溶解
化学
生物制药分类系统
热稳定性
溶解度
结晶学
磁导率
立体化学
多态性(计算机科学)
有机化学
膜
生物化学
基因
基因型
作者
Manish Kumar Bommaka,M. K. Chaitanya Mannava,K. Sunil,Kuthuru Suresh,Ashwini Nangia
标识
DOI:10.1021/acs.cgd.1c00381
摘要
Entacapone (ETP) is a catechol-O-methyltransferase (COMT) drug used to treat Parkinson's disease. ETP is available in the marketplace under the brand name Comtan since 2010, and ETP form-I was first reported in a patent published in 2001. However, analysis of its X-ray crystal structures and stability relationship of ETP polymorphs and their dissolution and permeability profile have not yet been reported. We crystallized two new conformational polymorphs of ETP from a water and acetone mixture and studied the structural origin of polymorphism and their phase transformations, stability, equilibrium solubility, dissolution, and permeability properties. The ETP molecule adopts different conformations in the polymorphic structures with slight changes in carbonyl and nitrile group orientations. Thermal analysis suggests that form-III and form-IV are enantiotropically related to form-I, which is the thermodynamically stable form at ambient conditions. In contrast, form-II is monotropically related to form-I. Equilibrium solubility, dissolution, and permeability studies show that form-II persists in the slurry medium and dissolves faster with a high flux rate compared to the stable form-I in phosphate buffer solution at 37 ± 0.5 °C.
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