The Experts below are selected from a list of 270 Experts worldwide ranked by ideXlab platform
Marie-christine Poelman - One of the best experts on this subject based on the ideXlab platform.
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Bicontinuous sucrose ester microemulsion: a new vehicle for topical delivery of niflumic acid
International Journal of Pharmaceutics, 1998Co-Authors: Marie-alexandrine Bolzinger, C. Carduner Thevenin, Marie-christine PoelmanAbstract:The bicontinuous sucrose ester based microemulsion microstructure was characterised by a freeze fracture electron micrograph (FFEM) technique. The relationship between the microstructure and the efficacy of the microemulsion (ME) as a drug carrier system was investigated. The bioavailability of niflumic acid, a potent anti-inflammatory drug, incorporated at different concentrations in the microemulsion vehicle was investigated in vivo and compared with Nifluril® ointment (3%), a commercially available form. The methyl Nicotinate model was used to induce inflammation. Following topical application of methyl Nicotinate, various niflumic acid forms were immediately applied to the skin. The vascular response to methyl Nicotinate on the treated areas was monitored by a Laser Doppler Flowmetry technique. The results exhibit the performance of the microemulsion vehicle as a niflumic acid carrier compared to the marketed form. The 1% niflumic acid microemulsion is as efficient as the 3% niflumic acid ointment.
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correlation between percutaneous penetration of methyl Nicotinate and sensitive skin using laser doppler imaging
Contact Dermatitis, 1998Co-Authors: N Issachar, M T Borrel, Y. Gall, Marie-christine PoelmanAbstract:Cutaneous penetration of methyl Nicotinate has been investigated in 20 women divided into reactors and non-reactors on the basis of response to 10% aqueous solution of lactic acid. The vasodilation induced was measured using a laser Doppler perfusion imager (LDPI) every 5 min for 1 h after application of methyl Nicotinate. The intensity and duration of inflammation generated by methyl Nicotinate were used to assess penetration of this chemical in persons with sensitive skin compared to those with normal skin. Significant differences were found between reactors and non-reactors. Reactors showed a significantly increased intensity of response to methyl Nicotinate as early as 5 min after application, and for 30 min afterwards, though the duration of inflammation in these 2 groups was the same. Correlation between increased penetration of methyl Nicotinate and skin response to lactic acid may suggest increased penetration of water-soluble chemicals in individuals with sensitive skin.
Myron K. Jacobson - One of the best experts on this subject based on the ideXlab platform.
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Analysis and Stability Study of Octyl Nicotinate in Aqueous Solutions and Skin Homogenate by LC
Chromatographia, 2008Co-Authors: Bassam M. Tashtoush, Amjad M. Qandil, Elaine L. Jacobson, Myron K. JacobsonAbstract:Octyl Nicotinate is an ester prodrug which is under development for delivery of nicotinic acid to skin for treatment and prevention of dermatological conditions that involve skin barrier impairment such as chronic photodamage and atopic dermatitis or for mitigating skin barrier impairment that results from therapy such as retinoids or steroids. We report here an isocratic RF-LC method with water/acetonitrile (10:90, v/v) as a mobile phase, for the rapid analysis of octyl Nicotinate in aqueous solutions. The method was validated in terms of linearity, precision, accuracy and mean recovery of octyl Nicotinate from skin homogenate ranging from 98.8 to 102.6%. Separation and quantification of amounts as low as 0.25 μg mL−1 octyl Nicotinate was accomplished. The kinetic of degradation of octyl Nicotinate in aqueous solution at 310, 333, 343, and 353 K was studied. The hydrolysis rate constants for degradation of octyl Nicotinate in phosphate buffer and skin homogenate were reported. This method will be effective for routine analysis of octyl Nicotinate stability in different formulations in future studies.
