Microemulsions containing lecithin and sugar-based surfactants: nanoparticle templates for delivery of proteins and peptides

Two pseudo-ternary systems comprising isopropyl myristate, soybean lecithin, water, ethanol and either decyl glucoside (DG) or capryl-caprylyl glucoside (CCG) as surfactant were investigated for their potential to form microemulsion templates to produce nanoparticles as drug delivery vehicles for proteins and peptides. All microemulsion and nanoparticle compounds used were pharmaceutically acceptable and biocompatible. Phase diagrams were established and characterized using polarizing light microscopy, viscosity, conductivity, electron microscopy, differential scanning calorimetry and self-diffusion NMR. An area in the phase diagrams containing optically isotropic, monophasic systems was designated as the microemulsion region and systems therein identified as solution-type microemulsions. Poly(alkylcyanoacrylate) nanoparticles prepared by interfacial polymerisation from selected microemulsions ranged from 145 to 660 nm in size with a unimodal size distribution depending on the type of monomer (ethyl (2) or butyl (2) cyanoacrylate) and microemulsion template. Generally larger nanoparticles were formed by butyl (2) cyanoacrylate. Insulin was added as a model protein and did not alter the physicochemical behaviour of the microemulsions or the morphology of the nanoparticles. However, insulin-loaded nanoparticles in the CCG containing system decreased in size when using butyl (2) cyanoacrylate. This study shows that microemulsions containing sugar-based surfactants are suitable formulation templates for the formation of nanoparticles to deliver peptides.     

In vitro release of diclofenac diethylamine from caprylocaproyl macrogolglycerides based microemulsions

The purpose of the present study was to determine the influence of both formulation parameters and vehicle structure on in vitro release rate of amphiphilic drug diclofenac diethylamine (DDA) from microemulsion vehicles containing PEG-8 caprylic/capric glycerides (surfactant), polyglyceryl-6 dioleate (cosurfactant), isopropyl myristate and water. From the constructed pseudo-ternary phase diagram at surfactant-cosurfactant mass ratio (K(m) 1:1), the optimum oil-to-surfactant-cosurfactant mass ratio values (O/SC 0.67-1.64) for formulation of microemulsions with similar concentrations of hydrophilic, lipophilic and amphiphilic phases (balanced microemulsions) were found. The results of characterization experiments indicated bicontinuous or nonspherical water-continuous internal structure of the selected microemulsion vehicles. Low water/isopropyl myristate apparent partition coefficient for DDA as well as elevated electrical conductivity and apparent viscosity values for the investigated microemulsion formulations containing 1.16% (w/w) of DDA, suggested that the drug molecules was predominantly partitioned in the water phase and most likely selfaggregate and interact with interfacial film. Release of DDA from the selected water-continuous (W/O), oil-continuous (O/W) and balanced microemulsions was investigated using rotating paddle dissolution apparatus modified by addition of enhancer cell. A linear diffusion of DDA through regenerated cellulose membrane was observed for the W/O and O/W formulations with the low content of dispersed phase. Non-linearity of the drug release profile in the case of bicontinuous formulations was related to the more complex distribution of DDA including interactions between the drug and vehicle. The membrane flux value increases from 25.02 microgcm(-2)h(-1) (W/O microemulsion) to 117.94 microgcm(-2)h(-1) (O/W microemulsion) as the water phase concentration increases. Moreover, the obtained flux values for balanced microemulsions (29.38-63.70 microgcm(-2)h(-1)) suggested that bicontinuous microstructure hampers the release of the amphiphilic drug.     

Amphotericin B in oil-water lecithin-based microemulsions: formulation and toxicity evaluation

A novel lecithin-based microemulsion containing AmB was developed to reduce the toxic effects of the drug, comparing it with the commercial formulation Fungizone. Phase diagrams containing the microemulsion region were constructed for pseudoternary systems composed of isopropil myristate (IPM)/Brij((R)) 96V/lecithin/water. The incorporation of AmB to the microemulsions was done following the Phase Inversion Temperature (PIT) method or by diluting the drug in the aqueous phase of the disperse system before forming the microemulsion. The percentage of drug entrapped in the microemulsion was analyzed by an HPLC method obtaining recoveries > 98%. Mean droplet size of the microemulsions chosen for the acute toxicity evaluation was of 45 nm, and the rheological studies showed that those microemulsions mentioned followed a Newtonian behavior. Different studies are described in this work to prove the stability of these new dosage forms. Acute toxicity results, determined by a graphic method, the probit binary model and the Reed and Muench method showed that lethal dose 50 (LD(50)) for AmB microemulsions was of 2.9 mgkg(-1) compared to 1.4 mgkg(-1) for the commercial deoxycholate suspension, Fungizone. The overall results indicate that treatment with AmB microemulsions was less toxic than Fungizone, suggesting a potential therapeutic application.     

