透皮吸收促进剂在巴布剂中的应用及研究宰

经皮给药系统不断完善并得到了发展,但许多药物透皮应用时并不能完全满足治疗要求,因此提高其透皮速率是开发透皮给药系统的关键.通过查阅近10年有关透皮吸收促进剂的文献资料,对透皮吸收促进剂及其在巴布荆中的应用情况进行分析、整理和归纳,为巴布剂的透皮吸收实验研究提供参考.     

盐酸西替利嗪巴布剂的研制及体外释放特性

目的:制备盐酸西替利嗪(CET)巴布剂并研究其体外释药性能和透皮吸收行为.方法:以水溶性高分子材料为基质制备CET巴布剂,采用HPLC法测定制剂中CET的含量.按2000年版中华人民共和国药典方法进行体外释放度的测定,利用Franz扩散池研究巴布剂的透皮吸收行为.结果:CET巴布剂含量稳定,体外释药符合Higuchi方程,释放速率为0.557 7mg·cm-2·h-1/2.透皮吸收符合零级动力学过程,渗透速率为14.58μg·cm-2·h-1.结论:CET巴布剂为皮肤控释型透皮给药系统,为临床治疗过敏性疾病提供了新的给药途径.     

透皮吸收促进剂的临床应用

透皮吸收促进剂(简称穿透促进剂)系指可以加快药物穿透皮肤的速度而不对皮肤形成严重刺激和损害的物质。最早主要应用于软膏剂、擦剂、涂布剂等,随着制剂技术的不断发展、外用制剂的剂型不断增加,其用途不断扩大如骨架型透皮释放给药系统、压敏微储库型给药系统、贴布剂等。     

透皮促进剂在透皮释放给药系统中的应用

本文介绍了透皮释放给药系统的特点,阐明了透皮促进剂的作用及其机理;介绍了国内外常用的透皮促进剂,综述其在透皮释放给药系统中合理知科学的应用。同时展示了透皮促进剂的新发展和药物增加透皮吸收的新研究。     

透皮促进剂对散结止痛巴布膏中次乌头碱透皮的影响

目的考察透皮促进剂对散结止痛巴布膏中次乌头碱透皮吸收的影响。方法建立皮肤渗透液中次乌头碱含量测定的HPLC方法。利用大鼠腹部皮肤和Franz垂直扩散池进行体外透皮扩散试验,比较不同浓度的氮酮和桉叶油对散结止痛巴布膏中次乌头碱透皮速率的影响。结果不加透皮促进剂的散结止痛巴布膏中次乌头碱的透皮速率为0．65mg·cm^-2·h^-1;2％氮酮与10％丙二醇组成的复合透皮促进剂使次乌头碱透皮速率增加9．87倍;2％桉叶油增加次乌头碱透皮速率12．23倍。结论散结止痛巴布膏的透皮促进剂可采用2％桉叶油或2％氮酮与10％丙二醇合用。     

薄荷醇、氮酮、丙二醇联合应用对速美减肥贴透皮速率的影响

中药透皮给药是近年来经皮给药制剂研究的趋势,为了提高经皮给药制剂中药物透进皮肤的量,经皮给药制剂中越来越多地使用透皮吸收促进剂,特别是中药透皮吸收促进剂与化学透皮吸收促进剂联合应用,可增强其促透效果.     

布洛芬巴布剂的制备与体外释放研究

目的 制备布洛芬巴布剂并研究其体外释药性能和透皮吸收行为. 方法 以水溶性高分子材料为基质制备布洛芬巴布剂,采用高效液相色谱(HPLC)法测定制剂中布洛芬的含量. 按《中华人民共和国药典》2010年版二部附录 方法 进行体外释放度的测定,利用Franz扩散池研究巴布剂的透皮吸收行为. 结果 布洛芬巴布剂含量稳定,体外释药符合Higuchi方程,释放速率为1.522 mg.(cm²)^-1.h^-1/2,渗透速率为1.071 mg.(cm²)^-1.h^-1,渗透速率小于释放速率. 结论 布洛芬巴布剂为皮肤控释型透皮给药系统,为临床提供新的给药途径.     

