依托泊苷固体脂质纳米粒的研制

目的:制备依托泊苷固体脂质纳米粒(ET-SLN)并考察其药剂学性质。方法:采用乳化-超声分散法制备ET-SLN,以单硬脂酸甘油酯(A)、大豆磷脂(B)、泊洛沙姆188(C)、依托泊苷(D)的处方用量为考察因素,包封率为指标设计正交试验,筛选最优处方。考察纳米粒的粒径、表面电位、包封率、体外释放情况等。结果:A、B、C、D分别为0.020、0.010、0.015、0.015mg;所制纳米粒平均粒径(83±0.5)nm,表面电位(-23±0.3)mV,包封率81.2%,可持续48h缓释。结论:所制ET-SLN符合药剂学性质要求。     

醋氯芬酸醇质体的制备及体外经皮渗透考察

目的:制备醋氯芬酸(ACF)醇质体并考察其对离体大鼠的透皮能力。方法:采用乙醇注入均质法制备醋氯芬酸醇质体,利用正交试验优化处方;对其粒径、包封率、形态及大鼠离体皮肤经皮渗透量进行考察。结果:优选处方为乙醇用量45%,大豆磷脂用量3%,醋氯芬酸用量0.35%。制备的醇质体平均粒径为102 nm,包封率为48%。醋氯芬酸醇质体的24 h经皮渗透量为821.8μg.cm-2是其45%乙醇溶液的6.36倍。结论:醇质体能显著提高醋氯芬酸经皮渗透量,是经皮给药的优良载体。     

根皮素醇质体的制备、表征及对体外透皮吸收的影响

目的：制备根皮素醇质体,考察醇质体作为根皮素经皮给药载体的可行性。方法：乙醇注入法制备根皮素醇质体。采用包封率和粒径为考察指标,正交试验优化大豆磷脂用量、胆固醇用量、乙醇体积及水浴温度。测定根皮素醇质体粒径分布、多分散指标和Zeta电位,采用Franz扩散池比较根皮素及其醇质体体外透皮特征。结果：根皮素醇质体最佳处方工艺：磷脂用量为220 mg、胆固醇用量为14 mg、乙醇体积为5 mL、水浴温度为40℃,根皮素醇质体平均包封率为（83.09±1.24）%,载药量为（4.86±0.89）%,粒径为（162.19±5.88） nm,PDI为（0.067±0.011）;Zeta电位为（-15.09±2.16） mV。根皮素以醇质体形式给药后单位累积透过量提高了3.43倍,且渗透过程符合零级动力学。结论：醇质体具有包封率高,粒径分布均匀等特点,可提高根皮素的渗透速率和经皮渗透量,值得进一步研究。     

星点效应面法对多西他赛他莫昔芬复方脂质体处方的优化

摘要：目的:优化多西他赛他莫昔芬复方脂质体处方。方法:采用单因素试验考察脂药比、大豆磷脂/胆固醇比、枸橼酸他莫昔芬/多西他赛比3个因素对脂质体粒径、ζ电位、分散度指数(PdI)、药物包封率和载药量的影响;采用2因素5水平的星点设计-效应面法,以多西他赛包封率和载药率为评价指标进行处方优化。结果:最优处方为脂药比为19∶1,大豆磷脂/胆固醇比为9∶1,多西他赛的包封率为(82.24±1.41)%,他莫昔芬的包封率为(93.14±2.67)%。结论:优化所得处方为多西他赛他莫昔芬复方脂质体的开发提供了基础保证。     

