Interaction of a lecithin microemulsion gel with human stratum corneum and its effect on transdermal transport (original) (raw)
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Colloids and Surfaces B-biointerfaces, 2006
Effect of composition of lecithin water-in-oil and oil-in-water microemulsion on in vitro transdermal permeation of tetracaine hydrochloride was studied on mice model. The results were compared with an aqueous solution of tetracaine hydrochloride (2.7 mg/ml). In vitro skin flux and permeability coefficients were obtained using the Franz diffusion cell. Differential scanning calorimetry (DSC), transmission electron microscopy (TEM) and confocal laser scanning microscopy (CLSM) were used to study the mechanism of action of the microemulsion. Micrographs of TEM and CLSM studies were analyzed by using Image Pro Plus image software. Skin flux of tetracaine hydrochloride was found to be dependent on the composition of lecithin/n-propanol/isopropyl myristate/water microemulsions. At lower K m ratio (i.e. 0.5:1 and 0.8:1) of microemulsion, the rate of permeation of tetracaine hydrochloride was higher when compared to the microemulsion of higher K m ratio (1:1 and 1.5:1). Image analysis of TEM micrograph, 6 h after application of lecithin microemulsion, showed 3.5 ± 0.75-fold (p < 0.001) increase in the intercellular space in the epidermis and 3.8 ± 0.4-fold (p < 0.001) enhancement in upper dermis. CLMS results show that sweat gland and hair follicles also provided path for permeation of the drug through the skin.
Transdermal permeation of tetracaine hydrochloride by lecithin microemulsion: In vivo
Colloids and Surfaces B-biointerfaces, 2006
In vivo transdermal permeation of tetracaine hydrochloride encapsulated in lecithin water-in-oil and oil-in-water microemulsion was studied. The effect of the composition of the lecithin microemulsion on analgesic response of tetracaine hydrochloride was evaluated on Wistar rats by tail flick method. To find out the toxicity of lecithin/n-propanol/isopropyl myristate/water/tetracaine hydrochloride microemulsion histopathological and irritation response were measured in Swiss mice. Time course studies were also conducted for the biochemical response of microemulsion by measuring catalase, glutathione and lipid peroxidation levels of the treated mice skin. The analgesic response was found to be dependent on the drug concentration and composition of the systems. The histopathological, irritation and biochemical findings reveal that lecithin/npropanol/isopropyl myristate/water/tetracaine hydrochloride microemulsion is a safe carrier for transdermal drug delivery systems. Confocal laser scanning microscopy observation indicated that sweat gland and hair follicle also provided the path for transdermal permeation of lecithin/npropanol/isopropyl myristate/water microemulsion.
Journal of Pharmacy and Pharmacology, 2008
The purpose of the present study was to evaluate skin-compatible drug delivery systems for fluconazole. Pseudoternary phase diagrams were constructed, composed of different soybean lecithins/oil/isopropanol and water. The role of the various lecithin compositions was expressed in the different resulting isotropic areas. Based on these phase diagrams, two systems were chosen as drug delivery systems for fluconazole. The influence of phosphatidylethanolamine and of the oil component on the skin permeation of fluconazole was investigated. The more phosphatidylethanolamine, the greater was the fluconazole skin permeation, independent of the hydrophilicity of the system. The influence of oleic acid and isopropylmyristate as the oil component was compared and a greater penetration enhancing effect was found for the microemulsion containing oleic acid.
Lecithin microemulsion based systems for dermal delivery of drugs: a review
The purpose of this review is to give an insight into the considerable potential of lecithin based nanocarriers. The lecithin microemulsion and closely related microemulsion based systems are currently of interest to pharmaceutical researchers. Conventional systems for topical delivery of drugs meet many hindrances like reduced permeation and entrapment efficiency. Lecithin nanocarriers with their enhanced bioavailability of drugs present a viable option to address the drawbacks of conventional formulations. Soya and egg lecithin are widely being explored. However, the purity of lecithin plays a significant role in gelation process. The review encompasses lecithin microemulsions, lecithin based microemulsion gels, pluronic lecithin gels and lecithin stabilized microemulsion based hyrogels in improving the topical delivery of drugs. Biocompatible lecithin based systems are known to furnish ways of many promising discoveries in the field of safe and efficacious topical dosage forms.
