Topical Microemulsion Research Articles

Preparation and Evaluation of Topical Microemulsion System Containing Metronidazole for Remission in Rosacea

The aim of this study was to prepare a topical water-in-oil type microemulsion containing metronidazole and to compare its effectiveness with a commercial gel product in the treatment of rosacea. A pseudo-ternary phase diagram (K(m)=2:1) was constructed using lecithin/butanol/isopropyl myristate/water. The microemulsion was chosen from the microemulsion region in the phase diagram. The formulation was a water-in-oil type microemulsion (droplet size: 11.6 nm, viscosity: 457.3 mPa·s, conductivity: 1.5 µs/cm, turbidity: 6.89 NTU) and the addition of the metronidazole did not alter the properties of the system. The release experiment showed that the release rate of metronidazole from the commercial gel product was higher than that of the microemulsion. Stability experiments showed that the metronidazole microemulsion remained stable for at least 6 months; none of the characteristic properties of the microemulsion had changed, the system retained its clarity and there was no sign that crystallization of metronidazole has occurred. Microemulsion was compared to a gel product in a randomized, double-blind, baseline-controlled, split-face clinical trial for the treatment of patients. After the 6-week treatment period there was a statistically significant difference in reduction of the main symptoms of rosacea. Of the patients treated with the microemulsion, 17% experienced complete relief from inflammatory lesions, and 50% from erythema. The microemulsion resulted in complete relief in 38% of the patients with telangiectasia while the commercial product did not provide any relief of telangiectasia symptoms. In conclusion, the microemulsion containing metronidazole was found to be more effective in reducing the symptoms of rosacea compared to the commercial gel product.

Effects of a Topical Microemulsion in House Dust Mite Allergic Rhinitis

We have previously demonstrated that a topical microemulsion can attenuate symptoms and signs of seasonal allergic rhinitis. This likely reflects that the microemulsion interferes with the interaction between the allergen and the mucosa. Whether or not the finding translates to conditions caused by other inhaled agents such as house dust mite allergen is unknown. Patients with perennial allergic rhinitis caused by house dust mite were subjected to topical microemulsion treatment in a randomized, double-blinded and crossover design with isotonic saline as control. Morning symptoms were monitored, change from baseline was assessed and the treatments were compared. On the first days of the isotonic saline and microemulsion runs, before any treatment was given, total nasal symptoms were scored to 2.8 and 3.1 (range 0-9), respectively. Nasal symptoms were reduced by intervention with the microemulsion: the change from baseline was consistent for the microemulsion and the difference between the microemulsion and isotonic saline reached statistical significance in favour of the former. We conclude that intervention with a microemulsion may reduce symptoms of house dust mite allergic rhinitis at natural allergen exposure. Our findings suggest the possibility that topical microemulsions can be a useful option to reduce nasal mucosal exposure to allergen in perennial allergic rhinitis..

Preparation and evaluation of aceclofenac topical microemulsion.

A topical preparation containing aceclofenac was developed using an o/w microemulsion system. Isopropyl myristate was chosen as the oil phase as it showed a good solubilising capacity. Pseudo-ternary phase diagrams were used to obtain the concentration ranges of the oil, surfactant (Labrasol) and co-surfactant (plurol oleique) for microemulsion formation. Five different formulations were formulated with various amount of the oil (5-25%), water (10-50%), and the mixture of surfactant and co-surfactant at the ratio of 4 (45-65%). In vitro permeability of aceclofenac from the microemulsions was evaluated using Keshary Chien diffusion cells with 0.45-μm cellulose acetate membrane. The amount of the aceclofenac permeated was analyzed by HPLC and the droplet size and zeta potential of the microemulsions was determined using a Zetasizer Nano-ZS. The mean diameters of the microemulsion droplets approximately ranged between 154 - 434 nm, and the permeability of aceclofenac incorporated into the microemulsion systems was 3 folds higher than that of the marketed formulation. These results indicate that the microemulsion system studied is a promising tool for percutaneous delivery of aceclofenac.

