| Put forward on the concept of crystal engineering,supramolecular chemistry and molecular self-assembly,cocrystal drug is a novel supramolecular compound formed by the weak interaction which come from non-covalent bonds such as hydrogen bonds and van der Waals forces.Based on the retention of its molecular structure function and effectiveness,the drug cocrystal is a weak action synthesis and technology mean aiming at improving solubility and stability of the drug,optimizing its physical and chemical properties.At the same time,the cocrystal conformer combined with the active pharmaceutical ingredient in the same lattice can be an acid,base or neutral molecule which is acceptable to the organism.There are many methods for the preparation of cocrystal,including melting method,solution crystallization method,spray drying method,grinding method(divided into Solvent-Drop grinding method and Neat grinding method),ultrasonic method and supercritical method.Carbamazepine is a low-water-soluble drug,with slow and incomplete oral absorption.It is also difficult to form salt.Carbamazepine exists in the form of dimer,its molecule containing amide functional groups,which is easy to form cocrystals through hydrogen bonds.In the Cambridge crystal database alone,more than 40 kinds of cocrystal data exist.Carbamazepine is one of the first cocrystal drug widely studied.The main contents of this paper are as follows:1.Carbamazepine was used as a model to select a variety of substances which can synthesis cocrystal with carbamazepine according to the synthon structures such as carboxylic acid-amide and amide-amide.The cocrystal screening was carried out by grinding method and suspension method.Two cocrystal were obtainde,the corresponding CCF is gallic acid and methyl gallate.The cocrystal structures were analysisde and the characterization were characterized by means such as X-ray diffraction,infrared spectroscopy,and thermal analysis.Crystal structure shows that the API,CCF,H2 O three components exist in both two cocrystals lattice,connected through the O—H…O,N—H…O hydrogen bonding.2.The solid-state fluorescence analysis method was applied to the detection andprediction of cocrystal.Using the known carbamazepine obtained cocrystal abrasive samples,we test solid-state fluorescence and PXRD.The results show that the solid-state fluorescence of the synthesis of cocrystal is pre-determined by the redshift phenomenon and the verification experiment is also carried out.The results show that this method has a certain effect can form a set of independent cocrystal identification system.3.The interaction between carbamazepine,salicylic acid and human serum albumin(HSA)was analyzed by fluorescence spectroscopy.It was found that both of the binding of carbamazepine and salicylic acid to HSA was caused by hydrophobic interaction And the binding sites and site number of the two component were consistent.The experimental results showed that the two drugs had a competitive effect in the process of binding to HSA.Try to find out the perspective of the study further illustrates the advantages of cocrystal drugs,the pharmacokinetics properties of the carbamazepine cocrystal were also investigated.4.The dihydrochloride form of metformin was found by the polymorphism research experiment.The single crystal structure was synthesized and analyzed,and its physical and chemical properties were systematically characterized.The acidification ratio of metformin dihydrochloride was optimized by using metformin hydrochloride and concentrated hydrochloric acid as raw materials.Compared with metformin hydrochloride,the water solubility of metformin dihydrochloride was significantly improved. |
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