酮洛芬脂质体凝胶的研制及体外经皮渗透动力学考察

目的:研制酮洛芬(KPF)脂质体凝胶,并进行体外经皮渗透动力学研究。方法:通过均匀实验设计筛选KPF脂质体的最佳处方,采用薄膜分散法制备脂质体,再以泊洛沙姆-407为基质制成脂质体凝胶;以影响因素试验考察该制剂的稳定性,并用Franz扩散池研究KPF脂质体凝胶与KPF普通凝胶的经皮渗透规律。结果:KPF脂质体平均粒径为(886.2±12.08) nm,Zeta电位为(-15.05±2.36)mV,平均包封率为(76.13±1.27)%(n=3);KPF脂质体凝胶为类白色细腻粘稠胶体,对试验光照及温度条件稳定。体外透皮试验表明脂质体能促进药物的透皮吸收,脂质体凝胶在皮肤中的蓄积量为普通凝胶的2倍。结论:KPF脂质体凝胶制备工艺可行,质量稳定,检测方法可靠,能促进药物透皮渗透,值得进一步研究。     

甲氨蝶呤柔性纳米脂质体凝胶的构建及体外经皮渗透性研究

目的 制备甲氨蝶呤(methotrexate,MTX)柔性纳米脂质体凝胶,并研究其体外经皮渗透行为.方法 采用逆向蒸发法制备MTX柔性纳米脂质体,以卡波姆940为基质制成脂质体凝胶,并考察其初步稳定性;Franz扩散池研究MTX柔性纳米脂质体凝胶与普通凝胶的经皮渗透规律.结果 脂质体凝胶4℃下稳定性良好;体外透皮试验表明,MTX柔性纳米脂质体凝胶的累积透过量明显＜MTX普通凝胶(P＜0.05),皮肤滞留量＞MTX普通凝胶(P＜0.05).结论 MTX柔性纳米脂质体凝胶可显著提高药物的皮肤滞留量,而不增加药物进入血液循环的量,能有效降低药物潜在的全身毒性,有望成为MTX局部治疗的新剂型.     

丁卡因脂质体凝胶剂的研究

目的:研制丁卡因脂质体凝胶剂,为临床新制剂的开发提供参考。方法:以逆相蒸发—超声法等制备丁卡因脂质体凝胶剂;并采用改良Franz扩散池体外经皮渗透实验技术,对丁卡因脂质体凝胶剂及其普通凝胶剂的经皮渗透作用进行了比较。结果:丁卡因脂质体平均粒径为105.5 nm,平均包封率为 63.8％;体外透皮实验中,12 h累积透皮吸收百分率(Q％)为34.6％,明显高于普通凝胶制剂(17.7％);皮内药物滞留百分率(Q_滞％)分别为24.6％,明显高于普通凝胶制剂(0.65％)。结论:丁卡因脂质体凝胶剂有望成为适于临床给药的一种新剂型。     

伊曲康唑柔性脂质体的制备及体外性能研究

摘要：目的:制备伊曲康唑柔性脂质体,并考察其体外透皮性能。方法:以大豆卵磷脂为成膜材料和聚山梨酯80为边缘活化剂,薄膜分散法制备伊曲康唑柔性脂质体,考察粒径、Zeta电位、包封率、载药量及稳定性。采用Franz扩散池,以大鼠皮肤为透皮屏障,考察伊曲康唑柔性脂质体及其溶液的体外透皮性能差异。结果:伊曲康唑柔性脂质体平均粒径为（222.5±15.34） nm,多分散系数（PDI）为（0.226±0.09）,Zeta电位为（-5.09±1.52） m V,平均包封率为（83.80±2.18）%。体外透皮实验表明,伊曲康唑脂质体中伊曲康唑12 h的累积渗透量(Q12)是伊曲康唑溶液的2.21倍;渗透速率(Jss)是伊曲康唑溶液的2.20倍;皮肤滞留量（Qs）是伊曲康唑溶液的6.2倍。结论:伊曲康唑柔性脂质体可显著提高伊曲康唑的体外累积透皮量和皮肤滞留量,有望成为新型局部给药制剂。     

