Conference Papers / Δημοσιεύσεις σε Συνέδρια

A new onalytical procedure, combining sample pretreatment with solid phase extroction ond high performonce liquid chromatography, was developed and opplied to ketoprofen:cyclodextrin (CD) complexes. The significont differences in molar absorptivity between free and CD bound drugs leod to analytical errors up to 30%. Procedures routinely used to remove most of the common excipients proved to be inadequate, creating the necessity of more specific (HPLC) onalytical methods including the step of dissociotion ond separation of drugs from CDs before the quontitation by UV detector. In the case of complexes such as Ketoprofen: CDs, strong binding to CDs inhibits the dissociation. Prior to the anolysis, the addition of molecules competing the binding in the CD cavity fairly decreased the strength of the complexation. When molecules, competing the binding to CD such os 1-odomantanol, were added to the samples the results were improved. The extent of the selective binding and the drug displocement were monitored with 1H-NMR spectroscopy and it was revealed that only partial dissociation of the complexes was obtained. The combination of the sample pre-treatment with a solid phase extraction technique was proved to be inevitable for the dissociation of the complex. When analyzing supramolecules spectral changes, arising from intramolecular and/or intermolecular interactions, are expected. Cansequently, analytical methods utilized should be carefully revised.

The chromatographic behaviour of host-guest inclusion complexes was studied, in order to predict the optimal conditions for their accurate analysis and overcome the significant analytical errors generated by the presence of cyclodextrins. Complexes of tolfenamic acid and ketoprofen with β-cyclodextrtin (βCD), 2-hydroxypropyl-βCD (HPβCD) and methyl-βCD (MeβCD) prepared in different molar ratios, were studied. Since the drug release from cyclodextrins' complexes is a prerequisite for its accurate quantitation, several parameters affecting the dissociation during the analysis were evaluated. In an attempt to explain the drug release mechanism from cyclodextrins, during HPLC analysis, the possible correlation of the NMR structural findings with the binding constants and the thermodynamic quantities of complexation were examined, in relation to their chromatographic behaviour. Finally, the presence of the solvation spheres around the supramolecules, which affect the complex stability, is suggested to be crucial for our chromatographic findings. Particularly, entropy change in the system is considered the most critical factor, determining the time required for dissociation of drug-cyclodextrin complexes, during drug quantitation.

Tenoxicam (TXM) is an effective anti-inflammatory and analgesic drug, which presents fast photochemical decomposition. In this work in an attempt to investigate the potential β-CD photostabilizing effect on TXM, the photodegradation rate of β-CD complexed drug was monitored under simulated solar irradiation from Xenon arc lamp. The photodegradation was studied at pH 7.5. A new stability indicating Liquid Chromatography method, for TXM in the presence of β-CD was used. According to the obtained results, in the case of free molecules increasing the concentration the photostability is enhanced. The effect of complexation with CDs on the photodegradation rate seems to vary depending on TXM initial concentration. At low TXM concentrations photodecomposition is retarded upon CD complexation, while at high concentrations the process is accelerated. Molecular dimerisation was studied by 1H(1D) NMR and 2D NOESY experiments. 2D ROESY spectra of complexed molecule were evaluated in order to confirm the complexation. TXM dimers could be considered as a critical parameter affecting oxicams photostability, in combination with the already described ESIPT phenomenon.