三种新型布洛芬透皮脂质囊泡的比较及二元醇脂质体温敏凝胶的制备与评价

发布时间：2018-04-25 04:34

  本文选题：布洛芬 + 乙醇脂质体　； 参考：《兰州大学》2014年硕士论文

【摘要】：目的 (1)以布洛芬为模型药物,制备并比较乙醇脂质体、二元醇脂质体及固体脂质纳米粒三种新型透皮脂质囊泡。 (2)将透皮性能优者制备成温敏凝胶,考察新型布洛芬透皮脂质囊泡温敏凝胶作为经皮给药制剂的可行性。 方法 (1)采用注入法制备布洛芬乙醇脂质体和二元醇脂质体,以高温乳化-低温固化方法制备布洛芬固体脂质纳米粒,并测定其形态、Zeta-电位、粒径和包封率；采用冷溶法将透皮性能优的布洛芬脂质囊泡系统进一步制备成温敏凝胶,并采用搅拌子法测定其胶凝温度。 (2)采用单因素试验优化布洛芬乙醇脂质体、二元醇脂质体、固体脂质纳米粒及其脂质囊泡温敏凝胶的最优处方。 (3)通过Franz扩散池考察布洛芬乙醇脂质体、二元醇脂质体及固体脂质纳米粒的体外透皮性能。 (4)采用透析法测定布洛芬脂质囊泡温敏凝胶的体外释放度。 (5)采用HE染色技术考察布洛芬脂质囊泡温敏凝胶对小鼠的皮肤刺激性。 (6)将布洛芬乙醇脂质体、二元醇脂质体及固体脂质纳米粒置于室温和4℃下保存,于0、1、2和3个月时测定其包封率,考察其稳定性；将布洛芬脂质囊泡温敏凝胶置于40℃恒温箱和-20℃冰箱中避光保存,于第5、10天取样,观察外观性状,测定药物含量及胶凝温度,考察其稳定性。 结果 (1)布洛芬乙醇脂质体、二元醇脂质体(乙醇-丙二醇=7：3,v/v)及固体脂质纳米粒均呈球形或类球形,平均粒径分别为(108±4.3)nm、(103±5.6)nm和(195.2±16.88)nm,Zeta电位分别为(-9.8±4)mv、(-8.25±3.2)mv和(-22.3±6.94)mv,3种最优处方对布洛芬的包封率分别为(72.93±1.12)%、(73.58±1.35)%和(73.61±1.42)%。 (2)在布洛芬二元醇脂质体中,药物的经皮渗透性能随乙醇和丙二醇的比例不同而不同,当乙醇与丙二醇比例为7：3时制得的布洛芬二元醇脂质体透皮能力最强。 (3)布洛芬乙醇脂质体和二元醇脂质体(乙醇-丙二醇=7：3,v/v)的累计渗透百分数分别是固体脂质纳米粒的8.95倍和16.35倍；24h后固体脂质纳米粒在皮肤中的药物滞留量大于乙醇脂质体和二元醇脂质体,有显著性差异(P0.01) (4)以32.2%泊洛沙姆407和3.22%泊洛沙姆188溶液制备的布洛芬二元醇脂质体温敏凝胶的胶凝温度为(32.0±1.1)℃,且其体外释放度与布洛芬二元醇脂质体相比有较为显著的缓释效果。 (5)皮肤组织病理学实验结果表明布洛芬二元醇脂质体温敏凝胶未引起小鼠皮肤组织结构的明显改变。 (6)布洛芬乙醇脂质体、二元醇脂质体、固体脂质纳米粒分别放置于室温和4℃保存3个月后,包封率均未见明显改变；布洛芬二元醇脂质体温敏凝胶置于40℃恒温箱和-20℃冰箱中避光保存10天后,其外观性状、药物的含量及胶凝温度均未发生明显改变。 结论 (1)布洛芬乙醇脂质体、二元醇脂质体(乙醇-丙二醇=7：3,v/v)、固体脂质纳米粒均呈球形或类球形,三者间的包封率无显著性差异。 (2)乙醇脂质体、二元醇脂质体、固体脂质纳米粒均可改善布洛芬透皮能力,但以二元醇脂质体(乙醇-丙二醇=7：3,v/v)的透皮能力为最强,固体脂质纳米粒的滞留能力最强。 (3)布洛芬乙醇脂质体、二元醇脂质体、固体脂质纳米粒及布洛芬二元醇脂质体温敏凝胶均具有良好的稳定性。 (4)体外释放度实验表明,布洛芬二元醇脂质体温敏凝胶较其二元醇脂质体具有明显的缓释作用。皮肤刺激性实验表明,布洛芬二元醇脂质体温敏凝胶未见明显的皮肤刺激性。
[Abstract]:Purpose

( 1 ) Using ibuprofen as model drug , three novel lipid vesicles were prepared and compared with ethanol liposome , glycol liposome and solid lipid nanoparticles .

and ( 2 ) preparing a temperature - sensitive gel by using the transdermal performance superior , and investigating the feasibility of the novel ibuprofen transdermal lipid vesicle temperature - sensitive gel as a transdermal drug preparation .

method

( 1 ) preparing ibuprofen ethanol liposome and dihydric alcohol liposome by adopting an injection method , preparing ibuprofen solid lipid nanoparticles by a high - temperature emulsification - low - temperature curing method , and measuring the morphology , the zeta potential , the particle size and the encapsulation efficiency ;
The ibuprofen lipid vesicles system with excellent transdermal performance was further prepared into temperature - sensitive gel by cold - dissolving method , and the gelation temperature was measured by the method of stirring .

( 2 ) The optimal formulation of ibuprofen ethanol liposome , binary alcohol liposome , solid lipid nanoparticles and lipid vesicle temperature sensitive gel was optimized by single factor test .

( 3 ) The in vitro transdermal properties of ibuprofen ethanol liposome , glycol liposome and solid lipid nanoparticles were investigated by Franz diffusion cell .

( 4 ) The in vitro release of ibuprofen lipid vesicles was determined by dialysis .

( 5 ) The skin irritation of ibuprofen lipid vesicles was investigated by HE staining technique .

( 6 ) the ibuprofen alcohol liposome , the dihydric alcohol liposome and the solid lipid nanoparticles are stored at room temperature and 4 DEG C , the encapsulation rate is measured at 0 , 1 , 2 and 3 months , and the stability is investigated ;
The ibuprofen lipid vesicle temperature - sensitive gel was stored in a 40 鈩，

本文编号：1799795