不同纯度苦杏仁苷巴布剂的透皮吸收比较研究

目的:比较研究不同纯度的苦杏仁苷提取物制备的巴布剂对小鼠皮肤不同的透过吸收情况,以便确定合适纯度的苦杏仁苷作为经皮制剂给药原料.方法:采用Franz扩散池法,研究各种苦杏仁苷巴布剂中苦杏仁苷的透皮吸收情况;并采用高效液相色谱法检测透过小鼠皮肤的苦杏仁苷的透过量.结果:制得巴布剂中苦杏仁苷的透皮吸收符合Higuchi方程,累积渗透量(Q)与t1/2呈线性关系.纯度为38.7%、61.4%、86.7%的苦杏仁苷巴布剂,累积渗透量分别为2 121.339、1 597.441、1 614.173 μg·cm-2,透皮速率常数(J)分别为969.95、828.26、793.14 μg·cm-2·h-1.结论:苦杏仁苷巴布剂能较好地透过皮肤,且38.7%纯度的透皮效果最好,可以考虑选择该纯度的苦杏仁苷提取物制备巴布剂.     

中药巴布剂的研究现状与展望

巴布剂是经皮给药制剂的一种,作为外用贴剂的巴布剂,患者对其顺应性比较好,在治疗身体各种疾病等方面越来越受到患者的青睐.近年来,人们对皮肤形态、功能及角质层屏障作用的研究取得了突破性成果,从而促进了经皮给药吸收机制和透皮吸收促进剂的研究,使更多的以物理、化学、材料科学及工程学原理为基础的经皮给药促进方法在药物开发方面得到具体应用.实践证明,采用口服和中药巴布剂的中西结合方法,能较好地缓解疾病的症状,有效改善患者的生活质量.巴布剂可直接作用于靶部位发挥疗效,可以避免肝脏和胃肠道的首过效应及药物对胃肠道的刺激,在较长的时间内维持恒定的血药浓度,降低药物的不良反应并能减少给药次数,使用方便,可反复粘贴,透气性好.巴布剂已用于骨质增生、腹腔疾病、癌症、多种炎症等各种疾病引起的疼痛治疗,是具备优良的柔韧性和黏着性的新型贴剂.     

不同透皮吸收促进剂对士的宁透过离体猪皮的影响

目的初步探索开发士的宁透皮给药系统的可能性。方法采用体外透皮扩散法在规定时间点取样,高效液相色谱法测样品中士的宁的含量;以时间为横坐标,士的宁累积透皮量为纵坐标作图求透皮吸收速率、滞后时间等参数。结果各促透剂对士的宁促渗作用由弱至强依次为吐温-80<桉叶素<薄荷醇<香芹酮<油酸<柠檬烯<萜品油烯。结论选用适当的透皮吸收促进剂,士的宁体外透皮吸收速率可达到开发透皮给药系统的需要。     

Transdermal delivery system for zidovudine: in vitro, ex vivo and in vivo evaluation

The objective of this study was to prepare a transdermal delivery system (TDS) for zidovudine (AZT) with a combination of menthol and oleic acid as penetration enhancers incorporated in hydroxypropyl methylcellulose, and to evaluate ex vivo as well as in vivo permeation across rat skin. It was found that AZT in gel formulation was stable in both refrigerated as well as accelerated stability conditions for 3 months and further, the gel did not significantly retard the permeability of AZT across the skin in comparison with solution formulation. Ex vivo steady state flux of AZT across rat skin from gel was 2.26 mg cm(-2) h(-1), which is sufficient to achieve therapeutic plasma concentrations. Intravenous pharmacokinetic parameters of AZT in rats were determined and used together with ex vivo flux data to generate theoretical plasma profiles of AZT and compared with plasma concentrations achieved after application of TDS. Further, steady state plasma concentrations of drug following multiple applications of TDS were determined and good correlations between ex vivo and in vivo data were observed. In addition, the combination of penetration enhancers used at 2.5% w/w in this study proved efficient in achieving sufficient enhancement in the transdermal permeability of AZT across rat skin with reduced skin irritation potential when compared with individual penetration enhancers at higher concentrations.     

