脉冲电流对胰岛素经皮渗透的促进作用

实验结果表明,脉冲电流能有效地提高胰岛素的透皮扩散速率,并随着释放池中胰岛素浓度的递增,透皮扩散速率呈线性增加。同时,胰岛素在pH值偏离等电点的酸性溶液(pH3.6)中透皮速率最高,为324.2±33.4μU/(cm²·h),而在pH值高于等电点的溶液(pH7.4)中其透皮速率降至143.7±27.3μU/(cm²·h),在pH值接近等电点(pH5.3)时,胰岛素的透皮速率最低,为78.4±21.9μU/(cm²·h)。     

Drug Reservoir Composition and Transport of Salmon Calcitonin in Transdermal Iontophoresis

Purpose. The aim of the work was to study iontophoretic transdermal administration of salmon calcitonin (sCt) in rabbits, with particular attention to drug reservoir composition. A dry sCt disc, to be dissolved on the application site, was used for preparing the reservoir for transdermal iontophoresis. As a reference drug reservoir, a pad wetted with drug solution was used. Methods. Experiments were done in rabbits depositing 100 IU of salmon calcitonin on skin and applying anodal iontophoresis. Serum calcium concentration was measured during iontophoresis, passive diffusion and after i.v. administration. Parameters such as pH value and reservoir type were examined. Results. Transdermal iontophoresis of sCt elicited a decrease in the serum calcium level, whereas, in the absence of electric current, no significant fall was measured. Using the reservoir prepared from drug solution, anodal iontophoresis at pH 4.2 was more effective than at pH 7.4, probably due to higher sCt net positive charge. Using the reservoir prepared from dry disc, similar kinetics and extent of drug effect were observed at both pH values. The reservoir prepared from solid drug deposit concentrated sCt next to the skin. Conclusions. Anodal iontophoresis for transdermal calcitonin administration shows therapeutical applicability. The type of reservoir is an important parameter affecting sCt transdermal iontophoresis.     

In-vitro and in-vivo transdermal iontophoretic delivery of tramadol, a centrally acting analgesic

Objectives The feasibility of transdermal delivery of tramadol, a centrally acting analgesic, by anodal iontophoresis using Ag/AgCl electrodes was investigated in vitro and in vivo. Methods To examine the effect of species variation and current strength on skin permeability of tramadol, in‐vitro skin permeation studies were performed using porcine ear skin, guinea‐pig abdominal skin and hairless mouse abdominal skin as the membrane. In an in‐vivo pharmacokinetic study, an iontophoretic patch system was applied to the abdominal skin of conscious guinea pigs with a constant current supply (250 µA/cm²) for 6 h. An intravenous injection group to determine the pharmacokinetic parameters for estimation of the transdermal absorption rate in guinea pigs was also included. Key findings The in‐vitro steady‐state skin permeation flux of tramadol current‐dependently increased without significant differences among the three different skin types. In the in‐vivo pharmacokinetic study, plasma concentrations of tramadol steadily increased and reached steady state (336 ng/ml) 3 h after initiation of current supply, and the in‐vivo steady‐state transdermal absorption rate was 499 µg/cm² per h as calculated by a constrained numeric deconvolution method. Conclusions The present study reveals that anodal iontophoresis provides current‐controlled transdermal delivery of tramadol without significant interspecies differences, and enables the delivery of therapeutic amounts of tramadol.     

Transdermal iontophoretic delivery of salmon calcitonin

Electrically enhanced transdermal delivery of salmon calcitonin could be useful for chronic treatment of postmenopausal osteoporosis and other clinical indications as a superior alternative to parenteral delivery. Calcitonin (50 microg/ml) formulation was prepared in citrate buffer (pH 4.0). Epidermis separated from human cadaver skin was used. Most iontophoresis studies were done at a current density of 0.5 m A cm2. Silver/silver-chloride electrodes were used and calcitonin was found to be best delivered under the anode. The relationship between calcitonin flux and current density during iontophoresis was linear. Passive flux was zero. Flux increased with increasing concentration up to 250 microg/ml but then it levels off. Thus, transdermal delivery of salmon calcitonin may be accomplished to achieve therapeutic levels.     

