Investigating effect of microemulsion components: In vitro permeation of ketoconazole

The purpose of this study was to evaluate the effect of oil, surfactant/co-surfactant mixing ratios and water on the in vitro permeation of ketoconazole (KTZ) applied in O/W microemulsion vehicle through intact rat skin. Lauryl Alcohol (LA) was screened as the oil phase of microemulsions, due to a good solubilizing capacity of the microemulsion system. The pseudo-ternary phase diagrams for microemulsion regions were constructed using LA as the oil, Labrasol (Lab) as the surfactant (S) and ethanol (EtOH) as the cosurfactant (CoS). The formulation which showed a highest permeation rate of 54.65?±?1.72 µg/cm²/h¹ and appropriate physico-chemical properties was optimized as containing 2% KTZ, 10% LA, 20% Lab/EtOH (1:1) and 68% double distilled water (w/w). The efficiency of microemulsion formulation in the topical delivery of KTZ was dependent upon the contents of water and LA as well as Lab/EtOH mixing ratio. It was concluded that the percutaneous absorption of KTZ from microemulsions was enhanced with increasing the LA and water contents, and with decreasing the Lab/EtOH ratio in the formulation. Candida albicans was used as a model fungus to evaluate the antifungal activity of the best formula achieved, which showed the widest zone of inhibition as compared to KTZ reference. The studied microemulsion formulation showed a good stability for a period of three months. Histopathological investigation of rat skin revealed the safety of microemulsion formulations for topical use. These results indicate that the studied microemulsion formulation might be a promising vehicle for topical delivery of KTZ.     

Transdermal delivery of ketoprofen using microemulsions

A transdermal preparation containing ketoprofen was developed using O/W microemulsion system. Of the oils tested, oleic acid was chosen as the oil phase of the microemulsion, as it showed a good solubilizing capacity and excellent skin permeation rate of the drug. Pseudoternary phase diagrams were constructed to obtain the concentration range of oil, surfactant and cosurfactant for microemulsion formation, and the effect of these additives on skin permeation of ketoprofen was evaluated with excised rat skins. The optimum formulation of the microemulsion consisted of 3% ketoprofen, 6% oleic acid, 30% Labrasol/Cremophor RH 40 (1:1) and water. Terpenes were added to the microemulsion at the level of 5% and their effect on the skin permeation of ketoprofen from the microemulsion was evaluated. Of the four terpenes used, only limonene resulted in a powerful enhancing activity (3-fold increase over control).     

遗传算法在经皮给药微乳载体处方优化中的应用

以萘普生为模型药物，用遗传算法优化经皮给药微乳载体的处方。用伪三元相图法确定由Tween 80、IPM、乙醇和水组成的微乳区域。用3因素3水平的中心设计法制备载药量为1.12%的萘普生模型微乳，并进行离体兔皮的体外渗透实验。以稳态渗透速率的二次回归模型为目标函数，用遗传算法对中心设计结果进行优化，筛选出具有最大透皮速率的萘普生微乳载体处方。所得优化处方的组成为：21.41% Tween 80、15.17%乙醇、4.14% IPM和59.28%水，预计的稳态渗透速率为183.57 μg·cm^-2·h^-1。回代试验表明，以优化处方制备的萘普生微乳，其稳态渗透速率的平均值为189.43 μg·cm^-2·h^-1，高于预测值。结果表明，用遗传算法筛选微乳经皮给药载体处方，方法可行，结果合理、可靠。     

Investigation of microemulsion microstructures and their relationship to transdermal permeation of model drugs: ketoprofen, lidocaine, and caffeine

In this study, microemulsion microstructures, key formulation variables, and their relationship to drug transdermal permeation enhancement were investigated. A microemulsion system with high water soluble capacity was developed, using isopropyl myristate, Labrasol, and Cremophor EL as oil, surfactant, and co-surfactant, respectively. The microstructures of the microemulsions were characterized by a combination of techniques including electrical conductivity measurement (EC), differential scanning calorimetry (DSC), electro-analytical cyclic voltammetry (CV), dynamic light scattering (DLS). Three microemulsion formulations with the model drugs at water contents of 20%, 40%, and 70% representing the microstructures of W/O, Bi-continuous, and O/W were prepared along the water dilution line of oil to surfactant ratio of 1/9. Skin permeation of hydrophobic and hydrophilic model drugs, ketoprofen, lidocaine, and caffeine in the microemulsion formulations was studied using Franz-cells and dermatomed porcine skin. Permeation of all drugs from microemulsions was enhanced significantly compared with the control propylene glycol formulation. The drug permeation flux and the cumulative permeation amount after 24 h increased with water content in the microemulsions, thus correlated to the formulation microstructures of W/O, Bi-continuous, and O/W. The permeation of lipophilic drugs ketoprofen and lidocaine increased with water content in a more pronounced manner, which seemed to follow an exponential growth trend, while the permeation of hydrophilic drug caffeine appeared to increase linearly. Additionally, at the same water content, increasing oil content led to higher ketoprofen permeation.     

