美洛昔康脂质体凝胶剂的研制与质量评价

目的 制备含有美洛昔康的脂质体凝胶,并进行质量初步评价.方法用正交设计优选该脂质体的处方及制备工艺,并用扫描电镜观测其外观、大小及分布,用微型凝胶柱测定其包封率,并进一步制备成凝胶,初步考察该制剂的稳定性.结果所得脂质体外观圆整,分布较均匀,平均包封率(67.8±1.2)%(n=3),所得凝胶剂为半透明黏稠状胶体,稳定性良好.结论 该脂质体凝胶制备工艺可行,具有开发价值.     

复方克林霉素脂质体凝胶的制备及体外透皮释药研究

目的制备复方克林霉素脂质体凝胶并考察其粒径分布、包封率及体外透皮特性。方法采用薄膜分散法制备复方克林霉素脂质体,利用透射电镜观察其形态,用激光纳米粒度仪测定其粒径大小及分布,用HPLC法测定其包封率。将脂质体进一步制成凝胶剂后,考察其体外透皮情况。结果复方克林霉素脂质体的粒径在240nm左右,分布均匀,平均包封率为51.24%;脂质体中的克林霉素能缓慢透过大鼠皮肤,缓释效果明显。结论该制剂制备工艺简单,性质稳定,药物包封率较高,定量测定方法简便、准确;药物透皮速率缓慢,释药稳定。     

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。     

塞来昔布脂质体凝胶的研制及其体外经皮渗透动力学考察

目的研制塞来昔布脂质体凝胶,并对其体外经皮渗透动力学进行考察。方法采用薄膜分散法制备塞来昔布脂质体,均匀设计筛选最佳处方及制备工艺,并以卡波姆940为基质制成脂质体凝胶;用Franz扩散池研究塞来昔布脂质体凝胶与塞来昔布普通凝胶的经皮渗透规律。结果塞来昔布脂质体凝胶的平均粒径为(369.5±10.8)nm,平均包封率为(81.6±2.2)%(n=3);体外透皮试验表明塞来昔布脂质体凝胶的累积透过量显著大于普通凝胶(P<0.05),药物透皮速率与皮肤蓄积量显著大于普通凝胶(P<0.01)。结论塞来昔布脂质体凝胶制备简单,能促进药物透皮吸收,值得进一步研究。     

紫杉醇脂质体凝胶剂的制备及其镇痛抗炎作用

目的制备紫杉醇脂质体凝胶剂,对其镇痛抗炎作用进行初步研究。方法薄膜分散法制备紫杉醇脂质体,用透射电镜观测其形态,用激光纳米粒度仪测定粒径大小及分布,用HPLC测定其包封率。脂质体进一步制成凝胶剂后,体外透皮实验测定其不同时间的体外透皮量,考察其体外透皮情况。大鼠角叉菜胶致足肿胀模型及小鼠甲醛致痛模型,考察紫杉醇脂质体凝胶剂的镇痛抗炎作用。结果制得的紫杉醇脂质体形态规则、分布均匀,平均包封率为(73.6±0.3)%(n=3),所得凝胶呈半透明状;体外透皮实验中,紫杉醇脂质体凝胶剂符合一级动力学方程,起到较好的缓释作用。抗炎实验中,与模型组比较,各给药组在一定时间内均能显著性减轻致炎足趾的肿胀程度(P<0.05),并呈现明显的量效关系。甲醛致痛实验中,给药组与模型组比较,小鼠舔足次数明显减少(P<0.05)。结论紫杉醇脂质体凝胶具有明显镇痛抗炎作用。     

阿西美辛脂质体凝胶剂的研制

目的研制阿西美辛脂质体凝胶剂,并进行评价.方法采用不同方法、不同药-脂比处方制备脂质体,然后对其包封率进行比较,从而优选出最佳制备方法与最佳处方,并进一步制备成脂质体凝胶剂;采用HPLC测定制剂中阿西美辛的含量,葡聚糖凝胶柱结合HPLC测定制剂中阿西美辛的包封率;考察了制剂的皮肤刺激性与初步稳定性.结果制剂的含量控制在0.09%～0.110%范围之内;平均包封率为(58.76±12.47)%;无皮肤刺激性;不易高温贮存,对光不稳定.结论经初步评价,所制备的阿西美辛脂质体制备方法可行、简便、质量稳定.     

