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Issue 37, 2019
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Stepwise dissolution and composition determination of samples of multiple crystals using a dissolution medium containing aqueous alcohol and fluorocarbon phases

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Abstract

Crystallisations are widely used in pharmaceutical and fine chemical manufacturing to control impurity levels, however crystallisations do not always reduce impurities to acceptable levels. Information on the location and distribution of impurities in crystallised materials would be helpful in such cases. A two phase dissolution medium featuring a fluorocarbon non-solvent vehicle and a aqueous ethanol solvent phase has been used to determine the composition of multi-particle crystalline samples through a partial dissolution approach combined with particle sizing and HPLC analysis. 4-Chloro-2-nitroacetanilide (1) was chosen as the host compound for this study, with 4-methyl-2-nitroacetanilide (2) and 4-tert-butyl-2-nitroacetanilide (3) chosen as the guest impurities that were added to supersaturated toluene solutions of 1 at levels up to 5 mol%. The crystals that formed were subjected to a series of partial dissolution steps carried out using the biphasic dissolution medium composed of a 50% aqueous ethanol solvent phase and a perfluorohexane continuous phase. To inhibit particle agglomeration, the mixture also contained 13,13,14,14,15,15,16,16,17,17,18,18-dodecafluoro-2,5,8,11-tetraoxaoctadecane (4) as a non-ionic surfactant. The partial dissolution steps showed a relatively even dissolution with each sequential step as determined from particle sizing. Analysis of the solutions by HPLC from each partial dissolution step allowed the level of impurity to be determined, and when combined with the particle sizing data this allowed an impurity distribution to be generated. Impurity 2 was found to be relatively evenly distributed while impurity 3 was localised on or near the surfaces of crystals.

Graphical abstract: Stepwise dissolution and composition determination of samples of multiple crystals using a dissolution medium containing aqueous alcohol and fluorocarbon phases

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Supplementary files

Article information


Submitted
12 Apr 2019
Accepted
02 Jul 2019
First published
09 Jul 2019

This article is Open Access

RSC Adv., 2019,9, 21405-21417
Article type
Paper

Stepwise dissolution and composition determination of samples of multiple crystals using a dissolution medium containing aqueous alcohol and fluorocarbon phases

H. A. Moynihan and D. Armstrong, RSC Adv., 2019, 9, 21405
DOI: 10.1039/C9RA02781E

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