N,N′-二甲基-2-咪唑啉酮在药物透皮吸收制剂中的应用

目的:综述了新溶剂DMI的性质及其在药物透皮吸收制剂中的应用。方法:查阅关于DMI的国内外文献。结果:DMI能促进某些药物的透皮吸收能力。结论:DMI在药物透皮吸收剂中的应用仍有局限,有待进一步开发     

N,N‘—二甲基—2—咪唑啉酮在药物透皮吸收制剂中的应用

目的:综述了新溶剂DMI的性质及其在药物透皮吸收制剂中的应用.方法:查阅关于DMI的国内外文献.结果:DMI能促进某些药物的透皮吸收能力.结论:DMI在药物透皮吸收剂中的应用仍有局限,有待进一步开发.     

促透剂在透皮吸收制剂中的应用概况

目的 为透皮吸收制剂的研究与开发提供信息参考。方法 查阅近年来国内外透皮吸收制剂研究论文,总结10种透皮吸收促进剂的研究报告。结果 透皮吸收促进剂在速度吸收制剂研究中的合理选择是影响药物透皮吸收的一个关键因素。结论 透皮吸收促进剂在药物透皮吸收制剂研究和新药开发中有着广泛的应用前景。     

促透剂在透皮吸收制剂中的应用概况

目的为透皮吸收制剂的研究与开发提供信息参考。方法查阅近年来国内外透皮吸收制剂研究论文，总结10种透皮吸收促进剂的研究报告。结果透皮吸收促进剂在透皮吸收制剂研究中的合理选择是影响药物透皮吸收的一个关键因素。结论透皮吸收促进剂在药物透皮吸收制剂研究和新药开发中有着广泛的应用前景。     

4-萜品醇脂肪酸酯对氟比洛芬贴剂的促渗透体内外相关性考察

摘要：目的:考察4-萜品醇（TEN）、4-萜品醇庚酸酯（TEN-C7）及肉豆蔻酸异丙酯（IPM）对氟比洛芬（FP）贴剂家兔在体促渗透活性,并对促透剂的促透体内外相关性进行初步探究。方法:以含不同促透剂的FP贴剂进行大耳兔体内药动学实验,计算FP的药动学参数,并使用反卷积分法验证药物的体内外渗透相关性。最后通过体外释放实验以及衰减全反射-傅里叶变换红外光谱法（ATR-FTIR）研究促透剂在药物释放、吸收过程中的作用机制。结果:体内渗透研究表明TEN-C7对FP的透皮递送具有显著的促透作用,并具有良好的体内外相关性（R2>0.878 3）;体外释放实验表明促透剂通过与压敏胶黏合剂分子的相互作用促进药物的释放;ATR-FTIR结果表明不同促透剂对FP的透皮通量增加与角质层脂质迁移率的增加以及促透剂和角质蛋白的相互作用相关。结论:TEN-C7对FP贴剂具有显著促透活性,有必要进一步研究拓宽其应用范围。     

促透剂在透皮吸收制剂中的应用概况

目的为透皮吸收制剂的研究与开发提供信息参考.方法查阅近年来国内外透皮吸收制剂研究论文,总结10种透皮吸收促进剂的研究报告.结果透皮吸收促进剂在透皮吸收制剂研究中的合理选择是影响药物透皮吸收的一个关键因素.结论透皮吸收促进剂在药物透皮吸收制剂研究和新药开发中有着广泛的应用前景.     

离子导入对卡托普利透皮吸收的促进作用(英文)

目的:研究离子导入技术对卡托普利透皮吸收的促进作用。方法:应用离子导入技术研究了卡托普利体外透过大鼠离体皮肤的影响因素,并进行了卡托普利水凝胶贴片大鼠在体的试验,测定了血药浓度的变化。结果:离子导入技术可以有效地促进卡托普利的透皮吸收,透皮速率增加约7倍。药物贮库中的各种因素如pH,离子强度,药物浓度和电流强度均影响药物的透皮速率。随着pH的增加,离子强度的减小,药物浓度的增加及电流强度的增加,透皮速率也增加。大鼠在体试验也表明用药1h后血药浓度即可达到坪值(约0.9μg/mL),并在整个试验阶段维持稳定。结论:离子导入可以有效地促进卡托普利的透皮吸收。     

