Microemulsion Gels Research Articles

The photoprotective effectiveness of microemulsion gel made from an ethanol extract of kelakai root (Stenochlaena palustris (Brum. f) bedd.)

Background: Free radicals from sunlight have detrimental effects on the skin, such as black and dull colouration and dry- and easy-to-age skin. Prevention can be done by using antioxidants derived from plants as photoprotective. Kelakai root extract has a potent antioxidant activity of 19.06 ppm. Using typical preparations in the form of microemulsion gels protects the skin from free radicals. Objective: This study aimed to determine the photoprotective effectiveness of the microemulsion gel preparation of kelakai root extract. Method: The extraction method adopted maceration with 70% ethanol solvent. The microemulsion was incorporated into a gel dosage form with a concentration of 5%. The effectiveness of the photoprotective gel was measured using UV-Vis spectrophotometry, which included determining the value of the Sun Protector Factor (SPF), erythema transmission percentage (%Te), and pigmentation transmission percentage (%Tp). Result: The results showed that the microemulsion gel of kelakai root extract with a concentration of 80 ppm had an SPF value of 9.816 with a %Te value of 9.591% and a %Tp value of 16.779%. Conclusion: The microemulsion gel of the kelakai root extract has photoprotective effectiveness as a sunscreen in the sunblock category.

Potent drug delivery enhancement of betulinic acid and NVX-207 into equine skin in vitro - a comparison between a novel oxygen flow-assisted transdermal application device and microemulsion gels.

Gray horses are predisposed to equine malignant melanoma (EMM) with advancing age. Depending on the tumor's location and size, they can cause severe problems (e.g., defaecation, urination, feeding). A feasible therapy for EMM has not yet been established and surgical excision can be difficult depending on the location of the melanoma. Thus, an effective and safe therapy is needed. Naturally occurring betulinic acid (BA), a pentacyclic triterpene and its synthetic derivate, NVX-207 (3-acetyl-betulinic acid-2-amino-3-hydroxy-2-hydroxymethyl-propanoate) are known for their cytotoxic properties against melanomas and other tumors and have already shown good safety and tolerability in vivo. In this study, BA and NVX-207 were tested for their permeation potential into equine skin in vitro in Franz-type diffusion cell (FDC) experiments after incubation of 5 min, 30 min and 24 h, aiming to use these formulations for prospective in vivo studies as a treatment for early melanoma stages. Potent permeation was defined as reaching or exceeding the half maximal inhibitory concentrations (IC50) of BA or NVX-207 for equine melanoma cells in equine skin samples. The active ingredients were either dissolved in a microemulsion (ME) or in a microemulsion gel (MEG). All of the formulations were transdermally applied but the oil-in-water microemulsion was administered with a novel oxygen flow-assisted (OFA) applicator (DERMADROP TDA). All tested formulations exceeded the IC50 values for equine melanoma cells for BA and NVX-207 in equine skin samples, independently of the incubation time NVX-207 applied with the OFA applicator showed a significant time-dependent accumulation and depot-effect in the skin after 30 min and 24 h (P < 0.05). All tested substances showed promising results. Additionally, OFA administration showed a significant accumulation of NVX-207 after 30 min and 24 h of incubation. Further in vivo trials with OFA application are recommended.

Fabrication of ballpoint-ink via encapsulating inorganic pigments in microemulsion gels.

The fabrication of ballpoint-ink might open up a new perspective on physico-chemical solubility thermodynamics. In this report, we present a method to encapsulate inorganic pigments, such as Fe(CNS)3 (red), Fe2Fe(CN)6 (blue), CdS (yellow), and CuS (black) into w/o microemulsion gels. The area of w/o microemulsions was first determined by titrating surfactants Tween-60 into the given composition of water and cyclohexane in the pseudo-three phase diagram. Three prosperous phase areas were successfully mapped using this method, namely: microemulsion (w/o, and o/w) or (μE), lamellar liquid crystal (Lα), and hexagonal liquid crystal (Hα), respectively. The results show that inorganic pigments were well soluble in the w/o microemulsion gel of the Tween-60/cyclohexane/water system. The highest solubility of inorganic pigments in the microemulsion gel is 3.63 ± 0.05 mg g−1 for the red pigment of Fe(CNS)3, and the lowest is 2.92 ± 0.05 mg g−1 for the yellow pigment of CdS. Hence, the solubility limit distribution for all pigments is 2.9 ± 0.05 <>3.63 ± 0.05 mg g−1. The cation and anion size strongly affected the inorganic pigments' solubility in the w/o-microemulsion system. Some quantity of the ink-made of inorganic pigments encapsulated in the microemulsion gel has been inserted into empty ballpoint sleeves as prototypes. The resulting self-made inks demonstrated that the physical appearances of the ink could mimic the factory-made inks. Nevertheless, the self-made ink should be investigated further for long lifespan use, especially for long-term stability and corrosion resistance.

