Influence of solvent choice and operating conditions on Chlorzoxazone crystal shape and size

Abstract Solubility of pharmaceutical drugs in organic solvents is one of the important parameters to understand the equilibrium concentration of solute-solvent, which helps optimize and design crystallization conditions to obtain the desired product crystals. In the present study, Chlorzoxazone (CHZ) is used as a model pharmaceutical compound to investigate the equilibrium solubility, the influence of solvent and the operating conditions on the shape, and the size distribution. The solubility of CHZ is determined in organic solvents like Isopropanol, Ethanol, and 2-Ethoxyethylacetate, Ethylacetate and Ethyllactate using shake flask method from -5ºC to 60ºC. The solubility of CHZ in these solvents shows an increasing trend as the temperature increases in the following order: ethyllactate + water (0.5+0.5) < ethylacetate < isopropanol < ethanol < 2-ethoxyethylacetate < ethyllactate + water (0.75+0.25). The solvents, isopropanol, ethanol, and ethyl lactate, produce needle-shaped crystals, while 2-ethoxyethylacetate and ethyl acetate tend to produce plate shaped crystals. CHZ crystals obtained from 2-ethoxyethylacetate tend to have plate shaped crystals with a lower aspect ratio and are selected for batch cooling crystallization experiments performed at different cooling rates, and agitation. It is found that the agitation at 300 rpm and the cooling rate 0.2ºC/min produce more uniform crystal size distribution

Invited review: Crystals in cheese: More than a curiosity.

Scientific interest in cheese crystals extends back more than a century. However, starting around the 1970s, industry interest, and interest on the part of cheese scientists, grew dramatically as changes in cheesemaking technology and market changes caused the presence of crystals in the marketplace to increase; advanced analytical capabilities enabled new crystalline species to be identified, their origins and causative factors to be elucidated, and their contributions to cheese texture to be better understood. It is now evident that a host of organic- and inorganic-based crystals occur in natural cheeses. Some crystals form preferentially at the surface of rindless or rinded cheeses, others in the irregular openings or spherical eyes that occur within the body of some cheeses, and still others embedded within the cheese matrix. It is also evident that crystals may profoundly influence cheese texture, both as a direct consequence of their abundance, size, shape, and hardness, and as an indirect result of cascading physiochemical events initiated by crystal formation. Consumer response to increased incidence of crystals in the marketplace has been mixed. On the one hand, surface crystals of calcium lactate pentahydrate on Cheddar cheese came to be viewed quite negatively in some markets, often being mistaken for mold growth and spoilage. This triggered industry concern and led to considerable research to determine the underlying causes and to develop strategies to limit or prevent calcium lactate pentahydrate formation. At the same time, other forms of crystallization increasingly came to be viewed as positive features in the growing market dedicated to artisanal and traditional cheeses, giving rise to a bifurcated consumer response to cheese crystals that is evident today. Traditional artisanal cheesemakers perhaps have the most to gain from advances in cheese-crystal research. Traditional artisanal cheeses rely heavily on stories that are weaved around their identity to create uniqueness and add value. A challenge and opportunity for these cheesemakers in the United States and globally will be to translate the fascinating science of their cheese crystals into engaging narratives that capture the imagination, add value to their cheese, and enhance the enjoyment of their cheese by consumers.

Schema Matching and Data Integration with Consistent Naming on Protein Crystallization Screens.

The data representation as well as naming conventions used in commercial screen files by different companies make the automated analysis of crystallization experiments difficult and time-consuming. In order to reduce the human effort required to deal with this problem, we present an approach for computationally matching elements of two schemas using linguistic schema matching methods and then transform the input screen format to another format with naming defined by the user. This approach is tested on a number of commercial screens from different companies and the results of the experiments showed an overall accuracy of 97 percent on schema matching which is significantly better than the other two matchers we tested. Our tool enables mapping a screen file in one format to another format preferred by the expert using their preferred chemical names.

Economic model for obtaining cyclodextrins from commercial cgtase

A repetitive batch process was employed followed by membrane ultrafiltration system to produce low-cost cyclodextrins (CDs) using commercial enzymes Toruzyme® cyclomaltodextrin glucanotransferase (CGTase) and its kinetic parameters were determined. The ultrafiltration system enabled the removalof inhibitory products from the reaction medium, allowing the enzyme to be recovered for reuse. A 10 kDa membrane was used to separate the different CDs produced by the CGTase. The substrates evaluated were maltodextrin, corn starch and cassava starch at 5, 10 and 15% (w/V), in the presence and absence of 10% (V/V) ethanol. After reaction for 132 h, 10% (w/V) cassava starch in the presence of ethanol provided the best results with 32.1 mg/mL of ß-CD. Maximum production occurred after 72 h of reaction, with a yield of 87.4% of ß-CD and an α-CD, ß-CD and γ-CD production ratio of 1:1:0.08 g, respectively. When eight repetitive batches of 72 h followed by ultrafiltration and crystallization of ß-CD were performed, 2.1 g of precipitate was obtained with a purity of 67.6% ß-CD. The supernatant from the crystallization process was lyophilized and resulted in 35.3% α-CD. The developed model can be used industrially for the production of low cost CDs from easily obtained raw material

Cinder: keeping crystallographers app-y.

