Reliable and Selective Crystallization of the Metastable α-Form Glycine by Seeding

Abstract

This paper describes a reliable method to selectively produce metastable R-form glycine crystals with a controlled size in batch cooling crystallization. Seeding had a large effect both on the polymorphism and the size distribution of the product crystals. In the case of sufficient seed loadings of the R-form crystals, the metastable R-form crystals were obtained selectively as a product. Simultaneously, the crystal size distribution became unimodal with no fine crystals. However, at low seed loadings, mixtures of both the metastable R-and stable γ-form crystals were obtained. The measurement of supersaturation transient suggested that the low supersaturation caused by the growth of sufficient seeds played a key role in suppressing nucleation of the metastable R-and γ-form crystals, whereas, with no seeding, only the stable γ-form crystals were obtained. The seeding technique presented here could be a general and practical method to produce metastable polymorphs with controlled crystal size.

Process Control of Seeded Batch Cooling Crystallization of the Metastable α-Form Glycine Using an In-Situ ATR-FTIR Spectrometer and an In-Situ FBRM Particle Counter

“…It is known that the large amount of crystals can suppress secondary nucleation. 8 The transient supersaturation data obtained through the in-situ ATR-FTIR spectrometer are shown in Figure 6. The supersaturation with respect to the R-form glycine ∆C R , becomes minus on heating for a short period.…”

“…Many research papers dealing with the phenomenon have been published, [1][2][3][4][5] while only a few papers have proposed practical methodologies of the selective crystallization of a desired polymorphic crystals. [6][7][8] According to our previous study, 8 seeding was effective for the polymorphism control of glycine. The metastable R-form crystals of glycine were obtained selectively by cooling crystallization as product if sufficient seeds of the same R-form crystals were added to the system at the initial stage of a batch.…”

Combined Application of in Situ FBRM, ATR-FTIR, and Raman on Polymorphism Transformation Monitoring During the Cooling Crystallization

“…Therefore, solid composition is crucial in understanding polymorphism, which is of key importance in the pharmaceuticals. 3,4 With the aim of improving the understanding of pharmaceutical manufacturing processes and better controlling product quality, the control and consistency of solid phase properties through crystallization has been the focus of considerable industrial and academic researches. The studies of the polymorphic transformation by in situ technologies, such as FBRM, PVM, Raman, and ATR-FTIR, have been the focus of many investigations over the past few years.…”

Effects of pH and surface pressure on morphology of glycine crystals formed beneath the phospholipid Langmuir monolayers

“…Glycine crystals of different polymorphs with different shapes, such as plate, bipyramid, prism, spherulitic, and needlelike, have been obtained by making use of various methods, including from supersaturated aqueous solution through rapid cooling, slow cooling, and adding crystal seeds [5,6], adding ''tailor-made'' additives [7,8], changing pH values [8], adding alcohol [9], and exposing to intense pulses of plane-polarized laser light [10], from emulsions, microemulsions, and lameller phases formed by surfactants [11][12][13], by spray drying of supersaturated solutions [14], on the self-assembled monolayers [15,16], and at the air/liquid interfaces by Langmuir monolayer technique. Landau, Weissbuch et al synthesized various racemic and enantiomeric amphiphilic a-amino acid derivatives that formed Langmuir monolayers on the supersaturated aqueous solutions of glycine to study the interactions between the monolayers and glycine molecules, the crystallization behavior of glycine, the two-dimensional crystallization of racemic mixtures of a-amino acid amphiphiles, and the effect of glycine on the twodimensional crystallization [17,18].…”