十一酸睾酮二元醇质体处方优化及体外性质考察

摘 要 目的： 优选十一酸睾酮（TU）二元醇质体的最佳处方,并考察其体外性质,为TU透皮吸收给药系统的研究奠定基础。方法: 以乙醇和丙二醇的混合液为柔软剂,采用注入法制备TU二元醇质体。以药物与磷脂用量比（A）,含醇质量分数（B）,丙二醇和乙醇的用量比（C）为影响因素,以包封率为评价指标,通过正交设计优化TU二元醇质体的处方。对最优处方制备的TU二元醇质体的形态,粒径,Zeta电位,体外释药,稳定性影响因素等进行考察。结果: TU二元醇质体最优处方为：TU与磷脂用量比为1∶15,含醇质量分数为10%,丙二醇与乙醇的用量比为6∶4。最优处方制得的TU二元醇质体在光学显微镜下呈同心圆形,且大小均匀,达到纳米级,平均粒径为（185.5±52.8）nm, Zeta电位为（-15.87±0.26）mV,包封率为（79.14±0.66）%,体外透皮试验中,累积释药百分率Q与时间t的关系符合一级速度方程：Q=20.79t－11.01,r²=0.998 4。稳定性试验结果表明,除高温时包封率有明显降低之外,其他条件下各项指标均无明显变化。结论: 处方优化后的TU二元醇质体制备简单,质量理想,并具有缓释特性,值得进一步深入研究。     

姜黄素醇质体的制备及其质量评价

目的:制备姜黄素醇质体,并考察其理化性质.方法:采用乙醇注入法制备姜黄素醇质体,以包封率为考察指标,采用正交试验法优选处方,并用透射电镜观察其形态,激光粒度仪测定粒径和Zeta电位,以超速离心法分离含药醇质体与游离药物,用HPLC法测定姜黄素醇质体的包封率.结果:优选处方为:姜黄素10 mg、蛋黄卵磷脂350 mg、胆固醇50 mg、乙醇百分浓度25%.实验所制醇质体纳米粒子为类球形囊泡结构,粒径为(210.8±2.0)nm,Zeta电位为(-3.49±0.27)mV,粒径分布均匀,多分散指数(PDI)为(0.144±0.006),以优选后处方制备醇质体,其包封率为(85.55±2.12)%.结论:乙醇注入法适用于姜黄素醇质体的制备,所制醇质体纳米粒子各项物理指标稳定,可用于经皮渗透给药的研究.     

甘草次酸醇质体的制备研究

目的优选甘草次酸(GA)醇质体的最佳制备工艺。方法乙醇注入法制备GA醇质体,以包封率为评价指标,采用正交设计实验确定GA醇质体的最佳制备工艺。结果确定GA醇质体最佳制备工艺为:含GA0.5g的100mLGA醇质体中无水乙醇投入35mL,大豆磷脂3.0g,胆固醇0.2g。所制得的醇质体平均包封率为70.6%。结论以乙醇注入法制备的GA醇质体,包封率高、稳定。     

星点设计-效应面法优化环维黄杨星D醇质体的制备

目的:优化环维黄杨星D醇质体的处方。方法:以包封率和平均粒径为评价指标,采用星点设计-效应面法优化醇质体处方中大豆磷脂、药物和无水乙醇的最佳配比。结果:以各因素分别对评价指标建立二项式拟合方程,结合效应面法确定了优化处方中大豆磷脂-药物-无水乙醇为2.85%∶0.65%∶35.5%。结论:建立的模型可较好地描述该实验中因素与指标的关系,预测性良好。     

星点设计-响应面法优化石杉碱甲二元醇质体处方及其理化性质考察

目的 优化石杉碱甲二元醇质体的处方,并对其理化性质进行考察.方法 采用注入法制备石杉碱甲二元醇质体.以卵磷脂含量(X1)、无水乙醇含量(X2)、混合醇含量(X3)为考察因素,以包封率(Y1)与平均粒径(Y2)为评价指标,通过星点设计-响应面法优化醇质体处方.并考察醇质体的粒径、电位等理化性质.结果 优选的处方为卵磷脂含...     

