青藤碱凝胶剂的制备及体外渗透性能研究

目的：制备青藤碱凝胶剂，研究其透皮渗透性能。方法：以卡波姆980为辅料制备青藤碱凝胶剂．采用改良Franz扩散池，以离体大鼠皮肤为透皮屏障，用HPLC法测定青藤碱的累积渗透量。结果：实验结果表明，青藤碱凝胶剂体外透皮释药方程为Q=65.852 t=55．677（r=0．9919），10h累积渗透量为638μg／cm^2。结论：青藤碱凝胶剂为一种新颖的控释型外用制剂。凝胶剂中的青藤碱以一级动力学经皮渗透。     

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...     

不同剂型青藤碱的体外皮肤渗透性

目的:比较青藤碱微乳、固体脂质纳米粒和脂质体对离体大鼠皮肤的透皮能力。方法:采用改进的Franz扩散池研究三者的透皮行为,采用高效液相色谱法测定接受液中青藤碱浓度并比较三者的经皮渗透能力。结果:t检验结果表明,体外经皮渗透试验中,青藤碱不同剂型的经皮渗透速率差异明显,差异具统计学意义(P<0.01),微乳>固体脂质纳米粒>脂质体。结论:青藤碱微乳有较强的透皮能力,适合青藤碱的新型透皮给药剂型。     

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。     

月桂氮芯卓酮对青藤碱凝胶剂的透皮吸收作用

目的:考察不同浓度月桂氮(艹卓)酮(azone)对青藤碱凝胶透皮作用的影响,为青藤碱凝胶剂的处方筛选提供依据。方法:采用改良Franz扩散池,以离体大白鼠皮肤为透皮屏障,配制含不同浓度月桂氮(廿卓)酮的青藤碱凝胶,用HPLC法测定青藤碱的透皮吸收量,结果:青藤碱凝胶含2％azone时透皮吸收最好,其体外累积渗透量及促造速率最大。青藤碱凝胶剂的体外渗透药动学符合Higuchi方程。结论:选择2％azone作为青藤碱凝胶剂的促透剂。     

月桂氮zhuo酮对青藤碱凝胶剂的透皮吸收作用

目的：考察不同浓度月桂氮Zhuo酮（azone)对青藤碱凝胶透皮作用的影响，为青藤碱凝胶剂的处方筛选提供依据。方法：采用改良Franz扩散池，以离体大白鼠皮肤为透皮屏障，配制含不同浓度月桂氮Zhuo酮的青藤碱凝胶，用HPLC法测定青藤碱的透皮吸收量。结果：青藤碱凝胶含2%azone时透皮吸收最好。其体外累积渗透量及促透速率最大。青藤碱凝胶剂的体外渗透药动学符合Higuchi方程。结论：选择2%azone作为青藤碱凝胶剂的促透剂。     

青藤碱凝胶剂透皮吸收的研究

目的 研究青藤碱凝胶的制备方法及其皮肤通过量。方法 用卡巴姆934作为凝胶基质制备青藤碱凝胶,并采用HPLC测定药物的含量,采用TK-12A型透皮扩散池测定并比较其吸收量。结果 与羟丙基甲基纤维素凝胶相比,以卡巴姆934作为凝胶基质的青藤碱其经皮渗透效果较好。加入10%丙二醇对药物的经皮渗透影响不大。结论 青藤碱在以卡巴姆为基质的凝胶剂中具有较好的经皮渗透效果。     

青藤碱凝胶剂透皮吸收的研究

目的研究青藤碱凝胶的制备方法及其皮肤通过量。方法用卡巴姆934作为凝胶基质制备青藤碱凝胶,并采用HPLC测定药物的含量,采用TK-12A型透皮扩散池测定并比较其吸收量。结果与羟丙基甲基纤维素凝胶相比,以卡巴姆934作为凝胶基质的青藤碱其经皮渗透效果较好。加入10%丙二醇对药物的经皮渗透影响不大。结论青藤碱在以卡巴姆为基质的凝胶剂中具有较好的经皮渗透效果。     