Transdermal delivery of diclofenac using microemulsions

A transdermal preparation containing diclofenac diethylammonium (DDA) was developed using an O/W microemulsion system. Of the oils tested, lauryl alcohol was chosen as the oil phase of the microemulsion, as it showed a good solubilizing capacity and excellent skin permeation rate of the drug. Pseudoternary phase diagrams were constructed to obtain the concentration range of oil, surfactant and cosurfactant for microemulsion formation, and the effect of these additives on skin permeation of DDA was evaluated with excised rat skins. The optimum formulation of the microemulsion consisted of 1.16% of DDA, 5% of lauryl alcohol, 60% of water in combination with the 34.54% of Labrasol (surfactant)/ethanol (cosurfactant) (1:2). The efficiency of formulation in the percutaneous absorption of DDA was dependent upon the contents of water and lauryl alcohol as well as Labrasol:ethanol mixing ratio. It was concluded that the percutaneous absorption of DDA from microemulsions was enhanced with increasing the lauryl alcohol and water contents, and with decreasing the Labrasol:ethanol mixing ratio in the formulation.     

Formulation development of a cream containing fennel extract: in vivo evaluation for anti-aging effects

This study was aimed to formulate and evaluate anti-aging effects of a topical cream (w/o emulsion) containig extract of Fennel (Foeniculum vulgare) versus its base. Formulation containing 4% concentrated extract of Foeniculum vulgare was developed by entrapping in the inner aqueous phase of w/o emulsion and base contained no extract. Both the base and formulation were stored under different storage conditions to predict their stability. The formulation and base were evaluated for effect on skin moisture and transepidermal water loss (TEWL). The base showed insignificant while the formulation showed significant effects on skin moisture and TEWL. The parameter volume and surface evaluation of living skin (SELS) parameters SEr, SEsc, SEsm, SEw were also evaluated and showed a significant (p < or = 0.05) decline. The texture parameter energy showed a significant increase proving that the formulation possesses potential anti-aging effects.     

Novel microemulsion-based gel formulation of tazarotene for therapy of acne

The objective of this study was to develop and evaluate a novel microemulsion based gel formulation containing tazarotene for targeted topical therapy of acne. Psudoternary phase diagrams were constructed to obtain the concentration range of oil, surfactant, and co-surfactant for microemulsion formation. The optimized microemulsion formulation containing 0.05% tazarotene was formulated by spontaneous microemulsification method consisting of 10% Labrafac CC, mixed emulsifiers 15% Labrasol–Cremophor–RH 40 (1:1), 15% Capmul MCM, and 60% distilled water (w/w) as an external phase. All plain and tazarotene-loaded microemulsions were clear and showed physicochemical parameters for desired topical delivery and stability. The permeation profiles of tazarotene through rat skin from optimized microemulsion formulation followed the Higuchi model for controlled permeation. Microemulsion-based gel was prepared by incorporating Carbopol®971P NF in optimized microemulsion formulation having suitable skin permeation rate and skin uptake. Microemulsion-based gel showed desired physicochemical parameters and demonstrated advantage over marketed formulation in improving the skin tolerability of tazarotene indicating its potential in improving its topical delivery. The developed microemulsion-based gel may be a potential drug delivery vehicle for targeted topical delivery of tazarotene in the treatment of acne.     

