| Incorporation of solvent molecules into the crystal structure of an organic compound has strong effects on the solvate's chemical and physical properties; and hence, pharmacokinetics. Therefore, a study on pseudopolymorphic transitions and the ability of solvents to form pseudopolymorphs with pharmaceutical compounds is important for the pharmaceutical industries.;The main goals of this study were to provide quantitative descriptions of the crystallization and solid-state transformation of pseudopolymorphs of sodium naproxen in mixed alcohol-water solvents. Furthermore, organic alcohol solvates of sodium naproxen were discovered, and characterized qualitatively and quantitatively.;Several pseudopolymorphic forms of sodium naproxen were crystallized from methanol-water and ethanol-water solutions, including hydrated and alcohol-solvated forms. Results showed that the transitions of the pseudopolymorphic forms occurred at temperatures that depended upon the solvent concentration. Results also revealed that water activity was a controlling factor for the transitions because regardless of which alcohol solvent mixture was used, the water activity was the same for similar transitions.;A methanol-solvated form of sodium naproxen was discovered and fully characterized using a variety of analytical techniques. The methanol solvate was crystallized from pure methanol at 10°C and was determined to be in a one to one ratio of sodium naproxen to methanol. For further analysis, a single crystal study of crystals obtained by slowly evaporating methanol at approximately 4°C was performed and revealed a solvate with a two to three ratio of sodium naproxen to methanol. The 1.5 solvate was shown to not be representative of the entire sample, but still provided insight into the bonding of the methanol solvent in sodium naproxen. Hydrogen bonding was determined to be the main force in solvation, along with Na-O coordination between methanol and sodium naproxen.;The heats of solution for each pseudopolymorph were estimated by fitting the solubility data with the van't Hoff equation. The stability of hydrated forms over solvated forms at higher temperatures was proven for enantiotropic systems from a thermodynamic cycle.;Additionally, the ability of sodium naproxen to solvate with other alcohol solvents was explored, specifically looking at comparisons between ethanol, 1-propanol, 2-propanol, 1-butanol, and isobutanol solvents. It was shown that as the size and/or branching of the alcohol increased the ability to solvate decreased in relation to the molar amount of the alcohol present in the crystal structure. Additionally larger, branched alcohols required more energy to desolvate based on the energy per mole of alcohol. This is related to the fact that these solvates had a smaller amount of alcohol present in the solvate; and hence, had strong bonding with the sodium naproxen molecule. |