醋氯芬酸贴剂的制备

目的以体外释放度和经皮渗透性为指标,制备醋氯芬酸贴剂并优化压敏胶和促渗剂的处方。方法采用不同类型丙烯酸酯压敏胶为基质制备醋氯芬酸贴剂,以体外释放度为指标考察筛选压敏胶;以不同种类促渗剂制备醋氯芬酸贴剂,采用改良Franz扩散池,以离体大鼠皮肤为渗透屏障,考察其经皮渗透性能,筛选经皮渗透促进剂。结果醋氯芬酸贴剂在12 h内体外释放曲线遵循Higuchi动力学方程,经皮渗透曲线遵循零级动力学方程,且以Duro Tak 87-2677为压敏胶基质、质量分数为5%的氮酮为促渗剂时醋氯芬酸贴剂具有较快的释放和经皮渗透速率。结论醋氯芬酸贴剂为皮肤控释型骨架释药系统,选择适宜的基质和促渗剂可保证足够的药物释放并穿透皮肤发挥理想的治疗作用。     

乳酸左氧氟沙星脂质体凝胶剂经小鼠在/离体的透皮吸收

目的:研究乳酸左氧氟沙星脂质体凝胶剂的皮肤渗透性。方法:以普通凝胶剂为对照,将乳酸左氧氟沙星脂质体制备成凝胶剂并应用于小鼠皮肤,用改良的Franz扩散池研究其透皮速率,以高效液相色谱法测定接受液、皮肤、血液及其他组织中的乳酸左氧氟沙星的含量。结果:所制脂质体凝胶剂有较大的透皮速率,平均为(13.5±1.0)μg.cm-2.h-1(n=6),透皮吸收行为符合Fick’s第一定律;经皮吸收结果显示体内吸收量均较普通凝胶剂低,而皮内滞留量无论是在体还是离体均较高。结论:该制剂具有良好的局部皮肤靶向性。脂质体有促进药物进入皮肤的能力,而药物进入血循环的量并不增加。     

Water-activated, pH-controlled patch in transdermal administration of timolol. I. Preclinical tests.

Previously, transdermal patches with internal pH-controlled release were described. The aim of this study was to test the suitability of the patch design in transdermal delivery and, further, to select such transdermal patch formulations to a clinical study with timolol. In vitro release of timolol from the patches was determined as well as timolol permeation across the human cadaver skin. The effect of the skin on drug release were evaluated in vitro. In vitro data and pharmacokinetic parameters from the literature were used to construct a pharmacokinetic model for the prediction of in vivo performance of the devices. With water-activated, pH-controlled silicone reservoir devices, both the rate of drug release and the duration of constant release were controlled. The rate of timolol release was decreased when the devices were placed on human cadaver skin, and thus, the skin partly controls the rate and extent of timolol delivery to the systemic circulation in vivo. On the basis of in vitro data and kinetic simulations, devices of 10-cm(2) volume releasing timolol in vitro at the rates of 119 and 10 microgh(-1)cm(-2) were selected for human tests.     

Investigation of formulation factors affecting in vitro and in vivo characteristics of a galantamine transdermal system

Because of low treatment compliance with the Alzheimer disease patients, there have been clinical needs for the alternative administration route to effective and well-tolerated approaches of galantamine (Small and Dubois, 2007). In this study, drug-in-adhesive transdermal patches with galantamine were prepared and evaluated in vitro and in vivo. The in vitro permeation studies indicated that DT-2510 was the most suitable pressure-sensitive-adhesive and oleic acid was the most promising enhancer for galantamine drug-in-adhesive patch. The optimized galantamine drug-in-adhesive patch could be physicochemically stable for 28 days at 40°C/75% RH. The in vivo studies of the optimized galantamine drug-in-adhesive patch showed high absolute bioavailability of around 80% and sustained effect on the drug plasma levels for 24h. The in vitro and in vivo studies of galantamine drug-in-adhesive patches with different pressure-sensitive-adhesive functional groups showed a strong correlation between the skin permeation rate and the area under the curve. The results suggest that the transdermal application of galantamine drug-in-adhesive patches might be the alternative dosage form to have good efficacy and tolerability for the treatment of Alzheimer disease.     

