Aqueous solubilization of furosemide by supramolecular complexation with 4-sulphonic calix[n]arenes.
The solubilization of the practically water insoluble drug furosemide by guest:host inclusion complexation with 4-sulphonic calix[n]arenes has been reported. The 4-sulphonic calix[n]arenes are water-soluble phenolic cyclooligomers that form inclusion complexes with neutral molecules. The solubility of furosemide in acidic (pH < 4) aqueous solutions containing increasing concentrations of the calixarenes was determined at 30 degrees C and the concentration of furosemide in solution was determined by HPLC. Results showed that the molecular size of the 4-sulphonic calix[n]arenes and the concentration of the calix[n]arenes significantly influenced the increase in the solubility of furosemide. 4-Sulphonic calix[6]arene improved the solubility of furosemide the most (+/-104%) followed by 4-sulphonic calix[8]arene (+/-84-102%), while 4-sulphonic calix[4]arene increased the solubility of furosemide the least (+/-73-81%). The increase in furosemide solubility afforded by the calixarenes was most probably the result of the incorporation of the non-polar portions of the furosemide molecule into the non-polar cavities of the calixarenes similar to furosemide:cyclodextrin complexes. The driving force for this interaction was the reduction in the non-polar-water interfacial surface area when the furosemide (guest) molecules were inserted into the 4-sulphonic calix[n]arenes (host).
Yang
Wenzhan
W
School of Pharmacy, The University of Louisiana at Monroe, 700 University Avenue, Monroe, LA 71209, USA.
de Villiers
Melgardt M
MM
D001557:Benzenesulfonates / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D004232:Diuretics / Q000737:chemistry*; D005665:Furosemide / Q000737:chemistry*; D010636:Phenols / Q000737:chemistry*; D012995:Solubility; D013818:Thermogravimetry
D001557:Benzenesulfonates; D004232:Diuretics; D010636:Phenols; D005665:Furosemide