联苯乙酸透皮贴剂的体外透皮性能研究

目的:研究促进渗透剂对联苯乙酸贴剂(BPAA-TTS)体外透皮性能的影响.方法:用高体豚鼠皮肤为透皮屏障,采用改进的Franz扩散池,通过体外渗透性实验对含有不同处方的BPAA-TTS进行了透皮性能的研究.结果:体外渗透曲线符合平方根方程(Q=k×t1/2),含10%乙醇和8%的1,2-丙二醇的复合促进渗透剂的BPAATTS具有良好的透皮性能.结论:将加入复合促进渗透剂的贴剂中的BPAA的透皮速率与不加促进渗透剂贴剂的透皮速率进行比较,贴剂中药物的透皮性能有明显提高.     

双氯芬酸钠贴片的制备及体外释放、透皮吸收测定

目的:制备双氯芬酸钠贴片,研究其体外释放、透皮吸收性能.方法:制备以聚丙烯酸酯为骨架的双氯芬酸钠贴片,以蛇皮为模型,采用改进Franz扩散池考察药物经皮渗透性能,并按中国药典方法考察了贴片的体外释放性能.结果:双氯芬酸钠贴片体外释放速率为21.98μg·cm-2·h1/2,体外透皮速率为17.97 μg·cm-2·h-1/2.结论:双氯芬酸钠贴片释放度曲线及24 h累计渗透量均符合Higuchi方程,是一种新颖的缓释型外用制剂.     

莫索尼定贴片的制备及体外释放、透皮吸收研究

研究了莫索尼定贴片的制备、释放度及体外透皮吸收过程。该贴片释放度曲线符合Higuchi方程 ;莫索尼定从贴片中缓慢释放 ,72h累积透皮量符合Q～t方程     

双氯芬酸钠贴片的制备及体外释放、透皮吸收测定分析

目的探讨双氯芬酸钠贴片的制备方法,分析其体外释放与透皮吸收能力。方法制备以聚丙烯酸酯为骨架的双氯芬酸钠贴片,进行体外透皮与释放度试验、制备DCF标准曲线、进行DCF贴片释放度试验,用蛇皮进行体外经皮渗透试验,以改进Franz扩散池检验药物的经皮渗透性能。结果成功制作了以聚丙烯酸酯为骨架的双氯芬酸钠贴片,测定显示,双氯芬酸钠贴片的体外释放速率为21.98μg/(cm2 h1/2),体外透皮速率为17.97μg/(cm2 h1/2)。结论本次研究制定的双氯芬酸钠贴片的释放度曲线与24h累计渗透量与Higuchi方程相符合,是一种新型的缓释型外用制剂。     

高效液相色谱法测定可乐定透皮贴剂中可乐定的含量

<正>可乐定透皮贴剂是以透皮控释方式使可乐定以恒定的速度通过皮肤各层进入人体血液循环,产生全身降压作用。可乐定透皮贴剂国家现标准含量检测方法是紫外分光光度法,本文对可乐定透皮贴剂中含量检测方法进行了优化研究,建立高效液相色谱法测定可乐定含量的方法。1材料与仪器1.1材料:乙腈为色谱纯(Fish公司),水为纯化水,盐酸可乐定对照品(批号:100071-199905,中国药品生物制品检定所)。     

盐酸川芎嗪透皮贴剂体外透皮速率测定和体外释放研究

目的研究盐酸川芎嗪透皮贴剂的经皮吸收的可行性。方法采用高效液相色谱法测定透皮接受液和释放接受液中盐酸川芎嗪的浓度。结果体外透皮实验和体外释放实验结果表明：盐酸川芎嗪在24h内以一定的速率（0．1014mg／cm^2h^1恒速渗透,其释放符合Higuchi方程。此外,该贴剂的体外释放速率为0．1332mg／cm^2h^1/2。结论盐酸川芎嗪透皮贴剂为皮肤限速型的骨架控释透皮给药系统。     

