Understanding Phase Transitions of Pharmaceutical Materials

Morritt, Alex (2020) Understanding Phase Transitions of Pharmaceutical Materials. Doctoral thesis, University of East Anglia.

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Abstract

The effect of confinement on pharmaceuticals is a growing field of interest for drug delivery because of the ability to customise both shapes and sizes of pore space. The pore diameters, volumes and surface areas affect the properties and structural arrangement of pharmaceuticals in ways we cannot currently predict. Nanometre sized pores also provide an interesting landscape for experiments into crystalline/amorphous and polymorphic transitions. However, due to the process of encapsulation, the analysis of these materials presents a challenge. In this work we demonstrate how combined material characterisation techniques such as solid-state NMR, DSC, TGA, PXRD, FT-IR and N2 sorption can be used in order to gain insight into the properties, structural characteristics and phase transitions of these encapsulated materials. We have also demonstrated how solvent mediated phase transitions can drive the same polymorphic interconversions that can be achieved by thermally dehydrating an API called acyclovir.

A cocrystal of flufenamic acid and nicotinamide, and nicotinamide on its own were chosen as pharmaceuticals to encapsulate in mesoporous silica hosts. At low loadings (<30% wt%) we have shown that FFA/NA remains in an amorphous state inside different mesoporous silica hosts, whereas at high loadings (>40% wt%) in larger pores of silica we have given evidence of crystalline ordering existing. Through the use of variable temperature MAS NMR and the 19F-19F NOESY pulse sequence we were able to distinguish three distinct components with different ordering and dynamics of FFA/NA that existed inside the same pore space. 13C solid state NMR and PXRD of nicotinamide inside pores larger than 6 nm revealed a polymorphic interconversion from form I to a previously unknown form which we later characterised as form [delta]. Polymorphic conversion of ACV hydrates into anhydrous forms was achieved through slurrying dry solvents with high polarity.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Science > School of Pharmacy
Depositing User: Chris White
Date Deposited: 28 Apr 2022 09:03
Last Modified: 28 Apr 2022 09:03
URI: https://ueaeprints.uea.ac.uk/id/eprint/84825
DOI:

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