基于D-最优混料设计法的塞来昔布微乳凝胶处方优化与评价

目的 制备塞来昔布微乳凝胶，并考察其体外透皮性能。方法 测定塞来昔布在不同油、乳化剂、助乳化剂中的溶解度，通过绘制伪三元相图确定塞来昔布微乳的处方组成；以油相、混合乳化剂、水为考察因素，微乳的载药量和粒径为评价指标，利用D-最优混料设计法优化塞来昔布微乳的处方；以卡波姆980为基质制备塞来昔布微乳凝胶，并测定粒径、粒度分布、Zeta电位、透光率及黏度，透射电镜观察塞来昔布微乳的外观形态；采用Franz扩散池法考察塞来昔布微乳凝胶的体外释放性能。结果 优化的塞来昔布微乳处方组成为油相4%、混合乳化剂20%、水76%；塞来昔布微乳凝胶的平均粒径为（59.65±1.09）nm，PDI为0.106，Zeta电位为（-25.76±0.92）mV；透射电镜观察微乳凝胶呈圆整、规则球形，分布较为均匀；与微乳相比，塞来昔布微乳凝胶黏度增大，便于涂布和经皮给药；塞来昔布微乳凝胶24 h累积透皮释放量为（80.12±3.37）μg·cm^-2，显著高于塞来昔布混悬液。结论 塞来昔布微乳凝胶可以显著增加药物的累积透皮量，有望成为新型局部给药制剂。     

马钱子总碱脂质体凝胶的制备及其体外透皮作用

目的：制备马钱子总碱脂质体凝胶,研究马钱子总碱脂质体凝胶体外透皮特点。方法：采用硫酸铵梯度法制备马钱子总碱脂质体,以泊洛沙姆407为基质制备成脂质体凝胶,采用Franz扩散池比较马钱子总碱脂质体凝胶和普通凝胶的经皮渗透性和皮肤滞留量。结果：马钱子总碱脂质体的平均粒径为140 nm,其中马钱子碱的包封率为82.2%,士的宁的包封率为90.3%。体外透皮实验表明,脂质体凝胶能缓慢的透过小鼠皮肤,皮肤滞留量大于普通凝胶。结论：脂质体是马钱子总碱经皮吸收的理想载体。     

5-氟尿嘧啶脂质体凝胶剂的制备和评价

目的 研制5-氟尿嘧啶(5-Fu)脂质体凝胶剂,并进行质量评价.方法 采用逆相蒸发-冻融法制备5-Fu脂质体,再用卡波普为基质制成凝胶剂;以离心法测定脂质体的包封率;以体外经皮渗透释药法,比较5-Fu脂质体凝胶剂及5-Fu普通凝胶剂中的经皮渗透作用.结果 5-Fu脂质体平均粒径为2.16±0.30μm,平均包封率为(56.17±2.52)%;体外透皮实验中,脂质体凝胶剂24h的药物浓度为158.6 mg·mL-1,明显高于普通凝胶剂91.2mg·mL-1.结论 载药脂质体凝胶剂可显著减少药物经皮吸收,可维持较长释药时间.     

盐酸利多卡因脂质体凝胶剂的体外透皮扩散研究

目的 对盐酸利多卡因(lidocaine hydrochloricde,LDH)脂质体凝胶剂体外透皮量、皮肤层滞留量进行评价.方法 超声法制备LDH脂质体,再用卡波普为基质制成凝胶剂;以体外经皮渗透释药法,比较LDH脂质体凝胶剂及LDH凝胶剂中的经皮渗透规律.结果 平均包封率为(83.4±1.81)%;LDH 凝胶剂的渗透符合Higuchi方程,其中脂质体凝胶剂24h内药物渗透速率为770.32μ g·h-1,明显高于游离药物凝胶渗透率280.01μg·h-1.结论 载药脂质体凝胶剂可显著促进药物经皮吸收,为经皮吸收药物的理想载体.     

丹皮酚脂质体凝胶剂的透皮作用机制考察

目的 研究丹皮酚脂质体凝胶的体外透皮扩散作用。方法 采用Franz扩散池,以大鼠皮肤进行体外经皮渗透试验,考察丹皮酚脂质体凝胶的经皮渗透行为及皮肤内药物滞留量。结果 制得的丹皮酚脂质体凝胶包封率为78.62%,平均粒径为127 nm。体外经皮渗透试验表明,与丹皮酚凝胶相比,丹皮酚脂质体凝胶透皮速率较慢,但皮肤中药物滞留量明显增加。结论 丹皮酚脂质体凝胶制备工艺可行,其体外释放有明显缓释特征,有望成为丹皮酚应用的新剂型。     

尼莫地平脂质体的制备及体外透皮研究

目的:采用2种方法制备尼莫地平脂质体,并考察其包封率与体外透皮性。方法:用薄膜法和乙醇注入法制备尼莫地平脂质体,考察2种方法所制脂质体的粒径分布及包封率;采用Franz扩散装置对脂质体进行体外透皮试验,并与尼莫地平溶液比较。结果:薄膜法和乙醇注入法制备的脂质体平均粒径分别为(768.7±190.6)、(1 742±270)nm,平均包封率均高达97%以上。与尼莫地平溶液比较,脂质体中药物透皮缓慢,其中以薄膜法制备的脂质体在48h以后其单位面积累积透皮量显著更高。结论:2种制备方法中以薄膜法更优。     

