Patch Adhesion Research Articles

Pain relief associated with decreased oxyhemoglobin level in left dorsolateral prefrontal cortex.

Pain in the elbow, shoulder, knee, lower back, and various other joints is relieved by adhesion of pyramidal thorn patches. To elucidate the pain relief mechanism induced by the patches, we established a quantitative method for estimating the pain reduction and investigated the brain regions that change in association with pain relief. We first attempted to quantify the pain relief using transcutaneous electric stimulation (TCES) and a visual analog scale (VAS), and then applied near-infrared spectroscopy (NIRS) to the prefrontal cortex, including the dorsolateral prefrontal cortex (DLPFC) and the orbitofrontal cortex (OFC). We also examined the salivary oxytocin levels, which are thought to reflect oxytocin secretion levels from the posterior pituitary in the brain. Application of pyramidal thorn patches to pain regions decreased the pain degree estimated using TCES and VAS. Oxyhemoglobin levels were likely to be decreased in the left DLPFC on the basis of NIRS measurements during patch treatment, suggesting that the left DLPFC is involved in pain relief. On the other hand, the salivary oxytocin levels varied widely. A potential reason for the varying salivary oxytocin levels is its utilization in the pain region as an analgesic agent. Our results suggest that the left DLPFC will become a target brain region for pain therapy.

Stretchable and Bioadhesive Gelatin Methacryloyl-Based Hydrogels Enabled by in Situ Dopamine Polymerization.

Hydrogel patches with high toughness, stretchability, and adhesive properties are critical to healthcare applications including wound dressings and wearable devices. Gelatin methacryloyl (GelMA) provides a highly biocompatible and accessible hydrogel platform. However, low tissue adhesion and poor mechanical properties of cross-linked GelMA patches (i.e., brittleness and low stretchability) have been major obstacles to their application for sealing and repair of wounds. Here, we show that adding dopamine (DA) moieties in larger quantities than those of conjugated counterparts to the GelMA prepolymer solution followed by alkaline DA oxidation could result in robust mechanical and adhesive properties in GelMA-based hydrogels. In this way, cross-linked patches with ∼140% stretchability and ∼19 000 J/m3 toughness, which correspond to ∼5.7 and ∼3.3× improvement, respectively, compared to that of GelMA controls, were obtained. The DA oxidization in the prepolymer solution was found to play an important role in activating adhesive properties of cross-linked GelMA patches (∼4.0 and ∼6.9× increase in adhesion force under tensile and shear modes, respectively) due to the presence of reactive oxidized quinone species. We further conducted a parametric study on the factors such as UV light parameters, the photoinitiator type (i.e., lithium phenyl-2,4,6-trimethylbenzoylphosphinate, LAP, versus 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone, Irgacure 2959), and alkaline DA oxidation to tune the cross-linking density and thereby hydrogel compliance for better adhesive properties. The superior adhesion performance of the resulting hydrogel along with in vitro cytocompatibility demonstrated its potential for use in skin-attachable substrates.

Towards the advance of a novel iontophoretic patch for needle-free buccal anesthesia

The aim of this work was to develop a mucoadhesive iontophoretic patch for anesthetic delivery in the buccal epithelium. The patch was comprised of three different layers, namely i) drug release (0.64 cm2); ii) mucoadhesive (1.13 cm2); and iii) backing (1.13 cm2). Prilocaine and lidocaine hydrochlorides were used as model drugs (1:1 ratio, 12.5 mg per unit). An anode electrode (0.5 cm2 spiral silver wire) was placed in between the drug release and mucoadhesive/backing layers to enable iontophoresis. Surface microscopy; mechanical and in vitro mucoadhesive properties; drug release kinetics and mechanism; and drug permeation through the porcine esophageal epithelium were assessed. Topographic analysis evidenced differences in the physical structures for the several layers. All layers presented suitable handling properties i.e., flexibility, elasticity and resistance. Both the release and mucoadhesive layers presented features of a soft and tough material, while the backing layer matched the characteristics of a hard and brittle material. A synergy between the drug release and mucoadhesive layers on the mucoadhesive force and work of adhesion of the tri-layered patch was observed. Passive drug release of both drugs fitted to First-order, Hixson-Crowell and Weibull kinetic models; and the release mechanism was attributed to anomalous transport. Iontophoresis remarkably enhanced the permeation of both drugs, but mainly prilocaine through the mucosa as evidenced by the permeability coefficient parameter (3.0-fold). The amount of these amino amide salts retained in the mucosa were also equally enhanced (4.7-fold), while the application of a tiny constant electric current (1 mA·cm−2·h−1) significantly decreased the lag time for lidocaine permeation by about 45%. In view of possible in vitro / in vivo correlations, the buccal iontophoretic patch displays a promising strategy for needle-free and patient-friendly local anesthesia in dentistry.

