Building solids inside nano-space: from confined amorphous through confined solvate to confined ‘metastable’ polymorph

Nartowski, K. P., Tedder, J., Braun, D. E., Fabian, L. and Khimyak, Y. Z. (2015) Building solids inside nano-space: from confined amorphous through confined solvate to confined ‘metastable’ polymorph. Physical Chemistry Chemical Physics, 17 (38). pp. 24761-24773. ISSN 1463-9076

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Abstract

The nanocrystallisation of complex molecules inside mesoporous hosts and control over the resulting structure is a significant challenge. To date the largest organic molecule crystallised inside the nano-pores is a known pharmaceutical intermediate – ROY (259.3 g mol1). In this work we demonstrate smart manipulation of the phase of a larger confined pharmaceutical – indomethacin (IMC, 357.8 g mol1), a substance with known conformational flexibility and complex polymorphic behaviour. We show the detailed structural analysis and the control of solid state transformations of encapsulated molecules inside the pores of mesoscopic cellular foam (MCF, pore size ca. 29 nm) and controlled pore glass (CPG, pore size ca. 55 nm). Starting from confined amorphous IMC we drive crystallisation into a confined methanol solvate, which upon vacuum drying leads to the stabilised rare form V of IMC inside the MCF host. In contrast to the pure form, encapsulated form V does not transform into a more stable polymorph upon heating. The size of the constraining pores and the drug concentration within the pores determine whether the amorphous state of the drug is stabilised or it recrystallises into confined nanocrystals. The work presents, in a critical manner, an application of complementary techniques (DSC, PXRD, solid-state NMR, N2 adsorption) to confirm unambiguously the phase transitions under confinement and offers a comprehensive strategy towards the formation and control of nano-crystalline encapsulated organic solids.

Item Type: Article
Faculty \ School: Faculty of Science
Faculty of Science > School of Pharmacy
Depositing User: Pure Connector
Date Deposited: 04 Nov 2015 15:00
Last Modified: 24 Jun 2020 23:55
URI: https://ueaeprints.uea.ac.uk/id/eprint/54997
DOI: 10.1039/C5CP03880D

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