Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.699604
Title: Crystallisation of amorphous fenofibrate and potential of the polymer blend electrospun matrices to stabilise in its amorphous form
Author: Tipduangta, Pratchaya
ISNI:       0000 0004 5990 4012
Awarding Body: University of East Anglia
Current Institution: University of East Anglia
Date of Award: 2016
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Abstract:
Fenofibrate was chosen as the drug of interest in this study because of its poor water-solubility, highly unstable amorphous state and unpredictable crystallisation behaviour. The crystallisation behaviour of amorphous fenofibrate is essential information that primarily corresponds to the physical stability of solid dispersion formulations. This project aims to probe how to control the crystallisation of amorphous fenofibrate, enhance its aqueous solubility and improve its physical stability by using electrospun polymer blend matrices. A range of characterisation technologies including MTDSC, ATR-FTIR, PXRD, SCXRD, SEM, TEM, HS-PLM, nano-TA and ss-NMR were used to characterise the physicochemical properties of both the crystallisation process of fenofibrate, and fenofibrate solid dispersions. The amorphous fenofibrate was crystallised using heterogeneous nucleation techniques, including surface disruption and impurity addition (talc). The presence or absence of an open top surface (OTS) was found to be one of the key factors which dictated the crystallisation of the amorphous fenofibrate into specific polymorphs. The use of thermal treatment in addition to OTS was able to finely tune the selectivity of the crystallisation of fenofibrate to form I or/and form IIa. The use of a low percentage of talc as heterogeneous nuclei resulted in the crystallisation of the new fenofibrate polymorph III. The polymer blend fibres prepared by electrospinning were phase separated solid dispersions that improved the aqueous solubility of the fenofibrate in comparison to the fenofibrate crystals. The drug-polymer and polymer-polymer miscibility were found to be the key parameters that affected the physical stability of the incorporated amorphous drug and the phase separation in the formulations. Additionally, the in situ phase separation of the hydrophilic and hydrophobic polymers in the blends led to modified drug release. The drug release rate could be fine-tuned by altering the ratio of the polymers. The new knowledge generated by this work relates to the following areas: 1) an improved understanding of the crystallization process of fenofibrate and its polymorphic control; 2) the use of polymer blend matrices in electrospun fibres that leads to the stabilization of amorphous drugs when they are incorporated in those fibres; and 3) the modification of the drug release profiles via the use of hydrophilic and hydrophobic polymer blend matrices for electrospinning.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.699604  DOI: Not available
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