The Experts below are selected from a list of 552 Experts worldwide ranked by ideXlab platform
Yasunori Morimoto - One of the best experts on this subject based on the ideXlab platform.
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effect of the absorption enhancer azone on the transport of 5 fluorouracil across Hairless Rat skin
Journal of Pharmacy and Pharmacology, 2011Co-Authors: Kenji Sugibayashi, Yasunori Morimoto, Kenichi Hosoya, William I HiguchiAbstract:The effect of the percutaneous absorption enhancer, Azone, on the transport of 5-fluorouracil across Hairless Rat skin has been investigated by an in-vitro permeation technique using 2-chamber diffusion cells. Azone (3% w/v) emulsions were used. Azone enhanced the permeability of drug 10-100 times across the full-thickness skin although there was a lag time about 10 h. The long lag time, however, disappeared with Azone pretreatment. Azone also affected the transport across stripped skin. These results suggest that Azone mainly affects the stRatum corneum. It seems to change the diffusivity of drug in that layer and is not so effective against diffusivities in the epidermis and dermis.
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comparison of depolarizing and direct current systems on iontophoretic enhancement of transport of sodium benzoate through human and Hairless Rat skin
Journal of Pharmacy and Pharmacology, 2011Co-Authors: Sachihiko Numajiri, Yasunori Morimoto, Kenji Sugibayashi, Harumi Omiya, Hidetomo Sakurai, Haruyuki Takenaka, Noriyoshi AkiyamaAbstract:— A direct current (DC) system and a pulsed depolarization (PD) system were evaluated for their iontophoretic permeation of sodium benzoate, as a model drug, through Hairless Rat and human skin. Approximately the same initial permeation of sodium benzoate through the Hairless Rat skin was obtained at 0·1 mA for the DC device and at 3·0 mA for the PD device. Study of the drug's permeation was performed using a two-chamber iontophoretic diffusion cell, over two cycles of three successive on-off experimental conditions [stage I (off) 0–4 h, II (on) 4–6 h, III (off) 6–10 h, saline washing 10–24 h, IV (off) 24–28 h, V (on) 28–30 h and VI (off) 30–34 h]. Skin permeation Rate during stage IV of the iontophoresis as compared with the control group through Hairless Rat or human skin for the DC system was 2–4 times that in stage I, whereas in the same stage using the PD system it was almost the same as in stage I. Impedance of skin decreased during the application of either system (stage II); however, the value significantly recovered during stage III only in the case of the PD system use on human skin. Histological observation revealed no tissue alteRation in the Hairless Rat skin after using either system. When the DC or PD system was applied to volunteers, the minimum current density producing pain was 0·016 or 2·7 mA cm−2, respectively. These results suggested that the PD system was more appropriate for iontophoresis application than the DC system from the point of view of skin permeability of the drug and effect on the skin.
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Transdermal Delivery of the Potent Analgesic Dihydroetorphine: Kinetic Analysis of Skin Permeation and Analgesic Effect in the Hairless Rat
Oxford University Press (OUP), 2010Co-Authors: Satoshi Ohmori, Kenji Sugibayashi, Teruaki Hayashi, Masami Kawase, Setsuo Saito, Yasunori MorimotoAbstract:Abstract Dihydroetorphine is an extraordinarily strong opioid analgesic. To assess its effectiveness after topical application in Hairless Rats we have examined the kinetic analysis of skin permeation through excised skin and the in-vitro reservoir effect of skin, and have investigated the predictability of plasma concentRation and analgesic effect following in-vivo transdermal application. Dihydroetorphine was modeRately permeable from an aqueous suspension through excised Hairless Rat skin. Dihydroetorphine flux from drug-dispersed pressure-sensitive adhesive tape was threefold that from the applied aqueous suspension. The fluxes through the abdominal and the dorsal skin during tape application fitted the Fickian diffusion equation well after the tape was removed peeling off the outer layer of the stRatum corneum. The relationship between the plasma concentRation and the analgesic effect was examined for four different Rates of infusion of dihydroetorphine. A non-linear pharmacokinetic disposition was observed. Following abdominal (0.28 cm2, 20μg) and dorsal (0.50 cm2, 35μg) applications of the dihydroetorphine tape, plasma concentRation (0.2-0.8 ng mL−1) and analgesic effect were maintained at a suitable level, for more than 8h, until removal of the tape. These profiles were predictable using the combined equation for percutaneous absorption, disposition and the analgesic effect, but the analgesic effect was slightly lower than the predicted value. The results show that it was possible to control the plasma concentRation and the analgesic effect of dihydroetorphine by topical application of the analgesic using pressure-sensitive adhesive tape in the Hairless Rat. It was possible to predict the result using mathematical modelling.