Bicontinuous Cyclosporin a Loaded Water-AOT/Tween 85-Isopropylmyristate Microemulsion: Structural Characterization and Dermal Pharmacokinetics In Vivo

Topical delivery of Cyclosporin A (CysA) is of great interest for the treatment of autoimmune skin disorders. Microemulsion systems prepared by AOT/Tween85/isopropyl myristate (IPM)/water possessing a potentially improved skin bioavailability of CysA were designed. The structure of microemulsions was investigated by diffusion-ordered NMR spectroscopy (DOSY) and differential scanning calorimetry (DSC) measurements. The DOSY measurements indicated the presence of bicontinuous and water-in-oil microemulsions depending on microemulsion composition. The DSC measurement confirmed that the microemulsion containing 30.0wt% water was bicontinuous type, in agreement with the DOSY findings. We also evaluated the therapeutic advantage of dermal administration of CysA in rat model. Local (subcutaneous and skin), systemic concentrations and organ distribution (liver and kidney) were evaluated serially following topical and oral application of the drug. In rat dermal applied with the bicontinuous microemulsion containing CysA, the deposition of the drug into skin and subcutaneous fat was respectively almost 30 and 15-fold higher than the concentrations compared with oral administration. Systemic distribution in blood, liver and kidney was much lower following topical administration than that of following oral administration. With high local concentrations and minimal distribution to other organs via the circulation, topical microemulsion vehicle loaded with CysA might deliver maximal therapeutic effect to local tissue while avoiding side effects seen with systemic therapy. The histopathological findings revealed that the new bicontinuous microemulsion was a safe vehicle for topical drug delivery of CysA.

In Vitro Evaluation of Topical Microemulsion of Capsaicin Free of Surfactant

Topical microemulsion of capsaicin without surfactant was developed in this study. In these systems, the oil phase was benzyl alcohol, and the cosurfactant was propylene glycol and ethanol. The drop-size of the systems was measured by dynamic light scattering method in order to distinguish true solution from microemulsion. The transdermal performance of the microemulsions was evaluated in vitro by Franz diffusion cells fitted with rat skins. The results showed the drop-size of the microemulsions without surfactant was smaller than that of the systems with Tween 80 and the permeation rate of capsaicin decreased as the content of Tween 80 increased. In the system composed of water, benzyl alcohol and propylene glycol, the permeation rate increased with the enhancement of benzyl alcohol and water. But water content had little effect on the permeation rate in the microemulsions with ethanol as cosurfactant.

Facilitated skin penetration of lidocaine: Combination of a short-term iontophoresis and microemulsion formulation

The objective of this study was to demonstrate the potential of the application of a short-term iontophoresis on the topical delivery of lidocaine hydrochloride from a microemulsion-based system. Five- and 10-min durations of anodal iontophoresis applied onto porcine skin were examined in combination with a microemulsion containing 2.5% lidocaine hydrochloride. A similar combination (10-min iontophoresis with microemulsion in the anodal electrode) was also examined in vivo in a rat model. It was shown in vitro that by combining microemulsion application with a 10-min iontophoresis of 1.13 mA/cm 2 electric current density, a significantly increased flux was obtained compared with a combination of aqueous drug solution with the same iontophoresis protocol. In vivo studies revealed that 57.71 ± 18.65 and 18.43 ± 9.17 μg cm −2 were reached in the epidermis and dermis, respectively, at t = 30 min of microemulsion application, when iontophoresis was applied for 10 min. In contrast, the application of aqueous solution-iontophoresis resulted in a relatively lower drug accumulation (21.44 ± 10.42 and 5.30 ± 2.25 μg cm −2 in the epidermis and dermis, respectively, at t = 30) with more rapid clearance of the drug from the skin. Ten-minute application of a low-current electric field on a new topical microemulsion appears to make significant changes in skin permeability. The potential advantages of this procedure include significantly increased flux, accumulation of a large skin drug depot, short lag times, reduced irritation (compared to long-term iontophoresis), simplicity and ease of compliance.

Enhanced skin permeation of rofecoxib using topical microemulsion gel

AbstractMicroemulsion 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.