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.     

In vitro studies of the hemolytic activity of microemulsions in human erythrocytes

Hemolytic activity in human erythrocytes as alternative to in vivo testing was used as a potential screening method to evaluate irritant potential of microemulsions for possible application in pharmaceutical and cosmetic formulations. Microemulsions were prepared by mixing surfactants and oil and slowly titrating the mixtures with aliquots of phosphate buffer saline or water. All microemulsions were characterized by dynamic light scattering to determine both the mean droplet size and droplet distribution. Microemulsion droplet size decreased as aqueous component increased. No differences in droplet size were observed between formulations containing phosphate buffered saline or water. The hemolytic activity was measured photometrically by the RBC assay, based in the cell membrane lysis, to estimate the potential irritation of both surfactants and microemulsions selected with water or PBS as aqueous component. The most hemolytic microemulsions corresponded to those containing the surfactant Labrasol^®, with or without butyl lactate, and no differences were found between the hemolytic activity between these components and microemulsions containing them. The highest hemolytic activity of microemulsions in this study may be attributed to the excipient used in the formulations. We should avoid the use of high amounts of Labrasol^® and butyl lactate in microemulsions because they may be potential irritants.     

Transdermal delivery of capsaicin derivative-sodium nonivamide acetate using microemulsions as vehicles

The objective of this study was to prepare sodium nonivamide acetate (SNA) microemulsion for topical administration. Microemulsions consisted of a mixed surfactant of Tween 80 and Span 20 as surfactant, ethanol as cosurfactant, isopropyl myristate (IPM) as an oil phase and water as an external phase. The effect of composition of microemulsion including the ratio of oil phase/surfactant/aqueous phase, various cosurfactant and polymer on the character and permeability of microemulsion were evaluated. The mean droplet size of SNA microemulsions ranged from 64 to 208 nm. Microemulsions showed potent enhancement effect for SNA transdermal delivery by a 3.7-7.1-fold increase when compared with the control group. Microemulsion containing ethanol as cosurfactant had the highest enhancement effect. With incorporated polymer, the viscosity of microemulsions increased resulting in the decrease in penetration rate of SNA. However, the permeability of SNA delivered from microemulsion was higher than SNA from volatile vehicles (pH 4.2 buffer containing 25% ethanol) reported in an earlier study, therefore microemulsions could be an effective vehicle for topical delivery of SNA.     

Positively charged microemulsions for topical application

The study reports pig-skin permeation and skin accumulation of miconazole nitrate (MCZ) from positively charged microemulsions containing water, 1-decanol/1-dodecanol (2:1, w/w), lecithin and/or decyl polyglucoside at different weight ratios, propylene glycol, 1,2 hexanediol and a cationic charge-inducing agent (stearylamine (ST), l-alanine benzyl ester (ALAB) or cetyltrimethylammonium bromide (CTAB)). Zeta-potential values of the positively charged microemulsions ranged from 14.2 to 37.5 mV and mean droplet size from 6.0 to 16.8 nm. In vitro pig-skin permeation of MCZ after a single 24h application was negligible for all microemulsions; accumulation from positively charged microemulsions was nearly twice that from their negatively charged counterparts. The increased accumulation might be ascribed to the interaction between positive microemulsive systems and negatively charged skin sites; no significant difference was observed among the various cationic charge-inducing agents. Skin accumulation from the microemulsion containing most lecithin was lower than those of other microemulsions; this was ascribed to the phase transformation from microemulsion to a liquid crystal system after skin contact. These results suggest that positively charged microemulsions could be used to optimize drug targeting without a concomitant increase in systemic absorption; ALAB, an ester of a natural amino acid, is an appropriate cationic charge-inducing agent.     

