Tag Archives: cyclodextrin

Characterization and Molecular Modelling of Cyclodextrin/Fluoroquinolone Inclusion Complexes

Székely-Szentmiklósi Blanka1, Tőkés B.2

1 Gedeon Richter Romania S.A., Târgu Mureş
2 Department of Physical-Chemistry, University of Medicine and Pharmacy, Târgu Mureş

Background: Cyclodextrins are widely used as complexing agents to increase the solubility of poorly water-soluble drugs, to improve their bioavailability and stability, to reduce or prevent gastrointestinal or ocular irritation, to reduce or eliminate unpleasant smells or tastes and to prevent drug-drug or drug-additive interactions. In recent years, cyclodextrins have been proven to be effective as host compounds in molecular recognition and chiral separation.
Aim: To evaluate the complexation role of cyclodextrins toward fluoroquinolones (FQ) in an attempt to assess their potential as new formulation additives for more efficient fluoroquinolone delivery and as chiral selectors in case of racemic mixture compounds.
Material and methods: Guest-host interactions of three second generation quinolones, ciprofloxacin, ofloxacin and norfloxacin with two parent cyclodextrins, beta-cyclodextrin (b-CD), gamma-cyclodextrin (g-CD) and a beta-cyclodextrin derivative, 2-hydroxypropyl beta-cyclodextrin (HP-b -CD), were tested. Computer aided molecular modelling (ChemBio3D Ultra 12.0) was utilized to predict the preferred orientation of fluoroquinolones in the cyclodextrin cavity and the main structural features responsible for the enhancement of their solubility and photostability. Ciprofloxacin/b-cyclodextrin complex was prepared and the formation of inclusion complex was
demostrated by IR spectroscopy.
Results: Our studies show that the orientation with the piperazinyl group included in the CD cavity is energetically more favorable.
Conclusions: The CDs act as complexing agents with the three FQ derivatives, which enter inside the CD torus, and interact with the hydroxyl groups of CD by Van der Waals, electrostatic forces ang hydrogen bonding. Our results suggest the 1:1 stoichiometry in the complex formation.

Keywords: , , ,
Full text: PDF

A Study Upon the Dissolution Properties of Bifonazole Through Complexation with Cyclodextrins

Trandafirescu Cristina1, Gyéresi Á2, Szabadai Z3, Sbârcea Laura1, Pătruţescu Cristina1, Kata M4, Aigner Z4

1 Victor Babeş University of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Timişoara
2 University of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Tîrgu Mureș
3 Victor Babeş University of Medicine and Pharmacy, Faculty of Pharmacy, Department of Drug Analysis, Timişoara
4 University of Szeged, Faculty of Pharmacy, Department of Pharmaceutical Technology, Szeged, Hungary

Introduction: The aim of this study is to characterize the interaction in solution between the antimycotic bifonazole and two cyclodextrins: random methyl-beta-cyclodextrin and beta-cyclodextrin.
Material and method: The interaction in solution between bifonazole and random methyl-beta-cyclodextrin/beta-cyclodextrin was characterized using dissolution studies and phase solubility studies. The dissolution of bifonazole was characterized through the index of the rate of dissolution and the dissolution efficiency, and from the phase solubility study we calculated the apparent stability constant of the complex.
Results: The bifonazole – random methyl beta-cyclodextrin binary systems revealed better dissolution properties as compared to bifonazole alone, and to the bifonazole – beta-cyclodextrin binary systems. The phase solubility studies revealed the formation of soluble complexes in the cyclodextrin concentration range, and an apparent stability constant of 17956 M-1 for bifonazole – random methyl-beta-cyclodextrin complex, and of 873 M-1 for bifonazole – beta-cyclodextrin complex.
Discussions: The dissolution studies and the phase solubility studies demonstrated an improvement of the wettability of the particles of bifonazole, due to a better contact between bifonazole and cyclodextrin, and the formation of soluble complexes in the dissolution medium.
Conclusions: The complexation with cyclodextrins determined the increase in the dissolution properties of bifonazole. The best results were obtained with random methyl-beta-cyclodextrin, which demonstrates a better interaction within the components in the liquid medium and the better solubilization properties of this cyclodextrin.

