For the purpose of enhancing the solubility and humidity stability of pymetrozine (PMZ), a highly active but nonbiocidal pesticide, new multicomponent crystals were developed based on the connotation of crystal engineering. In the coformer screening process, a combined method, the Conductor-like Screening Model for Realistic Solvents (COSMO-RS) approach together with Cambridge Structural Database (CSD) analysis, was employed to shorten the screening process. Further, seven single crystals of PMZ’s new multicomponent solids were obtained including three cocrystals and four salts. Single-crystal X-ray diffraction together with Hirshfeld surface analysis clarified the detailed structure and the molecular interactions in these new crystals. Thermodynamic properties and spectral data were characterized by thermogravimetric analysis, differential scanning calorimetry, and Fourier-transform infrared spectroscopy. Hygroscopicity and solubility of the seven cocrystals/salts were investigated by dynamic vapor sorption and equilibrium solubility measurement, respectively. Multicomponent crystals not only exhibit better stability against humidity and but also higher water solubility than PMZ. Meanwhile, the insecticidal activity of PMZ was preserved during the formation of cocrystals/salts. On this basis, we conducted the atoms-in-molecules (AIM) analysis and the molecular electrostatic potential surfaces (MEPs) analysis to assess the strength of hydrogen bonds and reveal the origins of salt/cocrystal formation. So, the variations and origins of these physicochemical properties were rationalized and explained on the atomic scale. On the whole, the efficiency of the novel combined coformers screening method was verified and new multicomponent crystalline forms of PMZ were successfully obtained to prevent the parent compound from hydrating transformation.

Propylthiouracil (PTU) is a clinically preferred drug to treat hyperthyroidism effectively. The sustained release of PTU is necessary because of the shortcomings of rapid release and hepatotoxicity. In this study, cocrystals of PTU with nutritional coformers were screened, and four new cocrystals of PTU with cinnamic acid (CA), gentistic acid (GA), ellagic acid (EA), and kaempferol (KA) were discovered. The cocrystals were characterized by single-crystal and powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, and scanning electron microscopy. The Hirshfeld surface analysis and reduced density gradient analysis reveal that the weak van der Waals interactions play an essential role in the crystal packing. The stability test indicates that all four cocrystals show excellent stability under accelerated storage conditions (40 °C and 75% RH) over 12 weeks. Moreover, PTU-CA, PTU-EA, and PTU-KA cocrystals all exhibit decreased solubility and decelerated intrinsic dissolution rate (IDR). Among them, the PTU-KA cocrystal shows the best performance. Specifically, the solubility decrease is up to 77.32% in pH 1.2 buffer and 85.15% in pH 6.8 buffer, and the lowest IDR is 12.0% and 20.8% of that of PTU in pH 1.2 and 6.8 buffers. According to the calculation result, the sustained-release effect could be attributed to the enhanced lattice energies and hydrophobic interaction. This work may be useful to design a sustained-release system via cocrystallization of APIs that have significant hepatotoxicity.

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2,4-dichlorophenoxyacetic acid (2,4-D) is a kind of plant growth regulator which exhibits hormesis effects at low dosages, while high dosages adversely affect the exposed organisms and act as herbicide. The...

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