Probing the Molecular and Macroscopic Structure of Solid Solutions by Dynamic Nuclear Polarization (DNP) Enhanced C and N Solid-State NMR Spectroscopy.

Crystallization is a widely used purification technique in the manufacture of active pharmaceutical ingredients (APIs) and precursor molecules. However, when impurities and desired compounds have similar molecular structures, separation by crystallization may become challenging. In such cases, some impurities may form crystalline solid solutions with the desired product during recrystallization.

Terminal crystalline solid solutions, solubility enhancements and T-X phase diagram of salicylic acid - 4-hydroxybenzoic acid.

The binary T-X phase diagram of salicylic acid (SA) and 4-hydroxybenzoic acid (4HBA) has been constructed from 20 °C to melting, revealing a partially miscible system with an eutectic composition of 27.3 mol% 4HBA in SA. Terminal crystalline solid solutions were obtained at the extremes of the phase diagram with solid-state miscibility limits below 0.

Complex oiling-out behavior of procaine with stable and metastable liquid phases.

During the crystallization of a solute from solvent(s), spontaneous liquid-liquid phase separation (LLPS) might occur, under certain conditions. This phenomenon, colloquially referred to as "oiling-out" in the pharmaceutical industry, often leads to undesired outcomes, including undesired particle properties, encrustation, ineffective impurity rejection, and excessively long process time. Therefore, it is critical to understand the thermodynamic driving force and phase boundaries of this phenomenon, such that rational strategies can be developed to avoid oiling-out or minimize its negative impact.

Enantiotropic inconstancy, crystalline solid solutions and co-crystal in the salicylic acid-anthranilic acid system.

The phase boundaries and thermodynamic properties of crystal phases in the salicylic acid (SA) - anthranilic acid (AA) system have been determined experimentally. The complete binary T-X diagram reveals a total of four crystalline phases, including a co-crystal and three crystalline solid solutions. The two eutectics were determined through triplicate DSC analyses at 33 compositions.

Prediction of solubility curves and melting properties of organic and pharmaceutical compounds.

The relationships between solubility, temperature dependence of solubility, melting temperature and melting enthalpy are investigated for the purpose of finding relations that can significantly reduce the need for experimental work in the selection of the solvent for processing of organic fine chemicals and pharmaceuticals. The relationships are investigated theoretically and by evaluation of experimental data for 41 organic and pharmaceutical compounds comprising a total of 115 solubility curves in organic and aqueous solvents. The work considers (i) selection of the equation for correlation of solubility data based on thermodynamic considerations and ability to predict melting properties of the solute from solubility data, (ii) prediction of the temperature dependence of solubility, and (iii) prediction of solubility curves in new solvents.

Polymorphism and thermodynamics of m-hydroxybenzoic acid.

Solution and solid-state properties of m-hydroxybenzoic acid have been investigated. Two polymorphs were found where the monoclinic modification exhibits a higher stability than the orthorhombic form. The solubility of the monoclinic polymorph was determined between 10 and 50 degrees C in methanol, acetonitrile, acetic acid, acetone, water and ethyl acetate.

Phase equilibria and thermodynamics of p-hydroxybenzoic acid.

The prevalence of phases and associated solubilities of p-hydroxybenzoic acid have been investigated in methanol, acetonitrile, acetic acid, acetone, water, and ethyl acetate at temperatures from 10 to 50 degrees C. Thermodynamic data was acquired through determination of van't Hoff enthalpy of solution, enthalpy of fusion, and melting temperature. Indications of polymorphic enantiotropy were found primarily through solubility analysis and FTIR-ATR.

Analysis of solution nonideality of a pseudomorphic drug system through a comprehensive thermodynamic framework for the design of a crystallization process.

Solutions of a semipolar drug belonging to the alpha(V) beta(iii) integrin antagonist class of compounds were studied in a comprehensive thermodynamic framework. The solubility of two pseudomorphic forms (an anhydrate and a monohydrate) was measured at several temperatures and various solvent mixtures of acetonitrile and water. Both forms displayed a "bell"-shaped solubility behavior as a function of cosolvent composition.

Advanced mercury removal from gold leachate solutions prior to gold and silver extraction: a field study from an active gold mine in Peru.

Mercury contamination in the Gold-Cyanide Process (GCP) is a serious health and environmental problem. Following the heap leaching of gold and silver ores with NaCN solutions, portions of the mercury-cyano complexes often adhere to the activated carbon (AC) used to extract the gold. During the electrowinning and retorting steps, mercury can be (and often is) emitted to the air as a vapor.