Enhancement of solubility and dissolution rate of dipyridamole by salifying: Preparation, characterization, and theoretical calculation

Abstract

Dipyridamole (DIP) is a medication utilized to treat cardiovascular diseases, belonging to the BCS II class of drugs with low solubility and high permeability. As the effectiveness of oral preparations is influenced by the solubility and dissolution rate of the active ingredients, this study developed eight salts for solid modification of DIP to overcome poor water solubility. These salts were characterized using single crystal X-ray diffraction, powder X-ray diffraction and thermal analysis. Dipyridamole-oxalate (DIP-OLA) and dipyridamole-malonate (DIP-MNA) showed significant increase in apparent solubility and dissolution rate in buffer compared to DIP. The crystal structure analysis showed that the improved solubility is due to the change of the dipyridamole conjugate system and the molecular arrangement in the crystal after the introduction of counterions. It is noteworthy that the fluorescence emission of some salts in the solid state is significantly stronger than that of DIP. According to the crystal structure, the destruction of π-π stacking of DIP molecules after salification is the main mechanism of fluorescence enhancement, and Hirshfeld analysis and HOMO-LUMO analysis are also used to further explain the fluorescence changes.