Controlled delivery of ropinirole hydrochloride through skin using modulated iontophoresis and microneedles

Abstract

The objective of this study was to investigate the effect of modulated current application using iontophoresis- and microneedle-mediated delivery on transdermal permeation of ropinirole hydrochloride. AdminPatch® microneedles and microchannels formed by them were characterized by scanning electron microscopy, dye staining and confocal microscopy. In vitro permeation studies were carried out using Franz diffusion cells, and skin extraction was used to quantify drug in underlying skin. Effect of microneedle pore density and ions in donor formulation was studied. Active enhancement techniques, continuous iontophoresis (74.13?±?2.20?µg/cm²) and microneedles (66.97?±?10.39?µg/cm²), significantly increased the permeation of drug with respect to passive delivery (8.25?±?2.41?µg/cm²). Modulated iontophoresis could control the amount of drug delivered at a given time point with the highest flux being 5.12?±?1.70?µg/cm²/h (5–7?h) and 5.99?±?0.81?µg/cm²/h (20–22?h). Combination of modulated iontophoresis and microneedles (46.50?±?6.46?µg/cm²) showed significantly higher delivery of ropinirole hydrochloride compared to modulated iontophoresis alone (84.91?±?9.21?µg/cm²). Modulated iontophoresis can help in maintaining precise control over ropinirole hydrochloride delivery for dose titration in Parkinson’s disease therapy and deliver therapeutic amounts over a suitable patch area and time.     

In Vitro Efficacy and Release Study with Anti-Inflammatory Drugs Incorporated in Adhesive Transdermal Drug Delivery Systems

The topical application of two different anti-inflammatory extracts incorporated in adhesive transdermal drug delivery systems (TDDSs) was investigated. Therefore, anti-inflammatory properties and percutaneous absorption behavior of adhesive TDDSs were characterized in vitro conducting experiments with a dermatologically relevant human skin model. Anti-inflammatory efficacy against UV irradiation of both TDDSs was determined in vitro with EpiDerm™. The reduction of the release of proinflammatory cytokines by topically applied TDDSs was compared with the reduction during the presence of the specific cyclooxygenase inhibitor diclofenac in the culture medium. A similar anti-inflammatory efficacy of the topically applied TDDSs in comparison with the use of diclofenac in the culture medium should be achieved. Furthermore, percutaneous absorption in efficacy tests was compared with percutaneous absorption in diffusion studies with porcine cadaver skin. Both the topically applied TDDSs showed a significant anti-inflammatory activity. Permeation coefficients through the stratum corneum and the epidermis gained from the release studies on porcine cadaver skin (Magnolia: 2.23·10⁻⁵ cm/h, licorice: 4.68·10⁻⁶ cm/h) were approximately five times lower than the permeation coefficients obtained with the EpiDerm™ skin model (Magnolia: 9.48·10⁻⁵ cm/h, licorice: 24.0·10⁻⁶ cm/h). Therefore, an adjustment of drug doses during experiments with the EpiDerm™ skin model because of weaker skin barrier properties should be considered. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:1142–1148, 2014     

Passive and Iontophoretic Transdermal Penetration of Chlorpromazine

The in vitro iontophoretic transdermal delivery of chlorpromazine (CPZ) across pig skin was investigated. Anodal iontophoresis considerably increased CPZ skin penetration and accumulation compared with the passive controls.

The effect of CPZ concentration in the donor solution was studied (1.4–8.2 mM). A higher penetration was observed with an increase of the concentration. In addition, the effect of NaCl concentration was also studied (154–200 mM). As expected, CPZ iontophoretic transport decreased with NaCl content. Finally, the influence of the current density (0.20–0.50 mA/cm²) was investigated. The iontophoretic transport of CPZ tends to increase with current density, although this effect was not statistically significant between 0.35 and 0.5 mA/cm². On the whole, this work shows that iontophoresis may be used to improve the transdermal delivery of CPZ for the treatment of chronic psychosis.     

