Improvements in crystallization of mefenamic acid using ultrasonic bath operating at two frequencies

Abstract

Crystallization of Mefanamic acid (MA), a pharmaceutically important drug has been investigated in the presence of ultrasound with an objective of improving the yield and particle size distribution (PSD). The conventional approach based on only stirring has also been compared with the ultrasound assisted approach to establish the improvements due to the use of ultrasound. Effect of various ultrasonic parameters on the crystallization yield, crystal habit, particle size and particle size distribution has been elucidated. For the ultrasound assisted approach, it was demonstrated that plate shaped particles are obtained which are more useful in terms of their bioavailability. The conventional method resulted in needle shaped crystals. Study of different operating conditions established that maximum yield (82.11 %) was obtained under conditions of 40 W as the ultrasonic power and 40 kHz frequency. Use of 22 kHz frequency gave slightly lower yield as 77.17 % at same power dissipation. Higher frequency of 40 kHz also resulted in smaller particle size as compared to 22 kHz frequency. The studies related to effect of irradiation time at the optimized values of frequency and power demonstrated that 10 min of irradiation is optimum in terms of giving higher yield of the crystals. Overall, ultrasound assisted approach was found to be much better than the conventional method and establishing best operating conditions in the study allowed obtaining enhanced yield and uniform shape coupled with reduction in the mean particle diameter.