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Sample records for method transdermal experiments

  1. TRANSDERMAL DRUG DELIVERY AND METHODS TO ENHANCE IT

    Directory of Open Access Journals (Sweden)

    E. G. Kuznetsova

    2016-01-01

    Full Text Available The paper presents the common methods employed in recent years for enhancing transdermal delivery of drug substances when applying transdermal therapeutic delivery systems. The chemical, physical and mechanical methods to enhance the transport of macromolecular compounds through the skin are considered in details. 

  2. A New Drug Release Method in Early Development of Transdermal Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Bing Cai

    2012-01-01

    Full Text Available In vitro drug release tests are a widely used tool to measure the variance between transdermal product performances and required by many authorities. However, the result cannot provide a good estimation of the in vivo drug release. In the present work, a new method for measuring drug release from patches has been explored and compared with the conventional USP apparatus 2 and 5 methods. Durogesic patches, here used as a model patch, were placed on synthetic skin simulator and three moisture levels (29, 57, 198 μL cm−2 were evaluated. The synthetic skin simulators were collected after 1, 2, 3, 4, 6, and 24 hours and extracted with pH 1.0 hydrochloric acid solution. The drug concentrations in the extractions were measured by isocratic reverse phase high-pressure liquid chromatography. The results showed that, with the increasing moisture level on the synthetic skin simulator, the drug release rate increased. In comparison with the conventional USP method, the drug release results performed by the new method were in more correlation to the release rate claimed in the product label. This new method could help to differentiate the drug release rates among assorted formulations of transdermal drug delivery systems in the early stage of development.

  3. Encapsulated Curcumin for Transdermal Administration

    African Journals Online (AJOL)

    Purpose: To develop a proniosomal carrier system of curcumin for transdermal delivery. Methods: Proniosomes of curcumin were prepared by encapsulation of the drug in a mixture of Span 80, cholesterol and diethyl ether by ether injection method, and then investigated as a transdermal drug delivery system (TDDS).

  4. "INTRODUCING A FULL VALIDATED ANALYTICAL PROCEDURE AS AN OFFICIAL COMPENDIAL METHOD FOR FENTANYL TRANSDERMAL PATCHES"

    Directory of Open Access Journals (Sweden)

    Amir Mehdizadeh

    2005-04-01

    Full Text Available A simple, sensitive and specific HPLC method and also a simple and fast extraction procedure were developed for quantitative analysis of fentanyl transdermal patches. Chloroform, methanol and ethanol were used as extracting solvents with recovery percent of 92.1, 94.3 and 99.4% respectively. Fentanyl was extracted with ethanol and the eluted fentanyl through the C18 column was monitored by UV detection at 230 nm. The linearity was at the range of 0.5-10 µg/mL with correlation coefficient (r2 of 0.9992. Both intra and inter-day accuracy and precision were within acceptable limits. The detection limit (DL and quantitation limit (QL were 0.15 and 0.5 µg/mL, respectively. Other validation characteristics such as selectivity, robustness and ruggedness were evaluated. Following method validation, a system suitability test (SST including capacity factor (k´, plate number (N, tailing factor (T, and RSD was defined for routine test.

  5. Transdermal granisetron.

    Science.gov (United States)

    Duggan, Sean T; Curran, Monique P

    2009-01-01

    Granisetron is a highly selective serotonin 5-HT(3) receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting. The transdermal granisetron system delivers continuous granisetron (3.1 mg/day) into the systemic circulation (via passive diffusion) for up to 7 days. In a large phase III trial in cancer patients receiving multi-day (3-5 days) moderately or highly emetogenic chemotherapy, transdermal granisetron applied 24-48 hours prior to chemotherapy and remaining in place for 7 days was noninferior to oral granisetron 2 mg once daily administered for 3-5 days 1 hour prior to chemotherapy. Efficacy was assessed according to the proportion of patients achieving complete response (no vomiting and/or retching, no more than mild nausea, no rescue medication) from the first day, until 24 hours after the start of the last day, of administration of the chemotherapy regimen. In a phase II trial in patients with cancer receiving single-day, moderately-emetogenic chemotherapy, transdermal granisetron applied at least 24 hours prior to chemotherapy and removed after 5 days was as effective as a single oral dose of granisetron 2 mg in achieving total control (no nausea, no vomiting/retching, no use of rescue medication and no study withdrawal) during the delayed (24-120 hours; primary endpoint) period after chemotherapy. Transdermal granisetron was generally well tolerated in clinical trials, with few adverse events being treatment related.

  6. Promotion of the transdermal delivery of protein drugs by N-trimethyl chitosan nanoparticles combined with polypropylene electret.

    Science.gov (United States)

    Tu, Ye; Wang, Xinxia; Lu, Ying; Zhang, He; Yu, Yuan; Chen, Yan; Liu, Junjie; Sun, Zhiguo; Cui, Lili; Gao, Jing; Zhong, Yanqiang

    We recently reported that electret, which was prepared by a corona charging system with polypropylene film, could enhance the transdermal delivery of several drugs of low molecular weight. The aim of this study was to investigate whether electret could enhance the transdermal delivery of protein drugs by N -trimethyl chitosan nanoparticles (TMC NPs) prepared by an ionic gelation method. A series of experiments were performed, including in vitro skin permeation assays and anti-inflammatory effects, to evaluate the transdermal delivery of protein drugs by TMC NPs in the presence of electret. The results showed that in the presence of electret, the transdermal delivery of protein drugs in TMC NPs was significantly enhanced, as demonstrated by in vitro permeation studies and confocal laser scanning microscopy. Notably, superoxide dismutase-loaded TMC NPs combined with electret exhibited the best inhibitory effect on the edema of the mouse ear. TMC NPs combined with electret represent a novel platform for the transdermal delivery of protein drugs.

  7. From high doses of oral rivastigmine to transdermal rivastigmine patches: user experience and satisfaction among caregivers of patients with mild to moderate Alzheimer disease.

    Science.gov (United States)

    Reñé, R; Ricart, J; Hernández, B

    2014-03-01

    Rivastigmine, a treatment for mild to moderate Alzheimer disease (AD), is the first cholinesterase inhibitor to be available in the transdermal format. We aim to describe user experience and satisfaction with the rivastigmine patch, as well as any clinical changes perceived in patients. Observational, cross-sectional, multicentre study with 239 investigators and 1851 informal caregivers of patients with mild to moderate AD. Patients were treated with transdermal rivastigmine patches for ≥ 6 months and had previously received high doses of oral rivastigmine. Mean caregiver age was 59.8±14.4 years and 70.9% were women. They spent 10.0±7.1hours per day providing care and 79.8% lived with the patient. Patch instructions were described as easy to follow by 97.1% of the caregivers and 92.1% of them rated patch application as easy or very easy. The most commonly cited disadvantage was adhesion problems (26.8%). Discontinuation of treatment was due to cutaneous reactions in most cases. Overall, 76.5% of the caregivers were satisfied or very satisfied with transdermal treatment and 77.4% considered that its interference with daily activities was minimal or null. The patch was preferred to oral treatment by 94.3% of caregivers. Clinical Global Impression of Change ratings improved according to 61.3% of the caregivers and 53% of the investigators. Few caregivers reported medication forgetfulness. Most caregivers of patients with mild to moderate AD preferred the transdermal format of rivastigmine to the oral format. Caregivers also reported overall satisfaction, ease of use, and reduced impact on daily activities for transdermal rivastigmine format, in addition to patient improvement compared to their condition under the previous treatment. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  8. Challenges and opportunities in dermal/transdermal delivery

    OpenAIRE

    Paudel, Kalpana S; Milewski, Mikolaj; Swadley, Courtney L; Brogden, Nicole K; Ghosh, Priyanka; Stinchcomb, Audra L

    2010-01-01

    Transdermal drug delivery is an exciting and challenging area. There are numerous transdermal delivery systems currently available on the market. However, the transdermal market still remains limited to a narrow range of drugs. Further advances in transdermal delivery depend on the ability to overcome the challenges faced regarding the permeation and skin irritation of the drug molecules. Emergence of novel techniques for skin permeation enhancement and development of methods to lessen skin i...

  9. Chemical Penetration Enhancers for Transdermal Drug Delivery ...

    African Journals Online (AJOL)

    for transdermal administration. The permeation of drug through skin can be enhanced by both chemical penetration enhancement and physical methods. In this review, we have discussed the chemical penetration enhancement technology for transdermal drug delivery as well as the probable mechanisms of action.

  10. [Matrix transdermal systems for caffeine delivery based on polymer and emulsion compounds].

    Science.gov (United States)

    Kuznetsova, E G; Kuryleva, O M; Salomatina, L A; Sevast'ianov, V I

    2008-01-01

    The goal of this work was to develop and test transdermal therapeutic systems for caffeine delivery. In vitro experiments showed that the rate of caffeine diffusion through untreated rabbit skin from a transdermal therapeutic systems based on polymer compound containing 50 mg medicine was 67.2 (9.1 microg/cm2h; for a system based on emulsion compound it was 173 (19 microg/cm2h. Methods for studying the caffeine release rate and quantitative measurement of caffeine content in the emulsion-based transdermal therapeutic system were developed. These methods are required to obtain data for standard drug documentation. The results of in vivo experiments in rabbits showed the absence of irritating effect of the emulsion-based transdermal therapeutic system. The obtained data on the specific efficiency of the transdermal therapeutic systems for caffeine delivery (50 mg) in healthy volunteers showed that this medicine could be used as a nonnarcotic psychoactivator for improving mental and physical activities and attention concentration.

  11. A Transdermal Measurement Platform Based on Microfluidics

    Directory of Open Access Journals (Sweden)

    Wen-Ying Huang

    2017-01-01

    Full Text Available The Franz diffusion cell is one of the most widely used devices to evaluate transdermal drug delivery. However, this static and nonflowing system has some limitations, such as a relatively large solution volume and skin area and the development of gas bubbles during sampling. To overcome these disadvantages, this study provides a proof of concept for miniaturizing models of transdermal delivery by using a microfluidic chip combined with a diffusion cell. The proposed diffusion microchip system requires only 80 μL of sample solution and provides flow circulation. Two model compounds, Coomassie Brilliant Blue G-250 and potassium ferricyanide, were successfully tested for transdermal delivery experiments. The diffusion rate is high for a high sample concentration or a large membrane pore size. The developed diffusion microchip system, which is feasible, can be applied for transdermal measurement in the future.

  12. Challenges and opportunities in dermal/transdermal delivery

    Science.gov (United States)

    Paudel, Kalpana S; Milewski, Mikolaj; Swadley, Courtney L; Brogden, Nicole K; Ghosh, Priyanka; Stinchcomb, Audra L

    2010-01-01

    Transdermal drug delivery is an exciting and challenging area. There are numerous transdermal delivery systems currently available on the market. However, the transdermal market still remains limited to a narrow range of drugs. Further advances in transdermal delivery depend on the ability to overcome the challenges faced regarding the permeation and skin irritation of the drug molecules. Emergence of novel techniques for skin permeation enhancement and development of methods to lessen skin irritation would widen the transdermal market for hydrophilic compounds, macromolecules and conventional drugs for new therapeutic indications. As evident from the ongoing clinical trials of a wide variety of drugs for various clinical conditions, there is a great future for transdermal delivery of drugs. PMID:21132122

  13. Transdermal uptake of diethyl phthalate and di(n-butyl) phthalate directly from air: Experimental verification

    DEFF Research Database (Denmark)

    Weschler, Charles J.; Bekö, Gabriel; Koch, Holger M.

    2015-01-01

    of phthalate esters. Objectives: This study investigated transdermal uptake, directly from air, of diethyl phthalate (DEP) and di(n-butyl) phthalate (DnBP) in humans. Methods: In a series of experiments, six human participants were exposed for 6 hr in a chamber containing deliberately elevated air...

  14. [Comparative study on transdermal osmosis in vitro of Aconitum brachypodium liniment, gel and patcher].

    Science.gov (United States)

    Lin, Ya-ping; Zhao, Ying; Zhang, Yong-ping; Liang, Guang-yi

    2007-02-01

    To study the transdermal osmosis process of Aconitum brachypodum's liniment, gel and patcher to provide basis for selecting dosage form and controlling the quality. Taking the cumulate rate of transdermal as index, a imitated Fick's diffusion device was used for the investigating the transdermal osmosis course of the three preparations. The best transdermal mathematics models are obtained and the relations between the transdermal course and the release course are analysed. The three preparations have different characteristics of transdermal osmosis course. The liniment meets dynamics 0 order process, the gel and the patcher meet dynamic 0 order process of non-corroded drug system. And the relation is good cubic equation between their transdermal course and release course. The transdermal osmosis experiment in vitro for three preparations can provide basis for selecting dosage form and the quality control in future studies.

  15. Granisetron Transdermal Patch

    Science.gov (United States)

    Granisetron transdermal patches are used to prevent nausea and vomiting caused by chemotherapy. Granisetron is in a class of medications called 5HT3 ... Granisetron transdermal comes as a patch to apply to the skin. It is usually applied 24 to ...

  16. Microneedle-assisted transdermal delivery of Zolmitriptan: effect of microneedle geometry, in vitro permeation experiments, scaling analyses and numerical simulations.

    Science.gov (United States)

    Uppuluri, Chandra Teja; Devineni, Jyothirmayee; Han, Tao; Nayak, Atul; Nair, Kartik J; Whiteside, Benjamin R; Das, Diganta B; Nalluri, Buchi N

    2017-08-01

    The present study was aimed to investigate the effect of salient microneedle (MN) geometry parameters like length, density, shape and type on transdermal permeation enhancement of Zolmitriptan (ZMT). Two types of MN devices viz. AdminPatch ® arrays (ADM) (0.6, 0.9, 1.2 and 1.5 mm lengths) and laboratory fabricated polymeric MNs (PM) of 0.6 mm length were employed. In the case of PMs, arrays were applied thrice at different places within a 1.77 cm 2 skin area (PM-3) to maintain the MN density closer to 0.6 mm ADM. Scaling analyses was done using dimensionless parameters like concentration of ZMT (C t /C s ), thickness (h/L) and surface area of the skin (Sa/L 2 ). Micro-injection molding technique was employed to fabricate PM. Histological studies revealed that the PM, owing to their geometry/design, formed wider and deeper microconduits when compared to ADM of similar length. Approximately 3.17- and 3.65-fold increase in ZMT flux values were observed with 1.5 mm ADM and PM-3 applications when compared to the passive studies. Good correlations were observed between different dimensionless parameters with scaling analyses. Numerical simulations, using MATLAB and COMSOL software, based on experimental data and histological images provided information regarding the ZMT skin distribution after MN application. Both from experimental studies and simulations, it was inferred that PM were more effective in enhancing the transdermal delivery of ZMT when compared to ADM. The study suggests that MN application enhances the ZMT transdermal permeation and the geometrical parameters of MNs play an important role in the degree of such enhancement.

  17. Transdermal fentanyl matrix patches Matrifen and Durogesic DTrans are bioequivalent

    DEFF Research Database (Denmark)

    Kress, Hans G; Boss, Hildegard; Delvin, Thomas

    2010-01-01

    AIM: The pharmacokinetic profiles of the two commercially available transdermal fentanyl patches Matrifen (100 microg/h) and Durogesic DTrans (100 microg/h), used to manage severe chronic pain, were compared regarding their systemic exposure, rate of absorption, and safety. METHODS: Transdermal m...

  18. Estradiol Transdermal Patch

    Science.gov (United States)

    ... menopause (change of life; the end of monthly menstrual periods). Transdermal estradiol is also used to prevent ... patch. Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.

  19. Transdermal drug delivery

    OpenAIRE

    Prausnitz, Mark R.; Langer, Robert

    2008-01-01

    Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, non-cavitational ultrasound and iontophoresis have also resulted in clinical products; the ability ...

  20. Alghedon Fentanyl Transdermal System.

    Science.gov (United States)

    Romualdi, Patrizia; Santi, Patrizia; Candeletti, Sanzio

    2017-04-01

    The efficacy of transdermal fentanyl for cancer pain and chronic non-cancer pain (chronic lower back pain, rheumatoid arthritis, osteoarthritis, neuropathic pain) is well established. Several formulations of fentanyl transdermal systems have been developed to improve the drug delivery and prevent misuse of the active principle. The addition of a rate controlling membrane to the matrix system represented an important advance. The design and functional features of Alghedon patch are compared with other approved generic fentanyl transdermal systems, emphasizing the distinctiveness of Alghedon patch. Alghedon patch has no liquid component in the finished product, therefore no leakage of active ingredient from the system can occur. A rate-controlling membrane provides controlled release of the active substance from the matrix reservoir, ensuring that fentanyl delivery and entry into the microcirculation is not solely controlled by the skin's permeability to this active substance. Alghedon patch contains part of the drug (approximately 15%) in the skin-contact adhesive: this innovative solution allows to overcome a typical drawback of transdermal patches, i.e. the long lag-time before the drug appears in plasma after the first administration, and provides rapid analgesia during the first hours of administration. Alghedon Fentanyl Transdermal System employs materials commonly used in other transdermal applications and having established safety profiles. For each strength level, the fentanyl content - and, thus, the resulting residual fentanyl remaining in the patch after use - is at the lowest end of the range used in commercially available fentanyl patches, minimizing the potential for abuse and misuse.

  1. TRANSDERMAL DRUG DELIVERY SYSTEM: REVIEW

    OpenAIRE

    Vishvakarama Prabhakar; Agarwal Shivendra; Sharma Ritika; Saurabh Sharma

    2012-01-01

    Various new technologies have been developed for the transdermal delivery of some important drugs. Today about 74% of drugs are taken orally and are found not to be as effective as desired. To improve such characters transdermal drug delivery system was emerged. Drug delivery through the skin to achieve a systemic effect of a drug is commonly known as transdermal drug delivery and differs from traditional topical drug delivery. Transdermal drug delivery systems (TDDS) are dosage forms involve...

  2. From the Cover: Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: Fabrication methods and transport studies

    Science.gov (United States)

    McAllister, Devin V.; Wang, Ping M.; Davis, Shawn P.; Park, Jung-Hwan; Canatella, Paul J.; Allen, Mark G.; Prausnitz, Mark R.

    2003-11-01

    Arrays of micrometer-scale needles could be used to deliver drugs, proteins, and particles across skin in a minimally invasive manner. We therefore developed microfabrication techniques for silicon, metal, and biodegradable polymer microneedle arrays having solid and hollow bores with tapered and beveled tips and feature sizes from 1 to 1,000 μm. When solid microneedles were used, skin permeability was increased in vitro by orders of magnitude for macromolecules and particles up to 50 nm in radius. Intracellular delivery of molecules into viable cells was also achieved with high efficiency. Hollow microneedles permitted flow of microliter quantities into skin in vivo, including microinjection of insulin to reduce blood glucose levels in diabetic rats. transdermal drug delivery | skin | microelectromechanical systems | solid microneedle | hollow needle injection

  3. Transdermal drug delivery

    Science.gov (United States)

    Prausnitz, Mark R.; Langer, Robert

    2009-01-01

    Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, non-cavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin’s barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase impact on medicine. PMID:18997767

  4. Comparison of estrus synchronization by controlled internal drug release device (CIDR) and adhesive transdermal progestin patch in postpartum beef cows.

    Science.gov (United States)

    Kajaysri, Jatuporn; Chumchoung, Chaiwat; Wutthiwitthayaphong, Supphathat; Suthikrai, Wanvipa; Sangkamanee, Praphai

    2017-09-15

    Estrous synchronization with progesterone based protocols has been essentially used in cattle industry. Although intravaginal devices have been commonly used, this technique may induce vaginitis. This study aimed at examining the efficiency of novel transdermal progestin patch on follicle development and comparing the progestin patch versus CIDR device on estrous synchronization, complication at treated site and pregnancy in beef cattle. In experiment 1, seven beef cows were treated with an adhesive transdermal progestin patch on the ventral surface of the proximal part of the tail for 7 days. The cows were daily examined the follicular development using ultrasonography starting on Day 0 till 3 days after hormone removal. Experiment 2, forty beef cows were divided into two equal groups (20 cows per group). The cows randomly allocated to received either vaginal insertion of CIDR (n = 20) or treated with an adhesive transdermal progestin patch (n = 20). The levels of plasma progesterone during the experiment and the numbers of standing estrous cows were recorded. Timed artificial inseminated (TAI) was performed at 60 h after CIDR or patch termination. Pregnancy rates were determined at 60 days after TAI. Experiment 1 revealed that the novel transdermal progestin patch could efficiently control follicular growth. All the seven treated cows had dominant follicle upon dermal patch removal indicating the effectiveness of the progestin patch. In experiment 2, the percentages of cows exhibited standing estrus were similar between transdermal patch (72.22%) and CIDR (70.00%). The levels of plasma progesterone during CIDR treatment were significantly higher (4.06 ± 1.65 ng/mL on Day 1 and 3.62 ± 1.60 ng/mL on Day 7) compared with transdermal patch (2.60 ± 1.43 ng/mL on Day 1 and 1.81 ± 1.57 ng/mL on Day 7). Three cows treated with CIDR (15%) developed vaginitis while none of cows had physically dermal reaction at adhesive site. Cows synchronized with

  5. Iontophoretic transdermal drug delivery: a multi-layered approach.

    Science.gov (United States)

    Pontrelli, Giuseppe; Lauricella, Marco; Ferreira, José A; Pena, Gonçalo

    2017-12-11

    We present a multi-layer mathematical model to describe the transdermal drug release from an iontophoretic system. The Nernst-Planck equation describes the basic convection-diffusion process, with the electric potential obtained by solving the Laplace's equation. These equations are complemented with suitable interface and boundary conditions in a multi-domain. The stability of the mathematical problem is discussed in different scenarios and a finite-difference method is used to solve the coupled system. Numerical experiments are included to illustrate the drug dynamics under different conditions. © The authors 2016. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

  6. Perspectives on Transdermal Electroporation

    Science.gov (United States)

    Ita, Kevin

    2016-01-01

    Transdermal drug delivery offers several advantages, including avoidance of erratic absorption, absence of gastric irritation, painlessness, noninvasiveness, as well as improvement in patient compliance. With this mode of drug administration, there is no pre-systemic metabolism and it is possible to increase drug bioavailability and half-life. However, only a few molecules can be delivered across the skin in therapeutic quantities. This is because of the hindrance provided by the stratum corneum. Several techniques have been developed and used over the last few decades for transdermal drug delivery enhancement. These include sonophoresis, iontophoresis, microneedles, and electroporation. Electroporation, which refers to the temporary perturbation of the skin following the application of high voltage electric pulses, has been used to increase transcutaneous flux values by several research groups. In this review, transdermal electroporation is discussed and the use of the technique for percutaneous transport of low and high molecular weight compounds described. This review also examines our current knowledge regarding the mechanisms of electroporation and safety concerns arising from the use of this transdermal drug delivery technique. Safety considerations are especially important because electroporation utilizes high voltage pulses which may have deleterious effects in some cases. PMID:26999191

  7. Recent trends in challenges and opportunities of Transdermal drug delivery system

    OpenAIRE

    P.M.Patil; P.D.Chaudhari; Jalpa K.Patel; K.A.Kedar; P.P.Katolkar

    2012-01-01

    Drug delivery system relates to the production of a drug, its delivery medium, and the way of administration. Drug delivery systems are even used for administering nitroglycerin. Transdermal drug delivery system is the system in which the delivery of the active ingredients of the drug occurs by the means of skin. Various types of transdermal patches are used. There are various methods to enhance the transdermal drug delivery system. But using microfabricated microneedles drugs are delivered v...

  8. Effect of Drug Loading Method and Drug Physicochemical Properties on the Material and Drug Release Properties of Poly (Ethylene Oxide Hydrogels for Transdermal Delivery

    Directory of Open Access Journals (Sweden)

    Rachel Shet Hui Wong

    2017-07-01

    Full Text Available Novel poly (ethylene oxide (PEO hydrogel films were synthesized via UV cross-linking with pentaerythritol tetra-acrylate (PETRA as cross-linking agent. The purpose of this work was to develop a novel hydrogel film suitable for passive transdermal drug delivery via skin application. Hydrogels were loaded with model drugs (lidocaine hydrochloride (LID, diclofenac sodium (DIC and ibuprofen (IBU via post-loading and in situ loading methods. The effect of loading method and drug physicochemical properties on the material and drug release properties of medicated film samples were characterized using scanning electron microscopy (SEM, swelling studies, differential scanning calorimetry (DSC, fourier transform infrared spectroscopy (FT-IR, tensile testing, rheometry, and drug release studies. In situ loaded films showed better drug entrapment within the hydrogel network and also better polymer crystallinity. High drug release was observed from all studied formulations. In situ loaded LID had a plasticizing effect on PEO hydrogel, and films showed excellent mechanical properties and prolonged drug release. The drug release mechanism for the majority of medicated PEO hydrogel formulations was determined as both drug diffusion and polymer chain relaxation, which is highly desirable for controlled release formulations.

  9. Transdermic absorption of Melagenina II

    International Nuclear Information System (INIS)

    Hernandez Gonzalez, I.; Martinez Lopez, B.; Ruiz Pena, M.; Caso Pena, R.

    1997-01-01

    The transdermic absorption of Melagenina II (MII) was evaluated. MII was a labelled with 125I by the yodogen method and purified by column chromatography with Sephadex LH-20 in ethanol: water (7:3). In vitro absorption of ( 125I ) - MII thought human skin was carried out in Keshary-Chien modified diffusion cells. Tape stripping method was applied after 24 hours to evaluate the accumulated activity in dermis and epidermis. In vivo assays were performed in Sprague Dawley rats to analyze absorption of MII until 24 hours after a single application and for five days a low penetrability of the drug while in vivo there were not found blood levels significantly greater than zero , nevertheless and important amount of radioactivity was found in feces and urine. The activity was concentrated mainly in the application site in both models

  10. Controlled release of optimized electroporation enhances the transdermal efficiency of sinomenine hydrochloride for treating arthritis in vitro and in clinic

    Science.gov (United States)

    Feng, Shun; Zhu, Lijun; Huang, Zhisheng; Wang, Haojia; Li, Hong; Zhou, Hua; Lu, Linlin; Wang, Ying; Liu, Zhongqiu; Liu, Liang

    2017-01-01

    Sinomenine hydrochloride (SH) is an ideal drug for the treatment of rheumatoid arthritis and osteoarthritis. However, high plasma concentration of systemically administered SH can release histamine, which can cause rash and gastrointestinal side effects. Topical delivery can increase SH concentration in the synovial fluid without high plasma level, thus minimizing systemic side effects. However, passive diffusion of SH was found to be inefficient because of the presence of the stratum corneum layer. Therefore, an effective method is required to compensate for the low efficiency of SH passive diffusion. In this study, transdermal experiments in vitro and clinical tests were utilized to explore the optimized parameters for electroporation of topical delivery for SH. Fluorescence experiment and hematoxylin and eosin staining analysis were performed to reveal the mechanism by which electroporation promoted permeation. In vitro, optimized electroporation parameters were 3 KHz, exponential waveform, and intensity 10. Using these parameters, transdermal permeation of SH was increased by 1.9–10.1 fold in mice skin and by 1.6–47.1 fold in miniature pig skin compared with passive diffusion. After the electroporation stimulation, the intercellular intervals and epidermal cracks in the skin increased. In clinical tests, SH concentration in synovial fluid was 20.84 ng/mL after treatment with electroporation. Therefore, electroporation with optimized parameters could significantly enhance transdermal permeation of SH. The mechanism by which electroporation promoted permeation was that the electronic pulses made the skin structure looser. To summarize, electroporation may be an effective complementary method for transdermal permeation of SH. The controlled release of electroporation may be a promising clinical method for transdermal drug administration. PMID:28670109

  11. Transdermal hyoscine induced unilateral mydriasis.

    LENUS (Irish Health Repository)

    Hannon, Breffni

    2012-03-20

    The authors present a case of unilateral mydriasis in a teenager prescribed transdermal hyoscine hydrobromide (scopolamine) for chemotherapy induced nausea and vomiting. The authors discuss the ocular side-effects associated with this particular drug and delivery system and the potential use of transdermal hyoscine as an antiemetic agent in this group.

  12. Transdermal microneedles for drug delivery applications

    International Nuclear Information System (INIS)

    Teo, Ai Ling; Shearwood, Christopher; Ng, Kian Chye; Lu Jia; Moochhala, Shabbir

    2006-01-01

    Transdermal drug delivery (TDD) has many advantages, the main one being the ability to maintain the prolonged release of drugs to attain optimal blood concentrations. Unfortunately, nature has provided a very effective protective barrier, the stratum corneum (sc), which limits TDD to certain types of drugs with specific properties. In order to enhance TDD, the idea of using microneedles to painlessly penetrate the sc barrier has previously been proposed. In this paper, we will review the different microneedles that are currently being developed as well as our own efforts in this area. Based on our experiences, we will offer our view on the key parameters for effective transdermal microneedle design as well as future directions in this area

  13. Transdermal microneedles for drug delivery applications

    Energy Technology Data Exchange (ETDEWEB)

    Teo, Ai Ling [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117510 (Singapore); Shearwood, Christopher [School of Mechanical and Aerospace Engineering, 50 Nanyang Avenue, Singapore 639798 (Singapore); Ng, Kian Chye [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117510 (Singapore); Lu Jia [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117510 (Singapore); Moochhala, Shabbir [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117510 (Singapore)]. E-mail: mshabbir@dso.org.sg

    2006-07-25

    Transdermal drug delivery (TDD) has many advantages, the main one being the ability to maintain the prolonged release of drugs to attain optimal blood concentrations. Unfortunately, nature has provided a very effective protective barrier, the stratum corneum (sc), which limits TDD to certain types of drugs with specific properties. In order to enhance TDD, the idea of using microneedles to painlessly penetrate the sc barrier has previously been proposed. In this paper, we will review the different microneedles that are currently being developed as well as our own efforts in this area. Based on our experiences, we will offer our view on the key parameters for effective transdermal microneedle design as well as future directions in this area.

  14. Experiments using coincidence methods

    International Nuclear Information System (INIS)

    Anwar Dhani.

    1978-01-01

    Experiments on γ spectroscopy using the simple coincidence techniques, including investigation of angular distribution of γ radiation from annihilation process in decay of Na 22 , γ - γ angular correlation technique in decay of Co 60 , decay scheme study of Bi 207 and life time measurement of nuclear Pb 207 excited state have been carried out. (author)

  15. Efficacy of a single dose of a transdermal diclofenac patch as pre ...

    African Journals Online (AJOL)

    Background: We compared the analgesic efficacy of a transdermal diclofenac patch 100 mg (NuPatch® 100, Zydus Cadila, Ahmedabad, India) and intramuscular diclofenac sodium 75 mg (Voveran®, Novartis, India) for postoperative analgesia, and the associated side-effects of the transdermal diclofenac patch. Method: ...

  16. Transdermal Delivery of Drugs with Microneedles—Potential and Challenges

    Directory of Open Access Journals (Sweden)

    Kevin Ita

    2015-06-01

    Full Text Available Transdermal drug delivery offers a number of advantages including improved patient compliance, sustained release, avoidance of gastric irritation, as well as elimination of pre-systemic first-pass effect. However, only few medications can be delivered through the transdermal route in therapeutic amounts. Microneedles can be used to enhance transdermal drug delivery. In this review, different types of microneedles are described and their methods of fabrication highlighted. Microneedles can be fabricated in different forms: hollow, solid, and dissolving. There are also hydrogel-forming microneedles. A special attention is paid to hydrogel-forming microneedles. These are innovative microneedles which do not contain drugs but imbibe interstitial fluid to form continuous conduits between dermal microcirculation and an attached patch-type reservoir. Several microneedles approved by regulatory authorities for clinical use are also examined. The last part of this review discusses concerns and challenges regarding microneedle use.

  17. Design and Development of a Proniosomal Transdermal Drug ...

    African Journals Online (AJOL)

    Purpose: The aim of the study was to develop a proniosomal carrier system for captopril for the treatment of hypertension that is capable of efficiently delivering entrapped drug over an extended period of time. Method: The potential of proniosomes as a transdermal drug delivery system for captopril was investigated by ...

  18. An experimental trial exploring the impact of continuous transdermal alcohol monitoring upon alcohol consumption in a cohort of male students.

    Science.gov (United States)

    Neville, Fergus G; Williams, Damien J; Goodall, Christine A; Murer, Jeffrey S; Donnelly, Peter D

    2013-01-01

    To examine the impact of continuous transdermal alcohol monitoring upon alcohol consumption in male students at a Scottish university. Using a within-subject mixed-methods design, 60 male university students were randomly allocated into three experimental conditions using AUDIT score stratified sampling. Participants in Conditions A and B were asked not to consume alcohol for a 14-day period, with those in Condition A additionally being required to wear a continuous transdermal alcohol monitoring anklet. Condition C participants wore an anklet and were asked to continue consuming alcohol as normal. Alcohol consumption was measured through alcohol timeline follow-back, and using data collected from the anklets where available. Diaries and focus groups explored participants' experiences of the trial. Alcohol consumption during the 14-day trial decreased significantly for participants in Conditions A and B, but not in C. There was no significant relative difference in units of alcohol consumed between Conditions A and B, but significantly fewer participants in Condition A drank alcohol than in Condition B. Possible reasons for this difference identified from the focus groups and diaries included the anklet acting as a reminder of commitment to the study (and the agreement to sobriety), participants feeling under surveillance, and the use of the anklet as a tool to resist social pressure to consume alcohol. The study provided experience in using continuous transdermal alcohol monitors in an experimental context, and demonstrated ways in which the technology may be supportive in facilitating sobriety. Results from the study have been used to design a research project using continuous transdermal alcohol monitors with ex-offenders who recognise a link between their alcohol consumption and offending behaviour.

  19. Transdermal Spray in Hormone Delivery

    African Journals Online (AJOL)

    market for the delivery system and ongoing development of transdermal sprays for hormone ... (DOAJ), African Journal Online, Bioline International, Open-J-Gate and Pharmacy Abstracts ... patches and gels have been very popular owing ... This product was developed for ... In a safety announcement, the US Food and.

  20. Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine

    Science.gov (United States)

    Hong, Xiaoyun; Wei, Liangming; Wu, Fei; Wu, Zaozhan; Chen, Lizhu; Liu, Zhenguo; Yuan, Weien

    2013-01-01

    Microneedles were first conceptualized for drug delivery many decades ago, overcoming the shortages and preserving the advantages of hypodermic needle and conventional transdermal drug-delivery systems to some extent. Dissolving and biodegradable microneedle technologies have been used for transdermal sustained deliveries of different drugs and vaccines. This review describes microneedle geometry and the representative dissolving and biodegradable microneedle delivery methods via the skin, followed by the fabricating methods. Finally, this review puts forward some perspectives that require further investigation. PMID:24039404

  1. Transferosomes - A vesicular transdermal delivery system for enhanced drug permeation

    Directory of Open Access Journals (Sweden)

    Reshmy Rajan

    2011-01-01

    Full Text Available Transdermal administration of drugs is generally limited by the barrier function of the skin. Vesicular systems are one of the most controversial methods for transdermal delivery of active substances. The interest in designing transdermal delivery systems was relaunched after the discovery of elastic vesicles like transferosomes, ethosomes, cubosomes, phytosomes, etc. This paper presents the composition, mechanisms of penetration, manufacturing and characterization methods of transferosomes as transdermal delivery systems of active substances. For a drug to be absorbed and distributed into organs and tissues and eliminated from the body, it must pass through one or more biological membranes/barriers at various locations. Such a movement of drug across the membrane is called as drug transport. For the drugs to be delivered to the body, they should cross the membranous barrier. The concept of these delivery systems was designed in an attempt to concentrate the drug in the tissues of interest, while reducing the amount of drug in the remaining tissues. Hence, surrounding tissues are not affected by the drug. In addition, loss of drug does not happen due to localization of drug, leading to get maximum efficacy of the medication. Therefore, the phospholipid based carrier systems are of considerable interest in this era.

  2. MICRONEEDLES AS A WAY TO INCREASE THE TRANSDERMAL INSULIN DELIVERY

    Directory of Open Access Journals (Sweden)

    E. G. Kuznetsova

    2016-01-01

    Full Text Available Aim: to prove the possibility of increasing the diffusion of insulin through the skin in vitro with pre-applying microneedles.Materials and methods. Microemulsion for transdermal therapeutic system of insulin has been used in vitro studies. Genetically engineered human insulin has been used in this research. Applicators with silicon microneedles (40 and 150 microns long have been used to enhance the diffusion fl ux of drug substance. The dynamics of insulin release from the transdermal therapeutic systems through the rabbit skin has been studied in glass Franz diffusion cells in analyzer diffusion of drugs HDT 1000 (Copley Scientifi c Ltd., UK. Insulin has been labeled with fl uorescein isothiocyanate to separate the insulin absorption spectrum from the spectra of native skin proteins at spectrophotometer measurements.Results. The amounts of insulin delivered through the skin in vitro after previous application of microneedles of 40 and 150 microns are 282.5 ± 61.1 and 372.3 ± 7.0 microgram, respectively. This is 1.4 and 1.9 times more than in the transdermal system without microneedles.Conclusion. The conditions for increasing the diffusion of insulin through the skin in a model transdermal therapeutic system with microneedles (length – 150 microns, duration of pre-application – 1 hour have been found.

  3. How can lipid nanocarriers improve transdermal delivery of olanzapine?

    Science.gov (United States)

    Iqbal, Nimra; Vitorino, Carla; Taylor, Kevin M G

    2017-06-01

    The development of a transdermal nanocarrier drug delivery system with potential for the treatment of psychiatric disorders, such as schizophrenia and bipolar disorder, is described. Lipid nanocarriers (LN), encompassing various solid:liquid lipid compositions were formulated and assessed as potential nanosystems for transdermal delivery of olanzapine. A previously optimized method of hot high pressure homogenization (HPH) was adopted for the production of the LN, which comprised solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsions (NE). Precirol  ® was selected as the solid lipid for progression of studies. SLN exhibited the best performance for transdermal delivery of olanzapine, based on in vitro release and permeation studies, coupled with results from physicochemical characterization of several solid:liquid lipid formulations. Stability tests, performed to give an indication of long-term storage behavior of the formulations, were in good agreement with previous studies for the best choice of solid:liquid lipid ratio. Overall, these findings highlight the SLN-based formulation as promising for the further inclusion in and production of transdermal patches, representing an innovative therapeutic approach.

  4. Conductive polymer nanotube patch for fast and controlled ex vivo transdermal drug delivery.

    Science.gov (United States)

    Nguyen, Thao M; Lee, Sebin; Lee, Sang Bok

    2014-10-01

    To uptake and release hydrophilic model drugs and insulin in a novel conductive polymer (CP) nanotube transdermal patch. The externally controlled transdermal delivery of model drugs and insulin were tested ex vivo and results were compared with CP films. The unique intrinsic properties of CPs provide electrostatic interaction between the model drugs and polymer backbone. When a pulsed potential was applied, the drug delivery release profile mimics that of injection delivery. With a constant potential applied, the release rate constants of the patch system were up to three-times faster than the control (0 V) and released approximately 80% more drug molecules over 24 h. The CP nanotube transdermal patch represents a new and promising drug method, specifically for hydrophilic molecules, which have been a large obstacle for conventional transdermal drug delivery systems.

  5. Simultaneous, noninvasive, and transdermal extraction of urea and homocysteine by reverse iontophoresis

    Directory of Open Access Journals (Sweden)

    et al

    2011-02-01

    Full Text Available Congo Tak-Shing Ching1,2,3, Tzong-Ru Chou1, Tai-Ping Sun1,2, Shiow-Yuan Huang3, Hsiu-Li Shieh21Graduate Institute of Biomedicine and Biomedical Technology; 2Department of Electrical Engineering, National Chi Nan University, Nantou, Taiwan; 3Department of Photonics and Communication Engineering, Asia University, Taichung, Taiwan, Republic of ChinaBackground: Cardiovascular and kidney diseases are a global public health problem and impose a huge economic burden on health care services. Homocysteine, an amino acid, is associated with coronary heart disease, while urea is a harmful metabolic substance which can be used to reflect kidney function. Monitoring of these two substances is therefore very important. This in vitro study aimed to determine whether homocysteine is extractable transdermally and noninvasively, and whether homocysteine and urea can be extracted simultaneously by reverse iontophoresis.Methods: A diffusion cell incorporated with porcine skin was used for all experiments with the application of a direct current (dc and four different symmetrical biphasic direct currents (SBdc for 12 minutes via Ag/AgCl electrodes. The dc and the SBdc had a current density of 0.3 mA/cm2.Results: The SBdc has four different phase durations of 15 sec, 30 sec, 60 sec, and 180 sec. It was found that homocysteine can be transdermally extracted by reverse iontophoresis. Simultaneous extraction of homocysteine and urea by reverse iontophoresis is also possible.Conclusion: These results suggest that extraction of homocysteine and urea by SBdc are phase duration-dependent, and the optimum mode for simultaneous homocysteine and urea extraction is the SBdc with the phase duration of 60 sec.Keywords: reverse iontophoresis, homocysteine, urea, monitoring, noninvasive, transdermal

  6. Improvement of the decision efficiency of the accuracy profile by means of a desirability function for analytical methods validation. Application to a diacetyl-monoxime colorimetric assay used for the determination of urea in transdermal iontophoretic extracts.

    Science.gov (United States)

    Rozet, E; Wascotte, V; Lecouturier, N; Préat, V; Dewé, W; Boulanger, B; Hubert, Ph

    2007-05-22

    Validation of analytical methods is a widely used and regulated step for each analytical method. However, the classical approaches to demonstrate the ability to quantify of a method do not necessarily fulfill this objective. For this reason an innovative methodology was recently introduced by using the tolerance interval and accuracy profile, which guarantee that a pre-defined proportion of future measurements obtained with the method will be included within the acceptance limits. Accuracy profile is an effective decision tool to assess the validity of analytical methods. The methodology to build such a profile is detailed here. However, as for any visual tool it has a part of subjectivity. It was then necessary to make the decision process objective in order to quantify the degree of adequacy of an accuracy profile and to allow a thorough comparison between such profiles. To achieve this, we developed a global desirability index based on the three most important validation criteria: the trueness, the precision and the range. The global index allows the classification of the different accuracy profiles obtained according to their respective response functions. A diacetyl-monoxime colorimetric assay for the determination of urea in transdermal iontophoretic extracts was used to illustrate these improvements.

  7. Pharmacokinetics of 2 Formulations of Transdermal Fentanyl in Cynomolgus Macaques (Macaca fascicularis)

    Science.gov (United States)

    Carlson, Amy M; Kelly, Richard; Fetterer, David P; Rico, Pedro J; Bailey, Emily J

    2016-01-01

    Fentanyl is a μ-opioid agonist that often is used as the analgesic component for balanced anesthesia in both human and veterinary patients. Minimal information has been published regarding appropriate dosing, and the pharmacokinetics of fentanyl are unknown in NHP. The pharmacokinetic properties of 2 transdermal fentanyl delivery methods, a solution (2.6 and 1.95 mg/kg) and a patch (25 µg/h), were determined when applied topically to the dorsal scapular area of cynomolgus macaques (Macaca fascicularis). Serum fentanyl concentrations were analyzed by using liquid chromatography–mass spectrometry. Compared with the patch, the transdermal fentanyl solution generated higher drug concentrations over longer time. Adverse reactions occurred in the macaques that received the transdermal fentanyl solution at 2.6 mg/kg. Both preparations showed significant interanimal variability in the maximal serum drug levels, time to achieve maximal fentanyl levels, elimination half-life, and AUC values. Both the maximal concentration and the time at which this concentration occurred were increased in macaques compared with most other species after application of the transdermal fentanyl patch and compared with dogs after application of the transdermal fentanyl solution. The pharmacokinetic properties of transdermal fentanyl in macaques are markedly different from those in other veterinary species and preclude its use as a long-acting analgesic drug in NHP. PMID:27423151

  8. Population pharmacokinetic model of transdermal nicotine delivered from a matrix-type patch.

    Science.gov (United States)

    Linakis, Matthew W; Rower, Joseph E; Roberts, Jessica K; Miller, Eleanor I; Wilkins, Diana G; Sherwin, Catherine M T

    2017-12-01

    Nicotine addiction is an issue faced by millions of individuals worldwide. As a result, nicotine replacement therapies, such as transdermal nicotine patches, have become widely distributed and used. While the pharmacokinetics of transdermal nicotine have been extensively described using noncompartmental methods, there are few data available describing the between-subject variability in transdermal nicotine pharmacokinetics. The aim of this investigation was to use population pharmacokinetic techniques to describe this variability, particularly as it pertains to the absorption of nicotine from the transdermal patch. A population pharmacokinetic parent-metabolite model was developed using plasma concentrations from 25 participants treated with transdermal nicotine. Covariates tested in this model included: body weight, body mass index, body surface area (calculated using the Mosteller equation) and sex. Nicotine pharmacokinetics were best described with a one-compartment model with absorption based on a Weibull distribution and first-order elimination and a single compartment for the major metabolite, cotinine. Body weight was a significant covariate on apparent volume of distribution of nicotine (exponential scaling factor 1.42). After the inclusion of body weight in the model, no other covariates were significant. This is the first population pharmacokinetic model to describe the absorption and disposition of transdermal nicotine and its metabolism to cotinine and the pharmacokinetic variability between individuals who were administered the patch. © 2017 The British Pharmacological Society.

  9. Electrospun polymeric nanofibers for transdermal drug delivery

    Directory of Open Access Journals (Sweden)

    Mahya Rahmani

    2017-04-01

    Full Text Available Conventional transdermal drug delivery systems (TDDS have been designed for drug delivery through the skin. These systems use the permeability property of stratum corneum, the outermost surface layer of the skin. Applying polymeric micro and nanofibers in drug delivery has recently attracted great attention and the electrospinning technique is the preferred method for polymeric micro-nanofibers fabrication with a great potential for drug delivery. More studies in the field of nanofibers containing drug are divided two categories: first, preparation and characterization of nanofibers containing drug and second, investigation of their therapeutic applications. Drugs used in electrospun nanofibers can be categorized into three main groups, including antibiotics and antimicrobial agents, anti-inflammatory agents and vitamins with therapeutic applications. In this paper, we review the application of electrospun polymeric scaffolds in TDDS and also introduce several pharmaceutical and therapeutic agents which have been used in polymer nanofibrous patches.