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analysis and stability study of myristyl Nicotinate in dermatological preparations by high performance liquid chromatography
Journal of Pharmaceutical and Biomedical Analysis, 2007Co-Authors: Bassam M. Tashtoush, Elaine L. Jacobson, Jaber G Qasem, Joshua D Williams, Tad P Dewald, Myron K. JacobsonAbstract:Myristyl Nicotinate is an ester prodrug under development for delivery of nicotinic acid to skin for treatment and prevention of conditions that involve skin barrier impairment such as chronic photodamage and atopic dermatitis or for mitigating skin barrier impairment that results from therapy such as retinoids or steroids. The formulation stability of myristyl Nicotinate is crucial because even small amounts of free nicotinic acid cause skin flushing, an effect that is not harmful but would severely limit tolerability. We report here reversed-phase HPLC methods for the rapid analysis of myristyl Nicotinate and nicotinic acid in dermatological preparations. Because of the large differences in polarity, myristyl Nicotinate and nicotinic acid were analyzed by different chromatographic conditions, but they can be rapidly extracted from cream formulations using HPLC mobile phase as a solvent followed by HPLC analysis in less than 10 min. The methods were validated in terms of linearity, precision and accuracy and mean recovery of myristyl Nicotinate from topical creams ranged from 97.0-101.2%. Nicotinic acid at levels of 0.01% in the formulations could be quantified. Stability studies show that myristyl Nicotinate formulations are stable at room temperature for 3 years with less than 0.05% conversion to nicotinic acid. These methods will be effective for routine analysis of myristyl Nicotinate stability in dermatological formulations.
Gerhard Burckhardt - One of the best experts on this subject based on the ideXlab platform.
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identification of a new urate and high affinity Nicotinate transporter hoat10 slc22a13
Journal of Biological Chemistry, 2008Co-Authors: Andrew Bahn, Yohannes Hagos, Stefan Reuter, Daniela Balen, Hrvoje Brzica, Wolfgang Krick, Birgitta C Burckhardt, Ivan Sabolic, Gerhard BurckhardtAbstract:Abstract The orphan transporter hORCTL3 (human organic cation transporter like 3; SLC22A13) is highly expressed in kidneys and to a weaker extent in brain, heart, and intestine. hORCTL3-expressing Xenopus laevis oocytes showed uptake of [3H]Nicotinate, [3H]p-aminohippurate, and [14C]urate. Hence, hORCTL3 is an organic anion transporter, and we renamed it hOAT10. [3H]Nicotinate transport by hOAT10 into X. laevis oocytes and into Caco-2 cells was saturable with Michaelis constants (Km) of 22 and 44 μm, respectively, suggesting that hOAT10 may be the molecular equivalent of the postulated high affinity Nicotinate transporter in kidneys and intestine. The pH dependence of hOAT10 suggests p-aminohippurate–/OH–, urate–/OH–, and Nicotinate–/OH– exchange as possible transport modes. Urate inhibited [3H]Nicotinate transport by hOAT10 with an IC50 value of 759 μm, assuming that hOAT10 represents a low affinity urate transporter. hOAT10-mediated [14C]urate uptake was elevated by an exchange with l -lactate, pyrazinoate, and Nicotinate. Surprisingly, we have detected urate–/glutathione exchange by hOAT10, consistent with an involvement of hOAT10 in the renal glutathione cycle. Uricosurics, diuretics, and cyclosporine A showed substantial interactions with hOAT10, of which cyclosporine A enhanced [14C]urate uptake, providing the first molecular evidence for cyclosporine A-induced hyperuricemia.
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Identification of a New Urate and High Affinity Nicotinate Transporter, hOAT10 (SLC22A13) *
Journal of Biological Chemistry, 2008Co-Authors: Andrew Bahn, Ivan Sabolić, Yohannes Hagos, Stefan Reuter, Daniela Balen, Hrvoje Brzica, Wolfgang Krick, Birgitta C Burckhardt, Gerhard BurckhardtAbstract:Abstract The orphan transporter hORCTL3 (human organic cation transporter like 3; SLC22A13) is highly expressed in kidneys and to a weaker extent in brain, heart, and intestine. hORCTL3-expressing Xenopus laevis oocytes showed uptake of [3H]Nicotinate, [3H]p-aminohippurate, and [14C]urate. Hence, hORCTL3 is an organic anion transporter, and we renamed it hOAT10. [3H]Nicotinate transport by hOAT10 into X. laevis oocytes and into Caco-2 cells was saturable with Michaelis constants (Km) of 22 and 44 μm, respectively, suggesting that hOAT10 may be the molecular equivalent of the postulated high affinity Nicotinate transporter in kidneys and intestine. The pH dependence of hOAT10 suggests p-aminohippurate–/OH–, urate–/OH–, and Nicotinate–/OH– exchange as possible transport modes. Urate inhibited [3H]Nicotinate transport by hOAT10 with an IC50 value of 759 μm, assuming that hOAT10 represents a low affinity urate transporter. hOAT10-mediated [14C]urate uptake was elevated by an exchange with l -lactate, pyrazinoate, and Nicotinate. Surprisingly, we have detected urate–/glutathione exchange by hOAT10, consistent with an involvement of hOAT10 in the renal glutathione cycle. Uricosurics, diuretics, and cyclosporine A showed substantial interactions with hOAT10, of which cyclosporine A enhanced [14C]urate uptake, providing the first molecular evidence for cyclosporine A-induced hyperuricemia.
