Administration Of Microemulsion Research Articles

Microemulsion for Prolonged Release of Fenretinide in the Mammary Tissue and Prevention of Breast Cancer Development.

The need of pharmacological strategies to preclude breast cancer development motivated us to develop a non-aqueous microemulsion (ME) capable of forming a depot after administration in the mammary tissue and uptake of interstitial fluids for prolonged release of the retinoid fenretinide. The selected ME was composed of phosphatidylcholine/tricaprylin/propylene glycol (45:5:50, w/w/w) and presented a droplet diameter of 175.3 ± 8.9 nm. Upon water uptake, the ME transformed successively into a lamellar phase, gel, and a lamellar phase-containing emulsion in vitro as the water content increased and released 30% of fenretinide in vitro after 9 days. Consistent with the slow release, the ME formed a depot in cell cultures and increased fenretinide IC50 values by 68.3- and 13.2-fold in MCF-7 and T-47D cells compared to a solution, respectively. At non-cytotoxic concentrations, the ME reduced T-47D cell migration by 75.9% and spheroid growth, resulting in ∼30% smaller structures. The depot formed in vivo prolonged a fluorochrome release for 30 days without producing any sings of local irritation. In a preclinical model of chemically induced carcinogenesis, ME administration every 3 weeks for 3 months significantly reduced (4.7-fold) the incidence of breast tumors and increased type II collagen expression, which might contribute to limit spreading. These promising results support the potential ME applicability as a preventive therapy of breast cancer.

Development of a microemulsion for encapsulation and delivery of gallic acid. The role of chitosan

A novel water-in-oil (W/O) microemulsion based on natural oils, namely extra virgin olive oil (EVOO) and sunflower oil (SO), in the presence of non-ionic surfactants was successfully formulated. The novel microemulsion was used as a carrier for gallic acid (GA) to assure its protection and efficacy upon nasal administration. The work presents evidence that this microemulsion can be used as a nasal formulation for the delivery of polar antioxidants, especially, after incorporation of chitosan (CH) in its aqueous phase. The structure of the system was studied by Small Angle X-ray Scattering (SAXS), Dynamic Light Scattering (DLS) and Electron Paramagnetic Resonance (EPR) spectroscopy techniques. By the addition of CH, the diameter of the microemulsion remained unaltered at 47 nm whereas after the incorporation of GA, micelles with 51 nm diameter were detected. The dynamic properties of the surfactant monolayer were affected by both the incorporation of CH and GA. Moreover, the antioxidant activity of the latter remained unaltered (99 %). RPMI 2650 cell line was used as the in vitro model for cell viability and for GA nasal epithelial transport studies after microemulsion administration. The results suggested that the nasal epithelial permeation of GA was enhanced, 3 h post administration, by the presence of 0.2 % v/v microemulsion in the culture medium. However, the concentration of the transported antioxidant in the presence of CH was higher indicating the polymer’s effect on the transport of the GA. The study revealed that nasal administration of hydrophilic antioxidants could be used as an alternative route besides oral administration.

Investigating the anti-apoptotic effect of sesame oil and honey in a novel nanostructure form for treatment of heart failure

Objective(s): Sesame oil is a lipophilic compound and has low aqueous solubility and low oral bioavailability. It is possible to enhance sesame oil solubility in aqueous media by applying the microemulsion system in the form of oil-in-water. In this study, the anti-cholesterol and anti-Apoptotic effects of a new combination of sesame oil and honey in a microemulsion form for cardiac muscle cells Apoptosis treatment were investigated. Materials and Methods: Two different formulations were prepared. Tween 80 was used as the main surfactant in both formulations. In the first formulation, glycerin was applied as co-surfactant. Span 80 was applied as a mixed surfactant in the second formulation.Results: Characterization results showed that the average size of droplets of microemulsion samples were in the range of 16.6±0.1-64.6±0.2 nm with a poly dispersity index (PDI) value of less than 0.5. No turbidity and phase sedimentation were observed in certain samples in a period of 6 months after the preparation, which confirmed the high stability of samples. The in-vivo results in Wistar male rats with heart failure showed that applying sesame oil and honey in the microemulsion form caused a significant reduction in the Apoptosis level. In addition, favorable therapeutic effects for microemulsion administration was observed in comparison to the Atorvastatin drug consumption. Furthermore, the protective effect of microemulsion dosage was more obvious with increasing the oil percentage and adding honey as a hydrophilic additive. Conclusion: Results confirmed that the new formulation containing sesame oil and honey as natural components with nano particle size could be useful for cardiac muscle cells Apoptosis treatment.

