电场方向对咖啡因电穿孔与离子导入经皮渗透的影响比较

目的研究电穿孔及离子导入时电场方向对分子型药物咖啡因经皮渗透的影响。方法采用双室扩散池方法,进行咖啡因饱和水溶液经人尸体皮肤被动扩散,电穿孔导入(指数衰减型脉冲,脉冲幅度为350 V,脉冲率为4次.m in-1,脉冲数为25,放电容量为22μF)、离子导入[0.25 mA.(cm2)-1,4 h]实验,考察电穿孔及离子导入对药物经皮渗透速率、累积经皮渗透量的影响,比较电穿孔与离子导入的促透作用。结果电穿孔与离子导入的咖啡因经皮渗透速率和累积渗透量均显著大于被动扩散。电场方向改变,电穿孔的促透作用无明显改变,离子导入的促透作用明显改变,正极离子导入的促透作用显著大于负极导入。在该实验条件下,外加脉冲的促透作用显著低于离子导入。结论与被动扩散相比,电穿孔和离子导入可显著增加分子型药物咖啡因的经皮渗透速率和累积渗透量。电场方向对电穿孔的促透作用无影响,而对离子导入的促透作用有明显影响。     

盐酸利多卡因经皮电离子导入的实验研究

目的：直流电经皮离子导入对局麻药盐酸利多卡因经过兔腹部皮肤的渗透进行研究。方法：采用不同的电流强度以考察电流强度对药物经皮转运的影响。结果：在电流强度分别为０．２５、０．５０和０．８０ｍＡ的条件下，盐酸利多卡因的透皮速率为１．１±０．４ｍｇ·ｈ－１·ｃｍ－２、１．４±０．５ｍｇ·ｈ－１·ｃｍ－２和２．５±０．８ｍｇ·ｈ－１·ｃｍ－２，分别是药物被动扩散透皮速率的３．５倍、４．２倍和７．８倍。结论：经皮离子导入可促进盐酸利多卡因的渗透     

乙醇对双氯芬酸钠经皮离子导入的影响

探讨了不同浓度乙醇对双氯芬酸钠（１）离子导入透过离体大鼠腹部皮肤的影响。乙醇对１波动扩散几乎不产生影响。但乙醇浓度为２０％～８０％的１饱和溶液，离子导入时的透皮速率均比药物饱和水溶液离子导入的透皮速率有不同程度的增加，浓度为６０％时药物的透皮速率最大，达到２９７±３４．７μｇ／ｈ／ｃｍ２，为波动扩散的１４．６倍，为饱和水溶液离子导入的透皮速率的３倍。     

吡罗昔康离子导入的实验研究

探讨了离子导入和月桂氮酮预处理对吡罗昔康通过离体大鼠皮肤的影响，选用Ｖａｌｉａ－Ｃｈｉｅｎ扩散池和改良的Ｆｒａｎｚ扩散池，得到吡罗昔康饱和液及其膜剂的透皮速率分别为４．８±０．１７和１．０±０．０４μｇ／ｈ·ｃｍ－２，采用电流强度为０．８ｍＡ的离子导入，药物的透皮速率分别增加１１倍和８倍．另外，月桂氮酮预处理合用离子导入能产生协同作用，其透皮速率为单用月桂氮酮与单用电场透皮速率之和的４倍。     

电渗作用对替硝唑经皮离子导入的影响

考察了电扬下电渗作用对分子型药物替硝唑经皮渗透的影响。实验结果表明,替硝唑从饱和水溶液经正极导入时,透皮速率比其被动扩散增加12.8倍,负极导入也产生一定的促进作用。替硝唑的透皮速率随电流强度而增加。另外,NaCl的加入使用电场下替硝唑的透皮速率明显下降,而在NaCl浓度为0.05mol/L时药物在电场下的透皮率相对较大。     

乙醇对萘普生经皮离子导入的影响

探讨了不同浓度乙醇对萘普生离子导入透过离体大鼠腹部皮肤的影响，乙醇对萘普生被动扩散具有一定的促渗作用，乙醇浓度为３０％到８０％的萘普生饱和溶液，离子导入时的透皮速率均比药物饱和水溶液离子导入的透皮速率有不同程度的增加，其中乙醇浓度为７０％时药物的透皮速率最大，达到１８５±２３．７ｕｇ／ｈ·ｃｍ２，为被动扩散的６．４倍，药物饱和水溶液离子导入透皮速率的３倍。     

