Sublimation crystallisation and polymorph stability

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Topological Pressure-Temperature State Diagram of the Crystalline Dimorphism of 2,4,6-trinitrotoluene

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Disappearing Conglomerates

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Deducing high pressure behavior for chemically fragile systems: the polymorphism of spironolactone

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Crystal structure of polymorph II and the pressure-temperature phase diagram of the dimorphic anesthetic butamben

The crystal structure of the low-temperature form II of butamben has been solved in a P21/c space group very similar to that of form I. Form II possesses virtually the same packing as that of the high-temperature form I, and the dimorphism is mainly represented by a small discontinuous change in the size of the unit cell and by a difference in the enthalpy. Because of the small enthalpy difference between the two polymorphs of 375 J·mol–1, it will be difficult to predict the change in the stability hierarchy by computer-aided methods. The pressure–temperature phase diagram, constructed using volume and enthalpy differences between the two phases at ordinary pressure, corresponds to a case of overall enantiotropy, as the I–II and I–L equilibrium lines diverge with increasing pressure. This conclusion is confirmed by the experimental pressure–temperature phase diagram obtained with differential thermal analysis measurements under pressurePeer ReviewedPostprint (author's final draft

Pressure-temperature phase diagram of the dimorphism of the anti-inflammatory drug nimesulide

Understanding the phase behavior of active pharmaceutical ingredients is important for formulations of dosage forms and regulatory reasons. Nimesulide is an anti-inflammatory drug that is known to exhibit dimorphism; however up to now its stability behavior was not clear, as few thermodynamic data were available. Therefore, calorimetric melting data have been obtained, which were found to be TI-L = 422.4 ± 1.0 K, ¿I ¿ LH = 117.5 ± 5.2 J g-1, TII-L = 419.8 ± 1.0 K and ¿II ¿ LH = 108.6 ± 3.3 J g-1. In addition, vapor-pressure data, high-pressure melting data, and specific volumes have been obtained. It is demonstrated that form II is intrinsically monotropic in relation to form I and the latter would thus be the best polymorph to use for drug formulations. This result has been obtained by experimental means, involving high-pressure measurements. Furthermore, it has been shown that with very limited experimental and statistical data, the same conclusion can be obtained, demonstrating that in first instance topological pressure-temperature phase diagrams can be obtained without necessarily measuring any high-pressure data. It provides a quick method to verify the phase behavior of the known phases of an active pharmaceutical ingredient under different pressure and temperature conditions.Postprint (author's final draft

Thermal expansion of L-ascorbic acid

The specific volume of vitamin C has been investigated by X-ray powder diffraction as a function of temperature from 110¿K up to complete degradation around 440¿K. Its thermal expansion is relatively small in comparison with other organic compounds with an expansivity av of 1.2(3) × 10-4¿K-1. The structure consists of strongly bound molecules in the ac plane through a dense network of hydrogen bonds. The thermal expansion is anisotropic. Along the b axis, the expansion has most leeway and is about 10 times larger than in the other directions.Postprint (author's final draft

Experimental And Topological Determination of the Pressure-Temperature Phase Diagram of Racemic Etifoxine, a Pharmaceutical Ingredient with Anxyolitic Properties

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Thermodynamics by synchrotron X-ray diffraction: phase relationships and crystal structure of L-tyrosine ethyl ester form III

In the case of small organic molecules, phase behaviour, which is important for pharmaceutical applications, is often only studied as a function of temperature. However, for a full thermodynamic description, not only the temperature but also the pressure should be taken into account, because pressure and temperature are the two characteristic variables for the Gibbs energy. The commercial form of L-tyrosine ethyl ester has been studied by synchrotron X-ray diffraction while subjected to different pressures and temperatures. At room temperature, it turns into a new previously unknown form around 0.45 GPa. The structure has been solved with an orthorhombic unit cell, space group P2(1)2(1)2(1), with parameters a = 12.655(4)angstrom, b = 16.057(4)angstrom, c = 5.2046(12)angstrom, and V = 1057.6(5)angstrom(3) at T = 323 K and P = 0.58 GPa. The enthalpy of the transition from the commercial form to the new form could be estimated from the slope of the transition obtained from the synchrotron diffraction data. In addition, the topological pressure-temperature phase diagram has been constructed involving the two solid phases, the liquid and the vapour phase. The solid phases are enantiotropic under low pressure, but the system becomes monotropic at high pressure with the new solid phase being the only stable one.Postprint (author's final draft

Polymorphism of spironolactone: An unprecedented case of monotropy turning to enantiotropy with a huge difference in the melting temperatures

Postprint (author's final draft