含醇脂质体在透皮给药系统中的应用研究进展

目的 探讨含醇脂质体在透皮给药系统中的应用。方法 通过阐述脂质体在透皮给药系统中的特点、醇质体的制备、透皮吸收的实验及临床研究。了解含醇脂质体在透皮给药系统中的应用。结果 含醇脂质体应用于透皮给药系统具有许多优点,如醇质体能显著促进渗透。增加药物在皮肤中的滞留量。结论 含醇脂质体在透皮给药系统中的应用有巨大的发展潜力,有望成为一类新型的皮肤给药制剂。     

重组人干扰素α-2b软膏透皮试验研究

目的：考察不同透皮吸收促进剂对重组人干扰素α-2b软膏透皮吸收的促进效果。方法：采用单室水平扩散池，计时2h后从接受室内取样，用细胞病变抑制法测定透过Swiss小鼠腹部皮肤的干扰素的活性。结果：在软膏中加入透皮吸收促进剂能明显改善透皮吸收．且以2％水溶性氮酮和2％1，2-丙二醇联合应用的效果最好。结论：2％水溶性氮酮和2％1，2-丙二醇联用，提高了药物生物利用度和疗效。     

功效函数法评价双氯芬酸钠的透皮吸收效果

目的:探讨功效函数法在药物透皮吸收研究中的应用。方法:以双氯芬酸钠为模型药物,BALB/c裸小鼠、KM小鼠、SD大鼠及小型猪的腹部、背部、耳背部皮肤为载体,双氯芬酸钠稳态流量、渗透系数和滞后时间为指标,在双室透皮扩散装置上,通过离体动物皮肤渗透释药实验,采用功效函数法进行多指标综合评价。结果:双氯芬酸钠在不同动物不同部位皮肤中的渗透效果不同,以双氯芬酸钠在BALB/c裸小鼠背部皮肤上的透皮吸收效果最好。结论:功效函数法能够比较客观、合理地评价药物的透皮吸收效果。     

Transdermal delivery of nicardipine: an approach to in vitro permeation enhancement

Nicardipine hydrochloride (NC-HCl), a calcium channel blocker for the treatment of chronic stable angina and hypertension, seems to be a potential therapeutic transdermal system candidate, mainly due to its low dose, short half-life, and high first-pass metabolism. The objective of the present study was to evaluate its flux and elucidate mechanistic effects of formulation components on transdermal permeation of the drug through the skin. Solubility of NC-HCl in different solvent systems was determined using a validated HPLC method. The solubility of drug in various solvent systems was found to be in decreasing order as propylene glycol (PG)/oleic acid (OA)/dimethyl isosorbide (DMI) (80:10:10 v/v) > PG > PG/OA (90:10 v/v) > polyethylene glycol 300 > ethanol/PG (70:30 w/w) > transcutol > dimethyl isosorbide (DMI) > ethanol > water and buffer 4.7 > 2-propanol. Propylene glycol was then selected as the main vehicle in the development of a transdermal product. As a preliminary step to develop a transdermal delivery system, vehicle effect on the percutaneous absorption of NC-HCl was determined using the excised skin of a hairless guinea pig. Vehicles investigated included pure solvents alone and their selected blends, chosen based on the solubility results. In vitro permeation data were collected at 37 degrees C, using Franz diffusion cells. The skin permeation was then evaluated by measuring the steady state permeation rate (flux) of NC-HCl, lag time, and the permeability constant. The results showed that no individual solvent was capable of promoting NC-HCl penetration. Permeation profiles of the drug through hairless guinea pig skin using saturated solutions of drug were constructed. Among the systems studied, the ternary mixture of PG/OA/DMI and binary mixture of PG/OA showed excellent flux. The flux value of the ternary system was nearly three times higher than the corresponding values obtained for the binary solvent. A similar trend also was observed for the permeation constant, while the values of lag time were reversed. The ternary mixture was then selected as a potential absorption enhancement vehicle for the transdermal delivery of drug. In general, higher fluxes were observed through hairless guinea pig skin as compared with the human stratum corneum. Based on the results obtained from the release study of NC-HCl from saturated solutions of the drug, a novel lecithin organogel (microemulsion-based gel) composed of soybean lecithin, propylene glycol, oleic acid, dimethyl isosorbide, and isopropyl myristate was developed as a possible matrix for transdermal delivery of NC-HCl. In vitro percutaneous penetration studies from this newly developed gel system through giunea pig skin and human stratum corneum revealed that the organogel system has skin-enhancing potential and could be a promising matrix for the transdermal delivery of nicardipine. Furthermore, higher permeation rates were observed when nicardipine free base was incorporated into the gel matrix instead of hydrochloride salt.     

