维A酸维生素C棕榈酸酯泡囊的体外释放、经皮渗透和皮肤贮留研究

目的研究维生素C棕榈酸酯泡囊作为维A酸载体时,主药的体外释放、经皮渗透和皮肤贮留情况。方法采用Franz扩散池测定维A酸从载体中的释放速度,扩散池与供给池之间为纤维素膜（截留分子量8000～14000）,扩散池面积为2.92cm^2。体外透皮试验用小鼠、大鼠或兔子背部皮肤替代半透膜。在体外透皮试验完结后,取下皮肤,剪碎匀浆,用50%异丙醇-生理盐水提取,提取液处理后用HPLC测定药物浓度。结果结果表明维A酸释放速率和累积经皮渗透量大于市售乳膏,同时具有较高的皮肤贮留量。结论维生素C棕榈酸酯泡囊作为维A酸载体有助于增加局部药物浓度。     

维A酸维生素C棕榈酸酯泡囊的体外释放、经皮渗透和皮肤贮留研究

目的 研究维生素C棕榈酸酯泡囊作为维A酸载体时,主药的体外释放、经皮渗透和皮肤贮留情况。方法 采用Franz扩散池测定维A酸从载体中的释放速度,扩散池与供给池之间为纤维素膜(截留分子量8 000~14 000),扩散池面积为2.92 cm²。体外透皮试验用小鼠、大鼠或兔子背部皮肤替代半透膜。在体外透皮试验完结后,取下皮肤,剪碎匀浆,用50%异丙醇-生理盐水提取,提取液处理后用HPLC测定药物浓度。结果 结果表明维A酸释放速率和累积经皮渗透量大于市售乳膏,同时具有较高的皮肤贮留量。结论 维生素C棕榈酸酯泡囊作为维A酸载体有助于增加局部药物浓度。     

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.     

氟尿嘧啶泡囊凝胶剂的体外透皮试验

目的:研究氟尿嘧啶泡囊凝胶剂的体外透皮扩散率及皮内滞留率。方法:建立用分光光度法测定氟尿嘧啶的方法,通过离体鼠皮透皮扩散试验,测定氟尿嘧啶泡囊凝胶的透皮扩散率及皮外残留率,并与氟尿嘧啶凝胶剂和医院制剂乳膏等作对照。结果:氟尿嘧啶泡囊凝胶剂的12 h的透皮累积扩散率仅为乳膏的10%,但皮内滞留率却增加2倍以上。结论:氟尿嘧啶泡囊凝胶剂可大大减少透过皮肤进入全身的药量,显著增加局部浓度,利于提高对皮肤病的疗效和降低全身毒性。     

高效液相色谱法测定环吡酮胺乳膏中药物的含量及其体外透皮释放量

目的采用高效液相色谱（HPLC）法测定环吡酮胺乳膏的含量及体外透皮量.方法色谱柱为Intersil ODS 3 C18柱（4.6 mm×200 mm,5 μm）,流动相为乙腈 0.1%乙二胺四醋酸二钠溶液（70：30）,检测波长304 nm.体外透皮释放实验采用单室Franz扩散池,大鼠皮肤,自制乳膏与市售乳膏的透皮结果对比.结果环吡酮胺在20～180 μg&;#8226;mL 1范围内,线性关系良好（r＝0.999 8）,平均回收率为99.7%,RSD为0.69%.体外透皮释放量与时间呈良好的线性关系,相关因素为0.967 9.自制乳膏与市售乳膏的透皮结果差异无显著性.结论该法测定环吡酮胺乳膏药物含量及体外透皮释放量操作简便,快速准确.软膏基质和皮肤中成分对测定无干扰.     