咳喘穴位贴片体外透皮速率和体外释放规律研究

目的:研究咳喘穴位贴片体外透皮速率和体外释放规律。方法:采用高效液相色谱法测定透皮接受液和释放液中指标成分盐酸麻黄碱的浓度,计算其渗透速率和体外释药速率。结果:麻黄碱以6.4679μg.cm-2.h-1/2的速率恒速渗透,其体外释药速率为21.382μg.cm-2.h-1/2,其释放过程符合Higuchi方程。结论:咳喘穴位贴片可研制为皮肤限速型的骨架控释系统。     

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。     

不同药物浓度双氯芬酸钠贴剂的体外经皮渗透研究

目的:研究不同药物浓度双氯芬酸钠贴剂的体外经皮渗透行为.方法:不同药物浓度双氯芬酸钠贴剂进行体外经皮渗透试验,用高效液相色谱法测定接收液中双氯芬酸钠含量,以零级、一级、Higuchi动力学方程分别对试验结果进行数据拟合,进而阐明不同载药量对贴剂经皮渗透速率的影响及其透皮规律.结果:双氯芬酸钠贴剂的药物浓度为2.5%时体外经皮渗透过程以Higuchi动力学方程拟合为优,表明贴剂在此浓度下属于骨架溶蚀型释药系统.药物浓度在4.9%~14.67%时,体外经皮渗透均以零级动力方程拟合为优,表明该贴剂此时透过皮肤是一个被动扩散过程,Q-t关系可用Ficks扩散定律来描述.结论:双氯芬酸钠贴剂中药物浓度不仅影响其体外经皮渗透速率,而且决定其释药类型.     

酮洛芬贴片体外透皮释放方法学研究

目的:建立酮洛芬贴片体外透皮释放方法学。方法 :采用HPLC法测定释放液中酮洛芬的含量,测定条件:DiamonsilC18色谱柱(150 mm×4.6 mm,5μm),流动相为pH 3.5磷酸盐缓冲液-乙腈-水(2∶53∶45),检测波长为253 nm,流速为1.0mL.min-1,柱温25℃。以裸鼠皮肤为实验皮肤,采用Frans扩散池方法进行三批酮洛芬贴片样品的体外透皮实验。结果:在该HPLC条件下,酮洛芬与其他杂质分离良好,进样量在0.509~40.72μg.mL-1时,酮洛芬浓度与峰面积呈良好的线性关系(r=0.999 9),回收率为101.09%,RSD为1.23%。三批酮洛芬贴片样品的透皮释放速率分别为18.157,17.973,20.001μg.cm-2.h-1,药物透皮释放符合零级动力学过程。结论:本文建立的酮洛芬贴片体外透皮释放方法简便,重现性好,可以用于控制产品质量。     

纳米级与微米级珍珠粉中碳酸钙对离体小鼠皮肤渗透性的研究

目的:比较纳米级与微米级珍珠粉中碳酸钙对离体无毛小鼠皮肤的渗透能力。方法:将离体无毛小鼠皮肤固定在渗透扩散装置中,在扩散室中分别加入纳米级与微米级珍珠粉,在不同时间观察接受室内碳酸钙的量,计算两者的经皮渗透速率和皮肤渗透累积量。结果:微米级珍珠粉24 h碳酸钙的累积渗透量为 (2．13±s 0．23)mg·cm~(-2),纳米级珍珠粉为(3．01±0．14)mg·cm~(-2),差异有非常显著意义(P<0．01)。微米级珍珠粉经皮渗透速率为0．089 1 mg·cm~(-2)·h~(-1);纳米级珍珠粉为0．126 1 mg·cm~(-2)·h~(-1)。结论:纳米级珍珠粉中碳酸钙经皮渗透速率及皮肤渗透累积量均高于微米级珍珠粉,提示将珍珠粉纳米化后,可以更充分地发挥出珍珠的美容及药用功效。     

月桂氮酮促氨茶碱透皮吸收作用

目的：观察不同浓度的月桂氮酮对氨茶碱小鼠离休皮肤渗透性的影响。方法：测定和计算药物累积释放量（Ｑ）,稳态流量（Ｊ）,渗透系数（Ｋｐ）。结果：表明含不同浓度氮酮的氨茶碱乳膏均能增加药物的皮肤渗透性。结论：药物从乳膏基质向皮肤的渗透符合Ｈｉｇｕｃｈｉ方程。     