Jonathan Hadgraft - One of the best experts on this subject based on the ideXlab platform.
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percutaneous absorption of methyl Nicotinate
International Journal of Pharmaceutics, 1995Co-Authors: Christine Lafforgue, I Eynard, Adam C. Watkinson, Francoise Falson, Jonathan HadgraftAbstract:Abstract The percutaneous absorption of methyl Nicotinate was measured in vitro across hairless rat skin. The methyl Nicotinate was applied in vehicles containing propylene glycol dipelargonate, Labrafac Hydrophile® and Transcutol®. In vitro experiments were analysed using solutions to Fick's laws of diffusion in order to determine permeation parameters.
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Phonophoresis of Methyl Nicotinate: A Preliminary Study to Elucidate the Mechanism of Action
Pharmaceutical Research, 1993Co-Authors: James C. Mcelnay, Heather A. E. Benson, Robin Harland, Jonathan HadgraftAbstract:The skin penetration enhancement effect of ultrasound (phonophoresis) on methyl Nicotinate was investigated in 10 healthy volunteers in a double-blind, placebo-controlled, crossover clinical trial. Each treatment consisted of the application of ultrasound massage (3.0 MHz, 1.0 W/cm^2 continuous output) or placebo massage (0 MHz) for 5 min to the forearms of the volunteers, followed by a standardized application of methyl Nicotinate at intervals of 15 sec, 1 min, and 2 min postmassage. Percutaneous absorption of methyl Nicotinate was monitored using laser Doppler velocimetry. Ultrasound treatment applied prior to methyl Nicotinate led to enhanced percutaneous absorption of the drug, for example, ultrasound treatment data versus control data at 2 min showed significant increases (P < 0.05; analysis of variance) in the peak blood flow (125.8 ± 12.0 vs 75.3 ± 10.4% flux) and in the area under the curve for blood flow (2630.3 ± 387.5 vs 1567.6 ± 183.5% flux · min). The results of this study suggest that ultrasound affects the skin structure to provide skin penetration enhancement. This finding is consistent with the proposed hypothesis that phonophoresis acts by disordering the structured lipids in the stratum corneum.
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Influence of Ultrasound on the Percutaneous Absorption of Nicotinate Esters
Pharmaceutical Research, 1991Co-Authors: Heather A. E. Benson, James C. Mcelnay, Robin Harland, Jonathan HadgraftAbstract:The influence of ultrasound on the percutaneous absorption of three Nicotinate esters was investigated in 10 healthy volunteers in a double-blind placebo controlled crossover clinical trial. Using a specially designed experimental protocol, the effect of continuous output ultrasound (at frequency 3.0 MHz and intensity 1.0 W/cm^2 for 5 min) on the percutaneous absorption of methyl, ethyl, and hexyl Nicotinates, from gel bases, was investigated. A placebo control, involving massage with each of the gels, without ultrasound for 5 min, was also incorporated. The pharmacodynamic parameter of vasodilation caused by the Nicotinates was used to monitor the percutaneous absorption of the drugs. Laser Doppler velocimetry, a noninvasive optical technique, was used to measure vasodilation of the cutaneous vessels within the treatment site. Ultrasound treatment led to enhanced vasodilator response to the Nicotinates, therefore indicating an enhancement of their percutaneous absorption. These agents may prove to be useful compounds in examination of the mechanism of action of phonophoresis.
Howard I. Maibach - One of the best experts on this subject based on the ideXlab platform.
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Hydration vs. skin permeability to Nicotinates in man.
