• Journal of Pharmaceutical Investigation
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• v.23 no.3
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• pp.41-50
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• 1993

The iontophoretic delivery across rat skin of quaternary ammonium salts (isopropamide: ISP, pyridostigmine: PS), which are positively charged over a wide pH range, was measured ill vitro. The study showed that: (a) iontophoresis significantly enhanced delivery of ISP and PS compared to respective passive transport; (b) delivery of ISP and PS was directly proportional to the applied continuous direct current density over the range of $0-0.69\;mA/cm^2;$ (c) delivery of ISP and PS was also proportional to the drug concentration in the donor compartment over the range of $0-2{\time}l0^{-2}M:$ (d) sodium ion in the donor compartment inhibited the drug transport possibly due to decreasing the electric transference number of the drug; (e) delivery of ISP and PS increased as the pH of the donor solution increased over the pH range 2-7 suggesting permselective nature of the epidermis, and inhibition of the transference number of the drugs by hydronium ion; (f) some organic anions such as taurodeoxycholate, salicylate and benzoate which form lipophilic ion-pair complexes with ISP inhibited the delivery of ISP. The degree of inhibition by the organic anions was linearly proportional to the extraction coefficient $(K_e)$ of ISP from the partition system with each counteranion between phosphate buffer (pH 7.4) and n-octanol. For PS, however, taurodeoxycholate, but not salicylate and benzoate inhibited the iontophoretic delivery. It suggests that not only sodium ion and hydronium ion but also the counteranions which form lipophilic ion-pairs with quaternary ammonium drugs are not favorable components in formulating the donor solution of the drugs to achieve an effective iontophoretic delivery.

• Biomolecules & Therapeutics
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• v.16 no.3
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• pp.226-230
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• 2008

Monoolein-based cubic liquid crystalline systems were formulated for the local delivery of oregonin and hirsutanonol for the treatment of atopic dermatitis. The liquid crystalline phase and its nanodispersion containing drugs were prepared. The skin permeation and deposition properties of the drugs were examined in normal and delipidized rat skin. The proportion of oregonin (%) deposited in normal skin after topical administration of the drugs in the form of aqueous solution, cubic phase or cubic nanodispersions were $1.53\;{\pm}\;0.46$, $3.62\;{\pm}\;0.17$ and $5.13\;{\pm}\;0.73$, and those of hirsutanonol were $2.46\;{\pm}\;0.02$, $5.44\;{\pm}\;0.27$ and $17.28\;{\pm}\;2.19$, respectively. The greater lipophilicity and thus greater skin affinity of hirsutanonol than oregonin contributed the greater amount of skin deposition. The monoolein-based liquid crystalline phases significantly increased the amount of both drugs permeated and deposited. Approximately 3.2, 2.1 and 3.0 times greater amount of oregonin, and 3.4, 2.1 and 2.2 times greater amount of hirsutanonol were deposited in delipidized skin after administration of each drug in the form of aqueous solution, cubic phase and cubic nanodispersions system, respectively, because of lowered barrier function of the delipidized skin. In this study, the effects of drug property, vehicles type and skin condition on skin deposition and permeation properties of drug were examined and concluded that monoolein-based liquid crystalline systems would be a promising formulation for the local delivery of drugs.

• The Journal of Korean Physical Therapy
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• v.14 no.4
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• pp.147-162
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• 2002

Transdermal permeation enhancer has been used to increased skin absorption. External control of drug release and skin absorption can also be achieved by iontophoresis or phonophoresis. However, because several problems with iontophoresis are that it has a risk to skin damage because of the change of pH and the increase of current density in applying it and that it can be applied only in the form of water solution, This study is to enhance drug permeation via skin following application of ultrasound. For this goal, in gel containing piroxicam, the degree of skin permeation in vitro and anti-inflammatory effect in in vivo were investigated. Permeation study using hairless mouse skin was performed at 37 $^{\circ}C$ using buffer saline as the receptor solution. The amount of piroxicam were quantified using a HPLC system consisting of solvent delivery system. Following adoption of ultrasound 1 MHZ, it showed relatively high permeation rate where it was compared with non treated by ultrasound. The influence of duty cycle having an effect on skin permeation rate was slight higher in the case of using pulsed mode. Skin permeation increase attended by intensity of ultrasound, the permeation of trice was accelerated at 2.0 W/$cm^{2}$ than 1.0 W/$cm^{2}$. The skin permeation of piroxicam was substantially influenced by ultrasound. Anti-inflammatory effects were determined using carrageenan-induced paw swelling method in SD rat. Paw swelling tests showed that pulsed phonophoresis group was more effective than control group and only gel application group. The conclusion of phonophoresis was found to improve significantly the skin permeation in vitro and the anti-inflammatory effect in vivo.

