Investigation of the amorphous properties of lactose and indometacin

Amorphous material can either be introduced in a formulation to aid bioavailability or induced accidentally during processing, which may have a detrimental effect on product performance, which means that its characterisation, detection and quantification are essential. My project aimed to characterise the amorphous material in order to better understand. This project aimed to investigate the influence of the variability of the amorphous and crystalline forms of a material on the quantification of amorphous content. A further aim of this project was to investigate the effect of the structural relaxation of amorphous material on its enthalpy of solution and dispersive surface energy and to develop a new methodology to characterise molecular mobility from enthalpy of solution and dispersive surface energy data.;Isothermal Perfusion Calorimetry and SC were employed to investigate the impact of the previous findings on the quantification of small amounts of amorphous material in low amorphous content samples with different anomeric composition. The quantification of amorphous content of a material with different initial anomeric composition, whose anomers exhibit different enthalpy crystallisation, is impossible unless the amorphous samples are prepared under the same conditions as those used to construct the calibration curves. Hence, unless the initial anomeric composition of the sample is known, one cannot have confidence in the amorphous content derived from the data. This observation had not previously been noted. A similar effect was noted for the SC data, because the anomers also had different enthalpies of solution.;SC and Inverse Phase Gas Chromatography (iGC) were used to investigate the effect of aging of amorphous lactose on its enthalpy of solution and dispersive surface energy, respectively. As aging time and temperature increase, enthalpy of solution and dispersive surface energies approach those of the crystalline state. Aging of amorphous material clearly affects its enthalpy of solution, which has a detrimental effect on the quantification of amorphous material using SC. The use of SC and iGC for the determination of the relaxation of an amorphous material was also investigated and compared to StepScanDSC. The relaxation of amorphous indometacin was also characterised using SSDSC, SC and iGC. The use of SC and iGC to follow the relaxation of amorphous materials is entirely novel and offers great promise.;Two principal methods were employed to quantify amorphous content; isothermal calorimetry (IC) and solution (ampoule-breaking) calorimetry (SC) and lactose was used as a model substance. IC allowed the quantification of amorphous content of lactose samples and a non-linear calibration curve could be plotted. This was ascribed to the fact that lactose exists as two anomers, each of which has a different enthalpy of crystallisation and amorphous lactose recrystallised to a final lactose with different anomeric composition, according to the initial amorphous content and anomeric composition of the initial crystalline portion.