Grinding-induced equimolar complex formation between thiourea and ethenzamide.
We prepared and characterized a grinding-induced equimolar complex of thiourea with ethenzamide. When thiourea and ethenzamide were co-ground at a molar ratio of 3 : 1, new powder X-ray diffraction (PXRD) peaks were observed in addition to PXRD peaks of thiourea crystals. The optimum stoichiometry of the new structure was confirmed as 1 : 1 mol/mol. Effect of grinding time on the thiourea-ethenzamide equimolar complex formation was investigated by using PXRD, differential scanning calorimetry and Fourier transform infrared spectroscopy. The equimolar crystal structure was confirmed by X-ray diffraction measurements of the single crystal which was recrystallized from ethanol. It was found that the intermolecular hydrogen bond formations between thiourea and ethenzamide molecules contributed to the equimolar complex formation. The complex formation was not observed in the cases where benzamide, salicylamide or 3-ethoxybenzamide was co-ground with thiourea. 2-Alcoxyl benzamide structures should be required for the grinding-induced equimolar complex formation with thiourea.
Analysis of molecular interactions in solid dosage forms; challenge to molecular pharmaceutics.
The molecular states of active pharmaceutical ingredients (APIs) in pharmaceutical dosage forms strongly affect the properties and quality of a drug. Various important fundamental physicochemical studies were reviewed from the standpoint of molecular pharmaceutics. Mechanochemical effects were evaluated in mixtures of APIs and pharmaceutical additives. Amorphization, complex formation and nanoparticle formation are observed after grinding process depending on the combination of APIs and pharmaceutical additives. Sealed-heating method and mesoporous materials have been used to investigate drug molecular interactions in dosage forms. Molecular states have been investigated using powder X-ray diffraction, thermal analysis, IR, solid state fluorometry, and NMR.
Structure and van der Waals energy study of the palmitic acid–choleic acid complex
The crystals are orthorhombic, space group P2,2121, a = 26.020 (4), b = 13.543 (2), c = 7.268 (1) ,~, and the structure has been refined to an R of 0.11 and R w of 0.16 for 2352 observed data with I > a(I). The packing is characterized by an assembly of bilayers similar to that of other orthorhombic phases. The shape of the canals, in which the palmitic acid is accommodated, differs slightly from that in the acetic acid-choleic acid complex. The guest molecules, which are probably arranged in four statistical orientations, run along c in a trans-planar conformation and occupy approximately three unit cells. Potential-energy calculations allowed the location of the occluded molecules and suggest a deoxycholic acid:palmitic acid: ethanol ratio of 8 : 1 : 1.