摘要
目的 制备托伐普坦纳米晶口崩片,并评价其质量。方法 采用反溶剂沉淀-高压均质法制备托伐普坦纳米晶,并通过Box-Behnken实验设计优化托伐普坦纳米晶的处方;以甘露醇作为载体,用喷雾干燥将托伐普坦纳米晶制备成固体颗粒,并制备成托伐普坦纳米晶口崩片;用扫描电镜观察托伐普坦纳米晶及固体颗粒的微观结构;考察托伐普坦纳米晶在喷雾干燥前、后的稳定性;比较托伐普坦纳米晶口崩片与市售托伐普坦口崩片的体外药物溶出速度。结果 羟丙基纤维素(HPC SL)的质量浓度为15 mg·mL^(-1),普朗尼克(pluronic F127)的质量浓度为5 mg·mL^(-1),水相与有机相的体积比为9∶1时,制备的托伐普坦纳米晶的平均粒径为(214.6±11.5) nm,多聚分散系数为(0.261±0.009),Zeta电位为(-11.6±0.3) mV;扫描电镜下可以观察到托伐普坦纳米晶呈球形颗粒;托伐普坦纳米晶经喷雾干燥后粒径有所增大;自制的托伐普坦纳米晶口崩片的体外药物溶出速度显著快于市售制剂。结论 将托伐普坦制备成纳米晶口崩片,处方设计合理,工艺可行,有望提高托伐普坦的生物利用度。
Objective To prepare Tolvaptan Nanocrystal Orally Disintegrating Tablets and to evaluate their quality.Methods Tolvaptan nanocrystals were prepared by antisolvent precipitation and high pressure homogenization method.The formulation of tolvaptan nanocrystals was optimized by Box-Behnken experimental design.The tolvaptan nanocrystal solid particles were obtained by spray drying by using mannitol as a carrier,and were prepared into tolvaptan nanocrystals orally disintegrating tablets.The microstructure of tolvaptan nanocrystals and solid particles was observed by scanning electron microscope(SEM).The stability of tolvaptan nanocrystals before and after spray drying was investigated.The in vitro drug dissolution rates of Tolvaptan Nanocrystal Orally Disintegrating Tablets and Tolvaptan Orally Disintegrating Tablets were compared.Results The concentration of hydroxypropyl cellulose(HPC SL)was 15 mg·mL^(-1),the concentration of pluronic F127 was 5 mg·mL^(-1),and the volume ratio of aqueous phase/organic phase was 9∶1.The tolvaptan nanocrystals had an average particle size of(214.6±11.5)nm,polymer dispersity index(PDI)of(0.261±0.009),and Zeta potential of(-11.6±0.3)mV.The tolvaptan nanocrystals were spherical particles under SEM.The particle size of tolvaptan nanocrystals increased after spray drying.The in vitro drug dissolution rate of tolvaptan nanocrystal orally disintegrating tablets was significantly faster than that of tolvaptan orally disintegrating tablets.Conclusion Tolvaptan was prepared into nanocrystal orally disintegrating tablets with reasonable prescription design and feasible process,which was expected to improve the bioavailability of tolvaptan.
作者
杨晨
YANG Chen(Xianyang Vocational and Technical College,Xianyang 712000,China)
出处
《西北药学杂志》
CAS
2023年第3期116-120,共5页
Northwest Pharmaceutical Journal
关键词
托伐普坦
纳米晶
口崩片
反溶剂沉淀-高压均质法
喷雾干燥
生物利用度
tolvaptan
nanocrystals
Orally Disintegrating Tablets
antisolvent precipitation and high pressure homogenization method
spray drying
bioavailability
