Effects of penetration enhancers on Shuangwu traumatic formula: In vitro percutaneous absorption and in vivo pharmacodynamic evaluation of an herb medicine

The purposes of this study were to improve the transdermal permeation of the Shangwu traumatic formula by chemical penetration enhancers and to investigate the pharmacodynamic changes of the formula caused by incorporated enhancers. The effects of different enhancers on the transdermal absorption of piperine, the representative component of formula, were investigated by in vitro permeation studies. The tests showed an increasing enhancement effect in the following order: Azone/N-methylpyrrolidone (NMP) > oleic acid > Azone/peppermint oil > Azone/oleic acid > Azone/propylene glycol > Azone > peppermint oil > NMP > propylene glycol. The ratio and the content of the most effective enhancer Azone/NMP were determined subsequently. The results suggested that the most significant penetration enhancement was achieved by 3% (w/w) Azone/NMP (3:7). Furthermore, the in vivo pharmacodynamic responses of the formula suspension with or without Azone/NMP were compared using hot-plate assay and xylene-induced ears edema test as models. The data indicated that the formula had positive effect on analgesis and anti-inflammatory, which can be enhanced with the addition of enhancers.     

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。     

促渗剂对奥沙普秦体外经皮渗透的影响

目的 研究几种常用促渗剂对奥沙普秦体外经皮渗透的影响。方法 用紫外分光光度法检测浓度,采用改进Franz扩散池,比较几种常用促渗剂对奥沙普秦渗透速率的影响。结果 氮酮(Azone)单独使用不能明显提高奥沙普秦的渗透速率(P>0.05),而丙二醇、薄荷醇、Azone 丙二醇(1:1)、丙二醇 薄荷醇(1:1)能显著提高奥沙普秦的渗透速率(P<0.01)。结论 丙二醇、薄荷醇、Azone 丙二醇(1:1)、丙二醇 薄荷醇(1:1)可作为促渗剂用于奥沙普秦经皮吸收制剂。     

不同透皮促进剂对双氯芬酸钾凝胶体外透皮效果的影响研究

目的:考察氮酮(Azone)、丙二醇(PG)、油酸(OA)3种透皮促进剂一元、二元、三元联合对双氯芬酸钾凝胶的体外促透作用。方法:配制以下13种含不同透皮促进剂的双氯芬酸钾凝胶处方:空白,3%Azone,5%OA,12%PG,6%PG+2.5%OA,12%PG+5%OA,1.5%Azone+2.5%OA,1.5%Azone+6%PG+5%OA,1.5%Azone+12%PG,3%Azone+5%OA,3%Azone+6%PG,3%Azone+6%PG+5%OA,3%Azone+12%PG,以透皮速率J等为指标,采用改良的Franz扩散池,以离体人皮肤为透皮屏障,测定并计算双氯芬酸钾凝胶加入上述不同透皮促进剂处理后药物的透皮性能。结果:与空白组比较,其它各组J值均升高,其中以3%Azone+12%PG组的J值最高,达10.253 0μg.cm-2.h-1。结论:3种透皮促进剂对双氯芬酸钾凝胶均有不同程度促透效果,但以Azone和PG二元联用效果最佳。     

改善美洛昔康体外经皮渗透的研究

目的:研究几种常用促渗剂对美洛昔康体外经皮渗透的影响,改善美洛昔康体外经皮.方法:用紫外分光光度法检测浓度,采用改进Franz扩散池,比较几种常用促渗剂对美洛昔康渗透速率的影响.结果:氮酮(Azone)单独使用不能明显提高美洛昔康的渗透速率(P>0.05),而丙二醇.薄荷醇、丙二醇 Azone(1:1),丙二醇 薄荷醇(1:1)能显著提高美洛昔康的渗透速率(P<0.01).结论:丙二醇、薄荷醇、丙二醇 Azone(1:1)、丙二醇 薄荷肆(1:1)可作为促渗剂用于美洛昔康经皮吸收制剂.     