The process of producing suitable crystals for X-ray diffraction analysis most often involves the setting up of hundreds (or thousands) of individual crystallization trials, each of which must be repeatedly examined for crystals or hints of crystallinity. Currently, the only real way to address this bottleneck is to use an automated imager to capture images of the trials. However, the images still need to be assessed for crystals or other outcomes. Ideally, there would exist some rapid and reliable machine-analysis tool to translate the images into a quantitative result. However, as yet no such tool exists in wide usage, despite this being a well recognized problem. One of the issues in creating robust automatic image-analysis software is the lack of reliable data for training machine-learning algorithms. Here, a mobile application, Cinder, has been developed which allows crystallization images to be scored quickly on a smartphone or tablet. The Cinder scores are inserted into the appropriate table in a crystallization database and are immediately available to the user through a more sophisticated web interface, allowing more detailed analyses. A sharp increase in the number of scored images was observed after Cinder was released, which in turn provides more data for training machine-learning tools.

Categorization of the main descriptors of different ampicillin crystal habits

With the purpose of enabling the analysis by digital methods of particles of multisource pharmaceutical raw materials, this study analyzed different crystal habits of ampicillin particles, by grouping the external shapes obtained from 3 different solvents (acetonitrile, ethanol, and methanol), thereby reducing the number of descriptors necessary to adequately represent each shape. For this purpose, a selection of morphological descriptors was used including: circularity, roughness, roundness, compactness, aspect ratio, effective diameter, solidity, convexity, fractal dimension, and 10 Complex Fourier descriptors. These measures cover highly diverse morphological properties and define the crystal habit of a particle. Principal Component Analysis (PCA) and the Cluster Analysis (CA) were the grouping techniques used, which demonstrated the possibility of using between 2 and 4 descriptors instead of the 18 proposed initially.

Com o objetivo de possibilitar a análise, por meio de métodos digitais, de partículas de matérias-primas farmacêuticas de múltiplas fontes, analisaram-se diferentes cristais de partículas de ampicilina através do agrupamento de formas externas obtidas de três diferentes solventes (acetonitrila, etanol e metanol), reduzindo, desse modo, o número de descritores necessários para representar adequadamente cada forma. Com esse propósito, utilizou-se seleção de descritores morfológicos, incluindo: circularidade, aspereza, arredondamento, compactação, relação de aspecto, diâmetro efetivo, solidez, convectividade, dimensão fractal e 10 descritores complexos de Fourier. Essas medidas cobrem diversas propriedades morfológicas e definem a cristalinidade de uma partícula. As análises do componente principal (PCA) e por grupamento (CA) foram as técnicas de agrupamento utilizadas, que demonstraram a possibilidade de utilizar entre 2 e 4 descritores ao invés dos 18, inicialmente propostos.

[Reproducibility of the classification of ocular ferning patterns in Sjogren's syndrome patients]. / Reprodutibilidade na classificação do teste de cristalização do filme lacrimal em pacientes com síndrome de Sjögren.

PURPOSE: To verify the reproducibility of Rolando's classification of the tear ferning test using five different examiners and to compare the patterns of crystallization found in Sjögren's syndrome patients and normal subjects. METHODS: Tear ferning analysis of 29 patients with Sjögren's syndrome and of 45 patients without ocular disease were done using polarized light microscopy and the Rolando classification for tear ferning. Five examiners classified the ferning patterns of all the patients. ROC curve (Receiver Operating Characteristic) was used to find out the best score for the correct syndrome diagnosis. Kappa index (p<0.0001) was used to compare the results of the examiners among them and check the test's reproducibility. Charts were drawn to compare the two groups' results. RESULTS: Throught the ROC curve the score of 2.50 for diagnosis of Sjögren's syndrome was stablished. Considering the aggregated patterns I with II and III with IV, the examiners' level of pattern agreement was excellent (Kappa ranging from 0.82 to 0.97, p<0.0001). The group with Sjögren's syndrome was classified mostly as patterns III and IV and the patients without ocular disease mostly as I and II. CONCLUSION: The patterns associated with Sjögren's syndrome and normal patients matched the ones in the literature. The tear ferning test classification is reproductible when the Rolando classification was used for Sjögren's syndrome patients.