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elucidation of the transport pathway in Hairless Rat skin enhanced by low frequency sonophoresis based on the solute water transport relationship and confocal microscopy
Journal of Controlled Release, 2005Co-Authors: Yasunori Morimoto, Liang Fang, Mizue Mutoh, Hideo Ueda, Kotaro Hirayama, Mahito Atobe, Daisuke KobayashiAbstract:Abstract In this study, we examined a relationship between hydrophilic solute and water (vehicle) transports in the excised Hairless Rat skin in the presence of ultrasound (41 kHz, 60–300 mW/cm 2 ) irradiation and also conducted skin surface observation using confocal microscopy. When the applied intensity was increased stepwise over the rage of 60–300 mW/cm 2 , the transport of tritiated water ( 3 H 2 O) was increased 140-fold in an intensity-dependent manner and this returned to normal on stopping the ultrasound application. The skin permeation clearance (μl/h) of model hydrophilic solutes, calcein (MW 623) and FITC-labeled dextrans [MW 4400 (FD-4) and MW 38000 (FD-40)], across the skin under the influence of ultrasound was plotted against the corresponding 3 H 2 O flux (μl/h) to estimate the potential contribution of convective solvent flow, induced by the ultrasound application, to the solute transport. Good correlations were observed between the 3 H 2 O flux and solute clearances and, unexpectedly, the slope values obtained from linear regression of the plots were consistent for all solutes examined (1.04±0.29 for calcein, 1.07±0.17 for FD-4, and 1.08±0.23 for FD-40, respectively). Transport of intact FD-4 and FD-40 was confirmed by gel permeation chromatography. When the skin surface and deeper regions of the skin after sonophoresis of FD-40 were observed using a confocal microscope, the fluorescence of FD-40 was uniformly distributed in the area under the ultrasound horn and also evident in crack-like structures in the boundary of the horn. On the other hand, a hexagonal structure of horny cells in the stRatum corneum (SC) observed by post-staining with rhodamine B was fully conserved in the area under the horn. These findings suggest that 41 kHz ultrasound can increase the transdermal transport of hydrophilic solutes by inducing convective solvent flow probably via both corneocytes and SC lipids as well as newly developed routes. Our observation also suggests that 41 kHz (low-frequency) ultrasound has the potential to deliver hydrophilic large molecules transdermally.
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characterization of transdermal solute transport induced by low frequency ultrasound in the Hairless Rat skin
Journal of Controlled Release, 2003Co-Authors: Mizue Mutoh, Daisuke Kobayashi, Hideo Ueda, Yasushi Nakamura, Kotaro Hirayama, Mahito Atobe, Yasunori MorimotoAbstract:Abstract Sonophoretic drug transport with low-frequency (41–445 kHz) and low-intensity (60–240 mW/cm 2 ) ultrasound was characterized using hydrophilic calcein and deuterium oxide (D 2 O) as a solvent vehicle in excised Hairless Rat skin. The excised skin was mounted in vertical diffusion chambers for measurement of skin resistance and sonophoretic transport of calcein and D 2 O. The calcein content of the skin was also measured after ultrasound application. When the stRatum corneum (sc) side was exposed to ultrasound at an intensity of 60 mW/cm 2 for 30 min, the calcein flux in the sc-to-dermis direction was increased by 22.3-, 6.3-, and 3.8-fold from a baseline of 0.0088±0.0100 nmol/(cm 2 ·h) at frequencies of 41, 158, and 445 kHz, respectively, without significant changes in skin resistance. The ultrasonically-enhanced fluxes returned to baseline following cessation of the ultrasound application. At 41 kHz, there was a further increase in the magnitude of enhancement and a significant decrease in skin resistance (by 50% of the baseline resistance) on increasing the intensity from 60 to 120 mW/cm 2 , whereas no further enhancement was observed at 158 and 445 kHz up to 240 mW/cm 2 . Comparison of the calcein content in the skin before, during, and after ultrasound application at 41 kHz, 120 mW/cm 2 , was consistent with a transient ultrasonically-induced increase in calcein flux. In the sonophoretic transport experiments at 41 kHz, 120 mW/cm 2 , calcein transport correlated well with D 2 O transport. When 41-kHz ultrasound was applied to the sc side at 120 mW/cm 2 , the calcein and D 2 O fluxes in the sc-to-dermis direction were 13.7- and 5.2-fold higher than those in the dermis-to-sc direction. Similar directionality was also observed in tape-stripped skin, suggesting possible induction of convection in the direction of sound propagation. However, dermal application under the same ultrasound conditions induced neither an increase in calcein and D 2 O transport nor a decrease in skin resistance. These results demonstRate that low frequency sonophoresis is a potentially useful technique for controlling transdermal drug transport. Convective solvent flow as well as structural alteRation of the skin induced by ultrasound are likely to be responsible for the observed sonophoretic transport enhancement.
