Cyclodextrin complexation improves aqueous solubility of the antiepileptic drug, rufinamide: solution and solid state characterization of compound-cyclodextrin binary systems

Zoltán István Szabó, Réka Gál, Zsolt Gáll, Szende Vancea, Emőke Rédai, Ibolya Fülöp, Emese Sipos, Gabriella Donáth-Nagy, B. Noszál, Gergő Tóth

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Rufinamide (RUF) was characterized in terms of cyclodextrin (CD) complexation in order to improve its aqueous solubility. Binary systems of RUF with three CDs—β-cyclodextrin (β-CD), randomly methylated-β-cyclodextrin (RAMEB) and sulfobutylether-β-cyclodextrin (SBE-β-CD)—were characterized with a wide variety of analytical techniques. Liquid state characterization was carried out by complementary techniques such as nuclear magnetic resonance spectroscopy (NMR), capillary electrophoresis (CE), mass spectrometry (MS) and phase solubility studies. The latter revealed that the stability of the complexes decreased in the order of RAMEB > β-CD > SBE-β-CD. AL-type diagrams were obtained in all cases, characteristic of 1:1 stoichiometry, with a maximum of over 15-fold increase in RUF solubility, when complexed with RAMEB. NMR Job plot and MS studies confirmed phase solubility results, regarding the binding stoichiometry. 1H NMR and 2D ROESY investigations revealed the inclusion of the triazole moiety of RUF, confirmed by molecular modeling. Solid state complexation in 1:1 molar ratio was carried out by kneading method and investigated by differential scanning calorimetry (DSC) and infrared spectroscopy (IR). Comparative dissolution studies indicated an over two-fold improvement in dissolution efficacy of the kneaded products, when compared to the pure drug. Results of the present study might pave the way for a drug formulation with improved bioavailability.

Original languageEnglish
Pages (from-to)43-52
Number of pages10
JournalJournal of Inclusion Phenomena and Macrocyclic Chemistry
Volume88
Issue number1-2
DOIs
Publication statusPublished - Jun 1 2017

Fingerprint

anticonvulsants
cyclodextrins
water solubility
Cyclodextrins
Complexation
Anticonvulsants
Solubility
magnetic resonance spectroscopy
drugs
solubility
solid state
nuclear magnetic resonance
Nuclear magnetic resonance spectroscopy
nuclear magnetic resonance spectroscopy
stoichiometry
dissolving
Magnetic Resonance Spectroscopy
mass spectroscopy
bioavailability
Stoichiometry

Keywords

  • Banzel
  • Comparative dissolution
  • DSC
  • Inclusion complexation
  • NMR spectroscopy
  • Solubility

ASJC Scopus subject areas

  • Food Science
  • Chemistry(all)
  • Condensed Matter Physics

Cite this

Cyclodextrin complexation improves aqueous solubility of the antiepileptic drug, rufinamide : solution and solid state characterization of compound-cyclodextrin binary systems. / Szabó, Zoltán István; Gál, Réka; Gáll, Zsolt; Vancea, Szende; Rédai, Emőke; Fülöp, Ibolya; Sipos, Emese; Donáth-Nagy, Gabriella; Noszál, B.; Tóth, Gergő.

In: Journal of Inclusion Phenomena and Macrocyclic Chemistry, Vol. 88, No. 1-2, 01.06.2017, p. 43-52.

Research output: Contribution to journalArticle

Szabó, Zoltán István ; Gál, Réka ; Gáll, Zsolt ; Vancea, Szende ; Rédai, Emőke ; Fülöp, Ibolya ; Sipos, Emese ; Donáth-Nagy, Gabriella ; Noszál, B. ; Tóth, Gergő. / Cyclodextrin complexation improves aqueous solubility of the antiepileptic drug, rufinamide : solution and solid state characterization of compound-cyclodextrin binary systems. In: Journal of Inclusion Phenomena and Macrocyclic Chemistry. 2017 ; Vol. 88, No. 1-2. pp. 43-52.
@article{295507f9319b4354b8a165c328fe3b6c,
title = "Cyclodextrin complexation improves aqueous solubility of the antiepileptic drug, rufinamide: solution and solid state characterization of compound-cyclodextrin binary systems",
abstract = "Rufinamide (RUF) was characterized in terms of cyclodextrin (CD) complexation in order to improve its aqueous solubility. Binary systems of RUF with three CDs—β-cyclodextrin (β-CD), randomly methylated-β-cyclodextrin (RAMEB) and sulfobutylether-β-cyclodextrin (SBE-β-CD)—were characterized with a wide variety of analytical techniques. Liquid state characterization was carried out by complementary techniques such as nuclear magnetic resonance spectroscopy (NMR), capillary electrophoresis (CE), mass spectrometry (MS) and phase solubility studies. The latter revealed that the stability of the complexes decreased in the order of RAMEB > β-CD > SBE-β-CD. AL-type diagrams were obtained in all cases, characteristic of 1:1 stoichiometry, with a maximum of over 15-fold increase in RUF solubility, when complexed with RAMEB. NMR Job plot and MS studies confirmed phase solubility results, regarding the binding stoichiometry. 1H NMR and 2D ROESY investigations revealed the inclusion of the triazole moiety of RUF, confirmed by molecular modeling. Solid state complexation in 1:1 molar ratio was carried out by kneading method and investigated by differential scanning calorimetry (DSC) and infrared spectroscopy (IR). Comparative dissolution studies indicated an over two-fold improvement in dissolution efficacy of the kneaded products, when compared to the pure drug. Results of the present study might pave the way for a drug formulation with improved bioavailability.",
keywords = "Banzel, Comparative dissolution, DSC, Inclusion complexation, NMR spectroscopy, Solubility",
author = "Szab{\'o}, {Zolt{\'a}n Istv{\'a}n} and R{\'e}ka G{\'a}l and Zsolt G{\'a}ll and Szende Vancea and Emőke R{\'e}dai and Ibolya F{\"u}l{\"o}p and Emese Sipos and Gabriella Don{\'a}th-Nagy and B. Nosz{\'a}l and Gergő T{\'o}th",
year = "2017",
month = "6",
day = "1",
doi = "10.1007/s10847-017-0710-z",
language = "English",
volume = "88",
pages = "43--52",
journal = "Journal of Inclusion Phenomena and Macrocyclic Chemistry",
issn = "0923-0750",
publisher = "Kluwer Academic Publishers",
number = "1-2",

