The effect of internal structure of selected water-Tween 40-Imwitor 308-IPM microemulsions on ketoprofene release

Microemulsions are a promising vehicle for administrating drugs. In order to lay the basis for predicting drug release under in vivo conditions, where the microemulsion composition is continuously varying, we have studied the release of ketoprofene as a model drug, from microemulsions on a dilution line containing, initially, 20 wt.% of isopropyl miristate (IPM) and 80 wt.% of the surfactant (Tween 40/co-surfactant (Imwitor 308, 1:1 wt.% mixture. Mixture compositions corresponding to the different types and structure of microemulsion were identified by measuring density, surface tension, electric conductivity, pH and differential scanning calorimetry. Ketoprofene release was then measured for each type and structure. The main factor influencing ketoprofene release was shown to be the strength of the interactions between microemulsion components. Strong interactions prevented rapid ketoprofene release in the water-in oil region, although the release was not dependent on the degree of percolation. Release kinetics in all cases follow zero order kinetics, indicating that the release rate is dependent on the diffusion of ketoprofene inside the microemulsion carrier. Combining different methods to obtain the physical and structural properties of microemulsions can be thus used to predict the release of ketoprofen from a microemulsion.     

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).     

Structural characterisation of water-Tween 40/Imwitor 308-isopropyl myristate microemulsions using different experimental methods

Pharmaceutically usable microemulsion systems were prepared from water and isopropyl myristate with a constant amount of Tween 40 and Imwitor 308 at a mass ratio of 1. Their type and structure were examined by measuring density and surface tension, and by viscometry, electric conductivity, differential scanning calorimetry (DSC) and small-angle X-ray scattering (SAXS), and the degree of agreement between the techniques was assessed. A model based on monodisperse hard spheres adequately fits the SAXS data in W/O microemulsions predicting, depending on composition, elongated or spherical droplets. It also suggests the involvement of strong attractive interactions in O/W systems. Results of conductivity, viscosity, density and surface tension measurements confirm the prediction of a percolation transition to a bicontinuous structure. DSC detects the degree of water interaction with surfactants thus identifying the type of microemulsion. The conclusions from all the techniques agree well and indicate that such studies could also be carried out on more complex systems. In future, the ability to determine type and structure of such microemulsion systems could enable partitioning and release rates of drugs from microemulsions to be predicted.     

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.     

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 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.     

Development and <Emphasis Type="Italic">in vitro</Emphasis> biopharmaceutical evaluation of a dihydroquercetin microemulsion

Dihydroquercetin (DHQ) is a readily available compound with a broad spectrum of biological activity that makes development of new drug forms based on this compound imperative. In particular, it exhibits capillary-protective, anti-oxidant, and anti-inflammatory effects. Microemulsions are promising systems for delivering drugs and can increase their biological availability and provide their controlled release. A water-in-oil microemulsion containing DHQ (2%), surfactant (Tween 80), cosurfactant (propyleneglycol), an oil phase (Labrafil M 1944 CS), and water was prepared. Physicochemical parameters (particle size, viscosity, refractive index, denisty, and pH) and the in vitro release of DHQ were studied by the paddle-over-disk method in systems modeling local transdermal application and the paddle method in systems modeling oral application. Release rate constants were calculated. The proposed microemulsion ensures uniform prolonged release of the active substance.     

Formulation and ex-vivo evaluation of metronidazole microemulsion loaded hydrogel for prevention of periodontitis