Yie W Chien - One of the best experts on this subject based on the ideXlab platform.
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mutual Hairless Rat skin permeation enhancing effect of ethanol water system and oleic acid
Journal of Pharmaceutical Sciences, 1996Co-Authors: Daeduk Kim, Julia Lee Kim, Yie W ChienAbstract:The mutual Hairless Rat skin permeation-enhancing effect of ethanol (EtOH)/water systems and oleic acid (OA) was investigated with model lipophilic (estradiol, progesterone, levonorgestrel) and hydrophilic drugs (zalcitabine, didanosine, zidovudine). The aqueous solubility and Hairless Rat skin permeation Rate of each drug, satuRated in various compositions of EtOH/water system (with and without OA), was determined at 37°C. The Hairless Rat skin permeation Rates of ethanol from EtOH/water systems (with and without OA) were also measured to investigate the skin permeation-enhancing mechanism of EtOH/water systems and OA. Both satuRated solubility and steady-state permeation Rates of each drug in EtOH/water systems increased exponentially as the volume fraction of ethanol increased, reached the maximum value, and then decreased with further increases in the ethanol volume fraction. Moreover, the Hairless Rat skin permeation Rate of each drug had a good linear relationship with that of ethanol up to 70% (v/v) of ethanol in the EtOH/water system. The addition of OA in the EtOH/water system (70:30 and 60:40 for lipophilic and hydrophilic drugs, respectively) further enhanced the skin permeation Rate of both ethanol and drugs. However, > 2.0% (v/v) OA was required to achieve the plateau level in the skin permeation Rate of lipophilic drugs, whereas only 0.3% (v/v) OA was required for hydrophilic drugs. The skin permeation Rate of ethanol also increased with the addition of OA in the EtOH/water systems (70:30 and 60:40), reached the plateau level with < 1.0% (v/v) OA, and did not significantly change with higher OA concentRation. These results suggest that the addition of OA in the EtOH/water system is a useful method to enhance the Hairless Rat skin permeation Rate of both hydrophilic and lipophilic drugs, with more enhancement for hydrophilic drugs.
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transdermal delivery of dideoxynucleoside type anti hiv drugs 2 the effect of vehicle and enhancer on skin permeation
Journal of Pharmaceutical Sciences, 1996Co-Authors: Daeduk Kim, Yie W ChienAbstract:The effects of vehicles and enhancers on the skin permeation of the dideoxynucleoside-type anti-HIV drugs Zalcitabine (DDC), Didanosine (DDI), and Zidovudine (AZT) were studied using Hairless Rat skin at 37 degrees C. After each drug was satuRated in various volume fractions of ethanol (EtOH)/water or EtOH/tricaprylin (TCP) cosolvent system for 48 h at 37 degrees C, an in vitro skin permeation study was conducted using Valia-Chien permeation cells for 30 h. The skin permeation Rates of DDC, DDI, and AZT from both EtOH/water and EtOH/TCP cosolvent systems increased as the volume fraction of ethanol was increased, reached maximum values at 50-60% (v/v) of ethanol, and then decreased with further increase of ethanol volume fraction. The EtOH/water cosolvent system seems to enhance the skin permeation of these drugs by increasing both the solubility of drug in the vehicles and partitioning of drug into the skin. The skin permeation enhancing effect of EtOH/TCP seems to be solely due to the increase in partitioning of drug into the skin. Addition of 1.0% (v/v) of permeation enhancers, such as oleic acid (OA) and N-methyl-2-pyrrolidone (NMP), in the EtOH/TCP (50:50) cosolvent system could not significantly increase the permeation Rate of these drugs. IncorpoRation of viscous TCP into ethanol probably reduced the thermodynamic activity of enhancers to distribute from the vehicle to the skin. However, incorpoRation of 1.0% (v/v) of OA in the EtOH/water (60:40) cosolvent system dramatically enhanced the skin permeation of these drugs while reducing the lag time. The permeation Rates of these drugs increased as OA concentRation was increased up to 0.3% (v/v) in the EtOH/water (60:40) cosolvent system and reached a plateau with further addition of OA. Using a satuRated solution in the EtOH/water (60:40) cosolvent system containing 1.0% (v/v) OA, DDC, and AZT reached the target permeation Rate required to maintain a therapeutic system level across Hairless Rat skin. Although only DDC reached the target permeation Rate across human cadaver skin, these results suggest that the mutual enhancement effect of ethanol and OA may make transdermal delivery of dideoxynucleoside-type anti-HIV drugs feasible.