Skin permeation enhancement effect and skin irritation of saturated fatty alcohols

Though the skin permeation enhancement effect of chemical penetration enhancers has been studied extensively, their skin irritation potential has not been adequately investigated. The objective of this study was to evaluate the skin permeation enhancement effect and skin irritation of saturated fatty alcohols using melatonin as a model compound. A saturated solution of melatonin in a mixture of water and ethanol (40:60) containing 5% w/v of saturated fatty alcohol was used in the skin permeation studies using Franz diffusion cells. For skin irritation studies, 230 microl of fatty alcohol solution was applied on the dorsal surface of the hairless rats using Hill top chamber. The skin irritation was evaluated by visual scoring method and bioengineering methods such as measurement of transepidermal water loss (TEWL) and skin blood flow. The flux of melatonin across hairless rat skin was found to be dependent on the carbon chain length of the fatty alcohols, with decanol showing the maximum permeation of melatonin. All fatty alcohols increased the TEWL and skin blood flow significantly compared with the vehicle. The fatty alcohols (decanol, undecanol and lauryl alcohol), which showed greater permeation of melatonin, also produced greater TEWL, skin blood flow and erythema. Tridecanol and myristyl alcohol showed lower permeation enhancement effect but caused greater skin irritation. Octanol and nonanol may be the most useful enhancers for the transdermal delivery of melatonin considering their lower skin irritation and a reasonably good permeation enhancement effect. However, further studies are needed to ascertain their safety as skin penetration enhancers. Skin permeation and skin irritation in experimental animals such as rats are generally higher compared with human skin. Further studies in human volunteers using fatty alcohols at the concentrations of 5% or lower may provide useful information on the utility of these fatty alcohols as permeation enhancers.     

Short term study of human skin irritation by single application closed patch test: assessment of four multiple emulsion formulations loaded with botanical extracts

Background: Assessment of skin irritation potential is a major concern in safety assessment of cosmetics, when long-term use of these products are expected. Non-invasive bioengineering probes have been used previously to measure skin irritation potential of cosmetic ingredients.

Objectives: Experimentation carried out to weigh up the skin irritation potential of four multiple emulsion formulations via visual and non-invasive measurements. Immediate effects of formulations and comparison of two assessment techniques were also tried to establish.

Methods: Four multiple emulsion formulations one control (without botanical active) and three containing the functional botanical actives plus additives were tested in this study using the following techniques: transepidermal water loss (TEWL), COLIPA visual scoring method (CVSM), Mexameter MPA 5 (Courage + Khazaka, Germany) and capacitance [Corneometer MPA 5 (Courage + Khazaka, Germany)]. Visual examination and non-invasive measurements were performed at baseline and after 24?h. The formulations were applied on the forearm of 12 healthy volunteers of same sexes aged 20–25 years.

Results: We found that none of the formulation produced irritation both on visual and instrumental evaluation. However, formulations MeB and MeC have comparable immediate effects on dryness, erythema, melanin and TEWL. Formulation MeC produced more effective results on different parameters, may be due to synergistic effect of two extracts, while MeA failed to produce any immediate effects on skin parameters. Moreover results of both assessment methods are parallel to each other.

Conclusions: None of the formulation produce irritant effects, barrier impairment effects or immediate effects except for the formulation MeC which produced appreciable results than other formulations but statistically these results were insignificant (p?>?0.05). Based on these results, it could be concluded that formulations may be implied safely as skin rejuvenating candidates.     

Solubility and Transdermal Permeation Properties of a Dehydroepiandrosterone Cyclodextrin Complex from Hydrophilic and Lipophilic Vehicles

The permeation ability of a compound is due principally to its concentration in the vehicle and to its aptitude to cross the stratum corneum of the skin. In this work ex-vivo permeation studies on newly developed formulations containing dehydroepiandrosterone (DHEA) were carried out to investigate vehicles that increase drug permeation through the skin. To enhance the solubility of DHEA, its complex form with α-cyclodextrin was used. In addition, the two forms (pure drug and complex form) were introduced in hydrophilic (water), lipophilic (paraffin oil), and microemulsion vehicles to evaluate the synergic effect of cyclodextrins and microemulsion vehicles on solubility and permeation. From the results, DHEA solubility is notably conditioned by the type of the vehicle used: the highest solubilities (both for pure and complex drug forms) were obtained with microemulsion, followed by paraffin oil and water. Moreover, in all the studied vehicles, the c-DHEA was more soluble than DHEA. Permeation profile fluxes showed very interesting differences. That reflect the varying drug forms (pure drug and complex form), vehicles used, and drug concentrations in the vehicles. The major flux was obtained in complex of DHEA with α-cyclodextrins in the microemulsion vehicle. Therefore, this type of vehicle and drug form would be very useful in the development of a topical formulation containing DHEA.     

