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。     

青藤碱微乳与凝胶的皮肤渗透性比较

目的比较青藤碱微乳和凝胶对离体大鼠皮肤的透皮能力。方法以油酸-聚山梨酯-80-无水乙醇-水作为微乳的组成,采用改进的Franz扩散池研究青藤碱微乳和凝胶的透皮行为,用高效液相色谱法测定青藤碱浓度。结果青藤碱微乳的透皮速率大于青藤碱凝胶(P<0.01),青藤碱微乳平均透皮速率为116.44μg.cm-2.h-1,青藤碱凝胶为89.93μg.cm-2.h-1。结论青藤碱微乳有很强的透皮能力,有望成为青藤碱的新型透皮给药制剂。     

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。     

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。     

透皮贴剂在中药研究中的应用及发展现状

透皮贴剂以其独特的给药途径及优势成为现代医药行业的关注热点,然而,现有的透皮贴剂主要以化学药物或一些中药有效单体成分为主,中药复方透皮贴剂只占极少数.本文从中药透皮贴剂的概述、基质、质量评价、市场现状及存在问题等几方面进行综述,以期为中药透皮贴剂的研究和发展提供参考.     

青藤碱凝胶兔体内经皮给药的药动学

目的:研究青藤碱凝胶经皮给药的药动学特征。方法:采用HPLC测定血浆中青藤碱的浓度,分别给予家兔1%,2%,5%的青藤碱凝胶,以口服给药为对照,测定不同时间的青藤碱血药质量浓度,用3P97药动学程序进行处理,计算药动学参数。结果:青藤碱凝胶经皮给药后血药质量浓度明显低于口服给药,但达峰时间和半衰期延长。结论:青藤碱凝胶可达到缓慢释放的效果。     

青藤碱贴剂透皮吸收实验接收液的筛选

目的:筛选青藤碱贴剂的接收液.方法:采用体外透皮实验法,以生理盐水-乙醇、PBS缓冲液、PBS缓冲液-乙醇溶液为考察对象,在不同时间点取样接收液,HPLC测定青藤碱浓度,以单位面积累积透皮量对时间进行零级、一级、Higuchi方程拟合,计算透皮速率常数.结果:表明零级拟合效果较好,Higuchi方程和一级拟合效果不佳.结论:PBS-ethanol接收液透皮速率较快,符合透皮吸收实验对接收液的要求.     

青藤碱对神经肌肉传递的作用

青藤碱对大鼠离体膈神经隔肌标本能可逆性阻滞神经肌肉的传递,呈浓度依赖性抑制作用;对神经干的兴奋性和传导性无明显影响。高Ca~(2+)溶液可拮抗青藤碱对神经肌肉传递的阻滞作用。在小鸡颈二腹肌实验,青藤碱可降低肌肉对ACh的敏感性。青藤碱与琥珀胆碱相似,均使蟾蜍腹直肌标本产生收缩反应。新斯的明不能桔抗青藤碱对神经肌肉传递的阻滞作用,且有加强作用。提示青藤碱具有去极化型肌松药的某些作用特点。     

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。     

电致孔条件下青风藤提取液体内外透皮给药的相关性分析

目的:研究电致孔条件下青风藤提取液体内、外透皮给药的最优电学参数组合,并对体内、外透皮给药的相关性进行分析。方法:在电致孔药物导入仪产生的多种电学参数下,体外实验利用高效液相色谱法检测透过小鼠离体皮肤后接受池中青藤碱的浓度;体内实验采用活体透皮仪进行,测定小鼠的血药浓度。通过正交试验分别得到体外和体内实验的电致孔最优电学参数组合,并对相同电致孔参数下的体外透过浓度(X)与体内血药浓度(Y)进行线性回归。结果:体外透皮给药的最优电学参数条件为脉冲时间1.2ms、脉冲电压300V、波形为正弦波、脉冲频率120个·min-1、脉冲数360个;体内透皮给药的最优电学参数条件为脉冲时间1.3ms、脉冲电压300V、波形为正弦波、脉冲频率120个·min-1、脉冲数360个,二者最优电学参数条件基本一致;回归方程为Y=0.657518X-16.255(r=0.9547),体内外相关性非常显著(α=0.001)。结论:此方法可以用于电致孔条件下药物透皮给药的体内、外相关性评价,有望为以后开发新型透皮给药系统提供参考依据。     

Glibenclamide transdermal patches: physicochemical, pharmacodynamic, and pharmacokinetic evaluations

