他达拉非自乳化片的制备与体外溶出研究

Preparation and in vitro dissolution of Fast-Dissolving Tablets tadalafil based on self-microemulsifying drug delivery system

目的研制他达拉非(TDF)自乳化片(TDF-SMEDDS-FDTs),并评价其质量。方法通过测定TDF在不同油相、乳化剂和助乳化剂中的溶解度,并结合伪三元相图确定TDF自乳化释药系统(TDF-SMEDDS)的处方组成;以硅酸镁铝作为载体,通过流化床制粒工艺将TDF-SMEDDS固化到载体上,并与其他辅料混合制备成TDF-SMEDDS-FDTs;在透射电镜下观察TDF-SMEDDS在固化前后形成微乳的粒径分布,在扫描电镜下观察TDF-SMEDDS颗粒的微观形态,比较TDF-SMEDDS-FDTs与他达拉非片的体外溶出速率,在加速条件下考察其稳定性。结果TDF-SMEDDS的处方组成为:丙二醇单辛酸酯(Capryol 90)作为油相,辛酸癸酸聚乙二醇甘油酯(Labrasol)作为乳化剂,聚乙二醇600(PEG600)作为助乳化剂,处方最佳配比为0.7∶0.2∶0.1。TDF-SMEDDS固化后形成微乳的粒径分布有所增大,在扫描电镜下可观察到TDF-SMEDDS分布在硅酸镁铝颗粒表面及孔隙中,覆盖较均匀;体外溶出显示,TDF-SMEDDS-FDTs中的药物在10 min内可完全溶出,显著高于他达拉非片中的药物溶出速率;稳定性结果显示,TDF-SMEDDS-FDTs在加速条件下放置6个月稳定性良好。结论将TDF制备成TDF-SMEDDS-FDTs,处方合理,工艺可行,显著提高了药物溶出速率,有望提高药物的生物利用度。

Objective To develop and evaluate the quality of Fast-Dissolving Tablets of tadalafil(TDF)based on self-microemulsifying drug delivery system(TDF-SMEDDS-FDTs).Methods The solubility of tadalafil in different oil phases,emulsifiers and co-emulsifiers was determined,and the pseudo-ternary phase diagram was combined to determine the formulation composition of tadalafil self-microemulsifying drug delivery system(TDF-SMEDDS).By using magnesium aluminometasilicate as a carrier,TDF-SMEDDS was solidified on the carrier through a fluidized bed granulation process,which was mixed with excipients and prepared by direct compression to obtain TDF-SMEDDS-FDTs.The particle size distribution of the microemulsion formed before and after solidification of TDF-SMEDDS was investigated.The microscopic morphology of TDF-SMEDDS particles was observed under scanning electron microscope.The in vitro dissolution rates of TDF-SMEDDS-FDTs and Tadalafil Tablets were compared,and their stability was investigated under accelerated conditions.Results The formulation was composed of Capryol 90 as oil phase,Labrasol as emulsifiers,PEG600 as co-emulsifiers.The ratio of oil phase,surfactant and co-surfactant was 0.7∶0.2∶0.1.The particle size distribution of the microemulsion formed after solidification of TDF-SMEDDS was increased.Under the scanning electron microscope,TDF-SMEDDS was distributed on the surface and pores of magnesium aluminosilicate particles,and the coverage was relatively uniform.The dissolution results show that TDF-SMEDDS-FDTs could be completely dissolved within 10 minutes,which was significantly higher than that of Tadalafil Tablets.The stability results showed that TDF-SMEDDS-FDTs had good stability after 6 months under accelerated conditions.Conclusion The tadalafil was prepared into TDF-SMEDDS-FDTs,the formulation design was reasonable and the process was feasible.The drug dissolution rate was significantly improved,and it was expected to improve the bioavailability.