喷他佐辛贴剂的质量控制及体外透皮试验

目的建立喷他佐辛贴剂的质量控制方法,并考察其体外透皮效果。方法以HPLC法测定喷他佐辛的含量,并测定粘附性能、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法可用来测定喷他佐辛的含量,在0.1～200mg.L-1范围内线性关系良好,该贴剂具有良好的粘附性能,24h内累积渗透量为2.486mg。结论建立的方法可用于喷他佐辛贴剂的质量控制,其体外透皮效果良好。     

圣肤霜乳膏中地塞米松体外透皮扩散及皮肤局部载药测定

目的:考察圣肤霜乳膏中醋酸地塞米松透过皮肤的能力。方法:通过Hanson透皮吸收扩散仪,对圣肤霜乳膏进行体外透皮扩散实验,以反相高效液相色谱法测定接收池中地塞米松含量和皮肤局部载药量。结果:圣肤霜乳膏中醋酸地塞米松只有少量缓慢透过皮肤。结论:圣肤霜乳膏中的醋酸地塞米松发挥的是局部治疗作用,而不是透过皮肤起全身治疗作用。     

芬太尼透皮贴剂联合唑来膦酸治疗恶性肿瘤骨转移疼痛临床研究

目的观察芬太尼透皮贴联合唑来膦酸治疗恶性肿瘤骨转移疼痛的疗效及毒性。方法 46例恶性肿瘤骨转移疼痛患者随机分为芬太尼透皮贴剂联合唑来膦酸组(A组)和芬太尼透皮贴剂组(B组),A组23例患者每72h接受芬太尼透皮贴剂4.2～8.4mg,并接受唑来膦酸4mg,加入生理盐水100mL内,静脉滴注15min,每月1次;B组23例接受芬太尼透皮贴剂的患者不接受唑来膦酸治疗。结果 A组:CR 4例(17.4%),PR 9例(39.1%),有效率52.2%;B组:CR 1例(4.4%),PR 4例(17.4%),有效率21.7%。结论芬太尼透皮贴联合唑来膦酸治疗恶性肿瘤骨转移疼痛疗效较好,不良反应轻,患者可耐受。     

中药骨伤凝胶贴剂的经皮渗透性研究

目的 探讨药粉目数及透皮吸收促进剂对中药骨伤凝胶贴剂经皮渗透作用的影响。方法 以羟基红花黄色素A和血竭素为评价指标，采用桨碟法评价凝胶贴剂的体外释放行为，采用Franz扩散池法考察药粉目数及透皮吸收促进剂对凝胶贴剂透皮吸收的影响。结果 与氮酮和薄荷脑相比，肉豆蔻酸异丙酯对于羟基红花黄色素A和血竭素的促渗作用最好，其最佳用量为3%，200目的药粉相对于80目在体外释放及有效成分的经皮吸收方面没有明显影响。结论 药粉目数对凝胶贴剂经皮渗透作用的影响不显著，肉豆蔻酸异丙酯透皮吸收促进剂能显著提高凝胶贴剂的透皮吸收。     

高效液相色谱法测定环吡酮胺乳膏中药物的含量及其体外透皮释放量的研究

目的：探讨环吡酮胺乳膏应用高效液相色谱法进行药物含量与体外透皮释放量测定的效果。方法检测波长305 nm;流动相：乙腈-0.1%乙二胺四醋酸二钠溶液（70：30）;Kromasil C18色谱柱;应用单室Franz扩散池、大鼠腹皮进行透皮释放实验,对比市面乳膏与自制乳膏的透皮结果。结果环吡酮胺范围介于20~180μg/mL间,平均回收率99.8%,RSD为0.70%,线性关系较好（r=0.9997）,相关因素为0.9673,市面乳膏与自制乳膏透皮结果差异无统计学意义（P〉0.05）。结论采用高效液相色谱法测定环吡酮胺乳膏不会受皮肤成分与软膏基质影响,且操作简便,准确率高,测定效果理想。     

自乳化基质乙氧苯柳胺乳膏的研制及透皮研究

目的：制备自乳化基质乙氧苯柳胺乳膏并对其体外透皮吸收行为进行考察。方法：采用Tefose63为自乳化基质制备乙氧苯柳胺乳膏并考察其稳定性，采用改进的Franz扩散池，以大鼠离体腹部皮肤为透皮模型，用HPLC法测定药物在透皮接收液中的浓度及皮肤中药物滞留量。结果：自乳化基质乳膏具有较好的稳定性，在皮肤中的渗透系数及药物滞留量明显大干市售软膏，离体条件下，自乳化基质乳膏8h渗透系数是市售软膏的1．56倍，皮肤中药物滞留量是市售软膏的2．31倍。结论：自乳化基质乙氧苯柳胺乳膏能促进药物渗透到皮肤并增加药物在皮肤中的滞留量，有望成为新型经皮给药制剂。     

