scholarly journals Esters of terpene alcohols as highly potent, reversible, and low toxic skin penetration enhancers

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Monika Kopečná ◽  
Miloslav Macháček ◽  
Anna Nováčková ◽  
Georgios Paraskevopoulos ◽  
Jaroslav Roh ◽  
...  
Keyword(s):  
Electrical Impedance ◽  
Ex Vivo ◽  
Skin Penetration ◽  
Transepidermal Water Loss ◽  
Penetration Enhancers ◽  
Cinnamyl Alcohol ◽  
Permeation Enhancers ◽  
Terpene Alcohols ◽  
Dermal Drug Delivery ◽  
Toxic Skin

Abstract Skin penetration/permeation enhancers are compounds that improve (trans)dermal drug delivery. We designed hybrid terpene-amino acid enhancers by conjugating natural terpenes (citronellol, geraniol, nerol, farnesol, linalool, perillyl alcohol, menthol, borneol, carveol) or cinnamyl alcohol with 6-(dimethylamino)hexanoic acid through a biodegradable ester linker. The compounds were screened for their ability to increase the delivery of theophylline and hydrocortisone through and into human skin ex vivo. The citronellyl, bornyl and cinnamyl esters showed exceptional permeation-enhancing properties (enhancement ratios up to 82) while having low cellular toxicities. The barrier function of enhancer-treated skin (assessed by transepidermal water loss and electrical impedance) recovered within 24 h. Infrared spectroscopy suggested that these esters fluidized the stratum corneum lipids. Furthermore, the citronellyl ester increased the epidermal concentration of topically applied cidofovir, which is a potent antiviral and anticancer drug, by 15-fold. In conclusion, citronellyl 6-(dimethylamino)hexanoate is an outstanding enhancer with an advantageous combination of properties, which may improve the delivery of drugs that have a limited ability to cross biological barriers.

scholarly journals The Optimization of a Dimenhydrinate Transdermal Patch Formulation Based on the Quantitative Analysis of In Vitro Release Data by DDSolver through Skin Penetration Studies

2021 ◽  
Vol 89 (3) ◽  
pp. 33
Author(s):  
Bazigha K. Abdul Rasool ◽  
Amira A. Mohammed ◽  
Yasmein Y. Salem
Keyword(s):  
Quantitative Analysis ◽  
Ex Vivo ◽  
Skin Irritation ◽  
In Vitro Release ◽  
Control Sample ◽  
Skin Penetration ◽  
Penetration Enhancers ◽  
Release Data ◽  
Skin Irritation Test

Dimenhydrinate is an over-the-counter medication that is used to relieve nausea, vomiting, and vertigo caused by motion sickness. It has a short elimination half-life, possibly due to its first-pass metabolism. The current study aimed to prepare and evaluate new transdermal formulations of dimenhydrinate to prolong the drug’s release and improve its cutaneous permeation. First, the patches were fabricated and evaluated to determine their properties. The results were statistically investigated and considered significant at the p < 0.05 level. Additionally, the quantitative analysis of the drug-release data and kinetic modeling was performed by using the DDSolver software to decide the candidate formula dependably. The effect of the penetration enhancers on the permeability of dimenhydrinate from the selected patch was then studied ex vivo compared to the control sample, and the patch’s safety was evaluated in rabbits, using the skin-irritation test.

scholarly journals A Review on Chemical Permeation Enhancers used in the Formulation of Transdermal Drug Delivery System

2021 ◽  
pp. 429-437
Author(s):  
. Shivani ◽  
Ritika Puri
Keyword(s):  
Drug Delivery ◽  
Transdermal Drug Delivery ◽  
Free Water ◽  
Skin Barrier ◽  
Skin Penetration ◽  
Penetration Enhancers ◽  
Permeation Enhancers ◽  
Transdermal Drug Delivery System ◽  
Chemical Permeation Enhancers ◽  
Chemical Permeation

