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International Journal of Chemical Engineering
Volume 2015, Article ID 560930, 7 pages
Research Article

The Metastability and Nucleation Thresholds of Ibuprofen in Ethanol and Water-Ethanol Mixtures

1Department of Pharmaceutics, College of Pharmacy and Dentistry, Buraidah Private Colleges, Al-Qassim 31717, Saudi Arabia
2School of Chemical Engineering, The University of Queensland, Brisbane, QLD 4072, Australia
3School of Chemical Engineering, Purdue University, West Lafayette, IN 47907-2100, USA
4Chemical Research & Development, Pfizer Worldwide Research and Development, Sandwich, Kent CT13 9NJ, UK

Received 4 June 2015; Revised 16 July 2015; Accepted 2 August 2015

Academic Editor: Jerzy Bałdyga

Copyright © 2015 Abdur Rashid et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


To investigate the crystallization of ibuprofen [((RS)-2-(4-(2-methylpropyl) phenyl) propanoic acid)] from ethanol and water-ethanol mixtures it is necessary to know the nucleation limits of its solutions. In the absence of crystals, nucleation will seldom occur below the PNT (primary nucleation threshold). If crystals are present, nucleation will seldom occur until below the lower SNT (secondary nucleation threshold). Below the SNT, crystals will still grow with negligible nucleation. PNT and SNT values (expressed as relative supersaturation σ) have been measured at 10, 25, and 40°C for ibuprofen in ethanol and in a range of mixtures of different ethanol (E)/water (W) ratios. The induction times were determined from observing the times to nucleate for a range of different supersaturated solutions at a given temperature and E/W ratio. As expected, lowering the supersaturation leads to longer induction times. In ethanol, the SNT values are small and thus the secondary metastable zone width (MSZW) is relatively narrow with a 1 h SNT relative supersaturation typically about σ ~ 0.05. The 1 h PNT values are much larger with values for σ around 0.3. In aqueous ethanolic mixtures at 25°C, both the PNT and SNT decrease as the water content increases.