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

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Materials Science

Background:

• Sorafenib (SOR) is an oral anti-cancer drug with limited bioavailability.
• Amorphous solid dispersions (ASDs) can enhance the solubility and bioavailability of poorly soluble drugs.
• Hydroxypropyl methylcellulose acetate succinate (HPMC-AS) is a polymer suitable for creating stable ASDs.

Purpose of the Study:

• To develop an immediate-release tablet formulation of sorafenib (SOR) using an amorphous solid dispersion (ASD) approach.
• To improve the oral bioavailability of sorafenib through ASD technology.
• To optimize the manufacturing process for SOR ASD tablets.

Main Methods:

• An amorphous solid dispersion (ASD) of sorafenib (SOR) was prepared with hydroxypropyl methylcellulose acetate succinate (HPMC-AS, M grade) via coprecipitation.
• The ASD was characterized for physical stability and dissolution properties.
• Dry granulation was employed to address poor powder flowability of the ASD.
• Tablet compaction conditions were optimized using a material-sparing approach.

Main Results:

• A 40% drug loading ASD of SOR in HPMC-AS exhibited superior physical stability and enhanced dissolution.
• Dry granulation effectively managed the poor flow properties of the SOR ASD.
• Optimized ASD tablets were manufactured with low friability and rapid disintegration.
• The SOR ASD tablets showed approximately 50% higher relative bioavailability in dogs compared to Nexavar®.

Conclusions:

• Amorphous solid dispersion technology with HPMC-AS is effective for developing immediate-release sorafenib tablets.
• The developed SOR ASD tablets offer a promising strategy for enhancing oral bioavailability.
• The optimized manufacturing process ensures the quality and performance of the final drug product.