Xingnaojing mPEG2000-PLA modified microemulsion for transnasal delivery: pharmacokinetic and brain-targeting evaluation

Xingnaojing microemulsion (XNJ-M) administered intranasally is used for stroke treatment. In order to decrease the XNJ-M-induced mucosal irritation, XNJ-M modified by mPEG2000-PLA (XNJ-MM) were prepared in a previous work. The present work aimed to assess the impact of mPEG2000-PLA on pharmacokinetic features and brain-targeting ability of XNJ-M. The bioavailability and brain-target effects of borneol and geniposide in XNJ-M and XNJ-MM were compared in mice after intravenous (i.v.) and intranasal (i.n.) administrations. Gas chromatography, high-performance liquid chromatography, and ultra-performance liquid chromatography/tandem mass spectrometry methods were developed for the quantification of borneol and geniposide. Blood and brain samples were collected from mice at different time points after i.v. and i.n. treatments with borneol at 8.0 mg/kg, geniposide at 4.12 mg/kg. In addition, near-infrared fluorescence dye, 1,1′-dioctadecyl-3,3,3′,3′-tetramethyl indotricarbocyanine iodide was loaded into microemulsions to evaluate the brain-targeting ability of XNJ-M and XNJ-MM by near-infrared fluorescence imaging in vivo and ex vivo. For XNJ-M and XNJ-MM, the relative brain targeted coefficients (Re) were 134.59% and 198.09% (borneol), 89.70% and 188.33% (geniposide), respectively. Besides, significant near-infrared fluorescent signal was detected in the brain after i.n. administration of microemulsions, compared with that of groups for i.v. administration. These findings indicated that mPEG2000-PLA modified microemulsion improved drug entry into blood and brain compared with normal microemulsion: the introduction of mPEG2000-PLA in microemulsion resulted in brain-targeting enhancement of both fat-soluble and water-soluble drugs. These findings provide a basis for the significance of mPEG2000-PLA addition in microemulsion, defining its effects on the drugs in microemulsion.

Therapeutic drug monitoring of cyclosporine microemulsion in patients with corticosteroid-resistant systemic lupus erythematosus

Objectives. We retrospectively examined how the cyclosporine-A (CSA) microemulsion administration mode affected blood CSA levels, as well as how the dose and blood levels of CSA affected its therapeutic effect against systemic lupus erythematosus (SLE).Methods. We calculated the area under the blood concentration time curve (AUC) of CSA in 16 patients with corticosteroid-resistant SLE, and analyzed its correlation with CSA levels at the blood sampling time points to investigate the optimum monitoring and dosing regimen.Results. The blood CSA level peaked at 2 h after administration (C2) in all patients. AUC0-6, which most markedly reflects the immunosuppressive effect, significantly correlated with C2 (R2 = 0.905), but not with the trough (C0). In concentration/dose ratio (C/D) of CSA, C2/D level was significantly higher when administered once daily before breakfast than when administered in the divided dose after meals (R2 = 0.355, P = 0.015), but not C0/D. During the 6-month follow-up, the CSA C2 tended to correlate with improvement in SLE disease activity index 2000 (R2 = 0.633, P = 0.067).Conclusions. The treatment with a single dose of CSA before breakfast, followed by monitoring of C2, may be useful for improving the therapeutic effect in patients with corticosteroid-resistant SLE.

Chitosan and cyclodextrin in intranasal microemulsion for improved brain buspirone hydrochloride pharmacokinetics in rats

The aim of this study was to develop buspirone hydrochloride microemulsion formulations for intranasal administration to improve the drug bioavailability and provide high drug brain levels. For the purpose, chitosan aspartate, and hydroxypropyl-β-cyclodextrin were incorporated in the microemulsions. The prepared formulations were characterized. Biological investigations including pharmacokinetic studies, brain drug targeting efficiency determinations and histopathological examinations were performed on rats. The results showed that safe and stable mucoadhesive microemulsion suitable for nasal administration were successfully prepared. Ex vivo drug permeation revealed high drug permeation from microemulsions. Absolute bioavailability after intranasal administration of buspirone mucoadhesive microemulsion increased significantly and plasma concentration peaked at 15min. The AUC0–360(brain) was 3 times that obtained after intravenous administration. A high brain targeting efficiency (86.6%) and a direct nose to brain transport (88%) confirmed the direct nose to brain transport of buspirone following nasal administration of the microemulsions.

