Abstract
Ibuprofen is a popular analgesic and is mostly marketed as tablet dosage form. It is helpful in tablet production to have feed crystals of regular shape and narrow size distribution. Controlled crystallization techniques can provide such a desired size and shape of ibuprofen crystal/powder. To design a controlled crystallizer for ibuprofen [((RS)-2-(4-(2-methylpropyl) phenyl) propanoic acid)] from ethanol and water - ethanol mixtures it is necessary to know the nucleation rate kinetics of its solutions. Secondary nucleation rates for the crystallization of racemic ibuprofen from aqueous ethanol have been measured by adding seeds to an ibuprofen solution supersaturated above the secondary nucleation threshold (SNT). After the onset of nucleation, crystal samples were taken over short time intervals and the numbers of crystals in the vessel determined. The rate of change in the number of crystals gave the nucleation rate B. It is assumed that the order of the nucleation rate dependence on supersaturation s and the order of dependence on the crystal content Mc are both first order, giving equation B = kB Mc s, where s is the supersaturation in Delta I/E (mass ratio ibuprofen to ethanol) units. For aqueous ethanolic solutions and for the nucleation rate B in number/min/(kg crystal/L slurry) units, kB = 2.4 x 109/T1.4 (independent of XW, the solution water content), where T is the solution temperature in oC. The estimated 95% probable uncertainty in the constant is +/- 6%, while that of the temperature exponent is +/- 30%. The correlation fits 95% of the experimental data within a factor of 6.