Design and preparation acid-activated montmorillonite sustained-release drug delivery system for dexibuprofen in vitro and in vivo evaluations

摘要

Montmorillonite (Mt) plays a very important role in controlling drug delivery. In this paper, the hydrochloric acid (HCl) treated Mt. was exploited to obtain composites, which were able to enhance dexibuprofen (IBU) loading and achieve to sustain release drug. The textural properties of the Mt. were strongly dependent on the treatment of HCl. The drug loading of pristine Mt. was 190 mg/g, while it was increased to 298 mg/g for Acid-Mt.In vitrorelease showed that the IBU was released about 92% from IBU/Acid-Mt within 12 h, while the pure IBU was released all within 4 h in simulated intestinal fluid, which meant that the IBU/Acid-Mt were able to retard the drug release with a controlled manner. The release profiles of IBU from composites were fitted byHiguchiandKorsmeyer-Peppasequations, which manifested that diffusion sustained release dominated the main mechanism. Meanwhile,in vivopharmacokinetics studies in rats displayed that the IBU/Acid-Mt exhibited better gradual drug release than the commercial IBU suspension. For the IBU/Acid-Mt composites, the area under the plasma concentration-time curve from 0 to 24 h (AUC0–24) and mean residence time (MRT0–24) were 644.49 ± 73.26 μg/h/mL and 7.65 ± 0.48 h, both of which were significantly larger than commercial IBU suspension (AUC0–24of 439.88 ± 84.41 μg/h/mL andMRT0–24of 3.10 ± 0.38 h), respectively (P < 0.05). The relative bioavailability of IBU/Acid-Mt was 154.11% ± 27.41% compared to commercial IBU suspension. As a result, the IBU/Acid-Mt is expected to achieve sustained release and extend residence time in plasma.