Effects of Sonocrystallization on Crystal Size Distribution of Cloxacillin Benzathine Crystals

Lecturer ： Jieqiong LiSupervisor ： Prof. Jingkang WangDate ： 2012.11.23

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Content

Introduction

Experimental Sections

Results and Discussion

Conclusions

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Introduction

Applications NERCICT

Introduction

Fig. 1 Effect of sonication on supersaturation.

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proteins/peptides

sugars

Introduction

buble growth buble collapse shockwave emerge shockwave impact

Sonofragmentation of Needle CrystalsNERCICT

seeding

transient cavitation

Efficacy of the

Seeding

Purity

Size

Amount

Introduction

Incline to AgglomerateEnsure the

Narrow CSD

Small Crystalsreaction

crystallization

ultrasound

Final CSD

primary nucleation rate

crystal fragmentation rate

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Different process conditions

Different lengths of insonated periods

Different seeding load

Different feeding rate

Experimental Sections

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.

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Conventional seeding

Seeding & ultrasonic interruption

Seeding in situ

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Fig.3 Optical photographs of cloxacillin benzathine crystals just precipitate from the solution under different process conditions. (1) non-insonated experiment; (2) insonated experiment.

Results & Discussion

Fig. 4 Crystal size distribution (left) and optical photographs (right) of cloxacillin benzathine under different process conditions. (A) non-insonated control experiment; (B) continuous insonation; (C) a short period of insonation interruption.(100×)

Effect of Different Process Conditions

Effect of Different Lengths of Insonated Periods

Fig. 5 Optical photos of cloxacillin benzathine 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.

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Results & Discussion

Fig. 7 Effect of seeding load on the final crystal size distribution.

Effect of Different Seeding LoadNERCICT

Results & Discussion

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 10.01

0.012

0.014

0.016

0.018

0.02

0.022

0.024

0.026

0.028

Feeding rate (mL/min)

Solu

te c

once

ntra

tion

Effect of Different Feeding Rate

Fig. 8 Effect of feeding rate of the reaction material solutions on the cloxacillin benzathine 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.

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a

b

c

d e

f

Results & Discussion

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.

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Thank You for Your Attention

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