Preparation Process and Growth Mechanism Analysis of Phenylacetyl‐7‐Aminodeacetoxycephalosporanic Acid Crystals with Controllable Morphology

Abstract A recrystallization process for phenylacetyl‐7‐aminodeacetoxycephalosporanic acid (phenylacetyl‐7‐ADCA) is used to obtain the monoclinic and tetragonal crystal forms. The purity of the process product is 99.7%, which is much higher than the 97.1% of the raw material, while the median (D 50 ) particle size is larger (144 µm) and the diameter span (DS) is reduced from 10.478 (raw material) to 2.070 (new process product). The results show that in water–ethanol systems when the mole fraction of water is less than 0.5, the products obtained are long rod‐shaped, while when the mole fraction of water is greater than 0.5, lamellar crystal products are obtained. The growth mechanism of phenylacetyl‐7‐ADCA with different habits is analyzed by Materials Studio molecular simulation software. The results show that a large number of oxygen and nitrogen atoms at both ends of the crystal are exposed to the crystal surfaces during the cooling recrystallization process and it is easy to form hydrogen bonds with free phenylacetyl‐7‐ADCA. Therefore, the crystal surfaces at both ends grow fastest and tend to disappear eventually. This work may provide a preparation process and simulation method for phenylacetyl‐7‐ADCA crystals, which would help improve the quality of cephalosporins.