Efficient development of sorafenib tablets with improved oral bioavailability enabled by coprecipitated amorphous solid dispersion

Sichen Song; Chenguang Wang; Shan Wang; Ronald A. Siegel; Changquan Calvin Sun

doi:10.1016/j.ijpharm.2021.121216

Efficient development of sorafenib tablets with improved oral bioavailability enabled by coprecipitated amorphous solid dispersion

Sichen Song, Chenguang Wang, Shan Wang, Ronald A. Siegel, Changquan Calvin Sun

Pharmaceutics

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

Abstract

An amorphous solid dispersion (ASD) of sorafenib (SOR) in hydroxypropyl methylcellulose acetate succinate (HPMC-AS), prepared by coprecipitation, was used to develop an immediate release tablet with improved oral bioavailability. An ASD of 40% drug loading with HPMC-AS (M grade), which exhibited superior physical stability and enhanced dissolution, was selected for tablet development. Systematic characterization of powder properties of the ASD led to the choice of the dry granulation process to overcome poor flowability of the ASD. The designed tablet formulation was evaluated using a material-sparing and expedited approach to optimize compaction conditions for manufacturing ASD tablets with low friability and rapid disintegration. The resulting SOR ASD tablets exhibited approximately 50% higher relative bioavailability in dogs than the marketed SOR tablet product, Nexavar®.

Original language	English (US)
Article number	121216
Journal	International journal of pharmaceutics
Volume	610
DOIs	https://doi.org/10.1016/j.ijpharm.2021.121216
State	Published - Dec 15 2021

Bibliographical note

Funding Information:
We thank Huadong Medicine Co., Ltd. for providing funding and collecting dog PK data. Parts of this work were carried out in the Characterization Facility, University of Minnesota, which receives partial support from the NSF through the MRSEC (Award Number DMR-2011401) and the NNCI (Award Number ECCS-2025124) programs. We thank Gerrit Vreeman (Department of Pharmaceutics, University of Minnesota) for collecting the SEM images. S.S. thanks Wenjuan Zhang, Prof. William Elmquist and Prof. Ronald Sawchuk (Department of Pharmaceutics, University of Minnesota) for helpful discussions of the PK data.

Funding Information:
We thank Huadong Medicine Co. Ltd. for providing funding and collecting dog PK data. Parts of this work were carried out in the Characterization Facility, University of Minnesota, which receives partial support from the NSF through the MRSEC (Award Number DMR-2011401) and the NNCI (Award Number ECCS-2025124) programs. We thank Gerrit Vreeman (Department of Pharmaceutics, University of Minnesota) for collecting the SEM images. S.S. thanks Wenjuan Zhang, Prof. William Elmquist and Prof. Ronald Sawchuk (Department of Pharmaceutics, University of Minnesota) for helpful discussions of the PK data.

Publisher Copyright:
© 2021 Elsevier B.V.

Keywords

Amorphous solid dispersion
Coprecipitation
Oral bioavailability
Sorafenib
Tablet

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title = "Efficient development of sorafenib tablets with improved oral bioavailability enabled by coprecipitated amorphous solid dispersion",

abstract = "An amorphous solid dispersion (ASD) of sorafenib (SOR) in hydroxypropyl methylcellulose acetate succinate (HPMC-AS), prepared by coprecipitation, was used to develop an immediate release tablet with improved oral bioavailability. An ASD of 40% drug loading with HPMC-AS (M grade), which exhibited superior physical stability and enhanced dissolution, was selected for tablet development. Systematic characterization of powder properties of the ASD led to the choice of the dry granulation process to overcome poor flowability of the ASD. The designed tablet formulation was evaluated using a material-sparing and expedited approach to optimize compaction conditions for manufacturing ASD tablets with low friability and rapid disintegration. The resulting SOR ASD tablets exhibited approximately 50% higher relative bioavailability in dogs than the marketed SOR tablet product, Nexavar{\textregistered}.",

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Efficient development of sorafenib tablets with improved oral bioavailability enabled by coprecipitated amorphous solid dispersion

Abstract

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Keywords

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