Lainé, A.-L., Price, D., Davis, J. et al. (5 more authors) (2016) Enhanced oral delivery of celecoxib via the development of a supersaturable amorphous formulation utilising mesoporous silica and co-loaded HPMCAS. International Journal of Pharmaceutics, 512 (1). pp. 118-125. ISSN 0378-5173
Abstract
Stabilization of amorphous formulations via mesoporous silica has gained considerable attention for oral delivery of poorly soluble drugs. The release of the drug from the silica is expected to generate supersaturation which is often associated with subsequent precipitation. The aim of the study was hence to develop a novel supersaturable amorphous formulation through the co-loading of a BCS class II drug Celecoxib (CXB) with a precipitation inhibitor hydroxypropyl methylcellulose acetate succinate (HPMCAS) onto the silica. The addition of HPMCAS did not hamper the adsorption but on the contrary promoted the complete solid state conversion of the drug as proved by DSC analysis. In an in vitro pH shift assay, the CXB-HPMCAS co-loaded silica achieved a 5-fold solubility increase over the crystalline CXB and over the CXB-loaded silica blended with HPMCAS which did not show any enhancement. The drug co-loaded silica was then suspended in an aqueous vehicle facilitating the dosing to animals. The CXB-HPMCAS co-loaded silica suspension achieved 15-fold solubility increase in vitro over the crystalline counterpart which translated in 1.35-fold Cmax increase in vivo after oral dosing in rats. This approach represents a novel formulation strategy to maximize in vivo exposure of poorly soluble drugs critical for discovery studies.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 Elsevier. |
Keywords: | Amorphous formulation; Pharmacokinetic study; Mesoporous material; In vitro pH shift assay |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Molecular Biology and Biotechnology (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 07 Oct 2019 09:13 |
Last Modified: | 07 Oct 2019 09:13 |
Status: | Published |
Publisher: | Elsevier |
Refereed: | Yes |
Identification Number: | 10.1016/j.ijpharm.2016.08.034 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:151829 |