本文選題：布洛芬 + 乙醇脂質(zhì)體��； 參考：《蘭州大學(xué)》2014年碩士論文

【摘要】：目的 (1)以布洛芬為模型藥物,制備并比較乙醇脂質(zhì)體、二元醇脂質(zhì)體及固體脂質(zhì)納米粒三種新型透皮脂質(zhì)囊泡。 (2)將透皮性能優(yōu)者制備成溫敏凝膠,考察新型布洛芬透皮脂質(zhì)囊泡溫敏凝膠作為經(jīng)皮給藥制劑的可行性。 方法 (1)采用注入法制備布洛芬乙醇脂質(zhì)體和二元醇脂質(zhì)體,以高溫乳化-低溫固化方法制備布洛芬固體脂質(zhì)納米粒,并測定其形態(tài)、Zeta-電位、粒徑和包封率；采用冷溶法將透皮性能優(yōu)的布洛芬脂質(zhì)囊泡系統(tǒng)進一步制備成溫敏凝膠,并采用攪拌子法測定其膠凝溫度。 (2)采用單因素試驗優(yōu)化布洛芬乙醇脂質(zhì)體、二元醇脂質(zhì)體、固體脂質(zhì)納米粒及其脂質(zhì)囊泡溫敏凝膠的最優(yōu)處方。 (3)通過Franz擴散池考察布洛芬乙醇脂質(zhì)體、二元醇脂質(zhì)體及固體脂質(zhì)納米粒的體外透皮性能。 (4)采用透析法測定布洛芬脂質(zhì)囊泡溫敏凝膠的體外釋放度。 (5)采用HE染色技術(shù)考察布洛芬脂質(zhì)囊泡溫敏凝膠對小鼠的皮膚刺激性。 (6)將布洛芬乙醇脂質(zhì)體、二元醇脂質(zhì)體及固體脂質(zhì)納米粒置于室溫和4℃下保存,于0、1、2和3個月時測定其包封率,考察其穩(wěn)定性；將布洛芬脂質(zhì)囊泡溫敏凝膠置于40℃恒溫箱和-20℃冰箱中避光保存,于第5、10天取樣,觀察外觀性狀,測定藥物含量及膠凝溫度,考察其穩(wěn)定性。 結(jié)果 (1)布洛芬乙醇脂質(zhì)體、二元醇脂質(zhì)體(乙醇-丙二醇=7：3,v/v)及固體脂質(zhì)納米粒均呈球形或類球形,平均粒徑分別為(108±4.3)nm、(103±5.6)nm和(195.2±16.88)nm,Zeta電位分別為(-9.8±4)mv、(-8.25±3.2)mv和(-22.3±6.94)mv,3種最優(yōu)處方對布洛芬的包封率分別為(72.93±1.12)%、(73.58±1.35)%和(73.61±1.42)%。 (2)在布洛芬二元醇脂質(zhì)體中,藥物的經(jīng)皮滲透性能隨乙醇和丙二醇的比例不同而不同,當(dāng)乙醇與丙二醇比例為7：3時制得的布洛芬二元醇脂質(zhì)體透皮能力最強。 (3)布洛芬乙醇脂質(zhì)體和二元醇脂質(zhì)體(乙醇-丙二醇=7：3,v/v)的累計滲透百分?jǐn)?shù)分別是固體脂質(zhì)納米粒的8.95倍和16.35倍；24h后固體脂質(zhì)納米粒在皮膚中的藥物滯留量大于乙醇脂質(zhì)體和二元醇脂質(zhì)體,有顯著性差異(P0.01) (4)以32.2%泊洛沙姆407和3.22%泊洛沙姆188溶液制備的布洛芬二元醇脂質(zhì)體溫敏凝膠的膠凝溫度為(32.0±1.1)℃,且其體外釋放度與布洛芬二元醇脂質(zhì)體相比有較為顯著的緩釋效果。 (5)皮膚組織病理學(xué)實驗結(jié)果表明布洛芬二元醇脂質(zhì)體溫敏凝膠未引起小鼠皮膚組織結(jié)構(gòu)的明顯改變。 (6)布洛芬乙醇脂質(zhì)體、二元醇脂質(zhì)體、固體脂質(zhì)納米粒分別放置于室溫和4℃保存3個月后,包封率均未見明顯改變；布洛芬二元醇脂質(zhì)體溫敏凝膠置于40℃恒溫箱和-20℃冰箱中避光保存10天后,其外觀性狀、藥物的含量及膠凝溫度均未發(fā)生明顯改變。 結(jié)論 (1)布洛芬乙醇脂質(zhì)體、二元醇脂質(zhì)體(乙醇-丙二醇=7：3,v/v)、固體脂質(zhì)納米粒均呈球形或類球形,三者間的包封率無顯著性差異。 (2)乙醇脂質(zhì)體、二元醇脂質(zhì)體、固體脂質(zhì)納米粒均可改善布洛芬透皮能力,但以二元醇脂質(zhì)體(乙醇-丙二醇=7：3,v/v)的透皮能力為最強,固體脂質(zhì)納米粒的滯留能力最強。 (3)布洛芬乙醇脂質(zhì)體、二元醇脂質(zhì)體、固體脂質(zhì)納米粒及布洛芬二元醇脂質(zhì)體溫敏凝膠均具有良好的穩(wěn)定性。 (4)體外釋放度實驗表明,布洛芬二元醇脂質(zhì)體溫敏凝膠較其二元醇脂質(zhì)體具有明顯的緩釋作用。皮膚刺激性實驗表明,布洛芬二元醇脂質(zhì)體溫敏凝膠未見明顯的皮膚刺激性。
[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，

本文編號：1799795