Preparation and evaluation of aceclofenac microemulsion for transdermal delivery system

To develop novel transdermal formulation for aceclofenac, microemulsion was prepared for increasing its skin permeability. Based on solubility and phase studies, oil and surfactant was selected and composition was determined. Microemulsion was spontaneously prepared by mixing ingredients and the physicochemical properties such was investigated. The mean diameters of microemulsion were approximately 90 nm and the system was physically stable at room temperature at least for 3 months. In addition, the in vitro and in vivo performance of microemulsion formulation was evaluated. Aceclofenac was released from microemulsion in acidic aqueous medium, and dissolved amounts of aceclofenac was approximately 30% after 240 min. Skin permeation of aceclofenac from microemulsion formulation was higher than that of cream. Following transdermal application of aceclofenac preparation to delayed onset muscle soreness, serum creatine phosphokinase and lactate dehydrogenase activity was significantly reduced by aceclofenac. Aceclofenac in microemulsion was more potent than cream in the alleviation of muscle pain. Therefore, the microemulsion formulation of aceclofenac appear to be a reasonable transdermal delivery system of the drug with enhanced skin permeability and efficacy for the treatment of muscle damage.     

长春西汀微乳的优化及其理化性质的考察

目的选择适宜比例的油相、表面活性剂、助表面活性剂和水相制备长春西汀微乳制剂以增加药物的溶解度和经皮渗透量，优化处方，并对其理化性质和刺激性进行研究。方法绘制伪三元相图，确定各相的比例，以经皮稳态渗透流量为指标，利用单纯形网格法优化处方，并考察优化微乳的pH、粘度、电导率、折光率、粒径分布等理化性质。采用MTT法考察微乳制剂对人体皮肤细胞系模型Hacat细胞的毒性。结果O/W微乳在相图中的区域随着表面活性剂和助表面活性剂比例的增加而增加；单纯形网格优化法预测的指标值与实测值相近，所得的优化微乳性质稳定，对Hacat细胞无刺激性，与阴性组无显著性差异。结论长春西汀微乳制剂中药物的溶解度极大提高，经皮稳态渗透流量显著增大，安全稳定，可作为经皮给药的新型载体。     

Antipsoriatic microemulsion gel formulations for topical drug delivery of babchi oil (Psoralea corylifolia)

The aim of this study was to investigate and evaluate a microemulsion gel-based system of babchi oil (Psoralea corylifolia) for the treatment of psoriasis, which could provide improved permeation of the drug through the skin and increased patient compliance. Babchi oil is used because its chief constituent psoralen is a photoactive furocoumarin that binds to DNA when exposed to UV light to form photoproducts with pyrimidine base. This action inhibits DNA synthesis and causes decrease in cell proliferation. Moreover, babchi oil, in addition to providing psoralen, also acts as an oily phase for microemulsion system. The presence of surfactant and cosurfactant increases the permeation. On the basis of qualitative and quantitative estimation of all eight brands of babchi oil, Bakuchi Tail was selected for microemulsion formulation. Microemulsions were prepared by aqueous phase-titration method. Pseudoternary phase diagrams were constructed for the identification of microemulsion existence zones. Prepared microemulsions were subjected to different thermodynamic stability tests and characterized for droplet size, viscosity and refractive index. In vitro skin permeation of babchi oil through rat abdominal skin was determined by the Franz diffusion cell. The in vitro skin permeation profile of formulation F2, which consisted of 1.67% v/v of babchi oil, 8.33% v/v of oleic acid, S(mix) 55% v/v of Tween 80 Transcutol-P (S/Co ratio 1:1) and 35% v/v of distilled water, was significant when compared with other microemulsion formulations (p < 0.05). Formulation F2 was converted into microemulsion gel by adding 1% Carbopol-940 and coded as MGF2. Formulation MGF2 was selected for its in vivo antiinflammatory effects determined by footpad edema. The results suggested that microemulsion gel is a potential vehicle for improved topical delivery of psoralen and that microemulsion gels are potential vehicles for improved topical delivery of babchi oil.     

Transdermal delivery of nalbuphine and its prodrugs by electroporation.