  10. Microneedle Coating Techniques for Transdermal Drug Delivery

    Directory of Open Access Journals (Sweden)

    Rita Haj-Ahmad

    2015-11-01

    Full Text Available Drug administration via the transdermal route is an evolving field that provides an alternative to oral and parenteral routes of therapy. Several microneedle (MN based approaches have been developed. Among these, coated MNs (typically where drug is deposited on MN tips are a minimally invasive method to deliver drugs and vaccines through the skin. In this review, we describe several processes to coat MNs. These include dip coating, gas jet drying, spray coating, electrohydrodynamic atomisation (EHDA based processes and piezoelectric inkjet printing. Examples of process mechanisms, conditions and tested formulations are provided. As these processes are independent techniques, modifications to facilitate MN coatings are elucidated. In summary, the outcomes and potential value for each technique provides opportunities to overcome formulation or dosage form limitations. While there are significant developments in solid degradable MNs, coated MNs (through the various techniques described have potential to be utilized in personalized drug delivery via controlled deposition onto MN templates.

  11. Iontophoretic and Microneedle Mediated Transdermal Delivery of Glycopyrrolate

    Directory of Open Access Journals (Sweden)

    Meera Gujjar

    2014-12-01

    Full Text Available Purpose: The objective of this study was to investigate the use of iontophoresis, soluble microneedles and their combination for the transdermal delivery of glycopyrrolate. Methods: In vitro permeation was tested using full thickness porcine ear skin mounted onto Franz diffusion cells. Iontophoresis (0.5 mA/cm2 was done for 4 h using Ag/AgCl electrodes. For microneedles, three line array (27 needles/line of maltose microneedles were used to microporate the skin prior to mounting. Pore uniformity was determined by taking fluorescent images of distribution of calcein into pores and processing the images using an image analysis tool, which measured the fluorescent intensity in and around each pore to provide a pore permeability index (PPI. The donor chamber contained 500 µL of a 1 mg/mL solution of glycopyrrolate, and the receptor chamber contained 5 mL of 50 mM NaCl in deionized water. Samples were collected at predetermined time points over a period of 24 h and analyzed by HPLC. Skin irritation testing was performed with a 3D cell culture kit of human skin. MTT assay determined cell viability; viability less than 50% was considered irritant. Results: A control experiment which investigated passive permeation of glycopyrrolate delivered an average cumulative amount of 24.92 ± 1.77 µg/cm2 at 24 h, while microneedle pretreatment increased permeability to 46.54 ± 6.9 µg/cm2. Both iontophoresis (158.53 ± 17.50 µg/cm2 and a combination of iontophoresis and microneedles (182.43 ± 20.06 µg/ cm2 significantly increased delivery compared to passive and microneedles alone. Glycopyrrolate solution was found to be nonirritant with cell viability of 70.4% ± 5.03%. Conclusion: Iontophoresis and a combination of iontophoresis with microneedle pretreatment can be effectively used to enhance the transdermal delivery of glycopyrrolate. Glycopyrrolate was found to be non-irritant to skin.

  12. Computational and experimental model of transdermal iontophorethic drug delivery system.

    Science.gov (United States)

    Filipovic, Nenad; Saveljic, Igor; Rac, Vladislav; Graells, Beatriz Olalde; Bijelic, Goran

    2017-11-30

    The concept of iontophoresis is often applied to increase the transdermal transport of drugs and other bioactive agents into the skin or other tissues. It is a non-invasive drug delivery method which involves electromigration and electroosmosis in addition to diffusion and is shown to be a viable alternative to conventional administration routs such as oral, hypodermic and intravenous injection. In this study we investigated, experimentally and numerically, in vitro drug delivery of dexamethasone sodium phosphate to porcine skin. Different current densities, delivery durations and drug loads were investigated experimentally and introduced as boundary conditions for numerical simulations. Nernst-Planck equation was used for calculation of active substance flux through equivalent model of homogeneous hydrogel and skin layers. The obtained numerical results were in good agreement with experimental observations. A comprehensive in-silico platform, which includes appropriate numerical tools for fitting, could contribute to iontophoretic drug-delivery devices design and correct dosage and drug clearance profiles as well as to perform much faster in-silico experiments to better determine parameters and performance criteria of iontophoretic drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Trojan Horse Method: Recent Experiments

    International Nuclear Information System (INIS)

    Cherubini, S.; Spitaleri, C.; Crucilla, V.; Gulino, M.; La Cognata, M.; Lamia, L.; Pizzone, R. G.; Romano, S.; Tudisco, S.; Tumino, A.; Mukhamedzhanov, A.; Trache, L.; Tribble, R.; Rolfs, C.; Typel, S.

    2006-01-01

    The Trojan Horse Method allows for the measurements of cross sections in nuclear reactions between charged particles at astrophysical energies. The basic features of the method are discussed and recent applications are presented

  14. Transdermal optogenetic peripheral nerve stimulation

    Science.gov (United States)

    Maimon, Benjamin E.; Zorzos, Anthony N.; Bendell, Rhys; Harding, Alexander; Fahmi, Mina; Srinivasan, Shriya; Calvaresi, Peter; Herr, Hugh M.

    2017-06-01

    Objective: A fundamental limitation in both the scientific utility and clinical translation of peripheral nerve optogenetic technologies is the optical inaccessibility of the target nerve due to the significant scattering and absorption of light in biological tissues. To date, illuminating deep nerve targets has required implantable optical sources, including fiber-optic and LED-based systems, both of which have significant drawbacks. Approach: Here we report an alternative approach involving transdermal illumination. Utilizing an intramuscular injection of ultra-high concentration AAV6-hSyn-ChR2-EYFP in rats. Main results: We demonstrate transdermal stimulation of motor nerves at 4.4 mm and 1.9 mm depth with an incident laser power of 160 mW and 10 mW, respectively. Furthermore, we employ this technique to accurately control ankle position by modulating laser power or position on the skin surface. Significance: These results have the potential to enable future scientific optogenetic studies of pathologies implicated in the peripheral nervous system for awake, freely-moving animals, as well as a basis for future clinical studies.

  15. [Studies on transdermal delivery of ferulic acid through rat skin treated by microneedle arrays].

    Science.gov (United States)

    Yang, Bing; Du, Shou-ying; Bai, Jie; Shang, Ke-xin; Lu, Yang; Li, Peng-yue

    2014-12-01

    In order to investigate the characteristics of transdermal delivery of ferulic acid under the treated of microneedle arrays and the influence on permeability of rat skin capillaries, improved Franz-cells were used in the transdermal delivery experiment with the rat skin of abdominal wall and the length of microneedle arrays, different insertion forces, retention time were studied in the influence of characteristics of transdermal delivery of FA. The amount of FA was determined by HPLC system. Intravenous injection Evans blue and FA was added after microneedle arrays treated. Established inflammation model was built by daubing dimethylbenzene. The amount of Evans blue in the rat skin was read at 590 nm wavelength with a Multiskan Go microplate reader. Compared with passive diffusion group the skin pretreated with microneedle arrays had a remarkable enhancement of FA transport (P Microneedle arrays with different length had a remarkable enhancement of FA transport, but was not related to the increase of the length. The research of FA on the reduce of permeability of rat skin capillaries indicated that the skin pretreated with microneedle arrays could reduce the content of Evans blue in the skins of rat significantly compared with the untreated group. The permeation rate of ferulic acid transdermal delivery had remarkable increase under the treated of microneedle arrays and the length of microneedle arrays ,the retention time so as to the insertion force were important to the transdermal delivery of ferulic acid.

  16. Use of electroporation and reverse iontophoresis for extraction of transdermal multibiomarkers

    Directory of Open Access Journals (Sweden)

    Ching CTS

    2012-02-01

    Full Text Available Congo Tak-Shing Ching1,2, Lin-Shien Fu3-5, Tai-Ping Sun1, Tzu-Hsiang Hsu1, Kang-Ming Chang21Department of Electrical Engineering, National Chi Nan University, Puli, Nantou County, 2Department of Photonics and Communication Engineering, Asia University, Wufeng, Taichung, 3Department of Pediatrics, National Yang Ming University, Taipei, 4Institute of Technology, National Chi Nan University, Puli, 5Department of Pediatrics, Taichung Veterans General Hospital, Taichung City, TaiwanBackground: Monitoring of biomarkers, like urea, prostate-specific antigen (PSA, and osteopontin, is very important because they are related to kidney disease, prostate cancer, and ovarian cancer, respectively. It is well known that reverse iontophoresis can enhance transdermal extraction of small molecules, and even large molecules if reverse iontophoresis is used together with electroporation. Electroporation is the use of a high-voltage electrical pulse to create nanochannels within the stratum corneum, temporarily and reversibly. Reverse iontophoresis is the use of a small current to facilitate both charged and uncharged molecule transportation across the skin. The objectives of this in vitro study were to determine whether PSA and osteopontin are extractable transdermally and noninvasively and whether urea, PSA, and osteopontin can be extracted simultaneously by electroporation and reverse iontophoresis.Methods: All in vitro experiments were conducted using a diffusion cell assembled with the stratum corneum of porcine skin. Three different symmetrical biphasic direct currents (SBdc, five various electroporations, and a combination of the two techniques were applied to the diffusion cell via Ag/AgCl electrodes. The three different SBdc had the same current density of 0.3 mA/cm2, but different phase durations of 0 (ie, no current, control group, 30, and 180 seconds. The five different electroporations had the same pulse width of 1 msec and number of pulses per second

  17. Spray-on transdermal drug delivery systems.

    Science.gov (United States)

    Ibrahim, Sarah A

    2015-02-01

    Transdermal drug delivery possesses superior advantages over other routes of administration, particularly minimizing first-pass metabolism. Transdermal drug delivery is challenged by the barrier nature of skin. Numerous technologies have been developed to overcome the relatively low skin permeability, including spray-on transdermal systems. A transdermal spray-on system (TSS) usually consists of a solution containing the drug, a volatile solvent and in many cases a chemical penetration enhancer. TSS promotes drug delivery via the complex interplay between solvent evaporation and drug-solvent drag into skin. The volatile solvent carries the drug into the upper layers of the stratum corneum, and as the volatile solvent evaporates, an increase in the thermodynamic activity of the drug occurs resulting in an increased drug loading in skin. TSS is easily applied, delivering flexible drug dosage and associated with lower incidence of skin irritation. TSS provides a fast-drying product where the volatile solvent enables uniform drug distribution with minimal vehicle deposition on skin. TSS ensures precise dose administration that is aesthetically appealing and eliminates concerns of residual drug associated with transdermal patches. Furthermore, it provides a better alternative to traditional transdermal products due to ease of product development and manufacturing.

  18. Transdermal patches: history, development and pharmacology

    Science.gov (United States)

    Pastore, Michael N; Kalia, Yogeshvar N; Horstmann, Michael; Roberts, Michael S

    2015-01-01

    Transdermal patches are now widely used as cosmetic, topical and transdermal delivery systems. These patches represent a key outcome from the growth in skin science, technology and expertise developed through trial and error, clinical observation and evidence-based studies that date back to the first existing human records. This review begins with the earliest topical therapies and traces topical delivery to the present-day transdermal patches, describing along the way the initial trials, devices and drug delivery systems that underpin current transdermal patches and their actives. This is followed by consideration of the evolution in the various patch designs and their limitations as well as requirements for actives to be used for transdermal delivery. The properties of and issues associated with the use of currently marketed products, such as variability, safety and regulatory aspects, are then described. The review concludes by examining future prospects for transdermal patches and drug delivery systems, such as the combination of active delivery systems with patches, minimally invasive microneedle patches and cutaneous solutions, including metered-dose systems. PMID:25560046

  19. Formal Methods: Practice and Experience

    DEFF Research Database (Denmark)

    Woodcock, Jim; Larsen, Peter Gorm; Bicarregui, Juan

    2009-01-01

    . Based on this, we discuss the issues surrounding the industrial adoption of formal methods. Finally, we look to the future and describe the development of a Verified Software Repository, part of the worldwide Verified Software Initiative. We introduce the initial projects being used to populate...... the repository, and describe the challenges they address. © 2009 ACM. (146 refs.)...

  20. Development, characterization & invivo evaluation of proniosomal based transdermal delivery system of Atenolol

    Directory of Open Access Journals (Sweden)

    S. Ramkanth

    2018-06-01

    Full Text Available The potential of proniosomes as a transdermal drug delivery system for Atenolol was investigated by encapsulating the drug in various formulations of proniosomal gel composed of various ratios of sorbitan fatty acid esters, cholesterol, lecithin prepared by Coacervation-phase separation method. The objectives of the present study were to define effects on the antihypertension activity and pharmacokinetics of a novel transdermal Proniosomal gel incorporating Atenolol. The formulated systems were characterized in vitro for size, drug entrapment, In vitro and in vivo drug permeation profiles and vesicular stability at different storage conditions. The optimized Atenolol proniosomes (AT8 showed nanometric vesicle size, high entrapment efficiency and marked enhancement in transdermal permeation. The prepared Proniosomal gel showed the relative bioavailability of 365.38 fold increased for AT8 than oral. The maximal concentrations (Cmax, of drug were significantly reduced while the areas under the plasma concentration–time curve (AUC, and mean residence times (MRT, t1/2 were evidently increased and extended, respectively. The results suggest that proniosomes can act as promising carrier which offers an alternative approach for transdermal delivery of Atenolol. Keywords: Proniosomes, Atenolol, Niosomes, Pharmacokinetic study, Transdermal delivery

  1. Formulation, in vitro and in vivo evaluation of transdermal patches containing risperidone.

    Science.gov (United States)

    Aggarwal, Geeta; Dhawan, Sanju; Hari Kumar, S L

    2013-01-01

    The efficacy of oral risperidone treatment in prevention of schizophrenia is well known. However, oral side effects and patient compliance is always a problem for schizophrenics. In this study, risperidone was formulated into matrix transdermal patches to overcome these problems. The formulation factors for such patches, including eudragit RL 100 and eudragit RS 100 as matrix forming polymers, olive oil, groundnut oil and jojoba oil in different concentrations as enhancers and amount of drug loaded were investigated. The transdermal patches containing risperidone were prepared by solvent casting method and characterized for physicochemical and in vitro permeation studies through excised rat skin. Among the tested preparations, formulations with 20% risperidone, 3:2 ERL 100 and ERS 100 as polymers, mixture of olive oil and jojoba oil as enhancer, exhibited greatest cumulative amount of drug permeated (1.87 ± 0.09 mg/cm(2)) in 72 h, so batch ROJ was concluded as optimized formulation and assessed for pharmacokinetic, pharmacodynamic and skin irritation potential. The pharmacokinetic characteristics of the optimized risperidone patch were determined using rabbits, while orally administered risperidone in solution was used for comparison. The calculated relative bioavailability of risperidone transdermal patch was 115.20% with prolonged release of drug. Neuroleptic efficacy of transdermal formulation was assessed by rota-rod and grip test in comparison with control and marketed oral formulations with no skin irritation. This suggests the transdermal application of risperidone holds promise for improved bioavailability and better management of schizophrenia in long-term basis.

  2. Some Recent Advances in Transdermal Drug Delivery Systems ...

    African Journals Online (AJOL)

    Some Recent Advances in Transdermal Drug Delivery Systems. ... Advances in Transdermal Drug Delivery Systems. EC Ibezim, B Kabele-Toge, CO Anie, C Njoku. Abstract. Transdermal delivery systems are forms of drug delivery involving the dermis, as distinct from topical, oral or other forms of parenteral dosage forms.

  3. Carbon Nanotube Membranes for use in the Transdermal Treatment of Nicotine Addiction and Opioid Withdrawal Symptoms

    Directory of Open Access Journals (Sweden)

    Audra L. Stinchcomb

    2009-01-01

    Full Text Available Transdermal systems are attractive methods of drug administration specifically when treating patients for drug addiction. Current systems however are deficient in therapies that allow variable flux values of drug, such as nicotine for smoking cessation or complex dosing regimens using clonidine when treating opioid withdrawal symptoms. Through the use of functionalized carbon nanotube (CNT membranes, drug delivery to the skin can be controlled by applying a small electrical bias to create a programmable drug delivery system. Clearly, a transdermal patch system that can be tailored to an individual’s needs will increase patient compliance as well as provide much more efficient therapy. The purpose of this paper is to discuss the applicability of using carbon nanotube membranes in transdermal systems for treatment of drug abuse.

  4. Biomaterials as novel penetration enhancers for transdermal and dermal drug delivery systems.

    Science.gov (United States)

    Chen, Yang; Wang, Manli; Fang, Liang

    2013-01-01

    The highly organized structure of the stratum corneum provides an effective barrier to the drug delivery into or across the skin. To overcome this barrier function, penetration enhancers are always used in the transdermal and dermal drug delivery systems. However, the conventional chemical enhancers are often limited by their inability to delivery large and hydrophilic molecules, and few to date have been routinely incorporated into the transdermal formulations due to their incompatibility and local irritation issues. Therefore, there has been a search for the compounds that exhibit broad enhancing activity for more drugs without producing much irritation. More recently, the use of biomaterials has emerged as a novel method to increase the skin permeability. In this paper, we present an overview of the investigations on the feasibility and application of biomaterials as penetration enhancers for transdermal or dermal drug delivery systems.

  5. Carbon Nanotube Membranes for use in the Transdermal Treatment of Nicotine Addiction and Opioid Withdrawal Symptoms

    Directory of Open Access Journals (Sweden)

    Caroline L. Strasinger

    2009-01-01

    Full Text Available Transdermal systems are attractive methods of drug administration specifically when treating patients for drug addiction. Current systems however are deficient in therapies that allow variable flux values of drug, such as nicotine for smoking cessation or complex dosing regimens using clonidine when treating opioid withdrawal symptoms. Through the use of functionalized carbon nanotube (CNT membranes, drug delivery to the skin can be controlled by applying a small electrical bias to create a programmable drug delivery system. Clearly, a transdermal patch system that can be tailored to an individual's needs will increase patient compliance as well as provide much more efficient therapy. The purpose of this paper is to discuss the applicability of using carbon nanotube membranes in transdermal systems for treatment of drug abuse.

  6. Pharmacokinetics of the transdermal delivery of benfotiamine.

    Science.gov (United States)

    Zhu, Zhen; Varadi, Gyula; Carter, Stephen G

    2016-04-01

    Accumulation of advanced glycation endpoints is a trigger to the development of diabetic peripheral neuropathy, which is a common complication of diabetes. Oral administration of benfotiamine (BFT) has shown some preclinical and clinical promise as a treatment for diabetic peripheral neuropathy. The purpose of this study was to evaluate the method of transdermal delivery of BFT as a possible, viable route of administration for the treatment of diabetic peripheral neuropathy. A single application of 10 mg of BFT was given to guinea pigs topically. The levels of thiamine (T), thiamine monophosphate, thiamine diphosphate, S-benzoylthiamine and BFT were measured in the blood, skin and muscle at different time points within 24 h. At the 24-h time point, following the single BFT dose, the T level was increased 10× in the blood, more than 7× in the skin and almost 4× in the muscle compared to the untreated animals. The total T content (total) was increased 7× in the blood, 17× in the skin and 3× in the muscle compared to the untreated animals. This strong increase in the tissue levels of T and the associated metabolic derivatives levels found in the blood and local tissues following a single dose indicate that topically applied BFT may be a viable and advantageous delivery method for the treatment of diabetic peripheral neuropathy.

  7. The experience sampling method: Investigating students' affective experience

    Science.gov (United States)

    Nissen, Jayson M.; Stetzer, MacKenzie R.; Shemwell, Jonathan T.

    2013-01-01

    Improving non-cognitive outcomes such as attitudes, efficacy, and persistence in physics courses is an important goal of physics education. This investigation implemented an in-the-moment surveying technique called the Experience Sampling Method (ESM) [1] to measure students' affective experience in physics. Measurements included: self-efficacy, cognitive efficiency, activation, intrinsic motivation, and affect. Data are presented that show contrasts in students' experiences (e.g., in physics vs. non-physics courses).

  8. Permeation enhancer strategies in transdermal drug delivery.

    Science.gov (United States)

    Marwah, Harneet; Garg, Tarun; Goyal, Amit K; Rath, Goutam

    2016-01-01

    Today, ∼74% of drugs are taken orally and are not found to be as effective as desired. To improve such characteristics, transdermal drug delivery was brought to existence. This delivery system is capable of transporting the drug or macromolecules painlessly through skin into the blood circulation at fixed rate. Topical administration of therapeutic agents offers many advantages over conventional oral and invasive techniques of drug delivery. Several important advantages of transdermal drug delivery are prevention from hepatic first pass metabolism, enhancement of therapeutic efficiency and maintenance of steady plasma level of the drug. Human skin surface, as a site of drug application for both local and systemic effects, is the most eligible candidate available. New controlled transdermal drug delivery systems (TDDS) technologies (electrically-based, structure-based and velocity-based) have been developed and commercialized for the transdermal delivery of troublesome drugs. This review article covers most of the new active transport technologies involved in enhancing the transdermal permeation via effective drug delivery system.

  9. Myth or Reality-Transdermal Magnesium?

    Science.gov (United States)

    Gröber, Uwe; Werner, Tanja; Vormann, Jürgen; Kisters, Klaus

    2017-07-28

    In the following review, we evaluated the current literature and evidence-based data on transdermal magnesium application and show that the propagation of transdermal magnesium is scientifically unsupported. The importance of magnesium and the positive effects of magnesium supplementation are extensively documented in magnesium deficiency, e.g., cardiovascular disease and diabetes mellitus. The effectiveness of oral magnesium supplementation for the treatment of magnesium deficiency has been studied in detail. However, the proven and well-documented oral magnesium supplementation has become questioned in the recent years through intensive marketing for its transdermal application (e.g., magnesium-containing sprays, magnesium flakes, and magnesium salt baths). In both, specialist and lay press as well as on the internet, there are increasing numbers of articles claiming the effectiveness and superiority of transdermal magnesium over an oral application. It is claimed that the transdermal absorption of magnesium in comparison to oral application is more effective due to better absorption and fewer side effects as it bypasses the gastrointestinal tract.

  10. Transethosomal gels as carriers for the transdermal delivery of colchicine: statistical optimization, characterization, and ex vivo evaluation

    Directory of Open Access Journals (Sweden)

    Abdulbaqi IM

    2018-04-01

    Full Text Available Ibrahim M Abdulbaqi, Yusrida Darwis, Reem Abou Assi, Nurzalina Abdul Karim Khan School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang, Malaysia Introduction: Colchicine is used for the treatment of gout, pseudo-gout, familial Mediterranean fever, and many other illnesses. Its oral administration is associated with poor bioavailability and severe gastrointestinal side effects. The drug is also known to have a low therapeutic index. Thus to overcome these drawbacks, the transdermal delivery of colchicine was investigated using transethosomal gels as potential carriers.Methods: Colchicine-loaded transethosomes (TEs were prepared by the cold method and statistically optimized using three sets of 24 factorial design experiments. The optimized formulations were incorporated into Carbopol 940® gel base. The prepared colchicine-loaded transethosomal gels were further characterized for vesicular size, dispersity, zeta potential, drug content, pH, viscosity, yield, rheological behavior, and ex vivo skin permeation through Sprague Dawley rats’ back skin.Results: The results showed that the colchicine-loaded TEs had aspherical irregular shape, nanometric size range, and high entrapment efficiency. All the formulated gels exhibited non-Newtonian plastic flow without thixotropy. Colchicine-loaded transethosomal gels were able to significantly enhance the skin permeation parameters of the drug in comparison to the non-ethosomal gel.Conclusion: These findings suggested that the transethosomal gels are promising carriers for the transdermal delivery of colchicine, providing an alternative route for drug administration. Keywords: transethosomes, ethosomal nanocarriers, colchicine, factorial design, skin permeation, rheology

  11. Optimization of Microemulsion Based Transdermal Gel of Triamcinolone.

    Science.gov (United States)

    Jagdale, Swati; Chaudhari, Bhagyashree

    2017-01-01

    Triamcinolone is a long acting corticosteroid used in the treatment of arthritis, eczema, psoriasis and similar conditions which cause inflammation. Triamcinolone has half-life of 88min. Prolonged oral use is associated with gastrointestinal adverse effects as peptic ulcer, abdominal distention and ulcerative esophagitis as described in various patents. Microemulgel offers advantage of better stability, better loading capacity and controlled release especially for drug with short half life. Objective of the present study was to optimize microemulgel based transdermal delivery of triamcinolone. Saturated solubility of triamcinolone in various oils, surfactants and co-surfactants is estimated. Pseudo-ternary phase diagrams were constructed to determine the region of transparent microemulsion. Microemulsion was evaluated for globule size (FE-SEM, zetasizer), % transmittance, pH, viscosity, conductivity etc. Design of experiment was used to optimize microemulsion based gel. Carbopol 971P and HPMC K100M were used as independent variables. Microemulsion based gel was evaluated for in-vitro as well as ex-vivo parameters. Microemulsion was formulated with oleic acid, lauroglycol FCC and propylene glycol. PDI 0.197 indicated microemulsion is mono-disperse. 32 factorial design gave batch F8 as optimized. Design expert suggested drug release; gel viscosity and bio-adhesive strength were three significant dependant factors affecting the transdermal delivery. F8 showed drug release 92.62.16±1.22% through egg membrane, 95.23±1.44% through goat skin after 8hr and Korsmeyer-Peppas release model was followed. It can be concluded that a stable, effective controlled release transdermal microemulgel was optimised for triamcinolone. This would be a promising tool to deliver triamcinolone with enhanced bioavailability and reduced dosing frequency. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Evaluation of paeonol-loaded transethosomes as transdermal delivery carriers.

    Science.gov (United States)

    Chen, Z X; Li, B; Liu, T; Wang, X; Zhu, Y; Wang, L; Wang, X H; Niu, X; Xiao, Y; Sun, Q

    2017-03-01

    Paeonol shows effective anti-allergic, anti-inflammatory and analgesic activities. However, because of its poor solubility in water and high volatility at room temperature, the application of this drug is restricted in the clinic. The objective of this research was to develop a biocompatible paeonol formulation with improved stability, skin delivery and pharmacokinetic efficiency. In this paper, paeonol-loaded vesicles were prepared using an ethanol injection method. Nano-vesicles were characterized for their physical properties and encapsulation efficiency (EE). Drug permeation behavior in vitro and deposition quantity in porcine ear skin were measured with a Valia-Chien (V-C) diffusion device. Additionally, a validated and sensitive high performance liquid chromatography (HPLC) method was developed to analyze paeonol concentrations in rat plasma after transdermal administration. The results showed that the particle-size order of the nano-vesicles was the following: transethosomes (122.5±7.5nm)transethosomes had a higher EE (85.5±5.2%), and they showed a spherical morphology with a smooth surface when viewed under a transmission electron microscope (TEM). In an in vitro permeation study, the paeonol transethosomes showed an enhanced transdermal flux of 95.7±8.8μg/cm 2 /h and a higher deposition quantity in porcine ear skin compared to the transfersomes. A one-compartment first-order absorption model could be used to describe the pharmacokinetics of paeonol in rats after transdermal administration. The AUC of the paeonol transethosomes was approximately 1.57- and 3.52-fold higher than those of the transfersomes and a saturated solution of paeonol in 35% ethanol, respectively. The results demonstrated that the paeonol transethosomes had a narrow size distribution, high encapsulation efficiency, and long residence in the plasma. This formulation remarkably enhanced the bioavailability of paeonol. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Transethosomal gels as carriers for the transdermal delivery of colchicine: statistical optimization, characterization, and ex vivo evaluation.

    Science.gov (United States)

    Abdulbaqi, Ibrahim M; Darwis, Yusrida; Assi, Reem Abou; Khan, Nurzalina Abdul Karim

    2018-01-01

    Colchicine is used for the treatment of gout, pseudo-gout, familial Mediterranean fever, and many other illnesses. Its oral administration is associated with poor bioavailability and severe gastrointestinal side effects. The drug is also known to have a low therapeutic index. Thus to overcome these drawbacks, the transdermal delivery of colchicine was investigated using transethosomal gels as potential carriers. Colchicine-loaded transethosomes (TEs) were prepared by the cold method and statistically optimized using three sets of 24 factorial design experiments. The optimized formulations were incorporated into Carbopol 940 ® gel base. The prepared colchicine-loaded transethosomal gels were further characterized for vesicular size, dispersity, zeta potential, drug content, pH, viscosity, yield, rheological behavior, and ex vivo skin permeation through Sprague Dawley rats' back skin. The results showed that the colchicine-loaded TEs had aspherical irregular shape, nanometric size range, and high entrapment efficiency. All the formulated gels exhibited non-Newtonian plastic flow without thixotropy. Colchicine-loaded transethosomal gels were able to significantly enhance the skin permeation parameters of the drug in comparison to the non-ethosomal gel. These findings suggested that the transethosomal gels are promising carriers for the transdermal delivery of colchicine, providing an alternative route for drug administration.

  14. Methylphenidate Transdermal System in Adults with Past Stimulant Misuse: An Open-Label Trial

    Science.gov (United States)

    McRae-Clark, Aimee L.; Brady, Kathleen T.; Hartwell, Karen J.; White, Kathleen; Carter, Rickey E.

    2011-01-01

    Objective: This 8-week, open-label trial assessed the efficacy of methylphenidate transdermal system (MTS) in 14 adult individuals diagnosed with ADHD and with a history of stimulant misuse, abuse, or dependence. Method: The primary efficacy endpoint was the Wender-Reimherr Adult ADHD Scale (WRAADS), and secondary efficacy endpoints included the…

  15. Methylphenidate Transdermal System in Adult ADHD and Impact on Emotional and Oppositional Symptoms

    Science.gov (United States)

    Marchant, Barrie K.; Reimherr, Frederick W.; Robison, Reid J.; Olsen, John L.; Kondo, Douglas G.

    2011-01-01

    Objective: This trial evaluated the effect of methylphenidate transdermal system (MTS) on the full spectrum of adult symptoms (attention-disorganization, hyperactivity-impulsivity, emotional dysregulation [ED], and oppositional-defiant disorder [ODD]) found in this disorder. Method: This placebo-controlled, double-blind, flexible-dose, crossover…

  16. Recent developments in skin mimic systems to predict transdermal permeation.

    Science.gov (United States)

    Waters, Laura J

    2015-01-01

    In recent years there has been a drive to create experimental techniques that can facilitate the accurate and precise prediction of transdermal permeation without the use of in vivo studies. This review considers why permeation data is essential, provides a brief summary as to how skin acts as a natural barrier to permeation and discusses why in vivo studies are undesirable. This is followed by an in-depth discussion on the extensive range of alternative methods that have been developed in recent years. All of the major 'skin mimic systems' are considered including: in vitro models using synthetic membranes, mathematical models including quantitative structure-permeability relationships (QSPRs), human skin equivalents and chromatographic based methods. All of these model based systems are ideally trying to achieve the same end-point, namely a reliable in vitro-in vivo correlation, i.e. matching non-in vivo obtained data with that from human clinical trials. It is only by achieving this aim, that any new method of obtaining permeation data can be acknowledged as a potential replacement for animal studies, for the determination of transdermal permeation. In this review, the relevance and potential applicability of the various models systems will also be discussed.

  17. The Effect and Mechanism of Transdermal Penetration Enhancement of Fu's Cupping Therapy: New Physical Penetration Technology for Transdermal Administration with Traditional Chinese Medicine (TCM) Characteristics.

    Science.gov (United States)

    Xie, Wei-Jie; Zhang, Yong-Ping; Xu, Jian; Sun, Xiao-Bo; Yang, Fang-Fang

    2017-03-27

    In this paper, a new type of physical penetration technology for transdermal administration with traditional Chinese medicine (TCM) characteristics is presented. Fu's cupping therapy (FCT), was established and studied using in vitro and in vivo experiments and the penetration effect and mechanism of FCT physical penetration technology was preliminarily discussed. With 1-(4-chlorobenzoyl)-5-methoxy-2-methylindole-3-ylacetic acid (indomethacin, IM) as a model drug, the establishment of high, medium, and low references was completed for the chemical permeation system via in vitro transdermal tests. Furthermore, using chemical penetration enhancers (CPEs) and iontophoresis as references, the percutaneous penetration effect of FCT for IM patches was evaluated using seven species of in vitro diffusion kinetics models and in vitro drug distribution; the IM quantitative analysis method in vivo was established using ultra-performance liquid chromatography-tandem mass spectrometry technology (UPLC-MS/MS), and pharmacokinetic parameters: area under the zero and first moment curves from 0 to last time t (AUC 0-t , AUMC 0-t ), area under the zero and first moment curves from 0 to infinity (AUC 0-∞ , AUMC 0-∞ ), maximum plasma concentration (C max ) and mean residence time (MRT), were used as indicators to evaluate the percutaneous penetration effect of FCT in vivo. Additionally, we used the 3 K factorial design to study the joint synergistic penetration effect on FCT and chemical penetration enhancers. Through scanning electron microscopy (SEM) and transmission electron microscope (TEM) imaging, micro- and ultrastructural changes on the surface of the stratum corneum (SC) were observed to explore the FCT penetration mechanism. In vitro and in vivo skin permeation experiments revealed that both the total cumulative percutaneous amount and in vivo percutaneous absorption amount of IM using FCT were greater than the amount using CPEs and iontophoresis. Firstly, compared with

  18. Studies on transdermal delivery enhancement of zidovudine.

    Science.gov (United States)

    Takmaz, Evrim Atilay; Inal, Ozge; Baykara, Tamer

    2009-01-01

    The purpose of this study was to investigate physicochemical characteristics and in vitro release of zidovudine from monolithic film of Eudragit RL 100 and ethyl cellulose. Films included 2.5% or 5% (w/w) zidovudine of the dry polymer weight were prepared in various ratios of polymers by solvent evaporation method from methanol/acetone solvent mixture. The release studies were carried out by vertical Franz cells (2.2 cm(2) area, 20 ml receptor fluid). Ex vivo studies were done on Wistar rat skin within the films F6 (Eudragit RL100) and F7 (Eudragit RL100/Ethylcellulose, 1:1) consisting 5% (w/w) zidovudine in comparison with the same amount of free drug. Either iontophoresis (0.1 and 0.5 mA/cm(2) direct currents, Ag/AgCl electrodes) or dimethyl sulfoxide (pretreatment of 1% and 5%, w/w, solutions) were used as enhancers. Films consisting of ethyl cellulose under the ratio of 50% (w/w) gave similar release profiles, and the highest in vitro cumulative released amount was achieved with F6 film which gave the closest results with the free drug. This result could be due to the high swelling capacity and re-crystallization inhibition effect of RL 100 polymer which also influenced the film homogenization. All the films were fitted to Higuchi release kinetics. It was also observed that both 0.5-mA/cm(2) current and 5% (w/w) dimethyl sulfoxide applications significantly increased the cumulative permeated amount of zidovudine after 8 h; however, the flux enhancement ratio was higher for 0.5-mA/cm(2) current application, especially within F6 film. Thus, it was concluded that Eudragit RL100 film (F6) could be further evaluated for the transdermal application of zidovudine.

  19. Introducing a method for mapping recreational experience

    DEFF Research Database (Denmark)

    Lindholst, Andrej Christian; Dempsey, Nicola; Burton, Mel

    2013-01-01

    spaces provide and support a range of recreational experiences. The exploration reported here is based on a short review of the methods background and an application in two test sites in Sheffield, South Yorkshire in early summer 2010. This paper critically appraises the application of rec......-mapping’, an innovative method of analysing and mapping positive recreational experiences in urban green spaces is explored and piloted within the UK planning context. Originating in the Nordic countries, this on-site method can provide urban planners and designers with data about the extent to which specific green......-mapping at smaller spatial scales and recommends further explorations within the UK planning context, as the method adds to existing open space assessment by providing a unique layer of information to analyse more fully the recreational qualities of urban green spaces....

  20. A commentary on transdermal drug delivery systems in clinical trials.

    Science.gov (United States)

    Watkinson, Adam C

    2013-09-01

    The number of drugs available as marketed transdermal products is limited to those that exhibit the correct physicochemical and pharmacokinetic properties that enable their effective delivery across the skin. In this respect, there are less than 20 drugs that are currently marketed in the US and EU as products that deliver systemic levels of their active ingredients. An analysis of clinical trials conducted in the transdermal sector shows a similar picture with only nine drugs accounting for approximately 80% of all transdermal clinical trials listed on ClinicalTrials.gov. Those drugs for which there are very few transdermal trials listed consist mostly of molecules that are inherently unsuitable for transdermal delivery and serve as a clear warning to drug developers that the science that governs transdermal drug delivery is well reflected by the successes and failures of drugs in development as well as those that make it to the market. Copyright © 2013 Wiley Periodicals, Inc.

  1. Alfuzosin hydrochloride transdermal films: evaluation of physicochemical, in vitro human cadaver skin permeation and thermodynamic parameters

    Directory of Open Access Journals (Sweden)

    Satyanarayan Pattnaik

    2009-12-01

    Full Text Available Purpose: The main objective of the investigation was to develop a transdermal therapeutic system for alfuzosin hydrochloride and to study the effects of polymeric system and loading dose on the in vitro skin permeation pattern. Materials and methods: Principles of experimental design have been exploited to develop the dosage form. Ratio of ethyl cellulose (EC and polyvinyl pyrrolidone (PVP and loading dose were selected as independent variables and their influence on the cumulative amount of alfuzosin hydrochloride permeated per cm2 of human cadaver skin at 24 h (Q24, permeation flux (J and steady state permeability coefficient (P SS were studied using experimental design. Various physicochemical parameters of the transdermal films were also evaluated. Activation energy for in vitro transdermal permeation has been estimated. Results: Ratio of EC and PVP was found to be the main influential factor for all the dependent variables studied. Drug loading dose was also found to influence the dependent variables but to a lesser extent. Physicochemical parameters of the prepared films were evaluated and found satisfactory. Activation energy for alfuzosin permeation has also been estimated and reported. Conclusion: The therapeutic system was found to be dermatologically non-irritant and hence, a therapeutically effective amount of alfuzosin hydrochloride can be delivered via a transdermal route.

  2. Hyaluronan-Based Nanohydrogels as Effective Carriers for Transdermal Delivery of Lipophilic Agents: Towards Transdermal Drug Administration in Neurological Disorders

    Directory of Open Access Journals (Sweden)

    Seong Uk Son

    2017-12-01

    Full Text Available We suggest a convenient nanoemulsion fabrication method to create hyaluronan (HA-based nanohydrogels for effective transdermal delivery. First, hyaluronan-conjugated dodecylamine (HA–Do HA-based polymers to load the lipophilic agents were synthesized with hyaluronan (HA and dodecylamine (Do by varying the substitution ratio of Do to HA. The synthetic yield of HA–Do was more than 80% (HA–Do (A: 82.7 ± 4.7%, HA–Do (B: 87.1 ± 3.9% and HA–Do (C: 81.4 ± 4.5%. Subsequently, nanohydrogels were fabricated using the nanoemulsion method. Indocyanine green (ICG simultaneously self-assembled with HA–Do, and the size depended on the substitution ratio of Do in HA–Do (nanohydrogel (A: 118.0 ± 2.2 nm, nanohydrogel (B: 121.9 ± 11.4 nm, and nanohydrogel (C: 142.2 ± 3.8 nm. The nanohydrogels were delivered into cells, and had excellent biocompatibility. Especially, nanohydrogel (A could deliver and permeate ICG into the deep skin layer, the dermis. This suggests that nanohydrogels can be potent transdermal delivery systems.

  3. Transdermal delivery of angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs) and others for management of hypertension.

    Science.gov (United States)

    Ahad, Abdul; Al-Mohizea, Abdullah Mohammed; Al-Jenoobi, Fahad Ibrahim; Aqil, Mohd

    2016-01-01

    Angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs) are some of the most commonly prescribed medications for hypertension. Most of all conventional dosage forms of ARBs and ACEIs undergo extensive first-pass metabolism, which significantly reduces bioavailability. Majority of ARBs and ACEIs are inherently short acting due to a rapid elimination half-life. In addition, oral dosage forms of ARBs and ACEIs have many high incidences of adverse effects due to variable absorption profiles, higher frequency of administration and poor patient compliance. Many attempts have been made globally at the laboratory level to investigate the skin permeation and to develop transdermal therapeutic systems of various ARBs, ACEIs and other anti-hypertensives, to circumvent the drawbacks associated with their conventional dosage form. This manuscript presents an outline of the transdermal research specifically in the area of ARBs, ACEIs and other anti-hypertensives reported in various pharmaceutical journals. The transdermal delivery has gained a significant importance for systemic treatment as it is able to avoid first-pass metabolism and major fluctuations of plasma levels typical of repeated oral administration. As we can experience from this review article that transdermal delivery of different ARBs and ACEIs improves bioavailability as well as patient compliance by many folds. In fact, the rationale development of some newer ARBs, ACEIs and other anti-hypertensives transdermal systems will provide new ways of treatment, circumventing current limitations for conventional dosage forms.

  4. A Comprehensive Review on: Transdermal drug delivery systems.

    OpenAIRE

    Kharat, Rekha; Bathe, Ritesh Suresh

    2016-01-01

    Transdermal drug delivery system was introduced to overcome the difficulties of drug delivery through oral route. Despite their relatively higher costs, transdermal delivery systems have proved advantageous for delivery of selected drugs, such as estrogens, testosterone, clonidine and nitro-glycerine. Transdermal delivery provides a leading edge over injectable and oral routes by increasing patient compliance and avoiding first pass metabolism respectively. Topical  administration  of  therap...

  5. Efficacy and safety of a transdermal contraceptive system.

    Science.gov (United States)

    Smallwood, G H; Meador, M L; Lenihan, J P; Shangold, G A; Fisher, A C; Creasy, G W

    2001-11-01

    To evaluate the efficacy, cycle control, compliance, and safety of a transdermal contraceptive system that delivers norelgestromin 150 microg and ethinyl estradiol 20 microg daily. In this open-label, 73-center study, 1672 healthy, ovulatory, sexually active women received ORTHO EVRA/EVRA for six (n = 1171) or 13 cycles (n = 501). The treatment regimen for each cycle was three consecutive 7-day patches (21 days) followed by 1 patch-free week. The overall and method-failure probabilities of pregnancy through 13 cycles were 0.7% and 0.4%, respectively. The incidence of breakthrough bleeding was low throughout the study. Perfect compliance (21 consecutive days of dosing, followed by a 7-day drug-free interval; no patch could be worn for more than 7 days) was achieved in 90% of subject cycles; only 1.9% of patches detached completely. Adverse events were typical of hormonal contraception, and most were mild-to-moderate in severity and not treatment limiting. The most common adverse events resulting in discontinuation were application site reactions (1.9%), nausea (1.8%), emotional lability (1.5%), headache (1.1%), and breast discomfort (1.0%). The transdermal contraceptive patch provides effective contraception and cycle control, and is well tolerated. The weekly change schedule for the contraceptive patch is associated with excellent compliance and wearability characteristics.

  6. Dissolving Microneedle Arrays for Transdermal Delivery of Amphiphilic Vaccines.

    Science.gov (United States)

    An, Myunggi; Liu, Haipeng

    2017-07-01

    Amphiphilic vaccine based on lipid-polymer conjugates is a new type of vaccine capable of self-delivering to the immune system. When injected subcutaneously, amphiphilic vaccines efficiently target antigen presenting cells in the lymph nodes (LNs) via a unique albumin-mediated transport and uptake mechanism and induce potent humoral and cellular immune responses. However, whether this new type of vaccine can be administrated via a safe, convenient microneedle-based transdermal approach remains unstudied. For such skin barrier-disruption systems, a simple application of microneedle arrays (MNs) is desired to disrupt the stratum corneum, and for rapid and pain-free self-administration of vaccines into the skin, the anatomic place permeates with an intricate mesh of lymphatic vessels draining to LNs. Here the microneedle transdermal approach is combined with amphiphilic vaccines to create a simple delivery approach which efficiently traffic molecular vaccines into lymphatics and draining LNs. The rapid release of amphiphilic vaccines into epidermis upon application of dissolving MNs to the skin of mice generates potent cellular and humoral responses, comparable or superior to those elicited by traditional needle-based immunizations. The results suggest that the amphiphilic vaccines delivered by dissolving MNs can provide a simple and safer vaccination method with enhanced vaccine efficacy. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Contingency Management for Alcohol Use Reduction: A Pilot Study using a Transdermal Alcohol Sensor*

    Science.gov (United States)

    Barnett, Nancy P.; Tidey, Jennifer; Murphy, James G.; Swift, Robert; Colby, Suzanne M.

    2011-01-01

    Background Contingency management (CM) has not been thoroughly evaluated as a treatment for alcohol abuse or dependence, in part because verification of alcohol use reduction requires frequent in-person breath tests. Transdermal alcohol sensors detect alcohol regularly throughout the day, providing remote monitoring and allowing for rapid reinforcement of reductions in use. Methods The purpose of this study was to evaluate the efficacy of CM for reduction in alcohol use, using a transdermal alcohol sensor to provide a continuous measure of alcohol use. Participants were 13 heavy drinking adults who wore the Secure Continuous Remote Alcohol Monitoring (SCRAM) bracelet for three weeks and provided reports of alcohol and drug use using daily web-based surveys. In Week 1, participants were asked to drink as usual; in Weeks 2 and 3, they were reinforced on an escalating schedule with values ranging from $5-$17 per day on days when alcohol use was not reported or detected by the SCRAM. Results Self-reports of percent days abstinent and drinks per week, and transdermal measures of average and peak transdermal alcohol concentration and area under the curve declined significantly in Weeks 2-3. A nonsignificant but large effect size for reduction in days of tobacco use also was found. An adjustment to the SCRAM criteria for detecting alcohol use provided an accurate but less conservative method for use with non-mandated clients. Conclusion Results support the efficacy of CM for alcohol use reductions and the feasibility of using transdermal monitoring of alcohol use for clinical purposes. PMID:21665385

  8. Experience with the Monte Carlo Method

    Energy Technology Data Exchange (ETDEWEB)

    Hussein, E M.A. [Department of Mechanical Engineering University of New Brunswick, Fredericton, N.B., (Canada)

    2007-06-15

    Monte Carlo simulation of radiation transport provides a powerful research and design tool that resembles in many aspects laboratory experiments. Moreover, Monte Carlo simulations can provide an insight not attainable in the laboratory. However, the Monte Carlo method has its limitations, which if not taken into account can result in misleading conclusions. This paper will present the experience of this author, over almost three decades, in the use of the Monte Carlo method for a variety of applications. Examples will be shown on how the method was used to explore new ideas, as a parametric study and design optimization tool, and to analyze experimental data. The consequences of not accounting in detail for detector response and the scattering of radiation by surrounding structures are two of the examples that will be presented to demonstrate the pitfall of condensed.

