非洛地平/美托洛尔复方贴剂体外透皮特性及皮肤刺激性考察

目的 制备非洛地平/美托洛尔复方透皮贴剂,考察其对离体兔皮的经皮渗透性及对家兔皮肤的刺激性.方法 采用改良的Franz透皮扩散装置,以离体兔皮为渗透屏障,NS-乙醇(6040)为接受液,用HPLC法同时测定经皮渗透液中两药浓度并计算其渗透动力学参数.通过皮肤刺激性试验法考察该贴剂对家兔皮肤的刺激性.结果 非洛地平/美托洛尔复方透皮贴剂中非洛地平和美托洛尔48h内均以零级动力学经兔皮转运,并具一定同步性;该贴剂对家兔皮肤无刺激性.结论 非洛地平/美托洛尔复方透皮贴剂缓释长效特征明显,药物体外经皮渗透性较好且稳定,符合经皮给药系统应对皮肤无刺激性的设计要求.     

双氯芬酸钠微乳的家兔皮肤刺激性及体外透皮吸收性能评价

目的:对双氯芬酸钠微乳(DS-ME)的性质、皮肤刺激性及体外透皮吸收进行考察,探讨其局部外用给药的可行性。方法:采用紫外分光光度法测定DS-ME中DS的含量;采用激光粒度仪测定DS-ME的粒径分布;家兔皮肤刺激性实验考察DS-ME和空白ME对单次给药正常皮肤、多次给药正常皮肤和单次给药破损皮肤的影响;Franz扩散池法比较DS-ME与市售DS凝胶经小鼠离体皮肤的透皮参数。结果:所制DS-ME为O/W型微乳,粒径为(30.140±9.020)nm;与空白ME比较,DS-ME对家兔皮肤的刺激评分无明显差异;DS-ME与市售DS凝胶的稳态渗透速率分别为34.16、18.62μg/(cm~2·h),渗透系数分别为1.029、0.561 cm/h,滞后时间分别为0.124 2、0.367 2 h。结论:DS-ME的粒径小,无皮肤刺激性,可提高DS的透皮吸收速率。     

胰岛素体外透皮特性研究

目的 考察胰岛素透皮吸收特性及透皮促进剂对其透皮行为的影响。方法 通过V-C扩散池，用紫外分光光度法测定胰岛素的透皮吸收动力特性及透皮促进剂的促进作用。结果 胰岛素经离体小鼠、家兔、大鼠和人体皮肤的渗透系数分别为16．37，17．54，8．23和9．15。而氮酮(Azone)、冰片、油酸有明显的促透作用，其中3％的Azone和2％的冰片使渗透系数分别增加了4．9和6．1倍。结论 胰岛素在大鼠皮肤中渗透系数与人体皮肤接近，冰片和Azone具有促进药物渗透作用。     

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。     

熵权系数法综合评价促透剂的促透效果

目的 探讨熵权系数法在透皮吸收促进剂中促透效果的综合评价.方法 研究单用及联用薄荷醇和月桂氮酮对模型药物扑热息痛在离体家兔皮肤上的透皮行为,计算稳态流量、渗透系数和滞后时间3个指标,采用熵权系数法进行多指标的综合评价.结果 2%薄荷醇对扑热息痛具有最佳的促透效果,1%薄荷醇+1%月桂氮酮、2%薄荷醇+1%月桂氮酮、1%...     

