Solubility calculation of pharmaceutical compounds – A priori parameter estimation using quantum-chemistry

Pure-component electrostatic properties for pharmaceutical compounds and intermediates (xanthene, ibuprofen, aspirin, p-hydroxyphenylacetic acid, p-toluic acid and o-anisic acid) were obtained by quantum-chemical methods. Afterwards, these properties were used for the a priori determination of the pure-component parameters for the Perturbed-Chain Polar Statistical-Associating Fluid Theory (PCP-SAFT). These parameters were applied to perform solubility calculations for binary solute–solvent mixtures. In these calculations the only parameter fitted was the binary parameter. The results show a good agreement of the modeled solubility and experimental data for the considered solutes in non-polar and polar solvents. Finally, the application of different combination rules to also predict the binary interaction parameter in the mixture was investigated.     

Application of the PC-SAFT equation of state to modeling of solid-liquid equilibria in systems with organic components forming chemical compounds

Equilibrium diagrams of liquid and solid phases were calculated by the equation of state, based on the perturbed-chain statistical associating fluid theory (PC-SAFT) for binary and ternary systems constituted by associating substances (water, alcohols, amines, phenol, bisphenol A, acetamide). Phase diagrams were considered for systems in which congruently and incongruently melting intermolecular compounds are formed and for a system with limited mutual solubility of the components in the liquid state. The results of prognostication of phase equilibria were illustrated by the example of a ternary system constituted by bisphenol A, phenol, and water, in which an adduct of bisphenol A and phenol is formed.     

Solubility,crystallization and oiling-out behavior of PEGDME: 1. Pure-solvent systems

Oiling out denotes a (metastable) liquid–liquid demixing during cooling crystallization prior to formation of the first crystals. This in most cases unwanted effect deteriorates the properties of the desired solid product. On the basis of the crystallization of the model substance polyethylenglycoldimethylether (PEGDME) from pure solvents, the influence of the molecular size of the solute and the type of solvent on the oiling-out behavior was systematically investigated. In this study the solubility data were determined gravimetrically as well as by using differential scanning calorimetry. The crystallization and oiling-out temperatures were detected visually in batch crystallization experiments. Oiling out was observed during the crystallization of PEGDME with a molar mass of 2000 g/mol (PEGDME2000) from diethylketone, ethyl acetate and 2-propanol, whereas no oiling out was detected during the cooling process of PEGDME with a molar mass of 1000 g/mol (PEGDME1000) from all solvents considered. Furthermore the oiling-out temperature for PEGDME2000 was not significantly influenced by the chosen solvents diethylketone, ethyl acetate and 2-propanol. In the second part of this study, it is shown that the appearance and absence of oiling out in all considered solvents can be qualitatively predicted by the pertubed chain statistical association theory (PC-SAFT) only using solubility data.