Non-invasive electrical cardiometry cardiac output monitoring during prehospital helicopter emergency medical care: a feasibility study

PurposeIntroducing advanced hemodynamic monitoring might be beneficial during Helicopter Emergency Medical Service (HEMS) care. However, it should not increase the on-scene-time, it should be easy to use and should be non-invasive. The goal of this study was to investigate the feasibility of non-invasive cardiac output measurements by electrical cardiometry (EC) and the quality of the EC signal during pre-hospital care provided by our HEMS.MethodsA convenience sample of fifty patients who required HEMS assistance were included in this study. Problems with respect to connecting the patient, entering patient characteristics and measuring were inventoried. Quality of EC signal of the measurements was assessed during prehospital helicopter care. We recorded the number of measurements with a signal quality indicator (SQI) ≥ 80 and the number of patients having at least 1 measurement with a SQI ≥ 80. Furthermore, the SQI value distribution of the measurements within each patient was analysed.ResultsIn the experience of the attending HEMS caregivers application of the device was easy and did not result in increased duration of on-scene time. Patch adhesion was reported as a concern due to clammy skin in 22% of all cases. 684 measurements were recorded during HEMS care. In 47 (94%) patients at least 1 measurement with an SQI ≥ 80 was registered. Of all recorded measurements 5.8% had an SQI < 40, 11.4% had an SQI 40–59, 14.9% had a SQI between 60 and 79 and 67.8% had SQI ≥ 80.ConclusionCardiac output measurements are feasible during prehospital HEMS care with good quality of the EC signal. Monitoring was easy to use and quick to install. In our view it is an promising candidate for the prehospital setting. Further research is needed to determine its clinical value during clinical decision making.

Topical 5% lidocaine patches for treating postherpetic neuralgia: a survey among nurses and patients

Introduction: Postherpetic neuralgia (PHN) is associated with moderate to severe pain with peripheral and central mechanisms. While there is no clear-cut first-line therapeutic approach to PHN pain control, lidocaine patches are frequently used as monotherapy or part of a multimodal pain regimen. Methods: An online survey, the first of its kind, was conducted among PHN patients (n = 153) and nurses (n = 151) in order to determine clinical and patient knowledge, attitudes and practices toward the lidocaine patch and current unmet needs. Results: Results of the survey indicated that PHN patients are prescribed a mean of 2.6 medications to control their PHN pain, including the lidocaine patch. There were negative responses related to the patches’ ability to adhere to the skin. Patients reported the use of tape to hold the patches in place and/or patches that detached completely, truncating the therapeutic dose period. Most nurses (53%) found the biggest obstacle to PHN pain control was noncompliance and 98% stated that reliable patch adhesion for the intended 12-hour application was “somewhat important” or “very important” for PHN pain control. Forty-five percent of nurses said that poor patient adherence to PHN analgesic regimens was related to poor adhesion of the lidocaine patch. Conclusion: A new bioequivalent lidocaine patch has been developed with better adhesive characteristics, nine-fold greater bioavailability, and improved form factor.

Characteristics of Analgesic Patch Formulations.

