盐酸罂粟碱 卵磷脂微乳的制备与透皮吸收

［摘要］目的探讨以卵磷脂微乳为载体，制备盐酸罂粟碱 卵磷脂微乳透皮给药系统，促进盐酸罂粟碱的透皮吸收。方法以伪三元相图考察油包水型微乳形成区域;以十四酸异丙酯 卵磷脂 乙醇 水作为微乳的组成部分，正交分析法筛选微乳处方，测定微乳黏度;采用智能透皮仪，大鼠离体皮肤作为透皮模型，与盐酸罂粟碱水溶液及盐酸罂粟碱 卵磷脂混悬液对比，用高效液相色谱（HPLC）法测定微乳中盐酸罂粟碱经皮渗透稳态流量。结果微乳各组分及比例对微乳粒径均有影响；盐酸罂粟碱 卵磷脂微乳的经皮渗透稳态流量大于对照组。结论微乳各组分及比例对微乳体系处方的选择具有重要意义；以微乳为载体可以促进盐酸罂粟碱的经皮渗透。     

藤己微乳喷雾剂的制备及其透皮特性的研究

目的制备藤己微乳喷雾剂,比较单方青风藤微乳喷雾剂和藤己微乳喷雾剂的透皮特性。方法分别提取单方和复方中生物碱类成分,以吐温-80和异丙醇为乳化剂,油酸为油相分别制备青风藤微乳喷雾剂和藤己微乳喷雾剂。采用改良Franz扩散池,以青藤碱的渗透量为指标,比较二者的透皮性质。结果单方青风藤微乳喷雾剂中青藤碱的体外透皮释药方程为y=19.489x+2.155(R=0.9982),12h的累积渗透量为239.393μg/mL;藤己微乳喷雾剂中青藤碱的体外透皮释药方程为y=31.264x+11.975(R=0.9978),12h的累积渗透量为385.696μg/mL。结论两种制剂中青藤碱的均以零级动力学经皮渗透,而且藤己微乳喷雾剂中青藤碱的透皮效果比单方更好。     

天山雪莲微乳体外经皮渗透特性

目的:研究天山雪莲微乳对离体大鼠皮肤的渗透能力。方法:采用Franz扩散池,以离体鼠皮为渗透屏障,HPLC法测定,以绿原酸和芦丁为检测指标,考察不同载药量的天山雪莲微乳体外透皮特点。结果:天山雪莲微乳的透过百分率(P)随着微乳载药量的增加而增加,皮内滞留率则随着微乳载药量的增加而降低。结论:天山雪莲微乳有较强的透皮能力,有望开发为天山雪莲的新型透皮给药制剂。     

蛇床子素微乳透皮吸收的研究

目的考察蛇床子素微乳对离体小鼠皮的透皮能力。方法用药物渗透扩散仪研究蛇床子素微乳的透皮速率,用HPLC法测定皮肤接受液中药物浓度,并与蛇床子素凝胶进行比较。结果蛇床子素微乳的透皮速率显著大于蛇床子素凝胶,蛇床子素微乳的平均透皮速率为(33.04±3.1)μg.cm-2.h-1(r=0.9950),蛇床子素凝胶的渗透速率为(7.204±1.06)μg.cm-2.h-1(r=0.9970)。结论蛇床子素微乳有很强的透皮能力,有望成为蛇床子素的新型透皮给药制剂。     

蛇床子素微乳的制备及其透皮能力的研究

目的:制备蛇床子素微乳,并考察其对离体小鼠皮肤的透皮能力。方法:通过测定蛇床子素在不同油相、乳化剂和助乳化剂中的溶解度,结合伪三元相图筛选空白微乳的处方。考察蛇床子素微乳的黏度、电导率和粒径;用药物渗透扩散仪测定蛇床子素微乳的透皮速率。结果:制得的蛇床子素微乳的黏度为8.07mpa·s,电导率为123μS·cm-1,平均粒径为58.0nm。微乳中药物经小鼠皮肤的稳态渗透速率为(33.042±3.1)μg·cm-2·h-1(r=0.9950),是蛇床子素饱和溶液稳态渗透速率的25.5倍。结论:蛇床子素微乳有很强的透皮能力,有望成为蛇床子素的新型透皮给药制剂。     

