非诺贝特-淀粉源介孔碳载体固体分散体双层渗透泵控释片的研究

Preparation of Double-layer Osmotic Pump Controlled Release Tablets of Fenofibrate-starch Source Mesoporous Carbon Carrier Solid Dispersion

目的用淀粉源介孔碳(SMC)作为载体来提高非诺贝特(FNB)的溶出速率,并结合双层渗透泵技术使药物得到控释释放,从而提高口服生物利用度。方法通过吸附法将药物FNB载入SMC的介孔孔道中制备载药体系(FNB-SMC)。通过差示扫描量热法(DSC)和粉末X射线衍射法(PXDR)对载药前后药物的存在状态进行表征。体外溶出实验考察FNB-SMC的溶出速率,并对双层渗透泵片进行优化。通过体内实验考察自制片的口服生物利用度。结果表征结果表明,FNB以无定型状态存在在SMC的介孔孔道中。体外溶出实验表明,SMC能显著提高FNB的溶出速率,并且双层渗透泵技术使药物达零级释放。体内实验表明,自制片的口服生物利用度得到明显改善。结论淀粉源介孔碳载体和双层渗透泵技术的联合防止了突释效应,明显改善FNB的口服吸收。

OBJECTIVE To improve the dissolution rate of fenofibrate（ FNB） by using starch source mesoporous carbon（ SMC）as a carrier and achieve controlled release of the drug by utilizing double-layer osmotic pump technology to improve the oral bioavailability. METHODS FNB was loaded into the mesoporous of NMS by adsorption method to prepare the drug loading system（ FNBSMC）. Differential scanning calorimetry（ DSC） and powder X-ray diffraction（ PXDR） were used to characterize the present state of the drug before and after being loaded. The dissolution rate of FNB-SMC was investigated by in vitro dissolution test,and the formulation of the double-layer osmotic pump tablets of FNB-SMC was optimized. The oral bioavailability of the self-made tablet was investigated by in vivo experiment in rabbits. RESULTS FNB existed in the mesoporous of SMC in an amorphous state. The in vitro dissolution test showed that NMS could significantly increase the dissolution rate of FNB,and the double-layer osmotic pump technology could achieve Zero-order release of the drug. The in vivo experiments showed that the oral bioavailability of the self-made tablets was significantly improved. CONCLUSION The combination of starch source mesoporous carbon carrier and double-layer osmotic pump technology prevente the burst effect and significantly improve the oral absorption of FNB.