Τίτλος:
The effect of pH dependent molecular conformation and dimerization phenomena of piroxicam on the drug:cyclodextrin complex stoichiometry and its chromatographic behaviour: A new specific HPLC method for piroxicam: cyclodextrin formulations
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
The complexation of piroxicam with various cyclodextrins was studied in the whole pH range, in an attempt to clarify the reported differences in stoichiometry of the resulting inclusion complexes. In this work, it was found that the pH dependent self-association phenomena, detected in both alkaline and acidic media, are the defining features for complex stoichiometry. Also, it was observed that the inclusion complexes of the piroxicam zwitterion with β-cyclodextrin (βCD), methyl-β-cyclodextrin and hydroxypropyl-β-cyclodextrin have a 2:2 stoichiometry in acidic pH, through inclusion of the benzyl ring moiety. As pH increased, it was determined that the different ionic state of the molecules creates new geometries, involving also the pyridyl-ring in the complexation. More stable inclusion complexes of 2:5 stoichiometry are observed at pH>4. A reversed phase liquid chromatography method, specific for the analysis of the included piroxicam, was developed and validated. The different stoichiometries and the dimers formation were investigated by interpretation of the two-dimensional 1H NMR spectroscopy. © 2004 Elsevier B.V. All rights reserved.
Συγγραφείς:
Rozou, S.
Voulgari, A.
Antoniadou-Vyza, E.
Περιοδικό:
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Λέξεις-κλειδιά:
2 hydroxypropyl beta cyclodextrin; benzyl derivative; beta cyclodextrin; cyclodextrin derivative; methyl beta cyclodextrin; piroxicam, acidity; alkalinity; article; complex formation; conformation; dimerization; drug formulation; drug structure; geometry; high performance liquid chromatography; ionic strength; pH; priority journal; proton nuclear magnetic resonance; stoichiometry, Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Cyclodextrins; Dimerization; Hydrogen-Ion Concentration; Molecular Conformation; Piroxicam; Stereoisomerism
DOI:
10.1016/j.ejps.2004.01.007
