介孔二氧化硅纳米粒增溶型非诺贝特片剂的制备及体内外研究

Preparation and in Vitro and in Vivo Experiments of Mesoporous Silica Nanoparticles Solubilizing Fenofibrate Tablets

目的制备介孔二氧化硅纳米粒(mesoporous silica nanoparticles,HK)增溶型非诺贝特(fenofibrate,FNB)片剂并进行体内外研究。方法用吸附法以HK为FNB的载体制成固体分散体(FNB-HK)。采用差示扫描量热法、X射线衍射法和傅里叶红外光谱法分析非诺贝特在FNB-HK中的存在状态。通过考察体外溶出度,优化处方并制片。将自制片和市售片分别对家兔单剂量口服给药,采用高效液相色谱法测定家兔血浆药物浓度。结果 FNB-HK表征表明HK能够抑制非诺贝特的结晶。经过处方优化,乳糖做填充剂,8%羧甲基淀粉钠为崩解剂时,片剂能够达到最理想的溶出速率。自制片与市售片相比,体内达峰时间提前,达峰浓度增大,相对生物利用度为149.95%。结论本研究研制的片剂能显著改善FNB的溶出速率,提高其口服生物利用度。

OBJECTIVE To explore the preparation and in vitro and in vivo experiments of mesoporous silica nanoparticles（HK） solubilizing fenofibrate（FNB） tablets. METHODS HK was used as a carrier for FNB to make the solid dispersion（FNB-HK） with the method of adsorption. The existing state of fenofibrate in FNB-HK was analyzed by differential scanning calorimetry, X-ray diffraction and Fourier transform infrared spectroscopy. The dissolution experiment in vitro was conducted to optimize the formulation. Rabbits were administrated with the self-made tablets made according to the optimized formulation and commercial tablets in a single oral dose. The concentration of the rabbits＇ plasma were determined by HPLC. RESULTS The characterization of FNB-HK showed that HK inhibited the crystallization of fenofibrate. Through optimizing formulation, the dissolution rate of tablets achieved an ideal state by using lactose as filler and 8% sodium carboxymethyl starch as a disintegrating agent. Compared with commercial tablets, the peak time of the self-made tablets advanced, and the peak concentration increased. The relative bioavailability was 149.95%. CONCLUSION This preparation of tablets can significantly improve the dissolution rate of FNB and improve the oral bioavailability.