Evaluation of the bioequivalence of two transdermal fentanyl systems following single and repeat applications

OBJECTIVE: Transdermal delivery of fentanyl has potential benefits over slow-release morphine, being largely preferred by patients owing to the combination of effective pain relief, a good safety profile and easy, pain-free dosing. The new drug-in-adhesive Durogesic D-TRANS fentanyl Matrix Delivery System (DDTDF) has improved pharmaceutical characteristics and patient acceptability compared to the original Durogesic transdermal reservoir system (fentanyl transdermal reservoir), whilst still providing reliable and consistent delivery of fentanyl. The bioequivalence of these two systems was evaluated in two studies. RESEARCH DESIGNS AND METHODS: Eighty healthy volunteers received single (72 h) or multiple (288 h) applications of DDTDF and the transdermal reservoir system (100 microg/h) in two separate randomised, crossover bioequivalence studies. Bioequivalence was assessed by calculating the ratio of least squares means based on log-transformed data following single system application and at steady-state during the fourth application. RESULTS: Both transdermal systems were bioequivalent with respect to all tested pharmacokinetic parameters. Inter-subject variability was comparable between the two systems and was greater than intra-subject variability. Transdermal delivery was well tolerated in both groups. CONCLUSIONS: The pharmacokinetic results demonstrate that DDTDF is bioequivalent to the original fentanyl transdermal reservoir system after single and multiple applications.     

脂质体经皮局部给药研究进展

目的：探讨脂质体在皮肤局部给药系统中的作用.方法：通过阐述脂质体在皮肤给药系统中透皮吸收的作用机制、影响因素以及在各领域的应用,了解脂质体在皮肤局部给药系统中的作用.结果：脂质体应用于皮肤局部给药系统具有许多优势.结论：脂质体在皮肤局部给药系统中有很大的发展潜力.     

Evaluation of the bioequivalence of two transdermal fentanyl systems following single and repeat applications

ABSTRACT

Objective: Transdermal delivery of fentanyl has potential benefits over slow-release morphine, being largely preferred by patients owing to the combination of effective pain relief, a good safety profile and easy, pain-free dosing. The new drug-in-adhesive Durogesic D-TRANS fentanyl Matrix Delivery System (DDTDF) has improved pharmaceutical characteristics and patient acceptability compared to the original Durogesic transdermal reservoir system (fentanyl transdermal reservoir), whilst still providing reliable and consistent delivery of fentanyl. The bioequivalence of these two systems was evaluated in two studies.

Research designs and methods: Eighty healthy volunteers received single (72?h) or multiple (288?h) applications of DDTDF and the transdermal reservoir system (100?µg/h) in two separate randomised, crossover bioequivalence studies. Bioequivalence was assessed by calculating the ratio of least squares means based on log-transformed data following single system application and at steady-state during the fourth application.

Results: Both transdermal systems were bioequivalent with respect to all tested pharmacokinetic parameters. Inter-subject variability was comparable between the two systems and was greater than intra-subject variability. Transdermal delivery was well tolerated in both groups.

Conclusions: The pharmacokinetic results demonstrate that DDTDF is bioequivalent to the original fentanyl transdermal reservoir system after single and multiple applications.     

