Application Of Transdermal Patch Research Articles

Maculopapular eruption to rivastigmine’s transdermal patch application and successful oral desensitization

Maculopapular eruption to rivastigmine’s transdermal patch application and successful oral desensitization

Percutaneous penetration of felbinac after application of transdermal patches: relationship with pharmacological effects in rats

We have evaluated the percutaneous penetration of felbinac following application of topical patches using a microdialysis technique, and have examined correlations with pharmacological effects. A linear microdialysis probe with a 20-mm dialysis fibre was inserted into the skin of anaesthetized rats. Probe perfusion was started at 2.0 microL min(-1) with physiological saline and after a 60-min baseline sampling of dialysate, 0.1 mL croton oil was applied to the skin surface at a concentration of 8%, v/v. A felbinac patch was then applied to the same point 60 min thereafter and dialysate was sampled at 60-min intervals up to 300 min after patch application, for determination of concentrations of felbinac and prostaglandin (PG) E2. Analgesic effects of felbinac patches in an iodoacetateinduced osteoarthritis model and an incisional pain model were evaluated using the weight bearing method. After application of patches, felbinac penetration into the skin was rapid, maximum concentrations in the dialysates with 0.07, 0.5 and 3.5% w/w felbinac patches being 0.046+/-0.02, 0.104+/-0.06 and 0.244+/-0.2 microg mL(-1), respectively. Dermal administration of croton oil caused an increment in PGE2 levels, which was significantly decreased by 0.5 and 3.5% felbinac patches 2-5 h after application. In pharmacological studies, 3.5% felbinac patches suppressed pain-associated behaviour induced by iodoacetate injection and plantar incision. These results suggested that the transdermal patch containing 3.5% felbinac may become a useful formulation.

Effect of transdermal nicotine replacement on alcohol responses and alcohol self-administration

Nicotine replacement is commonly used to treat tobacco use in heavy-drinking smokers. However, few studies have examined the effect of nicotine replacement on subjective and physiological responses to alcohol and alcohol drinking behavior. The primary aim of this within-subject, double-blind study was to examine whether transdermal nicotine replacement (0 mg vs 21 mg/day) altered response to a low-dose priming drink and subsequent ad libitum drinking behavior. Subjects (n=19) were non-treatment-seeking, non-dependent heavy drinkers who were daily smokers. Six hours after transdermal patch application, subjective and physiological responses to a priming drink [designed to raise blood alcohol levels (BALs) to 0.03 g/dl] were assessed. This was followed by a 2-h self-administration period where subjects could choose to consume up to eight additional drinks (each designed to raise BALs by 0.015 g/dl) or to receive monetary reinforcement for drinks not consumed. We found that 6 h after patch application, tobacco craving associated with withdrawal relief was decreased, and systolic blood pressure and heart rate were increased in the active patch condition compared to the placebo patch condition. Subjective intoxication in response to the priming drink was attenuated in the active nicotine patch condition compared to 6 h of nicotine deprivation (i.e., placebo patch). During the self-administration period, subjects had longer latencies to start drinking and consequently appeared to consume fewer drinks when administered the active patch compared to the placebo patch. In heavy drinkers, transdermal nicotine replacement compared to mild nicotine deprivation attenuated subjective and physiological alcohol responses and delayed the initiation of drinking.

In Vitro/in Vivo Correlation of Transdermal Naltrexone Prodrugs in Hairless Guinea Pigs

The purpose of this investigation was to evaluate the in vitro and in vivo percutaneous absorption of the following prodrugs of naltrexone (NTX): 2'-ethylbutyryl-3-O-ester-NTX (ETBUT-ester), methyl-3-O-carbonate-NTX (ME-carbonate), ethyl-3-O-carbamate-NTX (ET-carbamate), and N,N-dimethyl-3-O-carbamate-NTX (DME-carbamate) in hairless guinea pigs. In vitro fluxes of NTX and its prodrugs through guinea pig skin were determined using a flow-through diffusion cell system. The pharmacokinetics of NTX prodrugs were determined after topical application of transdermal patches in guinea pigs. All the prodrugs hydrolyzed to NTX on passing through the skin, and ME-carbonate provided the highest NTX flux and had the highest apparent permeability coefficient (K(p)). ME-carbonate and ET-carbamate underwent the highest extent of bioconversion to NTX upon passing through the skin as compared to ETBUT-ester and DME-carbamate. The results of the in vivo studies indicated that a significant amount of NTX was delivered after the application of transdermal patches of NTX prodrugs. A mean steady-state plasma concentration of 7.1 ng/ml was obtained after the application of transdermal patches of ME-carbonate. A good correlation was obtained between the in vitro and in vivo results. The results of the in vivo studies indicated that the ME-carbonate prodrug of NTX was the most promising drug candidate for transdermal delivery.

