安贝生坦的新多晶型物：特性与稳定性。

Novel polymorph of ambrisentan: Characterization and stability.

机构信息

University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Studies (CAS), Panjab University, Chandigarh 160 014, India.

出版信息

J Pharm Biomed Anal. 2018 May 10;153:102-109. doi: 10.1016/j.jpba.2018.02.006. Epub 2018 Feb 8.

DOI:10.1016/j.jpba.2018.02.006

PMID:29475138

Abstract

The present work highlights a novel polymorph (form II) of ambrisentan (AMT), a selective endothelin type A (ETA) receptor antagonist used in the treatment of pulmonary arterial hypertension (PAH). Form II was isolated by solution crystallization and characterised by differential scanning calorimetry, powder X-ray diffraction, solution calorimetry and aqueous solubility. The single crystal X-ray diffraction shows that it crystallizes in monoclinic system with space group P21/c different from the form I (commercial form). Form II was found to be enantiotropically related to form I. Apparent solubility of form II was performed in 0.1 N HCl (pH 1.2) was found to be higher (1.5 fold) than of form I. Solution mediated and stress-induced phase transformation studies revealed conversion of form II to form I. Accelerated stability studies (40 °C & 75% RH) also reveal that form II converted to form I after one month. However, this does not belittle the improved solubility of a new solid form.

摘要

本工作重点介绍了一种新型的安立生坦（AMT）多晶型物（II 型），AMT 是一种选择性内皮素 A（ETA）受体拮抗剂，用于治疗肺动脉高压（PAH）。II 型是通过溶液结晶法分离得到的，并通过差示扫描量热法、粉末 X 射线衍射、溶液量热法和水溶解度进行了表征。单晶 X 射线衍射表明，它结晶为单斜晶系，空间群为 P21/c，与 I 型（商业形式）不同。II 型被发现与 I 型具有假各向同性关系。在 0.1N HCl（pH1.2）中进行的 II 型的表观溶解度研究表明，其溶解度比 I 型高（1.5 倍）。溶液介导和应激诱导的相转变研究表明，II 型向 I 型转化。加速稳定性研究（40°C 和 75%RH）也表明，II 型在一个月后转化为 I 型。然而，这并没有贬低新固体形式的提高的溶解度。