4种透皮吸收促进剂对盐酸苯海拉明透皮性能的影响

目的:研究油酸、1,3-丙二醇、月桂氮酮、丙三醇4种透皮吸收促进剂对盐酸苯海拉明透皮性能的影响。方法:在一定量的盐酸苯海拉明溶液中分别加入4种不同浓度的透皮吸收促进剂,采用改良Franz扩散池进行体外透皮吸收试验,测定不同浓度下不同透皮吸收促进剂的24h累积透过量(Q)。结果:以Q为指标,促透作用油酸>1,3-丙二醇>月桂氮酮>丙三醇,且前三者分别以0.5%、0.5%、0.2%为最佳促透浓度,丙三醇未见有明显的促透作用。结论:4种透皮吸收促进剂在一定浓度下均可增强盐酸苯海拉明局部给药制剂的透皮吸收作用。     

不同透皮促进剂对环孢素A纳米粒丝素蛋白膜剂经皮渗透的影响研究

目的:研究不同透皮促进剂对环孢素A纳米粒丝素蛋白膜剂(简称环孢素A膜剂)经皮渗透的影响,并优选出其最佳透皮促进剂。方法:以不同浓度的氮酮、油酸、月桂醇、丙二醇、尿素单用及氮酮与其他辅料联用作为透皮促进剂,制备环孢素A膜剂;采用药物透皮扩散试验仪,以离体大鼠腹部皮肤为渗透屏障,40%乙醇-生理盐水为接收介质,高效液相色谱法为接收介质中药物含量的测定方法,比较不同透皮促进剂作用下环孢素A累积透皮量(Q)、稳态透皮速率(Js)、增渗倍数(ER)等。结果:氮酮、月桂醇、丙二醇、尿素对环孢素A膜剂均有透皮促进作用,其中以1%氮酮+2%丙二醇的透皮促进效果最好,令24h内Q提高至2.81倍、Js为6.59μg·cm-2·h-1、ER为2.59。结论:1%氮酮+2%丙二醇更适合作为环孢素A膜剂的透皮促进剂。     

促渗剂对氟比洛芬体外经皮渗透的影响

目的研究不同的促渗剂对氟比洛芬体外经皮渗透的促渗作用。方法采用TK-6A型透皮扩散仪,用人皮进行体外经皮渗透实验,考察不同的促渗剂[二甲基亚砜、月桂醇、丙二醇、月桂氮酮(氮酮)、尿素、油酸]及其组合对氟比洛芬体外透皮吸收的促渗作用,以HPLC法测定各时间点接受室中药物浓度,求算透皮吸收的有关参数,比较各促渗剂的促渗作用。结果15%二甲基亚砜、3%氮酮、1%尿素可使氟比洛芬经皮渗透速率分别提高1.8,1.5,1.1倍,促渗剂联用取得的促渗效果更佳,5%油酸 20%丙二醇 1%尿素可使该药物的经皮渗透速率提高6倍。结论单用促渗剂对氟比洛芬经皮渗透促渗效果有限,促渗剂联合使用可以显著提高氟比洛芬经皮渗透速率。     

中药复方制剂心安康贴剂的透皮吸收促进剂选择研究

目的：对中药复方制剂心安康贴剂的透皮吸收促进剂的选择进行研究。方法：采用Franz渗透扩散装置的气相色谱法，进行了大鼠皮肤贴剂的体外释放与渗透试验，对氮酮、十六醇、月桂醇硫酸钠，丙二醇4种透皮吸收促进剂单独应用和任意两种舍用的促进效果进行考察。结果：氮酮和丙二醇以2％：15％褥合，促进效果最强。结论：透皮促进剂对中药贴剂中的成分有较好的促透作用。     

渗透促进剂对止泻凝胶膏中胡椒碱透皮的影响

制备含不同渗透促进剂的止泻凝胶膏,采用Franz扩散池考察各处方的体外透皮行为.采用HPLC法测定制品中胡椒碱含量.结果表明,当促渗剂以4％的浓度单用时,N-甲基吡咯烷酮(NMP)的促渗效果最好,月桂氮时酮和1,2-丙二醇的效果相近.促进剂组合使用时促进胡椒碱透皮的作用更强,其中4％月桂氮艰酮+4％丙二醇+8％ NMP为本复方的渗透促进剂时效果较好.     