吡罗昔康外用微乳的制备及其透皮吸收的研究

目的制备吡罗昔康微乳并考察其体外经皮渗透特性。方法采用Lauroglycol FCC为油相、Labrasol、Cremo-phor EL为表面活性剂、Transcutol P、乙醇为助表面活性剂,绘制伪三元相图,制备吡罗昔康O/W微乳。采用智能透皮实验仪,大鼠背部皮肤作为透皮模型,HPLC测定药物透皮浓度,研究吡罗昔康微乳的透皮特性。结果本实验中微乳较优处方含：吡罗昔康0.5%,Lauroglycol FCC10%,Labrasol、Cremophor EL、Transcutol P各13.3%及水50%,吡罗昔康渗透速率可达10.04±1.73μg/（cm2.h）。结论吡罗昔康微乳有很强的透皮能力,有望成为吡罗昔康的新型透皮给药制剂。     

不同剂型青藤碱的体外皮肤渗透性

目的:比较青藤碱微乳、固体脂质纳米粒和脂质体对离体大鼠皮肤的透皮能力。方法:采用改进的Franz扩散池研究三者的透皮行为,采用高效液相色谱法测定接受液中青藤碱浓度并比较三者的经皮渗透能力。结果:t检验结果表明,体外经皮渗透试验中,青藤碱不同剂型的经皮渗透速率差异明显,差异具统计学意义(P<0.01),微乳>固体脂质纳米粒>脂质体。结论:青藤碱微乳有较强的透皮能力,适合青藤碱的新型透皮给药剂型。     

氟比洛芬微乳的制备及其透皮吸收的研究

目的:制备氟比洛芬微乳,考察氟比洛芬微乳对离体大鼠皮的透皮能力.方法:Zetapals多功能电位/粒度分析仪测定氟比洛芬微乳的粒度及其分布.用改进的Franz扩散池研究氟比洛芬微乳的透皮速率,进一步优化处方.结果:微乳最优处方舍1.0%氟比洛芬,5.0%油酸乙酯,22.5%聚山梨醇酯80,7.5%丙二醇和64.0%水,微乳中药物经大鼠皮肤的稳态渗透速率为(19.8±3.1)μg·cm-2·h-1(r=0.998 5).结论:氟比洛芬微乳有很强的透皮能力,有望成为氟比洛芬的新型透皮给药制剂.     

咪喹莫特微乳的制备及体外透皮评价

制备咪喹莫特微乳并考察其理化性质。载药微乳平均粒径为37.8nm,多分散指数为0.440。体外透皮试验表明,微乳8h累积渗透量明显高于咪喹莫特乳膏。     

碘化钾微乳的制备及其体外透皮吸收作用考察

目的:制备碘化钾微乳并考察其透皮吸收的效果。方法:以伪三元相图为基础,依据微乳区域大小,确定微乳的油相、乳化剂、助乳化剂和后二者的比例(Km),初步筛选微乳处方;采用改进的Franz扩散池和离体小鼠皮肤进行体外经皮渗透试验,比较所制5%、10%碘化钾微乳与5%碘化钾溶液单位面积的累积渗透量(Qn),并对微乳进行加速稳定性试验。结果:碘化钾微乳的最优处方为碘化钾10%(m/V)、水23%、混合乳化剂(月桂山梨坦-乙醇Km值为1∶1)61.6%、油相(丙二醇单辛酸酯)15.4%;所制微乳的渗透过程符合一级速率方程,3种样品的Q24 h分别为(5.40±0.28)、(8.75±0.42)、(2.12±0.20)mg/cm2;40℃下贮存4周后所制微乳与贮存前比较p H、含量、外观均未见明显变化。结论:成功制得具有透皮吸收作用的碘化钾微乳。     

