Application Of Transdermal Patch Research Articles

O1 | Pharmacodynamics of fentanyl following transdermal patch application in horses

Journal of Veterinary Pharmacology and TherapeuticsVolume 46, Issue S1 p. 28-28 ORAL PRESENTATIONS O1 | Pharmacodynamics of fentanyl following transdermal patch application in horses First published: 11 June 2023 https://doi.org/10.1111/jvp.13167Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Volume46, IssueS1Special Issue: 15th International Congress of the European Association for Veterinary Pharmacology and Toxicology held Bruges, Belgium, July 2–5, 2023June 2023Pages 28-28 RelatedInformation

On the possibility of therapeutic action after transdermal patch application

Background. As scientific knowledge about the peculiarities of the structure and functional properties of the skin increased, it became clearer that during transdermal administration, drug may accumulate in the deep layers of the dermis and subsequently get diffused into the bloodstream even after the transdermal therapeutic system (TTS), also called transdermal patch, had been removed. Objective: to quantify active drug substances remaining in an animal skin after TTS application. Materials and methods. Two previously developed transdermal patches containing Russian-made drug substances were chosen for the study: aminodihydrophthalazinedione sodium (immunomodulator) and bis(1-vinylimidazole-N) zinc diacetate (antidote for carbon monoxide). The study was performed on male Chinchilla rabbits weighing 2.5–3 kg. Five series of experiments were performed for each substance: immediately after removal of the patch, 4 hours later, at week 1, 2 and 3 after removal. High-performance liquid chromatography and atomic absorption spectroscopy methods were used to quantify residual drug substances left in the skin. Results. In the skin flap that was in contact with the aminodihydrophthalazinedione sodium TTS for 24 hours, 0.516 mg of the drug was detected immediately after removal of the patch. Over the next two weeks, the drug substance in the skin decreased with the immunomodulator significantly reducing to 0.41 mg in the first 4 hours. In the skin flap that had been in contact with zinc bis(1-vinylimidazole-N) diacetate for 24 hours, about 1 mg of the drug was present immediately after patch removal. Four hours after removal of the transdermal patch, the quantity of active substance in the skin remained practically unchanged. At week 1 and 2, the quantity of the antidote decreased slightly to ~0.7 mg and ~0.25 mg, respectively. Conclusion. For transdermal application of aminodihydrophthalazinedione sodium, the skin can act as a drug depot and prolong the effect of this drug even after the transdermal patch had been removed. No such effect was found in the case of bis(1-vinylimidazole-N) zinc diacetate, which is apparently due to the different solubility of the drugs in the biotissue.

Phospholipid and menthol based nanovesicle impregnated transdermal patch for nutraceutical delivery to diminish folate and iron deficiency

Adequate micronutrient availability is particularly important in women, children and infants. Micronutrient deficiencies are the major cause of maternal and neonatal morbidity. To overcome this, WHO recommends the use of folic acid and iron supplements for reducing anaemia and improving the health of the mother and infants. Oral intake of supplements for nutritional deficiencies are associated with gastric irritation, nausea, constipation and non-patient compliance due to associated taste. In case of absorption deficiency nutrients administered orally pass-through digestive tract unabsorbed. In the present study, we propose transdermal delivery of nutraceuticals to avoid the limitations associated with oral intake. Transdermal delivery has limited use because of the closely packed barrier of the stratum corneum that limits the permeability of molecules across skin. Here, we have used biomimetic nanovesicles impregnated in transdermal patches for delivery of folic acid and iron. Nanovesicles are prepared using an abundant component of cell membrane, phosphatidyl choline and a permeation enhancer. Further these nanovesicles are impregnated onto polyacrylate based transdermal patch. In vitro studies have shown the ability of nanovesicles to fluidise skin lipids and penetrate into deeper skin. In vivo application of transdermal patches gradually increased the systemic concentration of nutraceuticals. Post application of the patch, five-fold increase in plasma folic acid concentration and 1.5-fold increase in plasma iron concertation was achieved in 6 h. Developed nanovesicles were compatible with keratinocytes and fibroblasts as tested in vitro and have the potential to enhance the cellular uptake of molecules. Skin irritation studies on human volunteers have confirmed the safety of nutraceutical loaded nanovesicles. Thus, the developed nutraceutical loaded transdermal patches provide a potential, easy to use platform for micronutrient delivery in infants and mothers.

