<p>Owing to the rising demand for drug solubilization strategies, we herein explore the interaction of poorly soluble antibiotic drug, cefixime trihydrate (CFT) with three types of surface-active ionic liquids (SAILs) having similar chain lengths but different head groups, viz., 1-dodecyl-3-methyl imidazolium bromide (C<sub>12</sub>mimBr), dodecylbenzyldimethylammonium chloride (C<sub>12</sub>BzCl), and 1-dodecyl-3-methyl pyridinium chloride (C<sub>12</sub>PyCl), using UV-visible spectroscopy, fluorescence spectroscopy, conductivity, and dynamic light scattering (DLS) measurements. The interactions between SAILs and CFT were investigated spectroscopically, where in the monomeric form, both the components were found to form 1:1 complexes with binding constant values (<i>k</i><sub>a</sub>) varying in the order as C<sub>12</sub>BzCl &gt; C<sub>12</sub>PyCl &gt; C<sub>12</sub>mimBr. Using conductivity measurements, the various micellar parameters, viz., <i>cmc</i>, degree of counterion dissociation (α), standard Gibbs free energy of micellization (<InlineEquation ID="IEq1"> <EquationSource Format="TEX">\(\:{\varDelta\:G}_{mic}^{\circ}\)</EquationSource> </InlineEquation>), standard enthalpy of micellization (<InlineEquation ID="IEq2"> <EquationSource Format="TEX">\(\:{\varDelta\:\text{H}}_{mic}^{\circ}\)</EquationSource> </InlineEquation>) and standard entropy of micellization (<InlineEquation ID="IEq3"> <EquationSource Format="TEX">\(\:{\varDelta\:\text{S}}_{mic}^{\circ}\)</EquationSource> </InlineEquation>) were deduced to evaluate the effect of CFT on the micellar form of SAILs. The presence of CFT (1.0 mM, 2.5mM, and 5.0 mM) was found to induce early onset of micellization in SAILs, because of decreased electrostatic repulsions between head groups and enhanced hydrophobic interactions between solubilized CFT and micellar tails. As manifested by increase in hydrodynamic diameter (<i>D</i><sub>h</sub>) and quenching measurements, the drug CFT is assumed to be located in the micellar core of SAILs, with the molar solubilization capacity (χ) of SAILs being highest for C<sub>12</sub>mimBr, followed by C<sub>12</sub>PyCl and then C<sub>12</sub>BzCl. Further, in vitro release studies have been carried out using dialysis membrane which revealed that the CFT release kinetics follows <i>Higuchi</i> model of drug release with the releasing efficiency of SAILs varying in the order C<sub>12</sub>mimBr &gt; C<sub>12</sub>PyCl &gt; C<sub>12</sub>BzCl.</p>

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Detailed insights into interactions of cefixime trihydrate with surface active ionic liquids: solubilization and In-Vitro release kinetics

  • Ruchika,
  • Neha Sharma,
  • Reshu Sanan

摘要

Owing to the rising demand for drug solubilization strategies, we herein explore the interaction of poorly soluble antibiotic drug, cefixime trihydrate (CFT) with three types of surface-active ionic liquids (SAILs) having similar chain lengths but different head groups, viz., 1-dodecyl-3-methyl imidazolium bromide (C12mimBr), dodecylbenzyldimethylammonium chloride (C12BzCl), and 1-dodecyl-3-methyl pyridinium chloride (C12PyCl), using UV-visible spectroscopy, fluorescence spectroscopy, conductivity, and dynamic light scattering (DLS) measurements. The interactions between SAILs and CFT were investigated spectroscopically, where in the monomeric form, both the components were found to form 1:1 complexes with binding constant values (ka) varying in the order as C12BzCl > C12PyCl > C12mimBr. Using conductivity measurements, the various micellar parameters, viz., cmc, degree of counterion dissociation (α), standard Gibbs free energy of micellization ( \(\:{\varDelta\:G}_{mic}^{\circ}\) ), standard enthalpy of micellization ( \(\:{\varDelta\:\text{H}}_{mic}^{\circ}\) ) and standard entropy of micellization ( \(\:{\varDelta\:\text{S}}_{mic}^{\circ}\) ) were deduced to evaluate the effect of CFT on the micellar form of SAILs. The presence of CFT (1.0 mM, 2.5mM, and 5.0 mM) was found to induce early onset of micellization in SAILs, because of decreased electrostatic repulsions between head groups and enhanced hydrophobic interactions between solubilized CFT and micellar tails. As manifested by increase in hydrodynamic diameter (Dh) and quenching measurements, the drug CFT is assumed to be located in the micellar core of SAILs, with the molar solubilization capacity (χ) of SAILs being highest for C12mimBr, followed by C12PyCl and then C12BzCl. Further, in vitro release studies have been carried out using dialysis membrane which revealed that the CFT release kinetics follows Higuchi model of drug release with the releasing efficiency of SAILs varying in the order C12mimBr > C12PyCl > C12BzCl.