A Review of: “Excipient Development for Pharmaceutical,Biotechnology, and Drug Delivery Systems”

The feasibility of delivering hydromorphone by transdermal iontophoresis to obtain therapeutically effective analgesic concentrations for the management of cancer-related pain was evaluated. Anodal iontophoresis was performed, and the effect of current strength, current duration, solution pH, presence of buffer ions, and drug concentration on the transdermal permeation of hydromorphone was investigated in vitro. Freshly excised full‐thickness hairless rat skin and side-by-side permeation cells connected to the Phoresor II^TM with Ag/AgCl electrodes was used. The flux of hydromorphone was observed to significantly increase (P < 0.05) from 72.04–280.30 μg/cm²/h with increase in current strength from 0.10–0.50 mA. A linear relationship was obtained between hydromorphone flux and current strength. Furthermore, the flux of hydromorphone was influenced by solution pH and presence of buffer ions. Also, the in vitro permeation flux of hydromorphone was observed to significantly increase (P < 0.05) with a 10-fold increase in hydromorphone hydrochloride concentration from 0.01–0.10 M. However, with further increase to 0.50 M, there was no significant difference in flux. These results show that by manipulating electronic and formulation variables, the transdermal iontophoretic delivery of hydromorphone can be controlled, and therapeutically effective concentrations of hydromorphone for the management of cancer-related pain can be obtained.     

Effect of Electroporation on Transdermal lontophoretic Delivery of Luteinizing Hormone Releasing Hormone (LHRH) in Vitro

Electroporation, the creation of transient, enhanced membrane permeability using short duration (microseconds to millisecond) electrical pulses, can be used to increase transdermal drug delivery. The effect of an (electroporative) electric pulse (1000 V, = 5 msec) on the iontophoretic transport of LHRH through human skin was studied in vitro. Fluxes achieved with and without a pulse under different current densities (0- 4 mA/cm²) were compared. The results indicated that the application of a single pulse prior to iontophoresis consistently yielded higher fluxes (5—10 times the corresponding iontophoretic flux). For example, at 0.5 mA/cm² fluxes were 0.27 ± 0.08 and 1.62 ± 0.05 µg/hr/cm² without and with the pulse, respectively. At each current density studied, the LHRH flux decreased after iontophoresis, approaching pre-treatment values. The results show that electroporation can significantly and reversibly increase the flux of LHRH through human skin. These results also indicate the therapeutic utility of using electroporation for enhanced transdermal transport.     

In vitro and in vivo evaluation of a hydrogel-based prototype transdermal patch system of alfuzosin hydrochloride

The first-line therapy for moderate to severe benign prostatic hyperplasia is the oral therapy by alfuzosin hydrochloride. Unfortunately, the oral therapy of alfuzosin is associated with several route-specific systemic side-effects. The current study was aimed to develop a prototype transdermal patch system for alfuzosin using a hydrogel polymer and optimize the drug delivery through the skin for systemic therapy. The prospective of different chemical enhancers (polyethylene glycol (PEG 400), isopropyl myristate, propylene glycol, menthol and L-methionine; 5% w/v) and iontophoresis (0.3?mA/cm²) in the alfuzosin delivery across the full thickness rat skin was assessed in vitro. In vivo iontophoretic studies were carried out using selected patch system (PEG 400) for a period of 6?h in Sprague-Dawley rats. Passive permeation studies indicated that the incorporation of chemical agents have moderate effect (~?4- to 7-fold) on the alfuzosin skin permeability and reduced the lag time. Combined approach of iontophoresis with chemical enhancers significantly augmented the drug transport (~ 43- to 72-fold). In vivo pharmacokinetic parameters revealed that the iontophoresis (transdermal patch with PEG 400) significantly enhanced the C_max (~ 3-fold) and AUC_0-α (~ 4-fold), when compared to control. The current study concludes that the application of iontophoresis (0.3?mA/cm²) using the newly developed agaorse-based prototype patch with PEG 400 could be utilized for the successful delivery of alfuzosin by transdermal route.     

Microporation and ‘Iron’tophoresis for Treating Iron Deficiency Anemia

Purpose

Iontophoretic mediated transdermal delivery of ferric pyrophosphate (FPP) in combination with microneedle pretreatment was investigated as a potential treatment for iron deficiency anemia (IDA).

Methods

In vitro transdermal delivery studies were performed using hairless rat skin and pharmacodynamic studies were performed in hairless anemic rat model. The hematological and biochemical parameters like hemoglobin, hematocrit and % serum transferrin were monitored in rats at healthy, anemic condition and post treatment. Micropores created by the microneedles were visualized in histological skin sections after staining with hemotoxylin and eosin. The recovery of micropores was investigated in vivo by measuring Transepidermal water loss (TEWL) at different time points.