不同透皮吸收促进剂对左旋肉碱透皮特性的影响

目的:选择适宜的透皮吸收促进剂增加左旋肉碱的透皮百分率。方法:使用改良Franz体外释药装置,用RP-HPLC法检测接收液中左旋肉碱的浓度,计算药物的透皮累积释放量,采用滞留时间法求算经皮渗透相关系数,考察不同用量的丙二醇、尿素、氮酮对左旋肉碱的促透作用。结果:左旋肉碱的溶液在体外透皮释放试验中有透皮吸收。不同种类及不同用量的吸收促进剂对左旋肉碱的促透作用不同,且随着透皮时间的延长,促透量显著增加。3种透皮吸收促进剂中尿素和丙二醇的促透作用较好,氮酮的促透作用稍差。结论:透皮吸收促进剂能够增加左旋肉碱的透皮百分率,其中2.5%的丙二醇促透作用最强。     

透皮促进剂对酮基布洛芬体外经皮渗透的影响

酮基布洛芬(KP)体外经皮渗透性实验研究表明,KP经皮渗透是一个零级速率过程。利用离体鼠皮为渗透屏障考察KP在月桂氮艹卓酮(AZ)、油酸(OA)、1-甲基-2-吡咯烷酮(2P)、N,N-二甲基甲酰胺(DMF)、月桂醇(LA)、丙二醇(PG)6种透皮促进剂作用下的透皮效果,发现这些透皮促进剂对KP透皮速率的影响有明显差别。其中油酸、月桂氮艹卓酮、1-甲基-2-吡咯烷酮和丙二醇可促进KP吸收透皮,促进强度依次为OA>AZ>2P>PG,并且两种透皮促进剂OA与AZ或2P合用有较好的协同作用,而DMF、月桂醇和高浓度丙二醇则阻滞KP经皮渗透。     

不同促透剂对重组人干扰素α-2b体外透皮特性的影响

目的探讨不同促透剂对重组人干扰素α-2b体外透皮特性的影响。方法配制不同组成及比例的促透剂,采用改良的Franz扩散池装置,以离体家兔兔皮为透皮屏障,采用紫外分光光度法计算重组人干扰素α-2b的累积透皮吸收量。结果不同促透剂均有不同程度的促透作用,其促透作用强弱顺序为3%薄荷脑+3%丙二醇>3%薄荷脑>3%氮酮+3%丙二醇>1%氮酮+1%薄荷脑>1%薄荷脑>3%氮酮+3%薄荷脑>1%氮酮>1%氮酮+3%薄荷脑>3%氮酮+1%薄荷脑>3%氮酮。结论氮酮、薄荷脑、丙二醇均可作为重组人干扰素α-2b的透皮促进剂。     

不同促渗剂对咪康唑透皮吸收作用的研究

目的研究不同浓度的月桂氮卓酮（氮酮）、油酸、薄荷脑和丙二醇及混合物对咪康唑促渗作用的影响。方法采用改进Franz扩散池装置,离体小鼠鼠皮为透皮屏障,用紫外分光光度法测定接收池中咪康唑的含量,计算咪康唑累积透皮吸收量。结果氮酮、油酸、薄荷脑和丙二醇及混合物对咪康唑均有促渗作用．其促渗强弱顺序依次为2％氮酮＋5％油酸、3％氮酮＋3％丙二醇、2％氮酮＋3％丙二醇、3％氮酮＋5％油酸、2％氮酮＋5％薄荷脑、3％氮酮＋5％薄荷脑、2％氮酮、3％氮酮、1％氮酮、5％油酸、3％丙二醇、5％薄荷脑。结论油酸、薄荷脑、氮酮和雨二醇对咪康唑的促渗作用有量效关系。其中2％氮酮＋5％油酸促渗效果最好。     

不同促渗剂对眯康唑透皮吸收作用的研究

目的研究不同浓度的月桂氮卓酮（氮酮）、油酸、薄荷脑和丙二醇及混合物对咪康唑促渗作用的影响。方法采用改进Franz扩散池装置,离体小鼠鼠皮为透皮屏障,用紫外分光光度法测定接收池中咪康唑的含量,计算咪康唑累积透皮吸收量。结果氮酮、油酸、薄荷脑和丙二醇及混合物对咪康唑均有促渗作用．其促渗强弱顺序依次为2％氮酮＋5％油酸、3％氮酮＋3％丙二醇、2％氮酮＋3％丙二醇、3％氮酮＋5％油酸、2％氮酮＋5％薄荷脑、3％氮酮＋5％薄荷脑、2％氮酮、3％氮酮、1％氮酮、5％油酸、3％丙二醇、5％薄荷脑。结论油酸、薄荷脑、氮酮和雨二醇对咪康唑的促渗作用有量效关系。其中2％氮酮＋5％油酸促渗效果最好。     

Synthesis and In Vitro Evaluation of Aminoacyloxyalkyl Esters of 2-(6-methoxy-2-naphthyl)propionic Acid as Novel Naproxen Prodrugs for Dermal Drug Delivery

