Transdermal permeation of tetracaine hydrochloride by lecithin microemulsion: In vivo (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.
A soybean lecithin microemulsion gel has been studied as a possible matrix for transdermal drug delivery. This gel is transparent and viscous, and it is composed of soybean phosphatidylcholine (lecithin), isopropyl palmitate and a small amount of water. In vitro percutaneous penetration studies of two anti-inflammatory drugs, indomethacin and diclofenac, dissolved in the gel-system resulted in steady state fluxes of about 1 Ixg h -~ cm -2. In order to estimate the function of the gel as a potential transdermal penetration enhancing system, interaction studies with isolated human stratum corneum were performed using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) as well as low-temperature scanning electron microscopy. These studies indicated that the lecithin gel, in particular isopropyl palmitate, affects the stratum corneum lipid organization even after 1-day incubation (FFIR, DSC), whereas recent in vivo human skin irritation tests showed no significant irritancy.
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.
A Microemulsion-Based System for the Dermal Delivery of Therapeutics
2007
There has been a continuously increased interest during recent years in the use of topical vehicle systems that can enhance drug penetration through the skin barrier into the skin or the systemic circulation. In particular, transdermal drug delivery (TDD) is an attractive alternative to conventional oral and injectable dosage forms. Since its introduction about twenty years ago, TDD has generated much hype as a solution for drugs with short biological half-lives, narrow therapeutic windows and poor oral absorption. Transdermal ‘patches’ are currently available for motion sickness (scopolamine), cardiovascular diseases (clonidine and nitroglycerine), chronic pain (fentanyl, sulfentanil), hormone replacement (for example, estradiol, levonorgestrel), smoking cessation (nicotine), hypogonadism (testosterone) and overactive bladder (oxybutynin). Many more transdermal products for various diseases and disorders are at various stages of research and development.
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.
Development and Characterization of Transdermal Drug Delivery Systems for Diltiazem Hydrochloride
Drug Delivery, 2003
The objective of this study was to design and develop o/w microemulsion for transdermal delivery of poorly water soluble acyclovir by aqueous titration method. Oleic acid: castor oil (3:1), tween 80, and ethanol were selected as oily phase, surfactant and cosurfactant respectively. The Pseudoternary phase diagrams were constructed by aqueous titration method. The cosurfactant affect the shape and extant of microemulsion regions. Ethanol (cosurfactant) is expected to disorder the interfacial film gave extended microemulsion zones by destabilizing the liquid crystalline phase. Largest Microemulsion single phase region was found at S mix (2:1) than the system at other S mix . Characterization of microemulsion were done for droplet Shape and size, refractive index, pH, Viscosity, drug loading capacity. The mean droplet size of microemulsion was found below 50 nm. The maximum solubility of ACV in microemulsion system was found to be 47.4 mg/ml. The ex-vivo skin permeation studies were done using skin of Wistar albino rat by Franz diffusion cell, and microemulsion formulation MEC1 exhibited highest flux, was found to be 238.1±4.87 µg/cm 2 /hr, while flux of MEGel, aqueous solution and conventional emulsion of ACV were found to be 230.40±6.23 µg/cm 2 /hr, 2.47±0.76 µg/cm 2 /hr and 8.65 ±1.21 µg/cm 2 /hr respectively. The pharmacokinetic parameters of MEGel after topical application to the Wistar albino rat skin were significantly different from those of ACV in aqueous solution (PD) and conventional emulsion (CE). It can be concluded that microemulsion of ACV prepared with Oleic acid: castor oil (3:1) as oily phase, tween80 as surfactant, and ethanol as cosurfactant can be used as transdermal drug carrier for this and other poorly water soluble drug.
International Journal of Pharmaceutics, 2011
The aim of this study was to evaluate the potential application of microemulsions as a transdermal drug delivery for naproxen (Np). The pseudo-ternary phase diagrams were developed for microemulsions composed of isopropyl myristate, Span 80, Labrafil M, Labrasol, and Cremophor EL, ethanol and isopropyl alcohol and 0.5 N sodium hydroxide. The final concentration of Np in microemulsion systems was 10% (w/w). The microemulsions were characterised by conductivity, droplet size, viscosity and pH. Moreover, in vitro permeability studies were performed using diffusion cells from rat skin. The permeation rates of Np from microemulsions (M1 Np and M2 Np ) were higher than the commercial (C) gel formulation. The paw oedema test was performed in rats to evaluate the anti-inflammatory activity of Np. The volume increase in paw oedema after 6 hr was 0.71 ± 0.46% with M2 Np , whereas M1 Np and C exhibited 6.48 ± 2.71% and 14.97 ± 3.15% increases in oedema, respectively. Additionally, a significant analgesic effect was detected in the hot plate and tail-flick tests for all test microemulsion and C formulations when compared with the control. Histopathological examination of the treated skin was performed to investigate changes in skin morphology. In conclusion, the microemulsion formulations, especially the M2 Np formulation, may be used as an effective alternative for the transdermal delivery of Np.
Biomedical applications of microemulsion through dermal and transdermal route
Biomedicine & Pharmacotherapy, 2018
Microemulsions are thermodynamically stable, transparent, colloidal drug carrier system extensively used by the scientists for effective drug delivery across the skin. It is a spontaneous isotropic mixture of lipophilic and hydrophilic substances stabilized by suitable surfactant and co-surfactant. The easy fabrication, long-term stability, enhanced solubilization, biocompatibility, skin-friendly appearance and affinity for both the hydrophilic and lipophilic drug substances make it superior for skin drug delivery over the other carrier systems. The topical administration of most of the active compounds is impaired by limited skin permeability due to the presence of skin barriers. In this sequence, the microemulsion represents a cost-effective and convenient drug carrier system which successfully delivers the drug to and across the skin. In the present review work, we compiled various attempts made in last 20 years, utilizing the microemulsion for dermal and transdermal delivery of various drugs. The review emphasizes the potency of microemulsion for topical and transdermal drug delivery and its effect on drug permeability.
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