Uptake of α‐Linolenic Acid and Its Conversion to Long Chain Omega‐3 Fatty Acids in Rats Fed Microemulsions of Linseed Oil

The present work was designed to prepare linseed oil (LSO) microemulsion and explore the possibility of enhancing the uptake and utilization of α-linolenic acid (ALA) present in LSO. The bioavailability of encapsulated LSO as against native oil was monitored in rats by measuring the uptake in vitro using the intestinal everted sac model and in-vivo administration of microemulsions of LSO to rats for a period of 30 days. Microemulsions were prepared by using different binding materials such as gum acacia, whey protein and lipoid. When LSO was encapsulated with gum acacia, whey protein and lipoid, the levels of ALA uptake into intestinal sacs was increased by 6, 17 and 28% as compared to oil given without encapsulation. EPA and DHA were not observed in the oil absorbed by intestinal everted sacs when given as emulsions with gum acacia or whey protein. When LSO was given as microemulsions with lipoid, EPA + DHA was observed in oil absorbed by intestinal sacs. Similarly when LSO was given as a lipoid emulsion by intubation to rats, the EPA and DHA in serum lipids were found to be 41 and 34 μg/ml, respectively while rats given LSO without encapsulation contained EPA and DHA at 9.1 and 8.8 μg/ml, respectively. Similar changes in omega-3 fatty acid content in liver lipids were observed when LSO was given as a microemulsion with lipoid. This study indicated that ALA was taken up and metabolized to long chain omega-3 PUFA when given as microemulsion with lipoid.

Effect of Xiongbing compound on the pharmacokinetics and brain targeting of tetramethylpyrazine

To investigate the effect of the Xiongbing compound (XBC) on the pharmacokinetics and brain targeting of tetramethylpyrazine (TMP). Three microemulsions containing the same TMP concentration were prepared. XBC microemulsions were made from Rhizoma ligustric Chuanxiong extracts, borneol and TMP. TMP microemulsions were made with TMP only. Borneol microemulsions contained borneol and TMP. Microdialysis with high performance liquid chromatography (HPLC) was used to measure the concentration of TMP in the blood and striatum after intravenous (i.v.) or intragastric (i.g.) administration of the three different microemulsions. The pharmacokinetics of free TMP concentration in the blood and the striatum fit a first-order rate, open two-compartment model after intravenous and intragastric microemulsion administration. The maximal concentration (C(max) ) and area under curve (AUC) values in the XBC microemulsion i.v. group were significantly higher than that in the TMP microemulsion and borneol microemulsion i.v. groups. After XBC microemulsion i.g. administration, the t(½), mean residence time (MRT) and AUC of TMP in both plasma and brain tissues were greater than those with TMP microemulsion and borneol microemulsion administration. The relative brain targeting efficiency of TMP for the XBC microemulsion i.v and i.g. groups relative to the TMP microemulsion and borneol microemulsion groups were greater than 1. XBC microemulsion can enhance TMP oral bioavailability, brain targeting and tissue distribution, mainly through a synergistic action of Rhizoma ligustric Chuanxiong extracts and borneol.

