Improved Dissolution Behavior of Dipyridamole Formulation with Precipitation Inhibitor

Abstract

Background: Physiologically generated supersaturation and subsequent precipitation of a weakly basic drug in the small intestine leads to compromised bioavailability. Methods: In this work, the pH -induced precipitation of dipyridamole (DPD) as a model weakly basic drug in the presence of Eudragit L100 (Eu) and hydroxypropyl cellulose (HPC) was investigated. Inhibitory effects of the polymers on precipitation of DPD at varying drug/polymer ratios were examined. The effects of the polymers on the DPD dissolution property were assessed using drug/polymer physical mixtures (PMs) and solid dispersions (SDs). Results: Significant inhibitory effects on precipitation were found using Eu, while HPC as well inhibited precipitation, but to a lower level than found with Eu. The PMs resulted in higher area under the dissolution curve (AUDC) compared to SDs. For SDs, the AUDC was limited by the slow release of the drug from the polymers in acidic pH which in turn decreased supersaturation of DPD following acidic to neutral pH transition. Conclusion: From these results, it may be supposed that both the ability to create and stabilize supersaturation separately of each other to be important for enhancing dissolution of DPD.

Keywords

• supersaturation
• dipyridamole
• eudragit l100
• hydroxypropyl cellulose
• precipitation inhibition
• dissolution