Ambarkhane, Ameet Vijay; (2006) Characterisation of the amorphous solid state using solvent vapour induced transitions. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

There is increasing awareness about the amorphous form or disordered structure of material. The amorphous state is studied widely, due to two reasons; first, it is encountered without choice during many processes (e.g. milling/micronization) and second due to its advantages over the crystalline form (e.g. solubility). The important aspect of the amorphous form is its metastability (tendency to transform into a thermodynamically stable crystalline form). The current studies on the amorphous solid state involve, i) quantifying the disorders in otherwise ordered crystalline structures; ii) identifying the conditions under which its transformation into an ordered crystalline form could be controlled and iii) stabilizing the amorphous form by formulating as a solid dispersion. The characterisation of the amorphous state is mainly based on thermal analytical techniques (DSC) to estimate glass transition temperature. Other techniques, which are used routinely to study the amorphous state, involve spectroscopy (XRPD, FT-Raman, FT-IR, and Terahertz), microcalorimetric analysis (Solution calorimetry) and vapour sorption analysis (DVS). The aim of the thesis was to identify the techniques to characterise the amorphous state under the controlled conditions of temperature and humidity. These techniques would then be used to identify the conditions for the zero molecular mobility in the amorphous model substances selected for the study. The heating rate dependence of the glass transition was studied for amorphous indometacin. These studies were then used to calculate the fragility or the strength parameter and the activation energy (of relaxation process) for the amorphous solid. These parameters can be used to compare the relative stability of the different glasses. The StepScan DSC could successfully distinguish the process of aging in the amorphous states of indometacin, nifedipine and lactose. It was also observed that below a certain temperature for each amorphous state the relaxation time became extremely high, this temperature could be correlated to the Kauzmann temperature (Tk). The various transitions induced in the amorphous state of indometacin and lactose due to RH ramp were studied using DVS, perfusion calorimetry and IGC. The correlation of transitions from DVS was based on changes in weight gain profile as compared to changes in power output signal from perfusion calorimetry and changes in retention volume and pressure drop by using IGC. For amorphous lactose a sequence of transitions viz. mobility onset, glass transition, collapse and crystallisation could be followed as the RH was ramped. It was possible to characterise each transition with respect to a critical RH (%cRH) required for its induction e.g. %cRHg and %cRHcry as %RH required to induce glass transition and crystallisation respectively. The values of %cRH obtained using different techniques matched with each other. In the case of amorphous indometacin, the preferential surface plasticisation effect of sorbed water was demonstrated using IGC. Although the glass transition could be observed on the surface of amorphous particle, no spontaneous crystallisation could be seen with the RH ramp. Using a serial ramp of alcohol pressure (e.g. methanol, ethanol and propanol) by perfusion calorimetry it was possible to demonstrate glass transition and crystallisation in amorphous indometacin; these transitions could be observed from the power out put signal obtained. The different values of critical solvent pressures obtained at different temperatures were used to estimate Tk for amorphous indometacin and lactose. NIR studies demonstrated changes in amorphous nifedipine for the storage at room temperature, which otherwise would have been missed while characterising by IGC, DVS and TAM. The various techniques used in this work could be used very effectively to study the amorphous state.

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