Harding (2007) Dynamic light scattering as a relative tool for assessing the molecular integrity and stability of monoclonal antibodies, Biotechnology and Genetic Engineering Reviews, 24:1, 117-128,

No abstract

This work seeks to develop a calibration-free statistical approach based on Raman spectroscopy for on-line identification of impurities during co-crystallization. Caffeine-glutaric acidacetonitrile was employed as the model system, which forms co-crystals from solution at appropriate conditions. Raman spectra were collected in three classes of suspensions with a solid mixture of caffeine crystals and co-crystals, pure co-crystals, and a mixture of glutaric acid crystals and co-crystals, respectively at different temperatures. These suspensions were used to represent the possible products of co-crystallization processes during which single component could crystallize out concomitantly with the desired co-crystal. A statistical model combining principal component analysis (PCA) and discriminant analysis (DA) was developed to classify these suspensions. PCA was first performed for these spectra and the resulting first few principal components were subjected to DA. It was found that the three classes of suspensions can be distinguished clearly by DA.

The hydrate form of a poorly water-soluble active pharmaceutical ingredient (API), spironolactone (SP), was produced using antisolvent precipitation in the presence/ absence of polymer templates and stirring. Different crystal habits were observed depending on the polymer added. Superstructures consisting of primary constituent units were obtained in the presence of hydroxypropyl methylcellulose (HPMC), while tubular crystals with highly fused surfaces were observed in the presence of polyvinylpyrrolidone (PVP). In contrast, tubular and dendritic crystals were obtained in the absence of polymer. The structural evolution of the particle formation process was monitored by scanning electron microscopy (SEM), which reveals the growth mechanisms leading to different crystal habits. Superstructures are attributed to self-assembly growth, while tubular and dendritic crystals are formed under diffusion limited growth. The results suggest a potential way to produce crystals with the desired crystal habit by appropriate selection of polymer additive and precipitation conditions.