  9. Experience with the Monte Carlo Method

    International Nuclear Information System (INIS)

    Hussein, E.M.A.

    2007-01-01

    Monte Carlo simulation of radiation transport provides a powerful research and design tool that resembles in many aspects laboratory experiments. Moreover, Monte Carlo simulations can provide an insight not attainable in the laboratory. However, the Monte Carlo method has its limitations, which if not taken into account can result in misleading conclusions. This paper will present the experience of this author, over almost three decades, in the use of the Monte Carlo method for a variety of applications. Examples will be shown on how the method was used to explore new ideas, as a parametric study and design optimization tool, and to analyze experimental data. The consequences of not accounting in detail for detector response and the scattering of radiation by surrounding structures are two of the examples that will be presented to demonstrate the pitfall of condensed

  10. Multiscale modeling of transdermal drug delivery

    Science.gov (United States)

    Rim, Jee Eun

    2006-04-01

    This study addresses the modeling of transdermal diffusion of drugs, to better understand the permeation of molecules through the skin, and especially the stratum corneum, which forms the main permeation barrier of the skin. In transdermal delivery of systemic drugs, the drugs diffuse from a patch placed on the skin through the epidermis to the underlying blood vessels. The epidermis is the outermost layer of the skin and can be further divided into the stratum corneum (SC) and the viable epidermis layers. The SC consists of keratinous cells (corneocytes) embedded in the lipid multi-bilayers of the intercellular space. It is widely accepted that the barrier properties of the skin mostly arises from the ordered structure of the lipid bilayers. The diffusion path, at least for lipophilic molecules, seems to be mainly through the lipid bilayers. Despite the advantages of transdermal drug delivery compared to other drug delivery routes such as oral dosing and injections, the low percutaneous permeability of most compounds is a major difficulty in the wide application of transdermal drug delivery. In fact, many transdermal drug formulations include one or more permeation enhancers that increase the permeation of the drug significantly. During the last two decades, many researchers have studied percutaneous absorption of drugs both experimentally and theoretically. However, many are based on pharmacokinetic compartmental models, in which steady or pseudo-steady state conditions are assumed, with constant diffusivity and partitioning for single component systems. This study presents a framework for studying the multi-component diffusion of drugs coupled with enhancers through the skin by considering the microstructure of the stratum corneum (SC). A multiscale framework of modeling the transdermal diffusion of molecules is presented, by first calculating the microscopic diffusion coefficient in the lipid bilayers of the SC using molecular dynamics (MD). Then a

  11. Advanced progress of microencapsulation technologies: in vivo and in vitro models for studying oral and transdermal drug deliveries.

    Science.gov (United States)

    Lam, P L; Gambari, R

    2014-03-28

    This review provides an overall discussion of microencapsulation systems for both oral and transdermal drug deliveries. Clinically, many drugs, especially proteins and peptides, are susceptible to the gastrointestinal tract and the first-pass metabolism after oral administration while some drugs exhibit low skin permeability through transdermal delivery route. Medicated microcapsules as oral and transdermal drug delivery vehicles are believed to offer an extended drug effect at a relatively low dose and provide a better patient compliance. The polymeric microcapsules can be produced by different microencapsulation methods and the drug microencapsulation technology provides the quality preservation for drug stabilization. The release of the entrapped drug is controlled and prolonged for specific usages. Some recent studies have focused on the evaluation of drug containing microcapsules on potential biological and therapeutic applications. For the oral delivery, in vivo animal models were used for evaluating possible treatment effects of drug containing microcapsules. For the transdermal drug delivery, skin delivery models were introduced to investigate the potential skin delivery of medicated microcapsules. Finally, the challenges and limitations of drug microencapsulation in real life are discussed and the commercially available drug formulations using microencapsulation technology for oral and transdermal applications are shown. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Contingency management for alcohol use reduction: a pilot study using a transdermal alcohol sensor.

    Science.gov (United States)

    Barnett, Nancy P; Tidey, Jennifer; Murphy, James G; Swift, Robert; Colby, Suzanne M

    2011-11-01

    Contingency management (CM) has not been thoroughly evaluated as a treatment for alcohol abuse or dependence, in part because verification of alcohol use reduction requires frequent in-person breath tests. Transdermal alcohol sensors detect alcohol regularly throughout the day, providing remote monitoring and allowing for rapid reinforcement of reductions in use. The purpose of this study was to evaluate the efficacy of CM for reduction in alcohol use, using a transdermal alcohol sensor to provide a continuous measure of alcohol use. Participants were 13 heavy drinking adults who wore the Secure Continuous Remote Alcohol Monitoring (SCRAM) bracelet for three weeks and provided reports of alcohol and drug use using daily web-based surveys. In Week 1, participants were asked to drink as usual; in Weeks 2 and 3, they were reinforced on an escalating schedule with values ranging from $5 to $17 per day on days when alcohol use was not reported or detected by the SCRAM. Self-reports of percent days abstinent and drinks per week, and transdermal measures of average and peak transdermal alcohol concentration and area under the curve declined significantly in Weeks 2-3. A nonsignificant but large effect size for reduction in days of tobacco use also was found. An adjustment to the SCRAM criteria for detecting alcohol use provided an accurate but less conservative method for use with non-mandated clients. Results support the efficacy of CM for alcohol use reductions and the feasibility of using transdermal monitoring of alcohol use for clinical purposes. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  13. Transdermal drug delivery: approaches and significance

    OpenAIRE

    Murthy, SATHYANARAYANA

    2012-01-01

    S Narasimha MurthyDepartment of Pharmaceutics, The University of Mississippi, USATransdermal drug delivery systems deliver drugs through the skin as an alternative to oral, intravascular, subcutaneous, and transmucosal routes. Potential advantages of transdermal delivery include, but are not limited to, elimination of first-pass metabolism, steady delivery/blood levels, better patient compliance, reduced systemic drug interactions, possible dose intervention, avoidance of medically assisted d...

  14. Transdermal delivery of curcumin via microemulsion.

    Science.gov (United States)

    Sintov, Amnon C

    2015-03-15

    The objective of this study was to evaluate the transdermal delivery potential of a new curcumin-containing microemulsion system. Three series of experiments were carried out to comprehend the system characteristics: (a) examining the influence of water content on curcumin permeation, (b) studying the effect of curcumin loading on its permeability, and (c) assessing the contribution of the vesicular nature of the microemulsion on permeability. The skin permeability of curcumin from microemulsions, which contained 5%, 10%, and 20% of water content (1% curcumin), was measured in vitro using excised rat skin. It has been shown that the permeability coefficient of CUR in a formulation containing 10% aqueous phase (ME-10) was twofold higher than the values obtained for formulations with 5% and 20% water (Papp=0.116 × 10(-3)± 0.052 × 10(-3)vs. 0.043 × 10(-3)± 0.022 × 10(-3) and 0.047 × 10(-3)± 0.025 × 10(-3)cm/h, respectively. A reasonable explanation for this phenomenon may be the reduction of both droplet size and droplets' concentration in the microemulsion as the aqueous phase decreased from 20% to 5%. It has also been shown that a linear correlation exists between the decrease in droplet size and the increase of curcumin loading in the microemulsion. In addition, it has been demonstrated that a micellar system, S/O-mix, and a plain solution of curcumin resulted in a significantly lower curcumin permeation relative to that presented by the microemulsion, Papp=0.018 × 10(-3)± 0.011 × 10(-3), 0.005 × 10(-3)± 0.002 × 10(-3), and 0.002 × 10(-3)± 0.000 × 10(-3)cm/h, respectively, vs. 0.110 × 10(-3)± 0.021 × 10(-3)cm/h for the microemulsion. The enhancement ratio (ER=Jss-ME/Jss-solution) of CUR permeated via 1% loaded microemulsion was 55. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Current advances in the fabrication of microneedles for transdermal delivery

    NARCIS (Netherlands)

    Indermun, S.; Luttge, R.; Choonara, Y.E.; Kumar, Pradeep; Toit, Du L.C.; Modi, G.; Pillay, V.

    2014-01-01

    The transdermal route is an excellent site for drug delivery due to the avoidance of gastric degradation and hepatic metabolism, in addition to easy accessibility. Although offering numerous attractive advantages, many available transdermal systems are not able to deliver drugs and other compounds

  16. Social Experiments and Participatory Research as Method

    DEFF Research Database (Denmark)

    Dirckinck-Holmfeld, Lone

    2007-01-01

    Interdisciplinary research with stakeholders and users challenge the research methodologies to be used. These have to provide a shared language for all the participants, to build up trust, and to offer insights into the diverse perspectives of the participants. Further more it challenge ways to d...... practice-based methods where "social experiments with technology" and "dialogue research" are the key-words. ...... to discuss and validate contributions from each others - across different criteria for each discipline, and crosswise different agendas for stakeholders, politicians, practitioners and researchers. Participatory research and social experiments are methodologies which have been developed to cope......Interdisciplinary research with stakeholders and users challenge the research methodologies to be used. These have to provide a shared language for all the participants, to build up trust, and to offer insights into the diverse perspectives of the participants. Further more it challenge ways...

  17. Design, development, physicochemical, and in vitro and in vivo evaluation of transdermal patches containing diclofenac diethylammonium salt.

    Science.gov (United States)

    Arora, Priyanka; Mukherjee, Biswajit

    2002-09-01

    In this study, matrix-type transdermal patches containing diclofenac diethylamine were prepared using different ratios of polyvinylpyrrolidone (PVP) and ethylcellulose (EC) by solvent evaporation technique. The drug matrix film of PVP and EC was casted on a polyvinylalcohol backing membrane. All the prepared formulations were subjected to physical studies (moisture content, moisture uptake, and flatness), in vitro release studies and in vitro skin permeation studies. In vitro permeation studies were performed across cadaver skin using a modified diffusion cell. Variations in drug release profiles among the formulations studied were observed. Based on a physicochemical and in vitro skin permeation study, formulation PA4 (PVP/EC, 1:2) and PA5 (PVP/EC, 1:5) were chosen for further in vivo experiments. The antiinflammatory effect and a sustaining action of diclofenac diethylamine from the two transdermal patches selected were studied by inducing paw edema in rats with 1% w/v carrageenan solution. When the patches were applied half an hour before the subplantar injection of carrageenan in the hind paw of male Wistar rats, it was observed that formulation PA4 produced 100% inhibition of paw edema in rats 12 h after carrageenan insult, whereas in the case of formulation PA5, 4% mean paw edema was obtained half an hour after the carrageenan injection and the value became 19.23% 12 h after the carrageenan insult. The efficacy of transdermal patches was also compared with the marketed Voveran gel and it was found that PA4 transdermal patches produced a better result as compared with the Voveran gel. Hence, it can be reasonably concluded that diclofenac diethylamine can be formulated into the transdermal matrix type patches to sustain its release characteristics and the polymeric composition (PVP/EC, 1:2) was found to be the best choice for manufacturing transdermal patches of diclofenac diethylamine among the formulations studied. Copyright 2002 Wiley-Liss, Inc.

  18. Drug profile: transdermal rivastigmine patch in the treatment of Alzheimer disease.

    Science.gov (United States)

    Emre, Murat; Bernabei, Roberto; Blesa, Rafael; Bullock, Roger; Cunha, Luis; Daniëls, Hugo; Dziadulewicz, Edward; Förstl, Hans; Frölich, Lutz; Gabryelewicz, Tomasz; Levin, Oleg; Lindesay, James; Martínez-Lage, Pablo; Monsch, Andreas; Tsolaki, Magda; van Laar, Teus

    2010-08-01

    Cholinesterase inhibitors constitute one of the mainstays of treatment of Alzheimer disease (AD). Gastrointestinal side effects, difficulty accessing therapeutic doses and poor patient compliance have been identified as barriers to effective treatment with these substances. The rivastigmine transdermal patch provides continuous delivery of drug through the skin into the bloodstream, avoiding the fluctuations in plasma concentration associated with oral administration. This pharmacokinetic profile is associated with reduced side effects, resulting in easier access to expected target doses. These benefits, along with other practical advantages of the transdermal patch, may contribute to enhanced patient compliance. Here, we present a review of the current literature on rivastigmine patch, and offer advice based on our own collective clinical experience. Rivastigmine patch provides an efficient option for managing patients with AD, to be considered among the first line therapies for the disease.

  19. Solid‐in‐oil nanodispersions for transdermal drug delivery systems

    Science.gov (United States)

    Kitaoka, Momoko; Wakabayashi, Rie; Kamiya, Noriho

    2016-01-01

    Abstract Transdermal administration of drugs has advantages over conventional oral administration or administration using injection equipment. The route of administration reduces the opportunity for drug evacuation before systemic circulation, and enables long‐lasting drug administration at a modest body concentration. In addition, the skin is an attractive route for vaccination, because there are many immune cells in the skin. Recently, solid‐in‐oil nanodisperison (S/O) technique has demonstrated to deliver cosmetic and pharmaceutical bioactives efficiently through the skin. S/O nanodispersions are nanosized drug carriers designed to overcome the skin barrier. This review discusses the rationale for preparation of efficient and stable S/O nanodispersions, as well as application examples in cosmetic and pharmaceutical materials including vaccines. Drug administration using a patch is user‐friendly, and may improve patient compliance. The technique is a potent transcutaneous immunization method without needles. PMID:27529824

  20. Modeling of transdermal drug delivery with a microneedle array

    Science.gov (United States)

    Lv, Y.-G.; Liu, J.; Gao, Y.-H.; Xu, B.

    2006-11-01

    Transdermal drug delivery is generally limited by the extraordinary barrier properties of the stratum corneum, the outer 10-15 µm layer of skin. A conventional needle inserted across this barrier and into deeper tissues could effectively deliver drugs. However, it would lead to infection and cause pain, thereby reducing patient compliance. In order to administer a frequent injection of insulin and other therapeutic agents more efficiently, integrated arrays with very short microneedles were recently proposed as very good candidates for painless injection or extraction. A variety of microneedle designs have thus been made available by employing the fabrication tools of the microelectronics industry and using materials such as silicon, metals, polymers and glass with feature sizes ranging from sub-micron to nanometers. At the same time, experiments were also made to test the capability of the microneedles to inject drugs into tissues. However, due to the difficulty encountered in measurement, a detailed understanding of the spatial and transient drug delivery process still remains unclear up to now. To better grasp the mechanisms involved, quantitative theoretical models were developed in this paper to simultaneously characterize the flow and drug transport, and numerical solutions were performed to predict the kinetics of dispersed drugs injected into the skin from a microneedle array. Calculations indicated that increasing the initial injection velocity and accelerating the blood circulation in skin tissue with high porosity are helpful to enhance the transdermal drug delivery. This study provides the first quantitative simulation of fluid injection through a microneedle array and drug species transport inside the skin. The modeling strategy can also possibly be extended to deal with a wider range of clinical issues such as targeted nanoparticle delivery for therapeutics or molecular imaging.

  1. Comparative evaluation of rivastigmine permeation from a transdermal system in the Franz cell using synthetic membranes and pig ear skin with in vivo-in vitro correlation.

    Science.gov (United States)

    Simon, Alice; Amaro, Maria Inês; Healy, Anne Marie; Cabral, Lucio Mendes; de Sousa, Valeria Pereira

    2016-10-15

    In the present study, in vitro permeation experiments in a Franz diffusion cell were performed using different synthetic polymeric membranes and pig ear skin to evaluate a rivastigmine (RV) transdermal drug delivery system. In vitro-in vivo correlations (IVIVC) were examined to determine the best model membrane. In vitro permeation studies across different synthetic membranes and skin were performed for the Exelon(®) Patch (which contains RV), and the results were compared. Deconvolution of bioavailability data using the Wagner-Nelson method enabled the fraction of RV absorbed to be determined and a point-to-point IVIVC to be established. The synthetic membrane, Strat-M™, showed a RV permeation profile similar to that obtained with pig ear skin (R(2)=0.920). Studies with Strat-M™ resulted in a good and linear IVIVC (R(2)=0.991) when compared with other synthetic membranes that showed R(2) values less than 0.90. The R(2) for pig ear skin was 0.982. Strat-M™ membrane was the only synthetic membrane that adequately simulated skin barrier performance and therefore it can be considered to be a suitable alternative to human or animal skin in evaluating transdermal drug transport, potentially reducing the number of studies requiring human or animal samples. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. In vitro evaluation of transdermal nicotine delivery systems commercially available in Brazil

    Directory of Open Access Journals (Sweden)

    André Luís Morais Ruela

    2013-09-01

    Full Text Available The aim of this study was to develop and validate a method for evaluating the release and skin permeation from transdermal nicotine patches using the vertical diffusion cell (VDC. The VDC is an experimental apparatus employed in research, development, and the pharmaceutical field because it can simulate conditions closest to those established in clinical trials. Two transdermal nicotine delivery systems marketed in Brazil to release 14 mg over 24 hours were evaluated. Release studies were carried out using a regenerated cellulose dialysis membrane and permeation studies were carried out using excised porcine ear skin. The results indicated that nicotine release from both evaluated patches follows Higuchi's release kinetics, while skin permeation studies indicated zero-order release kinetics. Nicotine release rates were different between both evaluated patches, but drug permeation rates were not significantly different. According to validation studies, the method was appropriate for evaluating in vitro performance of nicotine patches. The proposed method can be applied to in vitro comparative studies between different commercial nicotine patches and may be used as an auxiliary tool in the design of new transdermal nicotine delivery systems.

  3. In vivo studies of transdermal nanoparticle delivery with microneedles using photoacoustic microscopy

    Science.gov (United States)

    Moothanchery, Mohesh; Seeni, Razina Z.; Xu, Chenjie; Pramanik, Manojit

    2017-01-01

    Microneedle technology allows micron-sized conduits to be formed within the outermost skin layers for both localized and systemic delivery of therapeutics including nanoparticles. Histological methods are often employed for characterization, and unfortunately do not allow for the in vivo visualization of the delivery process. This study presents the utilization of optical resolution-photoacoustic microscopy to characterize the transdermal delivery of nanoparticles using microneedles. Specifically, we observe the in vivo transdermal delivery of gold nanoparticles using microneedles in mice ear and study the penetration, diffusion, and spatial distribution of the nanoparticles in the tissue. The promising results reveal that photoacoustic microscopy can be used as a potential imaging modality for the in vivo characterization of microneedles based drug delivery. PMID:29296482

  4. Lipid Nanocapsule-Based Gels for Enhancement of Transdermal Delivery of Ketorolac Tromethamine

    Directory of Open Access Journals (Sweden)

    Jaleh Varshosaz

    2011-01-01

    Full Text Available Previous reports show ineffective transdermal delivery of ketorolac by nanostructured lipid carriers (NLCs. The aim of the present work was enhancement of transdermal delivery of ketorolac by another colloidal carriers, lipid nanocapsules (LNCs. LNCs were prepared by emulsification with phase transition method and mixed in a Carbomer 934P gel base with oleic acid or propylene glycol as penetration enhancers. Permeation studies were performed by Franz diffusion cell using excised rat abdominal skin. Aerosil-induced rat paw edema model was used to investigate the in vivo performance. LNCs containing polyethylene glycol hydroxyl stearate, lecithin in Labrafac as the oily phase, and dilution of the primary emulsion with 3.5-fold volume of cold water produced the optimized nanoparticles. The 1% Carbomer gel base containing 10% oleic acid loaded with nanoparticles enhanced and prolonged the anti-inflammatory effects of this drug to more than 12 h in Aerosil-induced rat paw edema model.

  5. Improvement in transdermal drug delivery performance by graphite oxide/temperature-responsive hydrogel composites with micro heater

    International Nuclear Information System (INIS)

    Yun, Jumi; Lee, Dae Hoon; Im, Ji Sun; Kim, Hyung-Il

    2012-01-01

    Transdermal drug delivery system (TDDS) was prepared with temperature-responsive hydrogel. The graphite was oxidized and incorporated into hydrogel matrix to improve the thermal response of hydrogel. The micro heater was fabricated to control the temperature precisely by adopting a joule heating method. The drug in hydrogel was delivered through a hairless mouse skin by controlling temperature. The efficiency of drug delivery was improved obviously by incorporation of graphite oxide due to the excellent thermal conductivity and the increased interfacial affinity between graphite oxide and hydrogel matrix. The fabricated micro heater was effective in controlling the temperature over lower critical solution temperature of hydrogel precisely with a small voltage less than 1 V. The cell viability test on graphite oxide composite hydrogel showed enough safety for using as a transdermal drug delivery patch. The performance of TDDS could be improved noticeably based on temperature-responsive hydrogel, thermally conductive graphite oxide, and efficient micro heater. - Graphical abstract: The high-performance transdermal drug delivery system could be prepared by combining temperature-responsive hydrogel, thermally conductive graphite oxide with improved interfacial affinity, and efficient micro heater fabricated by a joule heating method. Highlights: ► High performance of transdermal drug delivery system with an easy control of voltage. ► Improved thermal response of hydrogel by graphite oxide incorporation. ► Efficient micro heater fabricated by a joule heating method.

  6. Improvement in transdermal drug delivery performance by graphite oxide/temperature-responsive hydrogel composites with micro heater

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Jumi [Department of Fine Chemical Engineering and Applied Chemistry, BK21-E2M, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Lee, Dae Hoon [Environment Research Division, Korea Institute of Machinery and Materials, 171 Jang-dong, Yusong-gu, Daejeon 305-343 (Korea, Republic of); Im, Ji Sun [Department of Fine Chemical Engineering and Applied Chemistry, BK21-E2M, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Kim, Hyung-Il, E-mail: hikim@cnu.ac.kr [Department of Fine Chemical Engineering and Applied Chemistry, BK21-E2M, Chungnam National University, Daejeon 305-764 (Korea, Republic of)

    2012-08-01

    Transdermal drug delivery system (TDDS) was prepared with temperature-responsive hydrogel. The graphite was oxidized and incorporated into hydrogel matrix to improve the thermal response of hydrogel. The micro heater was fabricated to control the temperature precisely by adopting a joule heating method. The drug in hydrogel was delivered through a hairless mouse skin by controlling temperature. The efficiency of drug delivery was improved obviously by incorporation of graphite oxide due to the excellent thermal conductivity and the increased interfacial affinity between graphite oxide and hydrogel matrix. The fabricated micro heater was effective in controlling the temperature over lower critical solution temperature of hydrogel precisely with a small voltage less than 1 V. The cell viability test on graphite oxide composite hydrogel showed enough safety for using as a transdermal drug delivery patch. The performance of TDDS could be improved noticeably based on temperature-responsive hydrogel, thermally conductive graphite oxide, and efficient micro heater. - Graphical abstract: The high-performance transdermal drug delivery system could be prepared by combining temperature-responsive hydrogel, thermally conductive graphite oxide with improved interfacial affinity, and efficient micro heater fabricated by a joule heating method. Highlights: Black-Right-Pointing-Pointer High performance of transdermal drug delivery system with an easy control of voltage. Black-Right-Pointing-Pointer Improved thermal response of hydrogel by graphite oxide incorporation. Black-Right-Pointing-Pointer Efficient micro heater fabricated by a joule heating method.

  7. Preparation and the Biopharmaceutical Evaluation for the Metered Dose Transdermal Spray of Dexketoprofen

    Science.gov (United States)

    Luo, Huafei; Zhu, Zhuangzhi; Wu, Yubo; Luo, Jing; Wang, Hao

    2014-01-01

    The objective of the present work was to develop a metered dose transdermal spray (MDTS) formulation for transdermal delivery of dexketoprofen (DE). DE release from a series of formulations was assessed in vitro. Various qualitative and quantitative parameters like spray pattern, pump seal efficiency test, average weight per metered dose, and dose uniformity were evaluated. The optimized formulation with good skin permeation and an appropriate drug concentration and permeation enhancer (PE) content was developed incorporating 7% (w/w, %) DE, 7% (v/v, %) isopropyl myristate (IPM), and 93% (v/v, %) ethanol. In vivo pharmacokinetic study indicated that the optimized formulation showed a more sustainable plasma-concentration profile compared with the Fenli group. The antiinflammatory effect of DE MDTS was evaluated by experiments involving egg-albumin-induced paw edema in rats and xylene-induced ear swelling in mice. Acetic acid-induced abdominal constriction was used to evaluate the anti-nociceptive actions of DE MDTS. Pharmacodynamic studies indicated that the DE MDTS has good anti-inflammatory and anti-nociceptive activities. Besides, skin irritation studies were performed using rat as an animal model. The results obtained show that the MDTS can be a promising and innovative therapeutic system used in transdermal drug delivery for DE. PMID:24660066

  8. Preparation and the Biopharmaceutical Evaluation for the Metered Dose Transdermal Spray of Dexketoprofen

    Directory of Open Access Journals (Sweden)

    Wangding Lu

    2014-01-01

    Full Text Available The objective of the present work was to develop a metered dose transdermal spray (MDTS formulation for transdermal delivery of dexketoprofen (DE. DE release from a series of formulations was assessed in vitro. Various qualitative and quantitative parameters like spray pattern, pump seal efficiency test, average weight per metered dose, and dose uniformity were evaluated. The optimized formulation with good skin permeation and an appropriate drug concentration and permeation enhancer (PE content was developed incorporating 7% (w/w, % DE, 7% (v/v, % isopropyl myristate (IPM, and 93% (v/v, % ethanol. In vivo pharmacokinetic study indicated that the optimized formulation showed a more sustainable plasma-concentration profile compared with the Fenli group. The antiinflammatory effect of DE MDTS was evaluated by experiments involving egg-albumin-induced paw edema in rats and xylene-induced ear swelling in mice. Acetic acid-induced abdominal constriction was used to evaluate the anti-nociceptive actions of DE MDTS. Pharmacodynamic studies indicated that the DE MDTS has good anti-inflammatory and anti-nociceptive activities. Besides, skin irritation studies were performed using rat as an animal model. The results obtained show that the MDTS can be a promising and innovative therapeutic system used in transdermal drug delivery for DE.

  9. Physical, chemical and biological studies of gelatin/chitosan based transdermal fims with embedded silver nanoparticles

    Directory of Open Access Journals (Sweden)

    Sneha Paul

    2015-12-01

    Full Text Available Objective: To study the physical, chemical and biological properties of composite chitosangelatin transdermal film along with silver nanoparticles as binding agent and determine the compatibility of the prepared amalgamation towards wound management. Methods: Transdermal film preparations were done by solvent casting method containing different concentrations of biological synthesized silver nanoparticles. The films were characterized by using scanning electron microscope for their morphology and the determination of silver metal was done by using inductively coupled plasma atomic emission spectroscopy. Then a quantity of silver nanoparticles was further proceeded by physiochemical parameters (weight, thickness, temperature, solubility, absorption, tensile strength, in vitro drug release and skin permeation and biological parameters studies (anti-microbial, cytotoxicity and reactive oxygen species. Results: The film prepared by utilizing 2 g of gelatin and 0.5 g of chitosan exhibited better results. The physiochemical parameters studies revealed higher concentration of silver nanoparticles would give better results. In vitro drug release studies through dialysis and skin permeation showed the release of drug versus time (h. These films had shown excellent inhibition against Streptococcus and Escherichia coli species. Cytotoxicity study by MTT indicated the mild toxicity existed as the concentration of silver nanoparticles increased. Reactive oxygen species generation studies of transdermal film by using 2'7'-dichlorofluorescein diacetate assay demonstrated that the fluorescent cells were found in the higher concentration, which indicated cell damage (reactive oxygen species generated. Conclusions: Based on these observations, in vitro performances against various characteristics of transdermal film, would be utilized as a distinct dressing material and patches accessible in market.

  10. Thermoresponsive Hydrogels and Their Biomedical Applications: Special Insight into Their Applications in Textile Based Transdermal Therapy

    Directory of Open Access Journals (Sweden)

    Sudipta Chatterjee

    2018-04-01

    Full Text Available Various natural and synthetic polymers are capable of showing thermoresponsive properties and their hydrogels are finding a wide range of biomedical applications including drug delivery, tissue engineering and wound healing. Thermoresponsive hydrogels use temperature as external stimulus to show sol-gel transition and most of the thermoresponsive polymers can form hydrogels around body temperature. The availability of natural thermoresponsive polymers and multiple preparation methods of synthetic polymers, simple preparation method and high functionality of thermoresponsive hydrogels offer many advantages for developing drug delivery systems based on thermoresponsive hydrogels. In textile field applications of thermoresponsive hydrogels, textile based transdermal therapy is currently being applied using drug loaded thermoresponsive hydrogels. The current review focuses on the preparation, physico-chemical properties and various biomedical applications of thermoresponsive hydrogels based on natural and synthetic polymers and especially, their applications in developing functionalized textiles for transdermal therapies. Finally, future prospects of dual responsive (pH/temperature hydrogels made by these polymers for textile based transdermal treatments are mentioned in this review.

  11. Research of Ultrasound-Mediated Transdermal Drug Delivery System Using Cymbal-Type Piezoelectric Composite Transducer

    Science.gov (United States)

    Huan, Huiting; Gao, Chunming; Liu, Lixian; Sun, Qiming; Zhao, Binxing; Yan, Laijun

    2015-06-01

    Transdermal drug delivery (TDD) implemented by especially low-frequency ultrasound is generally known as sonophoresis or phonophoresis which has drawn considerable wide attention. However, TDD has not yet achieved its full potential as an alternative to conventional drug delivery methods due to its bulky instruments. In this paper, a cymbal-type piezoelectric composite transducer (CPCT) which has advantages over a traditional ultrasound generator in weight, flexibility, and power consumption, is used as a substitute ultrasonicator to realize TDD. First, theoretical research on a CPCT based on the finite element analysis was carried out according to which a series of applicable CPCTs with bandwidths of 20 kHz to 100 kHz were elaborated. Second, a TDD experimental setup was built with previously fabricated CPCTs aimed at the administration of glucose. Finally, the TDD performance of glucose molecule transport in porcine skin was measured in vitro by quantifying the concentration of glucose, and the time variation curves were subsequently obtained. During the experiment, the driving wave form, frequency, and power consumption of the transducers were selected as the main elements which determined the efficacy of glucose delivery. The results indicate that the effectiveness of the CPCT-based delivery is constrained more by the frequency and intensity of ultrasound rather than the driving waveform. The light-weight, flexibility, and low-power consumption of a CPCT can potentially achieve effective TDD.

  12. The value of oxybutynin in transdermal patches for treating overactive bladder.

    Science.gov (United States)

    Salinas-Casado, J; Esteban-Fuertes, M; Serrano, O; Galván, J

    2015-12-01

    There is currently a broad therapeutic arsenal of drugs for treating overactive bladder syndrome (OAB). However, there is still a need for new compounds and for improving known drugs in terms of efficacy, compliance and tolerability. To report the scientific evidence on the safety and efficacy of transdermal oxybutynin (OXY-TDS) for treating OAB. A systematic review without time restrictions was conducted until May 2015 in the MEDLINE/PubMed database. We also performed a manual review of abstracts published in international urogynaecology congresses. The evaluated studies show that patients treated with OXY-TDS experience a significant reduction in urinary incontinence episodes compared with placebo, which is comparable to that observed in patients treated with oral oxybutynin or with tolterodine. In all of the studies, we observed improvements in symptoms from the second or third week of treatment and in a sustained manner until the end of treatment (6, 12 or 24 weeks). The clinical practice study also showed improved quality of life, achieving benefits in numerous patient profiles, with an efficacy independent of previous treatments. The safety of the drug was demonstrated in the various patient profiles. OXY-TDS represents an effective alternative for the symptomatic treatment of adult patients with OAB, which, thanks to its pharmacokinetic profile, better tolerability, different administration method and dosage, could represent an added value in treating special populations. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Transdermal testosterone replacement therapy in men

    Directory of Open Access Journals (Sweden)

    Ullah MI

    2014-01-01

    Full Text Available M Iftekhar Ullah,1 Daniel M Riche,1,2 Christian A Koch1,31Department of Medicine, University of Mississippi Medical Center, 2Department of Pharmacy Practice, The University of Mississippi, 3GV (Sonny Montgomery VA Medical Center, Jackson, MS, USAAbstract: Androgen deficiency syndrome in men is a frequently diagnosed condition associated with clinical symptoms including fatigue, decreased libido, erectile dysfunction, and metabolic syndrome. Serum testosterone concentrations decline steadily with age. The prevalence of androgen deficiency syndrome in men varies depending on the age group, known and unknown comorbidities, and the respective study group. Reported prevalence rates may be underestimated, as not every man with symptoms of androgen deficiency seeks treatment. Additionally, men reporting symptoms of androgen deficiency may not be correctly diagnosed due to the vagueness of the symptom quality. The treatment of androgen deficiency syndrome or male hypogonadism may sometimes be difficult due to various reasons. There is no consensus as to when to start treating a respective man or with regards to the best treatment option for an individual patient. There is also lack of familiarity with treatment options among general practitioners. The formulations currently available on the market are generally expensive and dose adjustment protocols for each differ. All these factors add to the complexity of testosterone replacement therapy. In this article we will discuss the general indications of transdermal testosterone replacement therapy, available formulations, dosage, application sites, and recommended titration schedule.Keywords: hypogonadism, transdermal, testosterone, sexual function, testosterone replacement therapy, estradiol

  14. Enhancing the transdermal delivery of rigid nanoparticles using the simultaneous application of ultrasound and sodium lauryl sulfate.

    Science.gov (United States)

    Lopez, Renata F V; Seto, Jennifer E; Blankschtein, Daniel; Langer, Robert

    2011-01-01

    The potential of rigid nanoparticles to serve as transdermal drug carriers can be greatly enhanced by improving their skin penetration. Therefore, the simultaneous application of ultrasound and sodium lauryl sulfate (referred to as US/SLS) was evaluated as a skin pre-treatment method for enhancing the passive transdermal delivery of nanoparticles. We utilized inductively coupled plasma mass spectrometry and an improved application of confocal microscopy to compare the delivery of 10- and 20-nm cationic, neutral, and anionic quantum dots (QDs) into US/SLS-treated and untreated pig split-thickness skin. Our findings include: (a) ∼0.01% of the QDs penetrate the dermis of untreated skin (which we quantify for the first time), (b) the QDs fully permeate US/SLS-treated skin, (c) the two cationic QDs studied exhibit different extents of skin penetration and dermal clearance, and (d) the QD skin penetration is heterogeneous. We discuss routes of nanoparticle skin penetration and the application of the methods described herein to address conflicting literature reports on nanoparticle skin penetration. We conclude that US/SLS treatment significantly enhances QD transdermal penetration by 500-1300%. Our findings suggest that an optimum surface charge exists for nanoparticle skin penetration, and motivate the application of nanoparticle carriers to US/SLS-treated skin for enhanced transdermal drug delivery. Copyright © 2010 Elsevier Ltd. All rights reserved.

  15. Development of domperidone bilayered matrix type transdermal patches: physicochemical, in vitro and ex vivo characterization

    Directory of Open Access Journals (Sweden)

    S.K Madishetti

    2010-09-01

    Full Text Available "nBackground and the purpose of the study: Domperidone (DOM is a dopamine- receptor (D2 antagonist, which is widely used in the treatment of motion-sickness. The pharmacokinetic parameters make DOM a suitable candidate for transdermal delivery. The purpose of the present investigation was to develop transdermal delivery systems for DOM and to evaluate their physicochemical characteristics, in vitro release an ex vivo permeation through rat abdominal skin and their mechanical properties. "nMethods: Bilayered matrix type transdermal drug delivery systems (TDDS of DOM were prepared by film casting technique using hydroxypropyl methyl cellulose as primary and Eudragit RL 100 as secondary layers. Brij-35 was incorporated as a solubilizer, d-limonene and propylene glycol were employed as permeation enhancer and plasticizer respectively. The prepared TDDS were extensively evaluated for in vitro release, moisture absorption, moisture content, water vapor transmission, ex vivo permeation through rat abdominal skin, mechanical properties and stability studies. The physicochemical interaction between DOM and polymers were investigated by Differential Scanning Calorimetry (DSC and Fourier Transform Infrared Spectroscopy (FTIR. "nResults: All the formulations exhibited satisfactory physicochemical and mechanical characteristics. The optimized formulation F6 showed maximum cumulative percentage of drug release (90.7%, permeation (6806.64 μg in 24 hrs, flux (86.02 μg /hr/cm2 and permeation coefficient of 0.86x10-2 cm/hr. Values of tensile strength (4.34 kg/mm2 and elastic modulus (5.89 kg/cm2 revealed that formulation F6 was strong but not brittle. DSC and FTIR studies showed no evidence of interaction between the drug and polymers. A shelf life of 2 years is predicted for the TDDS. Conclusions: Domperidone bilayered matrix type transdermal therapeutic systems could be prepared with the required flux and suitable mechanical properties.

  16. Nonaqueous gel for the transdermal delivery of a DTPA penta-ethyl ester prodrug.

    Science.gov (United States)

    Zhang, Yong; Sadgrove, Matthew P; Sueda, Katsuhiko; Yang, Yu-Tsai; Pacyniak, Erik K; Kagel, John R; Braun, Brenda A; Zamboni, William C; Mumper, Russell J; Jay, Michael

    2013-04-01

    Diethylenetriamine pentaacetic acid penta-ethyl ester, designated as C2E5, was successfully incorporated into a nonaqueous gel for transdermal delivery. The thermal and rheological properties of a formulation containing 40% C2E5, 20% ethyl cellulose, and 40% Miglyol 840® prepared using the solvent evaporation method demonstrated that the gel had acceptable content uniformity and flow properties. In vitro studies showed that C2E5 was steadily released from the gel at a rate suitable for transdermal delivery. Topical application of the gel at a 200 mg C2E5/kg dose level in rats achieved significantly higher plasma exposures of several active metabolites compared with neat C2E5 oil at the same dose level. The results suggest that transdermal delivery of a chelator prodrug is an effective radionuclide decorporation strategy by delivering chelators to the circulation with a pharmacokinetic profile that is more consistent with the biokinetic profile of transuranic elements in contaminated individuals.

  17. Microemulsion for simultaneous transdermal delivery of benzocaine and indomethacin: in vitro and in vivo evaluation.

    Science.gov (United States)

    El Maghraby, Gamal M; Arafa, Mona F; Osman, Mohamed A

    2014-12-01

    This study investigated simultaneous transdermal delivery of indomethacin and benzocaine from microemulsion. Eucalyptus oil based microemulsion was used with Tween 80 and ethanol being employed as surfactant and cosurfactant, respectively. A microemulsion formulation comprising eucalyptus oil, polyoxyethylene sorbitan momooleate (Tween 80), ethanol and water (20:30:30:20) was selected. Indomethacin (1% w/w) and benzocaine (20% w/w) were incorporated separately or combined into this formulation before in vitro and in vivo evaluation. Application of indomethacin microemulsion enhanced the transdermal flux and reduced the lag time compared to saturated aqueous control. The same trend was evident for benzocaine microemulsion. Simultaneous application of the two drugs in microemulsion provided similar enhancement pattern. The in vivo evaluation employed the pinprick method and revealed rapid anesthesia after application of benzocaine microemulsion with the onset being 10 min and the action lasting for 50 min. For indomethacin microemulsion, the analgesic effect was recorded after 34.5 min and lasted for 70.5 min. Simultaneous application of benzocaine and indomethacin provided synergistic effect. The onset of action was achieved after 10 min and lasted for 95 min. The study highlighted the potential of microemulsion formulation in simultaneous transdermal delivery of two drugs.

  18. Nanostructured transdermal hormone replacement therapy for relieving menopausal symptoms: a confocal Raman spectroscopy study

    Directory of Open Access Journals (Sweden)

    Marco Antonio Botelho

    2014-02-01

    Full Text Available OBJECTIVE: To determine the safety and efficacy of a transdermal nanostructured formulation of progesterone (10% combined with estriol (0.1% + estradiol (0.25% for relieving postmenopausal symptoms. METHODS: A total of 66 postmenopausal Brazilian women with climacteric symptoms of natural menopause received transdermal nanostructured formulations of progesterone and estrogens in the forearm daily for 60 months to mimic the normal ovarian secretory pattern. Confocal Raman spectroscopy of hormones in skin layers was performed. Clinical parameters, serum concentrations of estradiol and follicle-stimulating hormone, blood pressure, BI-RADS classification from bilateral mammography, and symptomatic relief were compared between baseline and 60 months post-treatment. Clinicaltrials.gov: NCT02033512. RESULTS: An improvement in climacteric symptoms was reported in 92.5% of women evaluated before and after 60 months of treatment. The serum concentrations of estradiol and follicle-stimulating hormone changed significantly (p<0.05 after treatment; the values of serum follicle-stimulating hormone decreased after 60 months from 82.04±4.9 to 57.12±4.1 IU/mL. A bilateral mammography assessment of the breasts revealed normal results in all women. No adverse health-related events were attributed to this hormone replacement therapy protocol. CONCLUSION: The nanostructured formulation is safe and effective in re-establishing optimal serum levels of estradiol and follicle-stimulating hormone and relieving the symptoms of menopause. This transdermal hormone replacement therapy may alleviate climacteric symptoms in postmenopausal women.

  19. Deformable Nanovesicles Synthesized through an Adaptable Microfluidic Platform for Enhanced Localized Transdermal Drug Delivery

    Directory of Open Access Journals (Sweden)

    Naren Subbiah

    2017-01-01

    Full Text Available Phospholipid-based deformable nanovesicles (DNVs that have flexibility in shape offer an adaptable and facile method to encapsulate diverse classes of therapeutics and facilitate localized transdermal delivery while minimizing systemic exposure. Here we report the use of a microfluidic reactor for the synthesis of DNVs and show that alteration of input parameters such as flow speeds as well as molar and flow rate ratios increases entrapment efficiency of drugs and allows fine-tuning of DNV size, elasticity, and surface charge. To determine the ability of DNV-encapsulated drug to be delivered transdermally to a local site, we synthesized, characterized, and tested DNVs carrying the fluorescently labeled hydrophilic bisphosphonate drug AF-647 zoledronate (AF647-Zol. AF647-Zol DNVs were lyophilized, resuspended, and applied topically as a paste to the calvarial skin of mice. High-resolution fluorescent imaging and confocal microscopy revealed significant increase of encapsulated payload delivery to the target tissue—cranial bone—by DNVs as compared to nondeformable nanovesicles (NVs or aqueous drug solutions. Interestingly, NV delivery was not superior to aqueous drug solution. Our studies show that microfluidic reactor-synthesized DNVs can be produced in good yield, with high encapsulation efficiency, reproducibility, and stability after storage, and represent a useful vehicle for localized transdermal drug delivery.

  20. Protection against soman and sarin exposure by transdermal physostigmine and scopolamine

    Energy Technology Data Exchange (ETDEWEB)

    Meshulam, Y.; Davidovici, R.; Levy, A.

    1993-05-13

    The purpose of this study was to evaluate the prophylactic efficacy of physostigmine (physo), administered via sustained release (SR) methods, with and without scopolamine, against soman and sarin exposure in guinea-pigs. Transdermal physo pad (3 sq cm/kg; 60-80 ug/sq cm), containing a vehicle based on propionic acid, was applied onto the dorsal back of the animals, 24 hours before exposure to the cholinesterase (ChE) inhibitors. At the time of exposure, physo concentrations in brain and plasma were 3.6 ng/g and 4.1 ng/ml respectively. Brain and whole blood ChE activity were inhibited to 70% and 57% of their original activity. Transdermal physo by itself protected up to 70% of the animals exposed to 1.5 LD(50) of soman or sarin (100% mortality was recorded in the control group). Combining transdermal physo with Scopoderm (by Ciba Geigy Inc.) provided full protection against 1.5 LD(50).

  1. Nanostructured transdermal hormone replacement therapy for relieving menopausal symptoms: a confocal Raman spectroscopy study

    International Nuclear Information System (INIS)

    Botelho, Marco Antonio; Queiroz, Dinalva Brito; Barros, Gisele; Guerreiro, Stela; Umbelino, Sonia; Lyra, Arao; Borges, Boniek; Freitas, Allan; Almeida, Jackson Guedes; Quintans Junior, Lucindo

    2014-01-01

    Objective:to determine the safety and efficacy of a transdermal nanostructured formulation of progesterone (10%) combined with estriol (0.1%) + estradiol (0.25%) for relieving postmenopausal symptoms. Methods: a total of 66 postmenopausal Brazilian women with climacteric symptoms of natural menopause received transdermal nanostructured formulations of progesterone and estrogens in the forearm daily for 60 months to mimic the normal ovarian secretory pattern. Confocal Raman spectroscopy of hormones in skin layers was performed. Clinical parameters, serum concentrations of estradiol and follicle-stimulating hormone, blood pressure, BI-RADS classification from bilateral mammography, and symptomatic relief were compared between baseline and 60 months post-treatment. Clinicaltrials.gov: NCT02033512. Results: an improvement in climacteric symptoms was reported in 92.5% of women evaluated before and after 60 months of treatment. The serum concentrations of estradiol and follicle-stimulating hormone changed significantly (p<0.05) after treatment; the values of serum follicle-stimulating hormone decreased after 60 months from 82.04 ± 4.9 to 57.12 ± 4.1 IU/mL. A bilateral mammography assessment of the breasts revealed normal results in all women. No adverse health-related events were attributed to this hormone replacement therapy protocol. Conclusion: the nanostructured formulation is safe and effective in re-establishing optimal serum levels of estradiol and follicle-stimulating hormone and relieving the symptoms of menopause. This transdermal hormone replacement therapy may alleviate climacteric symptoms in postmenopausal women. (author)

  2. Formulation, characterization and clinical evaluation of propranolol hydrochloride gel for transdermal treatment of superficial infantile hemangioma.