青藤碱透皮贴剂定位给药传递能力的评价

目的评价青藤碱压敏胶分散型透皮贴剂的定位给药传递能力。方法通过经皮和经口两种给药途径的比较,采用小鼠局部组织分布研究评价青藤碱透皮贴剂的定位给药传递能力。结果与经口给药组相比,青藤碱的浓度在小鼠经皮给药组贴敷贴剂处的肌肉中更加平稳,而且肌肉-血浆浓度比更高。结论将青藤碱透皮贴剂应用于关节炎患病区域,可以定位传递药物至病灶部位,是一种更适宜的给药途径。     

Dermal penetration of fentanyl: inter- and intraindividual variations

Fentanyl is a potent synthetic opioid that is increasingly being used in transdermal drug delivery systems. The target organ concentration of a drug administered dermally will depend on the rate of dermal absorption and the systemic elimination. We have studied the intra- and interindividual variation in dermal penetration of fentanyl in an in vitro model (static diffusion cells) with human skin, and compared the absorption of fentanyl from an aqueous solution with absorption from a commercial patch. The intraindividual variation in dermal penetration of fentanyl in aqueous solution was limited (18%) and no differences in penetration characteristics were observed between breast and abdominal skin. The interindividual variation in dermal penetration of fentanyl was extensive, with maximal fluxes ranging from 21-105 ng/cm2/hr following application of an infinite dose of fentanyl to the donor chamber. Use of transdermal drug delivery systems (patches) reduced the inter-individual variation. The permeability coefficients after application of fentanyl in aqueous solution and through patches were identical (0.0011 cm/hr). One person had a higher than average penetration rate following patch application, which may indicate that the human skin and not the patch barrier was the rate-determining factor for the other individuals included in this study.     

维A酸贴剂的体外透皮扩散研究

目的:研究自制的维A酸贴剂的体外透皮扩散率及在皮肤内的蓄积量。方法:按《中国药典》2005年版规定测定含量均匀度,以酸性异丙醇为溶剂,在波长352nm处测定维A酸,用透皮扩散仪测定透皮贴剂与市售维A酸乳膏对小鼠皮的扩散率及皮肤内的蓄积量。结果:贴剂的含量均匀度合格;测定的平均回收率为97.99%。测得含量为9.73mg/片,为标示量的97.3%;贴剂的扩散率虽低于乳膏,但皮肤内的蓄积量明显高于乳膏。结论:该贴剂能使药物蓄积于皮肤内,有利于提高对皮肤病的疗效和降低毒性,值得进一步开发。     

美欧关于透皮贴剂临床研究要求的探究与思考

目的：为我国透皮贴剂的研发提供参考。方法：通过查阅美国和欧盟药监机构官网,就欧美关于透皮贴剂临床研究的要求及已上市透皮贴剂产品案例进行讨论和分析。结果与结论：结合欧美经验及我国法规现状,对我国透皮贴剂创新药、改良型透皮贴剂和透皮贴剂仿制药的临床研究要求分别提出了相应的思考建议：透皮贴剂创新药需开展充分的体内外研究以揭示其安全性和有效性;改良型透皮贴剂应与对照药开展桥接试验,并侧重于揭示经皮给药的临床特点和特有的不良反应;透皮贴剂仿制药可开展生物等效性试验、黏附性、皮肤刺激性和致敏性研究。     

盐酸特比萘芬醇类脂泡囊凝胶离体和在体透皮特点研究

目的:研究盐酸特比萘芬醇类脂泡囊凝胶在体和离体透皮特点。方法:采用Franz扩散池进行体外透皮实验,考察盐酸特比萘芬醇类脂泡囊凝胶、脂质体凝胶和普通凝胶经皮渗透性和皮肤滞留量;以小鼠为实验动物,3种凝胶腹部经皮给药,考察盐酸特比萘芬的血药浓度和皮肤滞留量,对比不同类型凝胶剂的透皮效果。结果:离体透皮扩散实验中,透皮速率排序为:脂质体凝胶>醇类脂泡囊凝胶>普通凝胶;皮肤内24 h累积滞留量排序为:醇类脂泡囊凝胶>脂质体凝胶>普通凝胶。在体透皮吸收实验中,皮肤内6 h累积滞留量排序为:醇类脂泡囊凝胶>脂质体凝胶>普通凝胶。3种凝胶中的盐酸特比萘芬在皮肤深层中的滞留量均远远大于角质层,醇类脂泡囊凝胶中药物在皮肤深层的滞留量远大于另外两种凝胶,而脂质体凝胶和普通凝胶在皮肤深层的滞留量无明显差异。结论:醇类脂泡囊对盐酸特比萘芬透皮吸收具有一定的促进作用,同时也能显著提高盐酸特比萘芬在皮肤内特别是皮肤深层中的滞留量,为治疗深部皮肤真菌感染提供了一种新方法。     

