Surface Defects and Crystal Growth of Apremilast Benzoic Acid Cocrystals

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2025-03-19 DOI:10.1021/acs.oprd.4c00480

Jan Jirát, Vít Zvoníček, Luděk Ridvan, Miroslav Šoóš

引用次数: 0

Abstract

A cocrystallization process of the active pharmaceutical ingredient apremilast with benzoic acid is explored in this work. The aim of the study is to adjust operating conditions during the crystallization to purposefully tune the dissolution properties of the final product. Understanding the cocrystallization is key to obtaining a consistent, high-quality product, as well as tuning other properties such as powder flowability or dissolution properties. It was discovered early in development that the studied cocrystallization process does not follow the common rules of crystallization. Better crystals were obtained at faster cooling rates and worse crystals at slower cooling rates. Interestingly, this can be explained by crystal collisions and a two-phase growth of the crystals. Standard operating conditions were further tested, resulting in different shapes and sizes of the product. Different types of produced crystals were tested in a dissolution apparatus and provided significantly modified dissolution profiles.

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来源期刊

Organic Process Research & Development 化学-应用化学

CiteScore

6.90

自引率

14.70%

发文量

251

审稿时长

2 months

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.