Directional crystallization of poly (ethylene oxide)

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An experimental conglomerate discovery method

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A New Device for In Situ Detection of Conglomerate Forming Systems in Suspension by Second Harmonic Generation (SHG)

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Urea derivatives as transporter molecules in sublimation crystallization

Interactions between pyrazinamide and urea derivatives (acetamide, urea and methyl and ethyl substituted urea molecules) in the vapor phase and in solution have been investigated. The presence of urea derivatives increases the crystallization rate and the crystal quality in sublimation crystallization. These effects depend on the vapor pressure of the urea derivatives and the possible interactions between pyrazinamide and the derivatives. No traces of solid solutions or co-crystals between pyrazinamide and the urea derivatives have been found, however.NMR results in CDCl3 demonstrate that the chemical shift of one hydrogen atom on the amide group (the one which is most removed from the pyrazine ring) of pyrazinamide changes with a change in concentration of pyrazinamide or with a change in concentration of the urea derivative. The chemical shift of the hydrogen atoms of the amide group of the urea derivative changes with a change in the concentration of pyrazinamide as well. Electrostatic potential distribution maps of pyrazinamide and the urea derivatives demonstrate that the highest electron density region is found on the carbonyl oxygen, and the lowest electron density region is found on the hydrogens of the amine group, which therefore clearly induces the interactions observed by NMR.The interactions revealed in solution appear to be present in the gas phase too and this influences the crystallization of PZA by sublimation in the presence of urea derivatives in terms of a higher crystallisation rate and higher quality crystals. This may be used to obtain a better control over crystal quality of APIs in general

Chlocyphos: Conglomerate forming derivatives (salts) for its resolution by preferential crystallization

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Propensity for amine family to form conglomerates with Chlocyphos and their resolution by preferential crystallization

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Impact of 1-3-dimethylurea on the Polymorphism of an active pharmaceutical ingredient: pyrazinamide. A thin film approach.

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The Phase Behaviour of Tetramorphic Pyrazinamide

International audienceThe phase behaviour of pyrazinamide has long been difficult to resolve,[1-3] in particular because of the strong hysteresis between the phase transitions. Vapour pressure data has allowed to improve our understanding resulting in the phase diagram below. Uncertainties in the transition temperatures between the phases and and the phases and still exist as they have not been measured directly. It is however likely that the equilibrium temperature of the - phase equilibrium is found between 0 and 25°C. At room temperature both solids must have the same solubility, as their vapour pressures are virtually the same. Because phase transformations are not observed at room temperature and is also stable above room temperature up to 120°C[1], stability-wise it would be the most logical form to use in formulations.The form possesses a more pronounced thermal expansion than the other polymorphs. This result is most likely due to its layered structure held together by weak interactions, which also leads to a large compressibility observed by synchrotron X-ray diffraction. Interestingly, forms and , which both exhibit uniaxial negative thermal expansion to some level, are only stable at low pressures.The high compressibility of the form possibly leads to a considerably curved - equilibrium with a temperature minimum in the equilibrium line (not indicated in the figure below). Such curvature presents a challenge to the topological approach with the aim of constructing phase diagrams with only ordinary pressure data (P 0 MPa) and the Clapeyron equation. From a large number of high-pressure studies,[4] it can be concluded that most solid-solid equilibria are straight lines in the pressure-temperature plane implying that compressibilities between polymorphs do not differ much; thus, the current finding appears to be a rare case

Propensity for amine family to form conglomerates with Chlocyphos and their resolution by preferential crystallization

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The pressure-temperature phase diagram of tetramorphic pyrazinamide by vapour pressure and synchrotron Xray diffraction under pressure

International audienceThe phase behaviour of drug molecules is important to control the desired polymorph in drug formulations, whether it is to ensure better stability of the formulation or better solubility (solubilization) of the drug. In the case of pyrazinamide, a drug against tuberculosis, four polymorphs are known to exist labelled α, β, γ, and δ [1,2]. Stability studies of this active pharmaceutical ingredient have been complicated due to the very slow transition kinetics observed in DSC measurements [1,2]. Using vapour pressure measurements, in which the reluctance of phase transformation is in fact an advantage, all solid-solid phase transformation temperatures have been determined. This method has been key to map the phase behaviour of pyrazinamide. The use of high-pressure measurements with synchrotron X-ray diffraction at several temperatures from room temperature up to 120 °C has allowed to construct the pressure-temperature phase diagram of the four solid phases of pyrazinamide and the liquid phase (Figure 1). The equations of state of the four polymorphs have been determined at various temperatures in addition to the thermal expansion