Topical and transdermal formulations are a common means of pharmaceutical drug delivery. If a drug is able to penetrate transcutaneously, the skin is an ideal site for the delivery of medications for both local (topical) and systemic (transdermal) effects. The administration of analgesics through the skin poses several potential advantages to those administered orally including compliance, the ability to deliver a drug to a peripheral target site and more stable and sustained plasma levels. One method of drug delivery is with the use of patch formulations – also known as patch systems. Typically, transdermal patches deliver medications intended to reach the systemic circulation, whereas topical patches are designed to keep medication localized for targeted delivery in proximity to the application site. There are a variety of technologies and materials utilized in patches, as well as penetration and formulation enhancers that ultimately affect the performance, efficacy and safety of the patch system. The degree of adherence to the skin is also of critical importance in drug delivery. Patches that lift up or fall off before the prescribed time period may represent a therapeutic failure and must be replaced, increasing patch utilization and cost to the healthcare system or to the patient. The added risk from accidental exposure makes poor patch adhesion a safety issue as well. A variety of analgesics are currently available as patch formulations including local anesthetics, capsaicin, nonsteroidal anti-inflammatory drugs and opioids. This review will highlight each of those patch delivery systems and introduce newer patch technologies that lend towards improved adhesion and compliance. Understanding the designs, limitations and benefits of patch systems will allow clinicians to select between these therapies when appropriate for their patients.

Comparison of a transdermal contraceptive patch with a newly sourced adhesive component versus EVRA patch: A double-blind, randomized, bioequivalence and adhesion study in healthy women

ObjectiveTo evaluate the bioequivalence of norelgestromin and ethinyl estradiol (NGMN-EE) and adhesion of a transdermal contraceptive patch containing a newly sourced adhesive component (test) compared with the marketed (reference) patch. Study designIn this randomized, double-blind, 2-way crossover study, healthy women received single 7-day application of both test and reference patches. Treatment phase included two treatment periods of 11 days each separated by a 21-day washout period starting from day of patch removal (day 8) of treatment period 1. Assessments included NGMN and EE pharmacokinetics (PK), adhesion using European Medicines Agency (EMA) 5-point scale, irritation potential and application-site reactions, and safety. Patches were bioequivalent if 90% CIs of ratios of means of test/reference for AUC168h, AUCinf, and Css fell within 80–125%. Patch adhesion was comparable if ratios of mean cumulative adhesion percentage values of test/reference were ≥90.0%. ResultsSeventy women were randomized; 57 completed both treatments with ≥80% adhesion (score 0–1). Bioequivalence of test and reference patches was demonstrated as 90% CI of ratio of geometric means for AUC168h, AUCinf, and Css for NGMN and EE fell within 80–125%. Both patches had similar adhesion properties (geometric mean ratio was 100.3% [90% CI, 93.2–107.9]). Similar rates of mild-to-moderate itching (11% vs 10%) and erythema events (79% vs 74%) were reported for test and reference patches, respectively, on day 8. ConclusionsThe test patch with the newly sourced adhesive component is bioequivalent to the currently marketed NGMN-EE transdermal patch and has similar adhesion and irritation potential. Implications statementThe norelgestromin and ethinyl estradiol transdermal patch containing a newly sourced adhesive component is bioequivalent to the currently marketed patch for both active moieties. Both patches had similar adhesion, irritation potential, and safety profiles.

Autonomous and Reversible Adhesion using Elastomeric Suction Cups for In-vivo Medical Treatments

Remotely controllable and reversible adhesion is highly desirable for surgical operations: it can provide the possibility of non-invasive surgery, flexibility in fixing a patch and surgical manipulation via sticking. In our previous work, we developed a remotely controllable, ingestible, and deployable pill for use as a patch in the human stomach. In this study, we focus on magnetically facilitated reversible adhesion and develop a suction-based adhesive mechanism as a solution for non-invasive and autonomous adhesion of patches. We present the design, model, and fabrication of a magnet-embedded elastomeric suction cup. The suction cup can be localised, navigated, and activated or deactivated in an autonomous way; all realised magnetically with a pre-programmed fashion. The use of the adhesion mechanism is demonstrated for anchoring and carrying, for patching an internal organ surface and for an object removal, respectively.

