Optimizing the Crystal Habit of Glycine by Using an Additive for Impinging Jet Crystallization

Abstract

Additives selectively inhibit or enhance the growth of crystal faces and effectively change the crystal morphology. For the first time, potassium chloride was used as additive during impinging jet crystallization of glycine. The structure of the powder particles was evaluated by X-ray powder diffraction, differential scanning calorimetry, scanning electron microscopy with energy dispersive X-ray spectroscopy, headspace gas chromatography, and flame atomic absorption spectrometry. Even a minor amount of KCl had a significant effect on the crystal roundness and reduced the particle size significantly, despite of the extremely rapid nature of the crystallization process. This method resulted in the a-polymorph of glycine with an appropriate low residual additive content and a minimal residual organic solvent content. The arrangement and the optimal concentration of the additive were determined.

Comparative Study of Different Crystallization Methods in the Case of Cilostazol Crystal Habit Optimization

“…The rich solution of the API and the antisolvent flow through two jet nozzles, which are arranged diametrically opposite each other, and it enables the generation of high-intensity micromixing of fluids to achieve high and continual supersaturation before the onset of nucleation at the impinging point [25,26]. Some recent literature developed the impinging jet method with different processes, such as combined with the use of additives to improve the crystal roundness of the products [27] or supplemented with cooling crystallization to narrow crystal size distribution [28].In the case of poorly water-soluble drugs, which belong to Biopharmaceutics Classification System (BCS) Classes II or IV, the crystal habit is particularly important [29,30]. The small particle size of the final crystallized product can increase dissolution rate and quantity from dosage forms, improve the bioavailability of the drug products, as well as enhance the stability and the uniformity of the API incorporated in tablets [31,32].…”

“…The rich solution of the API and the antisolvent flow through two jet nozzles, which are arranged diametrically opposite each other, and it enables the generation of high-intensity micromixing of fluids to achieve high and continual supersaturation before the onset of nucleation at the impinging point [25,26]. Some recent literature developed the impinging jet method with different processes, such as combined with the use of additives to improve the crystal roundness of the products [27] or supplemented with cooling crystallization to narrow crystal size distribution [28].…”

Computing Crystal Size Distribution by Focused‐Beam Reflectance Measurement when Aspect Ratio Varies

“…In chemical industry, the crystal size distribution (CSD) of crystalline, powder, or granular products significantly influences the efficiency of downstream processes [1,2], bioavailability of active pharmaceutical ingredients [3][4][5][6], catalytic activity [7][8][9][10], and so on. Therefore, it is essential for CSD to be obtained online in manufacturing processes.…”