Increased Chemical Purity Using a Hydrate

Abstract

Crystallization is usually a highly selective process, and this selectivity is exploited in the pharmaceutical and other industries as a method of chemical purification. Relatively little is known about how polymorphism and solvate formation can influence the selectivity of crystallizations. We describe a piperidene pharmaceutical intermediate that can crystallize as either a hydrate or an anhydrous form, with very different purities. The exploitation of this effect is described, and an explanation in terms of the crystal structures is proposed.

A Structured Approach To Cope with Impurities during Industrial Crystallization Development

“…The target polymorph should also be included in the product specification. It was noted that the presence of impurities has been reported to induce polymorphic transformations during crystallization which can directly affect impurity rejection behavior; 38 − 40 however, this was classified as out of scope during this work. It is assumed going forward that the crystallization leads to the isolation of the specified product polymorph.…”

“…Some strategies go beyond adaption of crystallization design. 40 A partial solid solution concentration beyond the upper limit impurity concentration for instance limits the achievable crystallization selectivity. The impurity rejection issues will have to be mitigated using other separation technologies or changes to process chemistry.…”

Solvate Formation of Bis(demethoxy)curcumin: Crystal Structure Analyses and Stability Investigations

“…Since solvents are unavoidably used during processing, manufacturing or storage of APIs, the investigation of solvate formation deserves particular attention 5,6 . Additionally, the solvate formation property could be used as a method of purification [7][8][9] . Moreover, desolvation of solvates could be an option to prepare new polymorphic forms, which might be inaccessible by the conventional crystallization methods [10][11][12][13] .…”

Controlled precipitation of nesquehonite (MgCO3·3H2O) by the reaction of MgCl2 with (NH4)2CO3

“…In the last 15 years, the development of new methodologies for design and operation of crystallization-based separation processes has become of interest to the chemical process sector [2][3][4][5]. For the usage of MgCl 2 resource the preparation of hydromagnesite (Mg 5 (CO 3 ) 4 (OH) 2 Á 4H 2 O) [6] or magnesium hydroxide [7] through different methods has been proposed.…”