• Journal of Pharmaceutical Investigation
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• v.40 no.1
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• pp.23-31
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• 2010

In our previous work on levodopa delivery at pH 2.5 using iontophoresis, we found that cathodal delivery showed higher permeation than anodal delivery and electroosmosis plays more dominant role than electrorepulsion. In this work, we studied the transdermal transport of levodopa at very low pH (pH=1.0) where all levodopa molecules are cations, and evaluated some factors which affect the transdermal transport. The transport study at pH 2.5 was also conducted for comparison. The contribution of electrorepulsion and electroosmosis on flux was also evaluated. Using stable aqueous solution, the effect of electrode polarity, current density, current type and drug concentration on transport through skin were studied and the results were compared. We also investigated the iontophoretic flux from hydroxypropyl cellulose (HPC) hydrogel containing levodopa. In vitro flux study was performed at $33^{\circ}C$, using side-by-side diffusion cell. Full thickness hairless mouse skin were used. Current densities applied were 0.2, 0.4 or $0.6\;mA/cm^2$. Contrary to the pH 2.5 result, anodal delivery showed higher flux, indicating that electrorepulsion is the dominant force for the transport, overcoming the electroosmotic flow which is acting against the direction of electrorepulsion. Cumulative amount of levodopa transported was increased as the current density or drug concentration was increased. When amount of current dose was constant, continuous current was more beneficial than pulsed current in promoting levodopa permeation. Similar transport results were obtained when hydrogel was used as the donor phase. These results indicate that iontophoretic delivery of zwitterion such as levodopa is much complicated than that can be expected from small ionic molecules. The results also indicate that, only at very low pH like pH 1.0, electrorepulsion can be the dominant force over the electroosmosis in the levodopa transport.

• Journal of Pharmaceutical Investigation
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• v.37 no.5
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• pp.281-286
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• 2007

For transdermal delivery of porcine placenta extract (PPE), various emulsion formulations were prepared and evaluated. Polysorbate surfactants were used as emulsifiers and various C-18 unsaturated fatty acids as enhancers. The skin permeation of PPE was tested using a cellulose nitrate membrane-loaded Franz cell apparatus. Among emulsifiers, Tween 20 provided higher penetration effect than did Tween 80. Meanwhile, of various fatty acids, linolenic acid (18:3) revealed the highest skin permeation of PPE than the other C-18 unsaturated fatty acids. Stability of PPE emulsions was determined by cycles of freezing and thawing processes. The stability of emulsions depended on the percentage of Tween 20. Minimum 20% of Tween 20 was required to stabilize emulsions at room temperature for several days. Taken together, our results suggest that Tween 20 and linolenic acids might be key components to formulate PPE emulsion to provide the desirable skin permeability and stability.

• Journal of Pharmaceutical Investigation
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• v.37 no.6
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• pp.365-368
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• 2007

The primary aim of this study was to investigate the enhancement effect of low-frequency ultrasound on skin permeation. In vitro permeation experiments were performed using Franz modified diffusion cells with ketoprofen as model drug. The effect of various ultrasound factors-ultrasound application mode (continuous mode and discontinuous mode), ultrasound intensity (0.26 $W/cm^2$, and 0.29 $W/cm^2$) and duty cycle (3%, 16%, 50%, and 83%) were studied. The highest permeation was observed at 0.29 $W/cm^2$ intensity, 50% duty cycle, and discontinuous mode. The result suggested the feasibility of low frequency ultrasound application for the phonophoretic transdermal drug delivery system.

• Journal of Microbiology and Biotechnology
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• v.26 no.5
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• pp.953-958
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• 2016

Chitosan-based film-forming gel is regarded as a promising vehicle for topical delivery of antimicrobial agents to skin wounds, since it protects from microbial infection and the cationic polymer itself possesses antibacterial activity. In this study, possible synergistic interaction against common skin pathogens between the cationic polymer and tyrothricin (TRC), a cyclic polypeptide antibiotic, was investigated, by determining the concentration to inhibit 90% of bacterial isolates (MIC). The addition of the polysaccharide to TRC dramatically reduced the MIC values of TRC by 1/33 and 1/4 against both methicillin-resistant and methicillin-susceptible Staphylococcus aureus, respectively. The synergism of TRC and chitosan combination against both strains was demonstrated by the checkerboard method, with a fractional inhibitory concentration index below 0.5. Moreover, co-treatment of TRC and chitosan exhibited antibacterial activity against Pseudomonas aeruginosa, due to the antibacterial activity of chitosan, whereas TRC itself did not inhibit the gram-negative bacterial growth. These findings suggested that the use of chitosan-based film for topical delivery of TRC could be an alternative to improve TRC antimicrobial activity against strains that are abundant in skin wounds.

