Understanding the thermodynamic properties of multicomponent mixtures is of critical importance in many chemical and industrial applications. Experimental measurements become progressively difficult as the number of solution components increases -- producing the need for predictive models. Problems in development of predictive models arise if the mixture has one or more components that interact through molecular complexation or association. Experimental solubilities of anthracene and pyrene dissolved in binary systems containing one or more alcohols were measured in order to address this problem. Alcohols examined in this study were: 1-propanol, 2-propanol, 1-butanol, 2-butanol, 2-methyl-1-propanol, 3-methyl-1-butanol, and 1-octanol. In binary solvent mixtures containing only a single self-associating alcoholic solvent, the alkane cosolvents studied were: n-hexane, n-heptane, n-octane, 2,2,4-trimethylpentane, cyclohexane, methylcyclohexane, tert-butylcyclohexane. Predictive solubility equations were developed using mobile order theory. This approach differs from classical solution models by representing hydrogen bonding with a probability term rather than with expressions derived from stepwise equilibria or expressions to represent hypothetical solution aggregates. Results were compared with the predicted solubilities found from using expressions developed using the Kretschmer-Wiebe and Mecke-Kempter approaches for modeling associated solutions. It was found that the mobile order approach provided reasonably accurate predictions for the solute solubilities in the systems studied. The limitations and applications for mathematical methods of representing experimental isothermal solubility data were also studied for 72 systems. Two possible descriptive forms for this mathematical representation were suggested based on the various nearly ideal binary solvent (NIBS) and modified Wilson models.

Call number: LD2668 .T4 1966 S457 / Master of Science

published_or_final_version / abstract / Dentistry / Doctoral / Doctor of Philosophy

No description available.

No description available.

University of Macau / Institute of Chinese Medical Sciences

The amorphous state is becoming increasingly important in the pharmaceutical setting. Formulation of poorly water soluble drugs in the amorphous form enhances physicochemical properties of the drug, such as solubility and dissolution rate, which in turn may lead to an increased bioavailability. However, despite these advantages, many properties of the amorphous state are not yet understood and amorphous materials pose a challenge for structural analysis since they lack three dimensional long range order. Hence, compared to crystalline materials often little structural information can be gained using standard characterisation techniques. In this thesis, a range of analytical techniques and data analysis tools were used to characterise as well as quantify amorphous drugs and compare them to their crystalline counterparts. Apart from established characterisation techniques such as X-ray powder diffraction, microscopy, and differential scanning calorimetry, molecular-level characterisation was carried out using vibrational spectroscopies including infrared, near infrared, and Raman spectroscopy combined with multivariate analysis methods. To obtain deeper understanding of the structure of amorphous drugs and their corresponding crystalline forms novel approaches such as pair distribution function analysis of X-ray diffraction data and computational chemistry were employed. Three model drugs namely indomethacin, saquinavir, and fenofibrate were investigated in the scope of this thesis. For indomethacin differences between amorphous forms of indomethacin prepared by ball milling, spray drying, as well as melting and subsequent cooling were analysed using infrared, near infrared, and Raman spectroscopy in combination with principal component analysis. While all spectroscopic techniques were able to differentiate between the differently prepared samples, Raman spectroscopy proved to be most sensitive to small differences in the solid state of different samples. Consistent with the study of indomethacin, Raman spectroscopy combined with principal component analysis was the most sensitive analytical technique to detect structural changes induced by milling or heating saquinavir. In addition, pair distribution function transforms of the X-ray powder diffraction data significantly contributed to the understanding of differences in short-range and long-range order between differently treated saquinavir samples. A combination of vibrational spectroscopy, quantum mechanical calculations, and multivariate analysis proved suitable for physicochemical analysis of amorphous fenofibrate. The results of the study support the idea that non hydrogen bonded molecules such as fenofibrate are likely to exhibit random molecular orientations and conformations in the amorphous phase since the weak intermolecular interactions that occur between such molecules can easily be disrupted. A study of ternary mixtures of crystalline and amorphous forms of indomethacin showed that Raman and near-infrared spectroscopy in conjunction with PLS regression are well suited for quantification of the different solid-state forms simultaneously. It was found that near-infrared spectroscopy can be used to more accurately quantify the mixtures compared to Raman spectroscopy when fluorescing components, such as amorphous indomethacin, are present. Nevertheless quantification with Raman spectroscopy was still possible. Overall, the analytical methods used in this thesis were successfully employed for qualitative and quantitative analysis of amorphous drugs and their crystalline counterparts. It could be shown that it is beneficial to use a combination of different analytical techniques and data analysis tools since results are complementary and allow a more comprehensive description of the solid state.

The purpose of this study was to investigate the formation of solid molecular dispersions of Itraconazole (ITZ) in a number of glassy polymers including PVP, crospovidone, PVP-EC, HPMCAS and HPMCAS-PEO to enhance its dissolution and achieve release control. Polarizing light microscopy was found to be more sensitive than DSC and XRD for detecting crystallinity. PVP, PVP-EC & crospovidone generated loading levels of ~20%, substantially greater than that of HPMCAS and HPMCAS-PEO (5%). The loaded ITZ was stabilized though molecular interactions with the polymer and reduced molecular mobility in a glassy polymer matrix. Overall, immediate release was achieve d using PVP and crospovidone, enteric delivery provided by HPMCAS, and controlled release generated with EC and PEO. Among all polymers studied, only ITZ in PVP failed to generate sufficient stability in the presence of moisture. In general, solid molecular dispersion is a useful approach to improve the poor solubility and bioavailability of Itraconazole.

The purpose of this study was to investigate the formation of solid molecular dispersions of Itraconazole (ITZ) in a number of glassy polymers including PVP, crospovidone, PVP-EC, HPMCAS and HPMCAS-PEO to enhance its dissolution and achieve release control. Polarizing light microscopy was found to be more sensitive than DSC and XRD for detecting crystallinity. PVP, PVP-EC & crospovidone generated loading levels of ~20%, substantially greater than that of HPMCAS and HPMCAS-PEO (5%). The loaded ITZ was stabilized though molecular interactions with the polymer and reduced molecular mobility in a glassy polymer matrix. Overall, immediate release was achieve d using PVP and crospovidone, enteric delivery provided by HPMCAS, and controlled release generated with EC and PEO. Among all polymers studied, only ITZ in PVP failed to generate sufficient stability in the presence of moisture. In general, solid molecular dispersion is a useful approach to improve the poor solubility and bioavailability of Itraconazole.

This thesis illustrates a comprehensive study on the PVT, solubility and surface tension properties of polylactic acid (PLA) with dissolved CO2 based on thermodynamic models. The solubility of CO2 in PLA melt was calculated by means of a gravimetric method, using a Magnetic Suspension Balance (MSB). The swelling volume of the polymer/gas mixture due to dissolution of gas was compensated for by direct measurement through a view cell or by theoretical models such as Simha Somcynsky (SS) - Equation of State (EOS) and Sanchez Lacombe (SL) - Equation of State (EOS). Three grades of PLA (i.e., PLA3001D, PLA8051D, and PLA4060D) were chosen. It was observed that the pressure, temperature, D-content and Molecular weight variance had an effect on the swelling and solubility. The surface Tension of PLA/CO₂ mixture was also calculated from the captured image using the Axsymmetric Drop Shape Analysis (ADSA). The effects of varying the pressure, temperature, and molecular weight on surface tension were investigated.