Addition Of Penetration Enhancers Research Articles

FORMULATION AND EVALUATION OF MEFENAMIC ACID OINTMENT USING PENETRATION ENHANCERS

Objective: The aim of study was to formulate and evaluate Mefenamic acid ointment by the addition of penetration enhancer’s clove oil.
 Methods: 1%, 2% and 3% formulations of Mefenamic acid ointment formulated as per B. P, by melting hard paraffin 4.75g at 60 °C initially and to this 4.75 g wool fatwas incorporated, followed by addition of soft paraffin 80.75g and then adding Cetostearyl alcohol 4.75g and 1,2 and 3 ml clove oil by continuous stirring later on ointment being cooled at room temperature. These formulations were checked for consistency, Spreadability, homogeneity, PH, viscosity, skin irritation, drug content, UV absorbance, Differential scanning calorimetry (DSC) and XRD (X. ray diffraction) studies. In vitro pattern via using Franz cells besides with the use of dialysis cellulose membrane was done.
 Results: All the synthesized formulations illustrated fine physicochemical characteristics. SEM and XRD Studies expressed that there were no physicochemical incompatibilities among active ingredient (Mefenamic acid salt) and additives combined as drug permeation enhancers (clove oil).3% formulation showed maximum released 65.199%.
 Conclusion: In the present study, it was noted that clove oil can enhance the permeation of Mefenamic acid topical ointment.

Evaluation Patch of Rhizoma Extract Kencur (Kaempferia galanga L.) as Anti-Inflammatory with Enhancer

Kencur (Kaempferia galanga L.) is a family of Zingiberaceae. Several studies have shown that kencur can help reduce inflammation because kencur is known to contain anti-inflammatory compounds, namely marker compounds from flavonoids, kaempferol. For the development of pharmaceutical preparations, research on anti-inflammatory plasters containing 96% ethanol extract, n-hexane extract, ethyl acetate extract and 70% ethanol extract from ginger rhizome with the addition of penetration enhancer (enhancer), namely propylene glycol. This anti-inflammatory plaster was tested for its activity in 5 groups of Wistar strain rat feet which had been induced 1% carrageenan (negative control); positive control (diclofenac sodium), ethanol96% extract, n-hexane extract, ethyl acetate extract and 70% ethanol extract from kencur rhizome and compared with plaster of kencur rhizome ethanol extract without enhancer. The results showed the effect of adding enhancers 30 minutes after administration. 96% ethanol extract and ethyl acetate extract had reduced inflammation by 79.99% in rat test animals compared to plaster ethanol extract of rhizome kencur without the addition of enhancers. Keywords : Kaempferia galanga. L., patch, anti-inflammatory, enhancer, propylene glycol

Development of Fast Photochemical Oxidation of Proteins for In Vivo Modification in Caenorhabditis elegans

Caenorhabditis elegans, part of the nematode family, are used as model systems for many human diseases including those involving protein misfolding such as Parkinson's disease. Structural studies on C. elegans strains expressing the aggregate forms of the proteins involved in these diseases would shed light on how these aggregate structures lead to disease. The protein footprinting method fast photochemical oxidation of proteins (FPOP) is especially suited for these in vivo studies because of the irreversible nature of the modification. FPOP utilizes hydroxyl radicals to oxidatively modify solvent accessible sites in proteins. Radicals are generated via hydrogen peroxide photolysis by a 248 nm excimer laser. Our lab has performed preliminary studies that indicate that FPOP can be used to study protein structure directly in C. elegans. We have designated this new iteration of the method in vivo FPOP (IV-FPOP). Here, we describe the use of penetration enhancers in order to increase the number of oxidatively modified proteins. C. elegans can uptake hydrogen peroxide directly through their skin and the addition of penetration enhancers (i.e. DMSO) will aid with hydrogen peroxide uptake. The viability of the worms in the presence of hydrogen peroxide and these enhancers were also tested. LC-MS/MS analysis revealed and increase in oxidatively modified proteins by IV-FPOP when worms were treated with penetration enhancers. This work further demonstrates the efficacy of IV-FPOP for studying proteins directly in an animal model.

Formulation Optimization and In-vitro and In-vivo Evaluation of Lornoxicam Ethosomal Gels with Penetration Enhancers.

Ethosomes, a novel type of percutaneous drug delivery carrier with a lipid bilayer structure, penetrate the skin barrier due to their deformability and malleability, and presence of ethanol that fluidizes lipids in the skin. In order to further enhance the delivery of drugs through the skin, penetration enhancers are widely used. The objective of this work was to develop an optimized formulation of lornoxicam ethosomal gels, investigate skin permeability with the addition of penetration enhancers, and evaluate the invivo pharmacodynamics of these formulations. Lornoxicam ethosomes were prepared by the ethanol injection method and optimized using the orthogonal design method. Lornoxicam ethosomal gels with enhancers were prepared and optimized using in-vitro transdermal delivery experiments. Experiments on lornoxicam ethosomal gels containing various enhancers such as azone, menthol, lauryl alcohol, and oleic acid were conducted using vertical Franz diffusion cells to measure the percutaneous permeability of the different formulations. Furthermore, the in-vivo analgesic effects of the optimized lornoxicam ethosomal gels were examined using the hot-plate and acetic acid-induced writhing tests. Anti-inflammatory activity was investigated using the dimethylbenzene-induced mouse ear swelling method. The results showed that compared to other formulations, the optimized lornoxicam ethosomal gels with 5 % menthol significantly increased transdermal penetration. Meanwhile, the optimized lornoxicam ethosomal gels showed remarkably anti-nociceptive and anti-inflammatory activity compared with the plain lornoxicam gels. These results suggest that the optimized ethosomal gel formulated in this study is a promising lornoxicam carrier in transdermal delivery systems to enhance anti-nociceptive and antiinflammatory efficiency.