    Science.gov (United States)

    Zhou, Wenhu; He, Shiying; Yang, Yijun; Jian, Dan; Chen, Xiang; Ding, Jinsong

    2015-01-01

    The objective of the present study is to formulate and characterize propranolol hydrochloride (PPL · HCl) gel, and to evaluate the efficacy of this formulation in transdermal treatment for superficial infantile hemangioma (IH). The transdermal PPL · HCl gel was prepared by a direct swelling method, which chose hydroxypropyl methylcellulose (HPMC) as the matrix and used terpenes plus alcohols as permeation enhancer. Permeation studies of PPL · HCl were carried out with modified Franz diffusion cells through piglet skin. Our results pointed to that among all studied permeation enhancers, farnesol plus isopropanol was the most effective combination (Q24, 6027.4 ± 563.1 μg/cm(2), ER, 6.8), which was significantly higher than that of control gel (p homemade PPL · HCl oral solution as a control. Clinical studies also confirmed the excellent therapeutic response and few side effects of the PPL · HCl gel. These results suggest that transdermal application of the PPL · HCl gel is an effective and safe formulation in treating superficial IH.

  3. Microneedle-mediated transdermal delivery of nanostructured lipid carriers for alkaloids from Aconitum sinomontanum.

    Science.gov (United States)

    Guo, Teng; Zhang, Yongtai; Li, Zhe; Zhao, Jihui; Feng, Nianping

    2017-09-12

    A combination method using microneedle (MN) pretreatment and nanostructured lipid carriers (NLCs) was developed to improve the transdermal delivery of therapeutics. The MN treatment of the skin and co-administration of NLCs loaded with total alkaloids isolated from Aconitum sinomontanum (AAS-NLCs) significantly increased the skin permeation of the drugs. Fluorescence imaging confirmed that MNs could provide microchannels penetrating the stratum corneum, and delivery of NLCs through the channels led to their deeper permeation. In vivo studies showed that combination of AAS-NLCs with MNs (AAS-NLCs-MN) in transdermal delivery could improve the bioavailability and maintain stable drug concentrations in the blood. Moreover, AAS-NLCs-MN showed benefits in eliminating paw swelling, decreasing inflammation and pain, and regulating immune function in adjuvant arthritis rats. After administration of AAS-NLCs-MN, no skin irritation was observed in rabbits, and electrocardiograms of rats showed improved arrhythmia. These results indicated that the dual approach combining MN insertion and NLCs has the potential to provide safe transdermal delivery and to improve the therapeutic efficacy through sustained release of AAS.

  4. Nanostructured transdermal hormone replacement therapy for relieving menopausal symptoms: a confocal Raman spectroscopy study

    Energy Technology Data Exchange (ETDEWEB)

    Botelho, Marco Antonio; Queiroz, Dinalva Brito; Barros, Gisele; Guerreiro, Stela; Umbelino, Sonia; Lyra, Arao; Borges, Boniek; Freitas, Allan, E-mail: marcobotelho@pq.cnpq.br [Universidade Potiguar, Natal, RN (Brazil). Lab. de Nanotecnologia; Fechine, Pierre [Universidade Federal do Ceara (GQMAT/UFCE), Fortaleza, CE (Brazil). Dept. de Quimica Analitica. Grupo Avancado de Biomateriais em Quimica; Queiroz, Danilo Caldas de [Instituto Federal de Ciencia e Tecnologia (IFCT), Fortaleza, CE (Brazil). Lab. de Biotecnologia; Ruela, Ronaldo [Instituto de Biotecnologia Aplicada (INBIOS), Fortaleza, CE (Brazil); Almeida, Jackson Guedes [Universidade Federal do Vale de Sao Francisco (UNIVALE), Petrolina, PE (Brazil). Fac. de Ciencias Farmaceuticas; Quintans Junior, Lucindo [Universidade Federal de Sergipe (UFSE), Sao Cristovao, SE (Brazil). Dept. de Fisiologia

    2014-06-01

    Objective:to determine the safety and efficacy of a transdermal nanostructured formulation of progesterone (10%) combined with estriol (0.1%) + estradiol (0.25%) for relieving postmenopausal symptoms. Methods: a total of 66 postmenopausal Brazilian women with climacteric symptoms of natural menopause received transdermal nanostructured formulations of progesterone and estrogens in the forearm daily for 60 months to mimic the normal ovarian secretory pattern. Confocal Raman spectroscopy of hormones in skin layers was performed. Clinical parameters, serum concentrations of estradiol and follicle-stimulating hormone, blood pressure, BI-RADS classification from bilateral mammography, and symptomatic relief were compared between baseline and 60 months post-treatment. Clinicaltrials.gov: NCT02033512. Results: an improvement in climacteric symptoms was reported in 92.5% of women evaluated before and after 60 months of treatment. The serum concentrations of estradiol and follicle-stimulating hormone changed significantly (p<0.05) after treatment; the values of serum follicle-stimulating hormone decreased after 60 months from 82.04 ± 4.9 to 57.12 ± 4.1 IU/mL. A bilateral mammography assessment of the breasts revealed normal results in all women. No adverse health-related events were attributed to this hormone replacement therapy protocol. Conclusion: the nanostructured formulation is safe and effective in re-establishing optimal serum levels of estradiol and follicle-stimulating hormone and relieving the symptoms of menopause. This transdermal hormone replacement therapy may alleviate climacteric symptoms in postmenopausal women. (author)

  5. Topical and transdermal drug delivery: principles and practice

    National Research Council Canada - National Science Library

    Benson, Heather A. E; Watkinson, Adam C

    2012-01-01

    .... Providing an overview of the current science in drug and cosmetic application to and through the skin, Topical and Transdermal Drug Delivery includes treatment of skin conditions, skin permeation...

  6. 3D printing applications for transdermal drug delivery.

    Science.gov (United States)

    Economidou, Sophia N; Lamprou, Dimitrios A; Douroumis, Dennis

    2018-06-15

    The role of two and three-dimensional printing as a fabrication technology for sophisticated transdermal drug delivery systems is explored in literature. 3D printing encompasses a family of distinct technologies that employ a virtual model to produce a physical object through numerically controlled apparatuses. The applicability of several printing technologies has been researched for the direct or indirect printing of microneedle arrays or for the modification of their surface through drug-containing coatings. The findings of the respective studies are presented. The range of printable materials that are currently used or potentially can be employed for 3D printing of transdermal drug delivery (TDD) systems is also reviewed. Moreover, the expected impact and challenges of the adoption of 3D printing as a manufacturing technique for transdermal drug delivery systems, are assessed. Finally, this paper outlines the current regulatory framework associated with 3D printed transdermal drug delivery systems. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Modified Transdermal Technologies: Breaking the Barriers of Drug ...

    African Journals Online (AJOL)

    In-depth analysis, formulation approaches, applications, advantages and disadvantages of these newer technologies are discussed. Keywords: Transdermal drug delivery, microneedles, macroflux, iontophoresis, ultrasound, powderject, skin abrasion. > Tropical Journal of Pharmaceutical Research Vol. 6 (1) 2007: pp. 633- ...

  8. Penetration Enhancement Effect of Turpentine Oil on Transdermal ...

    African Journals Online (AJOL)

    inflammation drastically affect the quality of life after SCI. ... inhibitors may reduce spinal cord ischemic injury. [11]. Various .... Healthy male Wistar rats (200-250 g) were used ..... Guy RH. Transdermal science and technology an update.

  9. Efficient Transdermal Delivery of Benfotiamine in an Animal Model

    OpenAIRE

    Varadi, Gyula; Zhu, Zhen; G. Carter, Stephen

    2015-01-01

    We designed a transdermal system to serve as a delivery platform for benfotiamine utilizing the attributes of passive penetration enhancing molecules to penetrate through the outer layers of skin combined with the advance of incorporating various peripherally-acting vasodilators to enhance drug uptake.  Benfotiamine, incorporated into this transdermal formulation, was applied to skin in an animal model in order to determine the ability to deliver this thiamine pro-drug effectively to the sub-...

  10. Enhancement of the bioavailability of an antihypertensive drug by transdermal protransfersomal system: formulation and in vivo study.

    Science.gov (United States)

    Morsi, Nadia M; Aboelwafa, Ahmed A; Dawoud, Marwa H S

    2018-06-01

    Timolol Maleate (TiM), a nonselective β-adrenergic blocker, is a potent highly effective agent for management of hypertension. The drug suffers from poor oral bioavailability (50%) due to its first pass effect and a short elimination half-life of 4 h; resulting in its frequent administration. Transdermal formulation may circumvent these problems in the form of protransfersomes. The aim of this study is to develop and optimize transdermal protransfersomal system of Timolol Maleate by film deposition on carrier method where protransfersomes were converted to transfersomes upon skin hydration following transdermal application under occlusive conditions. Two 2 3 full factorial designs were employed to investigate the influence of three formulation variables which were; phosphatidyl choline: surfactant molar ratio, carrier: mixture and the type of SAA each on particle size, drug entrapment efficiency and release rate. The optimized formulation was evaluated regarding permeation through hairless rat skin and compared with oral administration of aqueous solution on male Wistar rats. Optimized protransfersomal system had excellent permeation rate through shaved rat skin (780.69 μg/cm 2 /h) and showed six times increase in relative bioavailability with prolonged plasma profile up to 72 h. A potential protransfresomal transdermal system was successfully developed and factorial design was found to be a smart tool in its optimization.

  11. Rotigotine transdermal patch for the treatment of Parkinson's Disease.

    Science.gov (United States)

    Perez-Lloret, Santiago; Rey, María Verónica; Ratti, Pietro Lucca; Rascol, Olivier

    2013-02-01

    Rotigotine, a non-ergot dopamine agonist, has been developed as a novel transdermal formulation. The rotigotine transdermal patch has received EMEA marketing authorization for the treatment of adult patients with early or advanced Parkinson's disease (PD) or with moderate to severe restless legs syndrome (RLS). FDA originally granted a marketing authorization for early PD, which was later suspended, and is now studying the authorization for RLS. The aim of this review is to review the pharmacokinetics, pharmacodynamics as well as the clinical efficacy and tolerability of the rotigotine transdermal patch in PD. Source material was identified using a PubMed search for the term 'rotigotine' and PD. Articles published up to January 2011 or abstract submitted to most relevant international neurology congresses were reviewed. The rotigotine transdermal patch is efficacious for the treatment of PD. Tolerability profile appears to be well within the range of that observed with other non-ergot dopamine agonists in PD. Application-site reactions were the most frequent adverse event, and they were considered mild to moderate in the majority of cases. The rotigotine transdermal patch offers a safe and efficacious alternative for the treatment of PD. Further studies should focus on the possibility that continuous dopamine stimulation by means of the transdermal patch has any influence on levodopa-related motor complications. © 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de Pharmacologie et de Thérapeutique.

  12. Conductive polymer nanotube patch for fast and controlled in vivo transdermal drug delivery

    Science.gov (United States)

    Nguyen, Thao M.

    Transdermal drug delivery has created new applications for existing therapies and offered an alternative to the traditional oral route where drugs can prematurely metabolize in the liver causing adverse side effects. Opening the transdermal delivery route to large hydrophilic drugs is one of the greatest challenges due to the hydrophobicity of the skin. However, the ability to deliver hydrophilic drugs using a transdermal patch would provide a solution to problems of other delivery methods for hydrophilic drugs. The switching of conductive polymers (CP) between redox states cause simultaneous changes in the polymer charge, conductivity, and volume—properties that can all be exploited in the biomedical field of controlled drug delivery. Using the template synthesis method, poly(3,4-ethylenedioxythiophene (PEDOT) nanotubes were synthesized electrochemically and a transdermal drug delivery patch was successfully designed and developed. In vitro and in vivo uptake and release of hydrophilic drugs were investigated. The relationship between the strength of the applied potential and rate of drug release were also investigated. Results revealed that the strength of the applied potential is proportional to the rate of drug release; therefore one can control the rate of drug release by controlling the applied potential. The in vitro studies focused on the kinetics of the drug delivery system. It was determined that the drug released mainly followed zero-order kinetics. In addition, it was determined that applying a releasing potential to the transdermal drug delivery system lead to a higher release rate constant (up to 7 times greater) over an extended period of time (˜24h). In addition, over 24 hours, an average of 80% more model drug molecules were released with an applied potential than without. The in vivo study showed that the drug delivery system was capable of delivering model hydrophilic drugs molecules through the dermis layer of the skin within 30 minutes

  13. In vivo real-time monitoring system of electroporation mediated control of transdermal and topical drug delivery.

    Science.gov (United States)

    Blagus, Tanja; Markelc, Bostjan; Cemazar, Maja; Kosjek, Tina; Preat, Veronique; Miklavcic, Damijan; Sersa, Gregor

    2013-12-28

    Electroporation (EP) is a physical method for the delivery of molecules into cells and tissues, including the skin. In this study, in order to control the degree of transdermal and topical drug delivery, EP at different amplitudes of electric pulses was evaluated. A new in vivo real-time monitoring system based on fluorescently labeled molecules was developed, for the quantification of transdermal and topical drug delivery. EP of the mouse skin was performed with new non-invasive multi-array electrodes, delivering different amplitudes of electric pulses ranging from 70 to 570 V, between the electrode pin pairs. Patches, soaked with 4 kDa fluorescein-isothiocyanate labeled dextran (FD), doxorubicin (DOX) or fentanyl (FEN), were applied to the skin before and after EP. The new monitoring system was developed based on the delivery of FD to and through the skin. FD relative quantity was determined with fluorescence microscopy imaging, in the treated region of the skin for topical delivery and in a segment of the mouse tail for transdermal delivery. The application of electric pulses for FD delivery resulted in enhanced transdermal delivery. Depending on the amplitude of electric pulses, it increased up to the amplitude of 360 V, and decreased at higher amplitudes (460 and 570 V). Topical delivery steadily enhanced with increasing the amplitude of the delivered electric pulses, being even higher than after tape stripping used as a positive control. The non-invasive monitoring of the delivery of DOX, a fluorescent chemotherapeutic drug, qualitatively and quantitatively confirmed the effects of EP at 360 and 570 V pulse amplitudes on topical and transdermal drug delivery. Delivery of FEN at 360 and 570 V pulse amplitudes verified the observed effects as obtained with FD and DOX, by the measured physiological responses of the mice as well as FEN plasma concentration. This study demonstrates that with the newly developed non-invasive multi-array electrodes and with the

  14. Authentic Teaching Experiences in Secondary Mathematics Methods

    Science.gov (United States)

    Stickles, Paula R.

    2015-01-01

    Often secondary mathematics methods courses include classroom peer teaching, but many pre-service teachers find it challenging to teach their classmate peers as there are no discipline issues and little mathematical discourse as the "students" know the content. We will share a recent change in our methods course where pre-service…

  15. The Guided Autobiography Method: A Learning Experience

    Science.gov (United States)

    Thornton, James E.

    2008-01-01

    This article discusses the proposition that learning is an unexplored feature of the guided autobiography method and its developmental exchange. Learning, conceptualized and explored as the embedded and embodied processes, is essential in narrative activities of the guided autobiography method leading to psychosocial development and growth in…

  16. Interpretation of substitution experiments by homogenisation two-group method

    International Nuclear Information System (INIS)

    Sotic, O.

    1970-02-01

    This paper describes methods for interpretation of progressive substitution experiments for determining material buckling in homogeneous two-group approximation. These methods were applied for experiments on the zero power RB reactor in Vinca. Experiments were done on the reflected heavy water reactor core, the lattice pitch had unisotropy properties

  17. Peptide-chaperone-directed transdermal protein delivery requires energy.

    Science.gov (United States)

    Ruan, Renquan; Jin, Peipei; Zhang, Li; Wang, Changli; Chen, Chuanjun; Ding, Weiping; Wen, Longping

    2014-11-03

    The biologically inspired transdermal enhanced peptide TD1 has been discovered to specifically facilitate transdermal delivery of biological macromolecules. However, the biological behavior of TD1 has not been fully defined. In this study, we find that energy is required for the TD1-mediated transdermal protein delivery through rat and human skins. Our results show that the permeation activity of TD1-hEGF, a fusion protein composed of human epidermal growth factor (hEGF) and the TD1 sequence connected with a glycine-serine linker (GGGGS), can be inhibited by the energy inhibitor, rotenone or oligomycin. In addition, adenosine triphosphate (ATP), the essential energetic molecule in organic systems, can effectively facilitate the TD1 directed permeation of the protein-based drug into the skin in a dose-dependent fashion. Our results here demonstrate a novel energy-dependent permeation process during the TD1-mediated transdermal protein delivery that could be valuable for the future development of promising new transdermal drugs.

  18. Effect of components (polymer, plasticizer and solvent as a variable in fabrication of diclofenac transdermal patch

    Directory of Open Access Journals (Sweden)

    Chetna Modi

    2012-01-01

    Full Text Available Transdermal drug delivery influence consumer acceptance and marked increase in bioavailability of some drugs which undergoes hepatic first-pass metabolism. Fabrication of transdermal patch requires lots of attention regarding the amount of components used for it. Because of varied nature of polymer and plasticizer, transdermal patches have different properties and different drug release. This study is on the basis to evaluate the amount to be needed for fabrication of diclofenac transdermal patch. Study shows that Hydroxy Propyl Methyl Cellulose has great influence on transdermal patch, if it is used alone in combination with glycerin or PEG-4000 plasticizer.

  19. Transdermal delivery of paeonol using cubic gel and microemulsion gel

    Science.gov (United States)

    Luo, Maofu; Shen, Qi; Chen, Jinjin

    2011-01-01

    Background The aim of this study was to develop new systems for transdermal delivery of paeonol, in particular microemulsion gel and cubic gel formulations. Methods Various microemulsion vehicles were prepared using isopropyl myristate as an oil phase, polyoxyethylated castor oil (Cremophor® EL) as a surfactant, and polyethylene glycol 400 as a cosurfactant. In the optimum microemulsion gel formulation, carbomer 940 was selected as the gel matrix, and consisted of 1% paeonol, 4% isopropyl myristate, 28% Cremophor EL/polyethylene glycol 400 (1:1), and 67% water. The cubic gel was prepared containing 3% paeonol, 30% water, and 67% glyceryl monooleate. Results A skin permeability test using excised rat skins indicated that both the cubic gel and microemulsion gel formulations had higher permeability than did the paeonol solution. An in vivo pharmacokinetic study done in rats showed that the relative bioavailability of the cubic gel and microemulsion gel was enhanced by about 1.51-fold and 1.28-fold, respectively, compared with orally administered paeonol suspension. Conclusion Both the cubic gel and microemulsion gel formulations are promising delivery systems to enhance the skin permeability of paeonol, in particular the cubic gel. PMID:21904450

  20. Solid-in-oil nanodispersions for transdermal drug delivery systems.

    Science.gov (United States)

    Kitaoka, Momoko; Wakabayashi, Rie; Kamiya, Noriho; Goto, Masahiro

    2016-11-01

    Transdermal administration of drugs has advantages over conventional oral administration or administration using injection equipment. The route of administration reduces the opportunity for drug evacuation before systemic circulation, and enables long-lasting drug administration at a modest body concentration. In addition, the skin is an attractive route for vaccination, because there are many immune cells in the skin. Recently, solid-in-oil nanodisperison (S/O) technique has demonstrated to deliver cosmetic and pharmaceutical bioactives efficiently through the skin. S/O nanodispersions are nanosized drug carriers designed to overcome the skin barrier. This review discusses the rationale for preparation of efficient and stable S/O nanodispersions, as well as application examples in cosmetic and pharmaceutical materials including vaccines. Drug administration using a patch is user-friendly, and may improve patient compliance. The technique is a potent transcutaneous immunization method without needles. © 2016 The Authors. Biotechnology Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Biodegradable 3D printed polymer microneedles for transdermal drug delivery.

    Science.gov (United States)

    Luzuriaga, Michael A; Berry, Danielle R; Reagan, John C; Smaldone, Ronald A; Gassensmith, Jeremiah J

    2018-04-17

    Biodegradable polymer microneedle (MN) arrays are an emerging class of transdermal drug delivery devices that promise a painless and sanitary alternative to syringes; however, prototyping bespoke needle architectures is expensive and requires production of new master templates. Here, we present a new microfabrication technique for MNs using fused deposition modeling (FDM) 3D printing using polylactic acid, an FDA approved, renewable, biodegradable, thermoplastic material. We show how this natural degradability can be exploited to overcome a key challenge of FDM 3D printing, in particular the low resolution of these printers. We improved the feature size of the printed parts significantly by developing a post fabrication chemical etching protocol, which allowed us to access tip sizes as small as 1 μm. With 3D modeling software, various MN shapes were designed and printed rapidly with custom needle density, length, and shape. Scanning electron microscopy confirmed that our method resulted in needle tip sizes in the range of 1-55 μm, which could successfully penetrate and break off into porcine skin. We have also shown that these MNs have comparable mechanical strengths to currently fabricated MNs and we further demonstrated how the swellability of PLA can be exploited to load small molecule drugs and how its degradability in skin can release those small molecules over time.

  2. Opioids Switching with Transdermal Systems in Chronic Cancer Pain

    Directory of Open Access Journals (Sweden)

    Barbarisi M

    2009-05-01

    Full Text Available Abstract Background Due to tolerance development and adverse side effects, chronic pain patients frequently need to be switched to alternative opioid therapy Objective To assess the efficacy and tolerability of an alternative transdermally applied (TDS opioid in patients with chronic cancer pain receiving insufficient analgesia using their present treatment. Methods A total of 32 patients received alternative opioid therapy, 16 were switched from buprenorphine to fentanyl and 16 were switched from fentanyl to buprenorphine. The dosage used was 50% of that indicated in equipotency conversion tables. Pain relief was assessed at weekly intervals for the next 3 weeks Results Pain relief as assessed by VAS, PPI, and PRI significantly improved (p Conclusion Opioid switching at 50% of the calculated equianalgesic dose produced a significant reduction in pain levels and rescue medication. The incidence of side effects decreased and no new side effects were noted. Further studies are required to provide individualized treatment for patients according to their different types of cancer.

  3. VHTRC experiment for verification test of H∞ reactivity estimation method

    International Nuclear Information System (INIS)

    Fujii, Yoshio; Suzuki, Katsuo; Akino, Fujiyoshi; Yamane, Tsuyoshi; Fujisaki, Shingo; Takeuchi, Motoyoshi; Ono, Toshihiko

    1996-02-01

    This experiment was performed at VHTRC to acquire the data for verifying the H∞ reactivity estimation method. In this report, the experimental method, the measuring circuits and data processing softwares are described in details. (author)

  4. What role for qualitative methods in randomized experiments?

    DEFF Research Database (Denmark)

    Prowse, Martin; Camfield, Laura

    2009-01-01

    The vibrant debate on randomized experiments within international development has been slow to accept a role for qualitative methods within research designs. Whilst there are examples of how 'field visits' or descriptive analyses of context can play a complementary, but secondary, role...... history interviews have advantages over other qualitative methods, and offers one alternative to the conventional survey tool....... to quantitative methods, little attention has been paid to the possibility of randomized experiments that allow a primary role to qualitative methods. This paper assesses whether a range of qualitative methods compromise the internal and external validity criteria of randomized experiments. It suggests that life...

  5. Status of surfactants as penetration enhancers in transdermal drug delivery

    Directory of Open Access Journals (Sweden)

    Iti Som

    2012-01-01

    Full Text Available Surfactants are found in many existing therapeutic, cosmetic, and agro-chemical preparations. In recent years, surfactants have been employed to enhance the permeation rates of several drugs via transdermal route. The application of transdermal route to a wider range of drugs is limited due to significant barrier to penetration across the skin which is associated with the outermost stratum corneum layer. Surfactants have effects on the permeability characteristics of several biological membranes including skin. They have the potential to solubilize lipids within the stratum corneum. The penetration of the surfactant molecule into the lipid lamellae of the stratum corneum is strongly dependent on the partitioning behavior and solubility of surfactant. Surfactants ranging from hydrophobic agents such as oleic acid to hydrophilic sodium lauryl sulfate have been tested as permeation enhancer to improve drug delivery. This article reviews the status of surfactants as permeation enhancer in transdermal drug delivery of various drugs.

  6. Ultradeformable Liposomes: a Novel Vesicular Carrier For Enhanced Transdermal Delivery of Procyanidins: Effect of Surfactants on the Formation, Stability, and Transdermal Delivery.

    Science.gov (United States)

    Chen, Rencai; Li, Rongli; Liu, Qian; Bai, Chao; Qin, Benlin; Ma, Yue; Han, Jing

    2017-07-01

    The aims of this work were to develop a novel vesicular carrier, procyanidins, ultradeformable liposomes (PUDLs), to expand the applications for procyanidins, and increase their stability and transdermal delivery. In this study, we prepared procyanidins ultradeformable liposomes using thin film hydration method and evaluated their encapsulation efficiency, vesicle deformability, storage stability, and skin permeation in vitro. The influence of different surfactants on the properties of PUDLs was also investigated. The results obtained showed that the PUDLs containing Tween 80 had a high entrapment efficiency (80.27 ± 0.99%), a small particle size (140.6 ± 19 nm), high elasticity, and prolonged drug release. Compared with procyanidins solution, the stability of procyanidins in PUDLs improved significantly when stored at 4, 25, and 30°C. The penetration rate of PUDLs was 6.25-fold greater than that of procyanidins solution. Finally, the results of our study suggested that PUDLs could increase the transdermal flux, prolong the release and improve the stability of procyanidins, and could serve as an effective dermal delivery system for procyanidins.

  7. Microemulsions based transdermal drug delivery systems.

    Science.gov (United States)

    Vadlamudi, Harini C; Narendran, Hyndavi; Nagaswaram, Tejeswari; Yaga, Gowri; Thanniru, Jyotsna; Yalavarthi, Prasanna R

    2014-01-01

    Since the discovery of microemulsions by Jack H Schulman, there has been huge progress made in applying microemulsion systems in plethora of research and industrial process. Microemulsions are optically isotropic systems consisting of water, oil and amphiphile. These systems are beneficial due to their thermodynamic stability, optical clarity, ease of preparation, higher diffusion and absorption rates. Moreover, it has been reported that the ingredients of microemulsion can effectively overcome the diffusion barrier and penetrate through the stratum corneum of the skin. Hence it becomes promising for both transdermal and dermal drug delivery. However, low viscosity of microemulsion restrains its applicability in pharmaceutical industry. To overcome the above drawback, the low viscous microemulsions were added to viscous gel bases to potentiate its applications as topical drug delivery systems so that various drug related toxic effects and erratic drug absorption can be avoided. The present review deals with the microemulsions, various techniques involved in the development of organic nanoparticles. The review emphasized on microemulsion based systems such as hydrogels and organogels. The physicochemical characteristics, mechanical properties, rheological and stability principles involved in microemulsion based viscous gels were also explored.

  8. Transdermal delivery of diclofenac using microemulsions.

    Science.gov (United States)

    Kweon, Jang-Hoon; Chi, Sang-Cheol; Park, Eun-Seok

    2004-03-01

    A transdermal preparation containing diclofenac diethylammonium (DDA) was developed using an O/W microemulsion system. Of the oils tested, lauryl alcohol was chosen as the oil phase of the microemulsion, as it showed a good solubilizing capacity and excellent skin permeation rate of the drug. Pseudoternary phase diagrams were constructed to obtain the concentration range of oil, surfactant and cosurfactant for microemulsion formation, and the effect of these additives on skin permeation of DDA was evaluated with excised rat skins. The optimum formulation of the microemulsion consisted of 1.16% of DDA, 5% of lauryl alcohol, 60% of water in combination with the 34.54% of Labrasol (surfactant)/ethanol (cosurfactant) (1:2). The efficiency of formulation in the percutaneous absorption of DDA was dependent upon the contents of water and lauryl alcohol as well as Labrasol:ethanol mixing ratio. It was concluded that the percutaneous absorption of DDA from microemulsions was enhanced with increasing the lauryl alcohol and water contents, and with decreasing the Labrasol:ethanol mixing ratio in the formulation.

  9. Transdermal testosterone replacement therapy in men

    Science.gov (United States)

    Ullah, M Iftekhar; Riche, Daniel M; Koch, Christian A

    2014-01-01

    Androgen deficiency syndrome in men is a frequently diagnosed condition associated with clinical symptoms including fatigue, decreased libido, erectile dysfunction, and metabolic syndrome. Serum testosterone concentrations decline steadily with age. The prevalence of androgen deficiency syndrome in men varies depending on the age group, known and unknown comorbidities, and the respective study group. Reported prevalence rates may be underestimated, as not every man with symptoms of androgen deficiency seeks treatment. Additionally, men reporting symptoms of androgen deficiency may not be correctly diagnosed due to the vagueness of the symptom quality. The treatment of androgen deficiency syndrome or male hypogonadism may sometimes be difficult due to various reasons. There is no consensus as to when to start treating a respective man or with regards to the best treatment option for an individual patient. There is also lack of familiarity with treatment options among general practitioners. The formulations currently available on the market are generally expensive and dose adjustment protocols for each differ. All these factors add to the complexity of testosterone replacement therapy. In this article we will discuss the general indications of transdermal testosterone replacement therapy, available formulations, dosage, application sites, and recommended titration schedule. PMID:24470750

  10. Heat: A Highly Efficient Skin Enhancer for Transdermal Drug Delivery

    Directory of Open Access Journals (Sweden)

    Sabine Szunerits

    2018-02-01

    Full Text Available Advances in materials science and bionanotechnology have allowed the refinements of current drug delivery systems, expected to facilitate the development of personalized medicine. While dermatological topical pharmaceutical formulations such as foams, creams, lotions, gels, etc., have been proposed for decades, these systems target mainly skin-based diseases. To treat systemic medical conditions as well as localized problems such as joint or muscle concerns, transdermal delivery systems (TDDSs, which use the skin as the main route of drug delivery, are very appealing. Over the years, these systems have shown to offer important advantages over oral as well as intravenous drug delivery routes. Besides being non-invasive and painless, TDDSs are able to deliver drugs with a short-half-life time more easily and are well adapted to eliminate frequent administrations to maintain constant drug delivery. The possibility of self-administration of a predetermined drug dose at defined time intervals makes it also the most convenient personalized point-of-care approach. The transdermal market still remains limited to a narrow range of drugs. While small and lipophilic drugs have been successfully delivered using TDDSs, this approach fails to deliver therapeutic macromolecules due to size-limited transport across the stratum corneum, the outermost layer of the epidermis. The low permeability of the stratum corneum to water-soluble drugs as well as macromolecules poses important challenges to transdermal administration. To widen the scope of drugs for transdermal delivery, new procedures to enhance skin permeation to hydrophilic drugs and macromolecules are under development. Next to iontophoresis and microneedle-based concepts, thermal-based approaches have shown great promise to enhance transdermal drug delivery of different therapeutics. In this inaugural article for the section “Frontiers in Bioengineering and Biotechnology,” the advances in this field

  11. Heat: A Highly Efficient Skin Enhancer for Transdermal Drug Delivery.

    Science.gov (United States)

    Szunerits, Sabine; Boukherroub, Rabah

    2018-01-01

    Advances in materials science and bionanotechnology have allowed the refinements of current drug delivery systems, expected to facilitate the development of personalized medicine. While dermatological topical pharmaceutical formulations such as foams, creams, lotions, gels, etc., have been proposed for decades, these systems target mainly skin-based diseases. To treat systemic medical conditions as well as localized problems such as joint or muscle concerns, transdermal delivery systems (TDDSs), which use the skin as the main route of drug delivery, are very appealing. Over the years, these systems have shown to offer important advantages over oral as well as intravenous drug delivery routes. Besides being non-invasive and painless, TDDSs are able to deliver drugs with a short-half-life time more easily and are well adapted to eliminate frequent administrations to maintain constant drug delivery. The possibility of self-administration of a predetermined drug dose at defined time intervals makes it also the most convenient personalized point-of-care approach. The transdermal market still remains limited to a narrow range of drugs. While small and lipophilic drugs have been successfully delivered using TDDSs, this approach fails to deliver therapeutic macromolecules due to size-limited transport across the stratum corneum , the outermost layer of the epidermis. The low permeability of the stratum corneum to water-soluble drugs as well as macromolecules poses important challenges to transdermal administration. To widen the scope of drugs for transdermal delivery, new procedures to enhance skin permeation to hydrophilic drugs and macromolecules are under development. Next to iontophoresis and microneedle-based concepts, thermal-based approaches have shown great promise to enhance transdermal drug delivery of different therapeutics. In this inaugural article for the section "Frontiers in Bioengineering and Biotechnology," the advances in this field and the handful of

  12. Transdermal and Topical Drug Administration in the Treatment of Pain

    Directory of Open Access Journals (Sweden)

    Wojciech Leppert

    2018-03-01

    Full Text Available The comprehensive treatment of pain is multidimodal, with pharmacotherapy playing a key role. An effective therapy for pain depends on the intensity and type of pain, the patients’ age, comorbidities, and appropriate choice of analgesic, its dose and route of administration. This review is aimed at presenting current knowledge on analgesics administered by transdermal and topical routes for physicians, nurses, pharmacists, and other health care professionals dealing with patients suffering from pain. Analgesics administered transdermally or topically act through different mechanisms. Opioids administered transdermally are absorbed into vessels located in subcutaneous tissue and, subsequently, are conveyed in the blood to opioid receptors localized in the central and peripheral nervous system. Non–steroidal anti–inflammatory drugs (NSAIDs applied topically render analgesia mainly through a high concentration in the structures of the joint and a provision of local anti–inflammatory effects. Topically administered drugs such as lidocaine and capsaicin in patches, capsaicin in cream, EMLA cream, and creams containing antidepressants (i.e., doxepin, amitriptyline act mainly locally in tissues through receptors and/or ion channels. Transdermal and topical routes offer some advantages over systemic analgesic administration. Analgesics administered topically have a much better profile for adverse effects as they relieve local pain with minimal systemic effects. The transdermal route apart from the above-mentioned advantages and provision of long period of analgesia may be more convenient, especially for patients who are unable to take drugs orally. Topically and transdermally administered opioids are characterised by a lower risk of addiction compared to oral and parenteral routes.

  13. Heat: A Highly Efficient Skin Enhancer for Transdermal Drug Delivery

    Science.gov (United States)

    Szunerits, Sabine; Boukherroub, Rabah

    2018-01-01

    Advances in materials science and bionanotechnology have allowed the refinements of current drug delivery systems, expected to facilitate the development of personalized medicine. While dermatological topical pharmaceutical formulations such as foams, creams, lotions, gels, etc., have been proposed for decades, these systems target mainly skin-based diseases. To treat systemic medical conditions as well as localized problems such as joint or muscle concerns, transdermal delivery systems (TDDSs), which use the skin as the main route of drug delivery, are very appealing. Over the years, these systems have shown to offer important advantages over oral as well as intravenous drug delivery routes. Besides being non-invasive and painless, TDDSs are able to deliver drugs with a short-half-life time more easily and are well adapted to eliminate frequent administrations to maintain constant drug delivery. The possibility of self-administration of a predetermined drug dose at defined time intervals makes it also the most convenient personalized point-of-care approach. The transdermal market still remains limited to a narrow range of drugs. While small and lipophilic drugs have been successfully delivered using TDDSs, this approach fails to deliver therapeutic macromolecules due to size-limited transport across the stratum corneum, the outermost layer of the epidermis. The low permeability of the stratum corneum to water-soluble drugs as well as macromolecules poses important challenges to transdermal administration. To widen the scope of drugs for transdermal delivery, new procedures to enhance skin permeation to hydrophilic drugs and macromolecules are under development. Next to iontophoresis and microneedle-based concepts, thermal-based approaches have shown great promise to enhance transdermal drug delivery of different therapeutics. In this inaugural article for the section “Frontiers in Bioengineering and Biotechnology,” the advances in this field and the handful of

  14. Perioperative analgesia with a buprenorphine transdermal patch for hallux valgus surgery: a prospective, randomized, controlled study

    Directory of Open Access Journals (Sweden)

    Xu C

    2018-04-01

    Full Text Available Can Xu, Mingqing Li, Chenggong Wang, Hui Li, Hua Liu Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China Purpose: Hallux valgus surgery often results in significant postoperative pain. Adequate control of pain is essential for patient satisfaction and improves the outcome of the procedure. This study aimed to investigate the perioperative analgesic effect of a buprenorphine transdermal patch in patients who underwent hallux valgus surgery.Patients and methods: A total of 90 patients were randomly divided into the following three groups based on the perioperative analgesic method: flurbiprofen axetil intravenous injection (Group F, oral celecoxib (Group C, and buprenorphine transdermal delivery system (BTDS (Group BTDS. The pain status, degree of satisfaction, adverse effects, and administration of tramadol hydrochloride for uncontrolled pain were recorded on the night before surgery, postoperative day 1, postoperative day 2, and postoperative day 3.Results: The BTDS could effectively control perioperative pain for patients undergoing ­hallux valgus surgery. The analgesic effect of the BTDS was better than that of oral celecoxib. In addition, statistically significant differences were not observed in the visual analog scale (VAS scores, adverse effects, and rescue analgesia between the patients who received the BTDS and the patients who received the flurbiprofen axetil intravenous injection. However, the degree of patient satisfaction of the BTDS group was significantly higher (P<0.05 than that of the other two groups.Conclusion: The BTDS (a preemptive analgesia regimen could exert an analgesic effect during the perioperative period for patients who had received hallux valgus surgery, and this effect is beneficial for sustaining postoperative physiological and psychological states and promoting functional rehabilitation. Keywords: hallux valgus, buprenorphine transdermal

  15. Increased skin permeation efficiency of imperatorin via charged ultradeformable lipid vesicles for transdermal delivery

    Directory of Open Access Journals (Sweden)

    Lin HW

    2018-02-01

    Full Text Available Hongwei Lin,1,2 Qingchun Xie,1,2 Xin Huang,1,2 Junfeng Ban,1,2 Bo Wang,1,2 Xing Wei,3 Yanzhong Chen,1,2 Zhufen Lu1,2 1Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 3Guangdong Shennong Chinese Medicine Research Institute, Guangzhou, People’s Republic of China Aim: The aim of this work was to develop a novel vesicular carrier, ultradeformable liposomes (UDLs, to expand the applications of the Chinese herbal medicine, imperatorin (IMP, and increase its transdermal delivery. Methods: In this study, we prepared IMP-loaded UDLs using the thin-film hydration method and evaluated their encapsulation efficiency, vesicle deformability, skin permeation, and the amounts accumulated in different depths of the skin in vitro. The influence of different charged surfactants on the properties of the UDLs was also investigated. Results: The results showed that the UDLs containing cationic surfactants had high entrapment efficiency (60.32%±2.82%, an acceptable particle size (82.4±0.65 nm, high elasticity, and prolonged drug release. The penetration rate of IMP in cationic-UDLs was 3.45-fold greater than that of IMP suspension, which was the highest value among the vesicular carriers. UDLs modified with cationic surfactant also showed higher fluorescence intensity in deeper regions of the epidermis. Conclusion: The results of our study suggest that cationic surfactant-modified UDLs could increase the transdermal flux, prolong the release of the drug, and serve as an effective dermal delivery system for IMP. Keywords: ultradeformable liposomes, cationic, imperatorin, skin permeation, transdermal drug delivery

  16. Transdermal carbamate poisoning – a case of misuse

    Directory of Open Access Journals (Sweden)

    Lalit Kumar Rajbanshi

    2017-01-01

    Full Text Available Acute pesticide poisoning is a common mode of intentional self harm. Oral ingestion is the usual mode of poisoning. However, inhalation, accidental or occupational transdermal exposure leading to acute or chronic poisoning can be the other route of poisoning. It has been seen that the purpose of poising is suicidal intensity in most of the cases. We report an unusual case where the victim had acute pesticide poisoning through transdermal route that was intended for non suicidal purpose. The patient was managed successfully with immediate decontamination and adequate antidote.

  17. Amphiphilic poly{[α-maleic anhydride-ω-methoxypoly(ethylene glycol]-co-(ethyl cyanoacrylate} graft copolymer nanoparticles as carriers for transdermal drug delivery

    Directory of Open Access Journals (Sweden)

    Jinfeng Xing

    2009-10-01

    Full Text Available Jinfeng Xing, Liandong Deng, Jun Li, Anjie DongDepartment of Polymer Science and Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, People’s Republic of ChinaAbstract: In this study, the transdermal drug delivery properties of D,L-tetrahydropalmatine (THP-loaded amphiphilic poly{[α-maleic anhydride-ω-methoxy-poly(ethylene glycol]-co-(ethyl cyanoacrylate} (PEGECA graft copolymer nanoparticles (PEGECAT NPs were evaluated by skin penetration experiments in vitro. The transdermal permeation experiments in vitro were carried out in Franz diffusion cells using THP-loaded PEGECAT NPs as the donor system. Transmission electron microscopy and Fourier transform infrared spectroscopy were used to characterize the receptor fluid. The results indicate that the THP-loaded PEGECAT NPs are able to penetrate the rat skin. Fluorescent microscopy measurements demonstrate that THP-loaded PEGECAT NPs can penetrate the skin not only via appendage routes but also via epidermal routes. This nanotechnology has potential application in transdermal drug delivery. Keywords: poly{[α-maleic anhydride-ω-methoxy-poly(ethylene glycol]-co-(ethyl cyanoacrylate}, nanoparticles, transdermal drug delivery, D,L-tetrahydropalmatine

  18. Enhanced Transdermal Delivery by Combined Application of Dissolving Microneedle Patch on Serum-Treated Skin.

    Science.gov (United States)

    Kim, Suyong; Dangol, Manita; Kang, Geonwoo; Lahiji, Shayan F; Yang, Huisuk; Jang, Mingyu; Ma, Yonghao; Li, Chengguo; Lee, Sang Gon; Kim, Chang Hyun; Choi, Young Wook; Kim, So Jeong; Ryu, Ja Hyun; Baek, Ji Hwoon; Koh, Jaesuk; Jung, Hyungil

    2017-06-05

    Dissolving microneedle (DMN), a transdermal drug delivery system in which drugs are encapsulated in a biodegradable polymeric microstructure, is designed to dissolve after skin penetration and release the encapsulated drugs into the body. However, because of limited loading capacity of drugs within microsized structures, only a small dosage can be delivered, which is often insufficient for patients. We propose a novel DMN application that combines topical and DMN application simultaneously to improve skin permeation efficiency. Drugs in pretreated topical formulation and encapsulated drugs in DMN patch are delivered into the skin through microchannels created by DMN application, thus greatly increasing the delivered dose. We used 4-n-butylresorcinol to treat human hyperpigmentation and found that sequential application of serum formulation and DMNs was successful. In skin distribution experiments using Alexa Fluor 488 and 568 dyes as model drugs, we confirmed that the pretreated serum formulation was delivered into the skin through microchannels created by the DMNs. In vitro skin permeation and retention experiments confirmed that this novel combined application delivered more 4-n-butylresorcinol into the skin than traditional DMN-only and serum-only applications. Moreover, this combined application showed a higher efficacy in reducing patients' melanin index and hyperpigmented regions compared with the serum-only application. As combined application of DMNs on serum-treated skin can overcome both dose limitations and safety concerns, this novel approach can advance developments in transdermal drug delivery.

  19. Synergistic effect of iontophoresis and chemical enhancers on transdermal permeation of tolterodine tartrate for the treatment of overactive bladder

    Directory of Open Access Journals (Sweden)

    D. Prasanthi

    2013-01-01

    Full Text Available Purpose The objective of the study was to evaluate the synergistic transdermal permeation effect of chemical enhancers and iontophoresis technique on tolterodine tartrate (TT transdermal gel and to evaluate its pharmacokinetic properties. Materials and Methods Taguchi robust design was used for optimization of formulations. Skin permeation rates were evaluated using the Keshary-chein type diffusion cells in order to optimize the gel formulation. In-vivo studies of the optimized formulation were performed in a rabbit model and histopathology studies of optimized formulation were performed on rats. Results Transdermal gels were formulated successfully using Taguchi robust design method. The type of penetration enhancer, concentration of penetration enhancer, current density and pulse on/off ratio were chosen as independent variables. Type of penetration enhancer was found to be the significant factor for all the responses. Permeation parameters were evaluated when maximum cumulative amount permeated in 24 hours (Q24 was 145.71 ± 2.00µg/cm2 by CIT4 formulation over control (91.89 ± 2.30µg/cm2. Permeation was enhanced by 1.75 fold by CIT4 formulation. Formulation CIT4 containing nerolidol (5% and iontophoretic variables applied (0.5mA/cm2 and pulse on/off ratio 3:1 was optimized. In vivo studies with optimized formulation CIT4 showed increase in AUC and T1/2 when compared to oral suspension in rabbits. The histological studies showed changes in dermis indicating the effect of penetration enhancers and as iontophoresis was continued only for two cycles in periodic fashion so it did not cause any skin damage observed in the slides. Conclusion Results indicated that iontophoresis in combination with chemical enhancers is an effective method for transdermal administration of TT in the treatment of overactive bladder.

  20. A dose-finding, cross-over study to evaluate the effect of a Nestorone®/Estradiol transdermal gel delivery on ovulation suppression in normal ovulating women.