胸腺五肽油包水型口服微乳的处方设计与评价

目的对胸腺五肽油包水(W/O)型口服微乳进行处方设计及评价。方法 Km值(Km=m乳化剂∶m助乳化剂)滴定法制备伪三元相图,考察油相、乳化剂、助乳化剂、Km值、温度和药物对W/O微乳区域面积和载水量的影响,求出W/O型微乳的最佳处方组合。结果物理化学性质稳定且W/O区域面积和载水量均较高的W/O型微乳的最佳处方组合为蒸馏水/豆磷脂/无水乙醇/辛癸酸三甘油酯(Km=1∶1),制备温度为室温(20±1)℃。根据最佳处方组合,将水溶性药物胸腺五肽溶于水相中,制备了含药微乳的伪三元相图。结论蒸馏水/豆磷脂/无水乙醇/辛癸酸三甘油酯(Km=1∶1)组合具有较大W/O区域面积和载水量,可成功地将水溶性肽类药物包载于水相,并可将其应用于口服药物传递载体。     

Microemulsions as colloidal vehicle systems for dermal drug delivery. Part IV: Investigation of microemulsion systems based on a eutectic mixture of lidocaine and prilocaine as the colloidal phase by dynamic light scattering

Stable oil-in-water (o/w) microemulsions used as vehicles for dermal drug delivery have been developed using lidocaine (lignocaine) and prilocaine in oil form (eutectic mixture), a blend of a high (Tween 80, hydrophilic-lipophilic balance (HLB) = 15.0) and a low (Poloxamer 331, HLB = 1.0) HLB surfactant and propylene glycol-water as hydrophilic phase. These microemulsions were able to solubilize up to 20% eutectic mixture of lidocaine and prilocaine without phase separation. The dispersity of the oil phase was investigated by dynamic light scattering. Small colloidal droplets for stable microemulsions of 5~10 nm were observed. At constant surfactant and hydrophilic phase concentration, increasing the total drug concentration in the microemulsion resulted in an increase in the droplet size of the dispersed, colloidal phase. It was observed that a monolayer of surfactant surrounds the oil (eutectic mixture) core. Colloidal droplets of the microemulsion interact via hard sphere with supplementary attractive interaction. This observed interparticle attractive interaction could explain the observed phase behaviour with respect to change in the basicity of the hydrophilic phase as well as the increase in volume fraction of the dispersed, colloidal phase. It was also observed that the stability and size of this dispersed phase depends on the pH of the composition. Because these microemulsions formed stable, isotropic systems in the range of pH 9.5 to 10.4 with alkali buffer or NaOH solution instead of water as hydrophilic phase, so one can produce microemulsions in this pH area.     

Pseudo-ternary Phase Diagrams of Lecithin-based Microemulsions: Influence of Monoalkylphosphates

The formation of macroscopically homogeneous, stable, fluid, optically transparent, isotropic solutions (microemulsions) was delineated, at 25°C, for systems containing water, soybean lecithin, sodium monoalkylphosphate (hexyl or octyl), alcohol and isopropyl myristate. Six straight or branched alcohols (1-butanol, 2-butanol, isobutanol, 1-pentanol, 2-pentanol, 3-pentanol) were investigated as co-surfactants. A constant lecithin/alcohol mixing ratio was used, while the aqueous phase consisted of a solution of alkylphosphates at different concentrations. An increase of the microemulsion domain was seen by increasing the concentration of the alkylphosphate. With 0·2 m hexylphosphate, as aqueous phase, the microemulsion domain consisted of a single, region, that, in the presence of butylic alcohols, spanded the greater portion of the phase diagram. In the presence of amyl alcohols the area of this region was much smaller. With 0·2 m octylphosphate the realm of existence of the microemulsions, except for 1-pentanol, consisted of two regions separated by a liquid-crystal region. With all the alcohols examined, the liquid-crystal phase solubilized a larger amount of oil in the presence of octylphosphate than in the presence of hexylphosphate. The stability ranges of microemulsions in systems containing soybean lecithin, alcohol, water, and isopropyl myristate can be greatly increased by using a second hydrophobic amphiphile, such as hexylphosphate, to adjust the hydrophilic-lipophilic balance or the spontaneous peaking properties of lecithin-alcohol systems.     