The aim of this study was to assess the effects of electroporation on transdermal permeation of nalbuphine (NA) and its prodrugs. The permeation characteristics were investigated under various electrical factors and skin barriers to elucidate the mechanisms involved in transdermal delivery of NA and its prodrugs by skin electroporation. The in vitro permeation studies were performed using side-by-side diffusion cells. The various electrical factors investigated were pulse voltage, pulse duration and pulse number; the different skin barriers studied were intact hairless mouse skin, stratum corneum (SC)-stripped skin, delipid skin as well as furry Wistar rat skin. The prodrugs were fully converted to parent drug after skin permeation. Application of electroporation significantly enhanced transdermal permeation of NA and its prodrugs. The enhancement ratios were highest for NA and the four prodrugs showed the similar permeability after electroporation. The permeation amounts of NA and its prodrugs may be increased by application of higher pulse voltage, pulse duration as well as pulse number. Various kinetics and mechanisms were observed for the permeation of the hydrophilic NA and lipophilic nalbuphine enanthate through different skin barriers by applying electroporation. This study demonstrated that electroporation may enhance and control transdermal permeation of NA and its prodrugs. The results also indicated that the physicochemical properties of prodrug had significant effects on kinetics as well as mechanisms of transdermal permeation by electroporation.     

Alteration of skin hydration and its barrier function by vehicle and permeation enhancers: a study using TGA, FTIR, TEWL and drug permeation as markers

Vehicles and permeation enhancers (PEs) used in transdermal drug delivery (TDD) of a drug can affect skin hydration, integrity and permeation of the solute administered. This investigation was designed to study the effect of the most commonly used vehicles and PEs on rat skin hydration, barrier function and permeation of an amphiphilic drug, imipramine hydrochloride (IMH). An array of well-established techniques were used to confirm the findings of the study. Thermogravimetric analysis (TGA) and Fourier transform infrared (FTIR) spectroscopy were used to determine changes in skin hydration. Alteration of the stratum corneum (SC) structure was investigated using FTIR studies. To monitor the barrier function alteration, transepidermal water loss (TEWL) measurement and permeation studies were performed. Our findings indicate that with hydration, there was an increase in the bound water content of the skin, and pseudoequilibrium of hydration (a drastic decrease in hydration rate) was achieved at around 12 h. Hydration increased the ratio between amide-I and amide-II peaks in FTIR and reduced the C-H stretching peak area. Both propylene glycol (PG) and ethanol (EtOH) dehydrated skin, with the latter showing a predominant effect. Furthermore, it was confirmed that PG and EtOH decreased the bound water content due to alteration in the protein domains and extraction of SC lipids, respectively. The effect of hydration on the SC was found to be similar to that reported for temperature. Permeation studies revealed that the dehydration caused by vehicles decreased IMH flux, whereas the flux was enhanced by PEs. The role of partition was predominant for the permeation of IMH through dehydrated skin. A synergistic effect was observed for PG and menthol in the enhancement of IMH. Further findings provided strong evidence that PG affects protein domains and EtOH extracts lipids from the bilayer. Both PG and EtOH, with or without PEs, increased TEWL. Initial TEWL was well correlated with the flux of IMH through the same skin. It was found that both PG and EtOH affect the permeation of solute and TEWL by dehydration. The experiments also proved that the initial TEWL value has a strong potential as a predictive tool for the permeation of the solute.     

Effect of emulsification on the skin permeation and UV protection of catechin

Abstract

An anti-aging effect may be obtained by skin application of tea catechins (Camellia sinensis) since they have high ultraviolet (UV)-protection activity. In this study, the skin permeation of catechin (C), epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECg) and epigallocatechin gallate (EGCg) was determined and compared, and the effect of emulsification on the skin permeation of C was measured. The UV-protective effect of C was also determined. The in vitro skin permeability of each catechin derivative was determined using side-by-side diffusion of cells. The UV-protective effect of C was determined by applying different concentrations of C to the solution or emulsion on a three-dimensional cultured human skin model or normal human epidermal keratinocytes with UV-irradiation. ECg and EGCg with gallate groups showed lower skin permeability than C, EC and EGC without gallate groups, suggesting that the skin permeability of catechin derivatives may be dependent on the existence of a gallate group. Interestingly, the skin permeation of C was increased by an o/w emulsification. In addition, the C emulsion showed a significantly higher UV-protective effect by C than that with its aqueous solution. These results suggest that the o/w emulsion of catechin derivatives is probably useful as a cosmetic formulation with anti-aging efficacy.     

