Influence of Polymorphs on the Transformation Water Activity of Theophylline

In this paper, the influence of polymorphs on the transformation water activity that corresponds to the transformation between hydrate and anhydrate of theophylline was investigated. Theophylline is known to exist either as anhydrates or a monohydrate. The transformation water activities of theophylline form II and IV were determined respectively, and the solubility data of these two forms in methanol, ethanol, acetonitrile, and acetone was also determined. The following thermodynamic derivation indicates that the transformation water activity ratio of theophylline forms II to IV can be correlated with the solubility ratio. According to the above study, the stability and intercoversion of theophylline polymorphs is discussed. This work will be useful in understanding the transformation process and benificial for industrial process control.