在体猪耳静脉灌流经皮吸收模型的建立与应用

目的建立在体猪耳静脉灌流经皮吸收模型，为经皮吸收制剂研究提供新方法。方法建立在体猪耳静脉灌流经皮吸收模型。以葡萄糖利用试验及乳酸脱氢酶活性检测评价模型的生物学活性，以酮洛芬异丙酯和水杨酸甲酯为模型药物考察系统的应用。结果葡萄糖利用及乳酸脱氢酶活性检测表明系统7 h内保持良好生物学活性。酮洛芬异丙酯经皮渗透过程中被完全代谢为酮洛芬，稳态时酮洛芬累积形成量Q与时间t回归的方程为Q=-0.024+0.120t，形成速率为0.120　μg·cm^-2·h^-1。水杨酸甲酯经皮渗透过程中部分被代谢为水杨酸，稳态时水杨酸甲酯累积渗透量Q与时间t回归的方程为Q=-3.809+6.129　t，渗透速率为6.129　μg·cm^-2·h^-1；水杨酸累积形成量Q与时间t回归的方程为Q=-1.785+0.879　t，形成速率为0.879　μg·cm^-2·h^-1。结论该模型操作简便、价格经济，不仅可以考察药物的经皮吸收，而且能够用于研究药物的皮肤代谢。     

In vitro and in vivo characterization of a newly developed clonidine transdermal patch for treatment of attention deficit hyperactivity disorder in children

The aim of this study was to characterize a newly developed clonidine transdermal patch, KBD-transdermal therapeutic system (TTS), for the treatment of attention deficit hyperactivity disorder in children. In vitro release, penetration, and in vivo pharmacokinetics in rabbits were investigated. The smaller size of KBD-TTS (2.5 mg/2.5 cm2) showed a similar in vitro penetration to those of Catapres-TTS (2.5 mg/3.5 cm2, a clonidine transdermal patch used for the treatment of hypertension, Alza Corporation, U.S.A.). The transdermal penetration rate of clonidine was mainly controlled by the ethylene vinylacetate membrane used in the patch. The skin layer may be only a minor rate-limiting barrier after the topical skin layer at the dosing site is saturated with penetrating clonidine in the initial phase (0 to 12 h). A sensitive liquid chromatography-mass spectrometry method for the quantification of clonidine in rabbit plasma was developed using solid-phase extraction and gradient elution on LC combined with the selected-ion monitoring (SIM) mode. A single dose of clonidine transdermal patch (KBD-TTS) or Catapres-TTS was transdermally administered to rabbits (n=6 each) and removed after 168 h. The average half-life, Tmax, Cmax and Css values of clonidine in rabbits following administration of KBD-TTS were 19.27+/-4.68 h, 52.56+/-25.77 h, 27.39+/-9.03 ng/ml, and 25.82+/-9.34 ng/ml, similar to those of Catapres-TTS, respectively. The clonidine plasma concentration of KBD-TTS reached a steady state at 24 h through 168 h. The in vitro release rate of the clonidine from KBD-TTS significantly correlated with the in vivo absorption rate (p<0.001).     

Transdermal-controlled administration of oxycodone.

The permeability of hairless mouse skin membrane to the weak base narcotic analgesic oxycodone (pKa = 8.53) was investigated. The effects of pH on the solubility and skin permeation rate were also studied. The results of the study of skin permeation of drug through hairless mouse skin suggest that the permeability of oxycodone base is approximately 7.4 times higher than that of protonated oxycodone. The nonionic species of oxycodone, at various drug loadings, was then incorporated in a Dow-Corning silicone elastomer for the evaluation of the release rate and skin permeation rate. It was found that Q/t1/2 is directly proportional to the square root of the drug loading dose, as expected by Higuchi's equation (where Q is the cumulative amount released and t is time). However, the skin permeation rate was observed to increase initially with drug loading and level off at the loading dose of 60 mg/cm3.     