}

TY - JOUR

T1 - Cyclodextrin complexation improves aqueous solubility of the antiepileptic drug, rufinamide

T2 - solution and solid state characterization of compound-cyclodextrin binary systems

AU - Szabó, Zoltán István

AU - Gál, Réka

AU - Gáll, Zsolt

AU - Vancea, Szende

AU - Rédai, Emőke

AU - Fülöp, Ibolya

AU - Sipos, Emese

AU - Donáth-Nagy, Gabriella

AU - Noszál, B.

AU - Tóth, Gergő

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Rufinamide (RUF) was characterized in terms of cyclodextrin (CD) complexation in order to improve its aqueous solubility. Binary systems of RUF with three CDs—β-cyclodextrin (β-CD), randomly methylated-β-cyclodextrin (RAMEB) and sulfobutylether-β-cyclodextrin (SBE-β-CD)—were characterized with a wide variety of analytical techniques. Liquid state characterization was carried out by complementary techniques such as nuclear magnetic resonance spectroscopy (NMR), capillary electrophoresis (CE), mass spectrometry (MS) and phase solubility studies. The latter revealed that the stability of the complexes decreased in the order of RAMEB > β-CD > SBE-β-CD. AL-type diagrams were obtained in all cases, characteristic of 1:1 stoichiometry, with a maximum of over 15-fold increase in RUF solubility, when complexed with RAMEB. NMR Job plot and MS studies confirmed phase solubility results, regarding the binding stoichiometry. 1H NMR and 2D ROESY investigations revealed the inclusion of the triazole moiety of RUF, confirmed by molecular modeling. Solid state complexation in 1:1 molar ratio was carried out by kneading method and investigated by differential scanning calorimetry (DSC) and infrared spectroscopy (IR). Comparative dissolution studies indicated an over two-fold improvement in dissolution efficacy of the kneaded products, when compared to the pure drug. Results of the present study might pave the way for a drug formulation with improved bioavailability.

AB - Rufinamide (RUF) was characterized in terms of cyclodextrin (CD) complexation in order to improve its aqueous solubility. Binary systems of RUF with three CDs—β-cyclodextrin (β-CD), randomly methylated-β-cyclodextrin (RAMEB) and sulfobutylether-β-cyclodextrin (SBE-β-CD)—were characterized with a wide variety of analytical techniques. Liquid state characterization was carried out by complementary techniques such as nuclear magnetic resonance spectroscopy (NMR), capillary electrophoresis (CE), mass spectrometry (MS) and phase solubility studies. The latter revealed that the stability of the complexes decreased in the order of RAMEB > β-CD > SBE-β-CD. AL-type diagrams were obtained in all cases, characteristic of 1:1 stoichiometry, with a maximum of over 15-fold increase in RUF solubility, when complexed with RAMEB. NMR Job plot and MS studies confirmed phase solubility results, regarding the binding stoichiometry. 1H NMR and 2D ROESY investigations revealed the inclusion of the triazole moiety of RUF, confirmed by molecular modeling. Solid state complexation in 1:1 molar ratio was carried out by kneading method and investigated by differential scanning calorimetry (DSC) and infrared spectroscopy (IR). Comparative dissolution studies indicated an over two-fold improvement in dissolution efficacy of the kneaded products, when compared to the pure drug. Results of the present study might pave the way for a drug formulation with improved bioavailability.

KW - Banzel

KW - Comparative dissolution

KW - DSC

KW - Inclusion complexation

KW - NMR spectroscopy

KW - Solubility

UR - http://www.scopus.com/inward/record.url?scp=85018407930&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85018407930&partnerID=8YFLogxK

U2 - 10.1007/s10847-017-0710-z

DO - 10.1007/s10847-017-0710-z

M3 - Article

AN - SCOPUS:85018407930

VL - 88

SP - 43

EP - 52

JO - Journal of Inclusion Phenomena and Macrocyclic Chemistry

JF - Journal of Inclusion Phenomena and Macrocyclic Chemistry

SN - 0923-0750

IS - 1-2

ER -