Cellulose Acetate Microparticles Synthesized from <i>Agave sisalana</i> Perrine for Controlled Release of Simvastatin

Abstract

Simvastatin (SIM) is widely prescribed to treat hyperlipidemia, despite its limitations, such as a short half-life and low oral bioavailability. To overcome these drawbacks, the development of a controlled-release formulation is desirable. This study aims to develop a microparticulate system based on cellulose acetate (ACT) obtained from Agave sisalana Perrine to promote a controlled SIM release. SIM-loaded microparticles (SMP) were prepared using the solvent emulsification-evaporation method. Several parameters were evaluated, including particle size, surface charge, morphology, encapsulation efficiency, thermochemical characteristics, crystallinity, and in vitro release profile. ACT exhibited favorable flow properties after acetylation, with a degree of substitution values superior to 2.5, as confirmed by both the chemical route and H-NMR, indicating the formation of cellulose triacetate. The obtained SMP were spherical with an average size ranging from 1842 to 1857 nm, a zeta potential of −4.45 mV, and a high SIM incorporation efficiency (98%). Thermal and XRD analyses revealed that SIM was homogeneously dispersed into the polymeric matrix in its amorphous state. In vitro studies using dialysis bags revealed that the controlled SIM release from microparticles was higher under simulated intestinal conditions and followed the Higuchi kinetic model. Our results suggest that ACT-based microparticles are a promising system for SIM delivery, which can improve its bioavailability, and result in better patient compliance.

Keywords

• microencapsulation
• cellulose
• controlled release
• new drug release systems
• bioavailability