Effect of penetration enhancers on the release and skin permeation of bupranolol from reservoir-type transdermal delivery systems

A reservoir-type transdermal delivery system (TDS) of bupranolol (BPL) was designed and evaluated for different formulation variables like gel reservoirs (made with anionic and nonionic polymers), rate controlling membranes and penetration enhancers on the drug release and in vitro skin permeation kinetics of the devices. Keshary-Chien type diffusion cells and pH 7.4 phosphate buffered saline (PBS) were used for drug release studies and excised rat skin was used as a barrier for permeation experiments. The release rate of BPL from nonionic polymer gel reservoirs [hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC)] was much higher than anionic polymer gel reservoirs [carboxymethyl cellulose (CMC), sodium carboxymethyl cellulose (Na CMC) and sodium alginate)]. Among different rate controlling membranes, Cotran-polyethylene microporous membrane demonstrated highest release rate for BPL than all other membranes. An optimized TDS formulation with HPC gel and Cotran-polyethylene microporous membrane was used to study the effect of penetration enhancers on the release and skin permeation rate of BPL from the TDS. Permeation rates of the devices containing 5% (w/v) pyrrolidone (PY) or 1-methyl-2-pyrrolidone (MPY) were about 3- and 1.5-fold higher than control (no enhancer, P<0.01) indicating PY to be better penetration enhancer for BPL than MPY. The permeation rates of devices containing partially methylated beta-cyclodextrin (PMbetaCD) and PMbetaCD-BPL complex were about 2.5- and 1.4-fold higher than control (P<0.01). Inclusion of 10 and 30% w/v propylene glycol (PG) in the devices increased the permeation rate by 1.4- and 1.8-fold higher than control (P<0.05). In conclusion, reservoir-type TDS of BPL was developed and penetration enhancers increased the skin permeation of BPL at 4-5 times higher levels than the desired target delivery rate.     

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.     

不同促渗剂对硫酸沙丁胺醇颊粘膜吸收的影响

目的：筛选硫酸沙丁胺醇经颊粘膜吸收促渗剂。方法；采用单室扩散池研究硫酸沙丁胺醇通过金黄地鼠颊粘膜的药物渗透，考察不同促渗剂对药物经颊粘膜吸收的影响。结果；在１０ｈ内，２０ｍｇ／ｍｌ的药物生理盐水溶液渗透速率为３９．１５μｇ（ｃｍ＾２．ｈ）。当分别以相同药物浓度的饱和β－环糊精生理盐水，３％Ｔｗｅｅｎ８０与５％Ａｏｎｅ生理盐水，５％聚氧乙烯壬苯工醚生理盐水为溶媒，其渗透速率分别为７５．４６，１５２．     

Penetration Enhancers and the Percutaneous Absorption of Drugs: An Update

Abstract

Dermatological preparations may be formulated for optimal bioavailability by ensuring that the drug has maximum tendency to leave the vehicle and pass into the skin. Alternatively, compounds (penetration enhancers, accelerants, or sorption promoters) may be included in the formulation that themselves pass into the skin and in so doing reversibly decrease its resistance to drug passage. The literature on penetration enhancers to 1981 was comprehensively reviewed by Barry. This paper discusses work performed since that time, with special reference to glycols, sulfoxides, amides and amines, pyrrolidones, and Azone. These and other compounds continue to be investigated as penetration enhancers for both local and systemic delivery of drugs. An important future role lies in their incorporation into transdermal delivery systems.     