Periodontal disease comprises a group of inflammatory conditions of periodontal tissues with common etiologic agent (bacteria) in the form of dental plaque. The objective of this research was to prepare a water-in-oil type microemulsion comprising metronidazole and equate its potency towards the effective treatment of periodontitis. A pseudo ternary phase diagram for microemulsion investigated using quaternary system containing water/captex 500/ tween 80/acconon CC6. The microemulsion was preferred from the microemulsion area on the phase diagram. Stable water-in-oil type metronidazole microemulsion was prepared successfully using the quaternary system of water/captex 500/ tween 80/acconon CC6 at 4:1 ratio having droplet size in the range of 81 ± 12.91 to 196 ± 10.73 nm, conductivity 50.6 ± 0.8 to 330.7 ± 1.1 μs/cm. In-vitro drug release, in vitro and ex vivo antimicrobial activities by agar well diffusion were investigated. Metronidazole Microemulsion loaded hydrogel formulations (F9 and F10) were found to be optimized for maximum release and antimicrobial activity in terms of zone of inhibition. The in vitro release evidenced that metronidazole microemulsion loaded hydrogel release rate was maximum as compared to other plain metronidazole gels. Stability study proved that microemulsion persisted stable for at least 6 months; with no changes in clarity, characteristic properties, and no sign of crystallization of metronidazole. In ex vivo evaluation, microemulsion based hydrogels were effective against the microbial flora of the human oral cavity suffering from periodontitis. The system was found to be appropriate for application and more effective in reducing the clinical symptoms of periodontitis.     

Gelation of microemulsions and release behavior of sodium salicylate from gelled microemulsions

A novel gelled microemulsion was prepared in the presence of the low molecular weight gelator N-stearine-N′-stearyl-l-phenylalanine at a very low concentration. It is completely different from the conventional microemulsion-based gels (MBGs) usually formed by polymeric gelling agents, such as gelatin, agar and κ-carrageenan. The microemulsion consists of i-propyl myristate, Tween 80, propylene glycol and water. The gelled microemulsions showed good thermo-reversibility. The gel-to-sol transition temperature (T_GS) of gelled microemulsion depends upon the concentration of gelator and the composition of the microemulsions. The gelation mechanism was investigated by polarized optical microscopy (POM) and FT-IR. POM images show elongated and strand-like crystallites formed by the aggregation of the gelator, ultimately resulting in the gelation of the microemulsion. FT-IR analysis indicates that intermolecular hydrogen bonds are responsible for the formation of gelator aggregates. Water-soluble sodium salicylate was used as a model drug for the investigation of the release from the gelled microemulsions. The release profiles exhibited a controlled release and followed the first-order release kinetics. The release rates decreased with an increase of the gelator and isopropyl myristate contents. These results reveal potential applications of gelled microemulsion in drug delivery systems.     

Preparation of griseofulvin nanoparticles from water-dilutable microemulsions

Nanoparticles of griseofulvin, a model drug with poor solubility and low bioavailability, were prepared from water dilutable microemulsions by the solvent diffusion technique. Solvent-in-water microemulsion formulations containing water, butyl lactate, lecithin, taurodeoxycholate sodium salt (TDC) or dipotassium glycyrrhizinate (KG), 1,2-propanediol or ethanol were used. The formation of macroscopically homogeneous, stable, fluid, optically transparent, isotropic solutions (microemulsions) was investigated by constructing pseudo-ternary phase diagrams. In the presence of TDC or KG, microemulsion systems that remained transparent on water dilution could be obtained. The displacement of butyl lactate, with an excess of water, from the internal phase of the microemulsions containing the drug into the external phase, lead to successful fabrication of drug nanosuspensions. Nanoparticle size was dependent on microemulsion composition: using KG, griseofulvin nanoparticles below 100 nm with low polydispersity and an increased dissolution rate were obtained.     

