This study examined the transdermal delivery of alendronate across hairless mouse skin. The effects of iontophoresis, perforation with a microneedle, and a combination of a microneedle pretreatment and iontophoresis were evaluated in vitro test. Hydrogel patches were polymerized by UN polymerization to supply a hydrogel patch to the iontophoretic transdermal drug delivery system. The alendronate content in the iontophoretic delivery patch was $5.0\;mg/cm^3$. The amounts of alendronate that permeated across the hairless mouse skin when current densities of 0.25 and $0.50\;mA/cm^2$ were supplied to the iontophoretic alendronate patch were $0.80{\pm}0.03$ and $2.00{\pm}0.02{\mu}g$, respectively. After pretreatment with a microneedle, the amounts of alendronate that permeated across the hairless mouse skin increased to $70.65{\pm}0.37$ and $162.23{\pm}0.40{\mu}g$, respectively. The biocompatibility of the iontophoretic alendronate patch was examined according to the international standardization organization 10993.
Journal of the Korean Academy of Clinical Electrophysiology
/
v.1
no.1
/
pp.45-56
/
2003
This study investigated the effects of triamcinolone acetonide by iontophoretic transdermal drug delivery on anti-inflammatory action into the human which had excentric exercise-induced delayed onset muscle soreness in the non-dominant arm. The degree of anti-inflammation was evaluated creatine posphokinase(CPK) by serum enzyme activity and subjective pain threshold by soreness muscle scale in clinical study. The results Were as follows; 1. In a subjective pain scale, all groups showed non-significant difference but, showed a tendency to decrease numerical value in human. 2. In the serum CPK level, iontophoresis group showed more significant reduction than other groups at 24, 48 and 72 hours. From the results, the iontophoresis with triamcinolone acetonide is more effective than using each groups. The continuous study is needed for many interesting issues of iontophoretic transdermal drug delivery in new future.
Purpose: The purpose of this study was to determined that the efficacy and comfort of iontophoretic transdermal delivery of lidocaine by comparison of local anesthetic duration, sensory threshold, pain threshold and pain tolerance levels according to four different cleansing regimes. Methods: Forty healthy volunteers were randomly assigned to four groups; oil cleansing group, lotion cleansing group, solution cleansing group and alcohol cleansing group. All subjects were received lidocaine iontophoresis on the forearm using direct current with 4 mA for 10 minutes. All subjects were measured the duration of local anesthesia after lidocaine iontophoresis, also evaluated the sensory threshold, pain threshold and pain tolerance level during iontophoresis. For comparisons of the efficacy and the sensory characteristics of iontophoresis within the groups, an one-way ANOVA was used. Results: The duration of local anesthesia were found significant difference between groups (p<0.001). The anesthetic duration in solution and alcohol cleansing groups were significantly longer than oil and lotion cleansing group by post hoc (p<0.05). Statistically significant difference were noted in respect to all sensory characteristics such as sensory threshold, pain threshold and pain tolerance between groups (p<0.001). The sensory threshold in solution and alcohol cleansing group were significantly lower than oil and lotion cleansing group by post hoc using Duncan multiple range test (p<0.05). The pain threshold and pain tolerance in solution and alcohol cleansing group were significantly higher than oil and lotion cleansing group by post hoc (p<0.05). Conclusion: These results demonstrated that cleansing regimes have affected the efficacy and discomfort of iontophoretic transdermal delivery of lidocaine. These findings indicate that cleansing agents without oil ingredient contributed to more comfort, and more successful achievement of the iontophoretic transdermal delivery.
