Transformation under pressure: Discovery of a novel crystalline form of anthelmintic drug Praziquantel using high-pressure supercritical carbon dioxide.

Supercritical carbon dioxide (CO) has been used as a processing technique to control polymorphism of pharmaceuticals. However, there are fewer reports of novel polymorphs being discovered by supercritical CO processing. As supercritical crystallization methods gain attention for potential in pharmaceutical processing, they may become a critical screening tool for discovery of new polymorphs.

Ternary Phase Diagram Development and Production of Niclosamide-Urea Co-Crystal by Spray Drying.

In this work, a ternary phase diagram was developed for a Niclosamide-urea co-crystal (NCS-UR) in isopropanol (IPA) using a combination of slurry and solvent addition methods. The ternary phase diagram showed that solubility of Niclosamide and urea differed by an order of magnitude in IPA, leading to an incongruently saturating system. Spray drying was explored as a method to generate NCS-UR.

Characterization of new crystalline forms of hydroxyprogesterone caproate.

A systematic polymorph screening process was conducted on the steroid hydroxyprogesterone caproate, which had only one previously described orthorhombic crystalline form (A), in order to fully elucidate its solid state properties. Cooling, anti-solvent and evaporative techniques largely reproduced the same polymorph, but slurries in various solvents over two days produced a new triclinic form (B). Experiments at different temperatures in ethyl acetate or isopropyl alcohol confirmed this was an enantiotropic system with a transition temperature of approximately 30°C.

A novel process for preparation of fatty acid oil mixture in solid form.

The present study describes a novel and scalable process for preparation of omega-3 and omega-6 fatty acids in solid form. The process involves multiple steps consisting of combining the oil with a metal base in alcohol to form a solution, followed by addition of reaction mixture to acetonitrile (anti-solvent) to form a slurry and further separating the solid through filtration. This process results in formation of a flowable solid with yield of 44-76% depending on the procedure employed.

Aminodifluorosulfinium salts: selective fluorination reagents with enhanced thermal stability and ease of handling.

Diethylaminodifluorosulfinium tetrafluoroborate (XtalFluor-E) and morpholinodifluorosulfinium tetrafluoroborate (XtalFluor-M) are crystalline fluorinating agents that are more easily handled and significantly more stable than Deoxo-Fluor, DAST, and their analogues. These reagents can be prepared in a safer and more cost-efficient manner by avoiding the laborious and hazardous distillation of dialkylaminosulfur trifluorides. Unlike DAST, Deoxo-Fluor, and Fluolead, XtalFluor reagents do not generate highly corrosive free-HF and therefore can be used in standard borosilicate vessels.

Thermodynamic modeling of activity coefficient and prediction of solubility: Part 1. Predictive models.

A new activity coefficient model was developed from excess Gibbs free energy in the form G(ex) = cA(a) x(1)(b)...

Thermodynamic modeling of activity coefficient and prediction of solubility: Part 2. Semipredictive or semiempirical models.

The solubility of stearic acid, ranitidine hydrochloride, and stavudine were predicted in selected organic solvents. The experimental solubility data of stearic acid and ranitidine hydrochloride were reported in previous work of the authors and stavudine's solubility was measured in this work. Equilibrium aqueous solubility of crystalline stauvudine was determined at controlled temperatures by stirring and filtration, with spectrophotometric quantification.

Stavudine.

The crystal structure of the title compound (systematic name: 2',3'-didehydro-2',3'-deoxythymidine), C10H12N2O4, consists of two molecules in the asymmetric unit bound together by hydrogen bonds. The conformational geometry differentiates this form of stavudine from its two previously published polymorphs. In addition, a different hydrogen-bonding scheme is observed compared with the previous two structures.

An approach to solvent screening for crystallization of polymorphic pharmaceuticals and fine chemicals.

It is desirable to have a systematic approach for predicting or interpreting the effect of the solvents on the production of polymorphs. A method based on the atomic electronegativity is suggested that calculates the partial charge distribution in the solute and solvent molecules. Using the calculated partial charges, correlations are developed to predict the hydrogen bonding ability of the solute and/or solvent molecules.

Improving the filterability and solid density of ranitidine hydrochloride Form 1.

Ranitidine hydrochloride Form 1 produced by the original method (Price et al., 1978 US patent) has poor filtration and drying characteristics, which make it less desirable commercially in comparison with Form 2. This article shows that the operating parameters have significant influence on the final properties of Form 1.