The Influence of the Acyl Chain on the Transdermal Penetration-Enhancing Effect of Synthetic Phytoceramides

Background/Aims: The skin has become very attractive as a route for drug administration. Optimization of topical drug formulations by the addition of penetration enhancers may facilitate the passage of drugs through the stratum corneum. Methods: In this paper, the skin penetration effect of phytosphingosine and 9 derived phytoceramides (PCERs) on 3 transdermal model drugs (i.e. caffeine, testosterone, ibuprofen) was investigated via Franz diffusion cell experiments using split-thickness human skin. Azone was included as a positive control. Results: The main finding in our study was that the PCERs exerted a compound-dependent penetration-enhancing effect. Some of the investigated PCERs exhibited a penetration-enhancing ratio of more than 2 (mean ± SE): for caffeine PCER1 (2.48 ± 0.44), PCER2 (2.75 ± 0.74), PCER3 (2.62 ± 0.93) and PCER6 (2.70 ± 0.45) and for testosterone PCER1 (2.08 ± 0.56), PCER2 (2.56 ± 0.13), PCER3 (3.48), PCER4 (2.53), PCER5 (2.04 ± 0.14), PCER6 (2.05 ± 0.48) and PCER10 (4.84 ± 0.79), but none of them had an influence on ibuprofen. Conclusion: The investigated PCERs exhibited a penetration-enhancing effect on caffeine and testosterone but not on ibuprofen.

Nano-proniosomes enhancing the transdermal delivery of mefenamic acid

Mefenamic acid (MA) is a BCS II class NSAID drug. It is available only in the form of tablets, capsules, and pediatric suspensions. Oral administration of MA is associated with severe gastrointestinal side effects. The aim of this study was to develop a convenient and low-cost transdermal drug delivery system for MA using proniosome as a novel carrier without the addition of penetration enhancers. The formulation factors, such as the presence of cholesterol, types of lecithin, and surfactants were investigated for their influence on the entrapment efficiency, rate of hydration, vesicle size, and zeta potential, in vitro drug release and skin permeation in order to optimize the proniosomal formulations with the minimum dose of the drug. Furthermore, the in vivo anti-inflammatory effect was evaluated on a formalin-induced rat paw edema model. The results showed that the type of surfactants had higher impact on the entrapment efficiency than the type of lecithins, with the highest in Span 80 (82.84%). The release of MA from Span 80 proniosomal gel was significantly affected by the type of lecithin used. The addition of cholesterol significantly increased both the drug release and the skin permeation flux of MA. Zeta potential showed a stable A4 noisomal suspension. DSC revealed the molecular dispersion of MA into the loaded proniosomes. In vivo study of the treatment group with MA proniosome gel showed a significant inhibition of rat paw edema compared with the same gel without the drug (control). The results of this study suggest that proniosomes are promising nano vesicular carriers and safe alternatives to enhance the transdermal delivery of MA.

Improving ex vivo skin permeation of non-steroidal anti-inflammatory drugs: Enhancing extemporaneous transformation of liposomes into planar lipid bilayers

Transdermal delivery of active principles is a versatile method widely used in medicine. The main drawback for the transdermal route, however, is the low efficiency achieved in the absorption of many drugs, mostly due to the complexity of the skin barrier. To improve drug delivery through the skin, we prepared and characterized liposomes loaded with ibuprofen and designed pharmaceutical formulations based on the extemporaneous addition of penetration enhancer (PE) surfactants. Afterwards, permeation and release studies were carried out. According to the permeation studies, the ibuprofen liposomal formulation supplemented with PEs exhibited similar therapeutic effects, but at lower doses (20%) comparing with a commercial formulation used as a reference. Atomic force microscopy (AFM) was used to investigate the effect caused by PEs on the adsorption mechanism of liposomal formulations onto the skin. Non-fused liposomes, bilayers and multilayered lipid structures were observed. The transformation of vesicles into planar structures is proposed as a possible rationale for explaining the lower doses required when a liposome formulation is supplemented with surfactant PEs.

Permeability of benzoic acid derivatives in excised guinea pig dorsal skin and effects of l-menthol

Penetration through excised guinea pig dorsal skin was examined for nine mono-substituents of benzoic acid derivatives. Permeability coefficients of the derivatives correlated well with their n-octanol/water partition coefficients. Since the regression coefficient was similar to the value obtained in human skin, it is suggested that the lipid lamellae of guinea pig skin resembled that of human skin in lipophilicity. Addition of penetration enhancer, 1% l-menthol in 15% ethanol markedly increased the flux and permeability coefficients of relatively hydrophilic derivatives and decreased the dependency of the permeability coefficients on the partition coefficients. Electron spin resonance analysis using 5-doxylstearic acid revealed the presence of a strongly immobilized component of the spin label in the skin and its disappearance in the presence of 1% l-menthol in 15% ethanol. These results suggest that the rigid lamellar structure of the stratum corneum was disrupted by l-menthol with ethanol, and caused the enhancement of penetration of relatively hydrophilic benzoic acid derivatives.