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comparison of skin permeation of dideoxynucleoside type anti hiv drugs alone versus combination
Drug Development and Industrial Pharmacy, 1996Co-Authors: Daeduk Kim, Yie W ChienAbstract:AbstractThe effects of vehicles and skin permeation enhancer on the skin permeation of dideoxynucleoside-type anti-HN drugs, Zalcitabine (DDC), Didanosine (DDI), and Zidovudine (AZT), alone and in combination, were compared using Hairless Rat and human cadaver skins. Each drug alone or a combination of three drugs was added to various compositions of ethanol/water or ethanol/tricaprylin cosolvent system to satuRation, and in vitro skin permeation studies were conducted using Valia-Chien skin permeation cells. In both ethanol/water and ethanol/tricaprylin systems, the Hairless Rat skin permeation Rates achieved by each drug alone and three drugs in combination were not significantly different. Addition of oleic acid [1.0% (v/v) for each drug alone and 5.0% (v/v) for drug combination] in ethanol/tricaprylin (50:50) could not significantly enhance the skin permeation of these drugs. In Hairless Rat skin permeation of each drug alone, the permeation Rates of all three drugs were dramatically enhanced with the...
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transdermal delivery of dideoxynucleoside type anti hiv drugs 1 stability studies for Hairless Rat skin permeation
Journal of Pharmaceutical Sciences, 1995Co-Authors: Daeduk Kim, Yie W ChienAbstract:Abstract The stability of dideoxynucleoside‐type anti‐HIV drugs in solution when in contact with Hairless Rat skin was investigated in order to study the feasibility of their transdermal delivery. The freshly excised dorsal region of Hairless Rat skin was mounted on Valia‐Chien skin permeation cells, and both epidermis (donor) and dermis (receptor) were extracted with isotonic phosphate buffer (pH 7.4) at 37 °C for 24 h. Zalcitabine (DDC), didanosine (DDI), and zidovudine (AZT) were found to be stable in the extract of the epidermis at 37 °C for at least 30 h. However, DDC and DDI degraded in the extract of the dermis following first‐order kinetics at both 25 and 37 °C, while AZT was stable at 37 °C for at least 30 h. The degradation mechanism(s) of DDC and DDI was (were) studied by analyzing HPLC chromatograms and by evaluating the drug stability in the extract which was filtered to remove any microbes. An unidentified peak produced by DDC in the dermis extract did not appear when the drug was added to the filtered extract, which suggested a bacterial degradation of DDC. On the other hand, DDI was unstable even in the filtered extract and produced a degradation product which corresponded to hypoxanthine, which suggested that a cutaneous enzyme is also involved in the degradation of DDI. DDC was stabilized by the addition of 0.01% (w/v) of an antibacterial agent, such as thimerosal or gentamicin, in the receptor solution, while DDI was stabilized by 0.01% (w/v) purine nucleoside phosphorylase inhibitor, i.e. , p ‐chloromercuri‐benzoic acid. These results show the importance of stability studies when designing skin permeation experiments using Hairless Rat since compounds with similar chemical structures can have different stability profiles when in contact with Hairless Rat skin.
Kenji Sugibayashi - One of the best experts on this subject based on the ideXlab platform.
