶态IBS相对于结晶态IBS所获得的溶解度优势。