Self-Shaping Microemulsion Gels for Cultural Relic Cleaning.

Cleaning is a foundational and essential operation of protection and restoration of cultural relics, which is also the key step of follow-up works. To overcome the problems of uncontrollable diffusion of cleaning solvents and poor coverage of the cleaning solvent carriers on rough surfaces, here, we propose a strategy of using a self-shaping microemulsion gel that is prepared via emulsifying oleophilic solvents into the specific shear-thinning hydrogel structures. The gel can adaptively cover rough surfaces during the cleaning process coupled with avoidance of unnecessary diffusion of the cleaning solvents, and the mechanical reinforcement of in situ polymerized double-network gels enables its easy peeling off from the surfaces without leaving determinable residues. As a representative demonstration, Paraloid B72, a widely used material for the repair and reinforcement of cultural relics, is employed as a model discolored coating, which can be effectively removed from the rough surface of simulated cultural relics after treatment with the resulting gels. Convincingly, the strategy of constructing agarose/polyacrylamide hybrid double-network gels with shear-thinning and self-shaping performances for the cleaning of cultural relics not only improves the convenience and accuracy of operation but also exhibits an efficient cleaning effect, which will greatly expand the application of microemulsion gels in the cleaning of rough surfaces of cultural relics.

Permeation, stability and acute dermal irritation of miroestrol and deoxymiroestrol from Pueraria candollei var. mirifica crude extract loaded transdermal gels

In this study, permeation behaviors and chemical stability of miroestrol and deoxymiroestrol from Pueraria candollei var. mirifica (PM), Thai traditional medicine, crude extract containing transdermal gels were firstly evaluated. Three different PM extract containing gels were formulated, including hydroalcoholic and microemulsion gels using carbomer, and silicone gel using silicone elastomer. In vitro permeation through porcine ear skin demonstrated that the flux and 24 h cumulative permeation of miroestrol and deoxymiroestrol were in the order of hydroalcoholic > silicone > microemulsion gels. Hydroalcoholic gel provided the highest partition coefficient from gel onto skin, and thus the skin permeability coefficient. After 24 h permeation, no miroestrol and deoxymiroestrol remained deposited in the skin. Accelerated study using heating-cooling revealed insignificant difference between the remaining percentages of miroestrol and deoxymiroestrol in aqueous and non-aqueous based gels. Long-term stability study showed that miroestrol contents remained constant for 90 d and 30 d under 5 ± 3 °C and 30 ± 2 °C, 75 ± 5%RH, respectively; whereas the percentage of deoxymiroestrol decreased significantly after 30 d storage, irrespective of storage conditions. Acute dermal irritation test on New Zealand White rabbits showed that PM hydroalcoholic gels were non-irritant, with no signs of erythema or oedema.

Microemulsion composed of combination of skin beneficial oils as vehicle: Development of resveratrol-loaded microemulsion based formulations for skin care applications