透皮促进剂对白花前胡甲素体外经皮渗透的影响

目的:考察透皮促进剂对白花前胡甲素(dl-praeruptorin A,Pd-Ia)体外经皮渗透的影响。方法:采用改进的Franz扩散池,以大鼠离体皮肤为渗透屏障,用高效液相色谱法对Pd-Ia进行含量测定,考察月桂氮酮(Azone)及1%Azone与不同浓度丙二醇(PG)混合物对Pd-Ia透皮吸收的影响。结果:使用Azone对Pd-Ia有促透作用,1%Azone效果较好,平均渗透速率达到4.064μg.cm-2.h-1;1%Azone与15%PG合用促透效果最好,平均渗透速率达到4.889μg.cm-2.h-1,且与单用1%Azone有显著性差异(P<0.05)。结论:1%Azone与15%PG合用时,含0.5%Pd-Ia溶液体外渗透具有最大促透效果,体现出协同作用。     

6种促进剂对西替利嗪体外经皮渗透的影响

目的 :研究 6种不同的促进剂对西替利嗪体外经皮渗透的促进作用。方法 :用Valia Chien水平扩散池 ,选择了丙二醇、月桂氮芯卓 酮 (azone)、柠烯 (dipentene)、水杨酸甲酯、含 10 %薄荷脑的丙二醇、含 10 %樟脑的丙二醇作为促进剂 ,采用离体SD大鼠腹部皮肤用促渗剂预处理的方式 ,建立以去氯羟嗪为内标的反相离子对高效液相色谱法 ,测定接收液中西替利嗪的含量。结果 :除丙二醇和水杨酸外其余几种促进剂对西替利嗪体外经皮渗透都有显著的促进作用 (P <0 .0 1)。以含 10 %薄荷脑的丙二醇的促渗效果最好。结论 :月桂氮芯卓 酮、柠烯、薄荷脑、樟脑可以作为促渗剂用于西替利嗪经皮吸收制剂     

Effect of oleic acid/ethanol and oleic acid/propylene glycol on the in vitro percutaneous absorption of 5-fluorouracil and tamoxifen and the macroscopic barrier property of porcine epidermis

Transdermal delivery of most drugs is precluded due to the impervious nature of the stratum corneum. Chemical penetration enhancers offer an approach to enhance the transdermal transport of drugs by partitioning into and interacting with skin constituents, inducing a temporary reversible increase in skin permeability. The effect of penetration enhancers (e.g. oleic acid/ethanol and oleic acid/propylene glycol) was investigated on the in vitro percutaneous absorption of a hydrophilic (5-fluorouracil) and a lipophilic (tamoxifen) anticancer drug through porcine epidermis. In vitro transepidermal water loss (TEWL) studies were undertaken to investigate the effect of the above enhancers on the macroscopic barrier properties of the epidermis. Oleic acid/ethanol and oleic acid/propylene glycol significantly enhanced (P<0.05) the permeability coefficient of 5-fluorouracil (5-FU) and tamoxifen in comparison to their controls. In vitro TEWL was significantly greater (P<0.01) through epidermis treated with the above enhancers in comparison with control (epidermis that was not treated). However, neither oleic acid/ethanol nor oleic acid/propylene glycol enhanced (P>0.05) TEWL in comparison with ethanol and propylene glycol alone. Thus, changes in the permeability of 5-FU and tamoxifen caused by oleic acid/ethanol or oleic acid/propylene glycol could not be correlated with the in vitro TEWL.     

盐酸普萘洛尔透皮吸收的研究

采用离体小白鼠皮肤为透皮屏障,用简单小室法,以生理盐水为接受液,研究了盐酸普萘洛尔在氮酮,薄荷油促进剂的作用下的透皮吸收效果,在1%盐酸普萘洛尔溶液中加入2%促吸剂,促进效果依次为氮酮、薄荷油。     

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。     

Effect of permeation enhancers on transdermal delivery of fluoxetine: In vitro and in vivo evaluation

The aim of this study was to investigate the feasibility of transdermal fluoxetine (FX) delivery. The effects of chemical forms (base or salt) and permeation enhancers on in vitro skin permeation of FX were assessed using hairless mouse, rat and human cadaver skin. The optimized formulations from the in vitro studies were then evaluated in an in vivo pharmacokinetic study in rats. The in vitro skin permeation studies suggested that the FX base (FXB) and isopropyl myristate (IPM)–limonene mixture could be suitable for transdermal delivery of FX. The permeation parameters of FX through human cadaver skin were well correlated with that through hairless mouse and rat skin, suggesting that these animal models can be used for predicting the permeability of FX through human skin. After transdermal administration of FX with IPM or the IPM–limonene mixture to rats, the mean steady-state plasma concentration (C_ss) was 66.20 or 77.55 ng/mL, respectively, which was maintained over 36 h and had a good correlation with the predicted C_ss from the in vitro data. These in vitro and in vivo data demonstrated that permeation enhancers could be a potential strategy for transdermal delivery of FX.     