电穿孔技术促进萘普生经皮渗透的研究

目的：研究电穿孔技术对小分子离子型药物经皮渗透的影响。方法：应用双室扩散池方法研究电穿孔技术对萘普生在离体大鼠腹部皮肤经皮渗透的影响。并与被动扩散和离子导入进行比较。结果：外加电脉冲（指数衰减型脉冲,脉冲幅度为４００Ｖ,电容器电容为２．２ｕＦ,脉冲率为２０ｐｕｌｓｅｓ．ｍｉｎ＾－１,脉冲宽度τ≈６．０ｍｓ）或离子导入（１ｍＡ．ｃｍ＾－２,６ｈ）时,萘普生的渗透速率和累积渗透量均大于被动扩散。外加脉     

脉冲施与方式对盐酸丁卡因电穿孔经皮渗透的影响

目的研究外加电脉冲的施与方式对小分子解离型药物盐酸丁卡因经皮渗透速率的影响。方法以盐酸丁卡因为小分子离子型模型药物,应用水平双室扩散池,大鼠腹部皮肤,研究使用多个脉冲时,外加脉冲的施与方式对药物体外电穿孔经皮渗透速率的影响,并与被动扩散和离子导入进行比较。结果电穿孔(方波脉冲,脉冲电压为130 V,脉冲率为40 pu lses.m in-1,脉冲时间为0.4 s)可显著提高盐酸丁卡因的经皮渗透速率,且电穿孔的促渗作用显著大于离子导入(0.2 mA.cm-2,4 h)。400个脉冲时,施加脉冲方式对经皮渗透速率无显著影响。200个脉冲时,施加脉冲后0.25 h和0.75 h时一次施加和分两次施加的经皮渗透速率没有显著性差异,随后一次施加脉冲的经皮渗透速率显著大于分两次加脉冲的经皮渗透速率。结论电穿孔可显著促进盐酸丁卡因的经皮渗透,且促渗效果优于离子导入;脉冲施与方式对盐酸丁卡因电穿孔经皮渗透速率的影响与所加的脉冲数有关。     

脉冲施与方式对盐酸丁卡因电穿孔经皮渗透的影响

目的研究外加电脉冲的施与方式对小分子解离型药物盐酸丁卡因经皮渗透速率的影响.方法以盐酸丁卡因为小分子离子型模型药物,应用水平双室扩散池,大鼠腹部皮肤,研究使用多个脉冲时,外加脉冲的施与方式对药物体外电穿孔经皮渗透速率的影响,并与被动扩散和离子导入进行比较.结果电穿孔(方波脉冲,脉冲电压为130 V,脉冲率为40 pulses·min-1,脉冲时间为0.4 s)可显著提高盐酸丁卡因的经皮渗透速率,且电穿孔的促渗作用显著大于离子导入(0.2 mA·cm-2,4 h).400个脉冲时,施加脉冲方式对经皮渗透速率无显著影响.200个脉冲时,施加脉冲后0.25 h和0.75 h时一次施加和分两次施加的经皮渗透速率没有显著性差异,随后一次施加脉冲的经皮渗透速率显著大于分两次加脉冲的经皮渗透速率.结论电穿孔可显著促进盐酸丁卡因的经皮渗透,且促渗效果优于离子导入;脉冲施与方式对盐酸丁卡因电穿孔经皮渗透速率的影响与所加的脉冲数有关.     

黄体酮透皮给药系统体外经皮渗透特性的研究

目的研究黄体酮透皮给药系统的体外经皮渗透特性。方法采用聚丙烯酸酯为骨架制备黄体酮透皮贴片,以离体人皮为透皮模型,采用Valia-Chien扩散池和高效液相色谱法研究促渗剂、药物含量对黄体酮透皮给药系统经皮渗透的影响。结果23%单月桂酸甘油酯与15%棕榈酸乙酯合用对黄体酮促渗效果明显,经皮渗透速率为1.50±0.64μg·cm-2·h-1,增渗倍数达到了21.4倍。贴片中黄体酮含量由0.75mg·cm-2提高到1.0mg·cm-2时,经皮渗透速率明显增大;含量提高到1.25mg·cm-2时,经皮渗透速率无明显变化。结论单月桂酸甘油酯和棕榈酸乙酯联用对黄体酮透皮给药系统体外经皮渗透具有显著的促进作用,黄体酮的最佳含量是1.0mg·cm-2。     