Microemulsion can be a potential delivery vehicle to deliver skin care actives to deep skin layer for chronic skin care benefits. On top of skin care active, microemulsion vehicle composed of multiple skin beneficial oils can deliver additional skin care efficacies. In this study, microemulsions were developed using combinations of two skin beneficial oils, tea tree oil and medium chain triglyceride instead of single oil. For that, pseudo ternary phase diagrams were constructed on these oil combinations at different ratios of surfactant/co-surfactants. Ratio of oils and surfactant/co-surfactant combinations exhibited significant impact on the microemulsion region. A few compositions were selected from the single phase microemulsion regions of these phase diagrams for the preparation of resveratrol-loaded microemulsion and microemulsion gel formulations. The particle size of the resveratrol-loaded microemulsions were <50 nm. Cryogenic scanning electron microscope image clearly showed nano-droplets dispersed in continuous phase. Both physical and chemical stability of the formulations varied depending on their compositions, such as surfactant/co-surfactant combination and % total oil. The presence of chelating agent and anti-oxidant was also crucial to stabilize the formulations. The selected formulations demonstrated good physicochemical stability at 5 °C, 25 °C, and 40 °C/75 % RH (relative humidity) stability conditions. The results further showed that the % total oil and surfactant phase composition had huge influence on resveratrol release and skin permeation patterns from the microemulsion gels. In vitro skin permeation result indicated that the microemulsion gels can help resveratrol penetration into deep skin layer. Therefore, the developed resveratrol-loaded microemulsion gels can be utilized as skin care product with multiple skin care benefits.

Development of microemulsion based topical ivermectin formulations: Pre-formulation and formulation studies

The aim of this work was to develop microemulsions and microemulsion gels which can be used as vehicles for the topical delivery of ivermectin. Tea tree oil and ethyl butanoate were found to be suitable for ivermectin-loaded microemulsion formulations due to the higher solubility of ivermectin in these two oils than other tested oils. The pseudo-ternary phase diagrams were constructed based on these selected oils and combination of different surfactant/co-surfactant at different ratios. Ivermectin-loaded stable microemulsions and microemulsion gels were successfully formulated based on the selected compositions from the phase diagrams. Ivermectin-loaded microemulsions showed spherical nano-droplets dispersed in the continuous phase (via cryogenic field emission scanning electron microscope image) and the particle size was less than 100 nm (via dynamic light scattering measurement). Ethyl butanoate based microemulsion appeared to be the best microemulsion formulation considering the stability and permeation profiles while tea tree oil based microemulsion showed the best stability profile. Overall, microemulsion gel formulations exhibited better stability profiles than their microemulsion counterparts. All microemulsion gel formulations demonstrated significantly faster in vitro membrane permeation (release) rate of ivermectin than Soolantra cream (reference marketed product by Galderma, USA).The developed microemulsion and microemulsion gel formulations appear to be promising vehicles for topical delivery of ivermectin.

Development and application of an osthole microemulsion hydrogel for external drug evaluation

The aim of the study is to provide a new type of drug delivery, combining the advantages of a microemulsion with the transdermal administration of osthole. Appropriate oil phases, surfactants, and cosurfactants were screened by their solubility, transmittance, etc. The appropriate microemulsion ratio formula was selected by measuring the area of the formed microemulsion region from the pseudoternary phase diagram among the different proportions. After measuring the pH, zeta potential, particle size, etc., a 2% osthole drug-containing microemulsion was prepared, and transdermal experiments were performed using a Franz cell. To select a microemulsion formula with high stability and a high skin transmittance rate, 65% distilled water (w/w) was embedded into the microemulsion (7% IPM (w/w), 14% Tween 80 (w/w) and 14% Labrasol (w/w)), and the microemulsion gel was made with different proportions of carbomer. The structure, water content and molecular stability of the microemulsion gels were measured by TEM and DSC. Transdermal experiments were then performed using Franz cells, and these microemulsion gels were applied to determine the subcutaneous residual amounts and optimal skin penetration microemulsion formulations. Thereby, the best microemulsion gel formulation was selected.

Extraction of male steroids and progesterone from water by vegetable oil gels and their determination by partial filling capillary micellar electrokinetic chromatography.

