US EPA

1117378 

Journal Article 

Solubility of Form III Piracetam in a Range of Solvents 

Maher, A; Croker, D; Rasmuson, AC; Hodnett, BK 

2010 

Yes 

Journal of Chemical and Engineering Data
ISSN: 0021-9568
EISSN: 1520-5134 

55 

11 

5314-5318 

10.1021/je1003934 

WOS:000284017600125 

The polymorph known as Form III of 2-oxo-1-pyrrolidine acetamide (piracetam) was isolated by cooling crystallization from methanol and characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). Form III is the thermodynamically stable polymorph of piracetam in the range of this solubility study. The solubility of Form III was determined by gravimetrically measuring the amount of Form III which was contained in a volume of saturated solution over the temperature range (278 to 323) K, following evaporation of the solvent. Five solvents were examined: methanol, ethanol, 2-propanol, acetone, and 1,4-dioxane. The results showed that the solubility values correlated positively with solvent polar characteristics from a qualitative point of view; an increase in solubility of Form 111 was observed with increasing solvent polarity and solvent acidity. As the number of carbons in the n-alcohols increases, the polarity of the solvent and its hydrogen donation ability decreases and so does the solubility of Form III in the solvent. 1,4-Dioxane and acetone are relatively nonpolar and non-hydrogen bond donating solvents compared to the n-alcohols, and accordingly Form III is much less soluble in these.