Aqueous solubilization of furosemide by supramolecular complexation with 4-sulphonic calix[n]arenes

Abstract

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).

Proparacaine complexation with β‐cyclodextrin and p‐sulfonic acid calix[6]arene, as evaluated by varied 1H‐NMR approaches

“…These experiments allow distinguishing compounds or complexes by their differences in diffusion coefficients. [14] Representative spectra are given in Figs 2 and 3 for pure 1 and for the 1/2 complex (2 mmol l −1 samples, 298 K, respectively). The diffusion coefficients of pure 1, 2 and 3 (at pH 5 and 10) were first Table 3), indicating that 1 forms host-guest complexes with either 2 or 3, at both pH.…”

Investigation into Drug Solubilisation Potential of Sulfonated Calix[4]Resorcinarenes

“…In particular, there is an established evidence base confirming that water-soluble calix[n]arenes which possess sulfonate groups in the 4-position on the upper rim are capable of solubilising drug molecules which otherwise possess poor solubility in aqueous media [9][10][11][12][13][14][15][16][17][18][19][20][21]. However, few investigations into the properties and utility of simple calix[4]resorcinarenes which bear sulfonate groups in the 2-position on the upper rim have been reported.…”

Simple Calix[n]arenes and Calix[4]resorcinarenes as Drug Solubilizing Agents

“…The solubility of nifedipine was increased when complexed with and whereas it was decreased when challenged with . In each case solubilization of the drugs by the sulfonatedcalix[n]arenes investigated reflected a tangible dependence upon a number of factors, including calix[n]arene cavity size, conformations of both the drug molecule and the calix[n]arene across a range of pH and concentration of the calix[n]arene [60][61][62].…”