Prediction of Corresponding Dose of Transdermal Blonanserin to Oral Dose Based on Dopamine D2 Receptor Occupancy: Unique Characteristics of Blonanserin Transdermal Patch.

Background/PurposeBlonanserin is an atypical antipsychotic, a potent selective antagonist of dopamine D2 receptor (D2), prescribed as oral formulations in patients with schizophrenia. Blonanserin transdermal patch was developed to provide a new treatment option, but the corresponding dose to oral blonanserin was not clear. The aims of this study were to clarify the pharmacokinetic (PK)-pharmacodynamic characteristics of blonanserin after transdermal patch application and to evaluate the corresponding dose to oral formulation based on striatal D2 occupancy.MethodsThe relationship between D2 occupancy and plasma blonanserin concentration was analyzed using an Emax model based on data from positron emission tomography study with oral and transdermal blonanserin. D2 occupancy was simulated using Emax models based on the observed plasma concentrations and the simulated plasma concentrations obtained from population PK model.ResultsPlasma blonanserin concentration levels after repeated patch applications were nearly stable throughout the day and no effect of sex, advanced age, or application site was detected. The concentration at half maximal D2 occupancy during transdermal patch applications, 0.857 ng/mL, was higher than that after oral doses, 0.112 ng/mL, suggesting metabolite contribution after oral doses. The median predicted D2 occupancy during blonanserin patch applications at doses of 40 and 80 mg/d was 48.7% and 62.5%, respectively, and the distribution of D2 occupancy at these doses could cover most of that at oral doses of 8 to 24 mg/d.ConclusionsPredicted D2 occupancy suggested that a 40- to 80-mg/d blonanserin transdermal patch dose corresponds to an 8- to 24-mg/d oral dose for the treatment of schizophrenia.

Application of transdermal patches with new skin test reagents for detection of latent tuberculosis.

Introduction. Current intradermal tuberculin skin tests for latent tuberculosis infection (LTBI) based on purified protein derivative (PPD) have poor specificity.Aims. Developing a better skin test antigen as well as a simple skin patch test may improve and facilitate diagnostic performance.Methodology. Defined recombinant antigens that were unique to Mycobacterium tuberculosis (MTB), including two potential latency-associated antigens (ESAT-6 and Rv2653c) and five DosR-encoded latency proteins (Rv1996, Rv2031c, Rv2032, DevR and Rv3716c), were used as diagnostic skin test reagents in comparison with a standard PPD. The performance of the skin tests based on the detection of delayed-type hypersensitivity (DTH) reaction in guinea pigs sensitized to MTB and M. bovis bacille Calmette-Guérin (BCG) vaccine was evaluated.Results. The latency antigens Rv1996, Rv2031c, Rv2032 and Rv2653c and the ESAT-6 protein elicited less reactive DTH skin responses in MTB-sensitized guinea pigs than those resulting from PPD, but elicited no response in BCG-vaccinated guinea pigs. The remaining two latency antigens (DevR and Rv3716c) elicited DTH responses in both groups of animals, as did PPD. The reactivity of PPD in BCG-vaccinated guinea pigs was greater than that of any of the selected skin test reagents. Using stronger concentrations of selected skin test reagents in the patch test led to increased DTH responses that were comparable to those elicited by PPD in guinea pigs sensitized with MTB.Conclusion. Transdermal application of defined purified antigens might be a promising method for LTBI screening.

Rotigotine Transdermal Patch: A Review in Parkinson's Disease.

