dc.description.abstract | There were three important chapters (chapter 3~5) in this study. In chapter 3, we used 24 solvents water, methanol, ethanol, isopropyl alcohol (IPA), n-butyl alcohol, benzyl alcohol, acetone, acetonitrile, nitrobenzene, N,N-Dimethylformamide (DMF), dimethy sulfoxide (DMSO), methyl ethyl ketone (MEK), ethyl acetate, methyl-t- butyl ester (MTBE), n-heptane, n-propanol N,N-dimethylaniline(DMA), xylene, p-xylene, toluene, benzene, 1,4 dioxane, tetrahydrofurn (THF), chloroform, and n-propanol) for initial solvent screening by temperature cooling. Results of investigation were shown as follows: (1) Sulfathiazole was soluble in MEK, THF, acetone, benzyl alcohol, n-propanol, acetonitrile, DMF, ethanol, DMSO, methanol, and H2O. The THF was the best solvent for scale-up. (2) The DSC may have induced the various forms of sulfathiazole of Form I, III, IV, and V in the single solvent. The Forms could be produced as a mixture in the solvent. (3) The various kinds of good solvent produced practically plate-like crystals except n-propanol. (4) The solubility curves could supply us the information of the different solubility at various temperature in different solvents and are essential for scale-up. (5) The solubility sphere predicted which solvents were good and which were bad. (6) The Form space could provide the solvents or the solvent combinations suitable for solvent screening. (7) The temperature cooling from 60°C to 25°C in crystallization linked up with industrial application and research.
In chapter 4, we used solvent mixtures (acetonitrile+n-propanol+H2O) for cocktail solvent by temperature cooling. Results of investigation were shown as follows: (1) Sulfathiazole was soluble in various molar ratios of solvent combinations. The 80:10:10, 60:20:20 and 45:10:45 combinations (acetonitrile: n-propanol: H2O) were optimum solvent combinations sulfathiazole Form III crystals for scale-up after comparing with solubility in the THF of the sulfathiazole Form III crystals. (2) The DSC revealed the various kinds of form: Form I, II, III, IV, V and IV of sulfathiazole generated from the cocktail solvents. (3) The various kinds of cocktail solvents produced small plate-like and large plate crystals. (4) The cocktail solvent was more suitable for scale-up than single solvent and it could reduce environmental pollution.
In chapter 5, we used the method of polymorph framing on a chip to screen sulfathiazole’s polymorphism. Results of investigation were shown as follows: (1) The template effect: Form I of sulfathiazole was formed on non-annealed chitosan film. Form III of sulfathiazole was formed on annealed chitosan film. Chitosan’s –OH and –NH2 group interacted with sulfathiazole’s S=O. (2) The volume effect provided different pathways to change the polymorphic outcome, which depended on concentration and time in this case. (3) The solvent effect showed that methanol (0.6 cP) of lower viscosity than water (0.89 cP) influenced molecular mobility affected the transformation rate of Form I to Form III. (4) The temperature effect showed that as the temperature increased and supersaturation decreased that gave rise to preferred the stable Form (G*III > G*I). Thus, we could just only harvested Form III of sulfathiazole in the evaporative process. | en_US |