双氯芬酸二乙胺凝胶的体外透皮扩散研究

目的:制备双氯芬酸二乙胺凝胶并考察其释药影响因素。方法:采用正交试验,对双氯芬酸二乙胺凝胶进行体外透皮试验,以透皮扩散速率常数为考察指标。结果:双氯芬酸二乙胺凝胶的处方中异丙醇浓度为15%,丙二醇为10%,卡泊姆934为0.5%时,药物的透皮扩散速率最快。结论:卡泊姆934的浓度为影响透皮扩散的主要因素。     

马来酸噻吗洛尔胶浆剂制备及其体外透皮特性研究

目的:制备马来酸噻吗洛尔胶浆剂,考察制剂性状和体外透皮能力以及药物浓度对透皮量的影响.方法:以羧甲基纤维素钠为胶浆剂基质,单因素试验优化处方,通过体外透皮扩散试验考察药物透皮能力.结果:该胶浆剂是一种粘稠液体,涂抹后可自发成膜,其透皮行为与自制的凝胶剂无统计学差异.本实验表明,制剂浓度会影响药物透皮量,浓度越高,透皮量越大.结论:马来酸噻吗洛尔胶浆剂制备简单,辅料安全,是一种具有独特优势的局部给药制剂.     

氟比洛芬透皮贴剂的质量控制及体外透皮试验

目的:建立氟比洛芬贴剂的质量控制方法,并考察其体外透皮效果.方法:以HPLC法测定氟比洛芬的含量,并测定黏附性能、含量均匀度等指标;同时对其小鼠离体皮肤透皮特性进行了测试.结果:建立的HPLC法可用来测定氟比洛芬的含量,在0.1～100 mg·L-1范围内线性关系良好,该贴剂具有良好的黏附性能,24 h内累积渗透量为979.9 μg.结论:建立的方法可用于氟比洛芬贴剂的质量控制,其体外透皮效果良好.     

更昔洛韦左氧氟沙星喷雾剂经皮渗透作用研究

目的:考察更昔洛韦左氧氟沙星喷雾剂经皮渗透作用。方法:采用改良型Franz扩散池(垂直式),吸收液为pH7.4的磷酸盐缓冲液,用高效液相色谱法同时测定接收液中主药更昔洛韦、左氧氟沙星的浓度,计算其累积透皮量、累积透皮率和单位面积累积透皮量。结果:更昔洛韦、左氧氟沙星渗透速度分别为2.1981、9.2203μg.cm-2.h-1。结论:更昔洛韦左氧氟沙星喷雾剂中2主药透皮吸收行为均符合Fick’s第一定律。     

芬太尼透皮贴剂不同治疗方案在癌痛治疗中的疗效观察

目的:评价芬太尼透皮贴剂不同治疗方案的镇痛效果与不良反应(ADR)。方法:将189例癌痛患者随机分为3组:芬太尼透皮贴剂常规剂量组(A组)、芬太尼透皮贴剂常规剂量+12h吗啡控释片组(B组)、2倍常规剂量芬太尼透皮贴剂+12h吗啡控释片组(C组),治疗6d后采用视觉模拟量表(VAS)疼痛评分比较3组的疗效。结果:A组与B、C组疗效比较有显著性差异(P<0.05或P<0.01),C组与B组治疗效果也有差异性(P<0.05),3组ADR比较无显著性差异(P>0.05)。结论:与A、B组比较,C组治疗方案发挥良好的镇痛效果,安全性高,有较高的临床应用价值。     

透皮促进剂对祖师麻膏药透皮吸收的影响

目的:筛选祖师麻膏药的透皮促进剂,提高其透皮利用率.方法:采用TP-3扩散池,选择离体大鼠皮肤为渗透屏障,从接收池取样,用HPLC检测法测定样品中瑞香素的含量,比较氮酮、薄荷脑和冰片对祖师麻膏药透皮吸收的影响.结果:4%的氮酮对瑞香素的促渗透作用最强.结论:4%的氮酮明显促进祖师麻膏药中主要有效成分瑞香素的透皮效率.