The solubilization of the poorly water soluble drug nifedipine by water soluble 4-sulphonic calix[ n]arenes

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 58; no. 3; pp. 629 - 636
• Main Authors: Yang, Wenzhan, de Villiers, Melgardt M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2004
• Subjects: 4-Sulphonic calix[ n]arenes; Calixarenes - analysis; Calixarenes - chemistry; Nifedipine; Nifedipine - analysis; Nifedipine - chemistry; Solubility - drug effects; Solubilization; Sulfur Compounds - analysis; Sulfur Compounds - chemistry; Water - analysis; Water - chemistry; Solubilization; 4-Sulphonic calix[ n]arenes; Nifedipine
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2004.04.010

In this study, the solubilizing effect of 4-sulphonic calix[ n]arenes on the poorly water soluble drug nifedipine was investigated. 4-Sulphonic calix[ n]arenes are water-soluble phenolic cyclooligomers that form complexes with neutral molecules such as nifedipine. Solubility experiments were performed at 30 °C using the Higuchi rotating bottle method. The amount of nifedipine in solution was determined by HPLC. The results showed that the size of the 4-sulphonic calix[ n]arenes, the pH of solubility medium, and the concentration of the calix[ n]arenes all significantly changed the solubility of nifedipine. 4-Sulphonic calix[8]arene improved the solubility of nifedipine the most, about 3 times the control at 0.008 M and pH 5, followed by 4-sulphonic calix[4]arene, about 1.5 times the control at 0.008 M and pH 5, while in the presence of 4-sulphonic calix[6]arene, the solubility of nifedipine was decreased. The possible mechanisms involving in the complexation between 4-sulphonic calix[4]arenes, 4-sulphonic calix[8]arene and nifedipine may be a combination of hydrogen bonding, hydrophobic bonding, and possibly electron donor–acceptor interactions. However, the degree to which these forces promote the formation of nifedipine:4-sulphonic calix[ n]arene complexes with increased solubility was limited by conformational changes in the 4-sulphonic calix[ n]arene molecules.