首页    期刊浏览 2024年12月05日 星期四
登录注册

文章基本信息

  • 标题:Study on Control of pH-Modulation Crystallization Utilizing Concept of Dissociation Equilibrium
  • 本地全文:下载
  • 作者:Eriko Sato ; Shoji Kudo ; Hiroshi Takiyama
  • 期刊名称:Chemical and Pharmaceutical Bulletin
  • 印刷版ISSN:0009-2363
  • 电子版ISSN:1347-5223
  • 出版年度:2019
  • 卷号:67
  • 期号:5
  • 页码:461-466
  • DOI:10.1248/cpb.c18-01004
  • 出版社:The Pharmaceutical Society of Japan
  • 摘要:

    Crystallization by pH adjustment, as a type of reaction crystallization, is a solid–liquid separation method widely used in the area of pharmaceutical and pharmaceutical intermediate manufacturing. On the other hand, 3-alkenyl cephem compound is a typical zwitterionic pharmaceutical intermediate that possesses both an amino group and a carboxylic acid group. Such structure affords three main pH regions in solution and results in difficulties using crystallization by pH adjustment for isolation. As a consequence, 3-alkenyl cephem compound is usually crystallized at the point away from the solubility curve, causing unrestricted nucleation and flocculation behavior for the deposited particles which is difficult to filtrate. In this study, the p K a of 3-alkenyl cephem compound was intensively investigated to inhibit the nucleation. An optimal pH level point was also sought to make monodisperse particles. In particular, during crystallization by pH-modulation operation, the key point was identified to be the number of primary particles aggregated in the secondary particles. It was revealed that the increment number of primary particles led to the generation of larger monodisperse particles. This investigation, combined with solid–liquid equilibrium, enabled the acquisition of target species with good operability for filtration process. This present investigation becomes the prosperity in the zwitterion compound production that it has hardships to crystallize and filtrate.

  • 关键词:pH-modulation crystallization;dissociation equilibrium;metastable zone width;aggregate;primary particle;filtration
国家哲学社会科学文献中心版权所有