In vitro cellular uptake of evodiamine and rutaecarpine using a microemulsion

ObjectiveTo investigate the cellular uptake of evodiamine and rutaecarpine in a microemulsion in comparison with aqueous suspensions and tinctures.Materials and methodsA microemulsion was prepared using the dropwise addition method. Mouse skin fibroblasts were cultured in vitro to investigate the optimal conditions for evodiamine and rutaecarpine uptake with different drug concentrations and administration times. Under optimal conditions, the cellular uptake of microemulsified drugs was assayed and compared to tinctures and aqueous suspensions. Rhodamine B labeling and laser scanning confocal microscopy (LSCM) were used to explore the distribution of fluorochrome transferred with the microemulsion in fibroblasts. Cellular morphology was also investigated, using optical microscopy to evaluate microemulsion-induced cellular toxicity.ResultsThe maximum cellular drug uptake amounts were obtained with a 20% concentration (v/v) of microemulsion and an 8 hour administration time. Drug uptake by mouse skin fibroblasts was lowest when the drugs were loaded in microemulsion. After incubation with rhodamine B-labeled microemulsion for 8 hours, the highest fluorescence intensity was achieved, and the fluorochrome was primarily distributed in the cytochylema. No obvious cellular morphologic changes were observed with the administration of either the microemulsion or the aqueous suspension; for the tincture group, however, massive cellular necrocytosis was observed.ConclusionThe lower cellular uptake with microemulsion may be due to the fact that most of the drug loaded in the microemulsion vehicle was transported via the intercellular space, while a small quantity of free drug (released from the vehicle) was ingested through transmembrane transport. Mouse skin fibroblasts rarely endocytosed evodiamine and rutaecarpine with a microemulsion as the vehicle. The microemulsion had no obvious effect on cellular morphology, suggesting there is little or no cellular toxicity associated with the administration of microemulsion on mouse skin fibroblasts.

A Comparison of Short-Term Exposure of Once-Daily Extended Release Tacrolimus and Twice-Daily Cyclosporine on Renal Function in Healthy Volunteers

Calcineurin inhibitor nephrotoxicity remains an issue for recipients of solid organ transplants. After cyclosporine A (CsA) microemulsion administration, effective renal plasma flow (ERPF) and glomerular filtration rate(GFR) are decreased coincident with the maximal concentration (Cmax) of CsA. The pharmacokinetic (PK) profile of the once-daily formulation of tacrolimus extended release (Tac ER) includes an equivalent AUCPK 0-24 hr and a lower Cmax versus twice-daily Tac immediate release. Eighteen healthy subjects were allocated once-daily Tac ER and twice-daily CsA in a prospective, randomized,open-label, two-period, two-sequence single crossover study. CsA was targeted to C2 of 700 to 1400 ng/mL, and Tac ER was targeted to C0 of 5 to 10 ng/mL. Pharmacodynamic (PD) assessments were conducted preexposure, and PD and PK were assessed during a 6-hr postdose period after 10-day exposure. The achieved mean C(o) Tac and CsA were 6.4 +/- 1.16 and 201 +/- 57 ng/mL, respectively. At Cmax, the change in ERPF was +30 +/- 127 vs. -70 +/- 96 mL/min/1.73 m2 relative to baseline for Tac ER and CsA (P=0.0085). The ERPF and GFR AUC (PD 0-6) hr were 3645 +/- 887 vs. 3210 +/- 582 mL/1.73 m2 (P=0.027) and 604 +/- 98 vs. 543+/- 79 mL/1.73 m2(P=0.023) for Tac ER versus CsA, respectively. Both systolic and diastolic blood pressures were significantly greater with exposure to CsA compared with Tac ER. Acute reductions in ERPF and GFR are attenuated with Tac ER compared with CsA and may correlate with the differing PK profiles of these calcineurin inhibitors.

Microemulsion based intranasal delivery system for treatment of insomnia

The aim of this investigation was to prepare and characterize microemulsions/mucoadhesive microemulsions of Diazepam (D), Lorazepam (L) and Alprazolam (A), evaluate their pharmacodynamic performances by performing comparative sleep induction studies in male albino rats to assess their role in effective management of insomnia patients. Microemulsions of Diazepam (DME), Lorazepam (LME) and Alprazolam (AME) were prepared by titration method and characterized for drug content, globule size distribution and zeta potential, nasal toxicity and sleep induction. DME, LME and AME were transparent and stable with mean globule size and zeta potential in the range of 95.6 nm to 141.7 nm and -2.205 to -0.111 mV respectively. The prepared microemulsions exhibited reversible nasal toxicity. Onset of sleep and duration of sleep were observed in the following order: Lorazepam > Alprazolam>Diazepam. Faster onset of sleep following intranasal administration of microemulsions (<20 min) compared to oral administration (29-33 min) and control group (>45 min) for all three drugs suggested selective nose-to-brain transport of drug(s). Intranasal administration of microemulsion based formulations resulted in even faster onset of sleep (<12 min) with intranasal mucoadhesive microemulsion(s) resulting in fastest onset of sleep (<9 min). Duration of sleep was longest with the intranasal mucoadhesive microemulsions. These results are suggestive of larger extent of distribution of drug(s) to brain after intranasal administration of mucoadhesive microemulsion(s). These results are further corroborated with by loss or rightening reflex and startle reflex at earlier time points (within 10 min and 15 min respectively) with mucoadhesive microemulsions. Thus, the results of this investigation indicated rapid and larger extent of drug transport to the rat brain resulting in rapid induction of sleep followed by prolonged duration of sleep in rats following intranasal administration of mucoadhesive microemulsion(s). However, the role of microemulsion based formulations developed in this investigation in clinical practice can only be established after animal studies in two different animal models followed by extensive clinical trials.