Microemulsion gels were synthetized from macadamia, linseed, olive, walnut, rapeseed, sesame, and coconut oils and frying oil made from sunflower, palm, and rapeseed oils. The gels were similar as polyacrylamide-based gels with exception of replacing dodecyl sulfate with vegetable oils. The gels were modified with celluloses, cotton, or lignin to make the emulsions sustainable for water purification. They were used to compare sorption properties when they were used as solid-phase adsorbents in isolation of steroids from water. Hydrophobicity features of the gels were compared by detecting adsorption and extraction efficiency of nonpolar androstenedione, testosterone, and progesterone, which exist in wastewater and drinking water. Quantification was done with partial filling-micellar electrokinetic chromatography with 29.5mM sodium dodecyl sulfate-3.4mM sodium taurocholate as the micelle and 20mM ammonium acetate (pH 9.68) as the electrolyte. UV-detection was used. Methanol was the best eluent for extraction of steroids from gels. The highest recoveries were from frying oil and rapeseed oil gels modified with celluloses. They also possessed the best floating properties on water surface. Lignin modified gels were too hydrophilic, when in touch with water they filled up with water. They also had the lowest capacity.

Design and study of poloxamer-based microemulsion gels with naproxen

In this study novel microemulsion-based gels with poloxamer 182 as a surfactant were designed and investigated as potential carriers for topical dosage forms with naproxen, non-steroidal anti-inflammatory drug. Based on the analysis of the pseudoternary phase diagrams obtained with the use of different components, oleic acid was selected as an oil phase and ethanol, isopropanol and Transcutol® were used as cosurfactants. As a polar phase pure water and poloxamer 407 solutions were tested. The extent of monophasic areas was similar in both cases, however, the poloxamer solutions were excluded from further experiments because of the lack of gelling properties in the studied systems. As a thickening agent Carbopol® EZ-3 was selected. In three microemulsion systems with different cosurfactans electrical conductivity was analysed as a function of polar phase content in order to find the transition points corresponding to microstructural changes leading to different microemulsion types. In the next step, three bicontinuous systems were transformed into semisolid polymer gels and subjected to rheological and texture profile analyses in order to assess mechanical parameters important in terms of topical drug delivery.

Effect of Hydrophobic Modification on the Properties of Polymer‐Blended Microemulsion Gels

AbstractPhase behavior of sodium oleate (NaOl)/isoamyl alcohol‐based lamellar gel phase in cedar oil/water medium in the presence of the nonionic polymer hydroxyethyl cellulose (HEC) and its hydrophobic modified product (HMHEC) is investigated for the development of polymer‐embedded surfactant gels. HMHEC is more soluble in oil‐in‐water (o/w) microemulsions, but nonionic HEC shows limited solubility in the lamellar microemulsion (o/w type). Quantitative estimation of rate of adsorption of the polymer on lamellae bilayers can be easily done by Sudan solubilization and methylene blue complexation methods. Addition of HMHEC to the lamellar gel phase increases the polymer solubilization limit of lamellar gels as well as the viscoelasticity and thermal stability. The polymer‐embedded microemulsion gel acts as a “clean gel” since it exhibits good solubilization in different hydrocarbon media at ambient conditions. Elastic modulus of the polymer‐embedded gel influences directly the suspension performance of gels at high temperature and yields a reasonable sand‐settling velocity acceptable according to fracturing standards. The thermal characteristics and viscoelastic properties of polymer‐embedded gel were found to be suitable for moderate‐temperature reservoir stimulation where the bottom hole temperature is in the range 70–75 °C. Already a large amount of experimental data on pure microemulsions (without polymer) exists. Our studies indicate that the developed polymer‐embedded microemulsion gel has great potential as a model system for the study of polymer–microemulsion interactions.

Microemulsion Based Bioadhesive Gel of Itraconazole Using Tamarind Gum: In-vitro and Ex-vivo Evaluation