胸腺五肽脂质体的研制

目的:制备胸腺五肽脂质体并进行质量评价。方法:采用复乳法制备胸腺五肽脂质体,以聚乳酸-羟基乙酸共聚物(PLGA)及卵磷脂为成球材料、以胸腺五肽为主药制备脂质体。以明胶浓度、PLGA浓度和卵磷脂浓度为考察因素,以包封率和载药量为考察指标设计L(934)正交试验优化基质处方并进行验证试验。通过测定优化处方所制脂质体粒径、包封率、体外累积释放百分率等评价脂质体质量。结果:优化基质处方为明胶、PLGA和卵磷脂浓度分别为100、200、100mg.mL-1。所制脂质体形态完整,平均粒径为(9.03±0.83)μm,载药量与包封率分别为(1.81±0.03)与(74.4±1.4),20d的累积释药百分率达90以上。结论:所制胸腺五肽脂质体工艺简单、重现性好,包封率和载药量高,具有显著的缓释作用。     

倍他司汀醇质体的制备与评价

目的:研究倍他司汀醇质体最佳处方工艺,并考察其体外透皮特性。方法:采用乙醇注入法制备倍他司汀醇质体,以大豆卵磷脂用量、乙醇用量和水浴温度作为考察因素,粒径、包封率为测定指标,采用星点设计-效应面法优化处方,并考察该制剂的初步稳定性;应用Franz扩散池进行体外透皮吸收试验,比较不同给药形式对倍他司汀经皮渗透的影响。结果:最佳处方工艺为倍他司汀100 mg、大豆卵磷脂311 mg、乙醇4.1 m L、水浴温度为39℃,制备的倍他司汀醇质体外观为泛有蓝光的澄清液体,包封率为(67.1±2.23)%,粒径为(59.6±4.81) nm,与预测值相差比例均<5%。倍他司汀醇质体的经皮渗透速率为10.76μg·cm^-2·h^-1,是水溶液的8.47倍、普通脂质体的3.09倍、体积分数为45%乙醇溶液的1.63倍。结论:制备的倍他司汀醇质体粒径小、分布均匀、稳定性较高,具有良好的透皮吸收特性。     

Deformable liposomes and ethosomes as carriers for skin delivery of ketotifen

Deformable liposomes and ethosomes were investigated as carriers for skin delivery of ketotifen (KT) in terms of vesicle size, entrapment efficiency, stability, in vitro permeation and skin deposition properties. Phosphatidylcholine (PC) from soybean lecithin was used in the preparation of all vesicles. Sodium cholate, sodium deoxycholate and Tween 80 were investigated as edge activators in preparation of KT deformable liposomes. KT ethosomes were prepared in two PC concentrations, 2% and 4.25% w/v, in 30% v/v ethanol. KT deformable liposomes showed improved entrapment efficiency over KT ethosomes. KT deformable liposomes with Tween 80 as an edge activator were more stable upon storage at 5 +/- 1 degree C than those prepared using sodium cholate or sodium deoxycholate and were more stable than KT ethosomes. In vitro permeation and skin deposition studies employed only deformable liposomes with Tween 80 as an edge activator and ethosomes with 4.25% w/v PC concentration. Both of them improved skin delivery of KT over controls and over traditional liposomes, with greater improvement of KT skin deposition than KT skin permeation, hence are more useful for dermal than for transdermal delivery of KT.     

Ethosomes,binary ethosomes and transfersomes of terbinafine hydrochloride: A comparative study