Evaluation of nicotinamide microemulsion on the skin penetration enhancement

This study purposed to evaluate a microemulsion containing nicotinamide for its characteristics, stability, and skin penetration and retention comparing with a solution of nicotinamide in 2:1 mixture of water and isopropyl alcohol (IPA). The microemulsion system was composed of 1:1 mixture of Span80 and Tween80 as a surfactant mixture, isopropyl palmitate (IPP) as an oil phase, and 2:1 mixture of water and IPA as an aqueous phase. Nicotinamide microemulsion was prepared by dissolving the active in the aqueous phase before simply mixing with the other components. It was determined for its characteristics and stability under various conditions. The skin penetration and retention studies of nicotinamide microemulsion and solution were performed by modified Franz diffusion cells, using newborn pig skin as the membrane. The results showed that nicotinamide microemulsion could be obtained as clear yellowish liquid, was water-in-oil (w/o) type, possessed Newtonian flow, and exhibited physicochemical stability when kept at 4?°C and room temperature (≈30?±?2?°C) during 3 months. From the skin penetration data, the microemulsion could enhance the skin penetration of nicotinamide comparing with the solution. Additionally, nicotinamide microemulsion could provide much higher amount of skin retention than that of skin penetration, resulting in suitability for a cosmeceutical product.     

Adapalene Microemulsion for Transfollicular Drug Delivery

The aim of this study was to develop a microemulsion formulation of adapalene for transfollicular delivery. A pseudoternary phase diagram was developed for microemulsion consisting of oleic acid as oil phase, tween 20 as surfactant, Transcutol® as cosurfactant, and deionized water. Differential tape stripping and confocal laser scanning microscopy were performed to determine the penetration of microemulsion through hair follicles. Transmission electron microscopy, dynamic light scattering, polarizing light microscopy, and differential scanning calorimetry were performed to characterize the microstructures of microemulsion. The pH and viscosity of the microemulsions were also determined. Permeation studies were carried out in vitro on porcine ear skin over a period of 24 h using Franz diffusion cells. The drug penetration in the hair follicles increased from 0.109 ± 0.03 to 0.292 ± 0.094 μg, as the microstructure of microemulsion shifted from oil-in-water to bi-continuous, with increase in water content of microemulsion. Confocal laser scanning microscopy images suggested that hair follicles provided the path for transfollicular permeation of adapalene microemulsion. These results suggest that microemulsion penetrated through hair follicles and are promising for transfollicular drug delivery. © 2013 Wiley Periodicals, Inc. and the American Pharmacists AssociationJ Pharm Sci 102:2622–2631, 2013     

槲皮素微乳凝胶制备及体外透皮研究

目的制备槲皮素微乳凝胶,并对其性能及透皮效果进行研究。方法根据已优化的槲皮素微乳的处方并将微乳制成凝胶,采用Franz扩散池对槲皮素微乳凝胶的体外透皮情况进行考察。结果从体外透皮实验可见,与槲皮素混悬液凝胶比较,槲皮素微乳凝胶的体外透过量明显增加(P0.05)。结论槲皮素微乳凝胶的制备工艺可行,且能促进槲皮素的透皮转运量。     

In vitro permeation of diclofenac sodium from novel microemulsion formulations through rabbit skin

