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Title: Amorphous sugar matrices : preparation, characterisation and the degradation of actives embedded in them
Author: Chopra, R.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2007
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The aim of this thesis was to understand the factors that control the chemical stability of the active in amorphous matrices. The actives used in the present study were (i) np-THP (2-(p-nitrophenoxy)tetrahydropyran) and (ii) CP-481,715 (quinoxaline-2-carboxylic acid [4(R)-carbamoyl-1(S)-(3-fluorobenzyl)-2(S)-7-dihydroxy-7-methyloctyl] amide). np-THP degrades via C-O bond cleavage and CP-481,715 via intramolecular lactonisation. The sugars used were sucrose, trehalose and raffinose. In the vicinity of Tg, matrix molecular mobility of an amorphous material follows non-Arrhenius temperature dependence. However, np-THP degradation did not show non-Arrhenius kinetics throughout this temperature range. At temperatures above Tg, np-THP degradation followed Arrhenius behaviour, whereas at temperatures below Tg, both, non-Arrhenius and Arrhenius behaviour was observed. The observed trends of np-THP degradation were explained by consideration of the possible degradation pathways, rate-limiting steps and crossover of the rates of steps involved in the degradation pathway. A novel explanation has been given for the Tg dependence of the degradation rate even though the reaction is not matrix molecular mobility-controlled. In order to distinguish between the role of water as a reactant or as a plasticizer, sucrose and trehalose sugars were used because of their similar molecular weight (MW 342 g/mol) (and hence likely similar packing efficiency) to attain matrices with similar Tg values but differing water content and vice versa. The work demonstrated that since the rate-limiting step for degradation may change with alteration in the experimental conditions, the factors that control the stability of an active under a set of experimental conditions may not be the same under a different set of conditions. Consideration of the reaction mechanism and the possible rate-limiting steps is therefore crucial.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available