不同促渗剂对盐酸氨酮戊酸原位凝胶体外透皮吸收的影响

目的：研究不同透皮促渗剂对盐酸氨酮戊酸原位凝胶体外透皮吸收的影响,为筛选最佳透皮促渗剂提供实验依据。方法：采用Franz扩散池法,以离体大鼠皮肤为模型,选择3种常用透皮促渗剂月桂氮芯卓酮（azone,AZ）、丙二醇（propylene glycol,PG）、二甲亚砜（dimethyl sulfoxide,DMSO）,分别考察单一促渗剂及二元促渗剂对盐酸氨酮戊酸原位凝胶体外透皮吸收的影响。结果：含促渗剂盐酸氨酮戊酸原位凝胶体外透皮吸收显著高于未添加促渗剂盐酸氨酮戊酸原位凝胶及市售制剂;采用单一促渗剂时,1% PG促渗效果最好;采用二元促渗剂时,3% AZ+1% PG促渗效果最好;3% AZ+1% PG促渗效果优于1% PG,含促渗剂3% AZ+1% PG的盐酸氨酮戊酸原位凝胶透皮性优于市售制剂艾拉。结论：添加促渗剂的方法能够显著改善盐酸氨酮戊酸的体外透皮吸收性,3% AZ+1% PG构成的二元促渗剂用于盐酸氨酮戊酸原位凝胶促渗效果最佳;本研究为设计优良的盐酸氨酮戊酸经皮给药系统药物奠定了重要基础。     

Convolution method to predict drug concentration profiles of 2,3,5,6-tetramethylpyrazine following transdermal application

The objective of this work is to predict the systemic drug concentration of 2,3,5,6-tetramethylpyrazine (TMP) following transdermal application in rabbits from the in vitro skin permeation data. The in vitro skin permeation was studied in Franz diffusion cells. Pharmacokinetic evaluation of TMP following transdermal application and bolus intravenous administration were carried out in New Zealand White (NZW) rabbits. Drug concentration-time curve following transdermal application was predicted via the convolution procedure using an in vitro skin permeation data as a weighting function, and the intravenous data as an unit impulse response. The results showed that the predicted drug concentration following transdermal application by convolution method was in good agreement with the observed drug absorption profiles. These findings indicated that in vitro skin permeation tests could be useful to predict in vivo drug absorption profiles following transdermal application.     

青藤碱游离碱凝胶体外经皮渗透特性研究

目的:研究凝胶中青藤碱游离碱的体外经皮渗透特性。方法:采用改良的Franz扩散池法考察经皮渗透性能,以离体大鼠皮肤为经皮渗透屏障,通过高效液相色谱法测定药物含量。结果:青藤碱游离碱的经皮渗透速率常数(J值)为(20.3±3.89)μg·cm-2·h-1,是盐酸青藤碱J值的4.72倍。5%含量的2-吡咯烷酮可以抑制青藤碱游离碱的经皮渗透(P<0.05),而5%含量的磷脂、油酸、薄荷醇、柠檬烯和氮酮均增加青藤碱游离碱的经皮渗透,分别达1.37、2.25、3.71、6.75和10.15倍。结论:青藤碱游离碱较其盐酸盐具有优良的经皮渗透性能,更加适合青藤碱透皮新制剂开发。     

Development and in-vitro evaluation of transdermal matrix films of metoprolol tartrate

The transdermal matrix films of metoprolol tartrate (MT) were prepared by casting on mercury substrate employing different ratios of polymers, ethyl cellulose (EC) and polyvinyl pyrrolidone (PVP), using dibutyl phthalate (DBT) as a plasticizer. Four formulations were prepared. Formulations MF-1, MF-2, MF-3 and MF-4 were composed of EC and PVP in the following ratios: 4.5:0.5, 4:1, 3:2 and 2:3 respectively. The formulations were subjected to various physical characterization studies namely, thickness, weight variation, drug content, moisture uptake, in vitro drug release and in vitro skin permeation. The in vitro permeation studies were carried out across excised porcine ear skin using Franz diffusion cell. Cumulative amounts of the drug released in 24 hours from the four formulations were 69.58%, 96.13%, 98.85% and 99.60%, respectively. Corresponding values for the cumulated amounts of drug permeated across the porcine skin for the above matrix films were 124.38, 153.22, 156.46 and 163.25 mug/cm(2) respectively. By fitting the data into zero order, first order and Higuchi model, it was concluded that drug release from matrix films followed Higuchi model (r(2)=0.9147-0.9823), and the mechanism of release was diffusion mediated. Based on the physical evaluation, in vitro drug release & permeation characteristics, it was concluded that for potential therapeutic use, monolithic drug matrix films MF-3, composed of EC: PVP (3:2), may be suitable for the development of a transdermal drug delivery system of MT.     

