The evaluation of supercritical fluid technology as a preparative technique for the manufacture of Flurbiprofen-methyl-β-cyclodextrin inclusion complexes: An approach to enhance the solubility and dissolution properties
Shashi Ravi Suman Rudrangi, Vivek Trivedi, Bruce D Alexander and Stephen R Wicks
University of Greenwich, UK
: J Pharm Drug Deliv Res
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 manufacture 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 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. The results obtained from different analytical studies suggest complete complexation or amorphisation of flurbiprofen and methyl-β-cyclodextrin binary samples prepared by supercritical carbon dioxide processing. 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 released from drug 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. 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. The preliminary data suggests that the complexation of flurbiprofen with methyl-β-cyclodextrin will lead to better therapeutic efficacy.
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