Preparation and evaluation in vitro of solutions and o/w microemulsions containing levobunolol as ion-pair

Aqueous and aqueous-PEG 200 solutions, and o/w microemulsions containing levobunolol (LB) coupled to octanoic acid (OA) as lipophilic ion-pair were submitted to a preliminary investigation in vitro, in view of possible ophthalmic applications. Evaluation of the following was carried out: n-octanol/water partition coefficient, permeation through an artificial lipophilic membrane and through hairless mouse skin, isotonicity and eye irritation in albino rabbits. Permeation studies in aqueous and in aqueous-PEG 200 solutions through the artificial membrane indicated a higher apparent lipophilicity of LB-OA with respect to the drug alone. The transport rate of LB-OA through hairless mouse skin was lower from a microemulsion containing 0.5% w/w drug than from a water-PEG 200 solution simulating the continuous phase, thus suggesting a possible reservoir effect of the dispersed phase of the microemulsion. The microemulsion, which was isotonic and non-irritating on rabbit eyes, appears as a potentially interesting ophthalmic vehicle for LB.     

Protein delivery using nanoparticles based on microemulsions with different structure-types

Poly(alkylcyanoacrylate) nanoparticles based on microemulsions with different structure-types and containing insulin as a model protein were prepared and characterised in this study. A phase diagram of the pseudoternary system isopropyl myristate, caprylocaproyl macrogolglycerides, polyglycerol oleate and water was established. All compounds used in this study were pharmaceutically acceptable and biocompatible. The area in the phase diagram containing optically isotropic, monophasic systems was designated as the microemulsion region. Systems within this region were identified as water-in-oil (w/o), bicontinuous and oil-in-water (o/w) microemulsions with viscosity, conductivity, differential scanning calorimetry and self-diffusion NMR. The size distributions of the resulting nanoparticles prepared by interfacial polymerisation from selected microemulsions using ethyl (2) cyanoacrylate and butyl (2) cyanoacrylate were unimodal but template- and monomer-dependent and ranged from 160 to 400 nm. Entrapment and release of insulin were also studied. Entrapment ranged from 11.5 to 20.9% and a near zero-order release was observed after an initial burst. Release of insulin was monitored for 6 h. Insulin-loaded nanoparticles were 320–350 nm in size. The microemulsion-structure was retained during the polymerisation process as determined by NMR. This study showed that these microemulsions with flexible formulation possibilities for the solubilisation of peptides and proteins depending on their microstructure could serve well as a platform for designing encapsulation processes for oral delivery of insulin.     

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.     

反相微乳制备的影响因素考察及处方优化

目的:考察油相、乳化剂和药物对反相微乳形成的影响。方法:采用伪三元相图法,考察乳化剂为司盘-80/吐温-80,模型药为胸腺五肽,油相为长链甘油酯、中链甘油酯、非甘油酯等各因素不同组成对反相微乳形成的影响,筛选最优处方。结果:以中链甘油酯为油相制得的反相微乳具有最大的W/O区域面积;确定最终处方为蒸馏水/司盘-80/吐温-80/辛癸酸三甘油酯(2∶3∶6∶9),胸腺五肽溶于水相中较宜。结论:乳化剂及油相组成、药物均对反相微乳的形成有影响,实际制备中应对各因素水平进行优化。     

Cremophor RH40-PEG 400 microemulsions as transdermal drug delivery carrier for ketoprofen

The aim of this study was to prepare novel microemulsion for transdermal drug delivery of ketoprofen (KP). The microemulsion composed of ketoprofen as model drug, isopropyl myristate (IPM) as oil phase, surfactant mixture consisting of polyoxyl 40 hydrogenated castor oil (Cremophor RH40) as surfactant and polyethylene glycol 400 (PEG400) as co-surfactant at the ratio 1:1, and water were prepared. The viscosity, droplet size, pH, conductivity of microemulsions, and skin permeation of KP through shed snake skin were evaluated. The particle size, pH, viscosity and conductivity of microemulsions were in the range of 114-210 nm, 6.3-6.8, 124-799 cPs and 1-45 μS/cm, respectively. The ratio of IPM, and surfactant mixture played the important role in the skin permeation of KP microemulsions. As the amount of surfactant mixture and IPM increased, the skin permeation of KP decreased. The formulation composed of 30% IPM, 45% surfactant mixture and 25% water showed the highest skin permeation flux. The incorporation of terpenes in the 2.5% KP microemulsions resulted in significant enhancement in skin permeation of KP. The rank order of enhancement ratio for skin permeation enhancement of terpenes was α-pinene > limonene > menthone. The results suggested that the novel microemulsion system containing IPM, water, Cremophor RH40:PEG400 and terpenes can be applied for using as a transdermal drug delivery carrier.     

