Synthesis And Characterization Of Pharmaceutical Crystals

The pharmaceutical crystals are an important series of materials, containedpharmaceutical polymorphism, pharmaceutical cocrystals, salts, solvates or hydratesmetal-drug complexes, which play a key role in the disease prevention and controlareas. Pharmaceutical cocrystals can improve the physicochemical andpharmaceutical properties without affecting its intrinsic structure. These materialsrepresent a class of crystalline forms that can be protected as intellectual property fordrug development. As a synthetic method of mature drug material, metal complexesdrugs also has high research value. As a product of multidisciplinary cross, thepharmaceutical crystals have been widely concerned by scientists.Based on the principle of supramolecular chemistry and crystal engineering,curcumin molecule as a linker, we designed and prepared the pharmaceutical crystalmaterials. At the same time, we explored the biological and chemical potentialapplications. The main contents are as follows:1. Two pharmaceutical cocrystals were successfully prepared, which werecomposed of curcumin and4,4’-bipyridine-N, N’-dioxide. The cocrystals contain thesame active pharmaceutical ingredient and the conformer in different systems. Singlecrystal X-ray diffraction indicated that the structure of JUC-C14curcumin existed in aenolic form, while the structure of JUC-C15curcumin existed in a di-keto form whichis rarely reported. Both cocrystals possess intermolecular O–H O hydrogen bonds. Itwas indicated that JUC-C14exhibits1D chain structure, while JUC-C15is a2D netstructure linked. Additionally, the solvent-induced crystal transformation from singlecrystal JUC-C14to single crystal of JUC-C15was investigated. Thepharmacokinetics studies and stability were performed to evaluate thepharmacokinetic (PK) studies.2. medi-MOF-1was successfully synthesized by the pharmaceutical ingredientcurcumin as the linker, and biocompatible metal Zn. It can display permanent porosityand a higher surface area (Langmuir model:3002m2/g) than the currently reportedbio-MOFs constructed from biomolecules solely. The MTT assay results show thatmedi-MOF-1exhibits a comparable cell growth inhibitory performance against theBxPC-3cells. We have studied the degradation process of medi-MOF-1as well as the capicity of drug ibuprofen or5-FU, which was chosen as model drug molecules tocodelivery, in order to realize the synergistic goal.3. Kinds of gases adsorption were perfromed to investigate the adsorption andcapture capacity of medi-MOF-1under different conditions. The product possesses ahigh amount of H2sorption capacity which can reached1.57wt%at77K. Also, itpossesses a certain amount of CO2adsorption capacity. Compared with CH4and N2,the CO2adsorption capacity of medi-MOF-1is much better. The PXRD patterns ofmedi-MOF-1after being heated at different temperatures show that it can retain itsintegrity at300°C. As evidenced by PXRD, it is also exhibited that medi-MOF-1maintains its crystallinity after soaking in various organic solvents, such as absoluteethanol, dichloromethane and n-hexane for three days. Additionally, activedmedi-MOF-1can display the ability of the uptake and release of I2at roomtemperature, which estimated by TGA is about0.5g g-1material. It is expected thatmedi-MOF-1would be designed as potential material with potentiality in thebiological field, since the linker of medi-MOF-1is active pharmaceutical ingredient.