Solubility of the metastable polymorph of piracetam (Form II) in a range of solvents

Anthony Maher, Åke C. Rasmuson, Denise M. Croker, Benjamin K. Hodnett

Research output: Contribution to journalArticlepeer-review

Abstract

The solid-liquid solubility of the polymorph known as Form II of 2-oxo-1-pyrolidine acetamide (Piracetam) has been determined gravimetrically in different solvents. Form II is the metastable polymorph of piracetam at ambient conditions and has been isolated and characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). Monitoring the solution concentration and the polymorphic composition of the solid phase displayed that this metastable form has a sufficient lifetime when in contact with the solvents to allow measurement of its solubility over the temperature range (278 to 323) K. Four solvents are included: ethanol, 2-propanol, acetone, and 1,4-dioxane. The results show that the solubility of Form II increases with increasing solvent polarity and solvent acidity. Form II has a slightly higher solubility than the stable Form III in all solvents at all temperatures, but the solubility difference is very small. Since Form II is known to transform to Form I below its melting point, a set of regression equations which can be used to extrapolate solubility data to the melting point of Form II were applied to the collected data.

Original languageEnglish
Pages (from-to)3525-3531
Number of pages7
JournalJournal of Chemical and Engineering Data
Volume57
Issue number12
DOIs
Publication statusPublished - 13 Dec 2012

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