Leela Christian-Tabak, Koji Machida, Hideo Kawachi, Hiroaki Tanaka, Kazuki Hashimoto
{"title":"Coupled-Batch Preferential Crystallization of Imeglimin Propionate on a 200 g Scale","authors":"Leela Christian-Tabak, Koji Machida, Hideo Kawachi, Hiroaki Tanaka, Kazuki Hashimoto","doi":"10.1021/acs.oprd.4c00291","DOIUrl":null,"url":null,"abstract":"The application of coupled-batch preferential crystallization (CB-PC) for the propionate salt of the active pharmaceutical ingredient imeglimin is demonstrated herein. Process conditions were chosen based on metastable zone width measurements, and an apparatus with 500 mL-sized crystallization vessels was constructed. A series of CB-PC experiments on an increasing scale were run, and observations on scaling up were made throughout, including the effect of the seeding method, productivity over time, and physical limits of the apparatus. The series culminated in two successive runs each on a 200 g scale, in which the mother liquor from the first run was recycled to the second.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"7 1","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Organic Process Research & Development","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1021/acs.oprd.4c00291","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, APPLIED","Score":null,"Total":0}
引用次数: 0
Abstract
The application of coupled-batch preferential crystallization (CB-PC) for the propionate salt of the active pharmaceutical ingredient imeglimin is demonstrated herein. Process conditions were chosen based on metastable zone width measurements, and an apparatus with 500 mL-sized crystallization vessels was constructed. A series of CB-PC experiments on an increasing scale were run, and observations on scaling up were made throughout, including the effect of the seeding method, productivity over time, and physical limits of the apparatus. The series culminated in two successive runs each on a 200 g scale, in which the mother liquor from the first run was recycled to the second.
期刊介绍:
The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools,process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.