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Additives selectively inhibit or enhance the growth of crystal faces and effectively change crystal morphology. This paper demonstrates the first use of potassium chloride as additive during impinging jet crystallization of glycine, and also describes the optimization of this process by means of a full factorial design. The structural evaluation of powder particles was carried out by i.a. X-ray powder diffraction, differential scanning calorimetry, scanning electron microscopy with energy dispersive X-ray spectroscopy, headspace gas chromatography and flame atomic absorption spectrometry. It was observed that even a minor amount of KCl had a significant effect on the roundness, and reduced the particle size significantly compared to the samples without additive, despite of the extremely rapid nature of the crystallization process. This method resulted in the α-polymorph of glycine with an appropriate low residual additive content and a minimal residual organic solvent content. Based on the elemental maps of the samples, the arrangement and the optimal concentration of the additive were determined.

The parameters of crystallization processes determine the habit and particle size distribution of the products. A narrow particle size distribution and a small average particle size are crucial for the bioavailability of poorly water-soluble pharmacons. Thus, particle size reduction is often required during crystallization processes. Impinging jet crystallization is a method that results in a product with a reduced particle size due to the homogeneous and high degree of supersaturation at the impingement point. In this work, the applicability of the impinging jet technique as a new approach in crystallization was investigated for the antisolvent crystallization of glycine. A factorial design was applied to choose the relevant crystallization factors. The results were analysed by means of a statistical program. The particle size distribution of the crystallized products was investigated with a laser diffraction particle size analyser. The roundness and morphology were determined with the use of a light microscopic image analysis system and a scanning electron microscope. Polymorphism was characterized by differential scanning calorimetry and powder X-ray diffraction. Headspace gas chromatography was utilized to determine the residual solvent content. Impinging jet crystallization proved to reduce the particle size of glycine. The particle size distribution was appropriate, and the average particle size was an order of magnitude smaller (d(0.5)=8-35 μm) than that achieved with conventional crystallization (d(0.5)=82-680 μm). The polymorphic forms of the products were influenced by the solvent ratio. The quantity of residual solvent in the crystallized products was in compliance with the requirements of the International Conference on Harmonization.