The aim of this study was to compare the skin permeation of ethosomes, binary ethosomes and transfersomes of Terbinafine Hydrochloride (TH) under non-occlusive conditions. These lipid vesicles were prepared and characterized for shape, size, zeta-potential and entrapment efficiency. Franz diffusion cells and confocal laser scanning microscopy (CLSM) were used for the percutaneous absorption studies. The quantity of drug in the skin from ethosomes, binary ethosomes (the weight ratio of ethanol to propylene glycol 7:3, ethanol-PG = 7:3, w/w), and transfersomes was 1.26, 1.51 (p <0.05), 1.56 (p <0.01) times higher than that of TH from traditional liposomes (control). The skin deposition of the applied dose (DD%) of TH from ethosomes, binary ethosomes, and transfersomes was 3.34 (p < 0.05), 9.88 (p < 0.01), 2.52 times higher than that of TH from control. The results of CLSM experiments showed that penetration depth and fluorescence intensity of Rhodamine B from binary ethosomes was much greater than that from ethosomes and transfersomes. These results indicated the binary ethosomes (ethanol-PG = 7:3, w/w) most effectively permitted drug penetration through skin; transfersomes made drug easiest to accumulate in the skin. Ethosomes improved drug delivery with greater improvement in skin permeation than improvement in skin deposition.     

Preparation and Characterization of Ethosomes for Topical delivery of Aceclofenac

The aim of present study was to prepare and characterized ethosomes of aceclofenac which may deliver the drug to targeted site more efficiently than marketed gel preparation and also overcome the problems related with oral administration of drug. The formulations were prepared with varying the quantity of ethanol 10-50% (v/v), lecithin 1-4% (w/v), propylene glycol 5-20% (v/v) and evaluated for their vesicle size, shape and surface morphology, entrapment efficiency and in vitro drug permeation study. Ethosomes of average size of 1.112 μm with a spherical shape bearing smooth surface were observed by transmission electron microscopy and surface electron microscopy. The maximum entrapment of ethosomes was 91.06±0.79%. Cumulative amount of drug permeated through the biological membrane was found to be in the range of 0.26±0.014 to 0.49±0.032 mg/cm(2). Stability profile of prepared system was assessed for 45 days and the results revealed that very less degradation of drug was observed during storage condition.     

Investigation of the phase behaviour of systems containing lecithin and 2-acyl lysolecithin derivatives.

A series of modified phospholipids (m-PC) possessing different acyl chains in position 2, from butanoyl to hexadecanoyl, were prepared by partial synthesis from soybean lysolecithin. They were used with soybean lecithin to construct phase diagrams containing ethanol as cosolvent, water and medium chain triglycerides (MCT) or isopropyl myristate (IPM) as oils. The weight ratios lecithin:m-PC and surfactants:ethanol were kept constant at 1:1.The results indicate that the m-PCs have a strong effect on the microemulsion (L) and liquid crystalline (LC) domains in the water-rich/oil-poor part of the phase diagrams, although all diagrams correspond to a single lecithin:m-PC ratio. On decreasing the acyl chain length, and thus increasing the hydrophilicity of the surfactant, there was a corresponding increase in the L area, which moved towards the aqueous corner of the phase diagrams. The LC phase was detected only in the presence of the hexadecanoyl derivative for the systems containing MCT, and it was not detected only in the presence of the butanoyl derivative for the systems containing IPM. The use of a second hydrophilic surfactant to adjust the packing properties of the lecithin-alcohol systems, and/or to increase the fluidity of the surfactant film, increased the region of existence of the isotropic systems. This may be of importance in the formulation of drug delivery systems, especially those which are diluted by biological fluids upon administration.     

正交试验优选盐酸川芎嗪脂质体的制备工艺

目的:优选盐酸川芎嗪脂质体的制备工艺。方法:以乙醚注入法制备川芎嗪脂质体,采用正交试验,以包封率为指标,以药物与大豆卵磷脂用量比、PBS缓冲液的pH值、胆固醇与大豆卵磷脂用量比、乙醚与PBS缓冲液用量比为考察因素,优选制备工艺。结果:最佳工艺条件为药物:大豆卵磷脂为1:12,PBS缓冲液pH为7.5,胆固醇:大豆卵磷脂为1:2,乙醚:PBS缓冲液为1:2。结论:该制备工艺可行、稳定、重现性好,可为工业化生产提供理论依据。