Andrey G. Ogienko

Phase Diagram and High-Pressure Boundary of Hydrate Formation in the Carbon Dioxide−Water System

Experimental investigation of the phase diagram of the system carbon dioxide-water at pressures up to 2.7 GPa has been carried out in order to explain earlier controversial results on the decomposition curves of the hydrates formed in this system. According to X-ray diffraction data, solid and/or liquid phases of water and CO2 coexist in the system at room temperature within the pressure range from 0.8 to 2.6 GPa; no clathrate hydrates are observed. The results of neutron diffraction experiments involving the samples with different CO2/H2O molar ratios, and the data on the phase diagram of the system carbon dioxide-water show that CO2 hydrate of cubic structure I is the only clathrate phase present in this system under studied P-T conditions. We suppose that in the cubic structure I hydrate of CO2 multiple occupation of the large hydrate cavities with CO2 molecules takes place. At pressure of about 0.8 GPa this hydrate decomposes into components indicating the presence of the upper pressure boundary of the existence of clathrate hydrates in the system.

Decreasing particle size helps to preserve metastable polymorphs. A case study of DL-cysteine

The contribution describes the effect of particle size on the interconversion between the high-temperature (I) and the low-temperature (II) polymorphs of crystalline DL-cysteine (+NH3–CH(CH2SH)–COO−) studied by X-ray powder diffraction, Raman spectroscopy, differential scanning calorimetry, scanning electron microscopy. Crystalline DL-cysteine undergoes a phase transition on cooling related to the rotation of its side-chain and a rearrangement of the H-bond network. For the crystals larger than ∼1 μm, the transition could be observed in the range 250–200 K and was characterized by a large (up to 110 K) hysteresis. If (I) was obtained as crystalline particles with characteristic size of ∼1 μm by grinding, no transformation into (II) was observed on cooling down even to 10 K. (I) was preserved down to 200 K, after which another low-temperature phase, (I)′, appeared, which was structurally related to (I), but with strongly disordered (possibly modulated) sulfhydryl side-chains. Nevertheless, (II) could be prepared as small (∼0.1 to 1 μm) particles directly at low temperatures by freeze-drying of DL-cysteine aqueous solutions. The sample could be then preserved as a metastable low-temperature polymorph on heating up to ∼333 K, and transformed completely to (I) at 373 K only. The small particles of (I) obtained by heating from small particles of (II) then transformed completely back to (II) on cooling down to 183 K. The effects are interpreted in terms of kinetic control of the polymorphic transitions and the relation between particle size, nucleation of a new phase, and relaxation of mechanical stresses.

Compressibility of Gas Hydrates

Experimental data on the pressure dependence of unit cell parameters for the gas hydrates of ethane (cubic structure I, pressure range 0-2 GPa), xenon (cubic structure I, pressure range 0-1.5 GPa) and the double hydrate of tetrahydrofuran+xenon (cubic structure II, pressure range 0-3 GPa) are presented. Approximation of the data using the cubic Birch-Murnaghan equation, P=1.5B(0)[(V(0)/V)(7/3)-(V(0)/V)(5/3)], gave the following results: for ethane hydrate V(0)=1781 Å(3) , B(0)=11.2 GPa; for xenon hydrate V(0)=1726 Å(3) , B(0)=9.3 GPa; for the double hydrate of tetrahydrofuran+xenon V(0)=5323 Å(3) , B(0)=8.8 GPa. In the last case, the approximation was performed within the pressure range 0-1.5 GPa; it is impossible to describe the results within a broader pressure range using the cubic Birch-Murnaghan equation. At the maximum pressure of the existence of the double hydrate of tetrahydrofuran+xenon (3.1 GPa), the unit cell volume was 86% of the unit cell volume at zero pressure. Analysis of the experimental data obtained by us and data available from the literature showed that 1) the bulk modulus of gas hydrates with classical polyhedral structures, in most cases, are close to each other and 2) the bulk modulus is mainly determined by the elasticity of the hydrogen-bonded water framework. Variable filling of the cavities with guest molecules also has a substantial effect on the bulk modulus. On the basis of the obtained results, we concluded that the bulk modulus of gas hydrates with classical polyhedral structures and existing at pressures up to 1.5 GPa was equal to (9±2) GPa. In cases when data on the equations of state for the hydrates were unavailable, the indicated values may be recommended as the most probable ones.

Bis(paracetamol) pyridine – a new elusive paracetamol solvate: from modeling the phase diagram to successful single-crystal growth and structure–property relations

Multi-component crystals – salts, co-crystals, or solvates – are usually designed based on the analysis of the complementarity of functional groups and intermolecular interactions of the components. However, no crystal design can do without a practical method of crystal growth. Not all compounds that should be expected to exist based on the “synthon approach” can be prepared in real experiments. This paper aims to illustrate that, in addition to the synthon approach, it is equally important to take into account phase diagrams when searching for practical methods of crystallising multi-component crystals, either as single crystals or as fine particles. Here, we describe the crystallization of a bis(paracetamol) pyridine solvate from a glass-like metastable phase produced by quench-freezing of a paracetamol–pyridine solution with subsequent low-temperature annealing. These procedures must be carried out strictly within the boundaries of the two-phase region “solid solvate + liquor”, which was found only as a result of modelling the phase diagram. The crystal structure was solved by single-crystal X-ray diffraction and compared with co-crystals of paracetamol found in the Cambridge Structural Database. The structure-forming role of the intermolecular interactions and their characteristics were studied by variable-temperature experiments over the range of 100–275 K. This was compared with the structures of pure paracetamol polymorphs and other solvates and co-crystals at ambient and non-ambient conditions.

Large porous particles for respiratory drug delivery. Glycine-based formulations

Abstract Large porous particles are becoming increasingly popular as carriers for pulmonary drug delivery with both local and systemic applications. These particles have high geometric diameters (5–30 &mgr;m) but low bulk density (˜ 0.1 g/cm3 or less) such that the aerodynamic diameter remains low (1–5 &mgr;m). In this study salbutamol and budesonide serve as model inhalable drugs with poor water solubility. A novel method is proposed for the production of dry powder inhaler formulations with enhanced aerosol performance (e.g. for salbutamol‐glycine formulation the fine particle fraction (FPF ≤ 4.7 &mgr;m) value is 67.0 ± 1.3%) from substances that are poorly soluble in water. To overcome the problems related to extremely poor aqueous solubility of the APIs, not individual solvents are used for spray freeze‐drying of API solutions, but organic‐water mixtures, which can form clathrate hydrates at low temperatures and release APIs or their complexes as fine powders, which form large porous particles after the clathrates are removed by sublimation. Zwitterionic glycine has been used as an additive to API directly in solutions prior to spray freeze‐drying, in order to prevent aggregation of powders, to enhance their dispersibility and improve air‐flow properties. The clathrate‐forming spray freeze‐drying process in the multi‐component system was optimized using low‐temperature powder X‐ray diffraction and thermal analysis. Graphical abstract Figure. No Caption available.

High-pressure gas hydrates of argon: compositions and equations of state.

Volume changes corresponding to transitions between different phases of high-pressure argon gas hydrates were studied with a piston-cylinder apparatus at room temperature. Combination of these data with the data taken from the literature allowed us to obtain self-consistent set of data concerning the equations of state and compositions of the high-pressure hydrates of argon.