Rotigotine (Neupro®), a non-ergolinic dopamine agonist (DA), is administered once daily via a transdermal patch (TP) that delivers the drug over a 24-h period. In the EU, the rotigotine TP is approved as monotherapy for the treatment of early Parkinson's disease (PD) and as combination therapy with levodopa throughout the course of the disease. It is also approved for the treatment of PD in numerous other countries, including Australia, the USA, China and Japan. Rotigotine TP effectively improved motor and overall functioning in clinical trials in Caucasian and Asian patients with early PD (as monotherapy) or advanced PD (in combination with levodopa); treatment benefits appeared to be maintained in open-label extensions that followed patients for up to 6years. Rotigotine TP was not consistently non-inferior to ropinirole and pramipexole in studies that included these oral non-ergolinic DAs as active comparators. Rotigotine TP variously improved some non-motor symptoms of PD, in particular sleep disturbances and health-related quality of life (HRQOL), based on findings from individual studies and/or a meta-analysis. Rotigotine TP was generally well tolerated, with an adverse event profile characterized by adverse events typical of dopaminergic stimulation and transdermal patch application. Available for more than a decade, rotigotine TP is a well-established, once-daily DA formulation for use in the short- and longer-term treatment of PD. It offers a convenient alternative when non-oral administration of medication is preferred and may be particularly useful in patients with gastrointestinal disturbances that reduce the suitability of oral medication.

Effect of preoperative application of buprenorphine transdermal patch on analgesic requirement in postoperative period in hip and knee replacement surgeries.

Background and Aims:Although no pain control following hip and knee replacement surgeries has attained gold standard, it is clear that patients should have optimum pain control after total knee arthroplasty and total hip arthroplasty for enhanced satisfaction and function. We conducted this study to evaluate the effect of preoperative application of buprenorphine transdermal patch on analgesic requirement in perioperative period after knee and hip replacement surgeriesMaterial and Methods:Following institutional ethical committee approval and written informed consent, a prospective study was conducted in 50 patients of either gender belonging to ASA1 or ASA2 status, requiring either knee or hip replacement. The patients were assessed in preoperative period, and buprenorphine patch of 10 mg (sustained release of 10 μg/h) was applied either on the chest or on outer side of the arm 12 h before surgery. Total knee arthroplasty/total hip arthroplasty was done under combined spinal epidural blockade. Epidural infusion with 0.125% bupivacaine at a rate of 4–5 mL/h was continued in postoperative period. Intravenous opioid analgesics were avoided in postoperative period, and whenever required only iv paracetamol 1g was given. Outcome in terms of requirement of iv analgesic, visual analog pain score, any associated nausea vomiting, itching, and level of somnolence was noted in postoperative period at 1,2,3,4,8,12,16,20,24,48, and 72 h, respectively.Results:None of the patient required rescue analgesia in the first 2 h. During 72 h postoperative period of observation 32% of patients demanded rescue analgesics at 8th hour, followed by 20% at 4th hour and 16% at 12th hour.Conclusion:Preoperative application of transdermal patch significantly reduces the requirement of postoperative intravenous opioid and nonopioid analgesic drugs.

Converting from Transdermal to Buccal Formulations of Buprenorphine: A Pharmacokinetic Meta-Model Simulation in Healthy Volunteers.

To develop a model to predict buprenorphine plasma concentrations during transition from transdermal to buccal administration. Population pharmacokinetic model-based meta-analysis of published data. A model-based meta-analysis of available buprenorphine pharmacokinetic data in healthy adults, extracted as aggregate (mean) data from published literature, was performed to explore potential conversion from transdermal to buccal buprenorphine. The time course of mean buprenorphine plasma concentrations following application of transdermal patch or buccal film was digitized from available literature, and a meta-model was developed using specific pharmacokinetic parameters (e.g., absorption rate, apparent clearance, and volumes of distribution) derived from analysis of pharmacokinetic data for intravenously, transdermally, and buccally administered buprenorphine. Data from six studies were included in this analysis. The final transdermal absorption model employed a zero-order input rate that was scaled to reflect a nominal patch delivery rate and time after patch application (with decline in rate over time). The transdermal absorption rate constant became zero following patch removal. Buccal absorption was a first-order process with a time lag and bioavailability term. Simulations of conversion from transdermal 20 mcg/h and 10 mcg/h to buccal administration suggest that transition can be made rapidly (beginning 12 hours after patch removal) using the recommended buccal formulation titration increments (75-150 mcg) and schedule (every four days) described in the product labeling. Computer modeling and simulations using a meta-model built from data extracted from publications suggest that rapid and straightforward conversion from transdermal to buccal buprenorphine is feasible.