In situ formed phase transited drug delivery system of ketoprofen for achieving osmotic, controlled and level a in vitro in vivo correlation

A dry process induced phase transited, non disintegrating, controlled release, in situ formed asymmetric membrane capsular system for poorly water soluble drug, ketoprofen, was developed and evaluated both in vitro and in vivo for osmotic and controlled release of the drug. In situ formed asymmetric membrane capsules were prepared using fabricated glass capsule holders via dry, phase inversion process. Effect of varying osmotic pressure of the dissolution medium on drug release was studied. Membrane characterization by scanning electron microscopy showed an outer dense region with less pores and an inner porous region for the prepared asymmetric membrane. In vitro release studies and statistical test for all the prepared and marketed formulation were done at P >0.05. The drug release was found to be independent of the pH, but dependent on the osmotic pressure of the dissolution medium. In vivo pharmacokinetic studies showed a level A correlation (R(2)>0.99) with 39.24 % relative bioavailability compared to immediate release tablet of ketoprofen. Excellent correlation achieved suggested that the in vivo performance of the phase transited in situ formed AMCs could be accurately predicted from their in vitro release profiles and could a means for controlled delivery of drugs with varying solubility.     

The effect of liquid crystalline structure on chlorhexidine diacetate release

The aim of this study was to examine different liquid crystalline preparations containing chlorhexidine diacetate and to find connection between their structure and the kinetic of drug release. Nonionic surfactant, Synperonic A7 (PEG(7)-C(13-15)) was selected for the preparation of the examined liquid crystalline systems. Mixtures of different ratios of Synperonic A7 and water were produced. By increasing the water content of the systems, lamellar and hexagonal liquid crystal structures were observed. For the analysis of the prepared liquid crystalline systems polarising microscopy, rheology study, differential scanning calorimetry and dynamic swelling tests were carried out. The chlorhexidine diacetate release was examined by Franz-type vertical diffusion cell apparatus. The chlorhexidine diacetate release from hexagonal liquid crystalline preparations was characterised by zero-order release kinetics, while the drug release from lamellar liquid crystalline systems was described by anomalous (non-Fickian) transport. The results indicate that the drug release kinetic is strongly dependent on the liquid crystalline structure.     

The novel formulation design of self-emulsifying drug delivery systems (SEDDS) type O/W microemulsion I: enhancing effects on oral bioavailability of poorly water soluble compounds in rats and beagle dogs

We examined the design of the versatile novel self-emulsifying drug delivery systems (SEDDS) type O/W microemulsion formulation which enhances the oral bioavailability by raising the solubility of poorly water soluble compounds. Namely, seven kinds of poorly water soluble compounds such as disopyramide, ibuprofen, ketoprofen, tolbutamide, and other new compounds, as the model compounds were used to compare the plasma concentration profile of the compound following single oral administration of each compound to rats and beagle dogs as a solution, an oily solution, a suspension (or a powder), an O/W microemulsion, and a SEDDS type O/W microemulsion. And the enhancing effect of the SEDDS type O/W microemulsion on the gastrointestinal absorption of these compounds was evaluated. In the components of the SEDDS type O/W microemulsion, medium chain fatty acid triglyceride (MCT), diglyceryl monooleate (DGMO-C), polyoxyethylene hydrogenated castor oil 40 (HCO-40), and ethanol were used as an oil, a lipophilic surfactant, a hydrophilic surfactant, and a solubilizer, at the mixture ratio of 25/5/45/25 (w/w%), respectively. Thereby, to six kinds of the model compounds except disopyramide, the solubility was from 340 to 98,000 times that in water, and the AUCs in plasma concentration of the compound were equivalent to that of solution or O/W microemulsion administration, or was increased by 1.5 to 78 times that of suspension administration. Accordingly, this novel SEDDS type O/W microemulsion is the versatile, useful formulation which enhances the oral bioavailability by raising the solubility of poorly water soluble compounds.     