International Journal of Pharmaceutics, 2002
The potential application of highly biocompatible o/w microemulsions as topical drug carrier systems for the percutaneous delivery of anti-inflammatory drugs, i.e. ketoprofen, was investigated. Microemulsions were made up of triglycerides as oil phase, a mixture of lecithin and n-butanol as a surfactant/co-surfactant system and an aqueous solution as the external phase. To evaluate the percutaneous enhancing effect of oleic acid, this compound was used as a component of some o/w microemulsions. The topical carrier potentialities of lecithin-based o/w microemulsions were compared with respect to conventional formulations, i.e. a w/o emulsion, a o/w emulsion and a gel. Physicochemical characterisation of microemulsions was carried out by light scattering and zeta potential analyses. Microemulsions showed mean droplet size B 35 nm and a negative zeta potential, that is − 39.5 mV for the oleic acid-lecithin microemulsion and − 19.7 mV for the lecithin-based microemulsion. The percutaneous adsorption of the various topical formulations was evaluated through healthy adult human skin, which was obtained from abdominal reduction surgery. Ketoprofen-loaded microemulsions showed an enhanced permeation through human skin with respect to conventional formulations. No significant percutaneous enhancer effect was observed for ketoprofen-loaded oleic acid-lecithin microemulsions. The human skin tolerability of various microemulsion formulations was evaluated on human volunteers. Microemulsions showed a good human skin tolerability.
Lecithin organogel as matrix for transdermal transport of drugs
Journal of Pharmaceutical Sciences, 1992
0 Organogels obtained by adding small amounts of water to a solution of lecithin in organic solvents were studied as matrices for the transdermal transport of drugs. Gels obtained from isopropyl palmitate and cyclooctane were used (molar ratios of water to lecithin of 3 and 12, respectively). Preliminarily histological studies showed that the gels have no harmful effect when applied to the skin for prolonged periods. Data relative to the stability of the organogels with time are also presented. Scopolamine and broxaterol were used as model drugs, and the transdermal experiments were done with a Franz diffusion cell and human skin obtained from plastic surgery. The transport rate of scopolamine obtained with the lecithin gels was about one order of magnitude higher than that obtained with an aqueous solution of the drug at the same concentration. In contrast, the transport rates of scopolamine obtained with the microemulsion solution prior to gelation (molar ratio of water to lecithin, 0) were not different from those obtained with the gel. The same variations in transport rates were observed for broxaterol, in which case the flux through the skin was directly proportional to the concentration of drug in the gel. At a concentration of broxaterol of 75 mglmL in the donor gel, the flux was 47 pg * h-' cm-*. Because preliminary results showed that transdermal transport is successful with amino acids and peptides also, it is concluded that lecithin gels may be efficient vehicles for the transdermal transport of various drugs. A the lecithin gels have the potential of a rather high transdermal / " A
Molecular Pharmaceutics, 2010
This research determined the uptake of individual components of topically applied microemulsions into the stratum corneum (SC) and assessed their molecular effects on skin barrier function. The microemulsions comprised oleic acid, Tween20, Transcutol and water. The effects of selected formulations, and of the individual components, on the conformational order of the SC intercellular lipids, and on SC hydration, were assessed by infrared spectroscopy. Measurements were made as a function of SC depth by progressively tape-stripping the membrane in the normal way. SC uptake of microemulsion components was quantified via extraction and analysis of the collected tape strips. SC hydration increased in proportion to the water content of the microemulsion. Each of the microemulsion components penetrated into the SC, but to different extents. Oleic acid decreased the conformational order of the SC lipids, and induced some phase separation, as revealed by the frequency shifts and peak areas of the absorbances associated with -CH 2 symmetric and asymmetric stretching vibrations. Tween20 extracted some of the SC intercellular lipids. In summary, SC structure was perturbed by all components of the microemulsions, and the degree of the effects detected was proportional to the level of the respective component present in the skin.
