Study On The Effect Of Ultrasound-assisted Reaction Crystallization Process Of Azlocillin Acid

Azlocillin acid (ALPC), semi-synthetic ampicillin derived acylureido penicillin,is a broad-spectrum antibiotic of strong sterilization, especially effectively toPseudomonadaceae. In this paper, considering the problem of uneven distribution ofparticle size, poor product quality, non-uniform crystal morphology, andagglomeration of Azlocillin acid (ALPC) in the production process, reactivecrystallization process of Azlocillin acid were systematically studied.Crystal structure of Azlocillin acid were determined by Material Studio softwareon the basis of X-ray powder diffraction data, and the crystallography data ofAzlocillin acid were also determined; crystal habit of BFDH model and AE modelwere forecasted and compared with the actual crystal habit.Degree of solubility of Azlocillin acid at different temperatures in the water wasmeasured by dynamic method; end point of the reaction titration was determined bymeasuring the dissolved situation at different pH values; the metastable areas ofazlocillin were determined by reaction titration method under ultrasound andnon-ultrasound environments, the thermodynamic basic data needed for the processoptimization were reached.Induction period of reaction crystallization of the azlocillin acid was measuredunder ultrasound and non-ultrasound environments by laser method, and themechanism of crystal nucleation was discussed; crystallization kinetics was measuredby intermittent dynamic method, nucleation rate and growth rate of the reactivecrystallization process of Azlocillin acid were reached by calculating the model withmoment transformation method.Combined with the crystal growth characteristics, thermodynamic properties,crystallization kinetics and the process model simulation analysis of Azlocillin acid,the optimum operating conditions were obtained through the change of experimentaloperating factors, such as ultrasound environment, initial concentration, dropping rateand agitation speed. It is drawn that the introduction of ultrasound can improve thecrystal habit of the Azlocillin acid products, distribution of particle size and reduce thedegree of coalescence, improve the quality of the product; the experimental productcomplies with the requirements of the manufactures. The results can provide basic data and theoretical basis for further industrial production.There is no similar report to above result has been published in literature up todate.