The role of transdermal buprenorphine in the treatment of chronic pain in elderly patients

Buprenorphine is a synthetic opioid with partially agonist effects on μ (MOR) receptors and slightly less internal activity compared to morphine. Buprenorphine binds with κ1 (KOR 1), κ2 (KOR 2), δ (DOR) receptors and with ORL–1 (orphan–related ligand–1, NOR) receptors. The drug is absorbed after transmucosal (approximately 30–50%) and transdermal (biological bioavailability equals approximately 50%) route of administration due to significant lipophilicity. Buprenorphine concentration in plasma slowly increases after transdermal patch application reaching minimal effective concentrations after approximately 12–24 h and maximal concentrations of the drug in the serum after approximately 60–80 h. The drug is metabolized in the liver, mainly through CYP3A4 to an active metabolite – norbuprenorphine. Both buprenorphine and norbuprenorphine undergo subsequently glucuronidation through conjugates and in this forms are excreted with the bile. The majority of the drug is excreted with the stool in the form of unbound buprenorphine or norbuprenorphine with 10–30% of the drug excreted with the urine. Buprenorphine metabolism causes that the risk of pharmacokinetic drug interactions is low. Moreover, buprenorphine is safe drug in patients with renal impairment. Mild and moderate hepatic impairment do not significantly influence buprenorphine pharmacokinetics. In this paper a review of buprenorphine clinical studies (with randomization and nonrandomized) conducted in elderly patients was undertaken. Buprenorphine administered in patches by the transdermal is frequently used in the treatment of chronic pain in cancer patients and in the course of other diseases. Buprenorphine may be used successfully in the treatment of neuropathic pain. Buprenorphine administered by transdermal route is preferred opioid analgesic in elderly patients with moderate to severe chronic pain due to beneficial pharmacodynamics and pharmacokinetics

Response to: Fentanyl-Norfentanyl Concentrations During Transdermal Patch Application: LC-MS-MS Urine Analysis.

Response to: Fentanyl-Norfentanyl Concentrations During Transdermal Patch Application: LC-MS-MS Urine Analysis.

Fentanyl-Norfentanyl Concentrations During Transdermal Patch Application: LC-MS-MS Urine Analysis.

Poklis and Backer published a survey of the concentrations of fentanyl and norfentanyl that could be expected in urine from patients using Duragesic®, a transdermal fentanyl patch. That study employed a relatively small number of patient data points and analysis by Gas Chromatography/Mass Spectrometry. This work examines a larger population of patient positives for fentanyl and norfentanyl to determine whether more than a decade later the original report remains accurate in predicting the range and median levels of fentanyl and norfentanyl concentrations physicians can expect to see from their patients. Additionally, these data were transformed to develop a model that results in a near Gaussian distribution of urine drug test results. This retrospective approach was developed to transform and normalize urine drug testing results to provide a historical picture of expected patient values for this important analgesic. The resulting near Gaussian distribution is dose independent and as such should be of value to physicians in quickly assessing whether their patient is consistent with this historical population in the broad terms of this model. While this comparison alone is not definitive for adherence with a treatment regimen, together with patient interviews, prescription history and other clinical criteria, it can add an idea of expected patient values from urine drug testing.