European Journal of Pharmaceutical Sciences, 2018
This study aimed to investigate the potential of lecithin-based nanoemulsions costabilized by sucrose esters, with and without skin pretreatment with stainless steel microneedles, to improve delivery of aceclofenac, as a model drug, into/across the skin. The characterization revealed favorable droplet size (about 180 nm), narrow size distribution (< 0.15), high surface charge (about −40 mV) and satisfying long-term stability (one year at 4 ± 1°C) of the formulation costabilized by sucrose palmitate, demonstrating a similar trend observed for the reference stabilized by widely used lecithin/polysorbate 80 combination. In vitro release/permeation testing and differential stripping on the porcine ear proved the superiority of the sucrose ester-over polysorbate-based nanoemulsion. However, in vitro findings were not fully indicative of the in vivo performancesno significant differences were observed between investigated formulations in pharmacokinetic profile and total amount of aceclofenac deposited in the rat skin 24 h after dosing, simultaneously pointing to delayed aceclofenac delivery into the systemic circulation. In addition, the ratio of plasma concentrations of aceclofenac and its major metabolite in rats, diclofenac, was remarkably changed after topical application of tested nanoemulsions compared to intravenous administration of aceclofenac solution. Finally, skin pretreatment with microneedles improved aceclofenac delivery into/across the rat skin from tested formulations, resulting in 1.4-2.1-fold increased bioavailability and 1.2-1.7-fold enhanced level of aceclofenac retained in the skin, as measured 24 h after administration. Moreover, the plasma concentrations of aceclofenac 24 h after application of tested formulations (lecithin/sucrose palmitate vs. lecithin/polysorbate 80) combined with microneedles (173.37 ± 40.50 ng/ml vs. 259.23 ± 73.18 ng/ml) were significantly higher than those obtained through intact skin (105.69 ± 19.53 ng/ml vs. 88.38 ± 14.46 ng/ml). However, obtained results suggest that combination of microneedles and sucrose palmitate-costabilized nanoemulsion could be useful to attain higher skin concentration, while combination of microneedles with polysorbate 80-costabilized nanoemulsion could be a preferable option for enhancing drug delivery into the bloodstream. enforced intensive research efforts towards exploring different percutaneous penetration enhancement technologies aiming to ensure effective treatment of various musculoskeletal disorders via skin. Considering that the success of topical NSAID therapy predominantly depends on the drug's capability to penetrate the stratum corneum (SC) layer in sufficiently high amount to exert its clinical effect, formulators
International Journal of Pharmaceutics, 2019
Nanostructured lipid carriers (NLC) and nanoemulsions (NE) are colloid carriers which could improve dermal delivery of tacrolimus. The aims of this study were to evaluate effects of different formulation and process parameters on physicochemical characteristics and stability of lecithin-based NLC with glyceryl palmitostearate as solid and propylene glycol monocaprylate as liquid lipid and to compare the influence of different inner structure of tacrolimus-loaded NLC and corresponding NE on physicochemical characteristics, stability, entrapment efficiency, in vitro drug release and overall skin performance. Solid/liquid lipid ratio, total amount of lipids, homogenization pressure and cooling after the preparation were identified as critical variables in NLC development. Moreover, tacrolimus-loaded NLC emerged as more stabile carrier than NE. Differential stripping performed on porcine ear skin revealed significantly higher tacrolimus amount in stratum corneum from nanocarriers compared to referent ointment (Protopic®). Similarly the highest amount of tacrolimus in hair follicles was obtained using NLC (268.54 ± 92.38 ng/cm 2), followed by NE (128.17 ± 48.87 ng/cm 2) and Protopic® (77.61 ± 43.25 ng/cm 2). Contrary, the highest permeation rate through full-thickness porcine ear skin was observed for Protopic®, implying that the selection of experimental setup is critical for reliable skin performance assessment. Overall, developed NLC could be suggested as promising carrier in a form of lotion for tacrolimus dermal delivery.
Transdermals as Novel Drug Delivery System: An Review
Skin penetration enhancement techniques have been developed to improve bioavailability and increase the range of drugs for which topical and transdermal delivery is a better therapeutic response. Transdermal drug delivery systems (TDDS) are dosage forms involves drug transport to viable epidermal and or dermal tissues of the skin for local therapeutic effect while a very major fraction of drug is transported into the systemic blood circulation. Several important advantages of transdermal drug delivery are limitation of hepatic first pass metabolism, enhancement of therapeutic efficiency and maintenance of steady plasma level of the drug. Skin of an average adult body covers a surface of approximately 2 m 2 and receives about one-third of the blood circulating through the body. Skin is an effective medium for absorption of the drug takes place and enters the circulatory system. The adhesive of the transdermal drug delivery system is critical to the safety, efficacy and quality of the product. Topical administration of therapeutic agents offers many advantages over conventional oral and invasive methods of drug delivery. Enhancement via modification of the stratum corneum by hydration, chemical enhancers acting on the structure of the stratum corneum lipids and keratin, partitioning and solubility effects are also discussed. Thus the aim of this review work is to focus on the recent innovations in Transdermal Drug Delivery Systems which can be a platform for the research and development of pharmaceutical drug dosage form for Transdermal Drug Delivery. The main disadvantage to transdermal delivery systems stems from the fact that the skin is a very effective barrier as a result, only medications those molecules are small enough to penetrate the skin can be delivered in this method.