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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ftopinvisindi:oai:opinvisindi.is:20.500.11815/2969 2023-05-15T16:51:22+02:00 Stabilization and solubilization of difluprednate in aqueous cyclodextrin solution and its characterization for ophthalmic delivery Prajapati, Manisha Loftsson, Thorsteinn Lyfjafræðideild (HÍ) Faculty of Pharmaceutical Sciences (UI) Heilbrigðisvísindasvið (HÍ) School of Health Sciences (UI) Háskóli Íslands University of Iceland 2022-01 103106 https://hdl.handle.net/20.500.11815/2969 https://doi.org/10.1016/j.jddst.2022.103106 en eng Elsevier info:eu-repo/grantAgreement/EC/H2020/MSCA-ITN-2017-765441 Journal of Drug Delivery Science and Technology;69 Manisha Prajapati, Thorsteinn Loftsson, Stabilization and solubilization of difluprednate in aqueous cyclodextrin solution and its characterization for ophthalmic delivery, Journal of Drug Delivery Science and Technology, Volume 69, 2022, 103106, ISSN 1773-2247, 1773-2247 https://hdl.handle.net/20.500.11815/2969 Journal of Drug Delivery Science and Technology doi:10.1016/j.jddst.2022.103106 info:eu-repo/semantics/openAccess Solubility Stability Cyclodextrins Difluprednate Lyfjaefnafræði Lyfjameðferð Skurðsjúklingar Bólgur Pharmaceutical chemistry info:eu-repo/semantics/article 2022 ftopinvisindi https://doi.org/20.500.11815/2969 https://doi.org/10.1016/j.jddst.2022.103106 2022-11-18T06:52:16Z 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 Article in Journal/Newspaper Iceland Opin vísindi (Iceland) Journal of Drug Delivery Science and Technology 69 103106 |
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Open Polar |
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Opin vísindi (Iceland) |
op_collection_id |
ftopinvisindi |
language |
English |
topic |
Solubility Stability Cyclodextrins Difluprednate Lyfjaefnafræði Lyfjameðferð Skurðsjúklingar Bólgur Pharmaceutical chemistry |
spellingShingle |
Solubility Stability Cyclodextrins Difluprednate Lyfjaefnafræði Lyfjameðferð Skurðsjúklingar Bólgur Pharmaceutical chemistry Prajapati, Manisha Loftsson, Thorsteinn Stabilization and solubilization of difluprednate in aqueous cyclodextrin solution and its characterization for ophthalmic delivery |
topic_facet |
Solubility Stability Cyclodextrins Difluprednate Lyfjaefnafræði Lyfjameðferð Skurðsjúklingar Bólgur Pharmaceutical chemistry |
description |
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 |
author2 |
Lyfjafræðideild (HÍ) Faculty of Pharmaceutical Sciences (UI) Heilbrigðisvísindasvið (HÍ) School of Health Sciences (UI) Háskóli Íslands University of Iceland |
format |
Article in Journal/Newspaper |
author |
Prajapati, Manisha Loftsson, Thorsteinn |
author_facet |
Prajapati, Manisha Loftsson, Thorsteinn |
author_sort |
Prajapati, Manisha |
title |
Stabilization and solubilization of difluprednate in aqueous cyclodextrin solution and its characterization for ophthalmic delivery |
title_short |
Stabilization and solubilization of difluprednate in aqueous cyclodextrin solution and its characterization for ophthalmic delivery |
title_full |
Stabilization and solubilization of difluprednate in aqueous cyclodextrin solution and its characterization for ophthalmic delivery |
title_fullStr |
Stabilization and solubilization of difluprednate in aqueous cyclodextrin solution and its characterization for ophthalmic delivery |
title_full_unstemmed |
Stabilization and solubilization of difluprednate in aqueous cyclodextrin solution and its characterization for ophthalmic delivery |
title_sort |
stabilization and solubilization of difluprednate in aqueous cyclodextrin solution and its characterization for ophthalmic delivery |
publisher |
Elsevier |
publishDate |
2022 |
url |
https://hdl.handle.net/20.500.11815/2969 https://doi.org/10.1016/j.jddst.2022.103106 |
genre |
Iceland |
genre_facet |
Iceland |
op_relation |
info:eu-repo/grantAgreement/EC/H2020/MSCA-ITN-2017-765441 Journal of Drug Delivery Science and Technology;69 Manisha Prajapati, Thorsteinn Loftsson, Stabilization and solubilization of difluprednate in aqueous cyclodextrin solution and its characterization for ophthalmic delivery, Journal of Drug Delivery Science and Technology, Volume 69, 2022, 103106, ISSN 1773-2247, 1773-2247 https://hdl.handle.net/20.500.11815/2969 Journal of Drug Delivery Science and Technology doi:10.1016/j.jddst.2022.103106 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/20.500.11815/2969 https://doi.org/10.1016/j.jddst.2022.103106 |
container_title |
Journal of Drug Delivery Science and Technology |
container_volume |
69 |
container_start_page |
103106 |
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1766041480578727936 |