"Stabilization" of Amorphous Ketoprofen in Thin Films.

It has been shown that depositing ketoprofen as thin films on glass substrates has a stabilizing effect on the amorphous state of ketoprofen. Polyethylene glycol ( = 6000 g/mol) was mixed with ketoprofen in a wide range of concentrations. Amorphous thin films were prepared by spin coating and subjected to storage conditions with different levels of relative humidity.

Overt and hidden polymorphism in the binary system involving the Z- and E- isomers of broparestrol.

Broparestrol has been used as a drug to treat acne in the form of a mixture of its two stereoisomers. Although it has been withdrawn from the market, the binary system is rich in polymorphism and understanding the phase behaviour of the binary system involving the E- and Z-isomers is challenging. Physical mixtures do not immediately give rise to equilibrium phase behaviour, whereas recrystallization often leads to metastable phases and the appearance of stable phases can take years.

An unexpected high-pressure stability domain for a lower density polymorph of benzophenone.

For over a century, it was thought that the crystalline polymorph II of benzophenone does not possess a stable domain in the pressure-temperature phase diagram. With a combination of new experimental results and literature data, this case of crystalline dimorphism has finally been solved and it is shown that form II possesses a stable domain at high pressure and high temperature, even though its density is lower than that of form I, the stable form under ordinary pressure and temperature conditions. The phase diagram of benzophenone is a clear demonstration of the fact that to understand the phase behaviour of a chemical substance both the exchange of heat (due to the change in intermolecular interactions) and work (due to the change of volume at a given pressure) need to be taken into account.

The Phase Diagram of the API Benzocaine and Its Highly Persistent, Metastable Crystalline Polymorphs.

The availability of sufficient amounts of form I of benzocaine has led to the investigation of its phase relationships with the other two existing forms, II and III, using adiabatic calorimetry, powder X-ray diffraction, and high-pressure differential thermal analysis. The latter two forms were known to have an enantiotropic phase relationship in which form III is stable at low-temperatures and high-pressures, while form II is stable at room temperature with respect to form III. Using adiabatic calorimetry data, it can be concluded, that form I is the stable low-temperature, high-pressure form, which also happens to be the most stable form at room temperature; however, due to its persistence at room temperature, form II is still the most convenient polymorph to use in formulations.

Solid-solid Phase Transitions between Crystalline Polymorphs of Organic Materials.

In this review, the analysis of solid-solid phase transitions between crystalline polymorphs of organic molecules is discussed. Although active pharmaceutical ingredients (APIs) are the scope of the review, whether an organic molecule has a biological activity or not does not particularly define its interactions in the crystalline state. Therefore, other small organic molecules have been included in this analysis and in certain cases, polymers have been discussed too.