Effects of Sonocrystallization on Crystal Size Distribution of Cloxacillin Benzathine Crystals

1. NERCICT Effects of Sonocrystallization on Crystal Size Distribution of CloxacillinBenzathine Crystals Lecturer：Jieqiong Li Supervisor：Prof. Jingkang Wang Date：2012.11.23

2. NERCICT Introduction Content Experimental Sections Results and Discussion Conclusions

3. Introduction • Applications NERCICT

4. Introduction NERCICT proteins/peptides sugars Fig.1Effect of sonication on supersaturation.

5. Introduction • Sonofragmentation of Needle Crystals NERCICT transient cavitation buble collapse buble growth shockwave emerge shockwave impact seeding

6. Introduction • reaction crystallization NERCICT Small Crystals • Final CSD primary nucleation rate • ultrasound crystal fragmentation rate

7. Experimental Sections NERCICT • Different process conditions • Different lengths of insonated periods • Different seeding load • Different feeding rate Conventional seeding Seeding & ultrasonic interruption Seeding in situ Fig. 2 Schematic Diagram of The Experimental Setup: (A) jacketed reactor; (B) stirrer driver; (C) propeller; (D and E) peristaltic pump; (F and G) feed tanks; (H) thermostatic bath; (I) ultrasonic bath.

8. Results & Discussion • Effect of Different Process Conditions NERCICT Fig.3 Optical photographs of cloxacillinbenzathine crystals just precipitate from the solution under different process conditions. (1) non-insonated experiment; (2) insonated experiment. Fig. 4 Crystal size distribution (left) and optical photographs (right) of cloxacillinbenzathine under different process conditions. (A) non-insonated control experiment; (B) continuous insonation; (C) a short period of insonation interruption.(100×)

9. Results & Discussion • Effect of Different Lengths of Insonated Periods NERCICT • Fig. 5 Optical photos of cloxacillinbenzathine with different lengths of insonation periods (200W): (A & a) seeding & without insonation; (B & b) seeding & insonated for 2min; (C & c) seeding & insonated for 4min. Fig. 6 Effect of different lengths of insonation periods on the final crystal size distribution: (left) at ultrasound nominal power of 100W;(right) at ultrasound nominal power of 200W.

10. Results & Discussion • Effect of Different Seeding Load NERCICT Fig. 7 Effect of seeding load on the final crystal size distribution.

11. Results & Discussion • Effect of Different Feeding Rate NERCICT f e d c b a Fig. 8 Effect of feeding rate of the reaction material solutions on the cloxacillinbenzathine crystals : (left) the concentration of the solution when the crystals were detectable; (right) optical photographs of the crystals after precipitation from the solution under different feeding rate. Fig. 9 Effect of feeding rate of the reaction material solutions on the final crystal size distribution.

12. Conclusions • The longer the ultrasound performed and the more powerful the ultrasound was, the smaller the needle crystals were. • Crystals produced with low seeding loads present widespread and bimodal PSD, while the CSD was narrower and approaching to unimodal with increased seeding load. • Relatively slower feeding rate is favorable to produce products with improved properties. • Prolonged application of ultrasound after the nucleation onset has the potential to improve the final CSD and produce crystals with regular shape. NERCICT

13. NERCICT Thank You for Your Attention