• Journal of Pharmaceutical Investigation
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• v.31 no.4
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• pp.225-232
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• 2001

The present study was carried out to observe the effect of liposome dispersed gel formulation (Lipogel) on topical delivery of ascorbyl palmitate (AsP). Neutral and negatively charged MLV liposomes containing AsP were prepared with dimyristoylphosphadtidylcholine (DMPC) and dicetyl phosphate (DCP), and dispersed to poloxamer gel matrix. In the hydrolysis study in rat's skin homogenates, AsP hydrolyzed to ascorbic acid (AsA) according to the first-order kinetics with the rate constant of $2.46{\times}10^{-2}\;min^{-1}$. In the passive skin penetration study using Franz diffusion cell, lipogel systems exhibited the greater values in the flux $(J_s)$ and the amount penetrated $(Q_p)$ compared to control hydrogels containing diethyleneglycol monoethyl ether $(Transcutol^{\circledR})$ as a solubilizing agent and a penetration enhancer for AsP. The total amount penetrated $(Q_{Total})$, which is expressed as a summation of $Q_P\;and\;Q_L$, for lipogel system was about 1.4 times higher in average than that of control hydrogel. However the amount localized in the skin $(Q_L)$ was similar in both formulations. As a result, lipogel system enhanced the skin penetration of AsP, possibly due to the increase in local concentration of AsP by preferential adsorption of liposome to the skin and the enhancing effect of phospholipid in liposome composition. Moreover it was expected that the penetrated AsP would generate AsA during skin penetration by the skin esterase. In conclusion, lipogel formulation was considered as a good candidate for topical delivery of AsP.

• Journal of Pharmaceutical Investigation
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• v.36 no.5
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• pp.299-304
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• 2006

The aim of this study was to investigate the effect of deformable liposomes with sodium cholate on the skin permeation and skin deposition of arbutin, a hydrophilic skin-whitening agent. Various compositions of liposomes were prepared by the extrusion method. Particle size distribution and entrapment efficiency were determined by the laser light scattering and the gel permeation chromatography, respectively. The in vitro rat skin permeation and deposition of arbutin in various skin layers were investigated using the Keshary-Chien diffusion cells at $37^{\circ}C$. The average particle size of the deformable liposomes ranged from 217.4 to 117.4 nm, depending on the composition. The entrapment efficiency was dependent on surfactant concentration and loading dose of arbutin. The permeation rate of 5% arbutin in deformable liposomes was $8.91({\pm}1.33){\mu}g/cm^2/h$, and was not significantly different from 5% arbutin aqueous solution $[9.82({\m}0.86){\mu}g/cm^2/h]$. The deposition of arbutin was $43.34({\pm}12.13)$ and $16.99({\pm}7.83){\mu}g/cm^2$ in stratum corneum layer and epidermis/dermis layer, respectively, after 12 h of permeation study. These results are consistent with several earlier studies for the localization effect of liposomal formulations in stratum corneum, and demonstrated the feasibility of the deformable liposomes as a promising carrier for the skin deposition of hydrophilic skin-whitening compounds.

• Journal of Pharmaceutical Investigation
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• v.25 no.3
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• pp.53-59
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• 1995

Ethinylestradiol (EE)-containing matrix was fabricated with ethylene-vinyl acetate(EVA) copolymer to control the release of the drug, Effect of addition of PEG 400 as receptor solution, the stripping of skin and Azone pretreatment on skin on the permeation of EE through the excised mouse skin was also studied. The permeation rate of EE through the excised mouse skin was affected by the PEG 400 volume fraction. The Azone pretreatment on skin didn't affect on the steady state flux, however, the lag time was shortened. The permeation rate of EE through the stripped skin was much larger than that through the whole skin. It showed that the stratum corneum acts as a barrier of skin permeation. The fact that there is little difference in EE permeation between the intact skin and the stripped skin with EVA membrane shows the permeation of EE through the mouse skin is mainly controlled by the membrane.