Amorphous Nanoparticulate Formulation of Sirolimus and Its Tablets

Abstract

Nanocrystallization and amorphization have proven to be two effective strategies to improve the bioavailability of water-insoluble drugs. The purpose of our work was to develop a nano-formulated tablet of sirolimus (SRL) for enhanced dissolution. Amorphous SRL nanocomposites were prepared using anti-solvent precipitation via a high-gravity rotating packed bed. Various factors that affect particle size and size distribution, such as excipients, rotating speed, antisolvent/solvent flow rate, were investigated. Structure, stability and in vitro dissolution of the as-prepared SRL were evaluated. Furthermore, the nanoparticulated SRL tablet formula was screened to control drug release. Importantly, SRL tablets exhibit different dissolution profile by adjusting HPMC (hydroxypropyl methyl cellulose) content, which makes them more suitable for various formulation developments.

Keywords

• amorphous sirolimus nanoparticles
• antisolvent precipitation
• high gravity rotating packed bed
• dissolution rate
• tablet formula