维生素D2脂质体凝胶剂的体外透皮扩散

目的：本文探讨了包封于脂质体中的维生素D2体外透皮扩散能力的变化。方法：将维生素D2包封于脂质体中。并进一步制备成羧甲基纤维素钠的凝胶剂,与未包封于脂质体中的维生素D2的羧甲基纤维素钠凝胶剂比较,进行了大鼠离体皮肤的扩散实验,比较不同类型的脂质体对维生素D2透皮的影响。结果：维生素D2在游离状态下,不易进入皮肤层,维生素D2脂质体可使维生素D2在皮肤层中滞留,而且多室脂质体凝胶剂比单室脂质体凝胶剂在皮肤层中维生素D2的滞留量多。结论：脂质体作为维生素D2皮肤局部给药的载体。能够提高对皮肤的穿透力。     

紫杉醇纳米脂质体凝胶剂的制备及体外透皮研究

目的制备紫杉醇纳米脂质体凝胶剂,考察其粒径、粒径分布、包封率、体外释放度及透皮特性。方法采用薄膜蒸发高压微射流法制备紫杉醇纳米脂质体,以卡波姆为凝胶基质,研制紫杉醇纳米脂质体凝胶剂,采用正交试验探索最佳工艺。用粒径测定仪测定脂质体的粒径及其粒径分布,低速-超速相结合法测定包封率,透析膜扩散法进行体外释放试验,以离体小鼠皮结合改良Franz扩散装置考察其体外透皮特性。结果紫杉醇纳米脂质体的最佳工艺:卵磷脂的含量为2%,药物与磷脂质量比为1∶30,磷脂与胆固醇的质量比为10∶1。测得的粒径为81.8 nm;粒径分布系数为0.180;平均包封率73.2%。纳米脂质体凝胶剂72 h累积释放百分率为79.04%;48 h的单位面积累积渗透量为429.68μg·cm?2。结论该制剂制备工艺简单,易于涂布,具有较高的包封率,粒径较小且分布均匀,体外释放缓慢。纳米脂质体能促进脂溶性药物紫杉醇透过皮肤。     

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。     

阿西美辛脂质体凝胶剂的体外透皮扩散研究

目的探究分析阿西美辛（ACM）脂质体凝胶剂的体外透皮扩散效果。方法使用离体鼠皮进行试验,在离体鼠皮上面使用阿西美辛脂质体凝胶剂还有阿西美辛凝胶剂,对比2种药物在不同时间点的体外透皮量、凝胶层滞留量还有皮肤层滞留量等数据,对比2种制剂的体外透皮规律,归纳其体外透皮扩散效果。结果2种制剂体外透皮扩散效果对比具有显著差异性（P〈0．05）,阿西美辛脂质体凝胶剂头皮扩散行为相对于阿西美辛凝胶剂更具有优越性,在24h透过药量累积达到40％,而相对于阿西美辛凝胶剂其皮肤层里面的滞留量也更具有优越性;而ACM没有经过包封则难以穿透皮肤,会有大量剂量依然存留在凝胶剂当中。结论使用阿西美辛脂质体凝胶剂能够使得药物透皮量极为显著的提高,是一种阿西美辛的外用新型制剂,值得临床推广。     

乌拉草总黄酮脂质体凝胶剂的制备工艺研究

目的 优化乌拉草总黄酮脂质体凝胶剂的制备工艺,并进行质量评价。方法 乙醇注入法制备乌拉草总黄酮（CMTF）脂质体,以包封率为指标,正交试验优化处方;以脂质体凝胶剂的外观、涂展性、均匀度、黏稠度等综合评分为指标,采用Box-Behnken响应面法优化CMTF脂质体凝胶的处方及制备工艺。通过观察性状、pH值、铺展性及可洗除性,以及离心试验、耐寒及耐热试验,考察CMTF脂质体凝胶稳定性;观察其对大鼠正常及破损皮肤的刺激性。结果 CMTF脂质体的最佳制备工艺为：大豆磷脂与胆固醇的质量比为5：3,大豆磷脂与CMTF的质量比为4：1,注入体积比例1：10;平均包封率为89.41%,粒径为（119.7±3.82）nm,Zeta电位为（-20.80±0.40）mV。CMTF脂质体凝胶剂的最佳处方为：1 g CMTF脂质体、2 g卡波姆940、20 g甘油、2 g三乙醇胺、10 mL水,该脂质体凝胶剂的稳定性良好,无皮肤刺激性。结论 优化后的CMTF脂质体凝胶制备工艺简单,质量稳定,为CMTF经皮制剂的开发提供依据。     

胸腺五肽脂质体的处方及制备工艺研究

目的研究胸腺五肽脂质体的处方筛选及制备工艺。方法采用逆向蒸发法制备胸腺五肽脂质体,超速离心法测其包封率,以包封率和粒径为指标,采用正交试验设计法优化处方,并对其表面特征、包封率、粒径等情况进行考察。结果最佳处方制备的胸腺五肽脂质体平均粒径为108.2 nm,药物的平均包封率为62.10%,Zeta电位为-48 mV,脂质体外观圆整均匀,分散性好。结论所制胸腺五肽脂质体工艺简单、重现性好,粒径小,包封率较高,为其进一步研究奠定了基础。     