Purpose. To synthesize and evaluate various novel aminoacyloxyalkyl esters of naproxen (3a-i) and naproxenoxyalkyl diesters of glutamic and aspartic acids (3j-m) as potential dermal prodrugs of naproxen. Methods. The prodrugs 3a-m were synthesized, and their aqueous solubilities, lipophilicities and hydrolysis rates were determined in a buffered solution and in human serum. The permeation of selected prodrugs across excised postmortem human skin was studied in vitro. Results. The aminoacyloxyalkyl prodrugs showed higher aqueous solubilities and similar lipid solubilities, in terms of octanol-buffer partition coefficients (log P_app) at pH 5.0, when compared with naproxen. At pH 7.4 the prodrugs were significantly more lipophilic than naproxen. Prodrugs3a-i showed moderate chemical stability in aqueous solutions at pH 5.0 and were rapidly converted to naproxen in human serum (t_1/2 = 4–19 min). The selected aminoacyloxyalkyl prodrugs possessed a higher flux across the skin than naproxen, with a maximum enhancement of 3-fold compared to naproxen. Prodrugs 3j-mshowed poor aqueous solubility and permeation across the skin. Conclusions. Combinations of adequate aqueous solubility and lipophilicity of naproxen aminoacyloxyalkyl prodrugs having fast rates of enzymatic hydrolysis resulted in improved dermal delivery of naproxen.     

The effects of Azone and capsaicin on the permeation of naproxen through human skin

The permeation of naproxen through excised human skin and isolated perfused rabbit ear skin has been determined. It was found that both Azone and capsaicin enhanced the permeation with an enhancement ratio of up to 4-fold. The magnitudes of the effect were similar in human and rabbit skin. The permeation of naproxen from a saturated solution of the drug through skin pre-treated with Azone was similar to that from a commercial preparation (Naprosyn). In the perfused rabbit ear experiments the presence of capsaicin had no effect on the vasodilatation of the blood vessels, inferring that the penetration enhancement was a direct result of capsaicin influencing the barrier function of the skin. Structural similarities between Azone and capsaicin were seen using molecular graphics.Copyright     

Angelica archengelica extract induced perturbation of rat skin and tight junctional protein (ZO-1) of HaCaT cells

BACKGROUND AND PURPOSE OF THE STUDY: Herbal enhancers compared to the synthetic ones have shown less toxis effects. Coumarins have been shown at concentrations inhibiting phospoliphase C-Y (Phc-Y) are able to enhance tight junction (TJ) permeability due to hyperpoalation of Zonolous Occludense-1 (ZO-1) proteins. The purpose of this study was to evaluate the influence of ethanolic extract of Angelica archengelica (AA-E) which contain coumarin on permeation of repaglinide across rat epidermis and on the tight junction plaque protein ZO-1 in HaCaT cells. METHODS: Transepidermal water loss (TEWL) from the rat skin treated with different concentrations of AA-E was assessed by Tewameter. Scanning and Transmission Electron Microscopy (TEM) on were performed on AA-E treated rat skin portions. The possibility of AA-E influence on the architecture of tight junctions by adverse effect on the cytoplasmic ZO-1 in HaCaT cells was investigated. Finally, the systemic delivery of repaglinide from the optimized transdermal formulation was investigated in rats. RESULTS: The permeation of repaglinide across excised rat epidermis was 7-fold higher in the presence of AA-E (5% w/v) as compared to propylene glycol:ethanol (7:3) mixture. The extract was found to perturb the lipid microconstituents in both excised and viable rat skin, although, the effect was less intense in the later. The enhanced permeation of repaglinide across rat epidermis excised after treatment with AA-E (5% w/v) for different periods was in concordance with the high TEWL values of similarly treated viable rat skin. Further, the observed increase in intercellular space, disordering of lipid structure and corneocyte detachment indicated considerable effect on the ultrastructure of rat epidermis. Treatment of HaCaT cell line with AA-E (0.16% w/v) for 6 hrs influenced ZO-1 as evidenced by reduced immunofluorescence of anti-TJP1 (ZO-1) antibody in Confocal Laser Scanning Microscopy studies (CLSM) studies. The plasma concentration of repaglinide from transdermal formulation was maintained higher and for longer time as compared to oral administration of repaglinide. MAJOR CONCLUSION: Results suggest the overwhelming influence of Angelica archengelica in enhancing the percutaneous permeation of repaglinide to be mediated through perturbation of skin lipids and tight junction protein (ZO-1).     

氯雷他定柔性脂质体的制备及体外透皮研究

目的:制备氯雷他定柔性脂质体并研究该脂质体中氯雷他定的体外透皮情况.方法:用逆向蒸发法制备柔性脂质体,采用改良的Franz扩散池进行体外透皮吸收试验.结果:与普通脂质体相比较,柔性脂质体能提高氯雷他定的透皮速率.结论:柔性脂质体可显著促进氯雷他定的透皮吸收情况.     