The feasibility study of transdermal drug delivery systems for antidepressants possessing hydrophilicity or hydrophobicity

The feasibility studies on the transdermal drug delivery systems have been performed to avoid the systemic side-effects and gastric disorders that could be occurred due to the transient high blood concentration after oral administration of antidepressants such as venlafaxine HCl and citalopram. When surfactants of tween 80^? and plasticizer of diethyl phthalate were combined with citalopram?Cethylene vinyl acetate (EVA) matrix, the permeation of citalopram showed the best enhancement. As well as, venlafaxine HCl gels were prepared using carbomer, oleic acid and/or propylene glycol to enhance the skin permeation of venlafaxine HCl. The citalopram-EVA matrix containing tween 80^? and diethyl phthalate as permeation enhancers might be a good transdermal delivery system for providing sustained plasma concentrations of citalopram. Also, venlafaxine HCl showed the possibility to be enhanced skin permeation in the formulation of gels with carbomer including penetration enhancer, oleic acid and/or propylene glycol.     

促渗剂对咪喹莫特体外经皮渗透的影响

目的研究几种促渗剂对咪喹莫特体外经皮渗透的影响。方法采用水平扩散池、离体SD大鼠腹部皮肤用渗透剂预处理的方法,测定接收液中咪喹莫特的含量及皮肤中药物的滞留量。结果在考察的促渗剂中,除卡必醇外(P>0.05),油酸、丙二醇、异硬脂酸、氮酮、月桂酸、松节油对咪喹莫特都有促渗作用;油酸、异硬脂酸能显著提高药物在皮肤中的滞留量(P<0.01),油酸对透过量影响不大(P>0.05);氮酮能使透过量显著增大(P<0.01),质量分数为3%的氮酮并不影响皮肤中的滞留量(P>0.05);松节油能使经皮透过量和皮肤中的滞留量都有所增加(P<0.05)。结论选用异硬脂酸作为咪喹莫特的渗透促进剂,该促渗剂能在不增加皮肤透过量的同时增加药物在皮肤中的滞留量。     

Effects of solvents on skin permeation of formoterol fumarate

Effects of various chemicals applied as penetration enhancers on the permeation of formoterol fumarate (FF) across excised rat skin were investigated. Remarkable enhancement was noted with terpenes, fatty acid esters, and higher alcohols, whereas no significant influence was observed in the case of lower alcohols, pyrrolidones, and amines. At high concentration, a cineole/N-methyl-2-pyrrolidone (NMP) mixed solvent system slightly enhanced the skin permeation of FF compared with cineole alone, and a l-menthol/NMP mixed solvent system caused significant further increase. Maximum skin permeation of FF was seen when the ratio of l-menthol/NMP was 60/40 w/w. From the present results, l-menthol/NMP and isopropyl myristate (IPM)/NMP mixed solvent systems can be considered effective for augmenting skin permeation of FF, with potential applications in transdermal delivery of the drug.     

促渗剂对复方黄芩巴布剂透皮吸收的影响

目的:研究不同促渗剂对复方黄芩巴布剂透皮吸收的影响。方法:在离体透皮实验装置上,以生理盐水为接受液,通过高效液相色谱法测定释放液中黄芩苷的含量以确定最佳促渗剂配比。结果:几种促渗剂对复方黄芩巴布剂均有促渗作用;采用混合透皮促进剂促渗作用较强,其中以油酸∶丙二醇∶氮酮=2∶2∶1为最强。结论:采用混合促渗剂对复方黄芩巴布剂中黄芩苷的经皮渗透有较好的促进作用。     

Pretreatment with Skin Permeability Enhancers: Importance of Duration and Composition on the Delivery of Diclofenac Sodium

The use of chemical penetration enhancers (CPEs) is one of the most common approaches to improve the dermal and transdermal delivery of drugs. However, often, incorporation of CPEs in the formulation poses compatibility and stability challenges. Moreover, incorporation of enhancers in the formulation leads to prolonged exposure to skin increasing the concern of causing skin reactions. This study was undertaken to assess whether pretreatment with CPEs is a rational approach to enhance the permeation of diclofenac sodium. In vitro experiments were performed across porcine epidermis pretreated with propylene glycol or oleic acid or their combinations for 0.5, 2, and 4 h, respectively. Pretreatment with combination of oleic acid in propylene glycol was found to enhance the permeation of diclofenac sodium significantly only at 10% and 20% (v/v) level, and only when the pretreatment duration was 0.5 h. Longer durations of pretreatment and higher concentration of oleic acid in propylene glycol did not enhance the permeation of diclofenac sodium. In vivo dermatokinetic studies were carried out on Sprague–Dawley rats. A twofold increase in AUC and C_max was observed in case of rats pretreated with enhancers over the group that was pretreated with buffer. In conclusion, this study showed that composition of the enhancers and duration of pretreatment are crucial in determining the efficacy of CPEs. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.     

