New Insights into Additive Structure Effect on Crystal Agglomeration of L‐Valine

Abstract

Specific small amounts of amino acids caused agglomeration of L‐valine (L‐Val) crystals during evaporative crystallization from aqueous solutions. The agglomeration of L‐Val occurred only under acidic condition when guest amino acids satisfied several conditions. Only L‐form amino acids that have carboxylic acid groups and sufficiently long alkyl chain in the side‐chains could induce agglomeration of L‐Val. The length of alkyl chain in the side‐chains controls the degree of agglomeration. Data indicated only 0.5 wt % of L‐2‐aminoadipic acid, which has a similar chemical structure to L‐glutamic acid (L‐Glu), produced the large agglomerates > 1000 μm. The particle size was ∼ 500 μm when using the same amount of L‐Glu. Based on the results from previous tests and this paper, the whole mechanism for the L‐Val agglomeration in the presence of specific guest amino acids has been revealed.

Preparation and Formation Mechanism of l-Valine Spherulites via Evaporation Crystallization

“…The recent attention given to the morphology modification of the l -valine crystal form has revealed its potential to form spherulites. , For example, l -valine spherulites have been prepared in the presence of specific guest amino acids during evaporative crystallization from aqueous solution (adjusted to be acidic by addition of glutamic acid) …”

“…The recent attention given to the morphology modification of the L-valine crystal form has revealed its potential to form spherulites. 30,31 For example, L-valine spherulites have been prepared in the presence of specific guest amino acids during evaporative crystallization from aqueous solution (adjusted to be acidic by addition of glutamic acid). 31 This paper reports a polymer-induced method to obtain spherulites via evaporation, by adding a smaller amount of additives in a neutral solvent environment.…”

“…30,31 For example, L-valine spherulites have been prepared in the presence of specific guest amino acids during evaporative crystallization from aqueous solution (adjusted to be acidic by addition of glutamic acid). 31 This paper reports a polymer-induced method to obtain spherulites via evaporation, by adding a smaller amount of additives in a neutral solvent environment. The effects of temperature, additives, supersaturation, and initial concentrations on the particle size distribution were studied.…”

Agglomeration Mechanism of Azithromycin Dihydrate in Acetone–Water Mixtures and Optimization of the Powder Properties

“…6 Considerable effort has been invested to develop crystallization processes for the production of crystalline compounds with consistent crystal properties, i.e., purity, size, morphology, and size distribution. 7 However, the crystal size distribution (CSD) and the crystal shape of the product not only play an important role in determining the product solid-state properties such as separation, flowability, compaction, dissolution, and packing but also have considerable impact on the bioavailability of the active pharmaceutical ingredient. 8 The particle size, crystal morphology, and size distribution sometimes can be changed by agglomeration in the crystallization process.…”

Preventing Crystal Agglomeration of Pharmaceutical Crystals Using Temperature Cycling and a Novel Membrane Crystallization Procedure for Seed Crystal Generation

“…In some cases, the formation of regular agglomerates (mostly spherical) is desired, since they are easy to handle during downstream operations and can be more efficiently compacted [ 8 ]. Spherical agglomerates can be formed using a bridging liquid [ 9 , 10 ], a specific additive [ 11 ] or by cooling an oil-in-water emulsion where the crystallizing solution is localized within oil droplets [ 12 ]. Spherical agglomerates have recently been produced successfully in a continuous MSMPR (mixed suspension, mixed product removal) reactor [ 12 ] and in a microfluidic device [ 13 ].…”