Effect of limonene on the in vitro permeation of nicardipine hydrochloride across the excised rat abdominal skin

The aim of the present investigation was to study the effect of limonene on in vitro permeation of nicardipine hydrochloride across the excised rat abdominal skin from a 2% w/w hydroxypropyl cellulose (HPC) gel. The HPC gel formulations containing 1% w/w of nicardipine hydrochloride and selected concentrations of limonene (0% w/w to 12% w/w) were prepared, and subjected to in vitro permeation of the drug through excised rat abdominal epidermis. The drug content in the gels was found to be uniform and the drug was found to be stable in the HPC gel formulations. The permeation flux of nicardipine hydrochloride across rat epidermis was increased markedly by the addition of limonene to the HPC gels. A maximum flux was observed (246 +/- 1 micrograms/cm2/h) with an enhancement ratio of about 8 when limonene was incorporated at a concentration of 4% w/w. However, there was no further increase in the permeability of nicardipine hydrochloride beyond 4% w/w of limonene. The DSC and FT-IR data indicated that limonene increased the permeability of nicardipine hydrochloride across the rat epidermis by partial extraction of lipids in the stratum corneum. The results suggest that limonene may be useful for enhancing the skin permeability of nicardipine hydrochloride from transdermal therapeutic system containing HPC gel as a reservoir.     

渗透促进剂对利多卡因经皮渗透的促进作用

考察了7种渗透促进剂对利多卡因游离碱的促渗作用，并提出了一促渗作用参数对油溶性和水溶性促渗剂的促渗作用进行系统比较，结果发现渍溶性促渗剂的促渗作用强于水溶性促渗剂（P＜0．05），但对药物经皮渗透的滞后时间无改善作用，水溶性促渗剂可使滞后时间有所缩短。     

Lipophilic metronidazole derivatives and their absorption through hairless mouse skin

Previously we have shown that the diacyl glyceryl ester of naproxen is absorbed into excised mouse skin and slowly degraded to release naproxen. In the present work we have synthesised some organic acid and fatty acid derivatives of metronidazole, and studied the in-vitro degradation in aqueous buffer solutions and serum as well as their permeation through hairless mouse skin. The derivatives were enzymatically degraded in serum to form metronidazole. Only the acetic acid and butyric acid derivatives were able to permeate hairless mouse skin intact. The fatty acid derivatives released metronidazole within the skin. The metronidazole delivery through the skin was significant when the metronidazole oleate was used. This compound could therefore be considered as a suitable pro drug for dermal applications.     

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.     

Influence of dimethylacetamide, N-N-diethyl-m-toluamide and 1-dodecylazacycloheptan-2-one on ex vivo permeation of phosphonoformic acid through rat skin

Transdermal permeation of trisodium phosphonoformate (PFA) alone and in presence of sorption promoters, dimethylacetamide (DMAC), N-N-diethyl-m-toluamide (NNDEMT) and 1-dodecylazacycloheptan-2-one (Azone) was studied using excised rat skin. DMAC in concentrations between 0.05% to 10% had no effect on amount of PFA in the skin or permeated across skin, flux or lag time. 10% NNDEMT doubled the amount of PFA in the skin, increased fourfold the amount permeated across the skin, and increased the flux fivefold. There was no influence on lag time. Azone doubled the amount of PFA in the skin, more than tripled the amount permeated across the skin, and increased the flux fourfold. There was no influence on lag time.     

In vitro percutaneous permeability enhancement of nimodipine by limonene across the excised rat abdominal skin

The purpose of the present study was to investigate the effect of limonene on the in vitro permeation of nimodipine across the excised rat abdominal skin from a 2% w/w hydroxypropyl methylcellulose (HPMC) gel drug reservoir system. The HPMC gel formulations containing 1.5% w/w of nimodipine and selected concentrations of limonene (0% w/w to 8% w/w) were prepared, and subjected to in vitro permeation of the drug through excised rat abdominal epidermis. The drug content in the gels was found to be uniform, and the drug was found to be stable in HPMC gel formulations. The flux of nimodipine across rat epidermis was markedly increased by the addition of limonene to the HPMC gels. A maximum flux of nimodipine was observed (203+/-0.6 microg/cm2 x h) with an enhancement ratio of about 5.7 when limonene was incorporated in HPMC gel at a concentration of 4% w/w. However, there was no further increase in the permeability of nimodipine beyond 4% w/w of limonene in the HPMC gel. FT-IR data indicated that limonene increased the permeability of nimodipine across the rat epidermis by partial extraction of lipids in the stratum corneum. The results suggest that limonene is useful for enhancing the skin permeability of nimodipine from transdermal therapeutic systems containing HPMC gel as a reservoir.