Study On The Evaporative Crystallization Of Penicillin V Potassium

Penicillin V Potassium is an important pharmaceutical raw materials andpharmaceutical intermediates. It is widely used in the oral dosage forms, theproduction of semi-synthetic penicillins and cephalosporins. In addition, it is alsoused as raw materials to prepare semi-synthetic antibiotic intermediates such as6-APA and7-ADCA. Currently, the main problems in the crystallization process ofpenicillin V potassium is the difficulty of particle size control, the unevendistribution and the low final yield. In oder to dissolve these problems, this paperdid systemaic research on the evaporation crystallization process of penicillin Vpotassium.From the viewpoint of thermodynamics, the solubility of penicillin Vpotassium in pure water and n-butanol-water mixed solvent were determined bythe dynamic method. At the same time, tne experimental solubility were correlatedby the Van’t Hoff equation and themodified Apelblat equation.On the basis of Van’tHoff equation, weobtained the heat of dissolution in various solvent composition.The(CNIBS)/Redlich-Kister equation was used to correlate the solubility withdifferent water content. Additionally, the solubility and supersolubility in themixing solvent with different water content were also measured. The experimentalmetastable zone data and solubility data provides a strong theoretical support forthe subsequentcrystallization process optimization.As to crystal morphology, the effects of solvents on the crystal habit and formsof potassium penicillin V were investigated experimentally. At the same time,thesingle crystal of potassium penicillin V were successfully prepared through themethod of solvent slow evaporation. On the basis of single structure, we obtainedthe crystal cell parameters, crystal system and space group. By virtue of theMaterials Studio software the crystal habit of penicillin V potassium and penicillinV acid were simulated respectively.Based on the study above, the key factors affecting the particle size andtheyield of penicillin V potassium were analyzed and summarized. And then,theeffects of degree of vacuum, the stirring blade and the stirring rate on the crystalsize were investigated. At the same time, on the basis of the thermodynamic dataobtained from experimental measurement, the effects of initial concentration, the initial solvent composition, and operating time on thecrystallization yield were alsostudied. Finally, the optimal crystallization process operating parameters wasdetermined by a number of experiments and analysis.No related reports have been reported in literature up to date.