天蟾胶囊联合羟考酮治疗中度癌痛的疗效观察

目的 优化苦参总黄酮脂质体凝胶剂的制备工艺,并进行质量评价。方法 薄膜分散制备苦参总黄酮脂质体,以苦参总黄酮的包封率为指标,正交试验优化处方;以脂质体凝胶剂的成型性、涂展性、光泽度、均匀度、pH值及稳定性等综合评分为指标,星点设计-效应面法优化苦参总黄酮脂质体凝胶的处方及制备工艺;通过离心试验、低温试验、热恒温试验考察苦参总黄酮脂质体凝胶剂稳定性,检测其pH值。结果 苦参总黄酮脂质体的最佳处方为：卵磷脂与胆固醇比为9：1,磷酸缓冲盐pH值为7.0,苦参总黄酮的质量为0.05 g;平均包封率83.45%,平均粒径173.00 nm。苦参总黄酮脂质体凝胶剂最佳处方为：卡波姆0.20 g、甘油2.59 g、三乙醇胺0.20 g,其脂质体凝胶剂的稳定性良好,当温度超过60℃时,凝胶剂的颜色变浅,pH值为6.53。结论 优化后的苦参总黄酮脂质体凝胶制备工艺简单可行,质量稳定,为苦参总黄酮经皮制剂的开发提供依据。     

异甘草素脂质体的制备及稳定性考察

目的:制备异甘草素脂质体并考察其包封率及稳定性.方法:采用超声波薄膜分散法制备异甘草素脂质体,正交设计优选制备工艺;透射电镜观察形态;激光粒径仪测定平均粒径;葡聚糖凝胶层析法分离含药脂质体与游离药物并测定包封率;离心加速实验考察脂质体的稳定性.结果:异甘草素脂质体的平均粒径为233.1 nm,跨距为0.74,平均包封率为82.57%,稳定性良好.结论:该法制备异甘草素脂质体工艺可行,质量稳定.     

辣椒素脂质体凝胶剂的制备与释放度的测定

目的研究辣椒素(capsaicin,CAP)脂质体以及脂质体凝胶的制备方法,并考察脂质体及脂质体凝胶对药物释放的影响。方法采用超声-薄膜分散法制备CAP脂质体,以卡波姆-941为基质制备脂质体凝胶。采用透析膜扩散法进行体外释放实验,以高效液相色谱法测定CAP的累积释放量,比较CAP脂质体凝胶以及CAP凝胶对CAP释放的影响。结果 CAP脂质体包封率为67.71%(n=3),脂质体凝胶中药物释放均符合Higuchi方程,Q=752.13t1/2+1 044.32(r=0.987 8),渗透速率为752.13μg·mL·h1/2,显著高于CAP凝胶的渗透速率268.41μg·mL·h1/2。结论辣椒素脂质体凝胶剂对药物有缓释作用,可延长药物作用时间。     

Physicochemical characterization and skin permeation of liposome formulations containing clindamycin phosphate

This study was undertaken to evaluate the physicochemical properties and skin permeation of liposome formulations containing clindamycin phosphate (CP), especially when charge was imparted to the liposome. Five different liposome formulations were prepared using Phospholipon 85G (PL) and cholesterol (CH) by conventional lipid film hydration technique. Molar ratio of CH to PL was varied in the range of 0.16–1.0. Charged liposomes were prepared in the same way with addition of 1,2-dioleoyl-3-trimethylammonium-propane chloride salt (DOTAP) and 1,2-dimyristoyl-sn-glycero-3-phosphate monosodium salt (DMPA) as charge carrier lipid for cationic or anionic charge of the liposome, respectively. Fresh full-thickness mice skin was taken and used for skin permeation study using Keshary-Chien diffusion cell with 1.77 cm² diffusion area at 37°C. All liposome formulations prepared showed homogeneous size distribution with mean particle size of about 1 μm or less. Among the five liposome formulations prepared, formulation with the molar ratio of 0.5 showed the best result in the physicochemical properties such as polydispersity index, entrapment efficiency, size evolution, and ability of the liposome to retain CP as of entrapped in the vesicles. Charge-impartation of the formulation with cationic charge carrier lipid resulted in additional benefit in terms of inhibition of size evolution, the ability of the liposome to retain CP in the vesicles, and skin permeation. Steady state flux of the drug through the mice skin in the cationic liposome vesicles was 0.75 ± 0.01 μg/cm²h while that in the control (dissolved into mixed alcohol solution) was 0.17 μg/cm²h. One half molar ratio of CH to PL was optimal in terms of physicochemical properties of the liposome formulation containing CP, and incorporation of cationic charge carrier lipid appeared to provide additional benefits for the stability of the liposome formulation and skin permeation of the drug.     