Results

The passive, microneedle and iontophoresis mediated delivery did not lead to significant improvement in hematological and biochemical parameters in anemic rats, when used individually. When iontophoresis (0.15 mA/cm² for 4 hours) was combined with microneedle pretreatment (for 2 min), therapeutically adequate amount of FPP was delivered and there was significant recovery of rats from IDA.

Conclusions

Microneedle and iontophoresis mediated delivery of iron via transdermal route could be developed as a potential treatment for IDA. The transdermal controlled delivery of iron could become a potential, safe and effective alternative to parenteral iron therapy.     

Transdermal Delivery of Insulin Using Combination of Iontophoresis and Deep Eutectic Solvents as Chemical Penetration Enhancers: In Vitro and in Vivo Evaluations

A serious challenge in transdermal iontophoresis (IP) delivery of insulin (INS) is the low permeability of the drug across the skin. In this paper, we introduced deep eutectic solvent (DESs) as novel chemical penetration enhancers (CPEs) for transdermal IP of INS across rat skin, both in vitro and in vivo. Three different DESs based on choline chloride (ChCl), namely, ChCl/UR (ChCl and urea), ChCl/GLY (ChCl and glycerol), and ChCl/EG (ChCl and ethylene glycol) in the 1:2 molar ratios have been prepared. To evaluate the capability of studied DESs as CPEs for IP delivery of INS, the rat skin sample was treated with each DES. The effects of different experimental parameters (current density, formulation pH, INS concentration, NaCl concentration, and treatment time) on the in vitro transdermal iontophoretic delivery of INS were investigated. The in vitro permeation studies exhibited that INS was easily delivered employing ChCl/EG, and ChCl/GLY treatments, compared with ChCl/UR: the cumulative amount of permeated INS at the end of the experiment (Q_24h) was found to be 131.0, 89.4, and 29.6 µg cm⁻² in the presence of ChCl/EG, ChCl/GLY, and ChCl/UR, respectively. The differences in Q_24h values of INS are due to the different capabilities of the studied DESs to treat the epidermis layer of skin. In vivo experiments revealed that the blood glucose level in diabetic rats could be decreased using ChCl/EG, and ChCl/GLY as novel CPEs in the IP delivery of INS. The presented work will open new doors towards searching for novel CPEs in the development of transdermal IP of INS.     

Transdermal iontophoresis of ranitidine: an opportunity in paediatric drug therapy

The objective of this study was to examine the use of transdermal iontophoresis for the delivery of ranitidine hydrochloride in children. Constant, direct current, anodal iontophoresis of ranitidine was performed in vitro across dermatomed pig skin. The effect of donor vehicle, current intensity, and drug concentration were first examined using aqueous solutions. It was found that drug delivery was higher at pH 7 (donor: 5 mM Tris) than pH 5.6 (donor: water). In the presence of low levels of competing background electrolyte, ranitidine delivery increased linearly with applied current but was independent of the donor drug concentration. The second part of the study evaluated two Pluronic^® F-127 gels as potential vehicles for ranitidine delivery. The formulations were characterised in terms of apparent viscosity, conductivity and passive permeation measurements. Iontophoretic delivery of ranitidine was only slightly affected when delivered from the gels relative to aqueous solutions. Overall the results demonstrated that therapeutic paediatric doses of ranitidine (neonates: 0.09–0.17 μmol/kg h; 1 month to 12 years: 0.36–0.71 μmol/kg h) could be easily achieved by transdermal iontophoresis with simple gel patches of practical surface area (0.2–1.5 cm²/kg).     

