Ternary cyclodextrin polyurethanes containing phosphate groups: Synthesis and complexation of ciprofloxacin.

Synthesis of ternary polyurethanes (PUs) from hexamethylenediisocyanate, ß-cyclodextrin and ß-glycerophosphate (acid and calcium salt) was studies varying synthesis parameters such as monomer proportion, heating method (reflux and microwave), and catalyst amount. Favorable conditions were provided by microwave irradiation and use of ß-glycerophosphoric acid although the results suggest that it is possible to obtain ternary PUs with the calcium salt. FTIR data indicated the existence of secondary urea linkages. After characterization of ternary PUs by FTIR spectroscopy, XRD and thermal analysis, as well as evidences that the cyclodextrin cavities remained active toward inclusion of guest molecules, the possibility of inclusion of the antibiotic ciprofloxacin was evaluated. Absence of ciprofloxacin melting peak in DSC curves indicated that it is molecularly dispersed within the polymer, possibly included in the cyclodextrin. In vitro release experiments suggested additional non-inclusion interactions, showing also that the use of dialysis membranes may mask the actual release profile.

Characterization, phase solubility and molecular modeling of alpha-cyclodextrin/pyrimethamine inclusion complex.

An inclusion complex between the dihydrofolate reductase inhibitor pyrimethamine (PYR) and alpha-cyclodextrin (alpha-CD) was prepared and characterized. From the phase-solubility diagram, a linear increase of PYR solubility was verified as a function of alpha-CD concentration, suggesting the formation of a soluble complex. A 1:1 host-guest stoichiometry can be proposed according to the Job's plot, obtained from the difference of PYR fluorescence intensity in the presence and absence of alpha-CD. Differential scanning calorimetry (DSC) measurements provided additional evidences of complexation such as the absence of the endothermic peak assigned to the melting of the drug. The inclusion mode characterized by two-dimensional (1)H NMR spectroscopy (ROESY) involves penetration of the p-chlorophenyl ring into the alpha-CD cavity, in agreement to the orientation optimized by molecular modeling methods.

Sulfadiazine/hydroxypropyl-beta-cyclodextrin host-guest system: Characterization, phase-solubility and molecular modeling.

In this work we prepared and characterized an inclusion complex of the dihydropteroate synthase inhibitor sulfadiazine (SDZ) in 2-hydroxypropyl-beta-cyclodextrin (HPBCD). From the phase-solubility diagram we observed an increase in the water solubility of the drug, calculating a binding constant of 1879M(-1). The inclusion mode involves a NH(2)-in orientation of the drug in the HPBCD cavity, according to the 2D NMR (ROESY) data and confirmed by molecular modeling using the semiempirical PM6 and RM1 methods.

Inclusion complexes of pyrimethamine in 2-hydroxypropyl-beta-cyclodextrin: characterization, phase solubility and molecular modelling.

The inclusion complexation of pyrimethamine in 2-hydroxypropyl-beta-cyclodextrin has been investigated by 2D (1)H NMR, FTIR and UV/visible spectroscopy and also by molecular modelling methods (AM1, PM3, MM3). From the phase-solubility diagram a linear increase was observed in pyrimethamine aqueous solubility in the presence of 2-hydroxypropyl-beta-cyclodextrin, evidencing the formation of a soluble inclusion complex. According to the continuous variation method (Job's plot) applied to fluorescence measurements, a 1:1 stoichiometry has been proposed for the complex. Concerning the structure of the complex, a Cl-in orientation of pyrimethamine in the 2-hydroxypropyl-beta-cyclodextrin cavity has been proposed from the theoretical calculations, being confirmed by two-dimensional (1)H NMR spectroscopy (ROESY). The thermal behaviour has also been studied, providing complementary evidences of complex formation.