Improved Crystallization of Ampicillin Trihydrate Based on the Use of Ultrasound

Ampicillin trihydrate (AT) is a widely used antibiotic and it is of utmost importance to control the particle size distribution, mean size, and morphology so as to achieve faster dissolution and enhanced bioavailability. In present work, ultrasound-assisted cooling crystallization of ampicillin trihydrate was studied with an objective to understand the effect of various ultrasonic parameters like sonication power, time, and duty cycle on the particle size and its distribution as well as yield and particle shape. In the presence of ultrasound, a reduction in induction time with higher yield was demonstrated as compared to the conventional approach. Microscopic analysis revealed plate-shaped crystals in the presence of ultrasound, whereas the conventional approach resulted in the formation of needle-shaped crystals. The mean particle size of the AT crystals reduced from 89.77 to 3.88 μm when treated using an ultrasonic horn under optimum ultrasonic conditions. Encouraging results were seen in the scale-up studies using an ultrasonic bath applied as the source of ultrasound. In summary, ultrasound-assisted cooling crystallization has been elucidated as an efficient way to obtain crystals of smaller size with improved bioavailability.