In the present study, matrix type transdermal patches containing glibenclamide were prepared using different ratios of ethyl cellulose (EC)/polyvinylpyrrolidone (PVP) and Eudragit RL-100 (ERL)/Eudragit RS-100 (ERS) by solvent evaporation technique. The possible drug and polymer interaction was studied by infrared spectroscopy, differential scanning calorimetry, and HPTLC analysis. All the prepared formulations were subjected to physicochemical studies (thickness, weight variation, drug content, moisture content and uptake, and flatness), in vitro release and in vitro permeation studies through mouse skin. The results suggested that there was no interaction between drug and polymers. Variations in drug release/permeation profiles among the formulations studied were observed. The microphotographs obtained by scanning electron microscopy showed the formation of pores on the surface of the patches after in vitro skin permeation studies. Based on physicochemical and in vitro skin permeation studies, the formulations with EC:PVP (3:2) and ERL:ERS (4:1) were selected for in vivo experiments. The hypoglycemic activity of the patches in comparison with oral glibenclamide administration was studied for acute (24 h) and long-term (6 weeks) effect in both normal and streptozotocin-induced diabetic mice. Various biochemical parameters (serum levels of high-density lipoprotein-cholesterol, triglycerides, total cholesterol, alanine transaminase, aspertate transaminase, urea, and creatinine and liver protein and glycogen content) and histopathological (liver, pancreas and stomach) studies were carried out in diabetic mice after treating for 6 weeks. The patches were subjected to skin irritation test (by both visual observation and histopathological evaluation), oral glucose tolerance test and pharmacokinetic evaluation in mice. The results revealed that the patches successfully prevented the severe hypoglycemia in the initial hours, which is the major side effect associated with oral route. The patches maintained similar effect during long-term treatment also. The transdermal systems produced better improvement with all the tested biochemical parameters compared to oral administration. They produced improved repair of the tissues after diabetes induced tissue injury and exhibited negligible skin irritation. The pharmacokinetic evaluation showed that the patches could maintain almost steady-state concentration of drug within the pharmacologically effective range for prolonged period of time. The better in vivo performance of the transdermal patches of glibenclamide in comparison with oral administration could be due to day-to-day glycemic control on long-term application.     

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。     

Formulation and biopharmaceutical evaluation of a transdermal patch containing aceclofenac

To reduce the adverse effects of aceclofenac that accompanied with oral administration of this drug, transdermal patches in the form of drug-in-adhesive (DIA) patches, containing aceclofenac, were formulated. The effect of formulation factors on the skin permeation of the drug and physical properties of the patch were evaluated using excised rat skins. The optimized patch contained 12 % aceclofenac and 20 % lauryl alcohol in DT-2852 as a pressure-sensitive adhesive. The pharmacokinetic characteristics of the DIA patch were determined after application of the transdermal patches to human volunteers. The calculated relative bioavailability of the aceclofenac DIA patch was 18.2 % compared to oral administration of the drug. The findings of this study suggest that transdermal application of aceclofenac can substitute for oral administration of the drug.     

Natural oils as skin permeation enhancers for transdermal delivery of olanzapine: in vitro and in vivo evaluation

The feasibility of development of transdermal delivery system of olanzapine utilizing natural oils as permeation enhancers was investigated. Penetration enhancing potential of corn (maize) oil, groundnut oil and jojoba oil on in vitro permeation of olanzapine across rat skin was studied. The magnitude of flux enhancement factor with corn oil, groundnut oil and jojoba oil was 7.06, 5.31 and 1.9 respectively at 5mg/ml concentration in solvent system. On the basis of in vitro permeation studies, eudragit based matrix type transdermal patches of olanzapine were fabricated using optimized concentrations of natural oils as permeation enhancers. All transdermal patches were found to be uniform with respect to physical characteristics. The interaction studies carried out by comparing the results of ultraviolet, HPLC and FTIR analyses for the pure drug, polymers and mixture of drug and polymers indicated no chemical interaction between the drug and excipients. Corn oil containing unsaturated fatty acids was found to be promising natural permeation enhancer for transdermal delivery of olanzapine with greatest cumulative amount of drug permeated (1010.68 μg/cm2/h) up to 24 h and caused no skin irritation. The fabricated transdermal patches were found to be stable. The pharmacokinetic characteristics of the final optimized matrix patch (T2) were determined after transdermal application to rabbits. The calculated relative bioavailability of TDDS was 113.6 % as compared to oral administration of olanzapine. The therapeutic effectiveness of optimized transdermal system was confirmed by tranquillizing activity in rotarod and grip mice model.     

Comparative in vivo evaluation of propranolol hydrochloride after oral and transdermal administration in rabbits.

