Solid-state flurbiprofen and methyl-β-cyclodextrin inclusion complexes prepared using a single-step, organic solvent-free supercritical fluid process

Shashi Ravi Suman Rudrangi, Waseem Kaialy, Muhammad U. Ghori, Vivek Trivedi, Martin J. Snowden, Bruce David Alexander

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The aim of this study was to enhance the apparent solubility and dissolution properties of flurbiprofen through inclusion complexation with cyclodextrins. Especially, the efficacy of supercritical fluid technology as a preparative technique for the preparation of flurbiprofen-methyl-β-cyclodextrin inclusion complexes was evaluated. The complexes were prepared by supercritical carbon dioxide processing and were evaluated by solubility, differential scanning calorimetry, X-ray powder diffraction, scanning electron microscopy, practical yield, drug content estimation and in vitro dissolution studies. Computational molecular docking studies were conducted to study the possibility of molecular arrangement of inclusion complexes between flurbiprofen and methyl-β-cyclodextrin. The studies support the formation of stable molecular inclusion complexes between the drug and cyclodextrin in a 1:1 stoichiometry. In vitro dissolution studies showed that the dissolution properties of flurbiprofen were significantly enhanced by the binary mixtures prepared by supercritical carbon dioxide processing. The amount of flurbiprofen dissolved into solution alone was very low with 1.11 ± 0.09% dissolving at the end of 60 min, while the binary mixtures processed by supercritical carbon dioxide at 45 °C and 200 bar released 99.39 ± 2.34% of the drug at the end of 30 min. All the binary mixtures processed by supercritical carbon dioxide at 45 °C exhibited a drug release of more than 80% within the first 10 min irrespective of the pressure employed. The study demonstrated the single step, organic solvent-free supercritical carbon dioxide process as a promising approach for the preparation of inclusion complexes between flurbiprofen and methyl-β-cyclodextrin in solid-state.

LanguageEnglish
Pages164-170
Number of pages7
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume104
Early online date7 May 2016
DOIs
Publication statusPublished - Jul 2016

Fingerprint

Flurbiprofen
Carbon Dioxide
Cyclodextrins
Solubility
Pharmaceutical Preparations
Powder Diffraction
Differential Scanning Calorimetry
X-Ray Diffraction
Electron Scanning Microscopy
methyl-beta-cyclodextrin
Technology
Pressure

Cite this

@article{29231da77b8a4e53810bb4f90d9246a3,
title = "Solid-state flurbiprofen and methyl-β-cyclodextrin inclusion complexes prepared using a single-step, organic solvent-free supercritical fluid process",
abstract = "The aim of this study was to enhance the apparent solubility and dissolution properties of flurbiprofen through inclusion complexation with cyclodextrins. Especially, the efficacy of supercritical fluid technology as a preparative technique for the preparation of flurbiprofen-methyl-β-cyclodextrin inclusion complexes was evaluated. The complexes were prepared by supercritical carbon dioxide processing and were evaluated by solubility, differential scanning calorimetry, X-ray powder diffraction, scanning electron microscopy, practical yield, drug content estimation and in vitro dissolution studies. Computational molecular docking studies were conducted to study the possibility of molecular arrangement of inclusion complexes between flurbiprofen and methyl-β-cyclodextrin. The studies support the formation of stable molecular inclusion complexes between the drug and cyclodextrin in a 1:1 stoichiometry. In vitro dissolution studies showed that the dissolution properties of flurbiprofen were significantly enhanced by the binary mixtures prepared by supercritical carbon dioxide processing. The amount of flurbiprofen dissolved into solution alone was very low with 1.11 ± 0.09{\%} dissolving at the end of 60 min, while the binary mixtures processed by supercritical carbon dioxide at 45 °C and 200 bar released 99.39 ± 2.34{\%} of the drug at the end of 30 min. All the binary mixtures processed by supercritical carbon dioxide at 45 °C exhibited a drug release of more than 80{\%} within the first 10 min irrespective of the pressure employed. The study demonstrated the single step, organic solvent-free supercritical carbon dioxide process as a promising approach for the preparation of inclusion complexes between flurbiprofen and methyl-β-cyclodextrin in solid-state.",
keywords = "Dissolution rate, Flurbiprofen, Inclusion complexes, Methyl-b-cyclodextrin, Solubility, Supercritical fluid technology",
author = "Rudrangi, {Shashi Ravi Suman} and Waseem Kaialy and Ghori, {Muhammad U.} and Vivek Trivedi and Snowden, {Martin J.} and Alexander, {Bruce David}",
year = "2016",
month = "7",
doi = "10.1016/j.ejpb.2016.04.024",
language = "English",
volume = "104",
pages = "164--170",
journal = "European Journal of Pharmaceutics and Biopharmaceutics",
issn = "0939-6411",
publisher = "Elsevier",

}

Solid-state flurbiprofen and methyl-β-cyclodextrin inclusion complexes prepared using a single-step, organic solvent-free supercritical fluid process. / Rudrangi, Shashi Ravi Suman; Kaialy, Waseem; Ghori, Muhammad U.; Trivedi, Vivek; Snowden, Martin J.; Alexander, Bruce David.