Investigation of surfactant/cosurfactant synergism impact on ibuprofen solubilization capacity and drug release characteristics of nonionic microemulsions

The current study investigates the performances of the multicomponent mixtures of nonionic surfactants regarding the microemulsion stabilisation, drug solubilization and in vitro drug release kinetic. The primary surfactant was PEG-8 caprylic/capric glycerides (Labrasol). The cosurfactants were commercially available mixtures of octoxynol-12 and polysorbate 20 without or with the addition of PEG-40 hydrogenated castor oil (Solubilisant gamma 2421 and Solubilisant gamma 2429, respectively). The oil phase of microemulsions was isopropyl myristate. Phase behaviour study of the pseudo-ternary systems Labrasol/cosurfactant/oil/water at surfactant-to-cosurfactant weight ratios (K(m)) 40:60, 50:50 and 60:40, revealed a strong synergism in the investigated tensides mixtures for stabilisation of microemulsions containing up to 80% (w/w) of water phase at surfactant +cosurfactant-to-oil weight ratio (SCoS/O) 90:10. Solubilization of a model drug ibuprofen in concentration common for topical application (5%, w/w) was achieved at the water contents below 50% (w/w). Drug free and ibuprofen-loaded microemulsions M1-M6, containing 45% (w/w) of water phase, were prepared and characterized by polarized light microscopy, conductivity, pH, rheological and droplet size measurements. In vitro ibuprofen release kinetics from the microemulsions was investigated using paddle-over-enhancer cell method and compared with the commercial 5% (w/w) ibuprofen hydrogel product (Deep Relief, Mentholatum Company Ltd., USA). The investigated microemulsions were isotropic, low viscous Bingham-type liquids with the pH value (4.70-6.61) suitable for topical application. The different efficiency of the tensides mixtures for microemulsion stabilisation was observed, depending on the cosurfactant type and K(m) value. Solubilisant gamma 2429 as well as higher K(m) (i.e., lower relative content of the cosurfactant) provided higher surfactant/cosurfactant synergism. The drug molecules were predominantly solubilized within the interface film. The amount of drug released from the formulations M3 (10.75%, w/w) and M6 (13.45%, w/w) (K(m) 60:40) was limited in comparison with the reference (22.22%, w/w) and follows the Higuchi model. Microemulsions M2 and M5 (K(m) 50:50) gave zero order drug release pattern and ～15% (w/w) ibuprofen released. The release profiles from microemulsions M1 and M4 (K(m) 40:60) did not fit well with the models used for analysis, although the amounts of ibuprofen released (24.47%, w/w) and 17.99% (w/w), respectively) were comparable to that of the reference hydrogel. The drug release mechanism was related with the surfactant/cosurfactant synergism, thus the lower efficiency of the tensides corresponded to the faster drug release.     

Investigation of self-microemulsifying and microemulsion systems for protection of prednisolone from gamma radiation

Radiation is efficient for terminal sterilization. Unfortunately, its use for liquid pharmaceuticals is difficult. This work investigated the potential radioprotective effect of self-microemulsifying (SMEDDS), microemulsions and their phase transition systems which were reported to enhance ocular drug delivery. Prednisolone solutions were prepared in SMEDDS, W/O microemulsions containing, 5% w/w (ME 5%) or 10% w/w (ME 10%) water, liquid crystalline system with 25% water (LC) and coarse emulsion containing 80% water (EM). These were subjected to gamma irradiation with aqueous solution and suspension being used as control. The physical properties of the formulations were monitored and the chemical potency of the drug was determined using a stability indicating HPLC method. The phase behavior of the formulations was not affected by irradiation but the viscosity of LC was significantly reduced. The SMEDDS, ME 5% and ME 10% showed excellent radiation protection as indicated by no change in the chemical potency. The LC retained 84% and the EM retained 39.8% of the chemical potency after exposure to 20 KGy. The aqueous solution was extensively degraded with the suspension retaining only 73.5% of the potency at 20 KGy. SMEDDS and W/O microemulsion can thus protect prednisolone from degradation by ionizing radiation.     