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Combined Use of N-Palmitoyl-Glycine-Histidine Gel and Several PenetRation Enhancers on the Skin Permeation and ConcentRation of Metronidazole
Pharmaceutics, 2018Co-Authors: Sabrina Dahlizar, Mika Futaki, Akie Okada, Chihiro Yatomi, Hiroaki Todo, Kenji SugibayashiAbstract:N-Palmitoyl-Glycine-Histidine (Pal-GH) is a novel low molecular weight gelator. In our previous report, ivermectin, a lipophilic drug, was effectively delivered to skin tissue after topical application with Pal-GH as a spray gel formulation, and a much higher skin concentRation was confirmed than with the administRation of a conventional oral formulation. The objective of this study was to increase the skin permeation of metronidazole (MTZ), a hydrophilic drug, after the topical application of Pal-GH gel. An evaluation of the combined effect of chemical penetRation enhancers (CPEs), such as isopropyl myristate (IPM), propylene glycol (PG), ethanol, diethylene glycol monoethyl ether, and dimethyl sulfoxide (DMSO), on skin permeation was also conducted. We found that a 5% Pal-GH gel containing 1% MTZ (F5MTZ) exhibited a 2.7-fold higher MTZ permeation through excised Hairless Rat skin than its solution. Furthermore, F5PG-MTZ and F5IPM-MTZ further increased the skin permeation of MTZ when compared to F5MTZ. Interestingly, F5PG-MTZ enhanced the skin penetRation of MTZ, although no enhancement effect was observed for an MTZ solution containing PG. Thus, a Pal-GH formulation containing PG and IPM may enhance the skin permeation of MTZ.
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prediction of skin permeation by chemical compounds using the artificial membrane stRat m
European Journal of Pharmaceutical Sciences, 2015Co-Authors: Takashi Uchida, Hiroaki Todo, Wesam R Kadhum, Sayumi Kanai, Takeshi Oshizaka, Kenji SugibayashiAbstract:Abstract Purpose The usefulness of the synthetic membrane, StRat-M™ as an alternative to human and animal skins was evaluated by estimating the skin permeabilities of chemical compounds. Method Thirteen chemical compounds with molecular weights (M.W.) of 152–289 and lipophilicities (log Ko/w) of −0.9 to 3.5 were selected. StRat-M™, excised human skin, or Hairless Rat skin was set in a Franz-type diffusion cell and a satuRated solution of each chemical compound was applied to determine membrane permeation profiles. The obtained permeability coefficients (log P) were compared among these membranes. Results and discussion Elevations were observed in log P for StRat-M™ with an increase in the log Ko/w of the applied compounds, and similar results were observed with the human and Hairless Rat skins. A correlation was obtained in log P values between StRat-M™ and human or Hairless Rat skin. Furthermore, the diffusion and partition parameters of chemicals in StRat-M™ were similar to those in the excised human and Rat skins. These results suggest that StRat-M™ could be used as an alternative to animal or human skin in permeation studies.
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comparison of depolarizing and direct current systems on iontophoretic enhancement of transport of sodium benzoate through human and Hairless Rat skin
Journal of Pharmacy and Pharmacology, 2011Co-Authors: Sachihiko Numajiri, Yasunori Morimoto, Kenji Sugibayashi, Harumi Omiya, Hidetomo Sakurai, Haruyuki Takenaka, Noriyoshi AkiyamaAbstract:— A direct current (DC) system and a pulsed depolarization (PD) system were evaluated for their iontophoretic permeation of sodium benzoate, as a model drug, through Hairless Rat and human skin. Approximately the same initial permeation of sodium benzoate through the Hairless Rat skin was obtained at 0·1 mA for the DC device and at 3·0 mA for the PD device. Study of the drug's permeation was performed using a two-chamber iontophoretic diffusion cell, over two cycles of three successive on-off experimental conditions [stage I (off) 0–4 h, II (on) 4–6 h, III (off) 6–10 h, saline washing 10–24 h, IV (off) 24–28 h, V (on) 28–30 h and VI (off) 30–34 h]. Skin permeation Rate during stage IV of the iontophoresis as compared with the control group through Hairless Rat or human skin for the DC system was 2–4 times that in stage I, whereas in the same stage using the PD system it was almost the same as in stage I. Impedance of skin decreased during the application of either system (stage II); however, the value significantly recovered during stage III only in the case of the PD system use on human skin. Histological observation revealed no tissue alteRation in the Hairless Rat skin after using either system. When the DC or PD system was applied to volunteers, the minimum current density producing pain was 0·016 or 2·7 mA cm−2, respectively. These results suggested that the PD system was more appropriate for iontophoresis application than the DC system from the point of view of skin permeability of the drug and effect on the skin.