Optimization and evaluation of amoxicillin medium chain fatty acids/salts microemulsions: intestinal absorption and cytotoxicity

Pseudoternary microemulsions have been developed which, in addition to non-ionic medium-chain glycerides and fatty acids such as caprylic (C 8 ) and capric acids (C 10 ), incorporate ionic lipids, i.e. the sodium salts of fatty acids. The permeability, absorption enhancing activity were evaluated using phenol red as a marker molecule and the cytotoxicity of these lipid microemulsions were investigated in rats by measuring the amount of proteins and lactate dehydrogenase enzyme released in the intestinal fluids. The histopathological follow up of colonic membranes after administration of microemulsions was used to assess tissue damage. In vitro permeability and absorption studies showed that caprate-based systems containing captex 200 (20%), surfactant mixture of polysorbate 80: sodium caprate 4:1 (60%), capmul MCM C 8 : capric acid 1:1(20%) significantly (P

Preliminary brain-targeting studies on intranasal mucoadhesive microemulsions of sumatriptan.

The aim of this investigation was to prepare microemulsions containing sumatriptan (ST) and sumatriptan succinate (SS) to accomplish rapid delivery of drug to the brain in acute attacks of migraine and perform comparative in vivo evaluation in rats. Sumatriptan microemulsions (SME)/sumatriptan succinate microemulsions (SSME) were prepared using titration method and characterized for drug content, globule size and size distribution, and zeta potential. Biodistribution of SME, SSME, sumatriptan solution (SSS), and marketed product (SMP) in the brain and blood of Swiss albino rats following intranasal and intravenous (IV) administrations were examined using optimized technetium-labeled (99mTc-labeled) ST formulations. The pharmacokinetic parameters, drug targeting efficiency (DTE), and direct drug transport (DTP) were derived. Gamma scintigraphy imaging of rat brain following IV and intranasal administrations were performed to ascertain the localization of drug. SME and SSME were transparent and stable with mean globule size 38±20 nm and zeta potential between -35 to -55 mV. Brain/blood uptake ratios at 0.5 hour following IV administration of SME and intranasal administrations of SME, SMME, and SSS were found to be 0.20, 0.50, 0.60, and 0.26, respectively, suggesting effective transport of drug following intranasal administration of microemulsions. Higher DTE and DTP for mucoadhesive microemulsions indicated more effective targeting following intranasal administration and best brain targeting of ST from mucoadhesive microemulsions. Rat brain scintigraphy endorsed higher uptake of ST into the brain. Studies conclusively demonstrated rapid and larger extent of transport of microemulsion of ST compared with microemulsion of SS, SMP, and SSS into the rat brain. Hence, intranasal delivery of ST microemulsion developed in this investigation can play a promising role in the treatment of acute attacks of migraine.

Outcome of microemulsion cyclosporine C2 concentration monitoring in kidney transplantation