Skin Research and Technology, 2002Co-Authors: Hongbo Zhai, K. J. Stone, Vladimir Gartstein, Alessandra Pelosi, Ranjit Chatterjee, Kenton D Juhlin, Jean-pierre Ebel, Howard I. MaibachAbstract:Background/aims: Prolonged skin occlusion increases stratum corneum water content and often increases skin permeability and irritant dermatitis. As skin wetness from wearing diapers is considered an important factor favouring the onset of diaper dermatitis, optimal diapering might decrease skin hyperhydration and dermatitis. Our aim is to define the quantitative relationship between Nicotinate ester (a model penetrant) skin permeability and hydration, as measured by water evaporation rate (WER), decay curves (at individual time points) and WER-area under the curve (WER-AUC); and also to determine the level of skin hydration and skin permeability to Nicotinates following a diapering simulation. Methods/results: Nine healthy Caucasian adult women were enrolled after a prescreening procedure (time to peak redness response to Nicotinate); each received three wet occlusive patches for different exposure times (10 min, 30 min, and 3 h) and two wet model diapers (3 and 8 h). Prior to patching or diapering of forearms, basal values of WER, skin blood flow volume (BFV), capacitance (Cap) and redness (a*) were measured on premarked sites (a, b, c and d). Immediately, following occlusive patch or diaper removal, 20 µL of each Nicotinate (methyl and hexyl Nicotinate) was applied to its respective site (a or b). The WER and Cap readings were recorded at designated sites (c and d) with the following intervals after Nicotinate applications: 0, 5, 10, 15 and 20 min. The a* and BFV measurements were made on each Nicotinate challenged site (a and b) with the following intervals after Nicotinate applications: 5, 10, 15, 20, 30, 40, and 60 min. Results: WER-AUC and thus, skin hyperhydration, increased with occlusive patch and diaper exposure time, but there was no statistical difference between 3 and 8 h diaper sites. All patched sites had significantly (P
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Hydration vs. skin permeability to Nicotinates in man
Skin Research and Technology, 2002Co-Authors: Hongbo Zhai, K. J. Stone, Vladimir Gartstein, Alessandra Pelosi, Ranjit Chatterjee, Kenton D Juhlin, Jean-pierre Ebel, Howard I. MaibachAbstract:BACKGROUND/AIMS: Prolonged skin occlusion increases stratum corneum water content and often increases skin permeability and irritant dermatitis. As skin wetness from wearing diapers is considered an important factor favouring the onset of diaper dermatitis, optimal diapering might decrease skin hyperhydration and dermatitis. Our aim is to define the quantitative relationship between Nicotinate ester (a model penetrant) skin permeability and hydration, as measured by water evaporation rate (WER), decay curves (at individual time points) and WER-area under the curve (WER-AUC); and also to determine the level of skin hydration and skin permeability to Nicotinates following a diapering simulation. METHODS/RESULTS: Nine healthy Caucasian adult women were enrolled after a prescreening procedure (time to peak redness response to Nicotinate); each received three wet occlusive patches for different exposure times (10 min, 30 min, and 3h) and two wet model diapers (3 and 8 h). Prior to patching or diapering of forearms, basal values of WER, skin blood flow volume (BFV), capacitance (Cap) and redness (a*) were measured on premarked sites (a, b, c and d). Immediately, following occlusive patch or diaper removal, 20 microL of each Nicotinate (methyl and hexyl Nicotinate) was applied to its respective site (a or b). The WER and Cap readings were recorded at designated sites (c and d) with the following intervals after Nicotinate applications: 0, 5,10,15 and 20 min. The a* and BFV measurements were made on each Nicotinate challenged site (a and b) with the following intervals after Nicotinate applications: 5, 10, 15, 20, 30, 40, and 60 min. RESULTS: WER-AUC and thus, skin hyperhydration, increased with occlusive patch and diaper exposure time, but there was no statistical difference between 3 and 8h diaper sites. All patched sites had significantly (P
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In vivo transcutaneous penetration of Nicotinates and sensitive skin.
Contact Dermatitis, 1991Co-Authors: Enzo Berardesca, Maddalena Cespa, N. Farinelli, Giacomo Rabbiosi, Howard I. MaibachAbstract:: Proclivity to develop irritant reactions and transcutaneous penetration of Nicotinates has been investigated in 20 subjects of both sexes, divided into reactors and nonreactors on the basis of the responses to irritant stimuli. 1% sodium lauryl sulphate (patch application for 24 h) and 5% lactic acid in aqueous solutions were used to detect chemical and sensory (subjective) irritation. The vasodilatation induced was measured using a chromameter for 1 h after topical application of the chemical. The area-under-the-curve response and the peak response was used to assess the in vivo penetration of methyl Nicotinate (10 mM in aqueous solution). Significant differences were found between reactors and non-reactors. Non-reactors showed a significantly decreased area-under-the-curve response and peak response to methyl Nicotinate compared to reactors. Nicotinate-induced vasodilatation has been used as a model to study transcutaneous penetration of chemicals; the correlation between increased penetration of Nicotinates and skin hyperreactivity to irritant substances may suggest an increased transcutaneous penetration of water-soluble chemicals in individuals with sensitive skin.