Effect of Different Carriers on in vitro Permeation of Meloxicam through Rat Skin

The ability of β-cyclodextrin, hydroxypropyl-β-cyclodextrin, polyvinyl pyrrolidone and urea to influence the percutaneous absorption of meloxicam through isolated rat skin was evaluated. Carrier complex were prepared by kneading method in 1:1 and 1:2 in molar ratios for β-cyclodextrin and hydroxypropyl-β-cyclodextrin and in 1:1, 1:3 and 1:5 in weight ratios for polyvinyl pyrrolidone and urea. The complexes were characterized by IR, DSC and evaluated for solubility, dissolution and skin permeability. The solubility, dissolution and permeability of meloxicam were enhanced by using the carriers. The influence of cyclodextrins, polyvinyl pyrrolidone and urea on in vitro permeation of meloxicam through rat skin was investigated by incorporation of prepared carrier complex in 1% carbopol gel. The prepared gel was evaluated for drug content, pH and viscosity and in vitro permeation. All the percutaneous parameters like flux (Jss), amount permeated (Q(6)), diffusivity (D), permeability coefficient (K(p)), partition coefficient (K) and release rate constant (k) were calculated statistically. In vitro permeation study showed the trend that the penetration flux and enhancement factor increases with increasing concentration of β-cyclodextrin and hydroxypropyl-β-cyclodextrin and then decrease dramatically in case of hydroxypropyl-β-cyclodextrin gel formulation with the increase to 1:2 ratio. Similar changes in pattern of permeation were also observed with polyvinyl pyrrolidone and urea carrier complex. These findings concluded that the carriers cyclodextrins, polyvinyl pyrrolidone and urea could be used as transdermal permeation enhancer in topical preparation of meloxicam.     

当归挥发油对尼莫地平透皮吸收的影响

目的研究当归挥发油对尼莫地平体外经皮渗透的影响。方法以30％乙醇 0.9%氯化钠溶液为接收液,不同浓度的当归挥发油为促渗剂,以预处理的体外兔皮肤作为渗透屏障,Franz扩散池进行体外渗透实验,高效液相色谱法测定尼莫地平的含量。结果不同浓度当归挥发油均能显著提高尼莫地平渗透速率（均P＜0.05）,其中1.0%当归挥发油促渗效果最好,渗透速率为36.63 μg&#8226;（cm2） 1&#8226;h 1,是对照组的3.25倍。结论当归挥发油可以作为尼莫地平经皮吸收制剂的促渗剂。     

氢溴酸加兰他敏贴剂的制备及体外释放和透皮特性研究

目的：制备氢溴酸加兰他敏贴剂,并对其体外释放度和体外透皮特性进行考察。方法：采用丙烯酸酯乳液型压敏胶为基质制备氢溴酸加兰他敏贴剂,按《中华人民共和国药典》规定方法进行贴剂的体外释放度测定;采用改良Franz扩散池,以离体小鼠皮肤为屏障进行氢溴酸加兰他敏贴剂的体外透皮特性研究。结果：氢溴酸加兰他敏贴剂的体外释放符合Higu-chi方程,24 h累积释药量占总药量的41.81%;体外透皮符合零级方程,24 h累积渗透量占总药量的19.99%。结论：采用丙烯酸酯乳液型压敏胶为基质制备的氢溴酸加兰他敏贴剂具有较好的体外释放和透皮特性。     

月桂氮(艹卓)酮对灭痤乳膏中螺内酯透皮作用研究

目的：研究不同浓度的月桂氮卓酮对灭痤乳膏中螺内酯小鼠离体皮肤渗透性的影响。方法：用改良的Franz扩散池，不同浓度月桂氮卓酮(0、1％、2％和5％)作促渗性试验，采用HPLC法测定和计算药物累积释放量(Q)，稳态流量（J），渗透系数(Kp)。结果：含1％～5％月桂氮卓酮的灭痤乳膏中螺内酯的Q值，较不含月桂氮卓酮者增加了73.66％～74.61％，但各浓度间Q值无显著性差异。结论：1％～5％月桂氮卓酮对灭痤乳膏中螺内酯有明显促渗作用。