    Science.gov (United States)

    Brache, Vivian; Merkatz, Ruth; Kumar, Narender; Jesam, Cristian; Sussman, Heather; Hoskin, Elena; Roberts, Kevin; Alami, Mohcine; Taylor, Deshawn; Jorge, Aidelis; Croxatto, Horacio; Lorange, Ellen; Mishell, Daniel R; Sitruk-Ware, Regine

    2015-10-01

    This study aims to determine the lowest effective of three Nestorone (NES)/estradiol (E2) transdermal gel doses to ensure ovulation suppression in 90-95% of cycles. This was a randomized, open-label, three-treatment-period cross-over study to evaluate the effects of NES/E2 transdermal gel on ovulation inhibition, suppression of follicular growth and pharmacokinetic parameters. The doses were low (1.5 mg NES/0.5 mg E2), medium (3.0 mg NES/1.0 mg E2) and high (4.5 mg NES/1.5 mg E2). Participants applied gel daily to a fixed area on the abdomen for 21 consecutive days. They were interviewed regarding their experiences using the gel. Eighteen participants were randomized; 16 completed the study. Median NES C(max) values for low, medium and high dose groups at day 21 were 318.6 pmol/L, 783.0 pmol/L and 1063.8 pmol/L, respectively. Median maximum follicular diameter was higher with the lowest dose with 16.2 mm versus 10.0 and 10.4 mm with the medium and high doses, respectively. Among adherent participants, ovulation was inhibited in all dose groups, except for one participant in the medium dose (6.7%) that had luteal activity and an ultrasound image suggestive of a luteinized unruptured follicle. There were few reports of unscheduled bleeding, with more episodes reported for the lower dose. Adverse events were mild, and no skin irritation was reported from gel application. While all three doses blocked ovulation effectively and were evaluated as safe and acceptable, the medium dose was considered the lowest effective dose based on a more adequate suppression of follicular development. Further development of this novel contraceptive delivering NES and E2 is warranted and has potential for improved safety compared to ethinyl-estradiol-based methods. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Determination of two capsaicinoids in analgesic transdermal patches using RP-HPLC and UV spectroscopy

    Directory of Open Access Journals (Sweden)

    F. Kobarfard

    2017-11-01

    Full Text Available Background and objectives: At the present time, a considerable frontier in the administration of therapeutic medications is transdermal drug delivery. Methods: In this study, a rapid, precise, sensitive and selective reversed-phasehigh performance liquid chromatography (RP-HPLC method has been evaluated, developed and validated to separate and quantitate capsaicin and dihydrocapsaicin (main active agents in analgesic dermal patches produced in Iran. Results: After isolation from laminated adhesive patches, capsaicinoids were analyzed on Lichrospher C18 analytical columns with reversed phase, using a mobile phase composition of methanol and distilled water (70:30 v/v and without any buffer (pH=6.5. The flow rate was 1 mL/min and the UV detector was operating at 281 nm. The assay was found to be linear over the range of 0.1-1.0 mg/mL. All validation parameters were within the acceptable range. Conclusion: It seems that the developed method was fairly sensitive and reliable in measuring capsaicinoids in commercially available analgesic transdermal patches in Iran.

  2. Observational Case Series Evaluation of the Granisetron Transdermal Patch System (Sancuso) for the Management of Nausea/Vomiting of Pregnancy.

    Science.gov (United States)

    Le, Tran N; Adler, Michael T; Ouillette, Holly; Berens, Pamela; Smith, Judith A

    2017-07-01

    Objective  The objective of this study was to observe the efficacy of antiemetic therapy (no emesis/retching episodes and no rescue medication use) when granisetron is administered via a transdermal patch system (TDS) in women who are 6 to 14 weeks pregnant when compared with oral ondansetron by evaluating the frequency of the use of rescue medications for control of nausea/vomiting of pregnancy (NVP). Methods  This was an observational case series study to observe the potential benefits of granisetron TDS compared with oral ondansetron for management of NVP in pregnant patients during the first trimester. Dates of data collection were September 1, 2014, through December 31, 2015. There was no direct contact with patient. The oral ondansetron and granisetron TDS patients were matched by age, 4:1. The proportion of patients who received rescue antiemetics was calculated from those patients who continued to experience NVP. Risk factors for NVP were identified and compared between groups. Descriptive statistics were used to describe study results. Results  Patients were prescribed rescue antiemetics in 0/3 patients in the granisetron TDS group compared with 2/12 patients in the oral ondansetron group. Conclusion  Prospective efficacy studies on the use of granisetron TDS for management of NVP are needed to confirm this clinical observation. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  3. Galactosyl Pentadecene Reversibly Enhances Transdermal and Topical Drug Delivery

    Czech Academy of Sciences Publication Activity Database

    Kopečná, M.; Macháček, M.; Prchalová, Eva; Štěpánek, P.; Drašar, P.; Kotora, Martin; Vávrová, K.

    2017-01-01

    Roč. 34, č. 10 (2017), s. 2097-2108 ISSN 0724-8741 Institutional support: RVO:61388963 Keywords : galactoside * penetration enhancers * sugar * topical drug delivery * transdermal drug delivery Subject RIV: FR - Pharmacology ; Medidal Chemistry OBOR OECD: Pharmacology and pharmacy Impact factor: 3.002, year: 2016

  4. Assessment of simvastatin niosomes for pediatric transdermal drug delivery.

    Science.gov (United States)

    Zidan, Ahmed S; Hosny, Khaled M; Ahmed, Osama A A; Fahmy, Usama A

    2016-06-01

    The prevalence of childhood dyslipidemia increases and is considered as an important risk factor for the incidence of cardiovascular disease in the adulthood. To improve dosing accuracy and facilitate the determination of dosing regimens in function of the body weight, the proposed study aims at preparing transdermal niosomal gels of simvastatin as possible transdermal drug delivery system for pediatric applications. Twelve formulations were prepared to screen the influence of formulation and processing variables on critical niosomal characteristics. Nano-sized niosomes with 0.31 μm number-weighted size displayed highest simvastatin release rate with 8.5% entrapment capacity. The niosomal surface coverage by negative charges was calculated according to Langmuir isotherm with n = 0.42 to suggest that the surface association was site-independent, probably producing surface rearrangements. Hypolipidemic activities after transdermal administration of niosomal gels to rats showed significant reduction in cholesterol and triglyceride levels while increasing plasma high-density lipoproteins concentration. Bioavailability estimation in rats revealed an augmentation in simvastatin bioavailability by 3.35 and 2.9 folds from formulation F3 and F10, respectively, compared with oral drug suspension. Hence, this transdermal simvastatin niosomes not only exhibited remarkable potential to enhance its bioavailability and hypolipidemic activity but also considered a promising pediatric antihyperlipidemic formulation.

  5. Plasma Concentrations of Fentanyl Achieved With Transdermal Application in Chickens

    NARCIS (Netherlands)

    Delaski, Kristina M; Gehring, Ronette; Heffron, Brendan T; Negrusz, Adam; Gamble, Kathryn C

    2017-01-01

    Providing appropriate analgesia is an important concern in any species. Fentanyl, a μ-receptor specific opioid, use is common in mammalian species but has been incompletely evaluated for this purpose in avian species. Transdermal fentanyl patches were applied to domestic chickens (n = 10) of varying

  6. Transdermal Physostigmine—Absence of Effect on Topographic Brain Mapping

    Directory of Open Access Journals (Sweden)

    M. Y. Neufeld

    1993-01-01

    Full Text Available Nine patients with primary degenerative dementia (PDD participated in an open trial of transdermal physostigmine (TPh. In order to evaluate the neurophysiologic effects of TPh, EEG data were recorded and compared at baseline and following 2 months of continuous treatment. There was no significant effect of TPh on EEG spectra in patients with PDD.

  7. Efficacy and transdermal absorption of permethrin in scabies patients

    NARCIS (Netherlands)

    van der Rhee, H.J.; Farquhar, J A; Vermeulen, N P

    1989-01-01

    The clinical efficacy and transdermal absorption of permethrin, a new synthetic insecticide was investigated in ten scabies patients. All patients were successfully treated with one application of a cream, containing 5% permethrin. Apart from mild postscabies dermatitis no side-effects were

  8. Transdermal deferoxamine prevents pressure-induced diabetic ulcers.

    Science.gov (United States)

    Duscher, Dominik; Neofytou, Evgenios; Wong, Victor W; Maan, Zeshaan N; Rennert, Robert C; Inayathullah, Mohammed; Januszyk, Michael; Rodrigues, Melanie; Malkovskiy, Andrey V; Whitmore, Arnetha J; Walmsley, Graham G; Galvez, Michael G; Whittam, Alexander J; Brownlee, Michael; Rajadas, Jayakumar; Gurtner, Geoffrey C

    2015-01-06

    There is a high mortality in patients with diabetes and severe pressure ulcers. For example, chronic pressure sores of the heels often lead to limb loss in diabetic patients. A major factor underlying this is reduced neovascularization caused by impaired activity of the transcription factor hypoxia inducible factor-1 alpha (HIF-1α). In diabetes, HIF-1α function is compromised by a high glucose-induced and reactive oxygen species-mediated modification of its coactivator p300, leading to impaired HIF-1α transactivation. We examined whether local enhancement of HIF-1α activity would improve diabetic wound healing and minimize the severity of diabetic ulcers. To improve HIF-1α activity we designed a transdermal drug delivery system (TDDS) containing the FDA-approved small molecule deferoxamine (DFO), an iron chelator that increases HIF-1α transactivation in diabetes by preventing iron-catalyzed reactive oxygen stress. Applying this TDDS to a pressure-induced ulcer model in diabetic mice, we found that transdermal delivery of DFO significantly improved wound healing. Unexpectedly, prophylactic application of this transdermal delivery system also prevented diabetic ulcer formation. DFO-treated wounds demonstrated increased collagen density, improved neovascularization, and reduction of free radical formation, leading to decreased cell death. These findings suggest that transdermal delivery of DFO provides a targeted means to both prevent ulcer formation and accelerate diabetic wound healing with the potential for rapid clinical translation.

  9. NMR characterisation and transdermal drug delivery potential of microemulsion systems

    DEFF Research Database (Denmark)

    Kreilgaard, Mads; Pedersen, E J; Jaroszewski, J W

    2000-01-01

    The purpose of this study was to investigate the influence of structure and composition of microemulsions (Labrasol/Plurol Isostearique/isostearylic isostearate/water) on their transdermal delivery potential of a lipophilic (lidocaine) and a hydrophilic model drug (prilocaine hydrochloride), and ...

  10. Transdermal deferoxamine prevents pressure-induced diabetic ulcers

    Science.gov (United States)

    Duscher, Dominik; Neofytou, Evgenios; Wong, Victor W.; Maan, Zeshaan N.; Rennert, Robert C.; Januszyk, Michael; Rodrigues, Melanie; Malkovskiy, Andrey V.; Whitmore, Arnetha J.; Galvez, Michael G.; Whittam, Alexander J.; Brownlee, Michael; Rajadas, Jayakumar; Gurtner, Geoffrey C.

    2015-01-01

    There is a high mortality in patients with diabetes and severe pressure ulcers. For example, chronic pressure sores of the heels often lead to limb loss in diabetic patients. A major factor underlying this is reduced neovascularization caused by impaired activity of the transcription factor hypoxia inducible factor-1 alpha (HIF-1α). In diabetes, HIF-1α function is compromised by a high glucose-induced and reactive oxygen species-mediated modification of its coactivator p300, leading to impaired HIF-1α transactivation. We examined whether local enhancement of HIF-1α activity would improve diabetic wound healing and minimize the severity of diabetic ulcers. To improve HIF-1α activity we designed a transdermal drug delivery system (TDDS) containing the FDA-approved small molecule deferoxamine (DFO), an iron chelator that increases HIF-1α transactivation in diabetes by preventing iron-catalyzed reactive oxygen stress. Applying this TDDS to a pressure-induced ulcer model in diabetic mice, we found that transdermal delivery of DFO significantly improved wound healing. Unexpectedly, prophylactic application of this transdermal delivery system also prevented diabetic ulcer formation. DFO-treated wounds demonstrated increased collagen density, improved neovascularization, and reduction of free radical formation, leading to decreased cell death. These findings suggest that transdermal delivery of DFO provides a targeted means to both prevent ulcer formation and accelerate diabetic wound healing with the potential for rapid clinical translation. PMID:25535360

  11. Avanafil Liposomes as Transdermal Drug Delivery for Erectile ...

    African Journals Online (AJOL)

    Avanafil is slightly soluble in ethanol, practically insoluble in water ... transdermal permeability and bioavailability for the treatment of .... Table 1 shows that the EE had higher values for the MLVs .... reason is the lower solubility of avanafil at pH.

  12. In vitro and ex vivo evaluations on transdermal delivery of the HIV inhibitor IQP-0410.

    Directory of Open Access Journals (Sweden)

    Anthony S Ham

    Full Text Available The aim of this study was to investigate the physicochemical and in vitro/ex vivo characteristics of the pyrmidinedione IQP-0410 formulated into transdermal films. IQP-0410 is a potent therapeutic anti-HIV nonnucleoside reverse transcriptase inhibitor that would be subjected to extensive first pass metabolism, through conventional oral administration. Therefore, IQP-0410 was formulated into ethyl cellulose/HPMC-based transdermal films via solvent casting. In mano evaluations were performed to evaluate gross physical characteristics. In vitro release studies were performed in both Franz cells and USP-4 dissolution vessels. Ex vivo release and permeability assays were performed on human epidermal tissue models, and the permeated IQP-0410 was collected for in vitro HIV-1 efficacy assays in CEM-SS cells and PBMCs. Film formulation D3 resulted in pliable, strong transdermal films that were loaded with 2% (w/w IQP-0410. Composed of 60% (w/w ethyl cellulose and 20% (w/w HPMC, the films contained < 1.2% (w/w of water and were hygroscopic resulting in significant swelling under humid conditions. The water permeable nature of the film resulted in complete in vitro dissolution and drug release in 26 hours. When applied to ex vivo epidermal tissues, the films were non-toxic to the tissue and also were non-toxic to HIV target cells used in the in vitro efficacy assays. Over a 3 day application, the films delivered IQP-0410 through the skin tissue at a zero-order rate of 0.94 ± 0.06 µg/cm(2/hr with 134 ± 14.7 µM collected in the basal media. The delivered IQP-0410 resulted in in vitro EC50 values against HIV-1 of 2.56 ± 0.40 nM (CEM-SS and 0.58 ± 0.03 nM (PBMC. The film formulation demonstrated no significant deviation from target values when packaged in foil pouches under standard and accelerated environmental conditions. It was concluded that the transdermal film formulation was a potentially viable method of administering IQP-0410 that warrants

  13. Transdermal influenza immunization with vaccine-coated microneedle arrays.

    Directory of Open Access Journals (Sweden)

    Dimitrios G Koutsonanos

    Full Text Available Influenza is a contagious disease caused by a pathogenic virus, with outbreaks all over the world and thousands of hospitalizations and deaths every year. Due to virus antigenic drift and short-lived immune responses, annual vaccination is required. However, vaccine coverage is incomplete, and improvement in immunization is needed. The objective of this study is to investigate a novel method for transdermal delivery using metal microneedle arrays (MN coated with inactivated influenza virus to determine whether this route is a simpler and safer approach than the conventional immunization, capable to induce robust immune responses and confer protection against lethal virus challenge.Inactivated A/Aichi/2/68 (H3N2 influenza virus was coated on metal microneedle arrays and applied to mice as a vaccine in the caudal dorsal skin area. Substantial antibody titers with hemagglutination inhibition activity were detected in sera collected two and four weeks after a single vaccine dose. Challenge studies in mice with 5 x LD(50 of mouse adapted Aichi virus demonstrated complete protection. Microneedle vaccination induced a broad spectrum of immune responses including CD4+ and CD8+ responses in the spleen and draining lymph node, a high frequency of antigen-secreting cells in the lung and induction of virus-specific memory B-cells. In addition, the use of MN showed a dose-sparing effect and a strong Th2 bias when compared to an intramuscular (IM reference immunization.The present results show that delivery of inactivated influenza virus through the skin using metal microneedle arrays induced strong humoral and cellular immune responses capable of conferring protection against virus challenge as efficiently as intramuscular immunization, which is the standard vaccination route. In view of the convenience of delivery and the potential for self-administration, vaccine-coated metal microneedles may provide a novel and highly effective immunization method.

  14. Transdermal therapeutic systems for memantine delivery. Comparison of passive and iontophoretic transport.

    Science.gov (United States)

    Del Río-Sancho, S; Serna-Jiménez, C E; Sebastián-Morelló, M; Calatayud-Pascual, M A; Balaguer-Fernández, C; Femenía-Font, A; Kalia, Y N; Merino, V; López-Castellano, A

    2017-01-30

    Memantine is a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist used in the treatment of moderate to severe dementia including the symptoms of Alzheimer's disease (AD). It is administered orally but compliance, swallowing problems and the routine use of multiple medications in elderly AD patients means that an alternative route of administration would be of interest. The aim of the present study was to develop memantine hydrochloride occlusive transdermal therapeutic systems (TTS) for passive and iontophoretic delivery across the skin. Polyvinyl pyrrolidone (PVP) and a mixture with polyvinyl alcohol (PVA) were employed as polymeric matrices. The study involved the TTS characterization in addition to quantification of the memantine transport across porcine skin in vitro. The evaluation of the TTS physical properties suggested that systems were made more mechanically resistant by including PVA (6%) or high concentrations of PVP (24%). Moreover, a linear correlation was observed between the concentration of PVP and the bioadhesion of the systems. Drug delivery experiments showed that the highest transdermal flux provided by a passive TTS (PVP 24% w/w limonene) was 8.89±0.81μgcm -2 h -1 whereas the highest iontophoretic transport was 46.4±3.6μgcm -2 h -1 . These innovative TTS would enable two dosage regimens that could lead to therapeutic plasma concentrations. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Numerical modelling of transdermal delivery from matrix systems: parametric study and experimental validation with silicone matrices.

    Science.gov (United States)

    Snorradóttir, Bergthóra S; Jónsdóttir, Fjóla; Sigurdsson, Sven Th; Másson, Már

    2014-08-01

    A model is presented for transdermal drug delivery from single-layered silicone matrix systems. The work is based on our previous results that, in particular, extend the well-known Higuchi model. Recently, we have introduced a numerical transient model describing matrix systems where the drug dissolution can be non-instantaneous. Furthermore, our model can describe complex interactions within a multi-layered matrix and the matrix to skin boundary. The power of the modelling approach presented here is further illustrated by allowing the possibility of a donor solution. The model is validated by a comparison with experimental data, as well as validating the parameter values against each other, using various configurations with donor solution, silicone matrix and skin. Our results show that the model is a good approximation to real multi-layered delivery systems. The model offers the ability of comparing drug release for ibuprofen and diclofenac, which cannot be analysed by the Higuchi model because the dissolution in the latter case turns out to be limited. The experiments and numerical model outlined in this study could also be adjusted to more general formulations, which enhances the utility of the numerical model as a design tool for the development of drug-loaded matrices for trans-membrane and transdermal delivery. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  16. Solid Microneedles for Transdermal Delivery of Amantadine Hydrochloride and Pramipexole Dihydrochloride

    Directory of Open Access Journals (Sweden)

    Mylien T. Hoang

    2015-09-01

    Full Text Available The aim of this project was to study the influence of microneedles on transdermal delivery of amantadine hydrochloride and pramipexole dihydrochloride across porcine ear skin in vitro. Microchannel visualization studies were carried out and characterization of the microchannel depth was performed using confocal laser scanning microscopy (CLSM to demonstrate microchannel formation following microneedle roller application. We also report, for the first time, the use of TA.XT Plus Texture Analyzer to characterize burst force in pig skin for transdermal drug delivery experiments. This is the force required to rupture pig skin. The mean passive flux of amantadine hydrochloride, determined using a developed LC–MS/MS technique, was 22.38 ± 4.73 µg/cm2/h, while the mean flux following the use of a stainless steel microneedle roller was 49.04 ± 19.77 µg/cm2/h. The mean passive flux of pramipexole dihydrochloride was 134.83 ± 13.66 µg/cm2/h, while the flux following the use of a stainless steel microneedle roller was 134.04 ± 0.98 µg/cm2/h. For both drugs, the difference in flux values following the use of solid stainless steel microneedle roller was not statistically significantly (p > 0.05. Statistical analysis was carried out using the Mann–Whitney Rank sum test.

  17. Neural network and area method interpretation of pulsed experiments

    Energy Technology Data Exchange (ETDEWEB)

    Dulla, S.; Picca, P.; Ravetto, P. [Politecnico di Torino, Dipartimento di Energetica, Corso Duca degli Abruzzi, 24 - 10129 Torino (Italy); Canepa, S. [Lab of Reactor Physics and Systems Behaviour LRS, Paul Scherrer Inst., 5232 Villigen (Switzerland)

    2012-07-01

    The determination of the subcriticality level is an important issue in accelerator-driven system technology. The area method, originally introduced by N. G. Sjoestrand, is a classical technique to interpret flux measurement for pulsed experiments in order to reconstruct the reactivity value. In recent times other methods have also been developed, to account for spatial and spectral effects, which were not included in the area method, since it is based on the point kinetic model. The artificial neural network approach can be an efficient technique to infer reactivities from pulsed experiments. In the present work, some comparisons between the two methods are carried out and discussed. (authors)

  18. Unfolding methods in high-energy physics experiments

    International Nuclear Information System (INIS)

    Blobel, V.

    1985-01-01

    Distributions measured in high-energy physics experiments are often distorted or transformed by limited acceptance and finite resolution of the detectors. The unfolding of measured distributions is an important, but due to inherent instabilities a very difficult problem. Methods for unfolding, applicable for the analysis of high-energy physics experiments, and their properties are discussed. An introduction is given to the method of regularization. (orig.)

  19. Unfolding methods in high-energy physics experiments

    International Nuclear Information System (INIS)

    Blobel, V.

    1984-12-01

    Distributions measured in high-energy physics experiments are often distorted or transformed by limited acceptance and finite resolution of the detectors. The unfolding of measured distributions is an important, but due to inherent instabilities a very difficult problem. Methods for unfolding, applicable for the analysis of high-energy physics experiments, and their properties are discussed. An introduction is given to the method of regularization. (orig.)

  20. Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine

    Directory of Open Access Journals (Sweden)

    Hong X

    2013-09-01

    Full Text Available Xiaoyun Hong,1,2,* Liangming Wei,3,* Fei Wu,2,* Zaozhan Wu,2 Lizhu Chen,2 Zhenguo Liu,1 Weien Yuan2 1Department of Neurology, Xinhua Hospital, Shanghai, People's Republic of China; 2School of Pharmacy, Shanghai JiaoTong University, Shanghai, People's Republic of China; 3Research Institute of Micro/Nano Science and Technology, Shanghai JiaoTong University, Shanghai, People's Republic of China *These authors contributed equally to this work Abstract: Microneedles were first conceptualized for drug delivery many decades ago, overcoming the shortages and preserving the advantages of hypodermic needle and conventional transdermal drug-delivery systems to some extent. Dissolving and biodegradable microneedle technologies have been used for transdermal sustained deliveries of different drugs and vaccines. This review describes microneedle geometry and the representative dissolving and biodegradable microneedle delivery methods via the skin, followed by the fabricating methods. Finally, this review puts forward some perspectives that require further investigation. Keywords: microneedle, dissolving, biodegradable, sustained release

  1. Analysis of nifedipine content in transdermal drug delivery system using non-destructive visible spectrophotometry technique

    International Nuclear Information System (INIS)

    Normaizira Hamidi; Normaizira Hamidi; Normaizira Hamidi; Mohd Nasir Taib; Mohd Nasir Taib; Wui, Wong Tin; Wui, Wong Tin

    2008-01-01

    The applicability of visible spectrophotometry technique as a tool to determine the drug content of polymeric film for use as a transdermal drug delivery system was investigated. Hydroxypropylmethycellulose (HPMC) was selected as the matrix polymer and nifedipine as the model drug. Blank and nifedipine-loaded HPMC films were prepared using the solvent evaporation method. The absorbance spectra of these films under the visible wavelengths between 400 and 800 nm were assessed and compared against the drug content values obtained by means of the conventional destructive UV- spectrophotometry technique. The latter required the use of a solvent system which contained methanol, a harmful organic component in pharmaceutical applications. The results indicated that the absorbance values, attributed to nifedipine, at the wavelengths of 545, 585, 638 and 755nm were significantly correlated to the drug content values obtained using the chemical assay method (Pearson correlation value: r = 0.990 and p < 0.01). The visible spectrophotometry technique is potentially suitable for use to determine the nifedipine content of films owing to its nature of characterization of transdermal drug delivery system which does not require sample destruction during the process of measurement. The samples are recoverable from test and analysis of the entire batch of samples is possible without the need of solvents and chemical reagents. (author)

  2. Hydrogels containing redispersible spray-dried melatonin-loaded nanocapsules: a formulation for transdermal-controlled delivery

    Science.gov (United States)

    Hoffmeister, Cristiane RD; Durli, Taís L.; Schaffazick, Scheila R.; Raffin, Renata P.; Bender, Eduardo A.; Beck, Ruy CR; Pohlmann, Adriana R.; Guterres, Sílvia S.

    2012-05-01

    The aim of the present study was to develop a transdermal system for controlled delivery of melatonin combining three strategies: nanoencapsulation of melatonin, drying of melatonin-loaded nanocapsules, and incorporation of nanocapsules in a hydrophilic gel. Nanocapsules were prepared by interfacial deposition of the polymer and were spray-dried using water-soluble excipients. In vitro drug release profiles were evaluated by the dialysis bag method, and skin permeation studies were carried out using Franz cells with porcine skin as the membrane. The use of 10% ( w/ v) water-soluble excipients (lactose or maltodextrin) as spray-drying adjuvants furnished redispersible powders (redispersibility index approximately 1.0) suitable for incorporation into hydrogels. All formulations showed a better controlled in vitro release of melatonin compared with the melatonin solution. The best controlled release results were achieved with hydrogels prepared with dried nanocapsules (hydrogels > redispersed dried nanocapsules > nanocapsule suspension > melatonin solution). The skin permeation studies demonstrated a significant modulation of the transdermal melatonin permeation for hydrogels prepared with redispersible nanocapsules. In this way, the additive effect of the different approaches used in this study (nanoencapsulation, spray-drying, and preparation of semisolid dosage forms) allows not only the control of melatonin release, but also transdermal permeation.

  3. Exploitation of sub-micron cavitation nuclei to enhance ultrasound-mediated transdermal transport and penetration of vaccines.

    Science.gov (United States)

    Bhatnagar, Sunali; Kwan, James J; Shah, Apurva R; Coussios, Constantin-C; Carlisle, Robert C

    2016-09-28

    Inertial cavitation mediated by ultrasound has been previously shown to enable skin permeabilisation for transdermal drug and vaccine delivery, by sequentially applying the ultrasound then the therapeutic in liquid form on the skin surface. Using a novel hydrogel dosage form, we demonstrate that the use of sub-micron gas-stabilising polymeric nanoparticles (nanocups) to sustain and promote cavitation activity during simultaneous application of both drug and vaccine results in a significant enhancement of both the dose and penetration of a model vaccine, Ovalbumin (OVA), to depths of 500μm into porcine skin. The nanocups themselves exceeded the penetration depth of the vaccine (up to 700μm) due to their small size and capacity to 'self-propel'. In vivo murine studies indicated that nanocup-assisted ultrasound transdermal vaccination achieved significantly (pultrasound-assisted vaccine delivery in the presence of nanocups demonstrated substantially higher specific anti-OVA IgG antibody levels compared to other transdermal methods. Further optimisation can lead to a viable, safe and non-invasive delivery platform for vaccines with potential use in a primary care setting or personalized self-vaccination at home. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  4. Design and Development of Repaglinide Microemulsion Gel for Transdermal Delivery.

    Science.gov (United States)

    Shinde, Ujwala A; Modani, Sheela H; Singh, Kavita H

    2018-01-01

    Microemulsion formulation of repaglinide, a BCS class II hypoglycemic agent with limited oral bioavailability, was developed considering its solubility in various oils, surfactants, and cosurfactants. The pseudo-ternary phase diagrams for microemulsion regions were constructed by water titration method at K m 1:1 and characterized for optical birefringence, percentage transmittance, pH, refractive index, globule size, zeta potential, viscosity, drug content, and thermodynamic stability. To enhance the drug permeation and residence time, the optimized microemulsions having mean globule size of 36.15 ± 9.89 nm was gelled with xanthan gum. The developed microemulsion-based gel was characterized for globule size, zeta potential, pH, and drug content. All evaluation parameters upon gelling were found to be satisfactory. Ex vivo permeability study across rat skin demonstrated higher steady-state flux (P microemulsion of repaglinide in comparison to the repaglinide microemulsion gel. At the end of 24 h, the cumulative drug permeation from microemulsion and microemulsion gel was found to be 229.19 ± 24.34 and 180.84 ± 17.40 μg/cm 2 , respectively. The microemulsion formulation showed 12.30-fold increase in flux as compared to drug suspension with highest enhancement ratio (E r ) of 12.36. Whereas microemulsion gel exhibited 10.97-fold increase in flux (with highest E r , 11.78) as compared to repaglinide (RPG) suspension. In vivo efficacy study was performed in normal Sprague-Dawley rats by using oral glucose tolerance test. Results of RPG transdermal microemulsion gel demonstrated remarkable advantage over orally administered RPG by reducing the glucose level in controlled manner. Hence, it could be a new, alternative dosage form for effective therapy of type 2 diabetes mellitus.

  5. The construction of optimal stated choice experiments theory and methods

    CERN Document Server

    Street, Deborah J

    2007-01-01

    The most comprehensive and applied discussion of stated choice experiment constructions available The Construction of Optimal Stated Choice Experiments provides an accessible introduction to the construction methods needed to create the best possible designs for use in modeling decision-making. Many aspects of the design of a generic stated choice experiment are independent of its area of application, and until now there has been no single book describing these constructions. This book begins with a brief description of the various areas where stated choice experiments are applicable, including marketing and health economics, transportation, environmental resource economics, and public welfare analysis. The authors focus on recent research results on the construction of optimal and near-optimal choice experiments and conclude with guidelines and insight on how to properly implement these results. Features of the book include: Construction of generic stated choice experiments for the estimation of main effects...

  6. Development of new HRA methods based upon operational experience

    International Nuclear Information System (INIS)

    Cooper, S.E.; Luckas, W.J.; Barriere, M.T.; Wreathall, J.

    2004-01-01

    Under the auspices of the US Nuclear Regulatory Commission (NRC), previously unaddressed human reliability issues are being investigated in order to support the development of human reliability analysis (HRA) methods for both low power and shutdown (LP and S) and full-power conditions. Actual operational experience, such as that reported in Licensee Event Reports (LERs), have been used to gain insights and provide a basis for the requirements of new HRA methods. In particular, operational experience has shown that new HRA methods for LP and S must address human-induced initiators, errors of commission, mistakes (vs. slips), dependencies, and the effects of multiple performance shaping factors (PSFs). (author)

  7. Transdermal granisetron: a guide to its use in preventing nausea and vomiting induced by chemotherapy.

    Science.gov (United States)

    Keating, Gillian M; Duggan, Sean T; Curran, Monique P

    2012-09-01

    Transdermal granisetron (Sancuso®) is effective in the prevention of nausea and vomiting in patients with cancer who are receiving moderately or highly emetogenic chemotherapy for 3-5 days. Transdermal granisetron is noninferior to oral granisetron in this indication, and is generally well tolerated in this indication. Thus, transdermal granisetron provides a convenient option for the prevention of chemotherapy-induced nausea and vomiting, with the potential to improve patient compliance.

  8. A thermal microjet system with tapered micronozzles fabricated by inclined UV lithography for transdermal drug delivery

    Science.gov (United States)

    Yoon, Yong-Kyu; Park, Jung-Hwan; Lee, Jeong-Woo; Prausnitz, Mark R.; Allen, Mark G.

    2011-02-01

    Transdermal drug delivery can be enabled by various methods that increase the permeability of the skin's outer barrier of stratum corneum, including skin exposure to heat and chemical enhancers, such as ethanol. Combining these approaches for the first time, in this study we designed a microdevice consisting of an array of microchambers filled with ethanol that is vaporized using an integrated microheater and ejected through a micronozzle contacting the skin surface. In this way, we hypothesize that the hot ethanol vapor can increase skin permeability upon contacting the skin surface. The tapered micronozzle and the microchamber designed for this application were realized using proximity-mode inclined rotational ultraviolet lithography, which facilitates easy fabrication of complex three-dimensional structures, convenient integration with other functional layers, low fabrication cost, and mass production. The resulting device had a micronozzle with an orifice inner and outer diameter of 220 and 320 µm, respectively, and an extruded height of 250 µm. When the microchamber was filled with an ethanol gel and activated, the resulting ethanol vapor jet increased the permeability of human cadaver epidermis to a model compound, calcein, by approximately 17 times, which is attributed to thermal and chemical disruption of stratum corneum structure. This thermal microjet system can serve as a tool not only for transdermal drug delivery, but also for a variety of biomedical applications.

  9. Increased skin permeation efficiency of imperatorin via charged ultradeformable lipid vesicles for transdermal delivery.

    Science.gov (United States)

    Lin, Hongwei; Xie, Qingchun; Huang, Xin; Ban, Junfeng; Wang, Bo; Wei, Xing; Chen, Yanzhong; Lu, Zhufen

    2018-01-01

    The aim of this work was to develop a novel vesicular carrier, ultradeformable liposomes (UDLs), to expand the applications of the Chinese herbal medicine, imperatorin (IMP), and increase its transdermal delivery. In this study, we prepared IMP-loaded UDLs using the thin-film hydration method and evaluated their encapsulation efficiency, vesicle deformability, skin permeation, and the amounts accumulated in different depths of the skin in vitro. The influence of different charged surfactants on the properties of the UDLs was also investigated. The results showed that the UDLs containing cationic surfactants had high entrapment efficiency (60.32%±2.82%), an acceptable particle size (82.4±0.65 nm), high elasticity, and prolonged drug release. The penetration rate of IMP in cationic-UDLs was 3.45-fold greater than that of IMP suspension, which was the highest value among the vesicular carriers. UDLs modified with cationic surfactant also showed higher fluorescence intensity in deeper regions of the epidermis. The results of our study suggest that cationic surfactant-modified UDLs could increase the transdermal flux, prolong the release of the drug, and serve as an effective dermal delivery system for IMP.

  10. A thermal microjet system with tapered micronozzles fabricated by inclined UV lithography for transdermal drug delivery

    International Nuclear Information System (INIS)

    Yoon, Yong-Kyu; Park, Jung-Hwan; Lee, Jeong-Woo; Prausnitz, Mark R; Allen, Mark G

    2011-01-01

    Transdermal drug delivery can be enabled by various methods that increase the permeability of the skin's outer barrier of stratum corneum, including skin exposure to heat and chemical enhancers, such as ethanol. Combining these approaches for the first time, in this study we designed a microdevice consisting of an array of microchambers filled with ethanol that is vaporized using an integrated microheater and ejected through a micronozzle contacting the skin surface. In this way, we hypothesize that the hot ethanol vapor can increase skin permeability upon contacting the skin surface. The tapered micronozzle and the microchamber designed for this application were realized using proximity-mode inclined rotational ultraviolet lithography, which facilitates easy fabrication of complex three-dimensional structures, convenient integration with other functional layers, low fabrication cost, and mass production. The resulting device had a micronozzle with an orifice inner and outer diameter of 220 and 320 µm, respectively, and an extruded height of 250 µm. When the microchamber was filled with an ethanol gel and activated, the resulting ethanol vapor jet increased the permeability of human cadaver epidermis to a model compound, calcein, by approximately 17 times, which is attributed to thermal and chemical disruption of stratum corneum structure. This thermal microjet system can serve as a tool not only for transdermal drug delivery, but also for a variety of biomedical applications.

  11. Electroporation-delivered transdermal neostigmine in rats: equivalent action to intravenous administration.

    Science.gov (United States)

    Berkó, Szilvia; Szűcs, Kálmán F; Balázs, Boglárka; Csányi, Erzsébet; Varju, Gábor; Sztojkov-Ivanov, Anita; Budai-Szűcs, Mária; Bóta, Judit; Gáspár, Róbert

    2016-01-01

    Transdermal electroporation has become one of the most promising noninvasive methods for drug administration, with greatly increased transport of macromolecules through the skin. The cecal-contracting effects of repeated transdermal electroporation delivery and intravenous administration of neostigmine were compared in anesthetized rats. The cecal contractions were detected with implantable strain gauge sensors, and the plasma levels of neostigmine were followed by high-performance liquid chromatography. Both intravenously and EP-administered neostigmine (0.2-66.7 μg/kg) increased the cecal contractions in a dose-dependent manner. For both the low doses and the highest dose, the neostigmine plasma concentrations were the same after the two modes of administration, while an insignificantly higher level was observed at a dose of 20 μg/kg after intravenous administration as compared with the electroporation route. The contractile responses did not differ significantly after the two administration routes. The results suggest that electroporation-delivered neostigmine elicits action equivalent to that observed after intravenous administration as concerning both time and intensity. Electroporation permits the delivery of even lower doses of water-soluble compounds through the skin, which is very promising for clinical practice.

  12. Rapid, low cost prototyping of transdermal devices for personal healthcare monitoring

    Directory of Open Access Journals (Sweden)

    Sanjiv Sharma

    2017-04-01

    Full Text Available The next generation of devices for personal healthcare monitoring will comprise molecular sensors to monitor analytes of interest in the skin compartment. Transdermal devices based on microneedles offer an excellent opportunity to explore the dynamics of molecular markers in the interstitial fluid, however good acceptability of these next generation devices will require several technical problems associated with current commercially available wearable sensors to be overcome. These particularly include reliability, comfort and cost. An essential pre-requisite for transdermal molecular sensing devices is that they can be fabricated using scalable technologies which are cost effective.We present here a minimally invasive microneedle array as a continuous monitoring platform technology. Method for scalable fabrication of these structures is presented. The microneedle arrays were characterised mechanically and were shown to penetrate human skin under moderate thumb pressure. They were then functionalised and evaluated as glucose, lactate and theophylline biosensors. The results suggest that this technology can be employed in the measurement of metabolites, therapeutic drugs and biomarkers and could have an important role to play in the management of chronic diseases. Keywords: Microneedles, Minimally invasive sensors, Continuous glucose monitoring (CGM, Continuous lactate monitoring (CLM, Interstitial therapeutic drug monitoring (iTDM

  13. Analyzing polymeric matrix for fabrication of a biodegradable microneedle array to enhance transdermal delivery.

    Science.gov (United States)

    Hwa, Kuo-Yuan; Chang, Vincent H S; Cheng, Yao-Yi; Wang, Yue-Da; Jan, Pey-Shynan; Subramani, Boopathi; Wu, Min-Ju; Wang, Bo-Kai

    2017-09-19

    Traditional drug delivery systems, using invasive, transdermal, and oral routes, are limited by various factors, such as the digestive system environment, skin protection, and sensory nerve stimulation. To improve the drug delivery system, we fabricated a polysaccharide-based, dissolvable microneedle-based array, which combines the advantages of both invasive and transdermal delivery systems, and promises to be an innovative solution for minimally invasive drug delivery. In this study, we designed a reusable aluminum mold that greatly improved the efficiency and convenience of microneedle fabrication. Physical characterization of the polysaccharides, individual or mixed at different ratios, was performed to identify a suitable molecule to fabricate the dissolvable microneedle. We used a vacuum deposition-based micro-molding method at low temperature to fabricate the model. Using a series of checkpoints from material into product, a systematic feedback mechanism was built into the "all-in-one" fabrication step, which helped to improve production yields. The physical properties of the fabricated microneedle were assessed. The cytotoxicity analysis and animal testing of the microneedle demonstrated the safety and compatibility of the microneedle, and the successful penetration and effective release of a model protein.

  14. Development of Novel Formulations to Enhance in Vivo Transdermal Permeation of Tocopherol

    Directory of Open Access Journals (Sweden)

    Nada Aly H.

    2014-09-01

    Full Text Available Tocopherol represents a big challenge for transdermal permeation owing to its extreme hydrophobicity and large molecular mass. The aim of the present study was to develop alpha-tocopherol (T topical formulations and evaluate their ex vivo and in vivo permeation. Franz diffusion cells were used for ex vivo permeation, and neonatal rats were used for in vivo permeation. Seven gel formulations and 21 liquid formulations were investigated for physical stability, viscosity and permeation of T. Analysis of T was performed by a validated HPLC method using a UV detector. The ex vivo permeation from gel and emulsion formulations was very poor (0.001-0.015 %. Highest permeation was observed from monophasic liquid formulations containing dimethyl sulfoxide (DMSO, tocopheryl polyethylene glycols (TPGs, propylene glycol, ethanol and 9.5 % T. The in vivo results demonstrated higher retention in the epidermis compared to subcutaneous tissues, 1377 and 1.13 μg g-1, respectively. Increasing T concentration from 4.8 to 9.5 % did not increase the amount permeated or % of T retained. It was concluded that simple solutions of T in the presence of DMSO and TPGs were more promising systems for effective transdermal permeation compared to gel, emulsion or oleaginous systems.

  15. Patient considerations in the use of transdermal iontophoretic fentanyl for acute postoperative pain

    Directory of Open Access Journals (Sweden)

    Hartrick CT

    2016-04-01

    Full Text Available Craig T Hartrick,1 Cecile R Pestano,1 Li Ding,2 Hassan Danesi,2 James B Jones,2 1Beaumont Health System, Troy, MI, 2The Medicines Company, Parsippany, NJ, USA Abstract: Opioids are commonly used in the management of moderate-to-severe postoperative pain. Patient-controlled analgesic techniques are recognized as preferred administration methods. Previously, research has focused on intravenously administered opioids via a programmable pump. More recently, an iontophoretic transdermal system (ITS, which is patient controlled, has been developed. The focus of this review is on pain management using the fentanyl ITS during the 24–72-hour time period immediately following surgery. Fentanyl ITS offers a needle-free alternative to traditional intravenous (IV patient-controlled analgesia (PCA system that is as effective and safe as IV PCA. This system is easy to use for both patients and nurses. The use of fentanyl ITS is generally associated with a better ease-of-care profile, including a greater ease of mobility, from a patients' perspective when compared with morphine IV PCA. Keywords: patient-controlled analgesia, fentanyl iontophoretic transdermal system, ease of care, mobility, patient perspective, review

  16. An unfolding method for high energy physics experiments

    International Nuclear Information System (INIS)

    Blobel, V.

    2002-06-01

    Finite detector resolution and limited acceptance require one to apply unfolding methods in high energy physics experiments. Information on the detector resolution is usually given by a set of Monte Carlo events. Based on the experience with a widely used unfolding program (RUN) a modified method has been developed. The first step of the method is a maximum likelihood fit of the Monte Carlo distributions to the measured distribution in one, two or three dimensions; the finite statistics of the Monte Carlo events is taken into account by the use of Barlow's method with a new method of solution. A clustering method is used before combining bins in sparsely populated areas. In the second step a regularization is applied to the solution, which introduces only a small bias. The regularization parameter is determined from the data after a diagonalization and rotation procedure. (orig.)

  17. Quasi-Experiments and Hedonic Property Value Methods

    OpenAIRE

    Christopher F. Parmeter; Jaren C. Pope

    2012-01-01

    There has recently been a dramatic increase in the number of papers that have combined quasi-experimental methods with hedonic property models. This is largely due to the concern that cross-sectional hedonic methods may be severely biased by omitted variables. While the empirical literature has developed extensively, there has not been a consistent treatment of the theory and methods of combining hedonic property models with quasi-experiments. The purpose of this chapter is to fill this void....

  18. Minimization of CYP2D6 Polymorphic Differences and Improved Bioavailability via Transdermal Administration: Latrepirdine Example.

    Science.gov (United States)

    Chew, Marci L; Mordenti, Joyce; Yeoh, Thean; Ranade, Gautam; Qiu, Ruolun; Fang, Juanzhi; Liang, Yali; Corrigan, Brian

    2016-08-01

    Transdermal delivery has the potential to offer improved bioavailability by circumventing first-pass gut and hepatic metabolism. This study evaluated the pharmacokinetics of oral immediate release and transdermal latrepirdine in extensive and poor CYP2D6 metabolizers (EM/PM). Latrepirdine transdermal solution was prepared extemporaneously. The solution was applied with occlusive dressing to upper or middle back for 24 h. Each subject received a single dose of 8.14 mg oral, 5 mg transdermal, and 10 mg transdermal (EMs only) latrepirdine free base in a fixed sequence. Twelve EMs and 7 PMs (50-79 years) enrolled and completed the study. Latrepirdine was well tolerated following both routes of administration. Dose-normalized latrepirdine total exposures were approximately 11-fold and 1.5-fold higher in EMs and PMs, respectively following administration of transdermal relative to oral. Differences between EM and PM latrepirdine exposures were decreased, with PMs having 1.9- and 2.7-fold higher peak and total exposures, respectively, following transdermal administration compared to 11- and 20-fold higher exposures, respectively, following oral administration. Transdermal delivery can potentially mitigate the large intersubject differences observed with compounds metabolized primarily by CYP2D6. Transdermal delivery was readily accomplished in the clinic using an extemporaneously prepared solution [NCT00990613].

  19. Transdermal and intradermal delivery of therapeutic agents: application of physical technologies

    National Research Council Canada - National Science Library

    Banga, Ajay K

    2011-01-01

    .... Commercialization of transdermal drug delivery requires technology from many disciplines beyond pharmaceutical sciences, such as polymer chemistry, adhesion sciences, mass transport, web film coating...

  20. Acceptability of a transdermal gel-based male hormonal contraceptive in a randomized controlled trial☆, ☆☆, ★

    Science.gov (United States)

    Roth, Mara Y.; Shih, Grace; Ilani, Niloufar; Wang, Christina; Page, Stephanie T.; Bremner, William J.; Swerdloff, Ronald S.; Sitruk-Ware, Regine; Blithe, Diana L.; Amory, John K.

    2014-01-01

    Objective Fifty percent of pregnancies in the United States are unintended despite numerous contraceptive methods available to women. The only male contraceptive methods, vasectomy and condoms, are used by 10% and 16% of couples, respectively. Prior studies have shown efficacy of male hormonal contraceptives in development, but few have evaluated patient acceptability and potential use if commercially available. The objective of this study is to determine if a transdermal gel-based male hormonal contraceptive regimen, containing testosterone and Nestorone® gels, would be acceptable to study participants as a primary contraceptive method. Study Design As part of a three-arm, 6-month, double-blind, randomized controlled trial of testosterone and nestorone gels at two academic medical centers, subjects completed a questionnaire to assess the acceptability of the regimen. Of the 99 men randomized, 79 provided data for analysis. Results Overall, 56% (44/79) of men were satisfied or extremely satisfied with this gel-based method of contraception, and 51% (40/79) reported that they would recommend this method to others. One third of subjects (26/79) reported that they would use this as their primary method of contraception if it were commercially available today. However, men with concerns about sexually transmitted disease were significantly less satisfied than men without such concerns (p=0.03). Conclusions A majority of the men who volunteered to participate in this trial of an experimental male hormonal contraceptive were satisfied with this transdermal male hormonal contraceptive. If commercially available, a combination of topical nesterone and testosterone gels could provide a reversible, effective method of contraception that is appealing to men. Implications A substantial portion of men report they would use this transdermal male contraceptive regimen if commercially available. This method would provide a novel, reversible method of contraception for men, whose

  1. Numerical experiment on finite element method for matching data

    International Nuclear Information System (INIS)

    Tokuda, Shinji; Kumakura, Toshimasa; Yoshimura, Koichi.