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effect of the absorption enhancer azone on the transport of 5 fluorouracil across Hairless Rat skin
Journal of Pharmacy and Pharmacology, 2011Co-Authors: Kenji Sugibayashi, Yasunori Morimoto, Kenichi Hosoya, William I HiguchiAbstract:The effect of the percutaneous absorption enhancer, Azone, on the transport of 5-fluorouracil across Hairless Rat skin has been investigated by an in-vitro permeation technique using 2-chamber diffusion cells. Azone (3% w/v) emulsions were used. Azone enhanced the permeability of drug 10-100 times across the full-thickness skin although there was a lag time about 10 h. The long lag time, however, disappeared with Azone pretreatment. Azone also affected the transport across stripped skin. These results suggest that Azone mainly affects the stRatum corneum. It seems to change the diffusivity of drug in that layer and is not so effective against diffusivities in the epidermis and dermis.
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PrepaRation and Evaluation of Liquid-Crystal Formulations with Skin-permeation-enhancing Abilities for Entrapped Drugs
Journal of Oleo Science, 2011Co-Authors: Keisuke Yamada, Keiko Miyamoto, Jun Yamashita, Yoshihiro Tokudome, Hiroaki Todo, Fumie Hashimoto, Satoru Hashimoto, Kenji SugibayashiAbstract:The usefulness of liquid crystals (LC) in topical formulations for application to skin was evaluated by measuring the in vitro permeation profile of a model compound, calcein, entrapped in a LC formulation, through excised Hairless Rat skin and a three-dimensional cultured human-skin model; the viability was determined using the MTT assay. Two physically stable LCs were prepared from a mixture of mono-, di-, and tri-esters 1, and monoesters 2, composed of erythritol and phytanylacetic acid. Cryo-transmission electron microscopy (cryo-TEM), electron diffraction patterns, and small-angle X-ray diffraction (SAXS) observations of the LC nanodispersions showed that the structures of the LCs were reverse hexagonal (LC-A) and cubic (LC-B). The skin-permeation properties of calcein were enhanced by entrapping in the LCs as a result of the increase in calcein partition from the LC dispersion solution into the skin; the properties were analyzed using a skin-permeation-time profile. Drug partitioning could also be modified by the LC structure. No skin damage was caused by the LC formulation in these experiments.The present study suggests that LC dispersions are potential additives in topical drug formulations and cosmetic formulations.
Daeduk Kim - One of the best experts on this subject based on the ideXlab platform.
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mutual Hairless Rat skin permeation enhancing effect of ethanol water system and oleic acid
Journal of Pharmaceutical Sciences, 1996Co-Authors: Daeduk Kim, Julia Lee Kim, Yie W ChienAbstract:The mutual Hairless Rat skin permeation-enhancing effect of ethanol (EtOH)/water systems and oleic acid (OA) was investigated with model lipophilic (estradiol, progesterone, levonorgestrel) and hydrophilic drugs (zalcitabine, didanosine, zidovudine). The aqueous solubility and Hairless Rat skin permeation Rate of each drug, satuRated in various compositions of EtOH/water system (with and without OA), was determined at 37°C. The Hairless Rat skin permeation Rates of ethanol from EtOH/water systems (with and without OA) were also measured to investigate the skin permeation-enhancing mechanism of EtOH/water systems and OA. Both satuRated solubility and steady-state permeation Rates of each drug in EtOH/water systems increased exponentially as the volume fraction of ethanol increased, reached the maximum value, and then decreased with further increases in the ethanol volume fraction. Moreover, the Hairless Rat skin permeation Rate of each drug had a good linear relationship with that of ethanol up to 70% (v/v) of ethanol in the EtOH/water system. The addition of OA in the EtOH/water system (70:30 and 60:40 for lipophilic and hydrophilic drugs, respectively) further enhanced the skin permeation Rate of both ethanol and drugs. However, > 2.0% (v/v) OA was required to achieve the plateau level in the skin permeation Rate of lipophilic drugs, whereas only 0.3% (v/v) OA was required for hydrophilic drugs. The skin permeation Rate of ethanol also increased with the addition of OA in the EtOH/water systems (70:30 and 60:40), reached the plateau level with < 1.0% (v/v) OA, and did not significantly change with higher OA concentRation. These results suggest that the addition of OA in the EtOH/water system is a useful method to enhance the Hairless Rat skin permeation Rate of both hydrophilic and lipophilic drugs, with more enhancement for hydrophilic drugs.
