Metastable Zone Width for Racemic Ibuprofen in Ethanol and Aqueous Ethanol Mixtures

  • Mr Abdur Rashid, Division of Chemical Engineering,The University of Queensland, Brisbane, QLD-4072.Australia, Australia
  • Prof Ted White, Division of Chemical Engineering,The University of Queensland, Brisbane, QLD-4072.Australia, Australia
  • A/Prof Tony Howes, Division of Chemical Engineering,The University of Queensland, Brisbane, QLD-4072.Australia, Australia
  • Prof Jim Litster, School of Chemical Engineering, Purdue University, West Lafayette IN 47907-, United States
  • Dr Ivan Marziano, Materials Science, Sandwich Laboratories, Pfizer Global Research &, United Kingdom

    • To investigate the crystallization of racemic ibuprofen [2-(4-isobutyl-phenyl)-propionic acid] from ethanol and aqueous ethanol mixtures it is necessary to know the nucleation limits of the solutions. In the absence of crystals, nucleation will not occur below the PNT (Primary Nucleation Threshold) and if crystals are present, below the lower SNT (Secondary Nucleation Threshold). PNT and SNT values (expressed as relative supersaturation σ) have been measured for ibuprofen in absolute ethanol and in a range of solutions of different ethanol (E) / water (W) ratios at three temperatures, 10, 25 and 40°C.

    The procedure was to prepare a range of different supersaturated solutions of ibuprofen at a given temperature and E/W ratio and determine the induction times (till nuclei were observed). As expected, lowering the supersaturation leads to longer induction times. In ethanol, the SNT values are small and thus the metastable zone is relatively narrow with a 1 hr SNT of σ ~ 0.04 above solubility. The 1 hr PNT values σ ~ 0.3 above solubility) are much larger.

    In aqueous ethanolic mixtures at 25ºC, both the PNT and SNT decrease as the water content increases. The SNT values are very close to the solubility value while the PNT values are significantly larger.