This study investigated the effects of triamcinolone acetonide by iontophoretic transdermal drug delivery on anti-inflammatory action into the rats and which had carrageenan-induced hyperalgesia and edema in the feet, trauma-induced tissue damage in the thigh. Each group was treated under the fellowing conditions. 1. Group I : Control group 2. Group II : Application of direct current 3. Group III : Application of 0.1$\%$ triamcinolone acetonide solution 4. Group IV : Iontophoresis of 0.1$\%$ triamcinolone acetonide solution The degree of anti-inflammation was evaluated by the paw withdrawal latency, the change in volume of foot the change of paw edema, histological change in rats. 1. In paw withdrawal latency, group IV showed the most significant therapeutic effect than the other groups at 0, 3, 6 and 9 hours(p < 0.001). 2. In paw edema experiment in the foot, group IV showed the most significant effect than group I at 0, 3, 6 and 9 hours. It meant that there was effective anti-inflammatory reaction in group I (p < 0.001). 3. In the light microscopic observation, group IV showed the most significant reduction of haemorrhage, hyperemia and infiltrative inflammation. From the results, the iontophoresis with triamcinolone acetonide is more effective than using each groups. It is one of the effective physical agent which delivered large molecular weight drug into the body. The continuous study is needed for many interesting issues of iontophoretic transdermal drug delivery in new future.
We have studied the stability and transdennal flux of prostaglandin $E_1\;(PGE_1)$ from various donor solutions through hairless mouse skin. Stability in HEPES buffer or in propylene glycol (PG) solution where enhancer (oleic acid (OA), propylene glycol monolaurate (PGML), transcutol (TC), ethanol (EtOH))s dissolved was investigated. $$PGE_1 was not stable in HEPES buffer. The concentration of $$PGE_1 decreased continuously for 7 days, and the degradation rate constant was $0.0028\;h^{-1}$, assuming first order reaction. The effect of current or penetration enhancer on the degradation was minimal. Percutaneous transport from HEPES buffer by passive or iontophoretic delivery without enhancer was close to nil. When OA or PGML was used together with PG, both passive and iontophoretic flux increased. PGML showed better enhancing effect than OA. Flux by cathodal delivery was about 2 times larger than that by passive delivery. Flux by anodal delivery was lower than that by passive delivery. TC and EtOH also increased the transdermal flux, but the effect was not as good as that observed when OA or PGML was used. These stability and flux data provide important information on how to formulate the patch, which will be the next step of this work, and on the polarity of current to use during iontophoresis.
In order to develop an optimum formulation for iontophoretic flux of vitamine C 2-phosphate (VCP), we have prepared three different hydrogels containing VCP, using carbopol, HPMC and poloxamer, and iontophoretic flux through hairless mouse skin from these hydrogels was carried out. Drug stability in phosphate buffer (PBS) solution (pH 7.4) with and without current application was studied. The effect of various factors, such as drug concentration, current density, and current profile on skin flux was also investigated. Stability study indicated that VCP in PBS (pH 7.4) solution was stable under the experimental condition, irrespective of the presence of current. Cathodal delivery increased the flux markedly, whereas the anodal and passive flux was negligible. Thus, cathodal delivery was used in all experiments. Flux increased as the drug concentration (2.5, 5.0, 7.5%) and current density $(0.2,\;0.4,\;0.6\;mA/cm^2)$ increased. Pulsed application of the current showed lower flux than constant current application. The results obtained suggest that VCP can be delivered into the skin and the amount delivered can be controlled by varying hydrogel, current density, drug concentration and current application profile.
Journal of the Korean Society of Physical Medicine
/
v.9
no.2
/
pp.133-140
/
2014
PURPOSE: The purpose of this study was to compare the effect of current density on penetration depth, tissue concentration and transdermal transport of methylene blue(MB) by iontophoretic transdermal delivery. METHODS: Twenty-four male Sprague-Dawley rats were randomly divided into 1 mA($0.11mA/cm^2$), 2 mA($0.22mA/cm^2$), 4 mA($0.44mA/cm^2$), and 8 mA($0.89mA/cm^2$) groups. These rats were exposed to anodic iontophoresis of 1% MB using a direct current for 15 minutes. The penetration depth were measured using light microscopy from cryosections of skin tissue. The tissue concentration and transdermal transport were measured using biochemical analysis from target skin tissues. The data were analyzed with one-way analysis of variance. RESULTS: The significant differences in the penetration depth, tissue concentration and transdermal transport were detected among the groups(p<.001). Post hoc comparisons of the penetration depth, tissue concentration and transdermal transport of he 2 mA, 4 mA, and 8 mA iontophoresis groups were greater than in the 1 mA iontophoresis group(p<.05). There was no significant difference, however, among 2 mA, 4 mA, and 8 mA iontophoresis group. CONCLUSION: There was no difference in the efficiency of iontophoresis from 2 mA($0.22mA/cm^2$) to 8 mA($0.89mA/cm^2$). Higher current density can cause skin injury and discomfort sensation. In general, $0.5mA/cm^2$ is proposed to be the maximum iontophoretic current which should be used on human. The appropriate current amplitude should be selected by considering the safety current density and the depth of the target tissue.
