Ion-Pair Compounds of Strychnine for Enhancing Skin Permeability: Influencing the Transdermal Processes In Vitro Based on Molecular Simulation

This research aimed to explore how Strychnine (Str) ion-pair compounds affect the in vitro transdermal process. In order to prevent the influence of different functional groups on skin permeation, seven homologous fatty acids were selected to form ion-pair compounds with Str. The in vitro permeation fluxes of the Str ion-pair compounds were 2.2 to 8.4 times that of Str, and Str-C10 had the highest permeation fluxes of 42.79 ± 19.86 µg/cm2/h. The hydrogen bond of the Str ion-pair compounds was also confirmed by Fourier Transform Infrared (FTIR) Spectroscopy, Nuclear Magnetic Resonance (NMR) Spectroscopy and molecular simulation. In the process of molecular simulation, the intercellular lipid and the viable skin were represented by ceramide, cholesterol and free fatty acid of equal molar ratios and water, respectively. It was found by the binding energy curve that the Str ion-pair compounds had better compatibility with the intercellular lipid and water than Str, which indicated that the affinity of Str ion-pair compounds and skin was better than that of Str and skin. Therefore, it was concluded that Str ion-pair compounds can be distributed from the vehicle to the intercellular lipid and viable skin more easily than Str. These findings broadened our knowledge about how Str ion-pair compounds affect the transdermal process.

EFECTO DE UN SURFACTANTE NO IONICO EN LA PERMEABILIDAD DE BUTORFANOL A TRAVES DE MUCOSA NASAL EQUINA

Implementation of intranasal administration for the delivery of drugs with site of action into the central nervous system, such as butorphanol, became a potential choice in equine medicine. In this study, using Franz-diffusion cells the in vitro permeation rate through respiratory and olfactory equine nasal mucosa of two butorphanol formulations was estimated and compared. Both formulations had the same composition, was the exception for formulation 2, that contained 2, 5 x 10 -4 M of a non-ionic surfactant (tween 80). Butorphanol administered dose was 24, 4 mg/cm2. Plots of the cumulative amounts of butorphanol against time were constructed, where maximum flux values at the steady state (Jss), apparent permeability coefficients (Kp) and lag-time (tlag) were estimated. The Jss and Kp show that permeation of butorphanol through olfactory mucosa is different than respiratory mucosa. Moreover, Jss for formulation 2 was higher than formulation 1 in both anatomical areas, probably for the effect of the surfactant. The present results are promising to carry on with the development of formulation of butorphanol for intranasal administration.

Enhancement of the Topical Bioavailability and Skin Whitening Effect of Genistein by Using Microemulsions as Drug Delivery Carriers

Genistein, the most abundant isoflavone of the soy-derived phytoestrogen compounds, is a potent antioxidant and inhibitor of tyrosine kinase, which can inhibit UVB-induced skin carcinogenesis in hairless mice and UVB-induced erythema on human skin. In current study, genistein-loaded microemulsions were developed by using the various compositions of oil, surfactants, and co-surfactants and used as a drug delivery carrier to improve the solubility, peremability, skin whitening, and bioavailbility of genistein. The mean droplet size and polydispersity index of all formulations was less than 100 nm and 0.26 and demonstrated the formation of microemulsions. Similarly, various studies, such as permeation, drug skin deposition, pharmacokinetics, skin whitening test, skin irritation, and stability, were also conducted. The permeability of genistein was significantly affected by the composition of microemulsion formulation, particular surfactnat, and cosurfactant. In-vitro permeation study revealed that both permeation rate and deposition amount in skin were significantly increased from 0.27 μg/cm2·h up to 20.00 μg/cm2·h and 4.90 up to 53.52 μg/cm2, respectively. In in-vivo whitening test, the change in luminosity index (ΔL*), tended to decrease after topical application of genistein-loaded microemulsion. The bioavailability was increased 10-fold by topical administration of drug-loaded microemulsion. Conclusively, the prepared microemulsion has been enhanced the bioavailability of genistein and could be used for clinical purposes.

Carotenoids from Persimmon (Diospyros kaki Thunb.) Byproducts Exert Photoprotective, Antioxidative and Microbial Anti-Adhesive Effects on HaCaT

Persimmon (Diospyros kaki Thunb.) fruits are a remarkable source of carotenoids, which have shown protective effects against UV radiation in bacteria, fungi, algae, and plants. The aim of this study was to analyze the photoprotection provided by an acetone extract, rich in carotenoids and obtained from byproducts derived from the persimmon juice industry, against UV-induced cell death in the keratinocyte HaCaT cell line. For this purpose, the cytotoxicity and phototoxicity of carotenoid extract, as well as its intracellular reactive oxygen species (ROS) scavenging and anti-adhesive activities towards HaCaT cells, were evaluated. The in vitro permeation test provided information about the permeability of the carotenoid extract. Persimmon extracts, rich in carotenoids (PEC), were absorbed by HaCaT keratinocyte cells, which reduced the UV-induced intracellular ROS production in treated cells. Thus, PEC exerted a photoprotective and regenerative effect on UV-irradiated HaCaT cells, and this protection was UV dose-dependent. No cytotoxic effect was observed in HaCaT cultures at the concentration tested. PEC treatment also stimulated the adhesion capacity of skin microbiome to HaCaT cells, while exhibiting a significant anti-adhesive activity against all tested pathogens. In conclusion, PEC showed potential for use as a functional ingredient in skin-care products.