TOXICOKINETIC EVALUATION OF A SELEGILINE TRANSDERMAL SYSTEM IN THE DOG

The toxicology and toxicokinetics of a selegiline transdermal system (STS) were evaluated in a 3 month dog study of daily 24 h applications of placebo 4, 8, or 12 STSs in 32 male and 32 female beagle dogs. Each STS delivered approximately 5 mg selegiline over 24 h. No drug-related signs of toxicity were noted in any group with respect to clinical observations, dermal effects, body weight, food consumption, hematology, urinalysis data, or ophthalmoscopic or electrocardiographic examinations. Clinical chemistry data revealed no consistent adverse effects except for an increase in alanine aminotransferase in dogs receiving 8 and 12 STSs. Histological evaluation of tissues revealed the presence of pigment in the Kupffer cells of dogs treated with 8 and 12 STSs. There were no pathology findings suggestive of hemolysis or cholestasis. The no-effect level (NOEL) was 4 STSs (2·9 mg kg⁻¹ d⁻¹). There were no degenerative or life-threatening toxic effects up to 12 STSs (8·5 mg kg⁻¹ d⁻¹). Gender-related differences in steady-state plasma levels were not observed. Steady-state plasma concentrations were similar to maximum plasma concentrations obtained in single-dose studies, suggesting that drug accumulation was not evident. Simulation of systemic exposure following oral administration of 16·8 mg kg⁻¹ d⁻¹ from previous toxicology studies indicated that selegiline exposure following 12 STSs is sixfold greater while N-desmethylselegiline, L-amphetamine, and L-methamphetamine exposure is 0·5, 0·15, and 0·14 times the exposure in the oral study. The threefold difference in NOEL between oral and transdermal studies in the dog (0·8 versus 2·9 mg kg⁻¹ d⁻¹) is probably related to greater L-amphetamine and L-methamphetamine exposure following oral administration. The reduction in metabolite formation, relative exposure of selegiline in the dog at the NOEL compared to oral toxicology studies, and margin of safety provided, given that the expected clinical dose is less than the dosage of oral Eldepryl^™ (0·15 mg kg⁻¹ d⁻¹), documents the safety of the selegiline drug substance and indicates that additional toxicologic findings with the STS may not be expected. © 1997 by John Wiley & Sons, Ltd.     

Transdermal Delivery of Interferon Alpha-2B using Microporation and Iontophoresis in Hairless Rats

Purpose To demonstrate transdermal delivery of interferon alpha-2b (IFNα2b) in hairless rats through aqueous microchannels (micropores) created in the skin and enhanced by iontophoresis. Materials and Methods The Altea Therapeutics PassPort™ System was configured to form an array of micropores (2.0 cm²; 72 micropores/cm²) on the rat abdomen. The transdermal patch (Iomed TransQ1-GS-hydrogel) was saturated with an IFNα2b solution (600 μg/ml) and applied for 4 h. Delivery was evaluated with and without cathodic iontophoresis (0.1 mA/cm²). Intravenous delivery (0.4 μg/100 g body weight) was performed to support pharmacokinetic calculations. Results IFNα2b was not delivered through intact skin by itself (passive delivery) or during iontophoresis. However, passive delivery through micropores was achieved in vivo in rats. A dose of 397 ± 67 ng was delivered over 6 h, with steady state serum concentrations reaching a plateau at 1 h post-patch application. These levels dropped rapidly after patch removal, and returned to baseline within 2 h of patch removal. Iontophoresis-enhanced delivery through micropores resulted in a two-fold increase in the dose delivered (722 ± 169 ng) in the hairless rat. Conclusions In vivo delivery of IFNα2b was demonstrated through micropores created in the outer layer of the skin. Iontophoresis enhanced delivery through microporated skin in hairless rats.     

Effect of iontophoresis on in vitro transdermal absorption of almotriptan

The aim of the present work was to characterize the in vitro transdermal absorption of almotriptan through pig ear skin. The passive diffusion of almotriptan malate and its iontophoretic transport were investigated using current densities of 0.25 and 0.50 mA/cm². In vitro iontophoresis experiments were conducted on diffusion cells with an agar bridge without background electrolytes in the donor compartment. Although both current densities applied produced a statistically significant increment with respect to passive permeation of almotriptan (p < 0.01), that of 0.50 mA/cm² proved to be the best experimental condition for increasing the transport of almotriptan across the skin. Under these experimental conditions, the transdermal flux of the drug increased 411-fold with respect to passive diffusion, reaching 264 ± 24 μg/cm² h (mean ± SD). Based on these results, and taking into account the pharmacokinetics of almotriptan, therapeutic drug plasma levels for the management of migraine could be achieved via transdermal iontophoresis using a reasonably sized (around 7.2 cm²) patch.     