Effect of low-molecular-weight beta-cyclodextrin polymer on release of drugs from mucoadhesive buccal film dosage forms

We investigated the effect of low-molecular-weight beta-cyclodextrin (beta-CyD) polymer on in vitro release of two drugs with different lipophilicities (i.e., lidocaine and ketoprofen) from mucoadhesive buccal film dosage forms. When beta-CyD polymer was added to hydroxypropylcellulose (HPC) or polyvinylalcohol (PVA) film dosage forms, the release of lidocaine into artificial saliva (pH 5.7) was reduced by 40% of the control. In contrast, the release of ketoprofen from the polymer film was enhanced by addition of beta-CyD polymer to the vehicle. When lidocaine and ketoprofen was incubated with beta-CyD polymer in the artificial saliva, concentration of free lidocaine molecules decreased in a beta-CyD polymer concentration-dependent manner. The association constant with beta-CyD polymer was 6.9+/-0.6 and 520+/-90 M(-1) for lidocaine and ketoprofen, respectively. Retarded release of the hydrophilic lidocaine by beta-CyD polymer might be due to the decrease in thermodynamic activity by inclusion complex formation, whereas enhanced release of the lipophilic ketoprofen by the beta-CyD polymer might be due to prevention of recrystallization occurring after contacting the film with aqueous solution. Thus, effects of low-molecular-weight beta-CyD polymer to the drug release rate from film dosage forms would vary according to the strength of interaction with and the solubility of active ingredient.     

酮洛芬固体脂质纳米粒的制备

目的：微乳法制备固体脂质纳米粒,以酮洛芬作为模型药物,考查其载药性能。方法：通过对空白微乳粒径和稳定性考查,确定优化处方,将其保温分散于冷水中制备固体脂质纳米粒。对影响其质量的工艺因素和处方因素进行考查和优化设计,筛选最优处方。结果：制备固体脂质纳米粒的直接影响因素包括脂质用量、药物的用量、冷水相温度和微乳保温温度等,所得固体脂质纳米粒的平均粒径（143.9±1.2）nm,多分散系数为0.443。载药固体脂质纳米粒包封率为81.47%,载药量为8.16%。结论：该法稳定可靠,可用于酮洛芬固体脂质纳米粒的制备。     

Microstructural and drug release properties of oven-dried and of slowly or fast frozen freeze-dried MCC-Carbopol pellets.

The influence of the procedure and conditions of drying (oven-drying and freeze-drying after slow or fast freezing) and of the CaCl(2) concentration in the wetting liquid on the physical characteristics and drug release behaviour of microcrystalline cellulose (MCC)-carbopol 40:60 pellets containing theophylline or ketoprofen has been evaluated. The microstructural, morphological and mechanical properties can be modulated, to a large extent, through the control of the drying step and the CaCl(2) proportion. The drying step determines the volumetric contraction of the pellets and, consequently, the porosity parameters. When freeze-drying is applied, the freezing conditions have a marked influence on total porosity and mean pore size of the pellets. Slowly frozen pellets present the lowest porosity but the pores are the greatest. Pore size appears as a critical factor for achieving controlled release; the greater the pores, the faster the entrance of water and, consequently, the drug release. Therefore, if freeze-drying is used to remove water from wet pellets, the control of the ice formation is essential to modulate the release profiles. The practical possibilities of such modulation are especially clear for a slightly-water soluble drug, such as ketoprofen.     

Enhancement of ketoprofen bioavailability by formation of microsponge tablets

The release of ketoprofen incorporated into modified release ketoprofen microsponge 200 mg tablets and Profenid Retard 200 mg was studied in vitro and in vivo. The formulation containing ketoprofen microsponges yielded good modified release tablets. An in vivo study was designed to evaluate the pharmacokinetic parameters and to compare them with the commercially available ketoprofen retard tablets containing the same amount of the active drug. Commercial ketoprofen retard tablets showed a more rapid absorption rate than modified release tablets and peak levels were reached within almost 3.6 h after administration. However, the new modified release tablets showed a slower absorption rate and peak levels were reached 8 h after administration.     

Formulation development,in vitro and in vivo evaluation of microemulsion-based gel loaded with ketoprofen

Abstract

Background: Anti-inflammatory agents are widely used to relieve inflammation caused by various factors.

Aim: This study was initiated with the intention to deliver low aqueous soluble ketoprofen to enhance its solubility by developing microemulsion system as a template and then incorporating it into gel phase.