阿司匹林透皮吸收的研究

离体兔皮进行体外释放试验表明氮酮对阿司匹林具较强的促进作用。家兔体内试验表明封闭技术、局部加温均可促进阿司匹林的透皮吸收。     

碘酊和聚维酮碘溶液的离体小鼠透皮吸收率及在体家兔甲状腺指标的比较

目的:研究碘酊和聚维酮碘溶液的离体小鼠透皮吸收率及在体家兔甲状腺指标。方法:采用硫代硫酸钠滴定法测定含碘量3%(3g/100ml)的碘酊和聚维酮碘溶液在Franz扩散池中3h透过小鼠离体皮肤的碘浓度,计算透皮吸收率。将家兔分为A(完整皮肤涂抹含碘量0.5%的聚维酮碘0.5ml)、B(破损皮肤涂抹含碘量0.5%的聚维酮碘0.5ml)、C(完整皮肤涂抹含碘量2%的碘酊0.5ml)、D(完整皮肤涂抹含碘量2%的碘酊0.5ml并脱碘2次)、E(不作任何处理)组,每组5只,作相应处理,每日2次,采用电化学发光仪器测定各组家兔给药前和给药30d后血清中促甲状腺激素(TSH)、三碘甲状腺原氨酸(T3)、甲状腺素(T4)的浓度,并测定各组家兔给药30d后甲状腺的质量。结果:碘酊在0.5h时已经有少量透过小鼠皮肤,且随着时间延长,透皮吸收率越大,3h时透皮吸收率为(56.41±10.02)%;聚维酮碘溶液3h内基本不透过小鼠皮肤。与E组家兔和给药前比较,B、C、D组家兔给药30d后T4浓度明显增加(P<0.01),其余指标均无明显变化(P>0.05);与C组家兔比较,D组家兔给药30d后T4浓度明显减少(P<0.01);与E组家兔比较,A、B、C、D组家兔的甲状腺质量均无明显变化(P>0.05)。结论:碘酊易透过皮肤,酒精脱碘可有效减少透过;聚维酮碘不能透过完整皮肤,但能透过破损皮肤。     

应用Excel进行密切值法综合评价几种促透剂的促透效果

目的探索Excel密切值法在促透剂促透效果综合评价中的应用。方法以对乙酰氨基酚为模型药物,研究氮酮、薄荷醇、石菖蒲挥发油、广藿香挥发油等几种促透剂在离体家兔背部皮肤上的透皮行为,计算滞后时间(T_(lag))、稳态流量(J_(ss))、渗透系数(K_P)3个指标,运用Excel密切值法综合评价促透效果。结果对对乙酰氨基酚促透效果的优劣顺序为:2%薄荷醇、5%广藿香挥发油、1%氮酮、7%石菖蒲挥发油。结论应用Excel进行密切值法可有效地评价几种促透剂的促透效果。     

月桂氮(艹卓)酮对10种药物透皮吸收的促进作用

月桂氮(艹卓)酮(Laurocapram)又名氮酮(Azone),为新型皮肤渗透促进剂,近年来不断报道其对药物的透皮吸收促进作用。现将其对10种药物的促透作用,简要归纳如下供参考。异烟肼于忠兴等采用离体兔皮在静     

聚类判别分析法评价4种促透剂的促透效果

目的:运用聚类判别分析法评价4种促透剂的促透效果。方法:研究氮酮、薄荷醇、石菖蒲挥发油、二甲基亚砜对模型药物对乙酰氨基酚在离体兔背部皮肤上透皮行为的影响,计算稳态流量、渗透系数、滞后时间、增渗倍数,运用聚类判别分析法中的欧氏距离值对促透效果进行综合评价。结果:聚类判别分析法分析结果与透皮试验所得数据处理的结果相符合。结论:聚类判别分析法对促透剂促透效果进行综合评价是可行的。     

角质层与活性皮肤层对硝酸异山梨酯透皮吸收的影响

目的:评价皮肤角质层和真皮层对药物经皮吸收的影响。方法:以硝酸异山梨酯(ISDN)为模型药物,采用Franz吸收池法,考察药物单独或与吸收促进剂肉豆蔻酸异丙酯(IPM)合用时,经完整皮肤和角质层剥离皮肤的透皮能力。结果:IS-DN经剥离角质层皮肤的表观透皮系数的Kp是经完整皮肤的1.68倍,IPM能分布在活性皮肤层,并可明显增加ISDN在角质层或真皮层的分布量及经皮累积透皮吸收百分率。结论:本实验为研究皮肤病态条件下(如皮肤受伤或溃疡等),药物透皮吸收规律,提供了一种新的方法。     

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.     