Transdermal Iontophoretic Delivery of Propofol: A General Anaesthetic in the Form of its Phosphate Salt

The main objective of this study was to investigate the feasibility of delivery of propofol phosphate (PP), a prodrug of propofol, via transdermal route using iontophoresis in combination with chemical permeation enhancers (CPEs). PP, a prodrug, was synthesized and its structure was characterized. In vitro passive and iontophoretic drug transport studies were carried out using Franz diffusion cell across freshly excised hairless rat skin at different concentrations of PP in combination with CPE. Among all the CPEs screened, 0.1% sodium dodecyl sulfate (SDS) increased the passive transdermal flux to 13.43 ± 0.73 μg/(cm² h) from 8.52 ± 0.82 μg/(cm² h) (control). Cathodal iontophoresis in combination with 0.1% SDS synergistically enhanced the flux [249.24 ± 6.12μg/(cm² h)] of PP. The Pharmacokinetic studies were performed in rat model to assess the feasibility of transdermal delivery of PP. The amount of propofol present in plasma samples in control group (passive) was below the detectable levels at all the time points during the study. The plasma concentration—time profile of iontophoresis group of rats was fit to a noncompartmental model and the pharmacokinetic parameters were calculated. These studies suggest the plausibility of achieving therapeutically relevant levels of propofol when delivered via transdermal route by combining iontophoresis with CPE.     

Iontophoretic Transdermal Delivery of Haloperidol

The in vitro iontophoretic transdermal delivery of haloperidol (HP) across pig skin was investigated. Anodal iontophoresis considerably increased HP skin penetration and accumulation as compared to the passive controls.

The effect of NaCl and HP concentrations on the vehicle were also studied. As expected, HP iontophoretic transport decreased with NaCl content. On the other hand, HP concentration did not modify its electrotransport in the range of concentrations between 0.4 and 0.9 mg/mL, except at 24 hours. The influence of the current density (0.20–0.50 mA/cm²) was also investigated. The iontophoretic transport of HP tends to increase with current density. On the whole, this work shows that iontophoresis may be used to improve the topical application of HP for the treatment of chronic psychosis.     

Response Surface Method: A Novel Strategy to Optimize lontophoretic Transdermal Delivery of Thyrotropin-releasing Hormone

Purpose. To maximize the iontophoretic transdermal delivery rate of thyrotropin-releasing hormone (TRH) facilitated by periodically monophase-pulsed current across excised skin. Methods. The pH of the buffer, the ionic strength in the solution, the frequency of the periodically monophase-pulsed current and the current on/off ratio were chosen as the key variables. A response surface method was applied to optimize the transdermal delivery rate of TRH under different operational conditions. Results. The optimum operating conditions were achieved via experimentation based on the response surface method by systematically adjusting the pH of the buffer, the ionic strength in the solution, the current amplitude, frequency and the active temporal ratio of the pulsed current. The rate of permeation of TRH crossing the skin during iontophoresis varied from two to ten-fold, depending on operating conditions. Conclusions. Only a few steps, two in this work, were needed to reach the optimal. The response surface near the region of the maximal point was thoroughly described with a quadratic function. A maximal transdermal rate of permeation of TRH, 103.2 µg h^–1 cm^–2, was obtained when the donor solution was at pH = 7.0, ionic strength = 0.037, and with a periodically monophase-pulsed current iontophoresis with duty cycle = 75%. The effect of pulse frequency was not statistically significant.     

Electrically Modulated Transdermal Delivery of Fentanyl

Purpose. Test to determine if iontophoresis and electroporation, alone or in combination, can be used for rapid and modulated delivery of fentanyl. Methods. Fentanyl citrate (5 mg/ml) dissolved in pH 4.0 citrate buffer was delivered in vitro across human epidermis. For iontophoresis, a current of 0.5 mA/cm² was applied for 5 h, using silver/silver chloride electrodes. Electroporation protocol consisted of applying 15 exponential pulses of 500V (applied voltage) and 200 msec duration at the rate of 1 pulse per minute at time zero and, in some cases, repeating at 1.5 and 2.5 h. Results. There was no measurable permeation of fentanyl through human epidermis under passive conditions. A significant flux (about 80 g/cm²-hr) was achieved using iontophoresis and decreased once the current was turned off. A 4-fold higher flux and shorter lag time was observed with electroporation as compared to iontophoresis. The flux was found to recover quickly (within 1 h) following pulsing. Modulation of transdermal delivery of fentanyl was demonstrated by both iontophoresis and electroporation. Conclusions. Electrically assisted transdermal delivery of fentanyl significantly increased transport compared to passive delivery. Also, rapid and modulated delivery was shown to be feasible by programming the electrical parameters.