Reprodutibilidade na classificação do teste de cristalização do filme lacrimal em pacientes com síndrome de Sjõgren / Reproducibility of the classification of ocular ferning patterns in Sjogren's syndrome patients

OBJETIVO: Verificar a reprodutibilidade da classificação dos padrões do teste de cristalização do filme lacrimal utilizando cinco examinadores diferentes e comparar os padrões de cristalização de pacientes portadores da síndrome de Sjõgren com os de indivíduos não portadores de doenças da superfície ocular. MÉTODOS: Análise da cristalização da lágrima de 29 pacientes com Sjõgren e 45 pacientes sem doenças da superfície ocular, através de microscópio com luz polarizada, utilizando a classificação de Rolando. Para fins estatísticos foi estudada a curva ROC (Receiver Operating Characteristic) para determinar a melhor nota de corte do exame que separa indivíduos normais dos portadores da síndrome, índice de concordância Kappa (p<0,0001) para averiguar a reprodutibilidade da classificação dos padrões de cristalização e tabelas de contingência para comparação dos resultados entre os grupos. RESULTADOS: Com os padrões agregados (I com II e III com IV) a concordância dos examinadores foi alta (Kappa=0,82 a 0,97 e p<0,0001). Por meio da curva ROC obtivemos nota de corte de 2,50 para o diagnóstico de Sjõgren. Na comparação entre os grupos, o grupo normal recebeu predominantemente classificações de padrões I e II, ao passo que o grupo com Sjõgren, padrões III e IV. CONCLUSÕES: Houve concordância com a literatura quanto aos padrões encontrados nos pacientes com Sjõgren e nos pacientes sem doença da superfície ocular. A classificação do teste de cristalização é reprodutível quando utilizada a classificação de Rolando.

PURPOSE: To verify the reproducibility of Rolando's classification of the tear ferning test using five different examiners and to compare the patterns of crystallization found in Sjõgren's syndrome patients and normal subjects. METHODS: Tear ferning analysis of 29 patients with Sjõgren's syndrome and of 45 patients without ocular disease were done using polarized light microscopy and the Rolando classification for tear ferning. Five examiners classified the ferning patterns of all the patients. ROC curve (Receiver Operating Characteristic) was used to find out the best score for the correct syndrome diagnosis. Kappa index (p<0.0001) was used to compare the results of the examiners among them and check the test's reproducibility. Charts were drawn to compare the two groups' results. RESULTS: Throught the ROC curve the score of 2.50 for diagnosis of Sjõgren's syndrome was stabilished. Considering the aggregated patterns I with II and III with IV, the examinors' level of pattern agreement was excellent (Kappa ranging from 0.82 to 0.97, p<0.0001). The group with Sjõgren's syndrome was classified mostly as patterns III and IV and the patients without ocular disease mostly as I and II. CONCLUSION: The patterns associated with Sjõgren's syndrome and normal patients matched the ones in the literature. The tear ferning test classification is reproductible when the Rolando classification was used for Sjõgren's syndrome patients.

Litiasis renal inducida por indinavir / Indinavir and renal lithiasis

El indinavir es un nuevo, específico y potente fármaco que actúa, como otros agentes anti-retrovirales, inhibiendo la proteasa del virus de la inmunodeficiencia humana (VIH-1) o de la inmunodeficiencia adquirida (SIDA). El indinavir se une al centro activo del enzima, originando un descenso en plasma de ARN VIH-1 y un aumento de los linfocitos T-CD4 "helper" dando origen a un descenso del enzima, necesaria para la maduración y replicación del VIH-1.El presente trabajo estudia la cristaluria de dos de los nueve pacientes que padecían VIH-1 y/o SIDA tratados con indinavir, así como el cálculo formado por uno de los dos pacientes que presentaban cristaluria.El estudio se realizó con microscopio de luz polarizada y por espectrofotometría infrarroja, mostrando que la visualización de la cristaluria con microscopio de luz polarizada es útil para la caracterización de las mismas, así como para el estudio de los cálculos renales es útil el análisis por espectrofotometría infrarroja

Indinavir is a new specific and potent drug that inhibits, like other antiretroviral agents, the proteaseof immune deficiency virus (HIV) or acquired immune deficiency syndrome (AIDS), an enzymenecessary to maduration and replication of the virus. Indinavir has the capacity to bind the activesite causing a decrease in plasma of HIV1-RNA and an increase of T-CD4 helper lymphocytes. Theaim of this work is to study in HIV and/or AIDS patients treated with indinavir the crystalluria andthe formation of renal calculi due to the clearance of this drug. Two out of nine patients studied inthis work presented abundant crystalluria and one of them presented spontaneously passed renalstone.Urinary crystals were studied under polarized-light microscopy and renal stone was analyzed byinfrared spectroscopy