博莱霉素脂质体凝胶的制备和体外透皮性比较

目的：研制博莱霉素（BLM）脂质体凝胶,并对其皮肤靶向性进行体外评价。方法：采用逆相蒸发-冻融法制备BLM脂质体,再用卡渡姆940为基质制成BLM脂质体凝胶;以离心法测定BLM脂质体的包封率;以体外透皮渗透释药法,比较BLM脂质体凝胶与BLM普通凝胶的透过作用。结果：BLM脂质体平均粒径为（885．20±12．08）nm,平均包封率为（66．80±1．38）％。在24h内,BLM脂质体凝胶累积透过量（Q）及稳态透皮速率（J）与BLM普通脂质体相比,均明显提高,而在皮肤中的滞留药量也显著提高（P〈0．05）。结论：BLM脂质体凝胶在体外可显著增加BLM的透皮吸收,增加皮肤中的滞留量,值得进一步研究。     

Enhanced transdermal delivery of acyclovir sodium via elastic liposomes

The elastic liposomes bearing acyclovir sodium were prepared for its enhanced transdermal delivery by conventional rotary evaporation method and characterized for various parameters such as vesicle shape and surface morphology, size and size distribution, entrapment efficiency, elasticity, polydispersity index, turbidity and in vitro release pattern. Permeability studies of acyclovir sodium incorporated in elastic liposomes were performed across artificial membranes and rat skin. Skin permeation potential of the developed formulation was assessed using confocal laser scanning microscopy, that revealed an enhanced permeation of the formulation to the deeper layers of the skin (up to 160 microm) following channel like pathways. Skin permeation profile of elastic liposomal formulation bearing acyclovir sodium was observed and the investigations revealed an enhanced transdermal flux (6.21 +/- 1.8 microg/cm(2)/hr) and decreased lag time (0.6 hr) for acyclovir sodium. The obtained flux was nearly 2.0 and 6.3 times higher than conventional liposomal formulation bearing acyclovir sodium and plain drug solution, respectively (p < 0.01). The elastic liposomal formulation for transdermal delivery of acyclovir sodium provides better transdermal flux, higher entrapment efficiency, ability as a self-penetration enhancer and effectiveness for transdermal delivery as compared with conventional liposomes. In vivo studies showed that on transdermal application of elastic liposomes, the concentration of acyclovir sodium in plasma was found to be 105 +/- 9.4 ng/ml after 24 hr which is about 4.2 times compared with conventional liposomes. Thus it is concluded that the elastic liposomes may be promising vehicles for the transdermal delivery of acyclovir sodium.     

Hyaluronic acid gel-core liposomes (hyaluosomes) enhance skin permeation of ketoprofen

Since FDA approval of the first transdermal patch in 1979, the utilizing of skin as a route of systemic drug administration has attracted the attention of the formulation scientists. The liposomes research in the area of transdermal drug delivery has been around for decades. This study aimed at comparing the latest gel-core liposomes (hyaluosomes) with nonconventional liposomal systems such as propylene glycol (PG)-liposomes, ethosomes, transferosomes and conventional liposomes loaded with ketoprofen. The modified thin-film hydration method was used to prepare these liposomal systems; size, zeta potential, EE%, TEM, rheological properties, in vitro release and ex vivo permeation studies were performed. Vesicle size and PDI ranged from 160?nm to 700?nm and 0.15 to 0.5, respectively. More interestingly, thermal gelation and shear-thinning characteristics were only recorded with hyaluosomes; while Newtonian behavior and low viscosity values (2 mPas.s to 6?mPa.s) were shown with all other liposomal systems. Hyaluosomes recorded superior (3-fold increases) transdermal permeation characteristics (flux and permeability coefficient), compared with other liposomal systems. With the advancement in liposomal sciences, this study warrants hyaluosomes as a promising transdermal liposomal system for favorable rheological characteristics as well as superior transdermal permeation that proved greater capacity than conventional and other non-conventional liposomal systems.     

吡喹酮脂质体凝胶的研制及其体外透皮扩散研究

目的：研制吡喹酮（PQ）的脂质体凝胶（PQ—LG）,并对其体外释药特性进行考察。方法：薄膜分散法制备PQ脂质体,以泊洛沙姆-407为凝胶基质,研制PQ—LG。采用均匀设计对PQ—LG的处方及制备工艺进行优化,对其体外主要性质进行考察,并采用鼠皮为吸收屏障,对其体外透皮透皮速度及程度进行评价。结果：PQ—LG的最佳处方及工艺条件为：类脂／药物为20：1,pH为6．5,蒸发温度为45℃,水化时间为30min。体外性质表明PQ—LG外形圆整,平均粒径为（866．6±18．8）nm,平均包封率（ER）为74．33±1．95％（n=3）;体外透皮实验表明PQ．LG的透皮累积透过量Q符合Higuehi方程：Q=34．15t1/2 2．76（r=0．9948）,与PQ凝胶相比,Q及稳态透皮速率J均有明显提高（P〈0．05）。结论：PQ—LG具有制备简单,质量理想,透皮吸收好等特点,值得进一步进行体内研究。     