Skin penetration enhancement technology is a rapidly evolving area that will greatly increase the quantity of transdermal drug delivery medications. Penetration enhancers are used to facilitate the movement of drugs through the skin barrier. Numerous methods exist for extending partition enhancement. The enhancers' contact with the polar head of the lipid groups is the potential means for increasing the penetration. Penetration enhancers improve the amount of free water molecules between the bilayer, leading to an improvement of the polar drug diffusion cross section. This article focuses on the different compounds assessed for improving penetration activity like sulphoxides, azones, pyrrolidones, alcohols and alkanols, glycols, surfactants and terpenes.

scholarly journals Microemulsions as Solubilizers and Penetration Enhancers for Minoxidil Release from Gels

Gels ◽  
2021 ◽  
Vol 7 (1) ◽  
pp. 26
Author(s):  
Miroslava Špaglová ◽  
Mária Čuchorová ◽  
Martina Čierna ◽  
Silvester Poništ ◽  
Katarína Bauerová
Keyword(s):  
Drug Release ◽  
Ex Vivo ◽  
Penetration Enhancers ◽  
Permeation Enhancers ◽  
Permeable Membrane ◽  
Ex Vivo Permeation ◽  
Residual Amount ◽  
Natural Surfactants

Micro- and nanoemulsions are potential drug solubilizers and penetration enhancers through the high surfactant/co-surfactant content. This study aimed to evaluate the influence of minoxidil (MXD) solubilized in the microemulsions (MEs) on drug release by in vitro/ex vivo diffusion through the semi-permeable membrane Spectra/Por® (Spectrum Laboratory, Gardena, CA, USA) and porcine ear skin. Moreover, a residual amount of drug in the skin after ex vivo diffusion was evaluated. The reference MER, lecithin-containing MEL, and gelatin-containing MEG were characterized in terms of their size, polydispersity index, density, viscosity, electrical conductivity and surface tension. Based on the in vitro diffusion, it can be argued that MEL slowed down the drug release, while MER and MEG have no significant effect compared to the sample, in which propylene glycol (PG) was used as a solubilizer. Determination of the residual drug amount in the skin after 6 h of the ex vivo permeation was demonstrated as the most valuable method to evaluate the effectiveness of the ME’s application. The results indicate that the most optimal MXD permeation enhancers in alginate gel were the natural surfactants containing MEs. MXD solubilization in MEG and MEL had caused more than 5% of the drug remaining in the skin, which is almost a 1.5-fold higher amount compared to the reference gel.

scholarly journals Development of Pranoprofen Loaded Nanostructured Lipid Carriers to Improve Its Release and Therapeutic Efficacy in Skin Inflammatory Disorders

Nanomaterials ◽  
2018 ◽  
Vol 8 (12) ◽  
pp. 1022 ◽  
Author(s):  
María Rincón ◽  
Ana Calpena ◽  
María-José Fabrega ◽  
María Garduño-Ramírez ◽  
Marta Espina ◽  
...  
Keyword(s):  
Linoleic Acid ◽  
Ex Vivo ◽  
Skin Permeation ◽  
Skin Penetration ◽  
Nanostructured Lipid Carriers ◽  
Penetration Enhancers ◽  
Morphological Properties ◽  
Anti Inflammatory ◽  
Dermal Oedema

Pranoprofen (PF)-loaded nanostructured lipid carriers (NLCs), prepared using a high-pressure homogenization method, have been optimized and characterized to improve the biopharmaceutical profile of the drug. The optimized PF-NLCs exhibited physicochemical characteristics and morphological properties that were suitable for dermal application. Stability assays revealed good physical stability, and the release behavior of PF from these NLCs showed a sustained release pattern. Cell viability results revealed no toxicity. Ex vivo human skin permeation studies in Franz diffusion cells were performed to determine the influence of different skin penetration enhancers (pyrrolidone, decanol, octanoic acid, nonane, menthone, squalene, linoleic acid, and cineol) on skin penetration and retention of PF, being the highest dermal retention in the presence of linoleic acid. The selected formulations of NLCs exhibited a high retained amount of PF in the skin and no systemic effects. In vivo mice anti-inflammatory efficacy studies showed a significant reduction in dermal oedema. NLCs containing linoleic acid presented better anti-inflammatory efficacy by decreasing the production of interleukins in keratinocytes and monocytes. The biomechanical properties of skin revealed an occlusive effect and no hydration power. No signs of skin irritancy in vivo were detected. According to these results, dermal PF-NLCs could be an effective system for the delivery and controlled release of PF, improving its dermal retention, with reduced dermal oedema as a possible effect of this drug.

