Polymorph conversion, monitoring

Figure 8.19 Polymorph conversion monitored by Raman spectroscopy. A suspension of polymorph A (dotted line) is seeded att = 0 with the more stable polymorph B (solid line) that eventually converts to the thermodynamically stable polymorph C (broken line).

DeBraekeleer, K. Cuesta Sanchez, F. Hailey, P.A. etal., Influence and correction of temperature perturbations on NIR spectra during the monitoring of a polymorph conversion process prior to self-modelling mixture analysis /. Pharm. Biomed. Anal. 1997, 17, 141-152. 

A fiber optic probe was used by Blanco et al. for analysis of spasmoctyl samples with the active compound otilonium bromide and cellulose, maize starch, sodium starch glycolate, and glyceryl palmitostearate as excipients. Another study from this group covered the identification, qualification of the substance, and the quantification of the active component. A library search with a comparison to the near-infrared spectra of 163 pharmaceuticals was involved. An on-line monitoring for the determination of the endpoint of polymorph conversions in pharmaceutical processes was recently described further investigations into this field were published and are noted previously. ... 

Differentiation between polymorphs was performed by pattern recognition in 1995 by Aldrich et The actual control of a process was reported in 1998 by DeBraekeleer et al., where they described using PCA, SIMPLISMA, and orthogonal projections to correct for temperature variation during the monitoring of polymorph conversion. This is a real-time, in-line procedure. 

K. De Braekeleer, R Cuesta Sanchez, P. A. Hailey, D. C. A. Sharp, A. J. Pettman, and D. L. Massart, Influence and Correction of Temperature Perturbations on NIR Spectra during the Monitoring of a Polymorph Conversion Process prior to Self-Modelling Mixture Analysis, /. Pharm. Biomed. Anal., 17, 141 (1998). 

S. Barnes, J. Gillian, A. Diederich, D. Burton and D. Ertl, In process monitoring of polymorphic form conversion by Raman spectroscopy and turbidity measurements. Am. Pharm. Rev., 11, 80, 82-85 (2008). 

In addition to the identification of crystal moditications, SSNMR has been used to monitor reactivity and phase changes in different polymorphic forms. For instance, Harris and Thomas (1991) followed the photochemical conversion of formyl-fran -cinnamic acid with SSNMR (see also Section 6.4). Variable temperature techniques have been used to study the interconversion of four polymorphic modifications of sulphanilamide (/ -amino-benzenesulphonamide), including interpretation of at least some of the molecular motions during the course of the transformation (Frydman et al. 1990). A similar combination was augmented with colourimetric techniques to study the coexistence of two phases in the course of a phase transition (Schmidt et al. 1999). Of course, differences between unsolvated and solvated or hydrated crystal moditications may also be readily characterized by the SSNMR technique, as was done with the anhydrous and monohydrate of oxyphenbutazone (Stoltz et al. 1991). Due to the availability of the crystal structures for both modifications the SSNMR results could be interpreted directly in terms of the different atomic environments, especially for the differences in hydrogen bonding in the presence... 

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