    1993-03-01

    Numerical experiments are presented on the finite element method by Pletzer-Dewar for matching data of an ordinary differential equation with regular singular points by using model equation. Matching data play an important role in nonideal MHD stability analysis of a magnetically confined plasma. In the Pletzer-Dewar method, the Frobenius series for the 'big solution', the fundamental solution which is not square-integrable at the regular singular point, is prescribed. The experiments include studies of the convergence rate of the matching data obtained by the finite element method and of the effect on the results of computation by truncating the Frobenius series at finite terms. It is shown from the present study that the finite element method is an effective method for obtaining the matching data with high accuracy. (author)

  2. The Experiment Method for Manufacturing Grid Development on Single Computer

    Institute of Scientific and Technical Information of China (English)

    XIAO Youan; ZHOU Zude

    2006-01-01

    In this paper, an experiment method for the Manufacturing Grid application system development in the single personal computer environment is proposed. The characteristic of the proposed method is constructing a full prototype Manufacturing Grid application system which is hosted on a single personal computer with the virtual machine technology. Firstly, it builds all the Manufacturing Grid physical resource nodes on an abstraction layer of a single personal computer with the virtual machine technology. Secondly, all the virtual Manufacturing Grid resource nodes will be connected with virtual network and the application software will be deployed on each Manufacturing Grid nodes. Then, we can obtain a prototype Manufacturing Grid application system which is working in the single personal computer, and can carry on the experiment on this foundation. Compared with the known experiment methods for the Manufacturing Grid application system development, the proposed method has the advantages of the known methods, such as cost inexpensively, operation simple, and can get the confidence experiment result easily. The Manufacturing Grid application system constructed with the proposed method has the high scalability, stability and reliability. It is can be migrated to the real application environment rapidly.

  3. DETERMINATION OF THE STABILITY OF A LOCAL ANESTHETIC BROMOKAIN TRANSDERMAL THERAPEUTIC SYSTEM

    Directory of Open Access Journals (Sweden)

    V. A. Ryzhikova

    2014-01-01

    Full Text Available Aim. To study the stability of biocompatible microemulsion composition-based bromokain transdermal therapeutic systems (TTS in order to confi rm the original shelf life and to identify the most appropriate TTS composition for storage.Materials and methods. The stability test using accelerated aging method was performed on the samples of TTS containing 50 and 100 mg of bromokain. Physicochemical properties of TTS were analyzed at the end of the 1st, 2nd, 3rd, and 6th month of storage. The physical confi guration of the dosage form, the content of bromokain in TTS, and drug release were evaluated at each stage of the study. The content of bromokain in the samples was recorded using high performance liquid chromatography (HPLC. As a control for each method, the newly manufactured TTS forms were used.Results. Unlike the samples containing 50 mg of bromokain, TTS with 100 mg of the anesthetic demonstrated changes in the physical confi guration and deterioration of the functional properties after the 6th month of storage. The quantitative content of the substance in TTS containing 50 and 100 mg of bromokain met the requirements of regulatory documentation (RD at allphases of the experiment and was within 50,0 ± 5,0 mg and 100,0 ± 10,0 mg, respectively. The release profi le of TTS with 50 mg of bromokain has remained unchanged during storage and complies with the RD. TTS with 100 mg of bromokain after the 3rd month of storage had a deviation from the release profi le indicated in the RD.Conclusion. The shelf life of 2 years at t = 25 °C preset by us for samples of TTS containing 50 mg of bromokain has been confi rmed. According to the test results, samples of TTS with the content of bromokain of 100 mg were declared unstable and unfi t for storage under the selected storage conditions.

  4. Preparation and Optimization of Labeled Chitosan Nanoparticles and Evaluation of their Release from Transdermal Drug Delivery System

    Directory of Open Access Journals (Sweden)

    Mohsen Sadeghi

    2015-09-01

    Full Text Available Biocompatible nanoparticles are widely used in biomedical engineering. In this study, chitosan nanoparticles were prepared using ionic gelation method in view of two determining factors namely method of adding chitosan into the tripolyphosphate (TPP solution and thermal shock application. With regard to the concentration of chitosan and TPP solutions as two variables, the mean particle size of chitosan nanoparticles and their preparation yield were optimized using response surface method. According to previous studies and some preliminary experiments, the chitosan and TPP solution concentration ranges were determined to be 0.5-2.5 mg/mL and 0.25-1.25 mg/mL, respectively. The optimum values of 1.25 mg/mL and 0.6 mg/mL were obtained for chitosan and TPP solution concentrations in the order given. The optimized response value for the chitosan nanoparticles size was found to be 54 nm and preparation yield was 62%. The Zeta potential of resulting spherical nanoparticles was around 31 mV. Chitosan-fluorescein isothiocyanate (FITC polymer was prepared based on the reaction between isothiocyanate functional group of FITC and primary amine functional group of chitosan. FTIR analysis was performed to demonstrate the presence of new bond formation. Labeled chitosan nanoparticles were prepared in the optimized condition using chitosan-FITC polymer. The release behavior of the labeled chitosan nanoparticles from transdermal patches was evaluated. The mean size of chitosan-FITC nanoparticles was determined to be 70 nm. Finally, it was shown that the chitosan nanoparticles were not able to release from acrylic adhesive film without using a method to speed up their diffusion.

  5. Evaluation of the Percutaneous Absorption of Ketamine HCl, Gabapentin, Clonidine HCl, and Baclofen, in Compounded Transdermal Pain Formulations, Using the Franz Finite Dose Model.

    Science.gov (United States)

    Bassani, August S; Banov, Daniel

    2016-02-01

    This study evaluates the ability of four commonly used analgesics (ketamine HCl, gabapentin, clonidine HCl, and baclofen), when incorporated into two transdermal compounding bases, Lipoderm and Lipoderm ActiveMax, to penetrate human cadaver trunk skin in vitro, using the Franz finite dose model. In vitro experimental study. Methods. Ketamine HCl 5% w/w, gabapentin 10% w/w, clonidine HCl 0.2% w/w, and baclofen 2% w/w were compounded into two transdermal bases, Lipoderm and Lipoderm ActiveMax. Each compounded drug formulation was tested on skin from three different donors and three replicate skin sections per donor. The Franz finite dose model was used in this study to evaluate the percutaneous absorption and distribution of drugs within each formulation. Rapid penetration to peak flux was detected for gabapentin and baclofen at approximately 1 hour after application. Clonidine HCl also had a rapid penetration to peak flux occurring approximately 1 hour after application and had a secondary peak at approximately 40 hours. Ketamine HCl exhibited higher overall absorption rates than the other drugs, and peaked at 6–10 hours. Similar patterns of drug distribution within the skin were also observed using both transdermal bases. This study suggests that the combination of these 4 analgesic drugs can be successfully delivered transdermally, using either Lipoderm or Lipoderm ActiveMax. Compounded transdermal drug preparations may then provide physicians with an alternative to traditional oral pain management regimens that can be personalized to the specific patient with the potential for enhanced pain control.

  6. A prospective randomized comparative study of the effects of intranasal and transdermal 17 β-estradiol on postmenopausal symptoms and vaginal cytology

    Directory of Open Access Journals (Sweden)

    Odabasi A

    2007-01-01

    Full Text Available Context: Investigating the adverse effects of oral hormone replacement therapy (HRT, the clinical effectiveness of alternative combinations and route of administrations. Aim: To compare the effects of intranasal and transdermal 17β-estradiol combined with vaginal progesterone on vasomotor symptoms and vaginal cytology. Settings and Design: A 12-week, prospective, randomized comparative study was conducted between July 2005 and September 2006. Materials and Methods: Eighty postmenopausal women aged between 42-57 years, who had scores of ≥1.7 on the menopause rating scale-I (MRS-I items "1-6", were randomly assigned to receive intranasal (300 µg/day, n =40 or transdermal (50 µg/day, n =40 17β-estradiol continuously. All patients also received a vaginal progesterone gel twice weekly. Vasomotor symptoms were evaluated at weeks 0, 4, 8 and 12. Vaginal maturation index (VMI was evaluated at weeks 0 and 12 of the study. Statistical Analyses: The Mann-Whitney U and the Wilcoxon tests were used. P < 0.05 was regarded as significant. Results: Thirty-two women in the intranasal and 29 women in the transdermal group completed the study. The total score of the MRS, the sum-scores of Factor 1 "HOT FLUSHES" and Factor 2 "PSYCHE" significantly decreased in both groups at week 4. Factor 3 "ATROPHY" scores significantly decreased only in the transdermal group at week 12. The VMI showed no changes within and between the two groups at the end of the study. Conclusion: Intranasal and transdermal 17β-estradiol combined with vaginal progesterone gel as a continuous HRT caused a similar decrease in vasomotor symptoms but did not have any significant effect on VMI after 12 weeks of treatment in this study population.

  7. The experiments and analysis of several selective video encryption methods

    Science.gov (United States)

    Zhang, Yue; Yang, Cheng; Wang, Lei

    2013-07-01

    This paper presents four methods for selective video encryption based on the MPEG-2 video compression,including the slices, the I-frames, the motion vectors, and the DCT coefficients. We use the AES encryption method for simulation experiment for the four methods on VS2010 Platform, and compare the video effects and the processing speed of each frame after the video encrypted. The encryption depth can be arbitrarily selected, and design the encryption depth by using the double limit counting method, so the accuracy can be increased.

  8. Studying collaborative information seeking: Experiences with three methods

    DEFF Research Database (Denmark)

    Hyldegård, Jette Seiden; Hertzum, Morten; Hansen, Preben

    2015-01-01

    , however, benefit from a discussion of methodological issues. This chapter describes the application of three methods for collecting and analyzing data in three CIS studies. The three methods are Multidimensional Exploration, used in a CIS study of students’ in-formation behavior during a group assignment......; Task-structured Observation, used in a CIS study of patent engineers; and Condensed Observation, used in a CIS study of information-systems development. The three methods are presented in the context of the studies for which they were devised, and the experiences gained using the methods are discussed....... The chapter shows that different methods can be used for collecting and analyzing data about CIS incidents. Two of the methods focused on tasks and events in work settings, while the third was applied in an educational setting. Commonalities and differences among the methods are discussed to inform decisions...

  9. Enhancement of transdermal delivery of ibuprofen using microemulsion vehicle.

    Science.gov (United States)

    Hu, Liandong; Hu, Qiaofeng; Yang, Jianxue

    2014-10-01

    The objective of this study was to find a stable microemulsion vehicle for transdermal delivery of ibuprofen to improve the skin permeability. Microemulsion was prepared using different sorts of oils, surfactants and co-surfactants. Pseudo-ternary phase diagrams were used to evaluate the microemulsion domain. The effects of oleic acid and surfactant mixture on skin permeation of ibuprofen were evaluated with excised skins. The optimum formulation F3 consisting of 6% oleic acid, 30% Cremophor RH40/Transcutol P (2:1, w/w) and 59% water phase, showed a high permeation rate of 42.98 µg/cm(2)/hr. The mean droplet size of microemulsion was about 43 nm and no skin irritation signs were observed on the skin of rabbits. These results indicated that this novel microemulsion is a useful formulation for the transdermal delivery of ibuprofen.

  10. Novel engineered systems for oral, mucosal and transdermal drug delivery.

    Science.gov (United States)

    Li, Hairui; Yu, Yuan; Faraji Dana, Sara; Li, Bo; Lee, Chi-Ying; Kang, Lifeng

    2013-08-01

    Technological advances in drug discovery have resulted in increasing number of molecules including proteins and peptides as drug candidates. However, how to deliver drugs with satisfactory therapeutic effect, minimal side effects and increased patient compliance is a question posted before researchers, especially for those drugs with poor solubility, large molecular weight or instability. Microfabrication technology, polymer science and bioconjugate chemistry combine to address these problems and generate a number of novel engineered drug delivery systems. Injection routes usually have poor patient compliance due to their invasive nature and potential safety concerns over needle reuse. The alternative non-invasive routes, such as oral, mucosal (pulmonary, nasal, ocular, buccal, rectal, vaginal), and transdermal drug delivery have thus attracted many attentions. Here, we review the applications of the novel engineered systems for oral, mucosal and transdermal drug delivery.

  11. Dissolving polymeric microneedle arrays for electrically assisted transdermal drug delivery.

    Science.gov (United States)

    Garland, Martin J; Caffarel-Salvador, Ester; Migalska, Katarzyna; Woolfson, A David; Donnelly, Ryan F

    2012-04-10

    It has recently been proposed that the combination of skin barrier impairment using microneedles (MNs) coupled with iontophoresis (ITP) may broaden the range of drugs suitable for transdermal delivery, as well as enabling the rate of delivery to be achieved with precise electronic control. However, no reports exist on the combination of ITP with in situ drug loaded polymeric MN delivery systems. Furthermore, although a number of studies have highlighted the importance of MN design for transdermal drug delivery enhancement, to date, there has been no systematic investigation of the influence of MN geometry on the performance of polymeric MN arrays which are designed to remain in contact with the skin during the period of drug delivery. As such, for the first time, this study reports on the effect of MN heigth and MN density upon the transdermal delivery of small hydrophilic compounds (theophylline, methylene blue, and fluorescein sodium) across neonatal porcine skin in vitro, with the optimised MN array design evaluated for its potential in the electrically faciliatated delivery of peptide (bovine insulin) and protein (fluorescein isothiocyanate-labelled bovine serum albumin (FTIC-BSA)) macromolecules. The results of the in vitro drug release investigations revealed that the extent of transdermal delivery was dependent upon the design of the MN array employed, whereby an increase in MN height and an increase in MN density led to an increase in the extent of transdermal drug delivery achieved 6h after MN application. Overall, the in vitro permeation studies revealed that the MN design containing 361 MNs/cm(2) of 600 μm height resulted in the greatest extent of transdermal drug delivery. As such, this design was evaluated for its potential in the MN mediated iontophoretic transdermal delivery. Whilst the combination of MN and ITP did not further enhance the extent of small molecular weight solute delivery, the extent of peptide/protein release was significantly

  12. Current advances in transdermal delivery of drugs for Alzheimer's disease

    Science.gov (United States)

    Nguyen, Thuy Trang; Giau, Vo Van; Vo, Tuong Kha

    2017-01-01

    Alzheimer's disease (AD) is a common, progressive, fatal neurodegenerative disorder, which will play an increasingly important role both socially and financially in the aging populations. Treatments for AD show modest improvements in cognition and global functioning among patients. Furthermore, the oral administration of treating AD has had some drawbacks that decrease the medication adherence and efficacy of the therapy. Transdermal drugs are proposed as an alternative remedy to overcome the disadvantages of current pharmaceutical dosage options for this chronic disorder. They could have different strengths, such as offering a stable diffusion of active substance, avoiding the first pass metabolism, and reducing system adverse reactions. This article reviews the technical principles, novel techniques of transdermal delivery drug, and prospects for future development for the management of cognitive and behavioral dysfunctions in AD patients. PMID:28706327

  13. Hybrid electrospun chitosan-phospholipids nanofibers for transdermal drug delivery

    DEFF Research Database (Denmark)

    Mendes, Ana Carina Loureiro; Gorzelanny, Christian; Halter, Natalia

    2016-01-01

    Chitosan (Ch) polysaccharide was mixed with phospholipids (P) to generate electrospun hybrid nanofibers intended to be used as platforms for transdermal drug delivery. Ch/P nanofibers exibithed average diameters ranging from 248 +/- 94 nm to 600 +/- 201 nm, depending on the amount of phospholipids...... used. Fourier Transformed Infra-Red (FTIR) spectroscopy and Dynamic Light Scattering (DLS) data suggested the occurrence of electrostatic interactions between amine groups of chitosan with the phospholipid counterparts. The nanofibers were shown to be stable for at least 7 days in Phosphate Buffer...... culture plate (control). The release of curcumin, diclofenac and vitamin B12, as model drugs, from Ch/P hybrid nanofibers was investigated, demonstrating their potential utilization as a transdermal drug delivery system....

  14. Inkjet printing of insulin microneedles for transdermal delivery.

    Science.gov (United States)

    Ross, Steven; Scoutaris, Nicolaos; Lamprou, Dimitrios; Mallinson, David; Douroumis, Dennis

    2015-08-01

    Inkjet printing technology was used to apply insulin polymeric layers on metal microneedles for transdermal delivery. A range of various polymers such as gelatin (GLN), polyvinyl caprolactame-polyvinyl acetate-polyethylene glycol (SOL), poly(2-ethyl-2-oxazoline) (POX) and trehalose (THL) were assessed for their capacity to form thin uniform and homogeneous layers that preserve insulin intact. Atomic force microscopy (AFM) showed homogeneous insulin-polymer layers without any phase separation while SOL demonstrated the best performance. Circular discroism (CD) analysis of rehydrated films showed that insulin's alpha helices and β-sheet were well preserved for THL and SOL. In contrast, GLN and POX insulin layers revealed small band shifts indicating possible conformational changes. Insulin release in Franz diffusion cells from MNs inserted into porcine skin showed rapid release rates for POX and GLN within the first 20 min. Inkjet printing was proved an effective approach for transdermal delivery of insulin in solid state.

  15. Current advances in transdermal delivery of drugs for Alzheimer's disease.

    Science.gov (United States)

    Nguyen, Thuy Trang; Giau, Vo Van; Vo, Tuong Kha

    2017-01-01

    Alzheimer's disease (AD) is a common, progressive, fatal neurodegenerative disorder, which will play an increasingly important role both socially and financially in the aging populations. Treatments for AD show modest improvements in cognition and global functioning among patients. Furthermore, the oral administration of treating AD has had some drawbacks that decrease the medication adherence and efficacy of the therapy. Transdermal drugs are proposed as an alternative remedy to overcome the disadvantages of current pharmaceutical dosage options for this chronic disorder. They could have different strengths, such as offering a stable diffusion of active substance, avoiding the first pass metabolism, and reducing system adverse reactions. This article reviews the technical principles, novel techniques of transdermal delivery drug, and prospects for future development for the management of cognitive and behavioral dysfunctions in AD patients.

  16. A Modified Cooling Method and Its Application in "Drosophila" Experiments

    Science.gov (United States)

    Qu, Wen-hui; Zhu, Tong-bo; Yang, Da-Xiang

    2015-01-01

    Chilling is a cost-effective and safe method of immobilising flies in "Drosophila" experiments. However, should condensation form on the plate, it would be fatal to the flies. Here we describe a modified cooling method using reusable commercial ice pack(s) (ca. 400 ml, 2-3 cm tall) rather than crushed ice. The ice pack is covered with a…

  17. Evaluation of Diclofenac Prodrugs for Enhancing Transdermal Delivery

    OpenAIRE

    Lobo, Shabbir; Li, Henan; Farhan, Nashid; Yan, Guang

    2013-01-01

    The purpose of this study was to evaluate the approach of using diclofenac acid (DA) prodrugs for enhancing transdermal delivery. Methanol diclofenac ester (MD), ethylene glycol diclofenac ester (ED), glycerol diclofenac ester (GD), and 1,3-propylene glycol diclofenac ester (PD) were synthesized and evaluated for their physicochemical properties such as solubilities, octanol/water partition coefficients, stratum corneum/water partition coefficients, hydrolysis rates, and bioconversion rates. ...

  18. Current advances in transdermal delivery of drugs for alzheimer's disease

    OpenAIRE

    Thuy Trang Nguyen; Vo Van Giau; Tuong Kha Vo

    2017-01-01

    Alzheimer's disease (AD) is a common, progressive, fatal neurodegenerative disorder, which will play an increasingly important role both socially and financially in the aging populations. Treatments for AD show modest improvements in cognition and global functioning among patients. Furthermore, the oral administration of treating AD has had some drawbacks that decrease the medication adherence and efficacy of the therapy. Transdermal drugs are proposed as an alternative remedy to overcome the...

  19. Optimization of transdermal delivery using magainin pore-forming peptide

    OpenAIRE

    Kim, Yeu-Chun; Ludovice, Peter J.; Prausnitz, Mark R.

    2008-01-01

    The skin's outer layer of stratum corneum, which is a thin tissue containing multilamellar lipid bilayers, is the main barrier to drug delivery to the skin. To increase skin permeability, our previous work has shown large enhancement of transdermal permeation using a pore-forming peptide, magainin, which was formulated with N-lauroyl sarcosine (NLS) in 50% ethanol-in-PBS. Mechanistic analysis suggested that magainin and NLS can increase skin permeability by disrupting stratum corneum lipid st...

  20. Review of track-fitting methods in counter experiments

    International Nuclear Information System (INIS)

    Regler, M.; Eichinger, H.

    1981-01-01

    We review track-fitting methods recently used in high-energy physics experiments. Assuming that the problem of pattern recognition, i.e. of grouping the often ambiguous coordinate information (as frequently measured by wire chambers) together to form track candidates, has already been solved, we try to point out the way to obtain the ultimate geometrical resolution with the smallest and fastest possible program; owing to the wide variety of detectors and experimental set-ups, no universal method has been found. Some applications will serve as examples, and based on the experience gained we will try to indicate when and under which conditions a known algorithm could be used, and this might even help in designing future experiments. (orig.)

  1. Enhancing user experience design with an integrated storytelling method

    NARCIS (Netherlands)

    Peng, Qiong; Matterns, Jean Bernard; Marcus, A.

    2016-01-01

    Storytelling has been known as a service design method and been used broadly not only in service design but also in the context of user experience design. However, practitioners cannot yet fully appreciate the benefits of storytelling, and often confuse storytelling with storyboarding and scenarios.

  2. Microneedle-based drug delivery systems for transdermal route.

    Science.gov (United States)

    Pierre, Maria Bernadete Riemma; Rossetti, Fabia Cristina

    2014-03-01

    Transdermal delivery offers an attractive, noninvasive administration route but it is limited by the skin's barrier to penetration. Minimally invasive techniques, such as the use of microneedles (MNs), bypass the stratum corneum (SC) barrier to permit the drug's direct access to the viable epidermis. These novel micro devices have been developed to puncture the skin for the transdermal delivery of hydrophilic drugs and macromolecules, including peptides, DNA and other molecules, that would otherwise have difficulty passing the outermost layer of the skin, the SC. Using the tools of the microelectronics industry, MNs have been fabricated with a range of sizes, shapes and materials. MNs have been shown to be robust enough to penetrate the skin and dramatically increase the skin permeability of several drugs. Moreover, MNs have reduced needle insertion pain and tissue trauma and provided controlled delivery across the skin. This review focuses on the current state of the art in the transdermal delivery of drugs using various types of MNs and developments in the field of microscale devices, as well as examples of their uses and clinical safety.

  3. Evaluation of mesotherapy as a transdermal drug delivery tool.

    Science.gov (United States)

    Kim, S; Kye, J; Lee, M; Park, B

    2016-05-01

    There has been no research about the exact mechanism of transdermal drug delivery during mesotherapy. We aimed to evaluate whether the commercial mesogun can be an appropriate technique for a transdermal drug delivery. We injected blue ink into the polyurethane foam or pig skin with three types of mesotherapy using a commercial mesogun, or local made intradermal injector, or a manual injection of syringe. To assess the internal pressure of the cylinder and drug delivery time, we designed the evaluation setup using a needle tip pressure transducer. All types of injectors induced adequate penetration of blue ink into the polyurethane foam without backflow. In the pig skin, blue ink leaked out rapidly with the backward movement of the needle in the commercial mesogun in contrast to the local made injector or the manual injection of syringe. When the time for backward movement of the syringe approaches 1000 ms, the cylinder pressure of the syringe is saturated at around 25 mmHg which can be translated into the dermal pressure of the pig skin. There should be sufficient time between the insertion and withdrawal of the needle of injector for the adequate transdermal drug delivery and it must be considered for mesotherapy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Microneedles for Transdermal Biosensing: Current Picture and Future Direction.

    Science.gov (United States)

    Ventrelli, Letizia; Marsilio Strambini, Lucanos; Barillaro, Giuseppe

    2015-12-09

    A novel trend is rapidly emerging in the use of microneedles, which are a miniaturized replica of hypodermic needles with length-scales of hundreds of micrometers, aimed at the transdermal biosensing of analytes of clinical interest, e.g., glucose, biomarkers, and others. Transdermal biosensing via microneedles offers remarkable opportunities for moving biosensing technologies and biochips from research laboratories to real-field applications, and envisages easy-to-use point-of-care microdevices with pain-free, minimally invasive, and minimal-training features that are very attractive for both developed and emerging countries. In addition to this, microneedles for transdermal biosensing offer a unique possibility for the development of biochips provided with end-effectors for their interaction with the biological system under investigation. Direct and efficient collection of the biological sample to be analyzed will then become feasible in situ at the same length-scale of the other biochip components by minimally trained personnel and in a minimally invasive fashion. This would eliminate the need for blood extraction using hypodermic needles and reduce, in turn, related problems, such as patient infections, sample contaminations, analysis artifacts, etc. The aim here is to provide a thorough and critical analysis of state-of-the-art developments in this novel research trend, and to bridge the gap between microneedles and biosensors. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Development and evaluation of transdermal organogels containing nicorandil.

    Science.gov (United States)

    Madan, J R; Sagar, Banode; Chellappan, Dinesh K; Dua, Kamal

    2013-01-01

    The objective of the study was to formulate a transdermal product containing Nicorandil as a model drug, because it has been first drug of choice to treat angina and hypertension. A further objective was to reduce its side effects. The transdermal product was prepared using various synthetic and natural gelling agents such as Carbopol 934p, Carbopol 974p, HPMC K15M and HPMC K100M. Various penetration enhancers were incorporated to enhance the diffusion across the rat skin. A further objective was to formulate organogels and minimize the concentration of penetration enhancer to 50% of the concentration used in gels and yet to achieve the maximum drug release. The prepared formulations were evaluated for their physical appearance, viscosity, spreadability, drug content and freeze thaw cycle. Based on in vitro studies across rat skin and human cadaver skin it was concluded that Nicrorandil transdermal organogel formulation using HPMC K100M with 2% w/w Transcutol-P shows increase in cumulative diffusion of Nicorandil amongst all other formulations.

  6. Microneedles array with biodegradable tips for transdermal drug delivery

    Science.gov (United States)

    Iliescu, Ciprian; Chen, Bangtao; Wei, Jiashen; Tay, Francis E. H.

    2008-12-01

    The paper presented an enhancement solution for transdermal drug delivery using microneedles array with biodegradable tips. The microneedles array was fabricated by using deep reactive ion etching (DRIE) and the biodegradable tips were made to be porous by electrochemical etching process. The porous silicon microneedle tips can greatly enhance the transdermal drug delivery in a minimum invasion, painless, and convenient manner, at the same time; they are breakable and biodegradable. Basically, the main problem of the silicon microneedles consists of broken microneedles tips during the insertion. The solution proposed is to fabricate the microneedle tip from a biodegradable material - porous silicon. The silicon microneedles are fabricated using DRIE notching effect of reflected charges on mask. The process overcomes the difficulty in the undercut control of the tips during the classical isotropic silicon etching process. When the silicon tips were formed, the porous tips were then generated using a classical electrochemical anodization process in MeCN/HF/H2O solution. The paper presents the experimental results of in vitro release of calcein and BSA with animal skins using a microneedle array with biodegradable tips. Compared to the transdermal drug delivery without any enhancer, the microneedle array had presented significant enhancement of drug release.

  7. Transdermal permeation of geniposide in the herbal complex liniment in vivo and in vitro.

    Science.gov (United States)

    Wang, Yugang; Li, Lele; Li, Huiying; Zhu, Zhaoyun; Hua, Lei; Lei, Fan; Kheir, Michael M; Du, Lijun

    2010-06-15

    Zhongtong Caji, a kind of liniment, is a traditional Chinese medicinal formula that is widely used for clinical treatment of inflammation and sprains. In this study, the principal effective compound of this formula, geniposide, was used as a criterion to represent the transdermal permeability of the whole formula. A passive diffusion of Zhongtong Caji through the stratum corneum was discovered by an in vitro experiment. The dosage-content relationship detected in subcutaneous tissue after in vivo drug administration was further evidence of its permeation. Blood analysis after different dosages showed that the geniposide could be absorbed and accumulated by subcutaneous tissue within 1h after drug administration, and it would be eliminated by blood circulation 1h after drug treatment. Copyright 2010 Elsevier B.V. All rights reserved.

  8. Acetylated cashew gum-based nanoparticles for transdermal delivery of diclofenac diethyl amine.

    Science.gov (United States)

    Dias, Sávia Francisca Lopes; Nogueira, Silvania Siqueira; de França Dourado, Flaviane; Guimarães, Maria Adelaide; de Oliveira Pitombeira, Nádia Aline; Gobbo, Graciely Gomides; Primo, Fernando Lucas; de Paula, Regina Célia Monteiro; Feitosa, Judith Pessoa Andrade; Tedesco, Antonio Claudio; Nunes, Lívio Cesar Cunha; Leite, José Roberto Souza Almeida; da Silva, Durcilene Alves

    2016-06-05

    Nanoprecipitation and dialysis methods were employed to obtain nanoparticles (NPs) of acetylated cashew gum (ACG). NPs synthesized by dialysis showed greater average size compared to those synthesized by nanoprecipitation, but they presented improved stability and yield. NPs were loaded with diclofenac diethylamine and the efficiency of the drug incorporation was over 60% for both methods, for an ACG:NP a weight ratio of 10:1. The cytotoxicity assay demonstrated that the NPs had no significant effect on the cell viability, verifying their biocompatibility. The release profile for the diclofenac diethylamine associated with the ACG-NPs showed a more controlled release compared to the free drug and a Fickian diffusion mechanism was observed. Transdermal permeation reached 90% penetration of the drug. Copyright © 2016. Published by Elsevier Ltd.

  9. Transdermic absorption of Melagenina II; Evaluacion de la absorcion transdermica de la Melagenina II

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez Gonzalez, I; Martinez Lopez, B; Ruiz Pena, M; Caso Pena, R [Centro de Isotopos, La Habana (Cuba)

    1998-12-31

    The transdermic absorption of Melagenina II (MII) was evaluated. MII was a labelled with {sup 125I} by the yodogen method and purified by column chromatography with Sephadex LH-20 in ethanol: water (7:3). In vitro absorption of ({sup 125I}) - MII thought human skin was carried out in Keshary-Chien modified diffusion cells. Tape stripping method was applied after 24 hours to evaluate the accumulated activity in dermis and epidermis. In vivo assays were performed in Sprague Dawley rats to analyze absorption of MII until 24 hours after a single application and for five days a low penetrability of the drug while in vivo there were not found blood levels significantly greater than zero , nevertheless and important amount of radioactivity was found in feces and urine. The activity was concentrated mainly in the application site in both models

  10. Future of the transdermal drug delivery market--have we barely touched the surface?

    Science.gov (United States)

    Watkinson, Adam C; Kearney, Mary-Carmel; Quinn, Helen L; Courtenay, Aaron J; Donnelly, Ryan F

    2016-01-01

    Transdermal drug delivery is the movement of drugs across the skin for absorption into the systemic circulation. Transfer of the drug can occur via passive or active means; passive transdermal products do not disrupt the stratum corneum to facilitate delivery whereas active technologies do. Due to the very specific physicochemical properties necessary for successful passive transdermal drug delivery, this sector of the pharmaceutical industry is relatively small. There are many well-documented benefits of this delivery route however, and as a result there is great interest in increasing the number of therapeutic substances that can be delivered transdermally. This review discusses the various transdermal products that are currently/have been marketed, and the paths that led to their success, or lack of. Both passive and active transdermal technologies are considered with the advantages and limitations of each highlighted. In addition to marketed products, technologies that are in the investigative stages by various pharmaceutical companies are reviewed. Passive transdermal drug delivery has made limited progress in recent years, however with the ongoing intense research into active technologies, there is great potential for growth within the transdermal delivery market. A number of active technologies have already been translated into marketed products, with other platforms including microneedles, rapidly progressing towards commercialisation.

  11. Transdermal administration of radiolabelled [14C]rotigotine by a patch formulation: A mass balance trial

    NARCIS (Netherlands)

    Cawello, W.; Wolff, H.M.; Meuling, W.J.A.; Horstmann, R.; Braun, M.

    2007-01-01

    Background and objective: The dopamine agonist rotigotine has been formulated in a silicone-based transdermal system for once-daily administration. The objective of the present study was to characterise the mass balance of rotigotine in humans after administration of a single transdermal patch

  12. Experiences using DAKOTA stochastic expansion methods in computational simulations.

    Energy Technology Data Exchange (ETDEWEB)

    Templeton, Jeremy Alan; Ruthruff, Joseph R.

    2012-01-01

    Uncertainty quantification (UQ) methods bring rigorous statistical connections to the analysis of computational and experiment data, and provide a basis for probabilistically assessing margins associated with safety and reliability. The DAKOTA toolkit developed at Sandia National Laboratories implements a number of UQ methods, which are being increasingly adopted by modeling and simulation teams to facilitate these analyses. This report disseminates results as to the performance of DAKOTA's stochastic expansion methods for UQ on a representative application. Our results provide a number of insights that may be of interest to future users of these methods, including the behavior of the methods in estimating responses at varying probability levels, and the expansion levels for the methodologies that may be needed to achieve convergence.

  13. Preparation and evaluation of microemulsion-based transdermal delivery of total flavone of rhizoma arisaematis

    Directory of Open Access Journals (Sweden)

    Shen LN

    2014-07-01

    Full Text Available Li-Na Shen,1 Yong-Tai Zhang,1 Qin Wang,2 Ling Xu,2 Nian-Ping Feng11Department of Pharmaceutical Sciences, 2Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaAbstract: The aims of the present study were to investigate the skin permeation and cellular uptake of a microemulsion (ME containing total flavone of rhizoma arisaematis (TFRA, and to evaluate its effects on skin structure. Pseudo-ternary phase diagrams were constructed to evaluate ME regions with various surfactants and cosurfactants. Eight formulations of ­oil-in-water MEs were selected as vehicles, and in vitro skin-permeation experiments were performed to optimize the ME formulation and to evaluate its permeability, in comparison to that of an aqueous suspension. Laser scanning confocal microscopy and fluorescent-activated cell sorting were used to explore the cellular uptake of rhodamine 110-labeled ME in human epidermal keratinocytes (HaCaT and human embryonic skin fibroblasts (CCC-ESF-1. The structure of stratum corneum treated with ME was observed using a scanning electron microscope. Furthermore, skin irritation was tested to evaluate the safety of ME. ME formulated with 4% ethyl oleate (weight/weight, 18% Cremophor EL® (weight/weight, and 18% Transcutol® P, with 1% Azone to enhance permeation, showed good skin permeability. ME-associated transdermal fluxes of schaftoside and isoschaftoside, two major effective constituents of TFRA, were 3.72-fold and 5.92-fold higher, respectively, than those achieved using aqueous suspensions. In contrast, in vitro studies revealed that uptake by HaCaT and CCC-ESF-1 cells was lower with ME than with an aqueous suspension. Stratum corneum loosening and shedding was observed in nude mouse skin treated with ME, although ME produced no observable skin irritation in rabbits. These findings indicated that ME enhanced transdermal TFRA delivery effectively and showed

  14. Electroporation-delivered transdermal neostigmine in rats: equivalent action to intravenous administration

    Directory of Open Access Journals (Sweden)

    Berkó S

    2016-05-01

    Full Text Available Szilvia Berkó,1,* Kálmán F Szűcs,2,* Boglárka Balázs,1,3 Erzsébet Csányi,1 Gábor Varju,4 Anita Sztojkov-Ivanov,2 Mária Budai-Szűcs,1 Judit Bóta,2 Róbert Gáspár2 1Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Szeged, Szeged, Hungary; 2Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary; 3Gedeon Richter Plc., Budapest, 4Dr Derm Clinic of Anti-Aging Dermatology, Aesthetic Laser and Plastic Surgery, Budapest, Hungary *These authors contributed equally to this work Purpose: Transdermal electroporation has become one of the most promising noninvasive methods for drug administration, with greatly increased transport of macromolecules through the skin. The cecal-contracting effects of repeated transdermal electroporation delivery and intravenous administration of neostigmine were compared in anesthetized rats. Methods: The cecal contractions were detected with implantable strain gauge sensors, and the plasma levels of neostigmine were followed by high-performance liquid chromatography. Results: Both intravenously and EP-administered neostigmine (0.2–66.7 µg/kg increased the cecal contractions in a dose-dependent manner. For both the low doses and the highest dose, the neostigmine plasma concentrations were the same after the two modes of administration, while an insignificantly higher level was observed at a dose of 20 µg/kg after intravenous administration as compared with the electroporation route. The contractile responses did not differ significantly after the two administration routes. Conclusion: The results suggest that electroporation-delivered neostigmine elicits action equivalent to that observed after intravenous administration as concerning both time and intensity. Electroporation permits the delivery of even lower doses of water-soluble compounds through the skin, which is very promising for clinical practice. Keywords: transdermal

  15. In vitro transdermal delivery of propranolol hydrochloride through rat skin from various niosomal formulations

    Directory of Open Access Journals (Sweden)

    Eskandar Moghimipour

    2013-09-01

    Full Text Available   Objective(s: The purpose of the present study was to prepare and to evaluate a novel niosome as transdermal drug delivery system for propranolol hydrochloride and to compare the in vitro efficiency of niosome by either thin film hydration or hand shaking method.   Materials and Methods: Niosomes were prepared by Thin Film Hydration (TFH or Hand Shaking (HS method. Propranolol niosomes were prepared using different surfactants (span20, 80 ratios and a constant cholesterol concentration. In vitro characterization of niosomes included microscopical observation, size distribution, laser light scattering evaluation, stability of propranolol niosomes and permeability of formulations in phosphate buffer (pH=7 through rat abdominal skin. Results: The percentage of entrapment efficiency (%EE increased with increase in surfactant concentration in all formulations. Among them, F3 formulation (containing span80:cholesterol ratio of 3:1 showed the highest entrapment efficiency (86.74±2.01%, Jss (6.33μg/cm2.h and permeability coefficient ( . By increasing the percentage of entrapment efficiency (resulting in increase in surfactant concentration, the drug released time is not prolonged. Among all the formulations, F4 needed more time for maximum drug release. Among these formulations, F4 was also found to have the maximum vesicle size as compared to other formulations. It was observed that niosomal suspension prepared from span 80 was more stable than span 20. Conclusion: This study demonstrates that niosomal formulations may offer a promise transdermal delivery of propranolol which improves drug efficiency and can be used for controlled delivery of propranolol

  16. Communications in Financial Markets: a Strategy method Experiment

    OpenAIRE

    Brice Corgnet; Angela Sutan

    2007-01-01

    The main objective of this paper is to analyze the impact of uninformative communications on asset prices. An experimental approach allows us to control for the release of a priori uninformative messages. We introduce the release of messages in standard experimental asset markets with bubbles using a strategy method experiment. We conjecture that messages that are a priori uninformative can significantly impact the level of asset prices. Such communications may be used by boundedly rational s...

  17. The Role of Qualitative Research Methods in Discrete Choice Experiments

    Science.gov (United States)

    Vass, Caroline; Rigby, Dan; Payne, Katherine

    2017-01-01

    Background. The use of qualitative research (QR) methods is recommended as good practice in discrete choice experiments (DCEs). This study investigated the use and reporting of QR to inform the design and/or interpretation of healthcare-related DCEs and explored the perceived usefulness of such methods. Methods. DCEs were identified from a systematic search of the MEDLINE database. Studies were classified by the quantity of QR reported (none, basic, or extensive). Authors (n = 91) of papers reporting the use of QR were invited to complete an online survey eliciting their views about using the methods. Results. A total of 254 healthcare DCEs were included in the review; of these, 111 (44%) did not report using any qualitative methods; 114 (45%) reported “basic” information; and 29 (11%) reported or cited “extensive” use of qualitative methods. Studies reporting the use of qualitative methods used them to select attributes and/or levels (n = 95; 66%) and/or pilot the DCE survey (n = 26; 18%). Popular qualitative methods included focus groups (n = 63; 44%) and interviews (n = 109; 76%). Forty-four studies (31%) reported the analytical approach, with content (n = 10; 7%) and framework analysis (n = 5; 4%) most commonly reported. The survey identified that all responding authors (n = 50; 100%) found that qualitative methods added value to their DCE study, but many (n = 22; 44%) reported that journals were uninterested in the reporting of QR results. Conclusions. Despite recommendations that QR methods be used alongside DCEs, the use of QR methods is not consistently reported. The lack of reporting risks the inference that QR methods are of little use in DCE research, contradicting practitioners’ assessments. Explicit guidelines would enable more clarity and consistency in reporting, and journals should facilitate such reporting via online supplementary materials. PMID:28061040

  18. Mass Spectrometry Coupled Experiments and Protein Structure Modeling Methods

    Directory of Open Access Journals (Sweden)

    Lee Sael

    2013-10-01

    Full Text Available With the accumulation of next generation sequencing data, there is increasing interest in the study of intra-species difference in molecular biology, especially in relation to disease analysis. Furthermore, the dynamics of the protein is being identified as a critical factor in its function. Although accuracy of protein structure prediction methods is high, provided there are structural templates, most methods are still insensitive to amino-acid differences at critical points that may change the overall structure. Also, predicted structures are inherently static and do not provide information about structural change over time. It is challenging to address the sensitivity and the dynamics by computational structure predictions alone. However, with the fast development of diverse mass spectrometry coupled experiments, low-resolution but fast and sensitive structural information can be obtained. This information can then be integrated into the structure prediction process to further improve the sensitivity and address the dynamics of the protein structures. For this purpose, this article focuses on reviewing two aspects: the types of mass spectrometry coupled experiments and structural data that are obtainable through those experiments; and the structure prediction methods that can utilize these data as constraints. Also, short review of current efforts in integrating experimental data in the structural modeling is provided.

  19. Nanocrystal cellulose as drug excipient in transdermal patch for wound healing: an overview

    Science.gov (United States)

    Zuki, S. A. Mohd; Rahman, N. Abd; Abu Bakar, N. F.

    2018-03-01

    Wound must be carefully treated to avoid serious infection that needs costly treatment. Method to enhance the recovery of the wound is crucial to have effective wound treatment. One of the technologies in wound treatment is transdermal patch that has the benefits of being non-invasive, easy to handle and permits constant drug dosage. In order to obtain a good controlled drug release, drug excipient needs to be investigated. Recently, natural Nanocrystal Cellulose (NCC) which can be synthesized from animal, algae, microorganism or plant has been actively used in drug delivery system as excipient. The application of NCC is advantageous due to its large surface area, biodegradable, non-toxic and abundance source.

  20. Effect of Electron-Beam Irradiation on Bacterial Cellulose Membranes Used as Transdermal Drug Delivery Systems

    International Nuclear Information System (INIS)

    Stoica-Guzun, A.

    2006-01-01

    Multiple methods are used to modify material surfaces. Radiation is an effective tool for polymer surfaces modification in order to obtain transdermal systems with different controlled release properties. Bacterial cellulose is a promising biomaterial synthesized by Acetobacter xylinum. It has a distinctive ultrafine reticulated structure that may become a perfect matrix as an optimal wound healing environment. In this work, high energy irradiation (γ rays from 137 C s) was applied to modify bacterial cellulose membranes. The effect of varying irradiation doses on membranes permeability was studied. Tetracycline was involved in the study of diffusivity as model drug. Release and permeation of drug from irradiated and non-irradiated membranes were done using a diffusion cell. The membrane permeability was determined using a psudo-steady state analysis based on Fick's law

  1. The Role of Qualitative Research Methods in Discrete Choice Experiments.

    Science.gov (United States)

    Vass, Caroline; Rigby, Dan; Payne, Katherine

    2017-04-01

    The use of qualitative research (QR) methods is recommended as good practice in discrete choice experiments (DCEs). This study investigated the use and reporting of QR to inform the design and/or interpretation of healthcare-related DCEs and explored the perceived usefulness of such methods. DCEs were identified from a systematic search of the MEDLINE database. Studies were classified by the quantity of QR reported (none, basic, or extensive). Authors ( n = 91) of papers reporting the use of QR were invited to complete an online survey eliciting their views about using the methods. A total of 254 healthcare DCEs were included in the review; of these, 111 (44%) did not report using any qualitative methods; 114 (45%) reported "basic" information; and 29 (11%) reported or cited "extensive" use of qualitative methods. Studies reporting the use of qualitative methods used them to select attributes and/or levels ( n = 95; 66%) and/or pilot the DCE survey ( n = 26; 18%). Popular qualitative methods included focus groups ( n = 63; 44%) and interviews ( n = 109; 76%). Forty-four studies (31%) reported the analytical approach, with content ( n = 10; 7%) and framework analysis ( n = 5; 4%) most commonly reported. The survey identified that all responding authors ( n = 50; 100%) found that qualitative methods added value to their DCE study, but many ( n = 22; 44%) reported that journals were uninterested in the reporting of QR results. Despite recommendations that QR methods be used alongside DCEs, the use of QR methods is not consistently reported. The lack of reporting risks the inference that QR methods are of little use in DCE research, contradicting practitioners' assessments. Explicit guidelines would enable more clarity and consistency in reporting, and journals should facilitate such reporting via online supplementary materials.

  2. Dynamic characterization of hydrophobic and hydrophilic solutes in oleic-acid enhanced transdermal delivery using two-photon fluorescence microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Tseng, Te-Yu; Yang, Chiu-Sheng; Chen, Yang-Fang [Department of Physics, National Taiwan University, Taipei, Taiwan (China); Tsai, Tsung-Hua [Department of Dermatology, Far Eastern Memorial Hospital, New Taipei City, Taiwan (China); Dong, Chen-Yuan, E-mail: cydong@phys.ntu.edu.tw [Department of Physics, National Taiwan University, Taipei, Taiwan (China); Center for Quantum Science and Engineering, National Taiwan University, Taipei, Taiwan (China); Center for Optoelectronic Biomedicine, National Taiwan University, Taipei, Taiwan (China)

    2014-10-20

    In this letter, we propose an efficient methodology of investigating dynamic properties of sulforhodamine B and rhodamine B hexyl ester molecules transporting across ex-vivo human stratum corneum with and without oleic acid enhancement. Three-dimensional, time-lapse fluorescence images of the stratum corneum can be obtained using two-photon fluorescence microscopy. Furthermore, temporal quantifications of transport enhancements in diffusion parameters can be achieved with the use of Fick's second law. Dynamic characterization of solutes transporting across the stratum corneum is an effective method for understanding transient phenomena in transdermal delivery of probe molecules, leading to improved delivery strategies of molecular species for therapeutic purposes.