In: European Journal of Pharmaceutics and Biopharmaceutics, Vol. 104, 07.2016, p. 164-170.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Solid-state flurbiprofen and methyl-β-cyclodextrin inclusion complexes prepared using a single-step, organic solvent-free supercritical fluid process

AU - Rudrangi, Shashi Ravi Suman

AU - Kaialy, Waseem

AU - Ghori, Muhammad U.

AU - Trivedi, Vivek

AU - Snowden, Martin J.

AU - Alexander, Bruce David

PY - 2016/7

Y1 - 2016/7

N2 - The aim of this study was to enhance the apparent solubility and dissolution properties of flurbiprofen through inclusion complexation with cyclodextrins. Especially, the efficacy of supercritical fluid technology as a preparative technique for the preparation of flurbiprofen-methyl-β-cyclodextrin inclusion complexes was evaluated. The complexes were prepared by supercritical carbon dioxide processing and were evaluated by solubility, differential scanning calorimetry, X-ray powder diffraction, scanning electron microscopy, practical yield, drug content estimation and in vitro dissolution studies. Computational molecular docking studies were conducted to study the possibility of molecular arrangement of inclusion complexes between flurbiprofen and methyl-β-cyclodextrin. The studies support the formation of stable molecular inclusion complexes between the drug and cyclodextrin in a 1:1 stoichiometry. In vitro dissolution studies showed that the dissolution properties of flurbiprofen were significantly enhanced by the binary mixtures prepared by supercritical carbon dioxide processing. The amount of flurbiprofen dissolved into solution alone was very low with 1.11 ± 0.09% dissolving at the end of 60 min, while the binary mixtures processed by supercritical carbon dioxide at 45 °C and 200 bar released 99.39 ± 2.34% of the drug at the end of 30 min. All the binary mixtures processed by supercritical carbon dioxide at 45 °C exhibited a drug release of more than 80% within the first 10 min irrespective of the pressure employed. The study demonstrated the single step, organic solvent-free supercritical carbon dioxide process as a promising approach for the preparation of inclusion complexes between flurbiprofen and methyl-β-cyclodextrin in solid-state.

AB - The aim of this study was to enhance the apparent solubility and dissolution properties of flurbiprofen through inclusion complexation with cyclodextrins. Especially, the efficacy of supercritical fluid technology as a preparative technique for the preparation of flurbiprofen-methyl-β-cyclodextrin inclusion complexes was evaluated. The complexes were prepared by supercritical carbon dioxide processing and were evaluated by solubility, differential scanning calorimetry, X-ray powder diffraction, scanning electron microscopy, practical yield, drug content estimation and in vitro dissolution studies. Computational molecular docking studies were conducted to study the possibility of molecular arrangement of inclusion complexes between flurbiprofen and methyl-β-cyclodextrin. The studies support the formation of stable molecular inclusion complexes between the drug and cyclodextrin in a 1:1 stoichiometry. In vitro dissolution studies showed that the dissolution properties of flurbiprofen were significantly enhanced by the binary mixtures prepared by supercritical carbon dioxide processing. The amount of flurbiprofen dissolved into solution alone was very low with 1.11 ± 0.09% dissolving at the end of 60 min, while the binary mixtures processed by supercritical carbon dioxide at 45 °C and 200 bar released 99.39 ± 2.34% of the drug at the end of 30 min. All the binary mixtures processed by supercritical carbon dioxide at 45 °C exhibited a drug release of more than 80% within the first 10 min irrespective of the pressure employed. The study demonstrated the single step, organic solvent-free supercritical carbon dioxide process as a promising approach for the preparation of inclusion complexes between flurbiprofen and methyl-β-cyclodextrin in solid-state.

KW - Dissolution rate

KW - Flurbiprofen

KW - Inclusion complexes

KW - Methyl-b-cyclodextrin

KW - Solubility

KW - Supercritical fluid technology

UR - http://www.scopus.com/inward/record.url?scp=84966262600&partnerID=8YFLogxK

U2 - 10.1016/j.ejpb.2016.04.024

DO - 10.1016/j.ejpb.2016.04.024

M3 - Article

VL - 104

SP - 164

EP - 170

JO - European Journal of Pharmaceutics and Biopharmaceutics

T2 - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

SN - 0939-6411

ER -