摘要
目的 制备介孔硅材料SBA-3负载非诺贝特(FNB),以提高其溶出速率及体内生物利用度。方法 制备载体SBA-3,并通过吸附法将FNB载入到SBA-3的介孔孔道形成FNB-SBA-3载药体系。通过透射电镜TEM考察SBA-3的微观结构。差示扫描量热法(DSC)检测FNB在SBA-3孔道中的状态。观察SBA-3对Caco-2细胞毒性。体外溶出实验比较FNB与FNB-SBA-3的溶出速率。通过单因素筛选填充剂,黏合剂和崩解剂的种类,确定FNB-SBA-3自制片的最佳处方。比较市售片和自制片在家兔体内的药物代谢情况。结果 通过TEM观察SBA-3具有有序均一的介孔孔道。通过药物吸附法使FNB在SBA-3中载药量为43.03%。DSC表征结果表明FNB与SBA-3无化学反应,且FNB是以无定形状态存在于SBA-3孔道中。毒性实验中SBA-3在最大浓度500μg·mL^(-1)下,Caco-2细胞存活率仍为90.66%。体外溶出实验显示SBA-3能显著提高FNB的溶出速率到93.3%。80 mg乳糖为填充剂,3 mg HPMC为黏合剂和30 mgCMS-Na为崩解剂是制备FNB-SBA-3自制片的最优处方。体内药动学相关参数表明FNB-SBA-3自制片相对于市售片能显著改善FNB的口服生物利用度达181.83%。结论 SBA-3显著提高FNB的溶出速率和口服生物利用度,SBA-3作为难溶性药物载体在口服给药系统中具有很大潜力。
Objective In this study,fenofibrate(FNB)loaded mesoporous silicon material SBA-3 was prepared to improve its dissolution rate and bioavailability in vivo.Methods The carrier SBA-3 was prepared,and FNB was loaded into the mesoporous pores of SBA-3 to form the drug loading system of FNB-SBA-3 by the adsorption method.The microstructure of SBA-3 was investigated by TEM.The status of FNB in the SBA-3 channel was detected by differential scanning calorimetry(DSC).The toxicity of SBA-3 was evaluated in Caco-2 cells.The dissolution rates of FNB and FNB-SBA-3 were compared in vitro.The best prescription of FNB-SBA-3 self-made tablets was determined by screening the types of fillers,binders,and disintegrators through the univariate screening.The drug metabolism of commercial tablets and self-made tablets in rabbits were compared.Results SBA-3 had ordered and uniform mesoporous channels observed by TEM.The drug loading of FNB in SBA-3 was 43.03%by the adsorption method.The DSC results of showed no chemical reaction between FNB and SBA-3,and FNB was present in SBA-3 channels in an amorphous state.In the cytotoxicity experiment,under the maximum SBA-3 concentration at 500μg·mL^(-1),the survival rate of Caco-2 cells was still 90.66%.The dissolution experiments in vitro showed that SBA-3 could significantly improve the dissolution rate of FNB to 93.3%.The prescription using 80 mg lactose as a filler,3 mg HPMC as an adhesive and 30 mg CMS-Na as a disintegrant were optimal for preparing FNB-SBA-3 self-made tablets.The pharmacokinetic parameters in vivo showed that FNB-SBA-3 self-made tablets could significantly improve the oral bioavailability of FNB to 181.83%compared with commercial tablets.Conclusion SBA-3 can significantly improve the dissolution rate and oral bioavailability of FNB.Therefore,SBA-3 as a carrier for insoluble drugs has excellent potential in the oral drug delivery system.
作者
李江
谢瑞
LI Jiang;XIE Rui(Department of Pharmacy,the First Affiliated Hospital,Zhejiang University of Traditional Chinese Medicine,Hangzhou 310000,China)
出处
《医药导报》
CAS
北大核心
2022年第6期863-868,共6页
Herald of Medicine
基金
浙江省自然科学基金联合基金项目(LYY21H300002)。