In vitro/in vivo correlation studies for transdermal Δ8-THC development

The present study was carried out in order to develop a transdermal therapeutic system (TTS) for Δ8-THC. The in vitro permeability studies of Δ8-THC in human skin and hairless guinea pig skin with and without a rate-controlling membrane were conducted in flow-through diffusion cells. Δ8-THC pharmacokinetic parameters were determined after topical application of transdermal patches and intravenous administration in guinea pigs. The in vitro results indicated that there was no significant difference in the mean flux or in the permeability coefficient of Δ8-THC in human skin versus hairless guinea pig skin. The flux of Δ8-THC through the human skin/membrane composite was not significantly lower than that through the hairless guinea pig skin/membrane composite; and the skin controlled the Δ8-THC delivery rate. Intravenous doses of Δ8-THC followed a two-compartment model with a significant distribution phase. On application of the TTS patch, the plasma concentration of Δ8-THC reached a mean steady-state level of 4.4 ng/mL within 1.4 h and was maintained for at least 48 h. Significant amounts of metabolites were observed in the plasma after topical application. The in vitro-study predicted plasma concentration following application of the transdermal patch was in agreement with the observed guinea pig plasma concentrations of Δ8-THC. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93: 1154–1164, 2004

The role of physical agents in modulating pain

This article presents a review of the literature on the use of physical agents in modulating pain associated the hand and upper extremity musculoskeletal conditions. The physical agents presented include superficial heating agents, cryotherapy, ultrasound, and transcutaneous electrical nerve stimulation. There has been increased interest in modes of transdermal drug delivery, including iontophoresis, phonophoresis, and the application of transdermal patches. Treatment applications, parameters, and integration strategies are suggested. The purposes of this article are to review which physical agents are used to treat pain or inflammation and to discuss their relevant application to hand therapy practice. Today's health care climate requires therapists to select treatment strategies that are efficient, safe, and clinically effective. Although physical agents are widely used to manage pain in hand therapy, there is little scientific evidence to support their efficacy. Most information regarding the rationale for the use of physical agents in pain management is based on tradition, data extrapolated from basic science research, and uncontrolled randomized clinical trials. This paper discusses the need for additional research to establish clinical efficacy and determine optimal treatment parameters for the physical agents used most often to modulate pain in hand therapy.

Bone metabolism changes after transdermal estradiol dose reduction during estrogen replacement therapy: A 1-year prospective study

Twenty-four surgically menopausal women were randomly allocated to one of two transdermally-administered estrogen replacement therapies (ERT): Group A was administered Estradiol (EO TTS 0.05 mg/day for 6 months and 0.025 mg/day for the following six months and group B, E 2 TTS 0.10 mg/day for the first 6 months and 0.05 mg/day for the following 6 months. For both groups, the treatment regimen was based upon the twice-weekly application of transdermal patches to the lower abdomen for three weeks a month. Serum E 2, alkaline phosphatase (AP), osteocalcin (BGP) and urinary hydroxyproline (OHP) excretion levels were measured before the operation, at the beginning of ERT and after 6 and 12 months of treatment. Bone mineral density (BMD) in the distal regions of the forearms was measured by single photon absorptiometry at the start of the study and after 6 and 12 months. In Group A, both mean cortical and trabecular BMD had increased by, respectively, 1.53% and 2.17% after 6 months of therapy; after the second 6 months a significant decrease was observed in both parameters (2.40% and 3.62%, respectively). In Group B, mean cortical and trabecular BMD increased by 1.50% and 2.10%, respectively (significant increase in trabecular bone) after the first 6 months of treatment; after the following 6 months, these values persisted (+0.15 and −0.03%, respectively). Mean AP, OHP and BGP serum levels rose after the operation. In Group A, AP and OHP showed a significant decrease after the first 6 months (−34.90% and −30.90%), followed by an increase at the last evaluation of 22.50% and 35.50%, that reached statistical significance only for OHP. TTS 0.05 mg/day led to a significant lowering in BGP levels (−30.70 %) ( P < 0.005) with respect to post-surgical values, but they rose again by 34.50% with the lower dose (range −45.10% to + 65.20%) ( P < 0.05). In group B, both AP and OHP levels were lower than pre-treatment values after the first 6 months (38.60% and 27.60%) ( P < 0.03 and P < 0.02, respectively), remaining unchanged after treatment with 0.05 mg/day (+3.50% and −6.80%, respectively). Osteocalcin levels dropped after 6 months (−16.60%), the same values being recorded at 12 months (+3.80%). Both TTS 0.10 and 0.05 mg/day proved to be effective in counteracting postmenopausal bone loss; the dose reduction from 0.10 to 0.05 mg/day did not lead to the reactivation of bone turnover. However, the lowest E 2 dose of 0.025 mg/day wasn't effective in avoiding bone demineralization.