Development of an in vitro skin permeation model simulating atopic dermatitis skin for the evaluation of dermatological products

Atopic dermatitis (AD) skin has a defective barrier function as indicated by increased transepidermal water loss (TEWL). In order to test potential new formulations for AD, it was our aim to develop a skin permeation model simulating AD skin by inducing barrier impairment to otherwise healthy skin simulating the barrier properties of AD skin as evaluated by TEWL measurements. Pig ear skin was mounted to Franz-type diffusion cells. Skin barrier impairment was induced by tape strippings. As the number of strips increased, higher TEWL values were obtained. By performing 25 tape strippings, the TEWL value within the range reported for involved skin of AD patients was reached. The in vitro skin permeation of fusidic acid and betamethasone-17-valerate was found to correlate with the number of tape strippings used to remove stratum corneum cell layers. A comparison of the permeability of fusidic acid and betamethasone-17-valerate from Fucicort cream to a new Fucicort Lipid formulation was studied with intact (0 strippings) and barrier-impaired skin simulating involved AD skin (25 strippings). As opposed to intact skin, no statistically significant difference through barrier-impaired skin was found for fusidic acid and betamethasone-17-valerate for the two formulations. This is in accordance with the clinical results of an international multicentre study and thus confirms the predictability of the model.     

Analysis of Simultaneous Transport and Metabolism of Ethyl Nicotinate in Hairless Rat Skin

Purpose. Simultaneous skin transport and metabolism of ethyl nicotinate (EN), a model drug, were measured and theoretically analyzed. Methods. Several permeation studies of EN or its metabolite nicotinic acid (NA) were done on full-thickness skin or stripped skin with and without an esterase inhibitor. Permeation parameters such as partition coefficient of EN from the donor solution to the stratum corneum and diffusion coefficients of EN and NA in the stratum corneum and the viable epidermis and dermis were determined by these studies. Enzymatic parameters (Michaelis constant K _m and maximum metabolism rate V _max were obtained from the production rate of NA from different concentrations of EN in the skin homogenate. Obtained permeation data were then analyzed by numerical method based on differential equations showing Fick's second law of diffusion in the stratum corneum and the law with Michaelis-Menten metabolism in the viable epidermis and dermis. Results. Fairly good steady-state fluxes of EN and NA through the skin were obtained after a short lag time for all the concentrations of EN applied. These steady-state fluxes were not proportional to the initial donor concentration of EN: EN and NA curves were concave and convex, respectively, which suggests that metabolic saturation from EN to NA takes place in the viable skin at higher EN application. The steady-state fluxes of EN and NA calculated by the differential equations with resulting permeation and enzymatic parameters were very close to the obtained data. Conclusions. The present method is a useful tool to analyze simultaneous transport and metabolism of many drugs and prodrugs, especially those showing Michaelis-Menten type-metabolic saturation in skin.     

Transdermal delivery of piroxicam using microemulsions

To improve the skin permeability of piroxicam, a new oil-in-water microemulsion containing 0.5% piroxicam was developed. Among various oils investigated for their suitability as an oil phase for the microemulsion system, oleic acid showed both excellent solubility and skin permeation enhancing effect for piroxicam. Microemulsion existence ranges were identified through the construction of the pseudo-ternary phase diagram. The effect of the content of oleic acid and the ratio of the surfactant/cosurfactant on skin permeation of piroxicam were evaluated with excised rat skins. The optimum formulation with the highest skin permeation rate (47.14 microg/cm2/h) consisted of 0.5% piroxicam, 10% oleic acid, 60% Labrasol/ethanol (1:5) and water.     

Microemulsion-based hydrogel formulation of ibuprofen for topical delivery

The purpose of this study was to construct microemulsion-base hydrogel formulation for topical delivery of ibuprofen. Ethyl oleate (EO) was screened as the oil phase of microemulsions, due to a good solubilizing capacity of the microemulison systems and excellent skin permeation rate of ibuprofen. The pseudo-ternary phase diagrams for microemulsion regions were constructed using ethyl oleate as the oil, Tween 80 as the surfactant, propylene glycol as the cosurfactant. Various microemulsion formulations were prepared and the abilities of various microemulsions to deliver ibuprofen through the skin were evaluated in vitro using Franz diffusion cells fitted with porcine skins. The in vitro permeation data showed that microemulsions increased the permeation rate of ibuprofen 5.72-30.0 times over the saturated solution. The optimum formulation consisted of 3% ibuprofen, 6% EO, 30% Tween 80/PG (2:1) and water, showed a high permeation rate of 38.06 microg cm(-2) h(-1). Xanthan gum as a gel matrix was used to construct the microemulsion-based hydrogel for improving the viscosity of microemulsion for topical administration. The studied microemulsion-based hydrogel showed a good stability. These results indicate that the studied microemulsion-based hydrogel may be a promising vehicle for topical delivery of ibuprofen.