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.
Osteoporosis was traditionally defined by the occurrence of nontraumatic fractures, especially of the spine, in the setting of low bone mass. Bisphosphonates are an important group of therapeutic agents for the management of osteoporosis, as they inhibit bone resorption and increase bone density, thereby potentially decreasing fracture risk. Risedronate sodium is a bisphosphonate class used by oral formulation. In this study, risedronate was transdermally delivered by iontophoresis. Effects of polarity, pH, current density, and drug concentration were studied using a side-by-side diffusion cell including the hairless mice skin. In addition we studied effect of enhancers. The flux was evaluated by HPLC/UV system. The amount of transported drug under iontophoretic delivery was approximately 186 fold higher than that under passive delivery. Flux was proportional to the increase of drug concentration and current density. The flux was observed about 0.68mg/$cm^2$ when the amout of Propyleneglycol monolaurate (PGML) used 1% as enhancer. Results indicated that iontophoresis is an effective method for transdermal administration of risedronate sodium
The objective of this work is to study transdermal delivery of levodopa using iontophoresis and evaluate various factors which affect the transdermal transport. Levodopa is unstable in aqueous solution, and, in order to establish a stable condition for levodopa for the duration of experiment, we investigated the stability of levodopa in aqueous solutions of different pHs with/without the addition of dextrose or the application of current. Using stable aqueous solution, we have studied the effect of pH, polarity and penetration enhancer (ethanol) on transdermal flux and compared the results. We also investigated the iontophoretic flux from hydroxypropyl cellulose (HPC) hydrogel. In vitro flux study was performed at $33^{\circ}C$, using side-by-side diffusion cell. Full thickness hairless mouse skin and rat skin were used for this work. Current densities applied were 0.4 or $0.6mA/cm^2$ and current was off after 6 hour application. Stability study showed that levodopa solution with a pH 2.5 or 4.5 maintained the initial concentration of levodopa for 24 hours with the addition of 5% dextrose. However, at pH 9.5, levodopa was unstable and 30 to 40% of levodopa degraded within 24 hours, even with the addition of 5% dextrose. Hydrogel swollen with dextrose added levodopa solution maintained about 97% of the initial concentration of levodopa for 13 days, when stored in $4^{\circ}C$. The application of current did not affect the stability of levodopa in hydrogel. Flux study from levodopa solution with pH 2.5 showed that cathodal delivery of levodopa was higher than passive or anodal delivery. When the pH of the donor solution was 4.5, anodal delivery of levodopa was higher than passive or cathodal delivery. These results seem to indicate that electroosmosis plays more dominant role than electrorepulsion in the flux of levodopa at pH 2.5, and the reverse situation applies for pH 4.5. The passive flux was unexpectedly high for the ionized levodopa. Similar to the results from aqueous solution, cumulative amount of levodopa transported trom HPC hydrogel by cathodal delivery was significantly higher than passive or anodal delivery. The treatment of 70% ethanol cotton ball by scrubbing increased passive, anodal and cathodal flux, with the largest increase for anodal flux. These results indicate that iontophoretic delivery of zwitterion such as levodopa is much complicated than that can be expected from small ionic molecules with single charge. The results also indicate that the balance between electroosmosis and electrorepulsion plays a very important role in the transport through skin.
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