In order to increase topical penetration of the nonsteroidal anti‐inflammatory drug, diclofenac sodium, new microemulsion formulations were prepared to increase drug solubility and in vitro penetration of the drug. The influence of dimethyl sulfoxide and propylene glycol were also investigated as enhancers on the in vitro penetration of diclofenac sodium using Franz diffusion cells using excised dorsal rabbit skin. Factorial randomized design was performed to analyze the results of in vitro permeation studies. Microemulsions prepared with isopropyl alcohol were superior to those prepared with propanol. Enhancers had different effects depending on the formulation. Propylene glycol was superior to dimethyl sulfoxide when incorporated into isopropyl alcohol microemulsion, whereas dimethyl sulfoxide was superior to propylene glycol in propanol microemulsions. There were no observable histopathological differences between the skin of the control group and the treated groups at the light microscope level due to swelling of the skin tissue. The present study shows that microemulsion formulations containing isopropyl alcohol as co‐surfactant and propylene glycol as enhancer represent a promising approach for a topical vehicle for diclofenac sodium. Drug Dev. Res. 65:17–25, 2005. © 2005 Wiley‐Liss, Inc.     

Assessment of the percutaneous penetration of indomethacin from soybean oil microemulsion: effects of the HLB value of mixed surfactants

The objective of this study was to evaluate the influence of the ratios or the hydrophile-lipophile balance (HLB) values of Cremophor EL and Span 80 on the phase behavior of the O/W microemulsions and the percutaneous absorption and penetration of indomethacin microemulsions. The existence of microemulsion regions is investigated in quaternary systems composed of soybean oil/Cremophor EL and Span 80 (mixed surfactants)/diethylene glycol monoethyl ether (cosurfactant)/water by constructing pseudo-ternary phase diagrams at various Cremophor EL/Span 80 ratios. In addition, five microemulsion formulations with various mixed surfactants HLB values were evaluated by in vitro penetration experiments using mouse skin and Franz diffusion cells. The flux and amount of indomethacin penetration from 5 microemulsion formulations were significantly different from the control, and the enhance ratios ranged from 2.38 to 4.68 and 2.11 to 4.23, respectively. The HLB value of mixed surfactants in the formulations was a principal factor in determining the percutaneous penetration of the drug. The flux and amount of drug penetration increased gradually with increasing content of the lipophilic surfactant Span 80 and skin retention was highest for mixed surfactants with a HLB value of 7.6. Therefore, it is suggested that the presence of mixed surfactants was beneficial in the formation of O/W microemulsions and enhanced percutaneous penetration of indomethacin.     

Characterisation of microemulsions containing orange oil with water and propylene glycol as hydrophilic components

The current study aims to investigate the effect of incorporation of orange oil, mainly consisting of the cyclic mono-terpene linolene, a known skin penetration enhancer, as oil component on microemulsion formation both in water and propylene glycol containing systems. Phase diagrams of pseudoternary mixtures containing orange oil, ethyloleate or a 1:1 mixture (w/w) of orange oil and ethyloleate as oil components, a 6:4 (w/w) mixture of polyoxyethylene 20 sorbitan monooleate and sorbitan monolaurate as surfactant components and water or propylene glycol as hydrophilic components were investigated. Smaller microemulsion regions were observed when orange oil was used as a substitute for ethyloleate in both water and propylene glycol containing systems. Polarising light microscopy, viscosity measurements, electrical conductivity measurements and cryo-field emission scanning electron microscopy were used to identify structural features of the microemulsions. Solution-type, w/o droplet-type microemulsions and microemulsion areas containing liquid crystals were found in varying areas in the phase diagrams of water containing systems. Liquid crystals formation occurs when the water concentration reaches 20%-22.5% (w/w). Only solution-type microemulsions were observed in propylene glycol containing systems. The dimension of solution-type microemulsion areas in the phase diagrams is likely to depend on the miscibility of components and larger microemulsion areas were found when ethyloleate was used instead of orange oil and propylene glycol was used instead of water. W/o droplet-type microemulsions of systems containing orange oil and ethyloleate as oil components appear in different areas of the phase diagrams. Incorporation of orange oil as a penetration enhancer into a topical microemulsion affects its physical characteristics. This in turn may lead to instability of the microemulsion and/or can influence the release patterns of drugs from these microemulsions when applied as topical formulations.     