氢醌经不同皮肤层的吸收差异

目的 :评价皮肤角质层和真皮层对药物经皮吸收的差异。方法 :选择氢醌 (HQ)为模型药物 ,采用Franz吸收池法 ,考察药物经完整皮肤和剥离角质层皮肤的体外透皮能力Kp ,并比较吸收促进剂肉豆蔻酸异丙酯(IPM)共存时的促透能力大小。结果 :HQ经剥离角质层皮肤的Kp 是经完整皮肤的3 29倍 ,加入IPM后HQ的Kp 分别提高到原来的4 95倍 (经完整皮肤 )和7 49倍 (经剥离角质层皮肤 )。结论 :本实验为皮肤病态条件 ,如皮肤受伤或溃疡等时的药物经皮吸收规律研究提供了一种新的方法。     

博莱霉素脂质体凝胶的制备和体外透皮性比较

目的：研制博莱霉素（BLM）脂质体凝胶,并对其皮肤靶向性进行体外评价。方法：采用逆相蒸发-冻融法制备BLM脂质体,再用卡渡姆940为基质制成BLM脂质体凝胶;以离心法测定BLM脂质体的包封率;以体外透皮渗透释药法,比较BLM脂质体凝胶与BLM普通凝胶的透过作用。结果：BLM脂质体平均粒径为（885．20±12．08）nm,平均包封率为（66．80±1．38）％。在24h内,BLM脂质体凝胶累积透过量（Q）及稳态透皮速率（J）与BLM普通脂质体相比,均明显提高,而在皮肤中的滞留药量也显著提高（P〈0．05）。结论：BLM脂质体凝胶在体外可显著增加BLM的透皮吸收,增加皮肤中的滞留量,值得进一步研究。     

姜黄素醇质体体外透皮及其稳定性研究

目的：对姜黄素醇质体体外透皮及其稳定性进行考察方法：采用透皮扩散仪进行体外透皮实验,比较姜黄素醇质体、溶液、脂质体经小鼠离体皮肤的累积渗透量及皮肤滞留量;并将姜黄素醇质体4℃条件下冷藏,考察其稳定性。结果：姜黄素醇质体12h内单位面积皮肤的累计渗透量和皮肤滞留量是其溶液（含0．5％吐温-80）的2．71倍和2．81倍;但与其脂质体无显著差异。姜黄素醇质体4℃条件下冷藏1个月,其外观、包封率、粒径及多分散指数（PDI）变化较小。结论：醇质体作为透皮给药载体能促进姜黄素的透皮吸收,并能增加皮肤中的滞留量;姜黄素醇质体具有一定的稳定性。     

Skin permeation: the years of enlightenment

Considerable advances in our understanding of the mechanisms by which drugs permeate the skin barrier have been made over the past 60 years. The key publications, which have influenced the field of skin permeation research are highlighted in the present review. The methodologies commonly employed for estimation of skin permeability are discussed as are the mechanisms proposed for skin permeation. The principal findings from the commonly employed in vitro and in vivo models are considered as well as the applications of enhancers and surfactants for optimization of skin delivery. As these studies presaged the emergence of transdermal drug delivery research in the 1970s, early approaches to model and predict dermal and transdermal absorption are also outlined. The published work on skin permeability in this period embodies the fundamental literature sources for consultation by scientists new to and currently engaged in transdermal drug delivery.     