  3. Applicability and safety of dual-frequency ultrasonic treatment for the transdermal delivery of drugs

    Science.gov (United States)

    Schoellhammer, Carl M.; Srinivasan, Sharanya; Barman, Ross; Mo, Stacy H.; Polat, Baris E.; Langer, Robert; Blankschtein, Daniel

    2016-01-01

    Low-frequency ultrasound presents an attractive method for transdermal drug delivery. The controlled, yet nonspecific nature of enhancement broadens the range of therapeutics that can be delivered, while minimizing necessary reformulation efforts for differing compounds. Long and inconsistent treatment times, however, have partially limited the attractiveness of this method. Building on recent advances made in this area, the simultaneous use of low- and high-frequency ultrasound is explored in a physiologically relevant experimental setup to enable the translation of this treatment to testing in vivo. Dual-frequency ultrasound, utilizing 20 kHz and 1 MHz wavelengths simultaneously, was found to significantly enhance the size of localized transport regions (LTRs) in both in vitro and in vivo models while decreasing the necessary treatment time compared to 20 kHz alone. Additionally, LTRs generated by treatment with 20 kHz + 1 MHz were found to be more permeable than those generated with 20 kHz alone. This was further corroborated with pore-size estimates utilizing hindered-transport theory, in which the pores in skin treated with 20 kHz + 1 MHz were calculated to be significantly larger than the pores in skin treated with 20 kHz alone. This demonstrates for the first time that LTRs generated with 20 kHz + 1 MHz are also more permeable than those generated with 20 kHz alone, which could broaden the range of therapeutics and doses administered transdermally. With regard to safety, treatment with 20 kHz + 1 MHz both in vitro and in vivo appeared to result in no greater skin disruption than that observed in skin treated with 20 kHz alone, an FDA-approved modality. This study demonstrates that dual-frequency ultrasound is more efficient and effective than single-frequency ultrasound and is well-tolerated in vivo. PMID:25662228

  4. FATAL, General Experiment Fitting Program by Nonlinear Regression Method

    International Nuclear Information System (INIS)

    Salmon, L.; Budd, T.; Marshall, M.

    1982-01-01

    1 - Description of problem or function: A generalized fitting program with a free-format keyword interface to the user. It permits experimental data to be fitted by non-linear regression methods to any function describable by the user. The user requires the minimum of computer experience but needs to provide a subroutine to define his function. Some statistical output is included as well as 'best' estimates of the function's parameters. 2 - Method of solution: The regression method used is based on a minimization technique devised by Powell (Harwell Subroutine Library VA05A, 1972) which does not require the use of analytical derivatives. The method employs a quasi-Newton procedure balanced with a steepest descent correction. Experience shows this to be efficient for a very wide range of application. 3 - Restrictions on the complexity of the problem: The current version of the program permits functions to be defined with up to 20 parameters. The function may be fitted to a maximum of 400 points, preferably with estimated values of weight given

  5. GPS surveying method applied to terminal area navigation flight experiments

    Energy Technology Data Exchange (ETDEWEB)

    Murata, M; Shingu, H; Satsushima, K; Tsuji, T; Ishikawa, K; Miyazawa, Y; Uchida, T [National Aerospace Laboratory, Tokyo (Japan)

    1993-03-01

    With an objective of evaluating accuracy of new landing and navigation systems such as microwave landing guidance system and global positioning satellite (GPS) system, flight experiments are being carried out using experimental aircraft. This aircraft mounts a GPS and evaluates its accuracy by comparing the standard orbits spotted by a Kalman filter from the laser tracing data on the aircraft with the navigation results. The GPS outputs position and speed information from an earth-centered-earth-fixed system called the World Geodetic System, 1984 (WGS84). However, in order to compare the navigation results with output from a reference orbit sensor or other navigation sensor, it is necessary to structure a high-precision reference coordinates system based on the WGS84. A method that applies the GPS phase interference measurement for this problem was proposed, and used actually in analyzing a flight experiment data. As referred to a case of the method having been applied to evaluating an independent navigation accuracy, the method was verified sufficiently effective and reliable not only in navigation method analysis, but also in the aspect of navigational operations. 12 refs., 10 figs., 5 tabs.

  6. Validation method training: nurses' experiences and ratings of work climate.

    Science.gov (United States)

    Söderlund, Mona; Norberg, Astrid; Hansebo, Görel

    2014-03-01

    Training nursing staff in communication skills can impact on the quality of care for residents with dementia and contributes to nurses' job satisfaction. Changing attitudes and practices takes time and energy and can affect the entire nursing staff, not just the nurses directly involved in a training programme. Therefore, it seems important to study nurses' experiences of a training programme and any influence of the programme on work climate among the entire nursing staff. To explore nurses' experiences of a 1-year validation method training programme conducted in a nursing home for residents with dementia and to describe ratings of work climate before and after the programme. A mixed-methods approach. Twelve nurses participated in the training and were interviewed afterwards. These individual interviews were tape-recorded and transcribed, then analysed using qualitative content analysis. The Creative Climate Questionnaire was administered before (n = 53) and after (n = 56) the programme to the entire nursing staff in the participating nursing home wards and analysed with descriptive statistics. Analysis of the interviews resulted in four categories: being under extra strain, sharing experiences, improving confidence in care situations and feeling uncertain about continuing the validation method. The results of the questionnaire on work climate showed higher mean values in the assessment after the programme had ended. The training strengthened the participating nurses in caring for residents with dementia, but posed an extra strain on them. These nurses also described an extra strain on the entire nursing staff that was not reflected in the results from the questionnaire. The work climate at the nursing home wards might have made it easier to conduct this extensive training programme. Training in the validation method could develop nurses' communication skills and improve their handling of complex care situations. © 2013 Blackwell Publishing Ltd.

  7. Inoculation method could impact the outcome of microbiological experiments

    DEFF Research Database (Denmark)

    Kragh, Kasper Nørskov; Alhede, Maria; Rybtke, Morten

    2018-01-01

    For the last 150 years, bacteria have primarily been investigated in liquid bacth cultures (LBC). Contrary to most expectations, these cultures are not a homogeneous mixture of single-celled bacteria as free-floating bacterial aggregates eventually develop in most LBC. These aggregates share...... coli and Staphylococcus aureus also produce aggregates in LBC. Our results stress the importance of inoculation consistency throughout experiments and the substantial impact aggregate development in LBC has on the output of microbiological experiments.IMPORTANCE Liquid pure cultures are fundamental...... to the field of microbiological research. These cultures are normally thought of as a homogeneous mix of single cell bacteria. The present study shows how this is not always true. Bacteria may aggregate in these liquid cultures. The aggregation can be induced by the method chosen for inoculation. The presence...

  8. An experiment teaching method based on the Optisystem simulation platform

    Science.gov (United States)

    Zhu, Jihua; Xiao, Xuanlu; Luo, Yuan

    2017-08-01

    The experiment teaching of optical communication system is difficult to achieve because of expensive equipment. The Optisystem is optical communication system design software, being able to provide such a simulation platform. According to the characteristic of the OptiSystem, an approach of experiment teaching is put forward in this paper. It includes three gradual levels, the basics, the deeper looks and the practices. Firstly, the basics introduce a brief overview of the technology, then the deeper looks include demoes and example analyses, lastly the practices are going on through the team seminars and comments. A variety of teaching forms are implemented in class. The fact proves that this method can not only make up the laboratory but also motivate the students' learning interest and improve their practical abilities, cooperation abilities and creative spirits. On the whole, it greatly raises the teaching effect.

  9. Application of heterogeneous method for the interpretation of exponential experiments

    International Nuclear Information System (INIS)

    Birkhoff, G.; Bondar, L.

    1977-01-01

    The present paper gives a brief review of a work which was executed mainly during 1967 and 1968 in the field of the application of heterogeneous methods for the interpretation of exponential experiments with ORGEL type lattices (lattices of natural uranium cluster elements with organic coolants moderated by heavy water). In the frame of this work a heterogeneous computer program, in (r,γ) geometry was written which is based on the NORDHEIM method using a uniform moderator, three energy groups and monopol and dipol sources. This code is especially adapted for regular square lattices in a cylindrical tank. Full use of lattice symmetry was made for reducing the numerical job of the theory. A further reduction was obtained by introducing a group averaged extrapolation distance at the external boundary. Channel parameters were evaluated by the PINOCCHIO code. Comparisons of calculated and measured thermal neutron flux showed good agreement. Equivalence of heterogeneous and homogeneous theory was found in cases of lattices comprising a minimum of 32, 24 and 16 fuel elements for respectively under-, well-, and over-moderated lattices. Heterogeneous calculations of high leakage lattices suffered the lack of good methods for the computation of axial and radial streaming parameters. Interpretation of buckling measurements in the subcritical facility EXPO requires already more accurate evaluation of the streaming effects than we made. The potential of heterogeneous theory in the field of exponential experiments is thought to be limited by the precision by which the streaming parameters can be calculated

  10. Chemistry, manufacturing and controls in passive transdermal drug delivery systems.

    Science.gov (United States)

    Goswami, Tarun; Audett, Jay

    2015-01-01

    Transdermal drug delivery systems (TDDS) are used for the delivery of the drugs through the skin into the systemic circulation by applying them to the intact skin. The development of TDDS is a complex and multidisciplinary affair which involves identification of suitable drug, excipients and various other components. There have been numerous problems reported with respect to TDDS quality and performance. These problems can be reduced by appropriately addressing chemistry, manufacturing and controls requirements, which would thereby result in development of robust TDDS product and processes. This article provides recommendations on the chemistry, manufacturing and controls focusing on the unique technical aspects of TDDS.

  11. Treatment of Severe Cancer Pain by Transdermal Fentanyl

    Directory of Open Access Journals (Sweden)

    Dženita Ljuca

    2010-05-01

    Full Text Available The goal of research was to determine the frequency, intensity, time of occurrence, duration and causes of breakthrough pain (BTP in patients whose carcinoma pain was treated by transdermal fentanyl. (TDF. A prospective study was conducted in a hospice for recumbent patients of the Centre for Palliative Care (hospice University Clinical Centre Tuzla from October 2009 to December 2010. 33 patients in terminal stage of carcinoma, who had been treated by transdermal fentanyl due to their excruciating pain (7-10 mark on numerica! scale with initial dosage of 25 μg as a strong opiate analgesic, were monitored within the time period of 10 days. In the statistics we used the even T - test, the Wilcox test and Mann -Whitney test. The difference was seen to be significant at p < 0,05. Treatment by transdermal fentanyl significantly reduces the intensity of strong carcinoma pain (p < 0.0001, with a frequent requirement for dose increase with bone metastasis. The intensity of BTP is higher compared to the pain experienced upon reception. The frequency and intensity of BTP are significantly reduced already in the second day of treatment by transdermal fentanyl (p = 0,0024. The BTP is most intense in patients with neck and head tumours (9,26 ± 0,66, and most frequent with abdomen and pelvic tumour. The biggest number of BTP (68.3 % occurs within first three days of treatment. BTP most frequently occurs in the evening or at night (between 18:00 and 06:00 h in 62,2 % of the cases, with the duration of usually less than 15 minutes (65,2% of the cases. In 61,6 % cases the occurrence of BTP is related to physical activities or psychosocial incidents, while the cause is undetermined in 38,4 % of examinees.BTP is most frequent within first three days of treatment by TDF. Using the optimal dosage a good control of carcinoma pain is enabled, regardless of the occurrence of bone metastasis, while it also helps reduce the frequency and intensity of BTP.

  12. Transdermal hormone therapy in postmenopausal women: A review of metabolic effects and drug delivery technologies

    Directory of Open Access Journals (Sweden)

    Nathan W Kopper

    2008-10-01

    Full Text Available Nathan W Kopper, Jennifer Gudeman, Daniel J ThompsonKV Pharmaceutical, St. Louis, MO, USAAbstract: Vasomotor symptoms (VMS associated with menopause can cause significant discomfort and decrease the quality of life for women in the peri-menopausal and post-menopausal stages of life. Hormone therapy (HT is the mainstay of treatment for menopausal symptoms and is currently the only therapy proven effective for VMS. Numerous HT options are available to treat VMS, including estrogen-only and estrogen-progestogen combination products to meet the needs of both hysterectomized and nonhysterectomized women. In addition to selecting an appropriate estrogen or estrogen-progestogen combination, consideration should be given to the route of administration to best suit the needs of the patient. Delivery systems for hormone therapy include oral tablets, transdermal patches, transdermal topical (nonpatch products, and intravaginal preparations. Oral is currently the most commonly utilized route of administration in the United States. However, evidence suggests that oral delivery may lead to some undesirable physiologic effects caused by significant gut and hepatic metabolism. Transdermal drug delivery may mitigate some of these effects by avoiding gut and hepatic first-pass metabolism. Advantages of transdermal delivery include the ability to administer unmetabolized estradiol directly to the blood stream, administration of lower doses compared to oral products, and minimal stimulation of hepatic protein production. Several estradiol transdermal delivery technologies are available, including various types of patches, topical gels, and a transdermal spray.Keywords: estradiol, hormone therapy, menopause, transdermal drug delivery, vasomotor symptoms

  13. Pharmacokinetic characteristics of formulated alendronate transdermal delivery systems in rats and humans.

    Science.gov (United States)

    Choi, Ahyoung; Gang, Hyesil; Whang, Jiae; Gwak, Hyesun

    2010-05-01

    The objective of this study was to examine the absorption of alendronate from formulated transdermal delivery systems in rats and humans. When alendronate was applied to rats by transdermal delivery systems (7.2 mg) and oral administration (30 mg/kg), a statistically significant difference was found in the amount remaining to be excreted at time t (Ae(t)) and the amount remaining to be excreted at time 0 (Ae(infinity)) (p transdermal delivery systems. There was a linear relationship (r(2) = 0.9854) between the drug loading dose and Ae(infinity). The Ae(infinity) values from the transdermal delivery system containing 6% caprylic acid (53.8 mg as alendronate) and an oral product (Fosamax), 70 mg as alendronate) in humans were 127.0 +/- 34.2 microg and 237.2 +/- 56.3 microg, respectively. The dose-adjusted relative Ae(infinity) ratio of the transdermal delivery system to oral product was calculated to be 69.7%. The long half-life of alendronate in the transdermal delivery system (50.6 +/- 6.4 h), compared to that of the oral product (3.5 +/- 1.1 h) could allow less-frequent dosing. In conclusion, this study showed that a transdermal delivery system containing 6% caprylic acid in PG could be a favorable alternative for alendronate administration.

  14. Development of Microemulsion Based Nabumetone Transdermal Delivery For Treatment of Arthritis.

    Science.gov (United States)

    Jagdale, Swati; Deore, Gokul; Chabukswar, Anuruddha

    2018-02-26

    Background Nabumetone is biopharmaceutics classification system (BCS) class II drug, widely used in the treatment of osteoarthritis and rheumatoid arthritis. The most frequently reported adverse reactions for the drug involve disturbance in gastrointestinal tract , diarrhea, dyspepsia and abdominal pain. Microemulgel has advantages of microemulsion for improving solubility for hydrophobic drug. Patent literature had shown that the work for drug has been carried on spray chilling, enteric coated tablet, and topical formulation which gave idea for present research work for development of transdermal delivery. Objective Objective of the present research work was to optimize transdermal microemulgel delivery for Nabumetone for treatment of arthritis. Method Oil, surfactant and co-surfactant were selected based on solubility study for the drug. Gelling agents used were Carbopol 934 and HPMC K100M. Optimization was carried out using 32 factorial design. Characterization and evaluation were carried out for microemulsion and microemulsion based gel. Results Field emission-scanning electron microscopy (FE-SEM) study of the microemulsion revealed globules of 50-200 nm size . Zeta potential -9.50 mV indicated good stability of microemulsion. Globule size measured by dynamic light scattering (zetasizer) was 160 nm. Design expert gave optimized batch as F7 which contain 0.2% w/w drug, 4.3% w/w liquid paraffin, 0.71% w/w tween 80, 0.35% w/w propylene glycol, 0.124% w/w Carbopol 934, 0.187% w/w HPMC K100M and 11.68% w/w water. In-vitro diffusion study for F7 batch showed 99.16±2.10 % drug release through egg membrane and 99.15±2.73% drug release in ex-vivo study. Conclusion Nabumetone microemulgel exhibiting good in-vitro and ex-vivo controlled drug release was optimized. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. The application of anethole, menthone, and eugenol in transdermal penetration of valsartan: Enhancement and mechanistic investigation.

    Science.gov (United States)

    Ahad, Abdul; Aqil, Mohd; Ali, Asgar

    2016-01-01

    The main barrier for transdermal delivery is the obstacle property of the stratum corneum. Many types of chemical penetration enhancers have been used to breach the skin barrier; among the penetration enhancers, terpenes are found as the most highly advanced, safe, and proven category. In the present investigation, the terpenes anethole, menthone, and eugenol were used to enhance the permeation of valsartan through rat skin in vitro and their enhancement mechanism was investigated. Skin permeation studies of valsartan across rat skin in the absence and the presence of terpenes at 1% w/v, 3% w/v, and 5% w/v in vehicle were carried out using the transdermal diffusion cell sampling system across rat skin and samples were withdrawn from the receptor compartment at 1, 2, 3, 4, 6, 8, 10, 12, and 24 h and analysed for drug content by the HPLC method. The mechanism of skin permeation enhancement of valsartan by terpenes treatment was evaluated by Fourier transform infrared spectroscopy (FTIR) analysis and differential scanning calorimetry (DSC). All the investigated terpenes provided a significant (p valsartan flux at a concentration of 1%, and less so at 3% and 5%. The effectiveness of terpenes at 1% concentration was in the following order: anethole > menthone > eugenol with 4.4-, 4.0-, and 3.0-fold enhancement ratio over control, respectively. DSC study showed that the treatment of stratum corneum with anethole shifted endotherm down to lower melting point while FTIR studies revealed that anethole produced maximum decrease in peak height and area than other two terpenes. The investigated terpenes can be successfully used as potential enhancers for the enhancement of skin permeation of lipophilic drug.

  16. Transdermal delivery of gentamicin using dissolving microneedle arrays for potential treatment of neonatal sepsis.

    Science.gov (United States)

    González-Vázquez, Patricia; Larrañeta, Eneko; McCrudden, Maelíosa T C; Jarrahian, Courtney; Rein-Weston, Annie; Quintanar-Solares, Manjari; Zehrung, Darin; McCarthy, Helen; Courtenay, Aaron J; Donnelly, Ryan F

    2017-11-10

    Neonatal infections are a leading cause of childhood mortality in low-resource settings. World Health Organization guidelines for outpatient treatment of possible serious bacterial infection (PSBI) in neonates and young infants when referral for hospital treatment is not feasible include intramuscular gentamicin (GEN) and oral amoxicillin. GEN is supplied as an aqueous solution of gentamicin sulphate in vials or ampoules and requires health care workers to be trained in dose calculation or selection of an appropriate dose based on the patient's weight band and to have access to safe injection supplies and appropriate sharps disposal. A simplified formulation, packaging, and delivery method to treat PSBI in low-resource settings could decrease user error and expand access to lifesaving outpatient antibiotic treatment for infants with severe infection during the neonatal period. We developed dissolving polymeric microneedles (MN) arrays to deliver GEN transdermally. MN arrays were produced from aqueous blends containing 30% (w/w) of GEN and two polymers approved by the US Food and Drug Administration: sodium hyaluronate and poly(vinylpyrrolidone). The arrays (19×19 needles and 500μm height) were mechanically strong and were able to penetrate a skin simulant to a depth of 378μm. The MN arrays were tested in vitro using a Franz Cell setup delivering approximately 4.45mg of GEN over 6h. Finally, three different doses (low, medium, and high) of GEN delivered by MN arrays were tested in an animal model. Maximum plasma levels of GEN were dose-dependent and ranged between 2 and 5μg/mL. The time required to reach these levels post-MN array application ranged between 1 and 6h. This work demonstrated the potential of dissolving MN arrays to deliver GEN transdermally at therapeutic levels in vivo. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Experiments study on attitude coupling control method for flexible spacecraft

    Science.gov (United States)

    Wang, Jie; Li, Dongxu

    2018-06-01

    High pointing accuracy and stabilization are significant for spacecrafts to carry out Earth observing, laser communication and space exploration missions. However, when a spacecraft undergoes large angle maneuver, the excited elastic oscillation of flexible appendages, for instance, solar wing and onboard antenna, would downgrade the performance of the spacecraft platform. This paper proposes a coupling control method, which synthesizes the adaptive sliding mode controller and the positive position feedback (PPF) controller, to control the attitude and suppress the elastic vibration simultaneously. Because of its prominent performance for attitude tracking and stabilization, the proposed method is capable of slewing the flexible spacecraft with a large angle. Also, the method is robust to parametric uncertainties of the spacecraft model. Numerical simulations are carried out with a hub-plate system which undergoes a single-axis attitude maneuver. An attitude control testbed for the flexible spacecraft is established and experiments are conducted to validate the coupling control method. Both numerical and experimental results demonstrate that the method discussed above can effectively decrease the stabilization time and improve the attitude accuracy of the flexible spacecraft.

  18. Analysis advanced methods of data bases of industrial experience return

    International Nuclear Information System (INIS)

    Lannoy, A.; Procaccia, H.

    1994-05-01

    This is a presentation, through different conceptions of data bases on industrial experience return, of the principal methods for treatments and analyses of the collected data, going from the frequency statistic and factorial analysis, to the the Bayesian statistical decision theory, which is a real decision assistance tool for responsibles, conceivers and operators. Examples in various fields are given (OREDA: Offshore REliability DAta bank for marine drilling platforms, CEDB: Component Event Data Bank for european electric power industry, RDF 93: reliability of electronic components of ''France Telecom'', EVT: failure EVenTs data bank in the french nuclear power plants by ''EDF''). (A.B.). refs., figs., tabs

  19. Practical methods of target preparation for use in nuclear experiments

    International Nuclear Information System (INIS)

    Sugai, Isao.

    1976-01-01

    This is the fifth report on the practical methods of target preparation for use in nuclear experiments following the previous one (INS-J-152, 1975). Electro-deposition is a very powerful technique well suited to the preparation of self-supporting targets of Ni, Cr, Zn, Rh, Cd, Sb and Pb metals over a wide range of thickness from 1 to 20 mg/cm 2 . The uniformities of the thicknesses of Cr, Zn, Rh, Cd and Pb targets were measured with α- and β-ray thickness gauges. The impurities in Cr target were checked by the measurement of elastically scattered protons, and by a optical spectrometer. (auth.)

  20. A mechanics approach to the study of pressure sensitive adhesives and human skin for transdermal drug delivery applications

    Science.gov (United States)

    Taub, Marc Barry

    Transdermal drug delivery is an alternative approach to the systemic delivery of pharmaceuticals where drugs are administered through the skin and absorbed percutaneously. This method of delivery offers several advantages over more traditional routes; most notably, the avoidance of the fast-pass metabolism of the liver and gut, the ability to offer controlled release rates, and the possibility for novel devices. Pressure sensitive adhesives (PSAs) are used to bond transdermal drug delivery devices to the skin because of their good initial and long-term adhesion, clean removability, and skin and drug compatibility. However, an understanding of the mechanics of adhesion to the dermal layer, together with quantitative and reproducible test methods for measuring adhesion, have been lacking. This study utilizes a mechanics-based approach to quantify the interfacial adhesion of PSAs bonded to selected substrates, including human dermal tissue. The delamination of PSA layers is associated with cavitation in the PSA followed by the formation of an extensive cohesive zone behind the debond tip. A quantitative metrology was developed to assess the adhesion and delamination of PSAs, such that it could be possible to easily distinguish between the adhesive characteristics of different PSA compositions and to provide a quantitative basis from which the reliability of adhesive layers bonded to substrates could be studied. A mechanics-based model was also developed to predict debonding in terms of the relevant energy dissipation mechanisms active during this process. As failure of transdermal devices may occur cohesively within the PSA layer, adhesively at the interface between the PSA and the skin, or cohesively between the corneocytes that comprise the outermost layer of the skin, it was also necessary to explore the mechanical and fracture properties of human skin. The out-of-plane delamination of corneocytes was studied by determining the strain energy release rate during

  1. Evaluation of the effect of transdermal nitroglycerine patch on intrathecal dexmedetomidine as additive, on postoperative analgesia after abdominal hysterectomy

    Directory of Open Access Journals (Sweden)

    Rama Chatterji

    2017-01-01

    Full Text Available Aim: The aim of this study is to evaluate the effect of transdermal nitroglycerin on intrathecal dexmedetomidine as additive, on postoperative analgesia after abdominal hysterectomy. Materials and Methods: Totally 140 patients of the American Society of Anesthesiologists Grade I or II, posted for abdominal hysterectomy under spinal anesthesia, were randomized to four groups using computer-generated random number list. Group B received 3 ml of 0.5% hyperbaric bupivacaine with 0.5 ml normal saline and placebo patch, Group BN received 3 ml of 0.5% hyperbaric bupivacaine with 0.5 ml NS and transdermal nitroglycerin (t-NTG, Group BD received 3 ml of 0.5% hyperbaric bupivacaine with 5 mcg (0.5 ml dexmedetomidine and placebo patch and Group BDN received 3 ml of 0.5% hyperbaric bupivacaine with 5 μg (0.5 ml dexmedetomidine and t-NTG patch. Outcomes measured include the total duration of analgesia, onset, and duration of sensory and motor block and any adverse effects. Results: The total duration of analgesia was longest in Group BDN (349.9 ± 40.6 min. It was significantly longer than Group BD (252.3 ± 34.0 min and Group B and BN (130.5 ± 18.8, 138.3 ± 19.2 min. Time taken for two segment regression was comparable in Group B (79.9 ± 14.4 min and Group BN (87.1 ± 22.6 min, but it was significantly longer in Group BD (122.5 ± 17.2 min and Group BDN (136.4 ± 25.5 min. There was no significant difference in other variables between the groups. Conclusion: Transdermal nitroglycerine itself does not exhibit any analgesic potential of its own but, it enhances the analgesic potential of intrathecal dexmedetomidine.

  2. Treatment with subcutaneous and transdermal fentanyl: results from a population pharmacokinetic study in cancer patients.

    Science.gov (United States)

    Oosten, Astrid W; Abrantes, João A; Jönsson, Siv; de Bruijn, Peter; Kuip, Evelien J M; Falcão, Amílcar; van der Rijt, Carin C D; Mathijssen, Ron H J

    2016-04-01

    Transdermal fentanyl is effective for the treatment of moderate to severe cancer-related pain but is unsuitable for fast titration. In this setting, continuous subcutaneous fentanyl may be used. As data on the pharmacokinetics of continuous subcutaneous fentanyl are lacking, we studied the pharmacokinetics of subcutaneous and transdermal fentanyl. Furthermore, we evaluated rotations from the subcutaneous to the transdermal route. Fifty-two patients treated with subcutaneous and/or transdermal fentanyl for moderate to severe cancer-related pain participated. A population pharmacokinetic model was developed and evaluated using non-linear mixed-effects modelling. For rotations from subcutaneous to transdermal fentanyl, a 1:1 dose conversion ratio was used while the subcutaneous infusion was continued for 12 h (with a 50 % tapering after 6 h). A 6-h scheme with 50 % tapering after 3 h was simulated using the final model. A one-compartment model with first-order elimination and separate first-order absorption processes for each route adequately described the data. The estimated apparent clearance of fentanyl was 49.6 L/h; the absorption rate constant for subcutaneous and transdermal fentanyl was 0.0358 and 0.0135 h(-1), respectively. Moderate to large inter-individual and inter-occasion variability was found. Around rotation from subcutaneous to transdermal fentanyl, measured and simulated plasma fentanyl concentrations rose and increasing side effects were observed. We describe the pharmacokinetics of subcutaneous and transdermal fentanyl in one patient cohort and report several findings that are relevant for clinical practice. Further research is warranted to study the optimal scheme for rotations from the subcutaneous to the transdermal route.

  3. Study on Mechanism Experiments and Evaluation Methods for Water Eutrophication

    Directory of Open Access Journals (Sweden)

    Jiabin Yu

    2017-01-01

    Full Text Available The process of water eutrophication involves the interaction of external factors, nutrients, microorganisms, and other factors. It is complex and has not yet been effectively studied. To examine the formation process of water eutrophication, a set of orthogonal experiments with three factors and four levels is designed to analyze the key factors. At the same time, with the help of a large amount of monitoring data, the principal component analysis method is used to extract the main components of water eutrophication and determine the effective evaluation indicators of eutrophication. Finally, the Bayesian theory of uncertainty is applied to the evaluation of the eutrophication process to evaluate the sample data. The simulation results demonstrate the validity of the research method.

  4. On the Road to Development of an in Vitro Permeation Test (IVPT) Model to Compare Heat Effects on Transdermal Delivery Systems: Exploratory Studies with Nicotine and Fentanyl.

    Science.gov (United States)

    Shin, Soo Hyeon; Ghosh, Priyanka; Newman, Bryan; Hammell, Dana C; Raney, Sam G; Hassan, Hazem E; Stinchcomb, Audra L

    2017-09-01

    At elevated temperatures, the rate of drug release and skin permeation from transdermal delivery systems (TDS) may be higher than at a normal skin temperature. The aim of this study was to compare the effect of heat on the transdermal delivery of two model drugs, nicotine and fentanyl, from matrix-type TDSs with different formulations, using in vitro permeation tests (IVPT). IVPT experiments using pig skin were performed on two nicotine and three fentanyl TDSs. Both continuous and transient heat exposures were investigated by applying heat either for the maximum recommended TDS wear duration or for short duration. Continuous heat exposure for the two nicotine TDSs resulted in different effects, showing a prolonged heat effect for one product but not the other. The J max enhancement ratio due to the continuous heat effect was comparable between the two nicotine TDS, but significantly different (p drug from the skin depot after TDS removal differently for two drugs, with fentanyl exhibiting a longer heat effect. This exploratory work suggests that an IVPT study may be able to discriminate differences in transdermal drug delivery when different TDS are exposed to elevated temperatures. However, the clinical significance of IVPT heat effects studies should be further explored by conducting in vivo clinical studies with similar study designs.

  5. Enhancement of skin permeation of flurbiprofen via its transdermal patches using isopulegol decanoate (ISO-C10) as an absorption enhancer: pharmacokinetic and pharmacodynamic evaluation.

    Science.gov (United States)

    Chen, Yang; Quan, Peng; Liu, Xiaochang; Guo, Wenjia; Song, Wenting; Cun, Dongmei; Wang, Zhongyan; Fang, Liang

    2015-09-01

    The study aimed to prepare a transdermal patch for flurbiprofen using isopulegol decanoate (ISO-C10) as a permeation enhancer, and to evaluate the in-vitro and in-vivo percutaneous permeation of the drug, as well as the pharmacodynamic efficacy of the formulation. The permeation experiments were conducted on rabbit skin, and the pharmacokinetic profiles and synovial fluid drug concentration were measured after in-vivo transdermal administration. A deconvolution approach was employed to analyse the correlation between the in-vitro and in-vivo drug permeation. The anti-inflammatory and analgesic effects were, respectively, assessed using the adjuvant arthritis model and the acetic acid induced pain model. ISO-C10 could increase the in-vitro permeation of flurbiprofen from 46.22 ± 5.65 μg/cm(2) to 101.07 ± 10.85 μg/cm(2) . The in-vivo absorption of the drug was also improved by the enhancer, and a good linear correlation was observed between the in-vitro and in-vivo drug permeation. Meanwhile, the ISO-C10 contained patches increased the drug disposition in synovial fluid and enhanced the pharmacodynamic efficacy of the formulation. ISO-C10 would be a promising permeation enhancer for improving the in-vitro and in-vivo delivery of flurbiprofen from its transdermal patches. © 2015 Royal Pharmaceutical Society.

  6. User Experience Evaluation Methods in Product Development (UXEM'09)

    Science.gov (United States)

    Roto, Virpi; Väänänen-Vainio-Mattila, Kaisa; Law, Effie; Vermeeren, Arnold

    High quality user experience (UX) has become a central competitive factor of product development in mature consumer markets [1]. Although the term UX originated from industry and is a widely used term also in academia, the tools for managing UX in product development are still inadequate. A prerequisite for designing delightful UX in an industrial setting is to understand both the requirements tied to the pragmatic level of functionality and interaction and the requirements pertaining to the hedonic level of personal human needs, which motivate product use [2]. Understanding these requirements helps managers set UX targets for product development. The next phase in a good user-centered design process is to iteratively design and evaluate prototypes [3]. Evaluation is critical for systematically improving UX. In many approaches to UX, evaluation basically needs to be postponed until the product is fully or at least almost fully functional. However, in an industrial setting, it is very expensive to find the UX failures only at this phase of product development. Thus, product development managers and developers have a strong need to conduct UX evaluation as early as possible, well before all the parts affecting the holistic experience are available. Different types of products require evaluation on different granularity and maturity levels of a prototype. For example, due to its multi-user characteristic, a community service or an enterprise resource planning system requires a broader scope of UX evaluation than a microwave oven or a word processor that is meant for a single user at a time. Before systematic UX evaluation can be taken into practice, practical, lightweight UX evaluation methods suitable for different types of products and different phases of product readiness are needed. A considerable amount of UX research is still about the conceptual frameworks and models for user experience [4]. Besides, applying existing usability evaluation methods (UEMs) without

  7. Effectiveness and tolerability of transdermal rivastigmine in the treatment of Alzheimer’s disease in daily practice

    Directory of Open Access Journals (Sweden)

    Seibert J

    2012-04-01

    Full Text Available Johannes Seibert1, Ferenc Tracik2,3, Konstantin Articus2, Stefan Spittler41Outpatient Clinic, Heidelberg, Germany; 2Novartis Pharma, Nürnberg, Germany; 3Department of Neurology, Heinrich-Heine University, Düsseldorf, Germany; 4Alexianer Krefeld, Maria Hilf Clinic, Krefeld, GermanyBackground: Oral cholinesterase inhibitors at doses efficacious for the treatment of Alzheimer’s disease (AD are often prematurely discontinued due to gastrointestinal side effects. In controlled clinical trials, transdermal rivastigmine demonstrated less such effects at similar efficacy. The current study aimed to verify the validity of this data in daily practice.Methods: This was a prospective, multicenter, observational study on transdermal rivastigmine in Germany. Eligible patients were those with AD who had not yet been treated with rivastigmine. Outcome measures were changes in clock-drawing test, Mini-Mental State Examination (MMSE, Caregiver Burden Scale, Clinical Global Impression (CGI, physicians’ assessments of tolerability, and the incidence of adverse events (AEs over 4 months of treatment.Results: In 257 centers 1113 patients were enrolled; 614 women and 499 men, mean age 76.5 years. In 58% of patients AD was treated for the first time and in 42% therapy was switched to transdermal rivastigmine, mostly due to lack of tolerability (13.6% or effectiveness (26.9%. After 4 months, 67.4% of patients were on the target dose of 9.5 mg/day and 21.8% were still on 4.6 mg/day. MMSE significantly improved in patients with and without pretreatment (ΔMMSE, 0.9 ± 3.4 and 0.8 ± 3.4, respectively, both P < 0.001; the CGI score improved in 60.9% and 61.3% of patients, respectively. Overall 11.7% of patients had AEs, mainly affecting the skin or the gastrointestinal tract; in 1.1% of cases AEs were serious; 14.7% of patients discontinued therapy, 6.0% due to AEs. With rivastigmine treatment the percentage of patients taking psychotropic comedication decreased

  8. Film forming systems for topical and transdermal drug delivery

    Directory of Open Access Journals (Sweden)

    Kashmira Kathe

    2017-11-01

    Full Text Available Skin is considered as an important route of administration of drugs for both local and systemic effects. The effectiveness of topical therapy depends on the physicochemical properties of the drug and adherence of the patient to the treatment regimen as well as the system's ability to adhere to skin during the therapy so as to promote drug penetration through the skin barrier. Conventional formulations for topical and dermatological administration of drugs have certain limitations like poor adherence to skin, poor permeability and compromised patient compliance. For the treatment of diseases of body tissues and wounds, the drug has to be maintained at the site of treatment for an effective period of time. Topical film forming systems are such developing drug delivery systems meant for topical application to the skin, which adhere to the body, forming a thin transparent film and provide delivery of the active ingredients to the body tissue. These are intended for skin application as emollient or protective and for local action or transdermal penetration of medicament for systemic action. The transparency is an appreciable feature of this polymeric system which greatly influences the patient acceptance. In the current discussion, the film forming systems are described as a promising choice for topical and transdermal drug delivery. Further the various types of film forming systems (sprays/solutions, gels and emulsions along with their evaluation parameters have also been reviewed.

  9. Development of antimigraine transdermal delivery systems of pizotifen malate.

    Science.gov (United States)

    Serna-Jiménez, C E; del Rio-Sancho, S; Calatayud-Pascual, M A; Balaguer-Fernández, C; Femenía-Font, A; López-Castellano, A; Merino, V

    2015-08-15

    The aim of this study was to develop and evaluate a transdermal delivery system of pizotifen malate. Pizotifen is frequently used in the preventive treatment of migraine, but is also indicated in eating disorders. In the course of the project, the effects of chemical enhancers such as ethanol, 1,8-cineole, limonene, azone and different fatty acids (decanoic, decenoic, dodecanoic, linoleic and oleic acids) were determined, first using a pizotifen solution. Steady state flux, diffusion and partition parameters were estimated by fitting the Scheuplein equation to the data obtained. Among the chemical enhancers studied, decenoic acid showed the highest enhancement activity, which seemed to be due to the length of its alkyl chain and unsaturation at the 9th carbon. The influence of iontophoresis and the involvement of electrotransport in said process was determined. The absorption profile obtained with iontophoresis was similar to that obtained with fatty acids and terpenes, though skin deposition of the drug was lower with the former. Transdermal delivery systems (TDS) of pizotifen were manufactured by including chemical enhancers, decenoic acid or oleic acid, and were subsequently characterized. When the results obtained with solutions were compared with those obtained with the TDS, a positive enhancement effect was observed with the latter with respect to the partitioning and diffusion of the drug across the skin. Our findings endorse the suitability of our TDS for delivering therapeutic amounts of pizotifen malate. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Hybrid electrospun chitosan-phospholipids nanofibers for transdermal drug delivery.

    Science.gov (United States)

    Mendes, Ana C; Gorzelanny, Christian; Halter, Natalia; Schneider, Stefan W; Chronakis, Ioannis S

    2016-08-20

    Chitosan (Ch) polysaccharide was mixed with phospholipids (P) to generate electrospun hybrid nanofibers intended to be used as platforms for transdermal drug delivery. Ch/P nanofibers exibithed average diameters ranging from 248±94nm to 600±201nm, depending on the amount of phospholipids used. Fourier Transformed Infra-Red (FTIR) spectroscopy and Dynamic Light Scattering (DLS) data suggested the occurrence of electrostatic interactions between amine groups of chitosan with the phospholipid counterparts. The nanofibers were shown to be stable for at least 7days in Phosphate Buffer Saline (PBS) solution. Cytotoxicity studies (WST-1 and LDH assays) demonstrated that the hybrid nanofibers have suitable biocompatibility. Fluorescence microscopy, also suggested that L929 cells seeded on top of the CH/P hybrid have similar metabolic activity comparatively to the cells seeded on tissue culture plate (control). The release of curcumin, diclofenac and vitamin B12, as model drugs, from Ch/P hybrid nanofibers was investigated, demonstrating their potential utilization as a transdermal drug delivery system. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Tolterodine Tartrate Proniosomal Gel Transdermal Delivery for Overactive Bladder

    Directory of Open Access Journals (Sweden)

    Rajan Rajabalaya

    2016-08-01

    Full Text Available The goal of this study was to formulate and evaluate side effects of transdermal delivery of proniosomal gel compared to oral tolterodine tartrate (TT for the treatment of overactive bladder (OAB. Proniosomal gels are surfactants, lipids and soy lecithin, prepared by coacervation phase separation. Formulations were analyzed for drug entrapment efficiency (EE, vesicle size, surface morphology, attenuated total reflectance Fourier transform infrared (ATR-FTIR spectroscopy, in vitro skin permeation, and in vivo effects. The EE was 44.87%–91.68% and vesicle size was 253–845 nm for Span formulations and morphology showed a loose structure. The stability and skin irritancy test were also carried out for the optimized formulations. Span formulations with cholesterol-containing formulation S1 and glyceryl distearate as well as lecithin containing S3 formulation showed higher cumulative percent of permeation such as 42% and 35%, respectively. In the in vivo salivary secretion model, S1 proniosomal gel had faster recovery, less cholinergic side effect on the salivary gland compared with that of oral TT. Histologically, bladder of rats treated with the proniosomal gel formulation S1 showed morphological improvements greater than those treated with S3. This study demonstrates the potential of proniosomal vesicles for transdermal delivery of TT to treat OAB.

  12. Evaluation of diclofenac prodrugs for enhancing transdermal delivery.

    Science.gov (United States)

    Lobo, Shabbir; Li, Henan; Farhan, Nashid; Yan, Guang

    2014-03-01

    Abstract Objective: The purpose of this study was to evaluate the approach of using diclofenac acid (DA) prodrugs for enhancing transdermal delivery. Methanol diclofenac ester (MD), ethylene glycol diclofenac ester (ED), glycerol diclofenac ester (GD) and 1,3-propylene glycol diclofenac ester (PD) were synthesized and evaluated for their physicochemical properties such as solubilities, octanol/water partition coefficients, stratum corneum/water partition coefficients, hydrolysis rates and bioconversion rates. In vitro fluxes across human epidermal membrane (HEM) in the Franz diffusion cell were determined on DA-, MD-, ED-, GD- and PD-saturated aqueous solutions. The formation of GD and ED led to the prodrugs with higher aqueous solubilities and lower partition coefficients than those of the parent drug. Prodrugs with improved aqueous solubility showed better fluxes across HEM in aqueous solution than that of the parent drug, with GD showing the highest aqueous solubility and also the highest flux. There is a linear relationship between the aqueous solubility and flux for DA, ED and PD, but GD and MD deviated from the linear line. Diclofenac prodrugs with improved hydrophilicity than the parent drug could be utilized for enhancing transdermal diclofenac delivery.

  13. Evaluation of Diclofenac Prodrugs for Enhancing Transdermal Delivery

    Science.gov (United States)

    Lobo, Shabbir; Li, Henan; Farhan, Nashid; Yan, Guang

    2016-01-01

    The purpose of this study was to evaluate the approach of using diclofenac acid (DA) prodrugs for enhancing transdermal delivery. Methanol diclofenac ester (MD), ethylene glycol diclofenac ester (ED), glycerol diclofenac ester (GD), and 1,3-propylene glycol diclofenac ester (PD) were synthesized and evaluated for their physicochemical properties such as solubilities, octanol/water partition coefficients, stratum corneum/water partition coefficients, hydrolysis rates, and bioconversion rates. In vitro fluxes across human epidermal membrane (HEM) in Franz diffusion cell were determined on DA, MD, ED, GD, and PD saturated aqueous solutions. The formation of GD and ED led to the prodrugs with higher aqueous solubilities and lower partition coefficients than those of the parent drug. Prodrugs with improved aqueous solubility showed better fluxes across HEM in aqueous solution than that of the parent drug, with GD showing the highest aqueous solubility and also the highest flux. There is a linear relationship between the aqueous solubility and flux for DA, ED and PD, but GD and MD deviated from the linear line. Overall, diclofenac prodrugs with improved hydrophilicity than the parent drug could be utilized for enhancing transdermal diclofenac delivery. PMID:24517636

  14. Nanostructured lipid carriers for transdermal delivery of acid labile lansoprazole.

    Science.gov (United States)

    Lin, Wen Jen; Duh, Yi Shein

    2016-11-01

    The aim of this study was to develop nanostructured lipid carriers (NLCs) for transdermal delivery of acid-labile lansoprazole (LPZ). The drug loading, particle size, zeta potential, thermal behavior and stability of NLCs were evaluated. The particle size of NLCs was in the range of 90-210nm and the zeta potential was -61.9 to +3.2mV dependent of the compositions. Stearylamine (SA) prevented lansoprazole degradation and maintained drug stable in NLCs. The anionic sodium dodecyl sulfate (SDS) adsorbed on the lipid surface and formed complex with cationic SA to prevent NLCs aggregation. The effects of type (e.g., isopropyl myristate (IPM), menthol) and concentration (e.g., 1.25, 2.50, 3.75%w/w) of enhancers on penetration of lansoprazole NLC hydrogels were investigated in vitro using Wistar rat skin. The steady-state flux of lansoprazole NLC hydrogel containing 3.75% IPM was the highest which was enhanced by 2.7 folds as compared to enhancer-free NLC hydrogel. In vivo pharmacokinetics of lansoprazole following transdermal delivery of NLC hydrogel showed that the elimination of drug was significantly reduced and the mean residence time of drug was prominently prolonged as compared to intravenous drug solution (p<0.005). The accumulation of drug in the skin and continuous penetration of drug through the skin accounted for the maintenance of drug concentration for at least 24h. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Efficient Transdermal Delivery of Benfotiamine in an Animal Model

    Directory of Open Access Journals (Sweden)

    Gyula Varadi

    2015-01-01

    Full Text Available We designed a transdermal system to serve as a delivery platform for benfotiamine utilizing the attributes of passive penetration enhancing molecules to penetrate through the outer layers of skin combined with the advance of incorporating various peripherally-acting vasodilators to enhance drug uptake.  Benfotiamine, incorporated into this transdermal formulation, was applied to skin in an animal model in order to determine the ability to deliver this thiamine pro-drug effectively to the sub-epithelial layers.  In this proof of concept study in guinea pigs, we found that a single topical application of either a solubilized form of benfotiamine (15 mg or a microcrystalline suspension form (25 mg resulted in considerable increases of the dephosphorylated benfotiamine (S-benzoylthiamine in the skin tissue as well as in significant increases in the thiamine and thiamine phosphate pools compared to control animals.  The presence of a ~8000x increase in thiamine and increases in its phosphorylated derivatives in the epidermis and dermis tissue of the test animals gives a strong indication that the topical treatment with benfotiamine works very well for the desired outcome of producing an intracellular increase of the activating cofactor pool for transketolase enzyme, which is implicated in the pathophysiology of diabetic neuropathy.

