Reduction of glycine particle size by impinging jet crystallization

Abstract

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.

Continuous Generation of Millimeter-Sized Glycine Crystals in Non-Seeded Millifluidic Slug Flow

“…The crystal size for Condition 3 was larger than that of Condition 1 and 2 ( Figure 5), which directly came from the different numbers of crystals (with secondary nucleation shut off for all three conditions). For a similar condition in batch cooling crystallization (with initial temperature of 35 • C and final temperature of 20 • C) [59], crystals with an average size of circa 600 µm were generated after 20 min to 6 h [60,61], and here, only 10 min were needed. Although glycine was the compound used here, a similar strategy (e.g., suppressing secondary nucleation) may potentially help generate large crystals of other compounds [62][63][64][65][66][67][68][69][70][71][72].…”

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

“…Higher sonication intensity and longer sonication time favour the formation of smaller crystals with narrow PSD [20][21][22].Impinging jet crystallization is a relatively new field for the researchers in pharmaceutical manufacturing and industrial crystallization [23]. However, it is proved that this method effectively reduces particle size, as well as it has the potential advantage to produce reproducible products with small average particle size and narrow PSD [24]. 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].…”

Continuous reactive crystallization of pharmaceuticals using impinging jet mixers

“…The previous work is inspiring though some design and operational conditions were not given in details. Other recent research on impinging jet crystallization was from Tari et al and Liu et al Tari et al studied antisolvent crystallization of glycine and found that it produced small crystals with narrow size distribution. In addition to experimental research, there was also work on modelling of impinging jet crystallizers …”