This thesis describes the influence of solvents, additives and degree of supersaturation on the crystallization of polymorphs of phenylbutazone, a model pharmaceutical compound.; The physical properties of the solvent of crystallization determine the rate at which supersaturation is achieved. When supersaturation is achieved relatively rapidly, the metastable polymorphs of phenylbutazone crystallize, while when the rate is relatively slow, the stable polymorph crystallizes. When the rates are similar in two solvents, the nature and strength of the phenylbutazone-solvent interaction determines the nature of the polymorph that crystallizes. Weaker solute-solvent interactions favor crystallization of the stable polymorph of phenylbutazone. The presence of selected structurally related additives, antipyrine, diphenylhydantoin, or urea in the crystallization solution favors crystallization of the metastable polymorphs. The presence of the additives promotes rapid crystallization, which kinetically stabilizes the metastable polymorphs.; The initial degree of supersaturation of the crystallization solution influences the induction time and the nature of the polymorph that crystallizes. The induction time decreases with increase in supersaturation. The degree of supersaturation determines the relative rates of nucleation and crystal growth of the polymorphs, thereby influencing the nature of the polymorph that crystallizes. Crystallization of phenylbutazone from certain solvents of low polarity results in the corresponding solvates. The size of the solvent molecule and the strength of phenylbutazone-solvent interactions determine the crystal structure and the physico-chemical properties of each solvate.; The application of Raman spectroscopy for in situ monitoring of the phase transformations of solute during common processing steps is demonstrated. The technique is used to monitor changes during crystallization and during solvent-mediated polymorphic transformation.; A computational method is developed to estimate the time of onset of nucleation from supersaturated solutions using molecular dynamics simulation and knowledge of the solubility of the solute and the density of the saturated solution. The calculated and experimental nucleation times in various solvents are related linearly and by rank order.
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