The current study was aimed to formulate and evaluate bioadhesive gel containing microemulsion (ME) of itraconazole (ITZ) and an attempt was made to investigate suitability of tamarind gum (TG) as a gelling agent. The solubility of ITZ in oils, surfactants and co-surfactant was evaluated for the selection of appropriate component. The ratio of surfactant and co-surfactant was optimized by constructing pseudoternary phase diagram. Ternary phase diagram was constructed using isopropyl myristate (IPM) and oleic acid (OA) as oil phase, tween 80 as surfactant and isopropyl alcohol (IPA) as cosurfactant in order to obtain ME region. The optimized ME of ITZ was characterized by its qualitative and quantitative tests and incorporated into polymeric gels of carbopol (CBP), xanthan gum (XG) and TG. The ME based ITZ gels were evaluated for pH, drug content, viscosity, ex-vivo bioadhesion, spreadability and in vitro drug release. Furthermore, antifungal activity of the gels was performed by agar cup diffusion technique using cultures of Candida albicans. ITZ showed maximum solubility in mixture of IPM and OA (1:1). Stable ME was obtained when IPM and OA was taken in the ratio of 1:1 as oil phase, Tween 80 as surfactant and isopropyl alcohol (IPA) as cosurfactant at the weight ratio of 10:45:45. The optimized ME based gels showed pH in the range of 6.11 to 6.48, spreadability in the range of 4.1 to 7.1gm.cm/sec and ex vivo bioadhesion in the range of 65 to 84gm. The viscosity study indicated pseudoplastic behaviour of all ME based gel formulations. Amongst the studied ME gels, TG containing gels exhibited fast and complete drug release at the end of 24h. Formulation F7 containing TG showed wide zone of inhibition and found to be stable for three months. These results indicate that the TG containing ME gel may be a used as vehicle for topical delivery of drugs.

Formulation and Evaluation of Fish Oil-based Rizatriptan Microemulsion for Intranasal Migraine Treatment

In the present study microemulsion based intranasal gel of rizatriptan using fish oil was prepared for treatment and management of migraine to sustain the drug release and improve the drug residence time in nasal cavity. Fish oil is reported to have antimigraine activity hence it has been used in the present formulation along with cremophore EL as surfactant and Transcutol P as co-surfactant. The pseudoternary phase diagram plotted with these components shown the microemulsion existence region in ratio of (1:9-9:1) surfactant and co-surfactant. The optimized micro-emulsion contained fish oil (45.29%), cremophore E/transcutol P (2:1) and was characterized for pH (6.3±0.02), viscosity (114 ± 3.00cp), % transmittance (99.5 ± 1.01), refractive index (1.335±0.01),). The prepared microemulsion gels were optimized and characterized for in-vitro studies, pH, drug content, rheological studies and stability study. The release of rizatriptan from micro-emulsion gel prepared from carbopol 934 (98.01%) was found to be higher and prolonged than plain gel. Thus, microemulsion based gel was able to prolong drug releaseand improve drug residence time in the nasal cavity.

Development and Validation of HPTLC Method for Estimation of Tenoxicam and its Formulations.

A simple, precise, accurate and rapid high performance thin layer chromatographic method has been developed and validated for the estimation of tenoxicam in the microemulsion gels. Tenoxicam was chromatographed on silica gel 60 F254 TLC plate, as a stationary phase. The mobile phase was toluene: ethyl acetate: formic acid (6:4:0.3 v/v/v), which gave a dense and compact spot of tenoxicam with a Rf value of 0.38±0.03. The quantification was carried out at 379 nm. The method was validated in terms of linearity, accuracy, precision and specificity. To justify the suitability, accuracy and precision of the proposed method, recovery studies were performed at three concentration levels. Statistical analysis proved that the proposed method is accurate and reproducible with linearity in the range of 100 to 400 ng. The limit of detection and limit of quantification for tenoxicam were 25 and 50 μg/spot, respectively. The proposed method can be employed for the routine analysis of tenoxicam as well as in pharmaceutical formulations.

Low-Surfactant Microemulsions for Enhanced Topical Delivery of Poorly Soluble Drugs