复合透皮促渗剂对氨氯地平的促渗透作用

目的：研究不同透皮促渗剂对氨氯地平混悬液的体外兔皮渗透作用.方法：以30%乙醇为溶媒,分别配制含不同透皮促渗剂的氨氯地平饱和混悬液,采用自制改良Franz’s扩散池测量其对体外兔皮的促渗透作用.结果：促渗剂对氨氯地平均有促渗透作用,不同透皮促渗剂促透作用的大小顺序为：丙二醇＜油酸＜阿佐恩＜阿佐恩＋丙二醇＜油酸＋丙二醇.与不含促渗剂相比,油酸＋丙二醇渗透系统稳态透皮渗透速率约为不含促渗剂的2.7倍.结论：复合透皮促渗剂对氨氯地平有良好的促渗透作用.     

Use of an 8(1)3(2) asymmetrical factorial design for the in vitro evaluation of ondansetron permeation through human epidermis

The in vitro permeation of ondansetron through human cadaver epidermis, as a preliminary step toward the development of a transdermal therapeutic system, was investigated. In vitro release studies were carried out using modified Franz diffusion cells and human epidermis, taken from cadaver skin by heat separation technique. To estimate the effect of the type and concentration of the penetration enhancers and the skin from different donors, an 8(1)3(2) asymmetrical factorial design was used. Formulations containing lauric acid and oleic acid as penetration enhancers, showed the largest Q values [amounts of ondansetron permeated per unit area of epidermal membrane (microg/cm2)] at 24, 48, and 72 hr, as well as steady-state flux values, among all formulations tested. The other enhancers increased the flux in the following order: lauryl alcohol>glycerol monooleate>Azone >cineole>oleyl alcohol>1-methyl-2-pyrrolidinone. Moreover, the concentration of the penetration enhancer and the type of the skin were proved to significantly affect the permeation rate of ondansetron through human epidermis. From the results obtained, it was shown that the formulations containing lauric acid or oleic acid at 5% or 10% could increase sufficiently the permeation of ondansetron. Therefore, the transdermal administration of ondansetron seems feasible.     

Effect of penetration enhancers on the permeation of mannitol, hydrocortisone and progesterone through human skin

Mannitol, hydrocortisone and progesterone were selected as model penetrants to assess the mode of action of eight potential penetration enhancers in human skin. Their partition coefficients, octanol: water and stratum corneum: water were measured and correlated with their postulated routes of penetration through human skin. The results suggest that mannitol penetrated via a polar route, hydrocortisone by a mainly lipid route and progesterone via a lipid pathway but its penetration rate was probably affected by aqueous layers. From permeation studies through cadaver skin in which an in-vivo mimic method was used, it was concluded that the penetration enhancers fell into three main categories: solvents which enhanced permeation of polar and non-polar compounds e.g. 2-pyrrolidone, N-methylpyrrolidone, N-methylformamide and propylene glycol plus Azone; enhancers which preferentially affected the polar route e.g. propylene glycol plus decylmethylsulphoxide, and accelerants which mainly modified the non-polar route e.g. propylene glycol plus oleic acid, propylene glycol alone and, to a limited extent, water.     

盐酸利多卡因凝胶剂处方优化及稳定性考察

目的:考察多种渗透促进剂对盐酸利多卡因凝胶经皮渗透的影响,并从中筛选其最佳处方组成。方法:采用离体皮肤渗透实验,以渗透速率为指标,均匀设计优化处方工艺,考察不同渗透促进剂对羧甲基纤维素钠(CMC-Na)基质的凝胶剂中利多卡因的经皮渗透效果。结果:含1.5%月桂氮(?)酮,4%聚乙二醇-400,2%泊洛沙姆和25%丙二醇(PG)的盐酸利多卡因凝胶剂具有最佳的经皮渗透速率,且处方稳定,对皮肤无刺激性。结论:渗透促进剂对盐酸利多卡因经皮渗透有显著的促进作用。