Optimization Of The Crystallization Technology Of Amoxicillin

Amoxicillin is a broad spectrum penicillin antibiotic. With the increase of domestics capacity of amoxicillin , the competition is severity more and more, so it is important to improve the quality continually, in order to improve the granularity and CSD, isoelectric point crystallization of amoxicillin was studied systematically both in experiment and theory. Crystal yield is decided by crystallization thermodynamics. The solubility of amoxicillin in pure water under different temperature and pH were measured. The solubility of amoxicillin in pure water increases with temperature. As a kind of zwitter, amoxicillin exists in solution as three forms: anions, cations and neutral dipolar species. Solution chemistry plays an important role with respect to pH effect on solubility. When pH is lower or higher than isoelectric point, the solubility of amoxicillin increases dramatically. Other basic physicochemical data of solution, such as viscosity, density and metastable zone of amoxicillin solution were also measured, which are useful information for design and control of crystallization process.By using the orthogonal experiment method, the effects of the crystallization conditions, such as the solvent concentration, the stirring speed, the feed rate on the quality (CSD and purity) and the yield of amoxicillin was studied. The effects of impurity were observed. The optimal operational conditions were determined. The high quality product was produced under the optimized operation condition, and also the stability of the producing process was improved.