A Study On The New Manufacturing Technology Of Ampicillin Sodium And The Clarity Of The Production

The manufacturing technology of ampicillin sodium and the clarity of the production and its stability were systematically studied in this thesis. After being analyzed, it is shown that the reaction between the rubber stopper and the small quantity of 2-ethtyhexanic acid and di-isopropylamine contained in the final product is the crucial reason for the unstable clarity of ampicillin sodium manufactured by the solvent-out crystallization process with dichloromethane. In order to eliminate the unfavorable effect of 2-ethtyhexanic acid and di-isopropylamine on the product clarity, a novel manufacturing technology, the solvent-out crystallization process with acetonitrile was developed. After being tested with various chemical reagents, salt forming agents and solvents, this new method was found having some outstanding advantages. By the orthogonal experiment, the process control conditions were optimized the solvent-out crystallization technology with acetonitrile was finally determined.Although comparing with the old crystallization method with dichloromethane, the content of the product of the new crystallization method with acetonitrile is lower, and the degradation product is also slightly higher, other indicators such as the clarity and the crystal form of the product and the production cost are much better. Furthermore, because 2-ethtyhexanic acid and di-isopropylamine are taken out in the new crystallization process, and the reaction between the product and the rubber stopper is lowered, thus the stability of product clarity is improved.