Development, characterization and in vivo evaluation of benzocaine-loaded liposomes.

This study reports the development and in vivo evaluation of a liposomal formulation of the local anaesthetic benzocaine. Multi-lamellar (MLV) and small uni-lamellar (SUV) vesicles entrapping benzocaine were prepared using 50:50 w/w phosphatidylcholine-cholesterol as lipophilic phase and 50:50 v/v ethanol-water as hydrophilic phase. Liposome size, Zeta-potential, encapsulation efficiency and skin penetration properties were determined. Drug permeation from liposomal dispersions, as such or formulated in Carbopol gel, was evaluated through artificial lipophilic membranes and excised abdominal rat skin, whereas in vivo anaesthetic effect was tested on rabbits. Interestingly, addition of the drug into the hydrophilic phase, rather than into the lipophilic one, during liposome preparation enabled an improvement of the MLV's entrapment efficiency from 29.7% to 82.3%. On the other hand, sonication conditions to obtain SUV influenced size and polydispersity index of the vesicles and reduced the entrapment efficiency by about 30%. All liposomal-benzocaine formulations showed sustained release properties and a more intense anaesthetic effect than plain drug. Permeation experiments from drug solutions in gel containing the same amount of ethanol as in the liposomal formulations made it possible to exclude a possible enhancer effect of this solvent, at least when not used in liposomal formulations. MLV with the drug added into the hydrophilic phase gave the most effective formulation, showing a permeability coefficient value 2.5 times higher than that of the plain drug and allowing a significant improvement (P<0.01) not only of intensity but also of duration of anaesthetic effect of benzocaine. These results suggest that a suitably developed liposomal formulation of benzocaine can be of actual value for improving its clinical effectiveness in topical anaesthesia.     

Development of vitamin loaded topical liposomal formulation using factorial design approach: drug deposition and stability

Long-term exposure of the skin to UV light causes degenerative effects, which can be minimized by using antioxidant formulations. The major challenge in this regard is that a significant amount of antioxidant should reach at the site for effective photoprotection. However, barrier properties of the skin limit their use. In the present study, Vitamin E acetate was encapsulated into liposome for improving its topical delivery. However preparation of liposomes is very difficult due to number of formulation variables involved therein. In the present work systematic statistical study for the formulation of liposomes for topical delivery of Vitamin E using the factorial design approach was undertaken. Amount of phospholipid (PL) and cholesterol (CH) were taken at three different levels and liposomes were prepared using ethanol injection method. Liposomes were characterized for encapsulation efficiency, vesicle size, zeta potential, and drug deposition in the rat skin. Gels containing liposomal dispersion (batch with higher skin deposition of VE) were prepared in Carbopol^® 980 NF and were characterized for gel strength, viscosity and drug deposition in the rat skin. Stability of liposome dispersion and gel formulation was studied at 30 °C/65% RH for 3 months. Results of regression analysis revealed that vesicle size and drug deposition in the rat skin were dependant on the lipid concentration and lipid:drug ratio. Drug deposition in rat skin had an inverse relationship with respect to PL and CH concentration. Prepared liposomal dispersion (50 mg PL:6 mg CH) showed seven-fold increase in drug deposition compared to control (plain drug dispersion). Gel formulation demonstrated six-fold and four-fold increase in drug deposition compared to control gel and marketed cream, respectively. Liposome dispersion and gel formulation were found to be stable for 3 months. Factorial design was found to be well suited to identify the key variables affecting drug deposition. Improved drug deposition from liposomal preparations demonstrates its potential for dermal delivery.     

喷雾冷冻干燥技术制备盐酸伊立替康脂质体冻干微粒及其理化性质考察

目的:考察喷雾冷冻干燥(SFD)技术制备脂质体冻干微粒的可行性。方法:以盐酸伊立替康为模型药物,采用硫酸铵梯度法制备盐酸伊立替康脂质体,SFD技术制备脂质体冻干微粒;以喷嘴高度、物料流速、雾滴/液氮质量比为因素,应用Box-Behnk-enDesign(BBD)试验考察三者之间的配比对微粒包封率的影响以优化SFD工艺,并对所制备的脂质体及冻干微粒的理化性质进行了考察。结果:SFD优化工艺为物料流速5.5mL·min-1,喷嘴高度18.5cm,雾滴/液氮质量比3.7%,由此制备的脂质体冻干微粒的外观和再分散性好,平均粒径、粒度分布、主药含量及包封率等理化性质与原脂质体基本保持一致,且放置6个月后与原脂质体溶液比较稳定性更好。结论:SFD技术制备脂质体冻干微粒具有可行性,并提高了脂质体的稳定性。