Dermal Penetration of Fentanyl: Inter‐ and Intraindividual Variations

Abstract: Fentanyl is a potent synthetic opioid that is increasingly being used in transdermal drug delivery systems. The target organ concentration of a drug administered dermally will depend on the rate of dermal absorption and the systemic elimination. We have studied the intra‐ and interindividual variation in dermal penetration of fentanyl in an in vitro model (static diffusion cells) with human skin, and compared the absorption of fentanyl from an aqueous solution with absorption from a commercial patch. The intraindividual variation in dermal penetration of fentanyl in aqueous solution was limited (18%) and no differences in penetration characteristics were observed between breast and abdominal skin. The interindividual variation in dermal penetration of fentanyl was extensive, with maximal fluxes ranging from 21–105 ng/cm²/hr following application of an infinite dose of fentanyl to the donor chamber. Use of transdermal drug delivery systems (patches) reduced the inter‐individual variation. The permeability coefficients after application of fentanyl in aqueous solution and through patches were identical (0.0011 cm/hr). One person had a higher than average penetration rate following patch application, which may indicate that the human skin and not the patch barrier was the rate‐determining factor for the other individuals included in this study.     

Development of drug-in-adhesive transdermal patch for α-asarone and in vivo pharmacokinetics and efficacy evaluation

A transdermal drug delivery system has been reported that can increase the bioavailability, reduce the administration duration, and maintain the concentration of drug in blood. In the present study, drug-in-adhesive transdermal patches of α-asarone using Eudragit E100 as pressure-sensitive adhesives and oleic acid plus isopropyl myristate as penetration co-enhancers were developed. In vitro permeation, in vivo pharmacokinetics in rabbits, and efficacy in asthmatic rats were evaluated. The results showed that co-enhancers could induce a synergistic effect on α-asarone permeability. In vivo study suggested that the patch can keep a relatively certain blood level of drug within 10-30?h in rabbits. Furthermore, the patch with the size of 4?cm2 containing drug 3?mg/cm2 showed a noticeable treating effect on asthmatic rats which is equivalent to the effect of dexamethasone, while avoiding the side-effect induced by the corticorsteroid. This suggests that the drug-in-adhesive transdermal patch is a promising delivery system containing α-asarone to be used for asthma treatment.     

青藤碱压敏胶分散型贴剂的制备及体外经皮渗透性考察

目的制备青藤碱压敏胶分散型贴剂并考察其体外经皮渗透性。方法将青藤碱及各种渗透促进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,研究青藤碱贴剂的体外经皮渗透行为。结果由DURO-TAK87-4098型压敏胶制备的贴剂的稳态渗透速率显著高于由DURO-TAK 87-2677制备的贴剂。加入各种渗透促进剂后,促渗作用由大到小的排列顺序为(质量分数):15%肉豆蔻酸异丙酯>10%肉豆蔻酸异丙酯>10%氮酮>5%肉豆蔻酸异丙酯>10%油酸>10%N-甲基吡咯烷酮。联合应用促进剂后促渗作用由大到小的排列顺序为(质量分数):10%肉豆蔻酸异丙酯+5%薄荷醇>10%肉豆蔻酸异丙酯+5%氮酮>10%肉豆蔻酸异丙酯+10%薄荷醇>10%肉豆蔻酸异丙酯+10%氮酮,但与10%的豆蔻酸异丙酯或10%氮酮相比,没有协同作用。结论应用DURO-TAK87-4098型压敏胶制备的青藤碱压敏胶分散型贴剂有望制成长效抗炎镇痛贴剂,值得进一步深入研究。