Phase Solubility Studies of Poorly Soluble Drug Molecules by Using O-Phosphorylated Calixarenes as Drug-Solubilizing Agents

Abstract

This study is the first report on the solubilizing effect of O-phosphorylated calix[n]arenes that form complexes with neutral molecules such as nifedipine, niclosamide, and furosemide by host–guest complexation. These complexation studies were carried out by using the phase solubility technique. From the obtained results, it was observed that the solubility of guest molecules such as nifedipine, niclosamide, and furosemide was significantly increased in the presence of host molecules tetrakis-O-(diethoxyphosphoryl)-p-tert-butylcalix[4]arene (1), tetrakis-O-(diethoxyphosphoryl)-calix[4]arene (2), bis-O-(diethoxyphosphoryl)-p-tert-butylcalix[4]arene (3), bis-O-(diethoxyphosphoryl)-calix[4]arene (4), and octakis-O-(diethoxyphosphoryl)-p-tert-butylcalix[8]arene (5). The increase in solubility of drugs by the calixarene host 1 to 5 was most probably due to inclusion complexation between drug molecules and cavities of the calixarene skeleton similar to drug–cyclodextrin complexes.