Effect of natural penetration enhancers on dermal delivery of hydrocortisone acetate

The purpose of the research work was to develop microemulsion (ME) of hydrocortisone acetate (HCA) using natural penetration enhancers and to determine its possibility in effective dermal delivery. Eucalyptus oil, clove oil and lemon grass oil were selected as natural penetration enhancers and pseudo-ternary phase diagrams were plotted using Tween 80 as surfactant and ethanol as cosurfactant. ME of each penetration enhancer was optimized using three factors, three levels Box–Behnken design, with independent variables as penetration enhancer, Tween 80 and ethanol. Formulations were assessed for percentage drug release as dependent variable. Response of these formulations decreased as the concentration of oil ranged from high to low and the response showed positive effect with increase in concentration of Tween 80 and ethanol. The globule size of optimized batches of eucalyptus oil, clove oil and lemon grass oil were found to be 226.1, 129.04 and 818.9 nm respectively. Optimized batches of MEs were then incorporated in carbopol 940 to form ME based gel without affecting their structure. Ex vivo permeation studies showed that amount of drug permeated from ME based gels was less than ME formulation indicating greater retention of HCA into skin layers. Retention of drug in skin layers both dermis and epidermis was higher for all three natural penetration enhancer. Hence natural penetration enhancers can be used for effective delivery of topical corticosteroids to the skin for improved treatment of several skin diseases and can be a better choice over synthetic penetration enhancers in terms of safety.     

罂粟碱凝胶的研制及不同透皮促进剂对其透皮作用的影响

目的：探讨透皮吸收促进剂对罂粟碱凝胶透皮吸收的影响。方法：采用简单扩散小室，用紫外分光光度测定了5种处方罂粟碱凝胶离体鼠皮透皮吸收药量。结果：罂粟碱透皮累积释药量与时间呈线性关系，与不含吸收促进剂的凝胶比较，吸收促进剂对罂粟碱透皮吸收的影响为油酸＞油酸＋月桂氨卓酮＞二甲亚砜＞月桂氮卓酮。结论：油酸能明显促进罂粟碱的透皮吸收，而水溶性的透皮吸收促进剂对罂粟碱的透皮吸收作用不明显。     

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     

新型经皮渗透促进剂的研究进展

介绍国内外近年来报道的新型经皮渗透促进剂的研究与开发进展,重点介绍若干具代表性的新合成的化合物以及新发现的天然产物,包括内酰胺类、糖苷类、氨基酸衍生物、聚合物、挥发油和酶类等,为合成和发现更加安全、高效的促渗剂提供线索.     

A new colorimetric assay for studying and rapid screening of membrane penetration enhancers

PURPOSE: This work aims to demonstrate a novel chemical assay for rapid screening and analysis of the mode of action of membrane interaction by penetration enhancers. METHODS: The new bio-mimetic membrane assembly, consisting of supramolecular aggregates of lipids and conjugated polydiacetylene, undergoes visible and quantifiable blue-red color transitions upon interaction with penetration enhancers. RESULTS: The new colorimetric model has been employed to examine various classes of penetration enhancers, including 1-dodecylhexahydro-2H-azepin-2-one (Azone), oleic acid, propylene-glycol, menthol, ethoxyglycol-diethyleneglycol-monoethyl-ether (Transcutol), polysorbate-polyethylenesorbitan-monolaurate (Tween-20), and the drug 7-chloro-1-methyl-5-phenyl-3H-1,4-benzodiazepin-2-one (Diazepam). The assay enables to evaluate the validity of various observations and hypotheses proposed in previous studies regarding permeation enhancement activities. Our results suggest, for example. that propylene glycol (PG) by itself does not interfere with membranes, but rather exhibits synergistic effect in combination with other penetration enhancers. Similarly, our data demonstrate that Transcutol does not independently interact with membranes. The colorimetric system also indicates that interaction of penetration enhancers with membranes depend upon the lipid phase, as well as the self-assembly properties of the enhancer molecules. CONCLUSIONS: The new biomimetic model membrane system can be applied for rapid screening of the activities of penetration enhancers, and provides insight into the mechanisms of permeability of membrane-active compounds.