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transdermal delivery of dideoxynucleoside type anti hiv drugs 2 the effect of vehicle and enhancer on skin permeation
Journal of Pharmaceutical Sciences, 1996Co-Authors: Daeduk Kim, Yie W ChienAbstract:The effects of vehicles and enhancers on the skin permeation of the dideoxynucleoside-type anti-HIV drugs Zalcitabine (DDC), Didanosine (DDI), and Zidovudine (AZT) were studied using Hairless Rat skin at 37 degrees C. After each drug was satuRated in various volume fractions of ethanol (EtOH)/water or EtOH/tricaprylin (TCP) cosolvent system for 48 h at 37 degrees C, an in vitro skin permeation study was conducted using Valia-Chien permeation cells for 30 h. The skin permeation Rates of DDC, DDI, and AZT from both EtOH/water and EtOH/TCP cosolvent systems increased as the volume fraction of ethanol was increased, reached maximum values at 50-60% (v/v) of ethanol, and then decreased with further increase of ethanol volume fraction. The EtOH/water cosolvent system seems to enhance the skin permeation of these drugs by increasing both the solubility of drug in the vehicles and partitioning of drug into the skin. The skin permeation enhancing effect of EtOH/TCP seems to be solely due to the increase in partitioning of drug into the skin. Addition of 1.0% (v/v) of permeation enhancers, such as oleic acid (OA) and N-methyl-2-pyrrolidone (NMP), in the EtOH/TCP (50:50) cosolvent system could not significantly increase the permeation Rate of these drugs. IncorpoRation of viscous TCP into ethanol probably reduced the thermodynamic activity of enhancers to distribute from the vehicle to the skin. However, incorpoRation of 1.0% (v/v) of OA in the EtOH/water (60:40) cosolvent system dramatically enhanced the skin permeation of these drugs while reducing the lag time. The permeation Rates of these drugs increased as OA concentRation was increased up to 0.3% (v/v) in the EtOH/water (60:40) cosolvent system and reached a plateau with further addition of OA. Using a satuRated solution in the EtOH/water (60:40) cosolvent system containing 1.0% (v/v) OA, DDC, and AZT reached the target permeation Rate required to maintain a therapeutic system level across Hairless Rat skin. Although only DDC reached the target permeation Rate across human cadaver skin, these results suggest that the mutual enhancement effect of ethanol and OA may make transdermal delivery of dideoxynucleoside-type anti-HIV drugs feasible.
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comparison of skin permeation of dideoxynucleoside type anti hiv drugs alone versus combination
Drug Development and Industrial Pharmacy, 1996Co-Authors: Daeduk Kim, Yie W ChienAbstract:AbstractThe effects of vehicles and skin permeation enhancer on the skin permeation of dideoxynucleoside-type anti-HN drugs, Zalcitabine (DDC), Didanosine (DDI), and Zidovudine (AZT), alone and in combination, were compared using Hairless Rat and human cadaver skins. Each drug alone or a combination of three drugs was added to various compositions of ethanol/water or ethanol/tricaprylin cosolvent system to satuRation, and in vitro skin permeation studies were conducted using Valia-Chien skin permeation cells. In both ethanol/water and ethanol/tricaprylin systems, the Hairless Rat skin permeation Rates achieved by each drug alone and three drugs in combination were not significantly different. Addition of oleic acid [1.0% (v/v) for each drug alone and 5.0% (v/v) for drug combination] in ethanol/tricaprylin (50:50) could not significantly enhance the skin permeation of these drugs. In Hairless Rat skin permeation of each drug alone, the permeation Rates of all three drugs were dramatically enhanced with the...