Transdermal patches for D-threo-methylphenidate (free base): Formulation aspects and in vivo pharmacokinetics

This study was designed to develop a drug-in-adhesive (DIA) type transdermal drug delivery system (TDDS) for D-threo-methylphenidate (D-threo-MP) that could be further developed for treating Attention-Deficit/Hyperactivity Disorder (ADHD) in children. During initial formulation optimization, three formulation factors, i.e., different adhesives, permeation enhancers and drug loading of D-threo-MP were screened using vertical Franz diffusion cells across newborn pig skin. A patch containing 15% (w/w) D-threo-MP in DURO-TAK®87-4098 was considered as an optimum patch which was selected for in vivo studies. The optimum D-threo-MP patch pharmacokinetic parameters were determined in Sprague Dawley (SD) rats and bama miniature pigs (Sus scrofa domestica) after application of transdermal patches, intravenous (i.v.) injection or oral administration. The absolute bioavailability and the relative bioavailability of D-threo-MP DIA patch in the SD rats model were 53.4% and 218.8%, respectively, and the relative bioavailability was 83.4% in the bama miniature pigs model. In this study, we showed that the optimized D-threo-MP patches could be further developed for treating Attention-Deficit/Hyperactivity Disorder (ADHD) in children.

The Effect of Rivastigmine Transdermal Patch on Sleep Apnea in Patients with Probable Alzheimer's Disease.

Background and PurposeThis study was designed to evaluate the effect on sleep of rivastigmine transdermal patch in patients with probable Alzheimer's disease (AD).MethodsPatients with probable AD underwent a sleep questionnaire, overnight polysomnography and neuropsychological tests before and after rivastigmine transdermal patch treatment. We analyzed the data from enrolled patients with AD.ResultsFourteen patients with probable AD were finally enrolled in this study. The respiratory disturbance index after the rivastigmine patch treatment was improved in patients with probable AD and sleep breathing disorder, compared with that of before treatment (p<0.05).ConclusionsRivastigmine transdermal patch application are expected to improve the symptoms of sleep disordered breathing in patients with probable AD. Further placebo controlled studies are needed to confirm these results.

Interpretation of urine drug testing results in patients using transdermal buprenorphine preparations for the treatment of chronic noncancer pain.

To determine whether the prevailing liquid chromatography and tandem mass spectroscopy assay (LC-MS/MS) assay designed to monitor buprenorphine compliance of the sublingual formulation used in the substance abuse treatment setting can be extrapolated to the transdermal formulation used in the chronic pain treatment setting, which is 1000-fold less concentrated. Retrospective chart review. Self-reported compliant patients using the transdermal or sublingual formulations of buprenorhphine. Transdermal patch application was also visually confirmed during clinic visits. Urine drug test results from a LC-MS/MS were compared between samples from transdermal and sublingual patients. While all sublingual patients tested positive for at least one metabolite of buprenorphine, only 69% of the transdermal patients did so. In addition, the most abundant metabolite in the transdermal patients was buprenorphine-glucuronide, as compared with norbuprenorphine-glucuronide in sublingual patients. These data suggest that currently available urine drug tests for buprenorphine, including the more expensive LC-MS/MS based assays, may not be sufficiently sensitive to detect the metabolites from transdermal buprenorphine patients. This study highlights the need to evaluate the value and sensitivity of urine drug tests given the wide range of buprenorphine dosing in clinical practice. These results underscore the need for additional cost benefit analyses comparing different confirmatory drug testing techniques including many commercially available drug testing options. © 2014 Wiley Periodicals, Inc.

Pharmacokinetic and biodistribution study of eserine and pralidoxime chloride in rabbits following a single application of a transdermal patch.

In the present study, a simple reverse-phase high-performance liquid chromatography method with diode array detection has been developed and validated for the simultaneous determination and quantification of eserine and pralidoxime chloride in rabbit plasma and its application to pharmacokinetic study. The pharmacokinetic study was performed after transdermal application of single patch in rabbits. The plasma levels of both drugs following transdermal application of single patch were maintained for 72h after removal of the patch. The maximal concentrations (C max) of both drugs were significantly reduced while the mean areas under the plasma concentration vs. time moment curve and mean residence times were evidently increased and extended, respectively. A sustained activity was observed over a period of 3days. This sustained activity was due to the controlled release of drug into the systemic circulation following transdermal application. Linear correlation was also observed when fraction of drug permeated was correlated with the fraction of drug absorbed at the same time point. Gamma scintigraphy imaging on rabbit following transdermal patch application was performed to ascertain the localization of drugs in rabbit brain.