Permeability of Ibuprofen in the Form of Free Acid and Salts of L-Valine Alkyl Esters from a Hydrogel Formulation through Strat-M™ Membrane and Human Skin

This paper aimed to evaluate the effect of vehicle and chemical modifications of the structure of active compounds on the skin permeation and accumulation of ibuprofen [IBU]. In vitro permeation experiments were performed using human abdominal skin and Strat-M™ membrane. The HPLC method was used for quantitative determinations. The formulations tested were hydrogels containing IBU and its derivatives and commercial gel with ibuprofen. The results obtained indicate that Celugel® had an enhancing effect on the skin penetration of IBU. The average cumulative mass of [IBU] after 24 h permeation test from Celugel® formulation through human skin was over 3 times higher than for the commercial product. Three ibuprofen derivatives containing [ValOiPr][IBU], [ValOPr][IBU], and [ValOBu][IBU] cation were evaluated as chemical penetration enhancers. The cumulative mass after 24 h of penetration was 790.526 ± 41.426, 682.201 ± 29.910, and 684.538 ± 5.599 μg IBU cm−2, respectively, compared to the formulation containing unmodified IBU-429.672 ± 60.151 μg IBU cm−2. This study demonstrates the perspective of the transdermal hydrogel vehicle in conjunction with the modification of the drug as a potential faster drug delivery system.

Development and Evaluation of Flupirtine Maleate Transdermal Patch Containing Different Permeation Enhancers

The present study was aimed at the formulation of transdermal patches of flupirtine maleate containing different permeation enhancers. It acts indirectly as N-methyl-D-aspartate (NMDA) receptor antagonist and activates the K+ channels; thereby acts as a skeletal muscle relaxant. Flupirtine maleate transdermal patches are intended to provide localized effect. The patches were prepared by solvent evaporation technique, using polyvinyl alcohol (PVA) as the polymer whereas dimethyl sulfoxide (DMSO) and polyethylene glycol (PEG-400) as the permeation enhancers. Methanol was used as a solvent to dissolve the drug and glycerol was used as the plasticizer. These patches were evaluated for in vitro permeation, tensile strength, percent moisture absorption, drug content uniformity, film thickness, weight variation and folding endurance. All the patches showed extended release properties. Formulation FDD8 containing 8% polymer and 2% DMSO was found to be the optimized formulation on the basis of evaluation parameters. In vitro permeation release was found to be 95.71 ± 0.01% at the end of 12 h. As the concentration of DMSO increased, the release profile of drug was enhanced. This indicated that DMSO improved the release profile of flupirtine maleate when compared to PEG-400. The release kinetics of the transdermal patches followed Higuchi matrix model. The stability studies showed that all the optimized patches were stable during their study period. From the present study, it can be concluded that addition of DMSO yields good result to enhance the permeation of the drug. Keywords: flupirtine maleate, transdermal patch, permeation enhancers, dimethyl sulfoxide DMSO, polyethylene glycol PEG-400, polyvinyl alcohol PVA.

Formulation and Evaluation of Ethosomal Nanoparticles of Avobenzone for Improved Sunscreen Efficacy

Ethosomes entrapping avobenzone were prepared using cold method and the effect of varying concentration of ethanol was considered for obtaining an optimized formulation. Lecithin (2%w/w) was used as the phospholipid to provide the structure to the vesicles and propylene glycol (10%) was used as the permeating agent. The vesicles were found to be of spherical to irregular shape ranged from 1.11 µm to 1.6 µm in size. The drug entrapment in the ethosomes was studied by analyzing the unentrapped drug spectrophotometrically. The in vitro permeation study suggested that the maximum permeation in the egg membrane occurred in AET3 (0.40 mg/cm2) with 30% ethanol concentration. It was observed that only about 2% degradation occurred at room temperature and all formulations were almost stable at 8° and 4° with only 1.3% degradation of avobenzone thereby proving the stability of the developed system. The best ethosomal formulation (AET3) was incorporated into gel base to obtain sunscreen gels and the results revealed a good protection of the ethosomal gel when 2% carbopol was used as the gelling base. It could be concluded that incorporation of avobenzone in the ethosomal carrier and formulating the same as gel formulation might help in reducing the dose of avobenzone as well as improving the sunscreen efficacy (sun protection over enhanced duration).

Optimization and Evaluation of the In Vitro Permeation Parameters of Topical Products with Non-Steroidal Anti-Inflammatory Drugs through Strat-M® Membrane

Pharmaceutical products containing non-steroidal anti-inflammatory drugs (NSAIDs) are among the most prescribed topical formulations used for analgesic and antirheumatic properties. These drugs must overcome the skin barrier to cause a therapeutic effect. Human skin has been widely used as a model to study in vitro drug diffusion and permeation, however, it suffers from many limitations. Therefore, to perform in vitro permeation test (IVPT), we used a Strat-M® membrane with diffusion characteristics well-correlated to human skin. This study’s objective was to optimize the IVPT conditions using Plackett–Burman experimental design for bio-predictive evaluation of the in vitro permeation rates of five non-steroidal anti-inflammatory drugs (diclofenac, etofenamate, ibuprofen, ketoprofen, naproxen) across Strat-M® membrane from commercial topical formulations. The Plackett–Burman factorial design was used to screen the effect of seven factors in eight runs with one additional center point. This tool allowed us to set the sensitive and discriminative IVPT final conditions that can appropriately characterize the NSAIDs formulations. The permeation rate of etofenamate (ETF) across the Strat-M® membrane was 1.7–14.8 times faster than other NSAIDs from selected semisolids but 1.6 times slower than the ETF spray formulation.