Insights to the phase solubility diagrams of flurbiprofen with inclusion complex

Flurbiprofen (FB) is one of the nonsteroidal anti-inflammatory drugs with poor water solubility.Cyclodextrins have a special structure (hydrophobic inner phase and hydrophilic outer phase), which have been widelyused to enhance the solubility and stability of drug substances in pharmaceutical applications. The present study isintended to improve the solubility of FB with the inclusion complexes assembled by using beta-cyclodextrin (β-CD) andhydroxypropyl beta-cyclodextrin (HPβ-CD) and to perform the phase solubility studies to estimate the stability constantand complexation efficiency. The results of phase solubility studies showed that the FB/β-CD complexes have Bs typeand FB/HPβ-CD complexes have AL type profiles in both PBS and water media. The interaction forces between FB andHPβ-CD were stronger than FB and β-CD for the formation of inclusion complex in water. Moreover, the complexationefficiency value of FB/HPβ-CD complex in water media was found higher than the FB/HPβ-CD complex in PBS media.These results of phase solubility studies absolutely demonstrated the advantage of HPβ-CD instead of β-CD to obtainthe inclusion complex with 1:1 Molar ratio in water and to improve the apparent water solubility of FB. According tothese results, the FB/HPβ-CD inclusion complex was prepared with the Freeze-drying method and it was achieved toenhance the water solubility of FB 52.6-fold with using HPβ-CD. In conclusion, the presence of the inclusion complexwas successfully confirmed by differential scattering calorimetry, X-ray diffraction, scanning electron microscopy andfourier transform infrared analysis.

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