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The use of biocompatible crystalline substrates for heterogeneous nucleation and polymorphic selection of indomethacin

Abstract

A heteroepitaxial nucleation approach was applied to control the nucleation rates and to selectively nucleate a single form of Indomethacin (IMC). Six organic functional crystalline substrates, L-Glutamic acid (GLU), L-Threonine (THR), Allantoin (ALT), Xanthine (XAN), Biotin (BIO) and L-Histidine (HIS) were selected as substrates. The efficacy of each substrate in promoting the nucleation of IMC was examined with a high throughput microscopic method. Polymorphic selectivity of each substrate towards stable γ-form and metastable α-form of IMC was investigated with a combination of microscopy, Raman spectroscopy, and powder X-ray diffraction. Induction experiments in ethanol demonstrated that all used substrates were highly effective in enhancing the nucleation rates of IMC. GLU showed complete selectivity towards the formation of γ-IMC and HIS increased the phase selectivity towards the metastable form by 33% compared to the homogeneous nucleation in ethanol. The combinatorial effect of the presence of HIS and supersaturation or the solvent, in promoting the polymorphic selection towards the metastable form was also investigated. Furthermore, Raman spectroscopy based crystal face indexing was conducted to identify the in contact faces for the substrate and IMC and demonstrated that major driving force for phase selective epitaxial growth in these organic molecular systems to be the level of functional group match at the substrate-solute interface.

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Publication details

The article was received on 06 Sep 2018, accepted on 02 Jan 2019 and first published on 11 Jan 2019


Article type: Paper
DOI: 10.1039/C8CE01517A
Citation: CrystEngComm, 2019, Accepted Manuscript
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    The use of biocompatible crystalline substrates for heterogeneous nucleation and polymorphic selection of indomethacin

    T. Wijethunga, X. Chen, A. S. Myerson and B. L. Trout, CrystEngComm, 2019, Accepted Manuscript , DOI: 10.1039/C8CE01517A

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