Application of Selective Crystallization Methods To Isolate the Metastable Polymorphs of Paracetamol: A Review,Organic Process Research & Development

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Application of Selective Crystallization Methods To Isolate the Metastable Polymorphs of Paracetamol: A Review
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2019-12-04 , DOI: 10.1021/acs.oprd.9b00322
Patrı́cia C. Cruz ₁ , Fernando A. Rocha ₁ , António M. Ferreira ₁

Affiliation

Paracetamol is a popular antipyretic and analgesic active pharmaceutical ingredient that is used worldwide in the production of several millions of tablets and other dosage forms every year. Paracetamol has three fully characterized polymorphs (forms I, II, and III), and also two high pressure polymorphs with unknown crystal structure (forms IV and V). Form I is the most stable polymorph, but unfortunately, it is not appropriate for direct compression into tablets due to its weak compression properties. On the other hand, forms II and III exhibit better compression properties; however, they are more difficult to harvest and isolate. This has been motivating the development of a diversity of crystallization methods that allow the selective production of forms II and III of paracetamol, which includes crystallization from melts, crystallization from liquid solutions, application of high pressures, seeding, heterogeneous nucleation, contact line crystallization, reaction coupling, ultrasound assisted crystallization, and multicomponent crystallization. In this review, we present a brief description of these methods and summarize their main advantages and disadvantages.

中文翻译：

选择性结晶方法在扑热息痛中分离亚稳态多晶型的研究进展

扑热息痛是一种流行的解热镇痛活性药物成分，每年在世界范围内用于生产数百万片片剂和其他剂型。扑热息痛具有三种完全表征的多晶型物（形式I，II和III），以及两种具有未知晶体结构的高压多晶型物（形式IV和V）。形式I是最稳定的多晶型物，但是不幸的是，由于其弱的压缩特性，它不适合直接压缩成片剂。另一方面，形式Ⅱ和Ⅲ表现出更好的压缩性能。但是，它们更难以收获和分离。这一直在推动着多种结晶方法的发展，这些方法可以选择性生产扑热息痛的II型和III型，包括从熔体中结晶，从液体溶液中结晶，施加高压，接种，异相成核，接触线结晶，反应耦合，超声辅助结晶和多组分结晶。在本文中，我们简要介绍了这些方法，并总结了它们的主要优点和缺点。

更新日期：2019-12-04

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