Improvement of the Layer Adhesion of Composite Cardiac Patches

The major purpose of cardiac patches is to deliver healthy cells to infarcted tissues. Such cardiac patches must fulfill specific mechanical as well as chemical requirements. Herein, bi‐component cardiac patches are investigated with regard to their layer adhesion. Combinations of salt‐leached porous poly (glycerol sebacate) (PGS) films with a layer of electrospun‐gelatin fibers are produced. Gelatin fibers are fabricated by solution electrospinning using 20 wt% gelatin in 98 v% formic acid. Fibers are attached to PGS films either via direct electrospinning on top of the film or via combining as spun fiber mats with PGS using gelatin as glue. Scanning electron microscopy (SEM) images show that fiber mats adapt to the rough surface of the porous PGS film. In contrast, fibers spun directly onto films show poor adhesion and only a few fibers are attached to the PGS substrate. Fourier transform infrared (FTIR) analysis, contact‐angle measurements, and pull‐off adhesion tests of the bi‐component patches confirm these results. Modified pull‐off adhesion tests of the two layers show that combining as spun gelatin fiber mats with porous PGS substrates by gluing leads to excellent material adhesion before and after incubation for up to 14 days.

Dissolving Microneedle Systems for the Oral Mucosal Delivery of Triamcinolone Acetonide to Treat Aphthous Stomatitis

A microneedle (MN) oral mucosal patch system was prepared to increase its adhesive strength, to improve the delivery of triamcinolone acetonide (TA) into the mucosa, and to protect the adhesive layer from mouth movement and saliva. The MN oral mucosal patch system consists of an adhesive layer containing TA and a backing layer. The adhesive layer consists of a base with a thickness of 50 μm, 300 μm long MNs, and 18% TA. After patches were attached to the tape-stripped porcine skin for a predetermined period of time, the adhesion of the patches was observed. TA was extracted from the skin, and the amount of TA was measured using high-performance chromatography. When the adhesive layer was applied for 10 s, the adhesive strength was 1.69 N mm/cm2 with microneedles and 0.41 N mm/cm2 without microneedles. An oral mucosal patch with MNs (TA MN-AL) delivered 42% more TA into the skin than an oral mucosal patch without MNs (TA AL). Also, as attachment time increased, the amount of TA delivered was significantly greater using a TA MN-AL compared to a TA AL. The addition of MNs can increase the adhesion of the oral mucosal patch to the mucosa and thus improve the efficiency of drug delivery.

Automatic Patch Adhesion Testing using Arduino

In order to study and evaluate the suitability method of predicting the long term adhesion properties of patches to human skin is the biggest challenges in the medical sectors. adhesion to the skin is strictly linked to the efficiently and safety of the therapeutic treatment, now-a- days numerous report of in vivo adhesion lacking are still addressed to regulatory agencies. In real time health care system involving human skin an adhesion patch need to be integrated into diagnostic device. In medical field it is efficient to provide a patch adhesive capacity. Our motive is to develop the patch adhesion tester to determine adhesiveness of the patch. When the patch is given to the proposed tester then the measured values of the given patch will be displayed.

Patient Experiences With Handling of Analgesic Transdermal Patches and Challenges in Correct Drug Administration: A Pilot Study on Patient Education.

Although problems during transdermal patch administration are primarily caused by insufficient knowledge, patient education programs are lacking. We compared patient education by a clinical pharmacist on knowledge on correct patch administration with routine counseling during patient-physician consultation in a pilot study. After baseline assessment of knowledge and difficulties with patch administration, patients in the outpatient pain clinic of Heidelberg University Hospital were allocated to intervention (n = 12) or control group (n = 11). In both groups, identical information leaflets on transdermal patch use were dispensed. Intervention patients additionally received verbal counseling on correct patch administration by a clinical pharmacist. After 4 weeks, patients were called for a follow-up assessment on knowledge and perspective on administration difficulties. Patients reported several difficulties with transdermal patch administration, such as local skin reaction, difficulties with opening the packaging, and poor adhesion. Although patient education increased the ratio of correct answers in the intervention group twice as much than in the control group, overall knowledge was comparable between groups after education (P = 0.602). Patients encountered numerous problems with transdermal patch administration although on long-term use. Patient education can improve knowledge on correct patch administration. However, the pilot study demonstrated the need for further efforts to improve ease of use of transdermal patch, such as patch adhesion.

