Influence of Additives on Glycine Crystal Characteristics

Abstract

Different quantities of additives (sodium chloride and oxalic acid) and antisolvent (ethanol) were used in order to define their influence on crystallization of glycine from aqueous solutions. The solubility curves were determined for all process conditions but the nucleation points only for the initial concentration of glycine. The obtained results showed that both the quantity and type of the additive affect the solubility curves, the metastable zone width as well as the granulometric characteristics of crystals (aspect ratio, external shape, and the crystal size distribution). X-ray analysis confirmed occurrences of c-glycine by adding sodium chloride and oxalic acid, regardless of the added mass while the a-polymorphs were achieved by adding ethanol. IntroductionCrystallization is one of the most important methods to obtain pure solid crystalline compounds. In different industries, the most important requirements a crystallized solid-state product has to fulfil are its phase or polymorph stability with respect to thermodynamics and kinetics during its storage life and growth. Additionally, the size distribution determines the product solid-state properties such as separation, flowability, compaction, dissolution, and packing [1].Here, cooling crystallization of glycine from solution in the presence of different additives is investigated. Glycine was chosen as the model system because its solution and solid chemistries have been well studied and characterized and due to the properties of glycine crystals to be crystallized in three different polymorphs. Glycine exists in three crystalline modifications: a-, ß-, and c-forms with different relative stabilities and structures. It is well-known that the least stable form of glycine is the ß-form which transforms readily to the a-or c-form in a humid environment. Although, the a-form is quite stable at room temperature but c-glycine is thermodynamically the most stable form and has some special properties which are important for the pharmaceutical industry (nonlinear optical materials) [2].The crucial factors which yield different polymorphs are the thermodynamic variables (temperature, pressure, and concentration) and the process variables (agitation, supersaturation, seeding, cooling rate, pH values, and additives) [3]. Foreign substances present in the medium, used for the growth of a variety of various substances, have long been recognized to have a profound influence on the external appearance of crystals. Understanding the conditions of occurrence of the polymorphic forms and their transformations from one form into the other would be of great interest and useful for pharmaceutical applications [4].ß-Glycine can be produced under high-supersaturation conditions [5] and is usually crystallized using methanol, ethanol, 2-propanol, or acetone as antisolvent [6][7][8][9]. Pure aqueous solutions lead to the a-form, and the c-form occurs from aqueous solution only in the presence of selected impurities (sodium chloride, sodium hydroxide, sodium fluoride, sodium ni...

Adjustment of Process Conditions in Seeded Batch Cooling Crystallization

“…In order to apply the seeding technique successfully, it is helpful to know the width of the metastable zone [16]. The methodology for determination of the metastable zone width is explained in our previous article [7]. Fig.…”

“…The apparatus used in this work was the flat-bottomed crystallizer with internal diameter of D = 0.097 m as presented in the previous work [7]. …”

“…Amounts of used additives were: 1. [7]. Crystals produced by these experiments were dry-grinded for 8 min in the Fritsch Pulverisette 5 planetary ball mill at a rotation speed of 200 rpm.…”

“…For that purpose, the width of the metastable zone of pure glycine (PG) solution had to be determined. The polythermal method was applied as explained in the previous work [7].…”

“…Another key variable in batch cooling is seeding. Our previous glycine studies [7] showed that regular CSD, due to secondary nucleation, was very difficult to obtain by unseeded batch crystallization. The influence of seeding on crystallization is often critical to control a process, and the importance of an appropriate seeding strategy cannot be overemphasized [5].…”