Effect of Mixed Solvents and Additives on the Habit Modification of 6-APA Crystals

6-aminopenicillanic acid (6-APA) crystals obtained under different physical and chemical conditions of the solutions may present different habits. The habits of diamond-shaped plates are desirable compared with other habits of 6-APA crystals. To obtain ideal 6-APA crystals, the effects of the mixed solvents and additives on 6-APA crystal habits were investigated. Ethanol or acetone was used as the organic solvent, and impurities existing in the 6-APA purification process were used as the additives. 6-APA growth habits were changed when the concentrations of ethanol, acetone or phenyl acetic acid were increased to exceed their critical concentration. The observed results show that the dominant face on 6-APA crystals was identified to be {020}, but the overall habit was controlled by the relative growth rates of the {101} and {002} faces. Crystal growth rates and habits can be appreciably changed by specific adsorption of additives on crystal faces.In some cases solvent molecules can act in a similar way and may be regarded as bulk additives. The effects of additives and organic solvents on 6-APA crystal habits were the results of adsorption effect, which fitted the experimental results quite well.

Preparation of 6-APA by Enzymatic Bioconversion in an Emulsion Liquid Membrane Reactor

Production of 6-aminopenicillanic acid (6-APA) by hydrolysis using penicillin acylase (PA) was studied as a model of an enzymatic emulsion liquid membrane (ELM) process. The loss of PA activity was examined for various membrane compositions (organic solvent, surfactant, carrier). The effects of some experimental variables on the stability of emulsion were investigated. It was found that the choice of organic solvent greatly affected the stability of the emulsion. Increasing the concentration of the carrier in the membrane phase increases the transfer rate of substrate and products but also has a destabilizing effect on the emulsion. The recovery of 6-APA obtained by a di-carrier system (N263-N1923) was much higher than those when either of the di-carriers was used separately. The whole process was controlled both by the enzymatic reaction rate and by the transfer rate of the substrate and the products, however, the ratio of them could be changed by varying the composition of the system. For an optimum condition, it was obtained that the recovery ratio of 6-APA was over 80% and the conversion of benzyl penicillin (PG) was up to 90% in the external phase after 30 minutes. Meanwhile, the breakage percentage of the emulsion was less than 2%.

FBRM and PVM investigations of the double feed semi-batch crystallization of 6-aminopenicillanic acid

6-Aminopenicillanic acid(6-APA)is a crucial pharmaceutical intermediate in the chemistry of semi-synthetic antibiotics.The focused beam reflectance measurement(FBRM)technology and particle vision measurement(PVM)technology were employed to the processes of online-monitoring of 6-APA crystallization behavior in a double-feeding semi-batch crystallizer.Experiments were carried out with four kinds of double-feeding policies and the results were compared with the traditional single-feeding.Records and analysis of FBRM indicated that the nucleation of double feeding policy was much higher than single policy,and chord length of 6-APA was almost determined and had little change after the nucleation peak.Ostwald ripening process had no significant effect on further growth of 6-APA crystal.PVM images showed that the crystal habit of 6-APA was continuously changed during the crystallization process.The development of(002)face in the final crystal for the five feeding policies were different.