Characterization of caprylocaproyl macrogolglycerides based microemulsion drug delivery vehicles for an amphiphilic drug

Microemulsion systems composed of water, isopropyl myristate, PEG-8 caprylic/capric glycerides (Labrasol), and polyglyceryl-6 dioleate (Plurol Oleique), were investigated as potential drug delivery vehicles for an amphiphilic model drug (diclofenac diethylamine). Pseudo-ternary phase diagram of the investigated system, at constant surfactant/cosurfactant mass ratio (Km 4:1) was constructed at room temperature by titration, and the oil-to-surfactant/cosurfactant mass ratios (O/SC) that exhibit the maximum in the solubilization of water were found. This allowed the investigation of the continuous structural inversion from water-in-oil to oil-in-water microemulsions on dilution with water phase. Furthermore, electrical conductivity (sigma) of the system at Km 1:4, and O/SC 0.250 was studied, and the percolation phenomenon was observed. Conductivity and apparent viscosity (eta') measurement results well described colloidal microstructure of the selected formulations, including gradual changes during their formation. Moreover, sigma, eta', and pH values of six selected microemulsion vehicles which differ in water phase volume fraction (phi(w)) at the selected Km and O/SC values, were measured. In order to investigate the influence of the amphiphilic drug on the vehicle microstructures, each system was formulated with 1.16% (w/w) diclofenac diethylamine. Electrical conductivity, and eta' of the investigated systems were strongly affected by drug incorporation. The obtained results suggest that diclofenac diethylamine interacts with the specific microstructure of the investigated vehicles, and that the different drug release kinetics from these microemulsions may be expected. The investigated microemulsions should be very interesting as new drug carrier systems for dermal application of diclofenac diethylamine.     

Enhance transdermal delivery of flurbiprofen via microemulsions: Effects of different types of surfactants and cosurfactants

Background and the purpose of the study

Microemulsions are thermodynamically stable, clear dispersions of water, oil, surfactant, and cosurfactant. This study was aimed to develop flurbiprofen microemulsion for enhanced transdermal delivery and investigate the effects of different surfactants and cosurfactants on its delivery and phase behavior.

Method

Various surfactant-cosurfactant mixtures in ratio of 2:1 (Smix) along with oleic acid (oil) were selected and phase diagrams were constructed. Six microemulsions each containing 5% drug, 5% oil, 56% Smix and 34% water, were prepared and compared for their permeation and phase behaviors to determine the effects of the type of Smix.

Results

In vitro transdermal permeation through rabbit skin of all microemulsions was high than saturated aqueous drug solution. Tween 20 and ethanol as Smix produced the highest flux amongst all the Smix, and were used to prepare formulations with different values of oil and Smix. While the type of surfactant did not affect the droplet size, propylene glycol as cosurfactant produced the largest droplets and highest viscosity. Decrease in oil or Smix concentration resulted in decrease of the droplet size and increase in permeation flux while decrease in viscosity also increased the permeation flux of microemulsions. Finally the selected microemulsion formulation comprising 5% flurbiprofen, 5% oleic acid, 46% Tween 20:ethanol (2:1) and 44% water, showed the highest transdermal flux and caused no skin irritation.

Conclusion

Type of surfactant and cosurfactant affect both the phase behavior and transdermal drug delivery of microemulsion; and results of this study showed that they are promising vehicles for improved transdermal delivery and sustained action of flurbiprofen.     

Formulation design of microemulsion for dermal delivery of penciclovir

The purpose of the present study was to evaluate the potential application of microemulsions as a dermal drug delivery loading penciclovir. The pseudo-ternary phase diagrams were developed for various microemulsion formulations composed of oleic acid (oil phase), Cremorphor EL (surfactant) and ethanol (cosurfactant). Composition of microemulsion systems was optimized using simplex lattice mixture design including the concentrations of surfactant, cosurfactant and water (independent variables) and the solubility and the cumulative amount of penciclovir permeated through excised mouse skins per unit area (response variables). The physicochemical properties of the optimized microemulsion and the permeating ability of penciclovir from microemulsions were also investigated. The results showed that the optimized microemusion formulation was composed of oleic acid (5%, w/w), Cremorphor EL (20%, w/w), ethanol (30%, w/w) and water (45%, w/w). The mean particle diameter was 36.5nm and solubility of penciclovir in the emulsion was 7.41 mg g(-1). The cumulative amount of penciclovir permeated through excised mouse skins from microemulsion was about 3.5 times that of the commercial cream. The conclusion was that the permeating ability of penciclovir was significantly increased from the microemulsion formulation compared with commercial cream.