Preparation and in vitro evaluation of an ilomastat microemulsion gel by a self-microemulsifying system

The purpose of this study was to construct a microemulsion gel formulation by a self-microemulsifying system for transdermal topical delivery of ilomastat. The optimum formulations were screened by penetration evaluation in vitro. Ilomastat microemulsion gel was prepared by drawing a ternary phase diagram and Pluronic F127 was added as gel matrix for the formulation. The optimal formulations had wide microemulsion existent field and good self-microemulsifying efficiency. The droplet size was within 100 nm. Statistical comparison of the permeation throughout 24 h showed that the two microemulsion gel preparations of ilomastat provided higher permeation than that of the normal gel which had only a low cumulative amount of ilomastat (6.03 microg x cm(-2)) 24 h after application. Cumulative amount of ilomastat from microemulsion gels A and B was 2.2 times and 1.8 times that of the normal gel at 24 h respectively. These results indicate that the microemulsion gel may be a promising vehicle for topical delivery of ilomastat.     

Formulation of ascorbic acid microemulsions with alkyl polyglycosides

Ascorbic acid microemulsions for topical application were developed. In this study, microemulsions were prepared using HLD (hydrophilic lipophilic deviation) concept to optimise the formulation. From this optimal formulation, the realisation of dilution ternary diagrams leads to obtain microemulsion zones. In addition, the effects of composition variable on the physicochemical characteristics of each system were investigated. After optimisation of the microemulsion systems, ascorbic acid was loaded in the formulations. Surface tension and small angle neutron scattering were used to characterise the surface properties and the structure of the microemulsions. Bicontinuous structure microemulsions were identified, and the influence of ascorbic acid localisation at the interface leading to modifications of the microemulsion structure was pointed out. The solubilisation of ascorbic acid, the stabilisation and in vitro transdermal penetration “Frantz cells” of ascorbic acid microemulsions were studied. Three different microemulsions were envisaged. The results confirmed that these microemulsion systems present a real interest for formulation and protection of ascorbic acid. Regarding their transcutaneous penetration behaviour, the different microemulsions studied could be useful for different topical applications. A major location of ascorbic acid found in the epidermis where the decomposition of melanin occurred indicates that microemulsion could be considered as a suitable carrier system for application of ascorbic acid as a whitening agent. In addition, a good passage of the drug in the dermis could be interesting for the relative oxygen matrix damage.     

丁香酚微乳凝胶的制备及其体外释放特性研究

目的制备高载药量、高黏附性的丁香酚微乳凝胶,以提高丁香酚的透皮渗透性和相对生物利用度。方法通过表观溶解度评价丁香酚在油、表面活性剂和助表面活性剂中的溶解度,以筛选微乳的处方组成。以油酸乙酯为油相,Solutol HS15为表面活性剂和PEG 400为助表面活性剂,纯化水为水相构建伪三元图。评价微乳的pH值、电导率、黏度、粒径和药物浓度。通过甘油润湿的卡波姆940配制成微乳凝胶,并评价微乳凝胶的pH值、粒径、黏度和药物浓度。采用改良Franz扩散池法对丁香酚微乳凝胶的体外释放性能进行考察。结果表面活性剂和助表面活性剂之比为1∶1时,形成的微乳区域最大;微乳(F3)的球体尺寸为83.27 nm,含量稳定。加入0.5%卡波姆940和6%甘油制得外观均匀、透明的微乳凝胶,微乳(F3)黏度为106.8 mPa·s,微乳凝胶(FG3)黏度增加到15.7 Pa·s。体外经皮渗透试验表明丁香酚对照品溶液、微乳和微乳凝胶的经皮累积渗透率依次增大,微乳凝胶(FG3)渗透12h后丁香酚经皮累积渗透量为55.08%。家兔刺激试验结果表明其在家兔皮肤上没有刺激或诱导炎症。结论丁香酚微乳凝胶比丁香酚对照品溶液、丁香酚微乳具有更好的应用性和稳定性,有望成为丁香酚的新型给药制剂。