Ding, Zhiyi; (2007) A calorimetry study of drug/polymer interaction. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Many drugs are poorly water soluble and their dissolution rate can limit bioavailability. Preparing drugs in dispersed systems can enable them to be readily absorbed when they enter the Gastrointestinal Tract. However, the stability of such systems is not always desirable. The aims of this work were to investigate the use of calorimetry as a method for investigating the stability of dispersed systems in a thermodynamic perspective. This work was also aimed at investigating the possibility of predicting the stability of solid dispersions by studying the interactions between drug and components in their liquid state. Isothermal Titration Caloriemetry (ITC) was employed to study the interactions between poloxamer and ibuprofen/ketoprofen suspensions. The significant variation shown from the interactions led to the study on the equilibration of poloxamer solutions and their association behaviour in water. It was found that poloxamer solutions were concentration dependent and poloxamer formed aggregates following the open association model. The investigation suggested that a large time scale was required for poloxamer solution to reach equilibrium which was essential in ensuring consistent performance and solutions were provided as to how to efficiently achieve equilibrium state of poloxamer solutions at different concentrations. All these findings significantly improved the poor reproducibility, enabled better application of poloxamer solutions and better understanding of how to handle poloxamer solutions. A calorimetric study was carried out to investigate the effect of a second excipient Poly(2-hydroxypropylmethacrylate) (PHPMA) on the stability of Griseofulvin / Indomethacin - Polyvinylpyrrolidone (PVP) solid dispersions. Studies were carried out in liquid state. It was found that the addition of PHPMA significantly increased the stability of solid dispersions in both binary and ternary systems. Systems in which PHPMA was added last showed the greatest stability indicating its order of addition was essential to the stability of the system. Correlation with previous studies suggested that calorimetry can be used to predict the stability of solid dispersions in their solid states by studying their properties in their liquid states and hence avoid of many uncertainties introduced during the manufacture processes.

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