6,355 research outputs found
PAT-based design of agrochemical co-crystallization processes : a case-study for the selective crystallization of 1:1 and 3:2 co-crystals of p-toluenesulfonamide/triphenylphosphine oxide
In this study, the selective crystallization and characterization of the stoichiometric forms of the p-toluenesulfonamide/triphenylphosphine oxide (p-TSA-TPPO) co-crystal system in acetonitrile (MeCN) is demonstrated using batch and semi-batch crystallizers. In the batch study, both 1:1 and 3:2 p-TSA-TPPO were successfully isolated as pure forms. However, process variability was observed in a few experimental runs. To address the batch process variability issue, a control strategy was implemented using temperature cycling, aided by in situ process analytical technologies (PAT) to convert from 3:2 to 1:1 p-TSA-TPPO. In the semi-batch co-crystallization studies, the two molecular co-formers, p-TSA and TPPO, were dissolved in MeCN and pumped separately to the crystallizer. Changing the flow rates of the respective active ingredients allowed control over the co-crystallization outcome, and presents as a promising opportunity for development of a continuous co-crystallization process
PAT-based design of agrochemical co-crystallization processes: a case-study for the selective crystallization of 1:1 and 3:2 co-crystals of p-toluenesulfonamide/triphenylphosphine oxide
In this study, the selective crystallization and characterization of the stoichiometric forms of the p-toluenesulfonamide/triphenylphosphine oxide (p-TSA-TPPO) co-crystal system in acetonitrile (MeCN) is demonstrated using batch and semi-batch crystallizers. In the batch study, both 1:1 and 3:2 p-TSA-TPPO were successfully isolated as pure forms. However, process variability was observed in a few experimental runs. To address the batch process variability issue, a control strategy was implemented using temperature cycling, aided by in situ process analytical technologies (PAT) to convert from 3:2 to 1:1 p-TSA-TPPO. In the semi-batch co-crystallization studies, the two molecular co-formers, p-TSA and TPPO, were dissolved in MeCN and pumped separately to the crystallizer. Changing the flow rates of the respective active ingredients allowed control over the co-crystallization outcome, and presents as a promising opportunity for development of a continuous co-crystallization process
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Co-crystal structures of furosemide:urea and carbamazepine:indomethacin determined from powder x-ray diffraction data
Co-crystallization is a promising approach to improving both the solubility and the dissolution rate of active pharmaceutical ingredients. Crystal structure determination from powder diffraction data plays an important role in determining co-crystal structures, especially those generated by mechanochemical means. Here, two new structures of pharmaceutical interest are reported: a 1:1 co‑crystal of furosemide with urea formed by liquid-assisted grinding and a second polymorphic form of a 1:1 co‑crystal of carbamazepine with indomethacin, formed by solvent evaporation. Energy minimization using dispersion-corrected density functional theory was used in finalizing both structures. In the case of carbamazepine:indomethacin, this energy minimization step was essential in obtaining a satisfactory final Rietveld refinement
Acetylene-ammonia-18-crown-6 (1/2/1)
The title compound, C2H2·C12H24O6·2NH3, was formed by co-crystallization of 18-crown-6 and acetylene in liquid ammonia. The 18-crown-6 molecule has threefold rotoinversion symmetry. The acteylene molecule lies on the threefold axis and the whole molecule is generated by an inversion center. The two ammonia molecules are also located on the threefold axis and are related by inversion symmetry. In the crystal, the ammonia molecules are located below and above the crown ether plane and are connected by intermolecular N-H...O hydrogen bonds. The acetylene molecules are additionally linked by weak C-H...N interactions into chains that propagate in the direction of the crystallographic c axis. The 18-crown-6 molecule [occupancy ratio 0.830 (4):0.170 (4)] is disordered and was refined using a split model
Multi-Component Diffusion in the Vicinity of a Growing Crystal
Co-crystallization from multi-component solutions occurs in many solids formation processes. The measurement or simulative description of concentration courses in the fluid vicinity of a growing crystalline substrate is difficult for such systems. These are relevant with respect to developing concentrations of crystallizing components at the solid-liquid interface due to diffusion fluxes in the solution. Concentrations may change such that unintended crystalline states can develop. With Fickian multi-component diffusion modeling we are able to simulate the timely evolution of the concentrations in the diffusion boundary layer during crystallization of various solid entities. Not only single solvate crystallization is modeled but also co-crystallization from multi-component solutions with different solvate states. The simulations are run with the assumption that diffusion limitation dominates. However, the model can be easily adapted to integration limitation. The interdependence of two diffusing components is taken into account in Fick’s multicomponent diffusion with a diffusion coefficient between these two components. We show that the consideration of so called cross-diffusion effects between dissolved materials can be neglected during crystallization of single decahydrates and during co-crystallization of anhydrous electrolytes. The presented model is also capable of fitting crystal growth kinetics with single point desupersaturation measurements in a thin film. In addition to the study of the kinetic parameters, the simulation allows the determination of the spatial concentration evolution from the single point concentration measurements
Co-Crystallization and Polymorphism of Naturally Occurring Peptide Derivatives