In vitro permeation of levothyroxine across the skin

The aim of this work was to investigate the in vitro transdermal permeation characteristics of sodium levothyroxine, in view of its topical application. Permeation experiments were performed in vitro, using rabbit ear skin as barrier. At the end of the experiments levothyroxine retained in the skin was extracted and quantified by HPLC. The formulations tested were solutions and a commercial cream. The use of dimethyl beta-cyclodextrin as solubilizing agent increased to a significant extent levothyroxine solubility, but reduced its skin accumulation. Skin stripping before drug application produced a considerable increase in the amount retained and levothyroxine was found also in the receptor compartment. The application of the commercial cream in occlusive conditions increased to a significant extent drug retention in the skin. In conclusion, levothyroxine skin administration is promising in view of a localized effect, because it was retained in the skin. On the contrary, transdermal administration in view of systemic effect does not represent a concrete possibility.     

Design,development, physicochemical,and in vitro and in vivo evaluation of transdermal patches containing diclofenac diethylammonium salt

In this study, matrix-type transdermal patches containing diclofenac diethylamine were prepared using different ratios of polyvinylpyrrolidone (PVP) and ethylcellulose (EC) by solvent evaporation technique. The drug matrix film of PVP and EC was casted on a polyvinylalcohol backing membrane. All the prepared formulations were subjected to physical studies (moisture content, moisture uptake, and flatness), in vitro release studies and in vitro skin permeation studies. In vitro permeation studies were performed across cadaver skin using a modified diffusion cell. Variations in drug release profiles among the formulations studied were observed. Based on a physicochemical and in vitro skin permeation study, formulation PA4 (PVP/EC, 1:2) and PA5 (PVP/EC, 1:5) were chosen for further in vivo experiments. The antiinflammatory effect and a sustaining action of diclofenac diethylamine from the two transdermal patches selected were studied by inducing paw edema in rats with 1% w/v carrageenan solution. When the patches were applied half an hour before the subplantar injection of carrageenan in the hind paw of male Wistar rats, it was observed that formulation PA4 produced 100% inhibition of paw edema in rats 12 h after carrageenan insult, whereas in the case of formulation PA5, 4% mean paw edema was obtained half an hour after the carrageenan injection and the value became 19.23% 12 h after the carrageenan insult. The efficacy of transdermal patches was also compared with the marketed Voveran gel and it was found that PA4 transdermal patches produced a better result as compared with the Voveran gel. Hence, it can be reasonably concluded that diclofenac diethylamine can be formulated into the transdermal matrix type patches to sustain its release characteristics and the polymeric composition (PVP/EC, 1:2) was found to be the best choice for manufacturing transdermal patches of diclofenac diethylamine among the formulations studied.     

Novel biomaterial for transdermal application: in vitro and in vivo characterization

The objective of the present study was to evaluate a novel film forming biomaterial for its potential application in the preparation of unilaminate transdermal adhesive matrix systems. The biomaterial, Damar Batu (DB), was tried alone and in combination with Eudragit RL100 as a matrixing agent in the preparation of transdermal patches. Developed transdermal patches of Diltiazem hydrochloride (DH) were evaluated for thickness uniformity, weight uniformity, folding endurance and drug content. USP dissolution apparatus V was used for in vitro drug release studies. Modified Franz diffusion cell used for permeation study using excised human cadaver skin. Total 6 formulations were developed and on the basis of in vitro drug release and in vitro skin permeation profile F5 composed of DB: Eudragit RL100 (60:40) and carrying 20 %w/w DH was selected as an optimized formulation for in vivo study. The in vivo study results showed that F5 achieved the Cmax of about 269.76 ± 1.52 ng/mL in 6 h and sustained the release of the drug till 24 h. The skin irritation study results proved that the novel biomaterial is non-sensitizing and non-irritating. Drug-polymer interaction study carried out to check the compatibility of drug and polymer showed the intactness of the drug in the formulation proving the compatibility of the polymer. It can be proposed from the outcome of the present study that by applying suitable adhesive layer and backing membrane, DB: Eudragit RL100 (60:40) transdermal patches can be of potential therapeutic use.     

