Έλεγχος ποιότητας και σταθερότητας βελτιωμένων σκευασμάτων με σύμπλοκα αντιμικροβιακών παραγόντων και συνθετικά τροποποιημένων κυκλοδεξτρινών. μελέτες δομής και ιδιοτήτων των συμπλόκων

Doctoral Dissertation uoadl:1308918 550 Read counter

Unit:
Τομέας ΦΑΡΜΑΚΕΥΤΙΚΗΣ ΧΗΜΕΙΑΣ
Library of the School of Science
Deposit date:
2011-12-08
Year:
2011
Author:
Ορφανού Φωτεινή
Dissertation committee:
Καθηγήτρια Αικατερίνη Αντωνιάδου-Βυζά Επιβλέπουσα
Original Title:
Έλεγχος ποιότητας και σταθερότητας βελτιωμένων σκευασμάτων με σύμπλοκα αντιμικροβιακών παραγόντων και συνθετικά τροποποιημένων κυκλοδεξτρινών. μελέτες δομής και ιδιοτήτων των συμπλόκων
Languages:
Greek
Summary:
The inclusion complexes of the antibacterials Oxolinic acid and Ciprofloxacin
with diverse cyclodextrins: natural, commercially available derivatives and new
modified cyclodextrins with selected sugar ligands were prepared.The complex
formation confirmed and the characterization of the complexes carried out by
Spectroscopy or Spectrometry methods.New photostability indicating HPLC-UV
methods for the quantification of Oxolinic acid and Ciprofloxacin werev
developed and optimised. Solubility of Oxolinic acid was significantly enhanced
by complexation.Investigation of Oxolinic acid photodegradation profiles
confirmed zero order kinetics at first part and faster degradation at high
concentrations and remarkable stabilization upon complexation.Studies of
ciprofloxacin degradation profiles confirmed first order kinetics and improved
stability at higher concentrations, at lower pH values and upon complexation
with all cyclodextrins studied, especially with the new derivatives of
cyclodextrins with covalently bound sugar molecules.The appropriate conditions
for the preparation of sterile aqueous solutions of the active compounds, safe
and also effective were determined.The microbiological test were evaluated and
the corresponding MIC values of Oxolinic acid, Ciprofloxacin and their
complexes with all studied cyclodextrins were determined and modification of
the activity was observed established in several cases.
Therefore, in accordance to ICH guidelines, a method suitable for the analysis
and quantification of cyclodextrins in addition to the active ingredients
should be developed.
Spectroscopy NMR method and HPLC-ELSD methods for the simultaneous
quantification of Ciprofloxacin and Maltosylβcyclodextrin in the presence of
their complex were developed and evaluated. The HPLC-ELSD method leads to lower
limits of detection and quantitation and is superior compared to qNMR
spectroscopy concerning the linearity and repeatability of the method, with the
disadvantage of the weakness of simultaneous determination of Ciprofloxacin and
Maltosylβcyclodextrin. The qNMR spectroscopy method developed predominates over
HPLC-ELSD in accuracy and in addition is the only method which allows the
simultaneous quantification of Ciprofloxacin and Maltosylβcyclodextrin in the
presence of their complex.
Keywords:
Ciprofloxacin, Oxolinic acid, Cyclodextrin complexes, quantitative NMR, HPLC-ELSD, Microbiological tests
Index:
No
Number of index pages:
0
Contains images:
Yes
Number of references:
227
Number of pages:
369
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