Carnosine is a dipeptide compound that is found in many dietary supplements and food products. Carnosine has many functions in the body, such as alleviating oxidative stress on tissues by acting as an antioxidant compound. Carnosine, therefore, has important anti-aging properties. Carnosine is also capable of forming protective sequestration structures around heavy metal ions; this process of chelating metals ions in solutions is very beneficial for maintaining the well-being of cells in the body. Thus, carnosine could be useful in pharmaceutical products for creating anti-aging drugs that would reduce tissue stress and promote a healthy cellular environment. I attempted to co-crystallize carnosine with four polycarboxylated aromatic acids and two Krebs cycle metabolites to generate various supramolecular structures based on the placement of carboxyl groups on the co-crystallants. If a co-crystallization method is created for carnosine, pharmaceutical products can utilize the same method in producing carnosine-based drugs. Furthermore, carnosine chelation of various metal ions was conducted to determine if carnosine would chelate in a variety of solution environments. Co-crystallization of carnosine with the four polycarboxylated aromatic acids and two Krebs cycle metabolites was not fully achieved, possibly due to environmental and stability conditions of solutions. Carnosine demonstrated metal-ion chelation properties with copper ions, whereas iron and zinc and iron ion solutions did not reveal carnosine chelation properties. In conclusion, more experiments with carnosine should be conducted to find optimal co-crystallization conditions for the production of pharmaceutical products
Co-Crystallization and Polymorphism of Naturally Occurring Peptide Derivatives
Carnosine is a dipeptide compound that is found in many dietary supplements and food products. Carnosine has many functions in the body, such as alleviating oxidative stress on tissues by acting as an antioxidant compound. Carnosine, therefore, has important anti-aging properties. Carnosine is also capable of forming protective sequestration structures around heavy metal ions; this process of chelating metals ions in solutions is very beneficial for maintaining the well-being of cells in the body. Thus, carnosine could be useful in pharmaceutical products for creating anti-aging drugs that would reduce tissue stress and promote a healthy cellular environment. I attempted to co-crystallize carnosine with four polycarboxylated aromatic acids and two Krebs cycle metabolites to generate various supramolecular structures based on the placement of carboxyl groups on the co-crystallants. If a co-crystallization method is created for carnosine, pharmaceutical products can utilize the same method in producing carnosine-based drugs. Furthermore, carnosine chelation of various metal ions was conducted to determine if carnosine would chelate in a variety of solution environments. Co-crystallization of carnosine with the four polycarboxylated aromatic acids and two Krebs cycle metabolites was not fully achieved, possibly due to environmental and stability conditions of solutions. Carnosine demonstrated metal-ion chelation properties with copper ions, whereas iron and zinc and iron ion solutions did not reveal carnosine chelation properties. In conclusion, more experiments with carnosine should be conducted to find optimal co-crystallization conditions for the production of pharmaceutical products
Production and Purification of Aromatase for Co-Crystallization
Aromatase (CYP19) is an enzyme that converts androgens into estrogens. It is a drug target to treat hormone-dependent breast cancer, yet current therapeutics often result in patient health deterioration due to unwanted side effects. We want to recombinantly express high yields of stable aromatase to co-crystallize with our new, potent inhibitors. These crystals will be used to produce a 3-D structure to visualize the protein-inhibitor complex. We hope that the structure will help us understand the interactions that are essential for drug potency. We currently produce 1 mg/mL of protein. We hope to increase the stability with mutants A419S, G156A, L240S, and V80S. Stable aromatase increases the likelihood of producing protein crystals. With the 3-D structure obtained from the protein crystals, we can design novel inhibitors as potential candidates to treat hormone-dependent breast cancer
The Development of Butterfly pea (Clitoria ternatea) Flower Powder Drink by Co-crystallization
Abstract— A method consist of co-crystallization, agglomeration, drying has been applied to develop a powder drink from butterfly pea flower (Clitoria ternatea) extract. The butterfly pea flower extract was concentrated by vacuum evaporation and incorporated with supersaturated sugar solution (more than 90 Brix), agglomerated and dried at 60oC for 12 hours. The anthocyanin stability and antioxidant activity of the powder drink was evaluated for 28 days at three levels of temperature (room temperature, 40oC, and 50oC). The stability of anthocyanin decreased as the increase of storage temperature. The half-life of anthocyanin in the powder drink at respective temperature was 27.99, 16.53, and 9.81 days. Despite the anthocyanin significantly degraded, the decrease of antioxidant activity of the powder drink was not significant. Hence, the beneficial effect of the butterfly pea powder drink retained.
Keywords— anthocyanin; butterfly pea; co-crystallization; stability; suga
Conformer of the peroxynitrite ion formed under photolysis of crystalline alkali nitrates – cis or trans?
The optical and infrared reflectance spectra of the crystalline powders prepared by co-crystallization of caesium nitrate, nitrite, and peroxynitrite from alkali solution have been studied. We find that the trans conformer forms under photolysis of crystalline pure caesium nitrate. Under its dissolution the trans conformer transforms to the cis conformer
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