应用导数光谱法考察苯呋洛尔溶液体外经皮渗透性

本文应用二阶导数紫外分光光度法考察了苯呋洛尔溶液体外经皮渗透性。考察了促进剂月桂氮(?)酮-丙二醉及PEG-400溶剂对其渗透性的影响。应用二阶导数紫外分光光度法消除了兔皮溶出物对一般紫外测定方法的干扰。结果表明:苯呋洛尔溶液具有体外经皮渗透性;月桂氮(?)酮-丙二醇系统及PEG-400均能增强苯呋洛尔溶液的体外经皮渗透性。     

Transdermal testing: practical aspects and methods

Interest in transdermal drug delivery has increased in recent years owing to its many advantages over other routes of administration. In order to evaluate a transdermal product effectively, three main issues need to be addressed: (1) the kind of skin model that will be used to evaluate the drug permeation; (2) the mathematical model that will be used to characterize the permeation of the drug across the skin; and (3) the diffusion apparatus that will be used to conduct the permeation study.     

关于电穿孔对咖啡因透皮过程影响的一种数学建模方法

目的建立描述电穿孔促渗药物经皮渗透的数学模型,分析电脉冲对经皮渗透过程的影响。方法以咖啡因为模型药物,测定不同电脉冲强度(电压、脉冲数等)下的渗透速率,建立快-慢响应双通道假设的近似数学模型。 结果对1组咖啡因实验资料,在仅视慢响应通道扩散系数的最大增加量D₁和快响应扩散通道的最大有效面积分数a₂为条件相关参数的假定下,模型偏差远小于重复实验误差,而且这两个参数与脉冲总能量E的线性相关系数各为0.955(P=0.00)和0.924(P=0.00)。结论模型很好地拟合数据,关于Fick扩散律及快-慢响应双通道假设均可接受;而且可视D₁和a₂为条件相关参数,余为条件无关参数。     

Ex vivo Permeation Kinetics of Zidovudine from Pseudolatex Acrylic Film Across Pig Ear Epidermis

The permeation of ionic compounds through lipophilic skin membrane can be enhanced by converting the impermeable ionized drug into a more permeable unionized form with pH-adjusting excipients. The osmotic influx of water into the device core, upon application on the human skin, dissolve the drug and pH-adjusting adjuvant allowing the partitioning and subsequent permeation of unionized drug from the transdermal device core. The present investigation was aimed to evaluate the feasibility of water activated pH-controlled pseudolatex films for transdermal delivery of zidovudine by ex vivo tests. The monolithic pseudolatex transdermal film of zidovudine was prepared by solvent change followed by solvent casting technique using Eudragit RL 100 and Eudragit RS 100 in varying proportions with pH 7.4 in the device core. The prepared films were of desired physicochemical properties. The SEM photomicrographs of drug loaded formulations exhibited uniformity with rough surface and no traces of crack or pores. The ex vivo skin permeation study across pig ear epidermis in Keshary-Chien glass diffusion cell showed that the drug permeability was controlled by the osmotic influx of water into the device core and consequent partition of dissolve drug into and diffusion through the skin. The formulation F2a with 10 % w/w of zidovudine dispersed in the polymer matrix composed of Eudragit RL 100 and Eudragit RS 100 at the ratio of 1:2, respectively, showed nearly the desired flux at 239.09 μg/cm2/h. A patch area of 117.48 cm2 would be required for transdermal delivery of zidovudine to obtain therapeutic plasma concentration at 0.3 μg/ml.     

固体脂质纳米粒作为水杨酸经皮给药载体的研究

目的 考察固体脂质纳米粒作为经皮给药载体对水杨酸经皮吸收的促渗透作用.方法 采用薄膜超声法制备水杨酸固体脂质纳米粒,以改良的Franz扩散池考察其体外透皮特性;并与水杨酸软膏剂比较,考察其促渗作用.结果 制备的水杨酸固体脂质纳米粒均匀圆整,包封率为46.4%,体外透皮特性优于普通软膏剂,24 h后皮肤药物累积透过量为654.3 μg/cm2,皮肤中药物残留量为22.99 μg,均分别显署高于软膏剂组(128.0 μg/cm2和0.84 μg,P<0.05).结论 固体脂质纳米粒作为水杨酸经皮给药载体,可有效促进药物透皮吸收和增加药物在皮肤中储留量,而且可延缓药物的释放,从而有效提高药物疗效及患者依从性.     

促渗剂对布洛芬透皮吸收速率的影响

以简单小室法研究了布洛芬分别在不加助渗剂、加１％月桂氮　酮、加１％尿素、加１％月桂氮　酮及１％吐温－８０时渗过离体小白鼠皮肤的吸收效果。结果表明，月桂氮　酮有显著的吸收促进作用，尿素次之。吐温－８０则有抑制作用。