Materials and methods: Initially ketoprofen was solubilized into microemulsion preparation made up of clove oil, Tween 20 and propylene glycol as oil phase, surfactant and co-surfactant respectively, then it was incorporated into different concentration of gelling phase using gelling agents namely Carbopol 940, Carbopol 934 and hydroxypropyl methyl cellulose K₄M (HPMC K₄M). Formulated emulgels were evaluated for their physical appearance, pH, rheological properties, globule size, extrudability, drug content, spreadability, bioadhesion strength, in vitro and ex vivo drug release, skin irritation test and anti-inflammatory activity.

Results: Microemulsion had shown globule size 396?nm, pH 6–6.7, viscosity 29.4?cps and zeta potential ?12?mV indicating good stability. Formulated emulgels showed good physical appearance, skin acceptable pH 6–6.9, non-Newtonian shear thinning system, drug content 99.28?±?0.16%, bioadhesion strength 48.4 gram force, globule size 473?nm, spreadability 22.96?gm.cm/s, good extrudability, in vitro release, ex vivo release did not showed any irritation reaction and possess a good anti-inflammatory activity.

Conclusions: Selected batch showed enhanced drug release (92.42?±?4.66%) as compared to marketed gel (65.94?±?3.30). Similarly ex vivo release of formulation showed 72.22% release through mice skin compared with marketed gel. Formulations followed Korsmeyer–Peppas diffusion kinetic model. It was observed from the results that the formulated emulgel can provide promising delivery of ketoprofen.     

Enhanced skin permeation of rofecoxib using topical microemulsion gel

Microemulsion gels containing rofecoxib and rofecoxib solid dispersion with polyethylene glycol (PEG) 4000 were prepared for the study of rapid percutaneous absorption. The solubility of rofecoxib in oil phase of microemulsion, e.g., isopropyl myristate, was increased by the addition of dimethyl formamide and ethanol. Topical microemulsion gels (MEGs) were prepared by using neat rofecoxib as well as its solid dispersion to compare the efficacy of individual MEG with conventional gel (CG). MEGs showed better spreadability than CG and also showed increased globular size with increasing concentration of the oil phase. The release of rofecoxib through dialysis membrane and excised rat abdominal skin was affected by the size of the oil globule in MEGs. Rofecoxib release was higher for MEGs when compared to CG. MEGs containing rofecoxib‐PEG 4000 solid dispersion exhibited higher cumulative drug permeation when compared to MEG containing neat rofecoxib. MEGs containing rofecoxib‐PEG 4000 solid dispersion exhibited faster antiinflammatory activity than CG. Drug Dev. Res. 63:33–40, 2004. © 2004 Wiley‐Liss, Inc.     

Preparation and evaluation of a microemulsion for oral delivery of berberine

The principal aim of this study was to develop an oral microemulsion formulation of berberine in order to improve its bioavailability. The Microemulsion was prepared with pharmaceutically acceptable ingredients such as oleic acid, Tween 80 and PEG400. Phase diagrams were drawn to elucidate the phase behavior of systems, which were composed of Tween 80 as surfactant and PEG400 as cosurfactant. A single isotropic region, considered to be a bicontinuous microemulsion, was detected in the pseudo ternary phase diagrams. The berberine-loaded microemulsion was characterized by viscosity, refractive index, electrical conductivity and particle size. In vivo pharmacokinetic profile and oral bioavailability were also investigated in rats. The optimized formulation was as follows: 15 wt.% oleic acid, 17 wt.% Tween-80, 17 wt.% PEG400, and 51 wt.% water. The formulated microemulsion was found to be relatively uniform in size (24.0 nm). The in vivo study indicated that the bioavailability of the oral berberine-loaded microemulsion formulation was 6.47 times greater than that of the berberine tablet suspensions. The results suggest that the microemulsion is a promising oral drug delivery system for berberine.