Stabilization and solubilization of difluprednate in aqueous cyclodextrin solution and its characterization for ophthalmic delivery

Publisher´s version / Útgefin grein Difluprednate is a synthetic glucocorticoid used for the treatment of postoperative inflammation and pain associated with endogenous uveitis. It is very lipophilic with limited aqueous solubility and stability. The only available marketed formulation is an oil-in-...

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Bibliographic Details
Published in:Journal of Drug Delivery Science and Technology
Main Authors: Prajapati, Manisha, Loftsson, Thorsteinn
Other Authors: Lyfjafræðideild (HÍ), Faculty of Pharmaceutical Sciences (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland
Format: Article in Journal/Newspaper
Language:English
Published: Elsevier 2022
Subjects:
Solubility
Stability
Cyclodextrins
Difluprednate
Lyfjaefnafræði
Lyfjameðferð
Skurðsjúklingar
Bólgur
Pharmaceutical chemistry
Iceland
Online Access:https://hdl.handle.net/20.500.11815/2969
https://doi.org/10.1016/j.jddst.2022.103106
Description
Summary:Publisher´s version / Útgefin grein Difluprednate is a synthetic glucocorticoid used for the treatment of postoperative inflammation and pain associated with endogenous uveitis. It is very lipophilic with limited aqueous solubility and stability. The only available marketed formulation is an oil-in-water ophthalmic emulsion that has many drawbacks. Cyclodextrin (CD) molecules are widely used to increase the solubility and stability of hydrophobic drugs through the for- mation of drug/CD complexes. This study aims to investigate degradation kinetics, stability and solubility of difluprednate in aqueous CD solutions in an effort to develop aqueous eye drop vehicle for ophthalmic delivery. Phase-solubility and kinetics studies were performed in presence of different CDs and polymers. Characterization of the drug/CD complexes was done using techniques like NMR, DSC, and FTIR. The results show that diflu- prednate has maximum stability at pH 5 in aqueous CD solution. HPγCD was found to be the best solubilizer and stabilizer among all the CDs tested. The stability was further improved with the combination of HPγCD and different polymers. Characterization of the difluprednate/HPγCD complex in solid and solution state confirmed the presence of a drug/CD complex. It was possible to solubilize 0.1% difluprednate using HPγCD and stabilize the drug using combination of CD and polymer in aqueous solution This work was financially supported by the European Union grant no. MSCA-ITN-2017-765441 (transMed) and the Faculty of Pharmaceutical Sciences, University of Iceland. Peer-Reviewed

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