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transdermal delivery of dideoxynucleoside type anti hiv drugs 1 stability studies for Hairless Rat skin permeation
Journal of Pharmaceutical Sciences, 1995Co-Authors: Daeduk Kim, Yie W ChienAbstract:Abstract The stability of dideoxynucleoside‐type anti‐HIV drugs in solution when in contact with Hairless Rat skin was investigated in order to study the feasibility of their transdermal delivery. The freshly excised dorsal region of Hairless Rat skin was mounted on Valia‐Chien skin permeation cells, and both epidermis (donor) and dermis (receptor) were extracted with isotonic phosphate buffer (pH 7.4) at 37 °C for 24 h. Zalcitabine (DDC), didanosine (DDI), and zidovudine (AZT) were found to be stable in the extract of the epidermis at 37 °C for at least 30 h. However, DDC and DDI degraded in the extract of the dermis following first‐order kinetics at both 25 and 37 °C, while AZT was stable at 37 °C for at least 30 h. The degradation mechanism(s) of DDC and DDI was (were) studied by analyzing HPLC chromatograms and by evaluating the drug stability in the extract which was filtered to remove any microbes. An unidentified peak produced by DDC in the dermis extract did not appear when the drug was added to the filtered extract, which suggested a bacterial degradation of DDC. On the other hand, DDI was unstable even in the filtered extract and produced a degradation product which corresponded to hypoxanthine, which suggested that a cutaneous enzyme is also involved in the degradation of DDI. DDC was stabilized by the addition of 0.01% (w/v) of an antibacterial agent, such as thimerosal or gentamicin, in the receptor solution, while DDI was stabilized by 0.01% (w/v) purine nucleoside phosphorylase inhibitor, i.e. , p ‐chloromercuri‐benzoic acid. These results show the importance of stability studies when designing skin permeation experiments using Hairless Rat since compounds with similar chemical structures can have different stability profiles when in contact with Hairless Rat skin.
Osamu Yamamoto - One of the best experts on this subject based on the ideXlab platform.
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subchronic exposure of titanium dioxide nanoparticles to Hairless Rat skin
Experimental Dermatology, 2013Co-Authors: Koji Adachi, Nanako Yamada, Yuichi Yoshida, Osamu YamamotoAbstract:The evaluation of the biological effects of industrial nanoparticles on the skin is necessary for their risk assessment. To clarify the influence of TiO2 nanoparticles on the skin, we carried out a subchronic exposure study of TiO2 nanoparticles to Hairless Rat skin. W/O emulsion containing 10 wt% TiO2 nanoparticles and control emulsion was applied to the dorsal skin of Hairless Wistar Yagi Rats once a day for a maximum period of 56 consecutive days. After 2, 4 and 8 weeks, skin samples were taken from the exposed skin area. Histopathologically, the particles were only located in the stRatum corneum layer of epidermis and follicular epithelium. Focal parakeRatosis and spongiosis were observed in the epidermis. Transmission electron microscopy with energy-dispersive X-ray spectrometry (EDX) analysis failed to show TiO2 nanoparticles in the viable skin areas. There was no evidence of TiO2 penetRation in the viable skin areas. In addition, titanium contents in several organs were determined using inductively coupled plasma mass spectroscopy. Increased titanium concentRation was detected in lung samples of the TiO2 emulsion-treated groups after 8 weeks. It was most likely that the presence of TiO2 in the lungs was not caused by direct absorption of nanoparticles from the skin but was due to Rats inhaling the nanoparticle. We did not find any obvious evidences of nano-TiO2 particle skin penetRation using several morphological methods after the subchronic exposure. We believe that the influence of subchronic exposure of TiO2 is not significant based on our study.
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in vivo effect of industrial titanium dioxide nanoparticles experimentally exposed to Hairless Rat skin
Nanotoxicology, 2010Co-Authors: Koji Adachi, Nanako Yamada, Yuichi Yoshida, Kazuhiro Yamamoto, Osamu YamamotoAbstract:We morphologically investigated animal skin exposed to W/O emulsion containing 10 wt % ultrafine TiO(2) particles that had been characterized. After 4 h, exposed skin was investigated by light microscopy, confocal laser scanning microscopy (CLSM) and electron microscopy with energy-dispersive X-ray spectrometry (EDX). Light microscopic evaluation was also performed on the exposed skin after 24, 72 and 168 h. Light microscopy did not show any morphological and immunohistochemical changes in the skin. Electron microscopy revealed that the most TiO(2) particles were localized in the interfollicular stRatum disjunctum and the keRatinized layer of follicular infundibulum. No TiO(2) particles were detected in the viable skin, which was confirmed by EDX. Furthermore, we demonstRated a specific TiO(2) affinity to the follicular opening area by light microscopy and low-vacuum scanning electron microscopy with EDX. Our study suggests that TiO(2) particles neither penetRate into viable cell layers nor biologically cause any cellular changes.
