New Insights into the Preparation of the Low-Melting Polymorph of Racemic Ibuprofen

Recently, a second crystalline polymorph (Form II) of racemic ibuprofen was reported to be obtained by crystallization from the supercooled liquid state. The reported procedure involved a temperature schedule that included the requirement to quench the sample to a temperature (168 K) significantly below the glass-transition temperature (228 K) followed by annealing at a temperature (typically 258 K) above the glass-transition temperature. In the present work, we show (by differential scanning calorimetry and in situ, variable-temperature powder X-ray diffraction) that Form II of racemic ibuprofen can be prepared by crystallization from the supercooled liquid at temperatures as high as 273 K, without the requirement for low-temperature quenching and without the requirement for the material to pass below the glass-transition temperature. Our results lead to a new interpretation of the experimental conditions for producing Form II of racemic ibuprofen and remove racemic ibuprofen from the set of crystalline materials that are obtained only via low-temperature quenching of a supercooled liquid.