酮洛芬二元醇质体凝胶的研制及其质量考察

目的:研制酮洛芬二元醇质体凝胶,并对其质量进行考察.方法:采用乙醇注入法制备酮洛芬二元醇质体,采用研和法制备醇质体凝胶;透析法测定包封率;Franz扩散池进行离体皮肤渗透试验,测定其体外累积渗透量及皮内滞留量;并对其体外稳定性进行了初步考察.结果:酮洛芬二元醇质体形态圆整,平均粒径为(289.86±44.75)nm,平均包封率为(73.85±2.62)%.体外透过皮肤进入接收液中的二元醇质体(乙醇/丙二醇=7:3)累积渗透量为一元醇质体的1.8倍,24 h时二元醇脂质体和醇质体皮肤中药物滞留量分别为(52.33±3.12)μg·cm-2和(40.25±2.85)μg·cm-2.在实验期内,体外稳定性较好.结论:酮洛芬二元醇质体具更好的透皮吸收性及皮肤滞留性,且质量稳定.     

喷他佐辛压敏胶分散型贴剂的制备研究

目的研制喷他佐辛压敏胶分散型贴剂并考察其体外经皮渗透性。方法将喷他佐辛及各种促渗剂直接溶于压敏胶中制备压敏胶分散型贴剂,采用卧式双室扩散池,研究其体外经皮渗透行为。结果由Duro-Tak 87-9301型压敏胶制备的贴剂具有较好的稳态渗透速率。5%氮酮与10%豆蔻酸异丙酯合用对喷他佐辛促渗效果明显,经皮渗透速率为(11.28±0.63)μg/(cm2.h),促渗倍率达3.01倍。贴剂中喷他佐辛的含量由2%增加到4%,经皮渗透速率明显增大,含量增加到6%和8%时渗透速率无明显变化。结论所得处方中各因素的组合有利于喷他佐辛的经皮吸收。     

氯雷他定包合物凝胶的体外透皮研究

目的:制备氯雷他定包合物凝胶,并进行体外透皮研究。方法:将氯雷他定与羟丙基-β-环糊精(HP-β-CD)形成包合物后再制成凝胶;采用Franz扩散池,以离体鼠皮为透皮屏障进行体外透皮扩散试验,比较氯雷他定包合物凝胶(实验组)与加入1%氮酮透皮促进剂(阳性组)及不含促透剂(阴性组)的氯雷他定凝胶的稳态透皮速率(J)。结果:所制包合物凝胶外观光滑、细腻,黏度适宜;实验组与阳性组的J值分别为(17.82±0.569)、(18.44±0.952)μg.cm-2·h-1,两者比较无显著性差异(P>0.05),但与阴性组((6.180±0.214)μg·cm-2·h-1)比较均具有显著性差异(P<0.05)。结论:氯雷他定与HP-β-CD形成包合物后能提高氯雷他定凝胶透皮性。     

不同促渗剂对马钱子碱贴剂体外透皮吸收的影响

目的:研究不同促渗剂对马钱子碱贴剂体外透皮促渗作用的影响.方法:采用不同浓度、不同种类促渗剂制备马钱子碱贴剂;采用改良Franz扩散池,以离体雄性大鼠皮肤为模型,通过高效液相色谱法测定药物浓度,拟合马钱子碱透皮吸收的累积透过量和透过速率.结果:以3%氮酮制备的马钱子碱贴剂具有较好的体外透过速率及累积透过量;促渗剂合用时...     

Elastic liposomes mediated transdermal delivery of an anti-hypertensive agent: propranolol hydrochloride

One major problem encountered in transdermal drug delivery is the low permeability of drugs through the skin barrier. In the present investigation ultradeformable lipid vesicles, that is, elastic liposomes were prepared incorporating propranolol hydrochloride for enhanced transdermal delivery. Elastic liposomes bearing propranolol hydrochloride were prepared by conventional rotary evaporation method and characterized for various parameters including vesicles shape and surface morphology, size and size distribution, entrapment efficiency, elasticity, turbidity, and in vitro drug release. In vitro flux, enhancement ratio (ER), and release pattern of propranolol hydrochloride were calculated for transdermal delivery. In vivo study conducted on male albino rats (Sprague Dawley) was also taken as a measure of performance of elastic liposomal, liposomal, and plain drug solution. The better permeation through the skin was confirmed by confocal laser scanning microscopy (CLSM). Results indicate that the elastic liposomal formulation for transdermal delivery of propranolol hydrochloride provides better transdermal flux, higher entrapment efficiency, ability as a self-penetration enhancer and effectiveness for transdermal delivery as compared to liposomes.