Dodecyl N,N-Dimethylamino Acetate and Azone Enhance Drug Penetration Across Human,Snake, and Rabbit Skin

The effectiveness of the penetration enhancers, dodecyl N, N-dimethylamino acetate (DDAA) and Azone, on pretreated human epidermis for the permeation of model drugs, indomethacin, 5-fluorouracil, and propranolol-HCl, was studied in in vitro diffusion cells. Snakeskin (Elaphe obsoleta) and rabbit pinna skin were compared as possible models for human skin. The drug concentrations were analyzed by HPLC. With all skins and all model drugs, DDAA increased drug permeability at least as well as Azone, and in most cases it was a more effective permeation enhancer. The relative permeation improvements in human skin, snakeskin, and rabbit skin were 10- to 20-, 5- to 50-, and 20- to 120-fold, respectively. Tritiated water served as an indicator of skin condition. Its penetration in the skin samples was independent of the drugs used, and both penetration enhancers significantly increased the flux of tritiated water through all skins. Thus, DDAA and Azone significantly increased the permeation of lipophilic and hydrophilic model compounds. Rabbit pinna skin was a poor model for human skin in vitro, while snakeskin was much closer to human skin in terms of transdermal permeability. In most cases drug permeability decreased in the order rabbit human > or < snake.     

Transdermal delivery of praziquantel: effects of solvents on permeation across rabbit skin

To explore a new method for the transdermal delivery of praziquantel (PZQ), the effects of solvents on permeation across rabbit skin were investigated. The solubility of PZQ in five different solvents, ethylene glycol monophenyl ether (EGPE), 1,4-dioxane, tetrahydrofuran, dimethyl sulfoxide, and oleic acid, were measured with a UV-Vis spectrophotometer. The determination of the n-octanol/water partition coefficient of PZQ in the five different solutions and assay of serum concentration following PZQ transdermal administration in rabbits were performed using HPLC. The results indicated that the transdermal absorption of the drug was related to the partition coefficient and lipophilic characteristics of the solvent. The optimal solvent for PZQ transdermal delivery was EGPE in our protocol. The solubility of PZQ in EGPE is >400 mg/ml, and the apparent partition coefficient of PZQ in the solution is 0.895 (log P value). After transdermal administration of PZQ in EGPE solution, the bioavailability is 2.85-fold that after oral administration. The serum drug concentration was maintained at 4.0 mug/ml over 4 h, which is sufficient for the treatment of schistosomiasis. At the same time, no apparent side effects were found on the skin. EGPE may thus be a promising vehicle for the transdermal delivery of PZQ in the future.     

非洛地平-美托洛尔复方经皮给药系统的制备及其兔体内生物利用度

制备了非洛地平-美托洛尔复方经皮给药系统，并研究其药剂学性质及经兔皮肤给药的药代动力学和生物利用度。先建立了同时测定贴剂和经皮渗透液中非洛地平与美托洛尔含量的RP-HPLC方法，以考察贴剂的药物体外稳态透皮速率和经皮渗透机制，并进行质量控制和评价；再以高灵敏度的GC-ECD方法分别测定非洛地平和美托洛尔的血药浓度，研究贴剂经皮给药后在兔体内的药代动力学和生物利用度。结果显示，该给药系统的复方药物体外透皮转运具有零级动力学特征，其含量均匀度检查符合2005版中国药典规定，稳定性好；经皮给药的血药浓度明显较口服平稳，且波动性小，达峰时间推后，持效时间延长，非洛地平与美托洛尔的相对生物利用度分别为275.37%和189.76%。以上结果表明，非洛地平-美托洛尔复方经皮给药系统具有明显缓释特征，可较长时间维持稳定有效的血药浓度。     

月桂氮酮对无环鸟苷霜体外透皮吸收作用的影响

考察不同浓度月桂氮酮对无环鸟苷霜的透皮促渗作用，进行合理的处方筛选。以离休兔皮为渗透屏障，采用改良Franz扩散池，研究不同浓度氮酮对无环鸟昔的透皮促渗作用。无环鸟苷霜的透皮吸收为零级动力学过程，氮酮对无环鸟苷的透皮促渗作用无浓度依赖性，经试验测得2％氮酮对无环鸟苷的促渗作用最强。