Chemical Permeation Enhancers for Transdermal Delivery of Thiocolchicoside: Assessment of Ex-vivo Skin Flux and In-vivo Pharmacokinetics

2017 ◽  
Vol 10 (5) ◽  
pp. 3827-3835
Author(s):  
Y Madhusudan Rao ◽  
Gayatri P ◽  
Ajitha M ◽  
P. Pavan Kumar ◽  
Kiran kumar
Keyword(s):  
Passive Control ◽  
Ex Vivo ◽  
Skin Permeation ◽  
In Vivo Studies ◽  
Permeation Enhancers ◽  
Casting Technique ◽  
Chemical Permeation Enhancers ◽  
Chemical Permeation ◽  
In Vivo Pharmacokinetics

Present investigation comprises the study of ex-vivo skin flux and in-vivo pharmacokinetics of Thiocolchicoside (THC) from transdermal films. The films were fabricated by solvent casting technique employing combination of hydrophilic and hydrophobic polymers. A flux of 18.08 µg/cm2h and 13.37µg/cm2h was achieved for optimized formulations containing 1, 8-cineole and oleic acid respectively as permeation enhancers. The observed flux values were higher when compared to passive control (8.66 µg/cm2h). Highest skin permeation was observed when 1,8-cineole was used as chemical permeation enhancer and it considerably (2-2.5 fold) improved the THC transport across the rat skin. In vivo studies were performed in rabbits and samples were analysed by LC-MS-MS. The mean area under the curve (AUC) values of transdermal film showed about 2.35 times statistically significant (p<0.05) improvement in bioavailability when compared with the oral administration of THC solution. The developed transdermal therapeutic systems using chemical permeation enhancers were suitable for drugs like THC in effective management of muscular pain.    

Status of Fatty Acids as Skin Penetration Enhancers-A Review

2009 ◽  
Vol 6 (3) ◽  
pp. 274-279 ◽  
Author(s):  
Ashu Mittal ◽  
U. Sara ◽  
Asgar Ali ◽  
Mohd. Aqil
Keyword(s):  
Fatty Acids ◽  
Skin Penetration ◽  
Penetration Enhancers

scholarly journals New Insights on the Mechanism of Fatty Acids as Buccal Permeation Enhancers

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 201 ◽  
Author(s):  
Cristina Padula ◽  
Silvia Pescina ◽  
Sara Nicoli ◽  
Patrizia Santi
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fluorescein Isothiocyanate ◽  
Penetration Enhancers ◽  
Systemic Delivery ◽  
Permeation Enhancers ◽  
Maximum Value ◽  
The Relationship ◽  
Insight Into ◽  
The Ideal

Buccal mucosa has recently received much attention as a potential route for systemic delivery of drugs, including biologics and vaccines. The aim of this work was to gain insight into the mechanism of fatty acids as buccal permeation enhancers, by studying the effect of a series of medium and long chain fatty acids on the permeation of a model high molecular weight and hydrophilic molecule, fluorescein isothiocyanate labelled dextran (FD-4, m.w. 4 kDa) across porcine esophageal epithelium. A parabolic relationship between fatty acid lipophilicity and enhancement was obtained, regardless of the presence and number of double bonds. The relationship, which resembles the well-known relationship between permeability and lipophilicity of transdermal delivery, presents a maximum value in correspondence of C10 (logP approx. 4). This is probably the ideal lipophilicity for the fatty acid to interact with the lipid domains of the mucosa. When the same analysis was performed on skin data, the same trend was observed, although the maximum value was reached for C12 (logP approx. 5), in agreement with the higher lipophilicity of the skin. The results obtained in the present work represent a significant advancement in the understanding of the mechanisms of action of fatty acids as buccal penetration enhancers.

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