Transdermal drug delivery of paroxetine through lipid-vesicular formulation to augment its bioavailability

Paroxetine (PAX) is the most potent serotonin reuptake blocker antidepressant clinically available. This study is aimed to reduce the side effects accompanied with the initial high plasma concentration after oral administration of PAX and fluctuations in plasma levels and also to decrease the broad metabolism of the drug in the liver by developing and optimizing liposomal transdermal formulation of PAX in order to improve its bioavailability. PAX liposomes were prepared by reverse phase evaporation technique using lecithin phosphatidylcholine (LPC), cholesterol (CHOL) and drug in different molar ratios. The prepared liposomes were characterized for size, shape, entrapment efficiency and in vitro drug release. The studies demonstrated successful preparation of PAX liposomes. The effect of using different molar ratios of (LPC:CHOL) on entrapment efficiency and on drug release was studied. Liposomes showed percentage entrapment efficiency (%EE) of 81.22 ± 3.08% for optimized formula (F5) which composed of (LPC:CHOL, 7:7) and 20mg of PAX, with average vesicle size of 220.53 ± 0.757 nm. The selected formula F5 (7:7) was incorporated in gel bases of HPMC-E4M (2%, 4%, and 6%). The selected formula of PAX liposomal gel of HPMC-E4M (2% and 4%) were fabricated in the reservoir type of transdermal patches and evaluated through in vitro release. After that the selected formula of PAX liposomal gel transdermal patch was applied to rabbits for in vivo bioavailability study in comparison with oral administration of the marketed PAX tablet. An HPLC method was developed for the determination of PAX in plasma of rabbits after transdermal patch application and oral administration of the marketed PAX tablets of 20mg dose. The intra- and inter-day accuracy and precision were determined as relative error and relative standard deviation, respectively. The linearity was assessed in the range of 5-200 ng/ml. Pharmacokinetic parameters were determined as the C(max) of PAX liposomal transdermal patch was found to be 92.53 ng/ml at t(max) of 12h and AUC(0-48) was 2305.656 ngh/ml and AUC(0-∞) was 3852.726 ngh/ml, compared to the C(max) of 172.35 ng/ml after oral administration of the marketed PAX tablet with t(max) of 6h and AUC(0-24) was 1206.63 ngh/ml and AUC(0-∞) was 1322.878 ngh/ml. These results indicate improvement of bioavailability of the PAX after liposomal transdermal patch application and sustaining of the therapeutic effects compared to oral administration.

Formulation and in vitro/in vivo correlation of a drug‐in‐adhesive transdermal patch containing azasetron

The aim of the present study was to develop a transdermal drug delivery system for azasetron and evaluate the correlation between in vitro and in vivo release. The effects of different adhesives, permeation enhancers, and loadings of azasetron used in patches on the penetration of azasetron through rabbit skin were investigated using two-chamber diffusion cells in vitro. For in vivo studies, azasetron pharmacokinetic parameters in Bama miniature pigs were determined according to a noncompartment model method after topical application of transdermal patches and intravenous administration of azasetron injections. The best permeation profile was obtained with the formulation containing DURO-TAK 87-9301 as adhesive, 5% of isopropyl myristate as penetration enhancer, and 5% of azasetron. The optimal patch formulation exhibited sustained release profiles in vivo for 216 h. The in vivo absorption curve in Bama miniature pigs obtained by deconvolution approach using WinNonlin® program was correlated well with the in vitro permeation curve of the azasetron patch. These findings indicated that the developed patch for azasetron is promising for the treatment of delayed chemotherapy-induced nausea and vomiting, and the in vitro skin permeation experiments could be useful to predict the in vivo performance of transdermal azasetron patches.