A systematic approach to the formulation of anti-onychomycotic nail patches

Nail patches have a potential role as drug carriers for the topical treatment of nail diseases such as onychomycosis, a common condition. Our aim was therefore to develop a systematic and novel approach to the formulation of a simple drug-in-adhesive ungual patch. Twelve pressure-sensitive adhesives (PSAs), four backing membranes, two release liners and three drugs were screened for pharmaceutical and mechanical properties. From this initial screening, two PSAs, two drugs, one backing membrane and one release liner were selected for further investigation. Patches were prepared by solvent-casting and characterised. The patches had good uniformity of thickness and of drug content, and showed minimal drug crystallisation during six months of storage. Meanwhile, the drug stability in the patch upon storage and patch adhesion to the nail was influenced by the nature of the drug, the PSA and the backing membrane. The reported methodology paves the way for a systematic formulation of ungual nail patches to add to the armamentarium of nail medicines. Further, from this work, the best patch formulation has been identified.

Matrix adhesive system containing plant extract

This work refers formulation of transdermal drug delivery system containing extract from Rhodiola rosea. A polymer matrix controls the rate at which the drug contained in the patch reservoir can pass through the skin into bloodstream. Transdermal patches are useful in developing new applications for existing therapeutics and reducing first-pass effect. Qualitative properties, e.g., patch adhesion or dissolution of drug, are important by formulation of the system influencing the bioavailability. Based on tested parameters, the most promising formulations were matrix systems containing two different combinations: gelatine with chitosan or pectin with polyethylene oxide. These two selected matrix systems will be further evaluated to study the drug permeation.

Elastic Properties of Pore-Spanning Apical Cell Membranes Derived from MDCK II Cells

The mechanical response of adherent, polarized cells to indentation is frequently attributed to the presence of an endogenous actin cortex attached to the inner leaflet of the plasma membrane. Here, we scrutinized the elastic properties of apical membranes separated from living cells and attached to a porous mesh in the absence of intracellular factors originating from the cytosol, organelles, the substrate, neighbors, and the nucleus. We found that a tension-based model describes the data very well providing essentially the prestress of the shell generated by adhesion of the apical membrane patches to the pore rim and the apparent area compressibility modulus, an intrinsic elastic modulus modulated by the surface excess stored in membrane reservoirs. Removal of membrane-associated proteins by proteases decreases the area compressibility modulus, whereas fixation and cross-linking of proteins with glutaraldehyde increases it.

The silencing effect of miR-30a on ITGA4 gene expression in vitro: an approach for gene therapy.

Integrins are adhesion molecules which play crucial roles in cell-cell and cell-extracellular matrix interactions. Very late antigen-4 or α4β1 and lymphocyte Peyer’s patch adhesion molecule-1 or α4β7, are key factors in the invasion of tumor cells and metastasis. Based on the previous reports, integrin α4 (ITGA4) is overexpressed in some immune disorders and cancers. Thus, inhibition of ITGA4 could be a therapeutic strategy. In the present study, miR-30a was selected in order to suppress ITGA4 expression. The ITGA4 3' UTR was amplified, cloned in the Z2827-M67-(ITGA4) plasmid and named as Z2827-M67/3'UTR. HeLa cells were divided into five groups; (1) untreated without any transfection, (2) mock with Z2827-M67/3'UTR transfection and X-tremeGENE reagent, (3) negative control with Z2827-M67/3'UTR transfection alone, (4) test with miR-30a mimic and Z2827-M67/3'UTR transfection and (5) scramble with miR-30a scramble and Z2827-M67/3'UTR transfection. The MTT assay was performed to evaluate cell survival and cytotoxicity in each group. Real-time RT-PCR was applied for the ITGA4 expression analysis. The findings of this study showed that miR-30a downregulated ITGA4 expression and had no effect on the cell survival. Due to the silencing effect of miR-30a on the ITGA4 gene expression, this agent could be considered as a potential tool for cancer and immune disorders therapy.

Poor adhesion of fentanyl transdermal patches may mimic end-of-dosage failure after 48 hours and prompt early patch replacement in hospitalized cancer pain patients.

