Design, Syntheses And Properties Of Pharmaceutical Co-crystal

Physical and chemical properties of the drug is one of the key factors in its clinical application, therefore, the research to improve the physical and chemical properties of the drug has been a focus of modern researchers. As a solid dosage form, crystal drug not only has various advantages of solid dosage forms, but also has more stable physical and chemical properties. The crystal drug also has been a research focus of the pharmaceutical dosage. In recent years, with the study of crystal drug deepening, the concept of supramolecular chemistry is introduced into the design of drug molecules. Through hydrogen bonding, π-π conjugated stacking interactions and other series of weak interaction, the pharmaceutical co-crystal can be formed. The most important feature of pharmaceutical co-crystal is that it has specific physical and chemical properties. The different physical and chemical properties of Active Pharmaceutical Ingredients (APIs) determine the efficacy of drugs in large part. The main research content of pharmaceutical co-crystal is that the physical and chemical properties of the Active Pharmaceutical Ingredients, such as mechanical properties, solubility, hygroscopicity, melting point, stability, and bioavailability, can be changed through the introduction of eutectic reagent (co-crystal former).In this article, we choose the 5-aminosalicylic acid and niacin as Active Pharmaceutical Ingredients (APIs). We try to put the API and a series of eutectic reagents together to form various pharmaceutical co-crystal and at last we totally get four 5-ASA pharmaceutical co-crystal and two niacin pharmaceutical co-crystal. During the research, we have tried various co-crystal preparation and summed up a series of efficient synthetic methods of the six pharmaceutical co-crystal. After we get the pharmaceutical co-crystal, we study the properties of the product, such as crystal structure, infrared, thermal stability, solubility and artificial membrane permeability. The main contents are divided into two parts as follows: 1. the research of pharmaceutical co-crystal of 5-aminosalicylic acidwe choose 5-ASA as API and make it react with a series of eutectic reagent(CCF), finally we obtain four pharmaceutical co-crystal of 5-ASA, such as 5-ASA-maleic acid co-crystal (1),5-ASA-2,6-dihydroxybenzoic acid co-crystal (2),5-ASA-4-aminopyridine co-crystal (3),5-ASA-2-aminopyridine co-crystal (4). In the synthesis process of a series of pharmaceutical co-crystal of 5-ASA, we have tried the mixing method, ultrasonic method and dosing polishing method. We initially concluded that the dosing polishing method has a greater advantage than others in the synthesis of pharmaceutical co-crystal. After we get the pharmaceutical co-crystal of 5-ASA, we characterize the properties of the products and study the solubility and artificial membrane permeability of the products. The experimental results show that after the formation of pharmaceutical co-crystal, the solubility and artificial membrane permeability of the original drug 5-ASA improve to some extent.2. the research of pharmaceutical co-crystal of NiacinOn the basis of the first part of the work, we use the dosing polishing method to give Niacin-2,6-dihydroxybenzoic acid co-crystal (5) and Niacin-4-aminopyridine co-crystal (6). After we get the pharmaceutical co-crystal of Niacin, we also characterize the properties of the products and study the solubility and artificial membrane permeability of the products. The solubility and artificial membrane permeability of the original drug Niacin also change.