Thermal analysis and crystallization from melts

The growth of atenolol, pindolol and betaxolol hydrochloride from melt was investigated by differential scanning calorimetry (DSC) and polarized light thermal microscopy (PLTM). Phase transitions occurring on cooling and subsequent reheating runs performed between −160 °C and a temperature above the respective melting points were studied by DSC. The thermal cycles were also followed by PLTM. Details about the dynamic of the crystallization front taken from microscopic observations are given. An explanation of the results on the basis of molecular supramolecular recognition is advanced.     

Infrared study of the acidic and basic forms of betaxolol

Betaxolol and its respective hydrochloride salt were studied in solution by computational calculations and infrared spectroscopy. The solution molecular conformations were taken to be the same as those exhibited by the compounds in the solid state given by X-ray diffraction and calculated after full geometry optimization by ab initio Hartree-Fock methods using the 6-31G(d) basis set. Infrared spectra of carbon tetrachloride solutions provide valuable information on the structure of the compounds in non-polar solvents at different concentrations.     

Infrared spectroscopy of racemic and enantiomeric forms of atenolol

The molecular structure of conformational isomorphs given by X-ray diffraction for racemic and enantiomeric atenolol were optimized at the HF/6-31G* level of theory and the infrared spectra of the structure were calculated. These spectra are used to characterize the differences between the various atenolol conformers. The spectra of the (R,S)- and S-atenolol solid forms were recorded and the bands corresponding to the functional groups identified with the aid of the calculated spectra, fitting analysis, temperature effect and H/D isotopic exchange. Particular attention was paid to the stretch vibration modes of the functional groups present in the atenolol.     

Dihydrofolate Reductase Inhibitors: The Pharmacophore as a Guide for Co-Crystal Screening

In this work, co-crystal screening was carried out for two important dihydrofolate reductase (DHFR) inhibitors, trimethoprim (TMP) and pyrimethamine (PMA), and for 2,4-diaminopyrimidine (DAP), which is the pharmacophore of these active pharmaceutical ingredients (API). The isomeric pyridinecarboxamides and two xanthines, theophylline (THEO) and caffeine (CAF), were used as co-formers in the same experimental conditions, in order to evaluate the potential for the pharmacophore to be used as a guide in the screening process. In silico co-crystal screening was carried out using BIOVIA COSMOquick and experimental screening was performed by mechanochemistry and supported by (solid + liquid) binary phase diagrams, infrared spectroscopy (FTIR) and X-ray powder diffraction (XRPD). The in silico prediction of low propensities for DAP, TMP and PMA to co-crystallize with pyridinecarboxamides was confirmed: a successful outcome was only observed for DAP + nicotinamide. Successful synthesis of multicomponent solid forms was achieved for all three target molecules with theophylline, with DAP co-crystals revealing a greater variety of stoichiometries. The crystalline structures of a (1:2) TMP:THEO co-crystal and of a (1:2:1) DAP:THEO:ethyl acetate solvate were solved. This work demonstrated the possible use of the pharmacophore of DHFR inhibitors as a guide for co-crystal screening, recognizing some similar trends in the outcome of association in the solid state and in the molecular aggregation in the co-crystals, characterized by the same supramolecular synthons.     

Infrared spectroscopy and the characterization of terfenadine crystallized from solvents

In this paper the structural characterization of terfenadine crystallized from ethanol-water, ethanol and methanol is performed by infrared spectroscopy. The OH stretching vibration, composed of three markedly overlapped bands, is analyzed by peak fitting. The assignment of the hydrogen bonds was conducted making use of band parameters, spectroscopic data for CCl₄ solutions, and molecular dynamics calculations from dimeric systems. Terfenadine just precipitated from solvents is never in the highest crystalline state. This state is reached when the samples are heated at a temperature above 100°C. Some amorphous solid is coprecipitated with the crystalline phase, particularly in methanol. This revised version was published online in August 2006 with corrections to the Cover Date.     

Enthalpy of Solution of Terfenadine in Different Solvents

Enthalpies of solution of various terfenadine samples in methanol and in ethanol were measured. Samples were prepared by crystallization in different solvents. The calorimetric results give important information on crystal structure of the terfenadine forms and on the solute/solvent interactions of this compound with the solvents.This revised version was published online in November 2005 with corrections to the Cover Date.     

Etude thermoanalytique et lyodisponibilite de dispersions solides du tolbutamide

We have established the phase diagram tolbutamide (TBM)-PEG 6000 and determined the eutectic composition 1/9 (w/w) in tolbutamide and melting temperature 56.2°C±0.3; no solid solution has been found. Negative mixing enthalpies of physical mixture (?2.5 J·g^?1) and solid dispersions coprecipitate (?3.9 J·g^?1) melt (?9.9 J·g^?1) for eutectic composition involve the existence of interactions between drug and carrier. We have determined the dissolution kinetics: amount % dissolved (10 min) 65.87±0.55 (physical mixture), 78.02±0.02 (coprecipitate), 99.90±0.10 (melt). We have observed a good agreement between dissolution kinetics and mixing enthalpies data.     

Melting Curves of Terfenadine Crystallized from Different Solvents

Several samples of terfenadine prepared by crystallization from different solvents under different experimental conditions were studied. The DSC curves obtained at a heating rate of 1°C min⁻¹ afforded the temperature of melting and the mole fractions of the components of each sample. Certain of the samples were composed of two solid phases mixed in molar ratios varying between nearly one and a single structural form. Three polymorphic forms were identified. This revised version was published online in August 2006 with corrections to the Cover Date.     

Study of Polymorphism From DSC Melting Curves; Polymorphs of Terfenadine

Terfenadine samples prepared by crystallization in different media and supersaturation conditions were used to investigate the polymorphism of the substance. The study was based on DSC melting curves. An empirical parametric equation was used for modelling the experimental data. The signal recorded was resolved into the corresponding overlapping peak components by fitting analysis. Four polymorphic phases were identified. This revised version was published online in August 2006 with corrections to the Cover Date.