Quantification of Fentanyl in Human Serum by Column-Switching Liquid Chromatography and Tandem Mass Spectrometry

Analytical methods for pharmacokinetic studies with quantification of the highly potent anaesthetic drug fentanyl in serum must be rugged, sensitive, precise and accurate. To address these analytical demands and facilitate an automated approach to sample clean-up, a new method was developed for human serum using back-flush columnswitching and high-performance liquid chromatography/tandem mass spectrometry (LC-MS/MS). Prior to injection, protein precipitation in trichloroacetic acid was performed in each sample. Samples were diluted with internal standard (D5-fentanyl) in 10% (w/v) trichloroacetic acid, kept at 4oC for 20 min and centrifuged followed by injection of 40μL supernatant onto a BioTrap 500 MS extraction column. Using a time programmed six-port valve switch, the extracted drug was back-flushed onto a Zorbax SB-Aq analytical column, gradient eluted and finally detected after electrospray ionisation with multiple reaction monitoring (MRM) of the transitions m/z 337 → m/z 188 and m/z 342 → m/z 188 for fentanyl and D5-fentanyl, respectively. Mean inter-assay accuracy (n=5) ranged from 93 to 101 % and inter-assay precision (n=5) ranged from 3.7 to 9.4% (C.V.). The method was used in a preliminary study of 4 patients after application of transdermal patches and found fully applicable for future pharmacokinetic studies. This is the first on-line, column-switching LC-MS/MS method validated and demonstrated suitable for quantification of fentanyl in human serum.

Evaluation of percutaneous permeation of flurbiprofen and ketoprofen after application of transdermal patches using a lateral sectioning approach in hairless rats

Objectives: The dispositions and pharmacokinetic parameters of non-steroidal anti-inflammatory drugs (NSAIDs) after patch applications have typically been evaluated on a whole-skin basis, and the detailed permeation profiles remain unclear. The aim of this study was to establish a new method for clearly analyzing the flow of drugs in the skin layers and evaluating the drug levels in the target area of the skin tissue.Methods: The skin tissue areas where flurbiprofen and ketoprofen patches were applied were cut into 20 μm-thick lateral slices from the surface to the deepest layer and the drug concentrations in the slices were measured.Results: The results revealed the presence of depth-dependent concentration gradients from the surface to the deep layer and that the drug concentration in the deepest layer was less than one tenth of the surface concentration for both flurbiprofen and ketoprofen. In addition, flurbiprofen yielded higher and more rapid concentrations in the deepest skin layer adjacent to the intramuscular tissue.Conclusions: The present data suggest that our technique involving lateral slicing of skin tissues and measurement of drug concentrations allows visual understanding of drug dispositions in the skin layers and makes it possible to evaluate the drug levels in the target area of the skin tissue.

Safety Concerns Involving Transdermal Patches and Magnetic Resonance Imaging (MRI)

Transdermal drug delivery systems have become more prevalent since their initial introduction in the 1980s. Recently, safety concerns have arisen regarding the continued application of transdermal patches during magnetic resonance imaging (MRI) procedures. Case reports have revealed that serious burns may occur in patients undergoing MRI who have transdermal patches with metallic content applied to their skin. The metallic component of these patches acts as a conductor for the radiofrequency pulses of the MRI, inducing an electric current and thereby resulting in intense heat and burns. Currently, over 20 brand and generic transdermal drug delivery systems are available. Not all available patches contain metallic components that necessitate removal prior to MRI. This review provides information related to the metallic content of available transdermal patches and also provides recommendations regarding reapplication of transdermal therapy after a scan. Health care professionals should be aware that published information regarding transdermal therapy and risk of burns appears to vary from source to source as the primary reference for such information is verbal communication with manufacturers. Given this issue, it may be often easier to err on the side of caution and remove the patch prior to MRI.