The Study Of Acetaminophen Crystallization Process

Acetaminophen(APAP), which is a kind of aniline antipyretic analgesics, has many good features, for example less adverse reaction, good treatment effect, cheap and readily available and so on. With these advantages, it has been used all over the world. At present, a large number of researches about APAP stay in the fields including pharmacokinetics, pharmaceutics, synthesis development. However, there is fewer research about the crystallization process of APAP. So, the systemic study on crystallization process of APAP was made in this paper.First, raw material of APAP was characterized by means of these characterization methods including DSC, TG-DTA, FT-IR and XRPD. In ethanol and ethyl acetate solvent, two kinds of APAP crystals were prepared. Their XRPD data was parsed by MS software and their crystal cell parameters, the crystal system, space group, crystal structure were obtained. In addition, the crystal habit of APAP was predicted by BFDH model.With the laser dynamic method, the solubility of APAP in seven pure solvents and two binary mixed solvents was determined. The solubility in pure solvents and binary mixed solvents increased with temperature. The experimental solubility data in pure solvents were correlated by the van't Hoff equation and the modified Apelblat equation, which in mixture solvents were correlated by the CNIBS/R-K model and the modified Jouyban-Acree model. The four models all can reasonably match the experimental data. The thermodynamic functions were calculated by van't Hoff equation. Besides, the metastable zone of APAP in ethanol was researched.The crystal of APAP was prepared in ethanol solvent by the method of cooling crystallization. Process conditions were explored one by one through the single variable method. At last, the best process conditions were that stirring speed was 150rpm, cooling rate was 0.6?·min-1, initial concentration was 23.07%, final temperature was 10?, adding crystal, crystal growing time was 1.5h.