Many analytical techniques, such as differential scanning calorimetry (DSC), X-ray diffraction (XRD), infrared spectroscopy (IR) and Raman spectroscopy can be used to differentiate between crystalline polymorphs of the same chemical entity. While all of these techniques are routinely applied to off-line analysis of materials, Raman spectroscopy has the advantage over these other techniques in that Raman technology currently exists for in situ monitoring of the solid-phase behavior within a mixed suspension of liquid and solid. In this work, we present our results from an in situ Raman study, demonstrating the solvent-mediated polymorphic phase transformation of progesterone. In situ Raman analysis has shown that the appearance of Form I progesterone is always preceded by the formation of Form II progesterone. Phase transformation rates were found to increase monotonically as the temperature increases, which indicates that the polymorphic system is monotropic. Form I was found to be thermodynamically more stable than Form II, while Form II was found to be kinetically favored over Form I. The results from this study are consistent with Ostwald's law of stages and lead to an in-depth understanding of the polymorphic transformation process of progesterone. The in situ monitoring capabilities of Raman spectroscopy have allowed us to define the processing parameters required to control the morphology of crystalline progesterone.

A continuum model for multicomponent distillation in the minimum reflux limit, first proposed by Nandakumar and Andres, is refined for the special case of constant relative volatility (CRV) and constant molar overflow (CMO) and is extended to columns with multiple feeds and multiple products. A relaxation algorithm for calculating steady-state conditins in any minimum reflux CRV, CMO column is established. This generalization of Underwood's classic treatment of single-feed columns is used to explore the characteristics of several single-feed and multiplefeed distillation systems. Critical operating points at which the steadystate composition profile in a minimum reflux column is indeterminate are identified and analytical expressions predicting the location of these points are established.

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