The purpose of this study was the in vivo evaluation of orally and transdermally administered propranolol hydrochloride in rabbits. Transdermal patches of propranolol hydrochloride (PPN) were formulated employing ethyl cellulose and polyvinylpyrrolidone as film formers. The pharmacodynamic (PD) and pharmacokinetic (PK) performance of PPN following transdermal administration was compared with that of oral administration. This study was carried out in a randomized cross-over design in male New Zealand albino rabbits. The PK parameters such as maximum plasma concentration (C(max)), time for peak plasma concentration (t(max)), mean residence time (MRT) and area under the curve (AUC(0-alpha)) were significantly (P<0.01) different following transdermal administration compared to oral administration. The terminal elimination half-life (t(1/2)) of transdermally delivered PPN was found to be similar to that following oral administration. In contrast to oral delivery, a sustained therapeutic activity was observed over a period of 24 h after transdermal administration compared to oral administration. The relative bioavailability of PPN was increased about fivefold to sixfold after transdermal administration as compared to oral delivery. This may be due to the avoidance of first pass effect of PPN. The sustained therapeutic activity was due to the controlled release of drug into systemic circulation following transdermal administration.     

青藤碱脂质体贴剂的经皮渗透行为研究

目的:研究青藤碱脂质体贴剂的经皮渗透行为.方法:以青藤碱脂质体贴剂与不含脂质体的普通贴剂为模型药物,分别采用离体和在体经皮渗透试验进行比较研究.结果:离体试验结果表明,脂质体贴剂的皮肤药物滞留率为21.20%,普通贴剂为5.38%;在体试验结果表明,青藤碱脂质体贴剂的皮肤药物滞留率为17.44%,普通贴剂为3.97%.结论:青藤碱脂质体能增强皮肤内的贮库效应,并能以零级均衡释放药物,从而更有效地形成对局部病灶组织的靶向.     

青藤碱电致孔给药的药动学及在关节腔中浓度的研究

目的比较电致孔与电加热条件下热敷给药时青藤碱在兔血液中的药动学及其在关节腔液中的浓度。方法在兔关节处分别进行电致孔和电加热热敷给药,给药后利用微透析技术收集关节腔透析液,同时通过耳缘静脉采血。串联质谱法测定血液及关节腔透析液中青藤碱浓度。DAS软件处理分析血药浓度数据,t检验分析关节腔透析液数据。结果电致孔给药组的AUC 0^∞为(3 915.0±537.7)ng·min·mL-1,是电加热给药组的2倍;Cmax为(29.3±4.9)ng·mL-1,是电加热给药组的2.5倍;tmax为(30.8±6.4)min比电加热给药组缩短20 min。电致孔给药时青藤碱在关节腔中的浓度是电加热给药的1.6∞为(3 915.0±537.7)ng·min·mL-1,是电加热给药组的2倍;Cmax为(29.3±4.9)ng·mL-1,是电加热给药组的2.5倍;tmax为(30.8±6.4)min比电加热给药组缩短20 min。电致孔给药时青藤碱在关节腔中的浓度是电加热给药的1.6⁶.9倍。结论电致孔与电加热给药相比增加了青藤碱入血的量,提高了青藤碱生物利用度,同时能让更多的青藤碱分布于关节腔局部。     

双藤巴布剂中青藤碱、雷公藤甲素的体外释放与体外透皮机制研究

目的:研究双藤巴布剂中青藤碱、雷公藤甲素的体外释放与体外透皮机制;比较以化学单体入药(青藤碱雷公藤甲素巴布剂,STP)与浸膏入药(双藤巴布剂,STEP)释放速率与透皮速率的差异。方法:通过释放度测定法测定体外释放度;通过Franze扩散池法测定药物的体外透皮性,皮肤为裸鼠背部皮肤。结果:STP与STEP中青藤碱、雷公藤甲素的体外释放以Higuchi方程拟合度较优(STP:r青=0.9955,r甲=0.9958;STEP:r青=0.9920,r甲=0.9963)。经皮渗透较好地拟合了零级动力学方程,青藤碱在STP、STEP中的r分别为0.9951与0.9926,透皮速率分别为21.729μg.cm-2.h-1与20.063μg.cm-2.h-1;雷公藤甲素在STP、STEP中的r分别为0.9942与0.9902,透皮速率分别为0.4783μg.cm-2.h-1与0.4168μg.cm-2.h-1。结论:青藤碱、雷公藤甲素在STP、STEP中的释放速率大于其经皮渗透速率,属于皮肤限速型经皮给药制剂。     

稳定性二氧化氯喷雾剂对家兔皮肤的刺激性实验

目的考察稳定性二氧化氯喷雾剂局部经皮给药的安全性。方法将健康家兔背部两侧对称脱毛3 cm×3 cm后,每次给予二氧化氯喷雾剂0.5 ml,对其完整皮肤和破损皮肤分别进行单次给药及多次给药的皮肤刺激性试验。结果该喷雾剂对于家兔完整皮肤和破损皮肤单次给药及多次给药后于1、24、48、72 h观察均无红肿或斑块出现。结论本试验条件下二氧化氯喷雾剂局部经皮给药无明显不良反应,表明安全性良好。为二氧化氯喷雾剂用于临床经皮给药提供可靠的试验依据和安全保障,为临床经皮给药提供一种新的二氧化氯新剂型。