Crystallization of Amoxicillin Trihydrate in the Presence of Degradation Products

Abstract

Amoxicillin is an important semi-synthetic antibiotic produced in large quantities around the world, and developing a highly cost-effective crystallization process for amoxicillin is of significant importance. In this study an in situ turbidity meter is used to measure the induction period for the onset of nucleation in the pH-controlled crystallization of amoxicillin from aqueous solutions. Amoxicillin trihydrate is crystallized at pH 4.7 at 4 °C. It is demonstrated that turbidimetry is an effective technique for detecting nucleation in industrial crystallization. The induction period decreases with an increase in supersaturation, and the degradation products inhibit the nucleation process. The powder X-ray diffraction patterns show that the resulting products purified by crystallization are confirmed as being identical to amoxicillin trihydrate standard material, and high-pressure liquid chromatography analysis demonstrates that the purity of amoxicillin obtained in the crystallization is at least as high as that of the standard material.