ContextRenewal of fentanyl transdermal patch (transdermal therapeutic system [TTS]) should occur every 3 days (72 hours) according to manufacturer’s guidelines. Some studies mentioned patients reporting end-of-dose failure, and thus, some authors recommend shortening the interval of application to 2 days (48 hours). However, reasons for early replacement are mostly unknown.ObjectivesThe objectives of this study were to assess the prevalence of early replacement of fentanyl TTS in a cancer center in Basel, Switzerland, and to assess the reasons for early replacement in stationary patients.MethodsWe retrieved all fentanyl TTS administered in a cancer center in Basel, Switzerland, between November 11, 2011, and January 31, 2015, from the electronic medical database.ResultsA total of 739 patients (mean age 71.4±11.5 years, 55% women) were administered 2,250 fentanyl TTS (dosage 6–500 µg/hour). Most replacements occurred after 72 hours (61.6%) and a few after 48 hours (7.4%). Patients with early replacement after 48 hours were significantly younger (63.8 years versus 71.5 years, p<0.001) and obtained higher mean dosages of fentanyl TTS (89 µg/hour versus 44.1 µg/hour, p<0.001) and rescue medication (calculated as oral morphine equivalent in milligrams: 185.1 mg versus 39.6 mg during the first 24 hours after replacement, p<0.001). No pharmacological rationale for early replacement was observed. According to 57 physicians, nurses, and pharmacists, the most often reasons for early TTS replacement were end-of-dosage pain (41.4%) and poor adhesion (31.4%).ConclusionIn the absence of any physiological, pharmacological, or environmental reasons recorded in the database to explain an early replacement of fentanyl TTS, skin adhesion problems may point practical reasons and mimic end-of-dosage failure.

Energy of Liposome Patch Adhesion to the Pipet Glass Determined by Confocal Fluorescence Microscopy.

The formation of the gigaseal in the patch clamp technique is dependent on the adhesion between the cell or liposome membrane and the glass pipet. The adhesion results in a capillary force causing creep of the patch membrane up the pipet. The membrane can be immobilized by counteracting the capillary force by positive pressure applied to the patch pipet. We use this phenomenon to develop a method for static measurement of the adhesion free energy of the lipid bilayer to the glass. Confocal fluorescent microscopy is used to track the bilayer creep inside the pipet and measure the immobilization pressure at various salt concentrations and pH. The adhesion energy is simply related to this pressure. For the studied phospholipid bilayers, its values were in the 0.3-0.7 mJ/m2 range, increased with salt concentration, and had a maximum as a function of pH. This method offers a way to measure bilayer-glass adhesion energy in patch clamp experiments that is more precise than dynamic methods.

Role of Pressure-Sensitive Adhesives in Transdermal Drug Delivery Systems

Transdermal drug delivery systems (TDDS) are employed for the delivery of drugs across skin into the systemic circulation. Pressure-sensitive adhesive (PSA) is one of the most critical components used in a TDDS. The primary function of PSA is to help in adhesion of patch to skin, but more importantly it acts as a matrix for the drug and other excipients. Hence, apart from adhesion of the patch, PSA also affects other critical quality attributes of the TDDS such as drug delivery, flux through skin and physical and chemical stability of the finished product. This review article provides a summary of the adhesives used in various types of TDDS. In particular, this review will cover the design types of TDDS, categories of PSAs and their evaluation and regulatory aspects.

Comparison of adhesion and dissolution of fentanyl patches: Fentadur® and Durogesic DTrans®

Fentanyl is a potent opioid used as an analgesic for pain therapy. Fentanyl patches have been developed using patch design technologies that use the transdermal route. The aim of this study was to compare the adhesion and dissolution properties of two fentanyl patches, Fentadur® (Pfizer Inc., USA) and Durogesic DTrans® (Janssen-Cilag, Inc., USA), which were designed as a reservoir and a matrix, respectively. For the characterization of fentanyl patches, a 180° peel adhesion test and a dissolution test were performed at 12 and 100 μg/h of fentanyl patches. Specifically, the dissolution of fentanyl patches was tested at 32 and 40 °C using the USP apparatus 6 and the released fentanyl was analyzed using LC–MS/MS. Fentadur® and Durogesic DTrans® had acceptable adhesion forces over 150 gf using 12 mm of fentanyl patches. Comparing adhesion forces of Fentadur® and Durogesic DTrans®, Fentadur® had lower adhesion force values than Durogesic DTrans®. The release of fentanyl in Fentadur® was lower than that in Durogesic DTrans®, except for 100 μg/h Fentadur® at 40 °C over 12–48 h. The results show that Fentadur® and Durogesic DTrans® had the different properties of adhesion and dissolution, which could be critical factors for the prediction of clinical use.