2种盐酸特比萘芬乳膏体外透皮扩散试验研究

目的:考察2种盐酸特比萘芬乳膏体外透过皮肤量及其在皮肤中贮药量以阐明其起效途径。方法:采用改良Franz扩散池,离体小型猪皮肤,取2种盐酸特比萘芬乳膏(国产与进口制剂)各1.0g进行体外透皮扩散试验,以反相高效液相色谱法测定接受液中盐酸特比萘芬的含量(计算透过率)和皮肤中贮药量。结果:国产及进口制剂中盐酸特比萘芬的体外皮肤透过率均低于0.05%,皮肤贮药量分别为(43.1±7.5)、(42.2±4.9)μg·cm-(2n=6)。结论:2种制剂中盐酸特比萘芬几乎不透过皮肤,皮肤贮药量相近,表明二者药效和安全性基本一致,并主要发挥局部治疗作用。     

Microemulsion-based gel of fluorouracil for transdermal delivery

This study is to prepare the microemulsion-based gel based on the W/O microemulsion and fluorouracil (5-Fu) as a model drug to study the transdermal characterization and observe its skin irritation of the microemulsion-based gel in vitro. IPM acted as oil phase, AOT as surfactant, Tween 85 as cosurfactant, water was added dropwise to the oil phase to prepare W/O microemulsion at room temperature using magnetic stirring, then 5-Fu powder was added. The gelatin was used as substrate to prepare 5-Fu microemulsion-based gel. The permeation flux of 5-Fu from 5-Fu microemulsion-based gel across excised mice skin was determined in vitro using Franz diffusion cell to study the influence of the amount of gelatin and the drug loading capacity. Refer to 5-Fu cream, the irritation of microemulsion and microemulsion-based gel on the rat skin was studied. Based on the water/AOT/Tween 85/IPM microemulsion, only the gelatin can form the microemulsion-based gel. At 25 degrees C, 32 degrees C and 40 degrees C, the amount of gelatin required for the formation of microemulsion-based gel were 7%, 14% and more than 17%, respectively. The 12 h transdermal cumulated permeation amount of 5-Fu from microemulsion-based gel containing 14% gelatin and 0.5% drug loading were (876.5 +/- 29.1) microg x cm(-2), 12.3 folds and 4.5 folds more than 0.5% 5-Fu aqueous solution and 2.5% (w/w) 5-Fu cream, respectively. Microemulsion-based gel exhibited some irritation, but could be subsided after drug withdrawal. Microemulsion-based gel may be a promising vehicle for transdermal delivery of 5-Fu and other hydrophilic drug.     

Transdermal kinetics of a mercurous chloride beauty cream: an in vitro human skin analysis

BACKGROUND: Crema de Belleza-Manning is a popular mercurous chloride-containing beauty cream used to smooth and lighten the complexion and treat acne. Hundreds of people in the Southwestern US border states have been identified with elevated (>20 microg/L) urine mercury levels believed to be secondary to using this cream. The kinetic characteristics of percutaneous mercury absorption are incompletely defined. The objective of this study was to determine the transdermal kinetics of two formulations of mercurous chloride from a beauty cream in an in vitro human skin model. METHODS: A proprietary formulation and an aqueous formulation of the beauty cream were studied using modified Franz diffusion cells. Mercury content in the skin samples and the underlying diffusion buffer was determined using atomic absorption spectrophotometry. RESULTS: A rapid initial increase in mercury content both in the skin and the buffer was noted for both formulations. Mercury concentrations in the aqueous samples were significantly (p < 0.05) higher in both the skin and the diffusion buffer compared to parallel samples containing glycerol. CONCLUSIONS: Mercury was readily absorbed through the skin in this in vitro human skin model. The aqueous preparation had a markedly increased rate and extent of mercury absorption relative to the proprietary formulation.     

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.