Multilayer-coating technology is the traditional method to achieve pulsatile drug release with the drawbacks of time consuming, more materials demanding and lack of efficiency. The purpose of this study was to design a novel pulsatile drug delivery system based on the physiochemical interaction between acrylic copolymer and organic acid with relatively simpler formulation and manufacturing process. The Enalapril Maleate (EM) pulsatile release pellets were prepared using extruding granulation, spheronization and fluid-bed coating technology. The ion-exchange experiment, hydration study and determination of glass transition temperature were conducted to explore the related drug release mechanism. Bioavailability experiment was carried out by administering the pulsatile release pellets to rats compared with marketed rapid release tablets Yisu ® . An obvious 4 h lag time period and rapid drug release was observed from in vitro dissolution profiles. The release mechanism was a combination of both disassociated and undisassociated forms of succinic acid physiochemically interacting with Eudragit ® RS. The AUC0-τ of the EM pulsatile pellets and the market tablets was 702.384 ± 96.891 h ng/mL and 810.817 ± 67.712 h ng/mL, while the relative bioavailability was 86.62%. These studies demonstrate this novel pulsatile release concept may be a promising strategy for oral pulsatile delivery system.
Enmin Chen,Lianqi Cao,David Julian McClements,Shilin Liu,Bin Li,Yan Li
The impact of incorporating different levels of cinnamaldehyde (CA) into the oil phase used to prepare whey protein isolate (WPI)-stabilized nanoemulsions was investigated. Stable nanoemulsions could not be formed by pure CA, which was attributed to gravitational separation, but they could be formed from mixtures of CA and triglycerides. The mean particle diameter produced by homogenization decreased with increasing CA, which was attributed to the reduction of oil phase interfacial tension and viscosity. CA enhanced the physical stability of the nanoemulsions to salt addition (0–500 mM) and thermal processing (30–90 °C), but could not prevent droplet flocculation near the protein's isoelectric point (around pH 5). SDS-PAGE and surface load measurements indicated that more protein accumulated at the droplet surfaces in the presence of CA, which was attributed to interfacial crosslinking. CA may therefore be a useful means of modulating the physicochemical properties of protein-stabilized nanoemulsions.
危险品化学品经营许可证（带存储）