No abstract

Vapor pressures for the saturated triglycerides (TGs) tricaprylin, tricaprin, and liquid densities of tricaprylin were experimentally determined. TG purecomponent parameters for the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) were fitted to that data and validated with densities of the binary mixtures octanol/tricaprin and octanol/trilaurin at different temperatures and TG mass fractions. Furthermore, pure-component parameters of the unsaturated TGs triolein and trilinolein were estimated by a group-contribution method. Correctly predicted solid−liquid equilibria of mixtures containing the before-mentioned TGs revealed that intermolecular interactions among TGs are quantitatively described by PC-SAFT.

Natural edible oils (NEOs) are common excipients for lipid-based formulations. Many of them are complex mixtures comprising hundreds of different triglycerides (TGs). One major challenge in developing lipid-based formulations is the variety in NEO compositions affecting the solubility of active pharmaceutical ingredients. In this work, solubilities of indomethacin (IND), ibuprofen (IBU), and fenofibrate (FFB) in soybean oil and in coconut oil were measured via differential scanning calorimetry, high-performance liquid chromatography, and Raman spectroscopy. Furthermore, this work proposes an approach that mimics NEOs using one key TG and models the API solubilities in these NEOs based on perturbed-chain statistical associating fluid theory (PC-SAFT). Key TGs were determined using the 1,2,3-random hypothesis, and PC-SAFT parameters were estimated via a group-contribution method. Using the proposed approach, the solubility of IBU and FFB was modeled in soybean oil and coconut oil. Furthermore, the solubilities of five more APIs (IND, cinnarizine, naproxen, griseofulvin, and felodipine) were modeled in soybean oil. All modeling results were found in very good agreement with the experimental data. The influence of different NEO kinds on API solubility was examined by comparing FFB and IBU solubilities in soybean oil and refined coconut oil. PC-SAFT was thus found to allow assessing the batch-to-batch consistency of NEO batches in silico.

This work provides experimental data and thermodynamic modeling on phase equilibria of binary mixtures that are relevant for esterification reactions. The components under investigation include water, succinic acid (SA), ethanol (EtOH), 1-butanol (1-BuOH), and the diesters of SA, namely, diethyl succinate (DES) and dibutyl succinate (DBS), respectively, as well as the organic solvents acetonitrile (ACN) and tetrahydrofuran (THF). Liquid−liquid equilibria (LLE) of water/DBS were measured at ambient pressure for temperatures between 313 and 353 K. Isobaric vapor−liquid equilibria (VLE) were measured for the binary systems ACN/DES, ACN/DBS, 1-BuOH/DBS, and THF/DBS at pressures of 10 or 20 or 30 kPa. Temperature ranges for the isobaric VLE varied between 300 and 500 K. The measured data and phase equilibria reported in literature were accurately modeled using perturbed-chain statistical associating fluid theory (PC-SAFT). For this purpose, pure-component PC-SAFT parameters, which were not already reported in the literature, were adjusted to experimental literature purecomponent data. Applying binary interaction parameters allowed precise phase-equilibrium modeling results of the binary systems under investigation. Two different association schemes for water were used ("2B" and "4C"). Both schemes appeared to be suitable to describe phase equilibria of aqueous mixtures; however, a binary parameter for the Wolbach−Sandler mixing rule was required for aqueous mixtures modeled with the 4C scheme. For LLE modeling the 2B scheme was found to give better modeling results. In general, the 4C association scheme for water yields better results for mixtures with two self-associating components while the 2B association scheme for water should be preferred if mixtures are considered with water and a non-selfassociating component. Further, the modeling concept of "induced association" has been investigated and discussed. Especially for mixtures with esters, which are of main importance for esterification mixtures, the induced-association approach turned out to be a more accurate modeling strategy compared to the nonassociative approach.

The spontaneous magnetization, the zero-field susceptibility, and the isothermal critical magnetization along the ferromagnetic axis of TbFs in the critical region have been measured and can best be described by mean-field laws with logarithmic corrections as predicted by recent renormalization-group calculations for uniaxial, dipolar-coupled ferromagnets. Furthermore, the three critical amplitudes satisfy the predicted amplitude relation between them.