Effect of ultrasonication on the dilution crystallization of naproxen

ABSTRACT

This work investigates the use of ultrasonication for the dilution crystallization of naproxen. Naproxen solution was prepared in acetone, while water was used as the anti-solvent. The main objective of this study was to determine the effect of sonication on the thermodynamic properties (solubility, metastable zone width, and induction time) and particle size of naproxen crystals. The use of sonication was compared to conventional stirred crystallization methods. When the solvent ratio (V_acetone/V_water) is low, no significant difference exists between the naproxen solubility in either the sonicated or stirred solutions. However, at higher solvent ratios (V_a/V_w = 9) and at low temperatures (0°C), ultrasonication increases the solubility of naproxen from 0.171 to 0.193 g/mL. Compared to conventional stirred crystallization techniques (the metastable zone width is 0.024 g/mL), ultrasonic crystallization is characterized by a narrower metastable zone (the width is 0.010 g/mL), and with ultrasonic crystallization the induction time decreases by about 50 seconds. During ultrasonic crystallization, the average naproxen particle size is reduced from 22.6 to 10.5 μm by increasing the power and time of ultrasonication. Particle sizes and crystal morphologies obtained using ultrasonication were significantly improved compared to those produced with stirring.

KEYWORDS:

• Dilution crystallization
• naproxen
• particle size
• thermodynamic properties
• ultrasonication

Funding

Financial support is acknowledged from the Natural Science Foundation of Jiangsu Province (BK2012763), and Fundamental Research Funds from the Central Universities (ZD2014YX0027) are also gratefully acknowledged.

Additional information

Funding

Financial support is acknowledged from the Natural Science Foundation of Jiangsu Province (BK2012763), and Fundamental Research Funds from the Central Universities (ZD2014YX0027) are also gratefully acknowledged.