Keywords: , , ,
Full text: PDF

Non-Steroidal Anti-Inflammatory Drugs’ Complexes with Cyclodextrins – Molecular Modelling Study

Fülöp Ibolya1, Gyéresi Á2, Laczkó-Zöld Eszter3, Croitoru MD1

1 Department of Biopharmacy and Pharmacokinetics, Faculty of Pharmacy, University of Medicine and Pharmacy, Tîrgu Mureș, Romania
2 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy, Tîrgu Mureș, Romania
3 Department of Pharmacognosy, Faculty of Pharmacy, University of Medicine and Pharmacy, Tîrgu Mureș, Romania

Objectives: Association of non-steroidal anti-inflammatory drugs with cyclodextrins is a largely used method to increase their stability and water solubility. The aim of our study was to clarify the interactions between seven nonsteroidal anti-inflammatory drugs and HP-β-CD and the spatial geometry of these inclusion complexes by using molecular modelling.
Methods: From the non-steroidal anti-inflammatory class seven representatives were chosen: ibuprofen, ketoprofen, piroxicam, meloxicam, tenoxicam, mefenamic acid and flufenamic acid. Computational study on host-guest complexes was carried out using molecular mechanics in Hyperchem software, both in vacuum and water periodic box condition.
Results: The obtained results show that all NSAIDs form inclusion complex with HP-β-CD. The spatial geometry of complexes was established by molecular mechanics computation and the complex formation energies were calculated.
Conclusions: Intermolecular hydrogen bonds and hydrophobic interactions play an important role in the binding of NSAIDs to HP-β-CD. The results show good correlation with literature data.

Keywords: , , ,
Full text: PDF

Characterization Of Albendazole – Random Methyl Beta-Cyclodextrin Binary Systems By Infrared Spectroscopy

Trandafirescu Cristina1, Szabadai Z2, Gyéresi Á3, Kata M4, Aigner Z2

1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Victor Babeş University of Medicine and Pharmacy, Timişoara, Romania
2 Department of Drug Analysis, Faculty of Pharmacy, Victor Babeş University of Medicine and Pharmacy, Timişoara, Romania
3 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy, Tîrgu Mureş, Romania
4 Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Szeged, Szeged, Hungary

Introduction: The purpose of this study is to investigate the host-guest interaction in solid state between anthelmintic drug albendazole and random methyl-beta-cyclodextrin using spectrophotometric method.
Material and method: Binary systems between albendazole and random methyl-beta-cyclodextrin were prepared in four molar ratios using two laboratory methods and the host-guest interaction was characterized by Fourier transform infrared spectroscopy.
Results: The absorption spectra of albendazole display some absorption bands in the 1800–1000 cm-1 domain and the absorption spectra of random methyl-beta-cyclodextrin present a wide absorption band the 1200–1000 cm-1 region. In order to examine the spectral changes of the binary systems, five characteristic bands in albendazole spectrum were chosen and their absorbances were represented for each molar ratio of albendazole in the binary systems.
Conclusions: The Fourier transform infrared spectroscopy analysis of the binary system reveals an emphasis of molecular interaction between albendazole and cyclodextrin as the amount of cyclodextrin in the binary system is increasing.

Keywords: , , ,
Full text: PDF

Study of Cyclodextrin/Fluoroquinolone Inclusion Complexes by Capillary Electrophoresis

Székely-Szentmiklósi Blanka1, Tőkés B2

1 Gedeon Richter Romania S.A., Tîrgu Mureş, Romania
2 Department of Physical-Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy, Tîrgu Mureş, Romania

 

DOI: 10.2478/amma-2013-0026

Introduction: In the present work we evaluated the complexation role of cyclodextrins toward fluoroquinolones in an attempt to assess their potential as new formulation additives for more efficient fluoroquinolone delivery and as selectors in capillary electrophoresis.
Material and method: Guest-host interactions of two second generation quinolones, ciprofloxacin and norfloxacin with four cyclodextrins, beta-cyclodextrin (β-CD), gamma-cyclodextrin (γ-CD) and two beta-cyclodextrin derivatives, 2-hydroxypropyl beta-cyclodextrin (HP-β-CD) and randomly methylated beta-cyclodextrin (RAMEB), were tested by capillary electrophoresis in borate running buffer. Experimental parameters like buffer concentration, pH, organic modifier, voltage and cyclodextrin concentration have been varied for a better resolution.
Results: In capillary zone electrophoresis ciprofloxacin and norfloxacin are migrating together, a difference in their migration times and thus separation occured by the addition of cyclodextrins.
Conclusion: Our results suggest formation of inclusion complexes between fluoroquinolones and cyclodextrins. Differences in their affinity to host molecules resulted in separation of the two fluoroquinolones.

Keywords: , , ,
Full text: PDF