To develop and characterize low-surfactant microemulsion (ME) gels to enhance topical delivery of poorly soluble drugs. Five low surfactant ME formulations were manufactured following the construction of pseudo-ternary phase diagrams. The MEs were screened for their ability to dissolve a poorly soluble new chemical entity (Model Drug X). Various viscosity imparting agents like Carbopol 934, Colloidal Silica, HPMC K100M, Lubrajel NP, and Xanthan Gum were evaluated for the manufacture of these ME gels. Each ME gel was then further evaluated for physical stability, including assessing rheological profiles. In vitro release profiles were also determined and compared to a conventional ointment. Three of the five low surfactant MEs developed (ME1, ME4 and ME5) were capable of dissolving Model Drug X up to 14 fold higher than the conventional ointment formulation. ME1 and ME4 gels comprising Xanthan gum or Carbopol 934 were physically stable, while ME5 gel was stable only with Colloidal Silica. The ME5 gel with Colloidal Silica showed an irreversible increase in its elastic modulus when exposed to high temperature, indicating that the formulation would be less suitable for commercial use. The Xanthan Gum and Colloidal Silica gels yielded significantly higher release rates (8 - 10 fold) compared to a conventional ointment and formulations containing Carbopol 934. The significant difference in drug release rates between Xanthan Gum and Carbopol 934 indicated that choice of viscosity imparting agent played an important role in governing drug release from ME gels. ME gels were developed with low surfactant concentrations and improved formulation characteristics, which increased the solubility and subsequent release of a poorly soluble drug. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

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

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

Rheological properties and microstructures of gelatin-containing microemulsion-based organogels

Gelatin-containing microemulsion-based organogels (MBGs) composed of isopropyl myristate (IPM), AOT, Tween85 and H 2O, loaded with and without a model drug (butenafine hydrochloride), have been prepared and characterized by rheological measurements and environmental scanning electron microscope (ESEM). The effects of gelatin and butenafine hydrochloride on the rheological properties and microstructures of the MBGs were investigated systematically. Transparent and homogeneous MBGs could be formed when the concentration of gelatin in the selected W/O microemulsion is in the range of 7.0–12.0 wt%. The rheological properties such as the yield stresses ( σ y), storage and loss moduli ( G′, G″) of the MBGs samples increased and the network structures of the MBGs became more compact with increasing the concentration of gelatin in the formulations. Furthermore, the addition of butenafine hydrochloride to the MBGs could weaken the interconnected network structures of the MBGs systems. Namely, when the concentration of butenafine hydrochloride was lower than 0.5 wt%, the samples are still microemulsion gels. These results show that the MBGs can be used as potentially transdermal drug delivery vehicles.

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.

Human Skin Irritation Studies of a Lecithin Microemulsion Gel and of Lecithin Liposomes

Soybean lecithin microemulsion gels offer promising features for the possible use as matrices in transdermal therapeutic systems. In order to assess the skin irritancy potential of the gel, acute and cumulative irriation tests were performed in human subjects in vivo using as comparison an unilamellar soybean lecithin liposome preparation and the solvent isopropyl palmitate (IPP). Acute irritation was tested in 151 volunteers in a 48-hour patch test, whereas cumulative irritation was assessed in a 21-day human repeated insult patch test in 20 volunteers. In the acute irritation test, discrete irritation (erythema only) developed with the gel in 2 subjects (1.3%), with the liposomes in 3 subjects (2.0%), and with IPP in 2 subjects (1.3%). For the assessment of cumulative irritation, the IT50 (irritation time of 50% of the test population) was calculated. IT50 was 13 days for the gel, 14 days for the liposomes and 17 days for IPP. This study shows a very low acute and a low cumulative irritancy potential for the soybean lecithin microemulsion gel making it a candidate matrix for transdermal therapeutic systems also under toxicological aspects.

Effects of phospholipid based formulations on in vitro and in vivo percutaneous absorption of methyl nicotinate

In this paper we evaluate the influence of phospholipid based formulations (PBFs) on skin absorption. In particular we describe the production and characterization of different PBFs, namely liposomes and w/o microemulsion gels, and their influence on in vitro and in vivo absorption of methyl nicotinate (MN) used as model compound. In order to compare the influence of various vehicles on skin absorption, Franz cell and MN induced erythema were used as in vitro and in vivo experimental models respectively. The formulations tested were: (a) unilamellar liposomes consisting of soybean lecithin/ cholesterol (9:1 w/w) suspended in water or incorporated into hydrophilic gels (Carbomer and carboxymethyl cellulose based gels) and (b) soybean lecithin based gels. The results indicate that vehicles containing phospholipids in liposomal form provided enhanced in vivo MN skin permeation compared to the corresponding vehicles without phospholipids. Lecithin gel showed a different behaviour characterized by a short and intense persistence of MN induced erythema.