The Use of Polyvinyl Alcohol to Inhibit the Hydrate Transformation of the Drug Theophylline

Advisor Information

Alan Gift

Location

UNO Criss Library, Room 107

Presentation Type

Oral Presentation

Start Date

7-3-2014 1:30 PM

End Date

7-3-2014 1:45 PM

Abstract

The solid form of active pharmaceutical ingredients (APIs) in drug tablets have the potential to transform into a hydrate state. These transformations are important to understand in order to prevent unwanted transformations when the anhydrate crystals are in the presence of water. Specific polymer excipients have the ability to inhibit this anhydrate to hydrate transformation. In this study, various properties of polyvinyl alcohol (PVA) were investigated to better understand the factors that inhibit this theophylline transformation. Anhydrous theophylline was added to solutions containing dissolved PVA and the transformation from anhydrate to hydrate theophylline was monitored using in-line Raman spectroscopy by collecting spectra every 30 seconds. A calibration model was used to quantify the extent of the transformation for each of the collected Raman spectra, which was then used to construct transformation profiles. The results showed that the inhibition of theophylline was dependent on chain length and percent hydrolysis of the polymer. In addition, intrinsic dissolution and solubility tests were performed to further examine the mechanism of this inhibition. These results indicate that the presence of PVA had little to no effect on the intrinsic dissolution and solubility of theophylline. This suggests that PVA is inhibiting the transformation of theophylline by affecting the growth of the hydrate phase.

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Mar 7th, 1:30 PM Mar 7th, 1:45 PM

The Use of Polyvinyl Alcohol to Inhibit the Hydrate Transformation of the Drug Theophylline

UNO Criss Library, Room 107

The solid form of active pharmaceutical ingredients (APIs) in drug tablets have the potential to transform into a hydrate state. These transformations are important to understand in order to prevent unwanted transformations when the anhydrate crystals are in the presence of water. Specific polymer excipients have the ability to inhibit this anhydrate to hydrate transformation. In this study, various properties of polyvinyl alcohol (PVA) were investigated to better understand the factors that inhibit this theophylline transformation. Anhydrous theophylline was added to solutions containing dissolved PVA and the transformation from anhydrate to hydrate theophylline was monitored using in-line Raman spectroscopy by collecting spectra every 30 seconds. A calibration model was used to quantify the extent of the transformation for each of the collected Raman spectra, which was then used to construct transformation profiles. The results showed that the inhibition of theophylline was dependent on chain length and percent hydrolysis of the polymer. In addition, intrinsic dissolution and solubility tests were performed to further examine the mechanism of this inhibition. These results indicate that the presence of PVA had little to no effect on the intrinsic dissolution and solubility of theophylline. This suggests that PVA is inhibiting the transformation of theophylline by affecting the growth of the hydrate phase.