Profiling of absorption of cyclosporine (CsA) microemulsion is a concept in therapeutic drug monitoring (TDM) designed to optimize the clinical benefits of the drug in transplant recipients. A single blood concentration at 2 h (C(2)) after CsA microemulsion administration in kidney transplant recipients accurately predicts graft outcome. An international guidelines has recommended the target C(2) over time-course post-transplantation. We determined whether this recommendation is appropriate for our patients who are Asian ethnic. The clinical data of these C(2) monitoring kidney transplant recipients were compared with the historical cohort of microemulsion CsA trough (C(0)) level monitoring during the first 24-month post-transplantation. The inclusion and exclusion criteria were applied for both C(2) and C(0) cohorts. The mean target C(2) concentrations at 1, 3, 6, and 12-month post-transplantation were achieved in the C(2) cohort as the international guildlines. At 3-month post-transplantation, patients who had C(2) concentrations over 1500 ng/mL had higher serum creatinine as compared with those who had C(2) levels <1300 ng/mL (2.23 +/- 0.8 vs. 1.44 +/- 0.38 mg/dL: p = 0.01). Also, at 6-month post-transplantation, patients who had C(2) concentrations over 1300 ng/mL had higher serum creatinine (1.96 +/- 0.29 vs. 1.37 +/- 0.34 mg/dL: p < 0.01) as compared with those who had C(2) levels <1100 ng/mL. There was no statistical difference of acute rejection episodes between the two cohorts. The international consensus for C(2) concentraion may be too high for Asian ethnic kidney transplant recipients. The data from this study indicated lower than recommended C(2) concentraion as an appropriate C(2) target concentraion.

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.

Synthesis of Ibuprofen Eugenol Ester and Its Microemulsion Formulation for Parenteral Delivery

The purpose of this study was to investigate the possibility of parenteral delivery of poorly water-soluble lipophilic drugs using a phospholipid-based microemulsion system. Ibuprofen eugenol ester (IEE), a highly lipophilic compound, was synthesized from ibuprofen and eugenol, and isolated as an amorphous whitish solid with a melting point at 40.2+/-0.1 degrees C, which structure was confirmed by IR, 1H-NMR and MS spectra. A pharmaceutically acceptable microemulsion system using Miglyol 812, soybean phosphatidylcholine (SbPC) and poly (ethylene glycol) (660)-12-hydroxystearate (Solutol HS-15), and PEG400 and ethanol as oil phase, surfactants and cosurfactants, respectively, was presented and characterized in terms of stability, droplet size distribution (DSD) and their solubilization capacity of IEE. The solubility of IEE in the optimized microemulsion formulation consisting of 6.4% ibuprofen eugenol, 9.6% Miglyol 812, 6% SbPC, 6% HS-15, 8.4% PEG400, 3.6% ethanol and 60% distilled water (w/w) was about 21,000 times higher than that in water. The ibuprofen blood concentration after intravenous administration of microemulsions was determined and compared with that of ibuprofen solution. It was concluded that the presented microemulsion system might be a promising intravenous dosage form of poorly water-soluble lipophilic drugs.

Effects of epidermal growth factor microemulsion formulation on the healing of stress-induced gastric ulcers in rats

The effects of intragastric (i.g.) administration of microemulsion formulation of epidermal growth factor (EGF) on the healing of acute gastric ulcers induced by cold-restraint stress in rats was studied and compared with intraperitoneal (i.p.) administration of solutions. In the microemulsion formulation (W/O), labrafil M 1944 CS was the oil phase. Arlacel 186 and Brij 35 were used as the surfactants. Absolute alcohol and distilled water were used as the co-surfactant and the aqueous phase, respectively. Acute gastric lesions were induced by cold-restraint stress for 4 h in the refrigerator (4.0±0.5 °C). EGF was administered at a dose of 6 μg/kg per day intraperitoneally and intraperitoneally for 7 days. Basal gastric acid secretion (μequiv. H +/30 min), ulcer score (mm 2) and tissue mucus levels (μg/g tissue) were measured. Basal gastric secretion was significantly reduced after the administration of EGF microemulsion (ME+EGF) ( P<0.05). There was no significant decrease in basal gastric acid secretion following i.p (IPEGF) and i.g (IG-EGF) of EGF administrations of solutions compared to their control groups ( P>0.05). The results indicate that the highest reduction in the basal acid secretion was seen after the administration of a microemulsion of EGF formulation. The mean ulcer score was reduced by i.g treatment with the microemulsion dosage form of EGF in 7 days from 15.9±1.4 to 1.16±0.45 mm 2 and was almost completely healed in four of the animals. The results demonstrate that the ulcer score was significantly reduced in i.p. (IPEGF) solution ( P<0.005), i.g (IG-EGF) solution ( P<0.01) and i.g. microemulsion (ME+EGF) ( P<0.01) treated groups compared to untreated group. In IG-EGF, ME+EGF treated groups, mucus levels increased significantly compared to their control groups( P<0.05 and P<0.01). In contrast, there was no significant change in the mucus levels following i.p. EGF administration ( P>0.05).