ABSTRACT
Piroxicam has polymorphism. Different crystalline forms can exhibit different physicochemical properties and biological activities. Analysis of the intermolecular interactions is essential to reveal the formation mechanism and differences of polymorphs. In this paper, Hirshfeld surface analysis and semi-empirical methods were used to calculate and analyze the intermolecular interactions in seven polymorphic forms of piroxicam. The results show that the Hirshfeld surface analysis method can clearly and intuitively reveal the intermolecular interactions, among which H…H, O…H/H…O and N…H/H…N interactions account for 95% of the total energy. There are differences in the proportion and distribution of the forces of different crystal forms. The energy calculation shows that the lattice energy of the hydrate is significantly lower than that of the anhydrous forms, and in the specific energy distribution, the contribution of the dispersion force is the most prominent. Further interaction energy analysis was found that within the distance of 3.8 Å from the center of the piroxicam molecule, different crystalline forms of piroxicam molecule have different interaction energies with surrounding molecules.
ABSTRACT
Meloxicam (MLX) is an anti-inflammatory drug susceptible to variations and crystalline transitions. In compounding pharmacies, the complete crystallographic evaluation of the raw material is not a routine procedure. We performed a complete crystallographic characterization of aleatory raw MLX samples from compounding pharmacies. X-ray diffraction indicated the presence of two crystalline forms in one sample. DSC experiments suggested that crystallization, or a crystal transition, occurred differently be-tween samples. The FTIR and 1H NMR spectra showed characteristic assignments. 13C solid-state NMR spectroscopy indicated the presence of more than one phase in a sample from pharmacy B. The Hirshfeld surface analysis, with electrostatic potential projection, allowed complete assignment of the UV spectra in ethanol solution. The polymorph I of meloxicam was more active than polymorph Ⅲ in an experi-mental model of acute inflammation in mice. Our results highlighted the need for complete crystal-lographic characterization and the separation of freely used raw materials in compounding pharmacies, as a routine procedure, to ensure the desired dose/effect.
ABSTRACT
Thalidomide was indicated as a sedative and antiemetic and prescribed for pregnant women. Its tragic teratogenic effects culminated in withdrawal from the market. Since the discovery of its anti-angiogenic and anti-inflammatory actions, thalidomide has been used in the treatment of leprosy and multiple myeloma, which justify studies of its stability. We investigated the effects of irradiation of thalidomide up to 100 kGy (fourfold the usual sterilizing dose for pharmaceutics). The β polymorph of thalidomide was obtained in an isothermal experiment at 270 °C. All samples underwent gamma irradiation for specific times. At different doses, decomposition of the pharmaceutical was not observed up to 100 kGy. The observed effect was angle turning between the phthalimide and glutarimide rings modulated by repulsion towards the carbonyl group, leading to a stable energetic configuration, as measured by the equilibrium in the torsion angle after irra-diation. The thalidomide molecule has a center of symmetry, so a full turn starting from 57.3° will lead to an identical molecule. Further irradiation will start the process again. Samples irradiated at 30 and 100 kGy have more compact unit cells and a lower volume, which leads to an increase in the intermolecular hydrogen interaction within the unit cel , resulting in higher thermal stability for polymorph α.
ABSTRACT
Objective Two co-crystals of isonicotinic acid hydrazide(INH)-malonic acid and INH-glutaric acid were prepared.The formation mechanism and intermolecular interaction were studied. Methods Three-dimensional structure of 2 co-crystals were obtained though single crystal X-ray diffraction(SXRD), and intermolecular interaction was analyzed using Hirshfeld surface method. Results INH-malonic acid crystalized in stoichiometric ratio of 1:0.5,while INH-glutaric acid in 1:1.Two co-crystals maintain their stable arrangement in space by hydrogen bond and van der Waals force. Conclusion With the existence of pyridine ring and carbohydrazide group in INH,which mainter-molecular interaction in co-crystal can be directly and clearly revealed by Hirshfeld surface analysis.