兰索拉唑自微乳释药系统的设计及对胃黏膜修护作用的研究
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摘要
目的研究兰索拉唑自微乳释药系统的基质组成、处方组成、质量评价,并与市售兰索拉唑肠溶片的对胃黏膜修护作用进行比较。方法采用加水相滴定法绘制伪三元相图和外观等级评分,筛选油相、乳化剂、助乳化剂的种类及乳化剂与助乳化剂的比例(Km值),通过透射电镜观察兰索拉唑自微乳的外观形态,利用激光粒度仪测定粒径大小、分布及Zeta电位,并以小鼠胃溃疡模型进行胃黏膜修护作用的药效学评价。结果兰索拉唑自微乳的最佳处方组成为:油相油酸乙酯(EO) 20%,乳化剂聚氧乙烯40-氢化蓖麻油(Cremophor RH40) 64%,助乳化剂丙二醇16%,Km为4∶1;三乙醇胺为稳定剂。电镜下自微乳的外观为球形,分布均匀,粒径68. 9 nm,Zeta电位-38. 17 m V,跨度为0. 501。与市售兰索拉唑肠溶片比较,兰索拉唑自微乳能使小鼠胃黏膜损伤指数(GI)显著性降低,胃脏器指数显著性升高,对急性胃黏膜损伤有较好的保护作用。结论制备的兰索拉唑自微乳给药系统质量稳定,符合2015年版《中国药典》中9014微粒制剂指导原则项下的规定,且有较好的保护胃黏膜的作用。
OBJECTIVE To study the matrix composition,formulation composition,quality evaluation of Lansoprazole self-microemulsion drug delivery system and compare its gastric mucosal repair effect with the commercially available lansoprazole enteric-coated tablets. METHODS Pseudo-ternary phase diagram and appearance grade score were drawn by the adding water phase titration method,and the types of oil phase,emulsifier and co-emulsifier and the proportion of each component,such as the ratio of emulsifier to co-emulsifier( Km value),were screened. The appearance of Lansoprazole from microemulsion was observed by transmission electron microscopy. The particle size,distribution and Zeta potential were measured by laser particle size analyzer,and the pharmacodynamic evaluation of gastric mucosal repair in mouse gastric ulcer model was performed.RESULTS Lansoprazole self-microemulsion drug delivery system( SMEDD) was composed as follow: Oil phase ethyl oleate( EO) of 20%,emulsifier polyoxyethylene-40-hydrogenated castor oil( Cremophor RH40) of 64%,co-emulsifier propylene glycol of 16%,Km of 4 ∶1,with the triethanolamine as a stabilizer. It has a spherical shape and uniform distribution under electron microscope. The particle size is 68. 9 nm,the Zeta potential is-38. 17 m V,and the span is 0. 501. The test results on gastric mucosal repair show that it is commercially available. Compared with the sorazol enteric-coated tablets,Lansoprazole SMEDD can significantly reduce the gastric mucosal injury index( GI) in mice,and the gastric organ index is significantly increased. It has a good protective effect on acute gastric mucosal injury. CONCLUSION The prepared Lansoprazole SMEDD has stable quality,which is in accordance with the guidelines of the 2015 edition of the Chinese Pharmacopoeia 9014 microparticle preparation guidelines,and it has a good protective effect on the gastric mucosa.
OBJECTIVE To study the matrix composition,formulation composition,quality evaluation of Lansoprazole self-microemulsion drug delivery system and compare its gastric mucosal repair effect with the commercially available lansoprazole enteric-coated tablets. METHODS Pseudo-ternary phase diagram and appearance grade score were drawn by the adding water phase titration method,and the types of oil phase,emulsifier and co-emulsifier and the proportion of each component,such as the ratio of emulsifier to co-emulsifier( Km value),were screened. The appearance of Lansoprazole from microemulsion was observed by transmission electron microscopy. The particle size,distribution and Zeta potential were measured by laser particle size analyzer,and the pharmacodynamic evaluation of gastric mucosal repair in mouse gastric ulcer model was performed.RESULTS Lansoprazole self-microemulsion drug delivery system( SMEDD) was composed as follow: Oil phase ethyl oleate( EO) of 20%,emulsifier polyoxyethylene-40-hydrogenated castor oil( Cremophor RH40) of 64%,co-emulsifier propylene glycol of 16%,Km of 4 ∶1,with the triethanolamine as a stabilizer. It has a spherical shape and uniform distribution under electron microscope. The particle size is 68. 9 nm,the Zeta potential is-38. 17 m V,and the span is 0. 501. The test results on gastric mucosal repair show that it is commercially available. Compared with the sorazol enteric-coated tablets,Lansoprazole SMEDD can significantly reduce the gastric mucosal injury index( GI) in mice,and the gastric organ index is significantly increased. It has a good protective effect on acute gastric mucosal injury. CONCLUSION The prepared Lansoprazole SMEDD has stable quality,which is in accordance with the guidelines of the 2015 edition of the Chinese Pharmacopoeia 9014 microparticle preparation guidelines,and it has a good protective effect on the gastric mucosa.
引文
[1]王晓妍,孙蓉.兰索拉唑临床联合用药研究进展[J].中国药物评价,2015,32(1):21-23.
[2]张正全,胡海英,邓基伟.兰索拉唑肠溶片厨房及工艺改进[J].华西药学杂志,2007,22(6):643-645.
[3]何娜,张莉,朱峰,等.胰岛素磷脂复合物自微乳传递系统的制备[J].华西药学杂志,2010,25(4):396-399.
[4] Guth PH,Aures D,Paulson G,et al. Topical aspirin plus Hcl gastric lesions in the rat[J]. Gastroenterology,1979,76(1):89-93.
[5]王钰涵,蒋殿欣,王黎荣,等.猴头菌胃黏附片对胃黏膜损伤保护作用的研究[J].人参研究,2016,2:26-28.
[6]卢秀霞,李伟镇,何琳,等.盐酸雷洛昔芬自微乳的制备及其体外评价[J].中国新药杂志,2015,24(15):1777-1785.
[2]张正全,胡海英,邓基伟.兰索拉唑肠溶片厨房及工艺改进[J].华西药学杂志,2007,22(6):643-645.
[3]何娜,张莉,朱峰,等.胰岛素磷脂复合物自微乳传递系统的制备[J].华西药学杂志,2010,25(4):396-399.
[4] Guth PH,Aures D,Paulson G,et al. Topical aspirin plus Hcl gastric lesions in the rat[J]. Gastroenterology,1979,76(1):89-93.
[5]王钰涵,蒋殿欣,王黎荣,等.猴头菌胃黏附片对胃黏膜损伤保护作用的研究[J].人参研究,2016,2:26-28.
[6]卢秀霞,李伟镇,何琳,等.盐酸雷洛昔芬自微乳的制备及其体外评价[J].中国新药杂志,2015,24(15):1777-1785.