  16. The effect of transdermal nicotine patches on sleep and dreams.

    Science.gov (United States)

    Page, F; Coleman, G; Conduit, R

    2006-07-30

    This study was undertaken to determine the effect of 24-h transdermal nicotine patches on sleep and dream mentation in 15 smokers aged 20 to 33. Utilising a repeated measures design, it was found that more time awake and more ASDA micro-arousals occurred while wearing the nicotine patch compared to placebo. Also, the percentage of REM sleep decreased, but REM latency and the proportion of time spent in NREM sleep stages did not change significantly. Dream reports containing visual imagery, visual imagery ratings and the number of visualizable nouns were significantly greater from REM compared to Stage 2 awakenings, regardless of patch condition. However, a general interaction effect was observed. Stage 2 dream variables remained equivalent across nicotine and placebo conditions. Within REM sleep, more dream reports containing visual imagery occurred while wearing the nicotine patch, and these were rated as more vivid. The greater frequency of visual imagery reports and higher imagery ratings specifically from REM sleep suggests that previously reported dreaming side effects from 24-h nicotine patches may be specific to REM sleep. Combined with previous animal studies showing that transdermally delivered nicotine blocks PGO activity in REM sleep, the current results do no appear consistent with PGO-based hypotheses of dreaming, such as the Activation-Synthesis (AS) or Activation, Input and Modulation (AIM) models.

  17. Methodical Specifics of Thermal Experiments with Thin Carbon Reinforced Plates

    Directory of Open Access Journals (Sweden)

    O. V. Denisov

    2015-01-01

    Full Text Available Polymer composite materials (CM are widely used in creation of large space constructions, especially reflectors of space antennas. Composite materials should provide high level of specific stiffness and strength for space structures. Thermal conductivity in reinforcement plane is a significant factor in case of irregular heating space antennas. Nowadays, data on CM reinforcement plane thermal conductivity are limited and existing methods of its defining are imperfect. Basically, traditional methods allow us to define thermal conductivity in perpendicular direction towards the reinforcement plane on the samples of round or rectangular plate. In addition, the thickness of standard samples is larger than space antenna thickness. Consequently, new methods are required. Method of contact heating, which was developed by BMSTU specialists with long hollow carbon beam, could be a perspective way. This article is devoted to the experimental method of contact heating on the thin carbon plates.Thermal tests were supposed to provide a non-stationary temperature field with a gradient being co-directional with the plane reinforcement in the material sample. Experiments were conducted in vacuum chamber to prevent unstructured convection. Experimental thermo-grams processing were calculated by 1-d thermal model for a thin plate. Influence of uncertainty of experimental parameters, such as (radiation emission coefficients of sample surface, glue, temperature sensors and uncertainty of sensors placement on the result of defined thermal conductivity has been estimated. New data on the thermal conductivity in reinforcement plane were obtained within 295 - 375 K temperature range, which can be used to design and develop reflectors of precision space antennas. In the future it is expedient to conduct tests of thin-wall plates from carbon fiber-reinforced plastic in wide temperature range, especially in the low-range temperatures.

  18. New Jersey's residential radon remediation program - methods and experience

    International Nuclear Information System (INIS)

    Pluta, T.A.; Cosolita, F.J.; Rothfuss, E.

    1986-01-01

    As part of a remedial action program to decontaminate over 200 residential properties, 12 typical properties were selected and a demonstration program was initiated in the spring of 1985. The residences selected represented a range of contamination levels and configurations and differing architectural styles representative of the age of construction. The physical limitations of the sites and the overall nature of a decontamination project in active residential communities imposed a number of severe restrictions on work methods and equipment. Regulations governing transportation and disposal set virtually zero defect standards for the condition of containers. The intrusive nature of the work in residential neighborhoods required continual interaction with local residents, public officials and citizen task forces. Media coverage was very high. Numerous briefings were held to allay fears and promote public understanding. Numerous issues ranging in content from public health and safety to engineering and construction methods arose during the remedial action program. These issues were resolved by a multi-disciplined management team which was knowledgeable in public administration, radiation physics, and engineering design and construction. This paper discusses the nature of the problem, the methods applied to resolve the problem and the experience gained as a result of a remedial action program

  19. Enhanced Controlled Transdermal Delivery of Torasemide Using ...

    African Journals Online (AJOL)

    Erah

    Methods: The solubility of torasemide was studied at various volume fraction of polyethylene glycol. (PEG) 400. ... transient high blood concentration of drug ... action, thereby allowing for potentially lower .... solubility in the permeability field,.

  20. Fractional Ablative Laser Followed by Transdermal Acoustic Pressure Wave Device to Enhance the Drug Delivery of Aminolevulinic Acid: In Vivo Fluorescence Microscopy Study.

    Science.gov (United States)

    Waibel, Jill S; Rudnick, Ashley; Nousari, Carlos; Bhanusali, Dhaval G

    2016-01-01

    Topical drug delivery is the foundation of all dermatological therapy. Laser-assisted drug delivery (LAD) using fractional ablative laser is an evolving modality that may allow for a greater precise depth of penetration by existing topical medications, as well as more efficient transcutaneous delivery of large drug molecules. Additional studies need to be performed using energy-driven methods that may enhance drug delivery in a synergistic manner. Processes such as iontophoresis, electroporation, sonophoresis, and the use of photomechanical waves aid in penetration. This study evaluated in vivo if there is increased efficacy of fractional CO2 ablative laser with immediate acoustic pressure wave device. Five patients were treated and biopsied at 4 treatment sites: 1) topically applied aminolevulinic acid (ALA) alone; 2) fractional ablative CO2 laser and topical ALA alone; 3) fractional ablative CO2 laser and transdermal acoustic pressure wave device delivery system; and 4) topical ALA with transdermal delivery system. The comparison of the difference in the magnitude of diffusion with both lateral spread of ALA and depth diffusion of ALA was measured by fluorescence microscopy. For fractional ablative CO2 laser, ALA, and transdermal acoustic pressure wave device, the protoporphyrin IX lateral fluorescence was 0.024 mm on average vs 0.0084 mm for fractional ablative CO2 laser and ALA alone. The diffusion for the acoustic pressure wave device was an order of magnitude greater. We found that our combined approach of fractional ablative CO2 laser paired with the transdermal acoustic pressure wave device increased the depth of penetration of ALA.

  1. Fuel coolant interaction experiment by direct electrical heating method

    International Nuclear Information System (INIS)

    Takeda, Tsuneo; Hirano, Kenmei

    1979-01-01

    In the PCM (Power Cooling Mismatch) experiments, the FCI (Fuel Coolant Interaction) test is one of necessary tests in order to predict various phenomena that occur during PCM in the core. A direct electrical heating method is used for the FCI tests for fuel pellet temperature of over 1000 0 C. Therefore, preheating is required before initiating the direct electrical heating. The fuel pin used in the FCI tests is typical LWR fuel element, which is surrounded by coolant water. It is undersirable to heat up the coolant water during preheating of the fuel pin. Therefore, a zirconia (ZrO 2 ) pellet which is similar to a UO 2 pellet in physical and chemical properties is used. Electric property (electric conductivity) of ZrO 2 is particularly suitable for direct electrical heating as in the case of UO 2 . In this experiment, ZrO 2 pellet (melting point 2500 0 C) melting was achieved by use of both preheating and direct electrical heating. Temperature changes of coolant and fuel surface, as well as the pressure change of coolant water, were measured. The molten fuel interacted with the coolant and generated shock waves. A portion of this molten fuel fragmented into small particles during this interaction. The peak pressure of the observed shock wave was about 35 bars. The damaged fuel pin was photographed after disassembly. This report shows the measured coolant pressure changes and the coolant temperature changes, as well as photographs of damaged fuel pin and fuel fragments. (author)

  2. Efficient Transdermal Delivery of Alendronate, a Nitrogen-Containing Bisphosphonate, Using Tip-Loaded Self-Dissolving Microneedle Arrays for the Treatment of Osteoporosis.

    Science.gov (United States)

    Katsumi, Hidemasa; Tanaka, Yutaro; Hitomi, Kaori; Liu, Shu; Quan, Ying-Shu; Kamiyama, Fumio; Sakane, Toshiyasu; Yamamoto, Akira

    2017-08-17

    To improve the transdermal bioavailability and safety of alendronate (ALN), a nitrogen-containing bisphosphonate, we developed self-dissolving microneedle arrays (MNs), in which ALN is loaded only at the tip portion of micron-scale needles by a dip-coating method (ALN(TIP)-MN). We observed micron-scale pores in rat skin just after application of ALN(TIP)-MN, indicating that transdermal pathways for ALN were created by MN. ALN was rapidly released from the tip of MNs as observed in an in vitro release study. The tip portions of MNs completely dissolved in the rat skin within 5 min after application in vivo. After application of ALN(TIP)-MN in mice, the plasma concentration of ALN rapidly increased, and the bioavailability of ALN was approximately 96%. In addition, the decrease in growth plate was effectively suppressed by this efficient delivery of ALN in a rat model of osteoporosis. Furthermore, no skin irritation was observed after application of ALN(TIP)-MN and subcutaneous injection of ALN, while mild skin irritation was induced by whole-ALN-loaded MN (ALN-MN)-in which ALN is contained in the whole of the micron-scale needles fabricated from hyaluronic acid-and intradermal injection of ALN. These findings indicate that ALN(TIP)-MN is a promising transdermal formulation for the treatment of osteoporosis without skin irritation.

  3. [Experience feedback committee: a method for patient safety improvement].

    Science.gov (United States)

    François, P; Sellier, E; Imburchia, F; Mallaret, M-R

    2013-04-01

    An experience feedback committee (CREX, Comité de Retour d'EXpérience) is a method which contributes to the management of safety of care in a medical unit. Originally used for security systems of civil aviation, the method has been adapted to health care facilities and successfully implemented in radiotherapy units and in other specialties. We performed a brief review of the literature for studies reporting data on CREX established in hospitals. The review was performed using the main bibliographic databases and Google search results. The CREX is designed to analyse incidents reported by professionals. The method includes monthly meetings of a multi-professional committee that reviews the reported incidents, chooses a priority incident and designates a "pilot" responsible for investigating the incident. The investigation of the incident involves a systemic analysis method and a written synthesis presented at the next meeting of the committee. The committee agrees on actions for improvement that are suggested by the analysis and follows their implementation. Systems for the management of health care, including reporting systems, are organized into three levels: the medical unit, the hospital and the country as a triple loop learning process. The CREX is located in the base level, short loop of risk management and allows direct involvement of care professionals in patient safety. Safety of care has become a priority of health systems. In this context, the CREX can be a useful vehicle for the implementation of a safety culture in medical units. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  4. Recent trends in the transdermal delivery of therapeutic agents used for the management of neurodegenerative diseases.

    Science.gov (United States)

    Ita, Kevin

    2017-06-01

    With the increasing proportion of the global geriatric population, it becomes obvious that neurodegenerative diseases will become more widespread. From an epidemiological standpoint, it is necessary to develop new therapeutic agents for the management of Alzheimer's disease, Parkinson's disease, multiple sclerosis and other neurodegenerative disorders. An important approach in this regard involves the use of the transdermal route. With transdermal drug delivery systems (TDDS), it is possible to modulate the pharmacokinetic profiles of these medications and improve patient compliance. Transdermal drug delivery has also been shown to be useful for drugs with short half-life and low or unpredictable bioavailability. In this review, several transdermal drug delivery enhancement technologies are being discussed in relation to the delivery of medications used for the management of neurodegenerative disorders.

  5. Turning theory into practice: the development of modern transdermal drug delivery systems and future trends.

    Science.gov (United States)

    Perumal, O; Murthy, S N; Kalia, Y N

    2013-01-01

    Despite its remarkable barrier function, the skin remains an attractive site for systemic drug delivery given its easy accessibility, large surface area and the possibility to bypass the gastrointestinal tract and the liver and so modify drug absorption kinetics. The pioneering work of Scheuplein, Higuchi and others in the 1960s helped to explain the processes involved in passive percutaneous absorption and led to the development of mathematical models to describe transdermal drug delivery. The intervening years have seen these theories turned to practice and a significant number of transdermal systems are now available including some that employ active drug delivery. This review briefly discusses the evolution of transdermal therapeutic systems over the years and the potential of newer transdermal technologies to deliver hydrophilic drugs and macromolecules through the skin. © 2013 S. Karger AG, Basel.

  6. Comparative enhancing effects of electret with chemical enhancers on transdermal delivery of meloxicam in vitro

    International Nuclear Information System (INIS)

    Cui, L L; Hou, X M; Li, G D; Jiang, J; Liang, Y Y; Xin, X

    2008-01-01

    Electret offers enhancing effect in transdermal drug delivery for altering of the arrangement of lipid molecules in the stratum corneum, forming many transient permeable apertures and enhancing the transdermal drug delivery. In this paper, meloxicam patch formulations were developed to make the comparative study of transdermal drug delivery between electret and chemical enhancers. Patches were made into control, electret, chemical enhancer and electret with chemical enhancer ones, according to the preparation procedure. The electret combined with chemical enhancer patch was designed to probe the incorporation between electret and chemical enhancer in transdermal drug delivery. The meloxicam release from the patch was found to increase in order of blank, chemical enhancer, electret and electret with chemical enhancer patch, in general.

  7. Transdermal and intradermal delivery of therapeutic agents: application of physical technologies

    National Research Council Canada - National Science Library

    Banga, Ajay K

    2011-01-01

    .... Advancements in science combined with the need for diverse drug delivery modalities have introduced a variety of transdermal and intradermal products for existing drugs at a fraction of the cost of new drug development...

  8. Tuning Parameters in Heuristics by Using Design of Experiments Methods

    Science.gov (United States)

    Arin, Arif; Rabadi, Ghaith; Unal, Resit

    2010-01-01

    With the growing complexity of today's large scale problems, it has become more difficult to find optimal solutions by using exact mathematical methods. The need to find near-optimal solutions in an acceptable time frame requires heuristic approaches. In many cases, however, most heuristics have several parameters that need to be "tuned" before they can reach good results. The problem then turns into "finding best parameter setting" for the heuristics to solve the problems efficiently and timely. One-Factor-At-a-Time (OFAT) approach for parameter tuning neglects the interactions between parameters. Design of Experiments (DOE) tools can be instead employed to tune the parameters more effectively. In this paper, we seek the best parameter setting for a Genetic Algorithm (GA) to solve the single machine total weighted tardiness problem in which n jobs must be scheduled on a single machine without preemption, and the objective is to minimize the total weighted tardiness. Benchmark instances for the problem are available in the literature. To fine tune the GA parameters in the most efficient way, we compare multiple DOE models including 2-level (2k ) full factorial design, orthogonal array design, central composite design, D-optimal design and signal-to-noise (SIN) ratios. In each DOE method, a mathematical model is created using regression analysis, and solved to obtain the best parameter setting. After verification runs using the tuned parameter setting, the preliminary results for optimal solutions of multiple instances were found efficiently.

  9. Data analysis method for plant experience feedback data bank

    International Nuclear Information System (INIS)

    Ployart, R.; Lannoy, A.

    1988-01-01

    French pressurized water reactors (PWRs) represent at the moment about fifty units, among which the oldest have been in operation for ten years. Furthermore, these PWRs developed according to a growth strategy of standardized plants and with a single plant operator are quite homogeneous in their design as well as in their operating and maintenance procedures. Lastly, the improvements brought about are usually passed on to the whole of the concerned standardized plant. In this context, the operating plant experience feedback data banks hold valuable information that starts being statistically significant. The reliability oriented methods are rather well known; the ones that enable to read out some information on performance and availability, susceptible to guide the plant operator in the decision making are less tested. It concerns changes of operating or maintenance procedure, or technical changes which could be decided from an assessment of the effects of previous changes, or by observing and explaining a posteriori natural evolutions in the behaviour of components. The method used within the framework of this report leads to reveal and explain singularities, correlations, regroupings and trends in the behaviour of the french PWRs

  10. Poly(lactic-co-glycolic) acid drug delivery systems through transdermal pathway: an overview

    OpenAIRE

    Naves, Lucas; Dhand, Chetna; Almeida, Luis; Rajamani, Lakshminarayanan; Ramakrishna, Seeram; Soares, Gra?a

    2017-01-01

    In past few decades, scientists have made tremendous advancement in the field of drug delivery systems (DDS), through transdermal pathway, as the skin represents a ready and large surface area for delivering drugs. Efforts are in progress to design efficient transdermal DDS that support sustained drug release at the targeted area for longer duration in the recommended therapeutic window without producing side-effects. Poly(lactic-co-glycolic acid) (PLGA) is one of the most promising Food and ...

  11. Ultrasound in Biomedical Engineering: Ultrasound Microbubble Contrast Agents Promote Transdermal Permeation of Drugs

    OpenAIRE

    Ai-Ho Liao

    2016-01-01

    This report discusses a new development in the use of ultrasound microbubble contrast agents on transdermal drug delivery. The medium surrounding the microbubbles at the optimum concentration from liquid to gel can be modified and it can still achieve the same enhancement for transdermal drug permeation as liquid medium. It was also found that under the same ultrasound power density, microbubbles of larger particle sizes can extend the penetration depths of dye at the phantom surface.

  12. Transdermal drug delivery: feasibility for treatment of superficial bone stress fractures.

    Science.gov (United States)

    Aghazadeh-Habashi, Ali; Yang, Yang; Tang, Kathy; Lőbenberg, Raimar; Doschak, Michael R

    2015-12-01

    Transdermal drug delivery offers the promise of effective drug therapy at selective sites of pathology whilst reducing systemic exposure to the pharmaceutical agents in off-target organs and tissues. However, that strategy is often limited to cells comprising superficial tissues of the body (rarely to deeper bony structures) and mostly indicated with small hydrophobic pharmacological agents, such as steroid hormones and anti-inflammatory gels to skin, muscle, and joints. Nonetheless, advances in transdermal liposomal formulation have rendered the ability to readily incorporate pharmacologically active hydrophilic drug molecules and small peptide biologics into transdermal dosage forms to impart the effective delivery of those bioactive agents across the skin barrier to underlying superficial tissue structures including bone, often enhanced by some form of electrical, chemical, and mechanical facilitation. In the following review, we evaluate transdermal drug delivery systems, with a particular focus on delivering therapeutic agents to treat superficial bone pain, notably stress fractures. We further introduce and discuss several small peptide hormones active in bone (such as calcitonins and parathyroid hormone) that have shown potential for transdermal delivery, often under the added augmentation of transdermal drug delivery systems that employ lipo/hydrophilicity, electric charge, and/or microprojection facilitation across the skin barrier.

  13. Engineering approaches to transdermal drug delivery: a tribute to contributions of prof. Robert Langer.

    Science.gov (United States)

    Mitragotri, S

    2013-01-01

    Transdermal drug delivery continues to provide an advantageous route of drug administration over injections. While the number of drugs delivered by passive transdermal patches has increased over the years, no macromolecule is currently delivered by the transdermal route. Substantial research efforts have been dedicated by a large number of researchers representing varied disciplines including biology, chemistry, pharmaceutics and engineering to understand, model and overcome the skin's barrier properties. This article focuses on engineering contributions to the field of transdermal drug delivery. The article pays tribute to Prof. Robert Langer, who pioneered the engineering approach towards transdermal drug delivery. Over a period spanning nearly 25 years since his first publication in the field of transdermal drug delivery, Bob Langer has deeply impacted the field by quantitative analysis and innovative engineering. At the same time, he has inspired several generations of engineers by collaborations and mentorship. His scientific insights, innovative technologies, translational efforts and dedicated mentorship have transformed the field. © 2013 S. Karger AG, Basel.

  14. Diamond encapsulated photovoltaics for transdermal power delivery.

    Science.gov (United States)

    Ahnood, A; Fox, K E; Apollo, N V; Lohrmann, A; Garrett, D J; Nayagam, D A X; Karle, T; Stacey, A; Abberton, K M; Morrison, W A; Blakers, A; Prawer, S

    2016-03-15

    A safe, compact and robust means of wireless energy transfer across the skin barrier is a key requirement for implantable electronic devices. One possible approach is photovoltaic (PV) energy delivery using optical illumination at near infrared (NIR) wavelengths, to which the skin is highly transparent. In the work presented here, a subcutaneously implantable silicon PV cell, operated in conjunction with an external NIR laser diode, is developed as a power delivery system. The biocompatibility and long-term biostability of the implantable PV is ensured through the use of an hermetic container, comprising a transparent diamond capsule and platinum wire feedthroughs. A wavelength of 980 nm is identified as the optimum operating point based on the PV cell's external quantum efficiency, the skin's transmission spectrum, and the wavelength dependent safe exposure limit of the skin. In bench-top experiments using an external illumination intensity of 0.7 W/cm(2), a peak output power of 2.7 mW is delivered to the implant with an active PV cell dimension of 1.5 × 1.5 × 0.06 mm(3). This corresponds to a volumetric power output density of ~20 mW/mm(3), significantly higher than power densities achievable using inductively coupled coil-based approaches used in other medical implant systems. This approach paves the way for further ministration of bionic implants. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Organisational reviews - requirements, methods and experience. Progress report 2006

    International Nuclear Information System (INIS)

    Reiman, T.; Oedewald, P.; Wahlstroem, B.; Rollenhagen, C.; Kahlbom, U.

    2007-04-01

    Organisational reviews are important instruments in the continuous quest for improved performance. In the nuclear field there has been an increasing regulatory interest in organisational performance, because incidents and accidents often point to organisational deficiencies as one of the major precursors. Many methods for organisational reviews have been proposed, but they are mostly based on ad hoc approaches to specific problems. The absence of well-established techniques for organisational reviews has already shown to cause discussions and controversies on different levels. The aim of the OrRe project is to collect the experiences from organisational reviews carried out so far and to reflect them in a theoretical model of organisational performance. Furthermore, the project aims to reflect on the criteria for the definition of the scope and content of organisational reviews. Finally, recommendations will be made for guidance for people participating in organisational reviews. This progress report describes regulatory practices in Finland and Sweden together with some case examples of organizational reviews and assessment in both countries. Some issues of concern are raised and an outline for the next year's work is proposed. Issues of concern include the sufficient depth of the assessment, the required competence in assessments, data and criteria problems, definition of the boundaries of the system to be assessed, and the necessary internal support and organisational maturity required for successful assessments. Finally, plans for next year's work are outlined. (au)

  16. Organisational reviews - requirements, methods and experience. Progress report 2006

    Energy Technology Data Exchange (ETDEWEB)

    Reiman, T.; Oedewald, P.; Wahlstroem, B. [VTT, Technical Research Centre of Finland (Finland); Rollenhagen, C.; Kahlbom, U. [Maelardalen University (FI)

    2007-04-15

    Organisational reviews are important instruments in the continuous quest for improved performance. In the nuclear field there has been an increasing regulatory interest in organisational performance, because incidents and accidents often point to organisational deficiencies as one of the major precursors. Many methods for organisational reviews have been proposed, but they are mostly based on ad hoc approaches to specific problems. The absence of well-established techniques for organisational reviews has already shown to cause discussions and controversies on different levels. The aim of the OrRe project is to collect the experiences from organisational reviews carried out so far and to reflect them in a theoretical model of organisational performance. Furthermore, the project aims to reflect on the criteria for the definition of the scope and content of organisational reviews. Finally, recommendations will be made for guidance for people participating in organisational reviews. This progress report describes regulatory practices in Finland and Sweden together with some case examples of organizational reviews and assessment in both countries. Some issues of concern are raised and an outline for the next year's work is proposed. Issues of concern include the sufficient depth of the assessment, the required competence in assessments, data and criteria problems, definition of the boundaries of the system to be assessed, and the necessary internal support and organisational maturity required for successful assessments. Finally, plans for next year's work are outlined. (au)

  17. An experiment with content distribution methods in touchscreen mobile devices.

    Science.gov (United States)

    Garcia-Lopez, Eva; Garcia-Cabot, Antonio; de-Marcos, Luis

    2015-09-01

    This paper compares the usability of three different content distribution methods (scrolling, paging and internal links) in touchscreen mobile devices as means to display web documents. Usability is operationalized in terms of effectiveness, efficiency and user satisfaction. These dimensions are then measured in an experiment (N = 23) in which users are required to find words in regular-length web documents. Results suggest that scrolling is statistically better in terms of efficiency and user satisfaction. It is also found to be more effective but results were not significant. Our findings are also compared with existing literature to propose the following guideline: "try to use vertical scrolling in web pages for mobile devices instead of paging or internal links, except when the content is too large, then paging is recommended". With an ever increasing number of touchscreen web-enabled mobile devices, this new guideline can be relevant for content developers targeting the mobile web as well as institutions trying to improve the usability of their content for mobile platforms. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  18. Brian Barry: innovative contributions to transdermal and topical drug delivery.

    Science.gov (United States)

    Williams, A C

    2013-01-01

    Brian Barry published over 300 research articles across topics ranging from colloid science, vasoconstriction and the importance of thermodynamics in dermal drug delivery to exploring the structure and organisation of the stratum corneum barrier lipids and numerous strategies for improving topical and transdermal drug delivery, including penetration enhancers, supersaturation, coacervation, eutectic formation and the use of varied liposomes. As research in the area blossomed in the early 1980s, Brian wrote the book that became essential reading for both new and established dermal delivery scientists, explaining the background mathematics and principles through to formulation design. Brian also worked with numerous scientists, as collaborators and students, who have themselves taken his rigorous approach to scientific investigation into their own research groups. This paper can only describe a small fraction of the many significant contributions that Brian made to the field during his 40-year academic career.

  19. Effects of vehicles and enhancers on transdermal delivery of clebopride.

    Science.gov (United States)

    Rhee, Yun-Seok; Huh, Jai-Yong; Park, Chun-Woong; Nam, Tae-Young; Yoon, Koog-Ryul; Chi, Sang-Cheol; Park, Eun-Seok

    2007-09-01

    The effects of vehicles and penetration enhancers on the skin permeation of clebopride were evaluated using Franz type diffusion cells fitted with excised rat dorsal skins. The binary vehicle system, diethylene glycol monoethyl ether/isopropyl myristate (40/60, w/w), significantly enhanced the skin permeation rate of clebopride. The skin permeation enhancers, oleic acid and ethanol when used in the binary vehicle system, resulted in relatively high clebopride skin permeation rates. A gel formulation consisting of 1.5% (w/w) clebopride, 5% (w/w) oleic acid, and 7% (w/w) gelling agent with the binary vehicle system resulted in a permeation rate of 28.90 microg/cm2/h. Overall, these results highlight the potential of clebopride formulation for the transdermal route.

  20. Current and future technological advances in transdermal gene delivery.

    Science.gov (United States)

    Chen, Xianfeng

    2017-12-19

    Transdermal gene delivery holds significant advantages as it is able to minimize the problems of systemic administration such as enzymatic degradation, systemic toxicity, and poor delivery to target tissues. This technology has the potential to transform the treatment and prevention of a range of diseases. However, the skin poses a great barrier for gene delivery because of the "bricks-and-mortar" structure of the stratum corneum and the tight junctions between keratinocytes in the epidermis. This review systematically summarizes the typical physical and chemical approaches to overcome these barriers and facilitate gene delivery via skin for applications in vaccination, wound healing, skin cancers and skin diseases. Next, the advantages and disadvantages of different approaches are discussed and the insights for future development are provided. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Microneedles for intradermal and transdermal delivery

    Science.gov (United States)

    Tuan-Mahmood, Tuan-Mazlelaa; McCrudden, Maeliosa T.C.; Torrisi, Barbara M.; McAlister, Emma; Garland, Martin J; Singh, Thakur Raghu Raj; Donnelly, Ryan F

    2014-01-01

    The formidable barrier properties of the uppermost layer of the skin, the stratum corneum impose significant limitations for successful systemic delivery of a broad range of therapeutic molecules, particularly macromolecules and genetic material. Microneedle delivery has been proposed as a strategy to breach the SC barrier function in order to facilitate effective transport of molecules across the skin. This strategy involves the use of micron sized needles fabricated from different materials and using different geometries to create transient aqueous conduits across the skin. Microneedles in isolation, or in combination with other enhancing strategies, have been shown to dramatically enhance the skin permeability of numerous therapeutic molecules including biopharmaceuticals either in vitro, ex vivo or in vivo. Progress in the areas of microneedle design, development and manufacture have proven promising in terms of the potential use of this emerging delivery method in clinical applications such as insulin delivery, transcutaneous immunisations and cutaneous gene delivery. This review article focuses on recent and potential future developments in microneedle technologies. This will include the detailing of progress made in microneedle design, an exploration of the challenges faced in this field and potential forward strategies to embrace the exploitation of microneedle methodologies, while considering the inherent safety aspects of such therapeutic tools. PMID:23680534

  2. Carbon nanotubes buckypapers for potential transdermal drug delivery

    International Nuclear Information System (INIS)

    Schwengber, Alex; Prado, Héctor J.; Zilli, Darío A.; Bonelli, Pablo R.

    2015-01-01

    Drug loaded buckypapers based on different types of carbon nanotubes (CNTs) were prepared and characterized in order to evaluate their potentialities for the design of novel transdermal drug delivery systems. Lab-synthesized CNTs as well as commercial samples were employed. Clonidine hydrochloride was used as model drug, and the influence of composition of the drug loaded buckypapers and processing variables on in vitro release profiles was investigated. To examine the influence of the drug nature the evaluation was further extended to buckypapers prepared with flurbiprofen and one type of CNTs, their selection being based on the results obtained with the former drug. Scanning electronic microscopy images indicated that the model drugs were finely dispersed on the CNTs. Differential scanning calorimetry, and X-ray diffraction pointed to an amorphous state of both drugs in the buckypapers. A higher degree of CNT–drug superficial interactions resulted in a slower release of the drug. These interactions were in turn affected by the type of CNTs employed (single wall or multiwall CNTs), their functionalization with hydroxyl or carboxyl groups, the chemical structure of the drug, and the CNT:drug mass ratio. Furthermore, the application of a second layer of drug free CNTs on the loaded buckypaper, led to decelerate the drug release and to reduce the burst effect. - Highlights: • Drug loaded buckypapers from carbon nanotubes were prepared and characterized. • Their potentialities for transdermal drug delivery applications were evaluated. • Characteristics of carbon nanotubes and the structure of the drug affected release • A higher carbon nanotube:drug mass ratio decelerated release • Up to one week controlled release profiles were obtained for the drug flurbiprofen

  3. Carbon nanotubes buckypapers for potential transdermal drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Schwengber, Alex [PINMATE-Departamento de Industrias, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, C1428EGA Buenos Aires (Argentina); Prado, Héctor J. [PINMATE-Departamento de Industrias, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, C1428EGA Buenos Aires (Argentina); Cátedra de Tecnología Farmacéutica II, Departamento de Tecnología Farmacéutica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, C1113AAD Buenos Aires (Argentina); Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. Rivadavia 1917, C1033AAJ Buenos Aires (Argentina); Zilli, Darío A. [PINMATE-Departamento de Industrias, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, C1428EGA Buenos Aires (Argentina); Bonelli, Pablo R. [PINMATE-Departamento de Industrias, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, C1428EGA Buenos Aires (Argentina); Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. Rivadavia 1917, C1033AAJ Buenos Aires (Argentina); and others

    2015-12-01

    Drug loaded buckypapers based on different types of carbon nanotubes (CNTs) were prepared and characterized in order to evaluate their potentialities for the design of novel transdermal drug delivery systems. Lab-synthesized CNTs as well as commercial samples were employed. Clonidine hydrochloride was used as model drug, and the influence of composition of the drug loaded buckypapers and processing variables on in vitro release profiles was investigated. To examine the influence of the drug nature the evaluation was further extended to buckypapers prepared with flurbiprofen and one type of CNTs, their selection being based on the results obtained with the former drug. Scanning electronic microscopy images indicated that the model drugs were finely dispersed on the CNTs. Differential scanning calorimetry, and X-ray diffraction pointed to an amorphous state of both drugs in the buckypapers. A higher degree of CNT–drug superficial interactions resulted in a slower release of the drug. These interactions were in turn affected by the type of CNTs employed (single wall or multiwall CNTs), their functionalization with hydroxyl or carboxyl groups, the chemical structure of the drug, and the CNT:drug mass ratio. Furthermore, the application of a second layer of drug free CNTs on the loaded buckypaper, led to decelerate the drug release and to reduce the burst effect. - Highlights: • Drug loaded buckypapers from carbon nanotubes were prepared and characterized. • Their potentialities for transdermal drug delivery applications were evaluated. • Characteristics of carbon nanotubes and the structure of the drug affected release • A higher carbon nanotube:drug mass ratio decelerated release • Up to one week controlled release profiles were obtained for the drug flurbiprofen.

  4. Efficacy of transdermal nitroglycerine in idiopathic pre-term labour.

    Science.gov (United States)

    Shaikh, Shahida; Shaikh, Abdul Hameed; Akhter, Saleem; Isran, Basma

    2012-01-01

    To determine the efficacy of transdermal Nitroglycerine patch in idiopathic pre-term labour and foetomaternal outcome. This quasi-experimental study was conducted at the Obstetrics Unit-II of Shaikh Zayed Hospital for Women, Chandka Medical College, Shaheed Mohtarma Benazir Bhutto Medical University, Larkana, from Jan 1 to June 30, 2010. Sixtyfive pregnant women at 28-34 weeks of gestation were recruited after they met the selection criteria based on non-probability consecutive sampling. Initially, 73 patients were selected, but 65 of them completed the treatment, while 8 patients refused to continue. Patients diagnosed with pre-term labour were given glyceryl trinitrate (GTN) 5 mg/12 hours transdermal patch which was applied on the anterior abdominal wall. The second patch of same dose was given after 12 hours. Arrest of labour, prolongation of pregnancy in days or weeks along with side effects of the agent were monitored. Patients were followed till delivery to know the foeto-maternal outcome. Dramatic effects were seen in around 60 (92.3%), of the total patients who had felt relief from premature labour pains within the first hour and only 5 (7.6%) patients could not go beyond 24 hours, as among them 3 (4.61%) had previous uterine scar and 2 (3.07%) developed ruptured membranes after 12 hours of admission and their babies also could not survive. Mean pregnancy prolongation was 15.35 +/- 9.45 days (min: 4 max: 35), so delivery was deferred up to 48 hours, 3 to 7 days and more than 7 days in 4 (6.15%), 6 (9.23%) and 50 (76.92%) respectively. Glyceryl trinitrate, trans dermal patch is effective and safe tocolytic in idiopathic preterm labour. By prolonging pregnancy it improves neonatal outcome.

  5. Effect of Microneedle Type on Transdermal Permeation of Rizatriptan.

    Science.gov (United States)

    Uppuluri, Chandrateja; Shaik, Ashraf Sultana; Han, Tao; Nayak, Atul; Nair, Karthik J; Whiteside, Benjamin R; Nalluri, Buchi N; Das, Diganta B

    2017-07-01

    The present study was aimed to investigate the effect of salient microneedle (MN) geometry parameters like length, density, shape and type on transdermal permeation of rizatriptan (RIZ). Studies were carried out using two types of MN devices viz. AdminPatch® arrays (ADM) (0.6, 0.9, 1.2 and 1.5 mm lengths) and laboratory-fabricated polymeric MNs (PMs) of 0.6 mm length. In the case of the PMs, arrays were applied three times at different places within a 1.77-cm 2 skin area (PM-3) to maintain the MN density closer to 0.6 mm ADM. Histological studies revealed that PM, owing to their geometry/design, formed wider and deeper microconduits when compared to ADM of similar length. Approximately 4.9- and 4.2-fold increases in the RIZ steady-state flux values were observed with 1.5 mm ADM and PM-3 applications when compared to the passive studies. A good correlation between different dimensionless parameters like the amount of RIZ permeated (C t /C s ), thickness (h/L) and surface area (S a /L 2 ) of the skin was observed with scaling analyses. Numerical simulations provided further information regarding the distribution of RIZ in MN-treated skin after application of different MNs. Overall, the study suggests that MN application enhances the RIZ transdermal permeation and the geometrical parameters of MNs play an important role in the degree enhancement.

  6. Single-molecule experiments in biological physics: methods and applications.

    Science.gov (United States)

    Ritort, F

    2006-08-16

    I review single-molecule experiments (SMEs) in biological physics. Recent technological developments have provided the tools to design and build scientific instruments of high enough sensitivity and precision to manipulate and visualize individual molecules and measure microscopic forces. Using SMEs it is possible to manipulate molecules one at a time and measure distributions describing molecular properties, characterize the kinetics of biomolecular reactions and detect molecular intermediates. SMEs provide additional information about thermodynamics and kinetics of biomolecular processes. This complements information obtained in traditional bulk assays. In SMEs it is also possible to measure small energies and detect large Brownian deviations in biomolecular reactions, thereby offering new methods and systems to scrutinize the basic foundations of statistical mechanics. This review is written at a very introductory level, emphasizing the importance of SMEs to scientists interested in knowing the common playground of ideas and the interdisciplinary topics accessible by these techniques. The review discusses SMEs from an experimental perspective, first exposing the most common experimental methodologies and later presenting various molecular systems where such techniques have been applied. I briefly discuss experimental techniques such as atomic-force microscopy (AFM), laser optical tweezers (LOTs), magnetic tweezers (MTs), biomembrane force probes (BFPs) and single-molecule fluorescence (SMF). I then present several applications of SME to the study of nucleic acids (DNA, RNA and DNA condensation) and proteins (protein-protein interactions, protein folding and molecular motors). Finally, I discuss applications of SMEs to the study of the nonequilibrium thermodynamics of small systems and the experimental verification of fluctuation theorems. I conclude with a discussion of open questions and future perspectives.

  7. Single-molecule experiments in biological physics: methods and applications

    International Nuclear Information System (INIS)

    Ritort, F

    2006-01-01

    I review single-molecule experiments (SMEs) in biological physics. Recent technological developments have provided the tools to design and build scientific instruments of high enough sensitivity and precision to manipulate and visualize individual molecules and measure microscopic forces. Using SMEs it is possible to manipulate molecules one at a time and measure distributions describing molecular properties, characterize the kinetics of biomolecular reactions and detect molecular intermediates. SMEs provide additional information about thermodynamics and kinetics of biomolecular processes. This complements information obtained in traditional bulk assays. In SMEs it is also possible to measure small energies and detect large Brownian deviations in biomolecular reactions, thereby offering new methods and systems to scrutinize the basic foundations of statistical mechanics. This review is written at a very introductory level, emphasizing the importance of SMEs to scientists interested in knowing the common playground of ideas and the interdisciplinary topics accessible by these techniques. The review discusses SMEs from an experimental perspective, first exposing the most common experimental methodologies and later presenting various molecular systems where such techniques have been applied. I briefly discuss experimental techniques such as atomic-force microscopy (AFM), laser optical tweezers (LOTs), magnetic tweezers (MTs), biomembrane force probes (BFPs) and single-molecule fluorescence (SMF). I then present several applications of SME to the study of nucleic acids (DNA, RNA and DNA condensation) and proteins (protein-protein interactions, protein folding and molecular motors). Finally, I discuss applications of SMEs to the study of the nonequilibrium thermodynamics of small systems and the experimental verification of fluctuation theorems. I conclude with a discussion of open questions and future perspectives. (topical review)

  8. New methods for assessing the fascinating nature of nature experiences.

    Science.gov (United States)

    Joye, Yannick; Pals, Roos; Steg, Linda; Evans, Ben Lewis

    2013-01-01

    In recent years, numerous environmental psychology studies have demonstrated that contact with nature as opposed to urban settings can improve an individual's mood, can lead to increased levels of vitality, and can offer an opportunity to recover from stress. According to Attention Restoration Theory (ART) the restorative potential of natural environments is situated in the fact that nature can replenish depleted attentional resources. This replenishment takes place, in part, because nature is deemed to be a source of fascination, with fascination being described as having an "attentional", an "affective" and an "effort" dimension. However, the claim that fascination with nature involves these three dimensions is to a large extent based on intuition or derived from introspection-based measurement methods, such as self-reports. In three studies, we aimed to more objectively assess whether these three dimensions indeed applied to experiences related to natural environments, before any (attentional) depletion has taken place. The instruments that were used were: (a) the affect misattribution procedure (Study 1), (b) the dot probe paradigm (Study 2) and (c) a cognitively effortful task (Study 3). These instrument were respectively aimed at verifying the affective, attentional and effort dimension of fascination. Overall, the results provide objective evidence for the claims made within the ART framework, that natural as opposed to urban settings are affectively positive (cfr., affective dimension) and that people have an attentional bias to natural (rather than urban) environments (cfr., attentional dimension). The results regarding the effort dimension are less straightforward, and suggest that this dimension only becomes important in sufficiently difficult cognitive tasks.

  9. New Methods for Assessing the Fascinating Nature of Nature Experiences

    Science.gov (United States)

    Joye, Yannick; Pals, Roos; Steg, Linda; Evans, Ben Lewis

    2013-01-01

    In recent years, numerous environmental psychology studies have demonstrated that contact with nature as opposed to urban settings can improve an individual’s mood, can lead to increased levels of vitality, and can offer an opportunity to recover from stress. According to Attention Restoration Theory (ART) the restorative potential of natural environments is situated in the fact that nature can replenish depleted attentional resources. This replenishment takes place, in part, because nature is deemed to be a source of fascination, with fascination being described as having an “attentional”, an “affective” and an “effort” dimension. However, the claim that fascination with nature involves these three dimensions is to a large extent based on intuition or derived from introspection-based measurement methods, such as self-reports. In three studies, we aimed to more objectively assess whether these three dimensions indeed applied to experiences related to natural environments, before any (attentional) depletion has taken place. The instruments that were used were: (a) the affect misattribution procedure (Study 1), (b) the dot probe paradigm (Study 2) and (c) a cognitively effortful task (Study 3). These instrument were respectively aimed at verifying the affective, attentional and effort dimension of fascination. Overall, the results provide objective evidence for the claims made within the ART framework, that natural as opposed to urban settings are affectively positive (cfr., affective dimension) and that people have an attentional bias to natural (rather than urban) environments (cfr., attentional dimension). The results regarding the effort dimension are less straightforward, and suggest that this dimension only becomes important in sufficiently difficult cognitive tasks. PMID:23922645

  10. Evaluation of skin absorption of drugs from topical and transdermal formulations

    Directory of Open Access Journals (Sweden)

    André Luís Morais Ruela

    Full Text Available ABSTRACT The skin barrier function has been attributed to the stratum corneum and represents a major challenge in clinical practice pertaining to cutaneous administration of drugs. Despite this, a large number of bioactive compounds have been successfully administered via cutaneous administration because of advances in the design of topical and transdermal formulations. In vitro and in vivo evaluations of these novel drug delivery systems are necessary to characterize their quality and efficacy. This review covers the most well-known methods for assessing the cutaneous absorption of drugs as an auxiliary tool for pharmaceutical formulation scientists in the design of drug delivery systems. In vitro methods as skin permeation assays using Franz-type diffusion cells, cutaneous retention and tape-stripping methods to study the cutaneous penetration of drugs, and in vivo evaluations as pre-clinical pharmacokinetic studies in animal models are discussed. Alternative approaches to cutaneous microdialysis are also covered. Recent advances in research on skin absorption of drugs and the effect of skin absorption enhancers, as investigated using confocal laser scanning microscopy, Raman confocal microscopy, and attenuated total reflectance Fourier-transform infrared spectroscopy, are reviewed.

  11. High-Performance Liquid Chromatographic Ultraviolet Determination of Memantine Hydrochloride after In Vitro Transdermal Diffusion Studies

    Directory of Open Access Journals (Sweden)

    Sergio del Rio-Sancho

    2013-01-01

    Full Text Available The purpose of the present work was to validate an accurate and precise high-performance liquid chromatography (HPLC method involving ultraviolet detection for the quantitative analysis of memantine hydrochloride. In order to analyze a molecule with no chromophoric groups that could be detected by a UV/visible detector, it was necessary to extract the drug and to perform a dansylation reaction that enabled the UV/visible detection of the derivatized molecule. Separation was carried out with a 150 mm Kromasil C18 column at room temperature. The detection response, at 218 nm, was found to be linear in the concentration range from 0.5 to 50 μg/mL. The method was validated for specificity, linearity, precision, accuracy, limit of detection, limit of quantification, and robustness. The limit of detection (LOD was 0.144 μg/mL, and the limit of quantification (LOQ was 0.437 μg/mL. The dansylated memantine complex was stable for at least five days in all the conditions evaluated. The potential use of this method has been demonstrated by the quantification of memantine hydrochloride contained in samples from the study of its in vitro transdermal permeation.

  12. Successful transdermal allergen delivery and allergen-specific immunotherapy using biodegradable microneedle patches.

    Science.gov (United States)

    Kim, Ji Hye; Shin, Jung U; Kim, Seo Hyeong; Noh, Ji Yeon; Kim, Hye Ran; Lee, Jungsoo; Chu, Howard; Jeong, Kyoung Yong; Park, Kyung Hee; Kim, Jung Dong; Kim, Hong Kee; Jeong, Do Hyeon; Yong, Tai-Soon; Park, Jung-Won; Lee, Kwang Hoon

    2018-01-01

    Allergen-specific immunotherapy (SIT) is an effective treatment modality for allergic diseases such as atopic dermatitis (AD). However, frequent visits over a 3-year period as well as looming adverse events tend to discourage patient compliance. Therefore, a more convenient, effective, and safe method of SIT is needed. For several decades, use of microneedles has been promoted as an efficient and precise transdermal drug delivery method. In this study, we developed Dermatophagoides farinae (D. farinae) extract (DfE)-loaded microneedle patches, and evaluated their safety and efficacy as a novel SIT method. After 4 weeks of patch application, efficient allergen delivery and successful induction of immune response to DfE were demonstrated in mice, with no apparent adverse events. AD-induced NC/Nga mice received microneedle immunotherapy (MNIT) (10 μg), subcutaneous immunotherapy (SCIT) (10 μg), SCIT (100 μg), or placebo. Both MNIT (10 μg) and SCIT (100 μg) treatments improved clinical and histologic manifestations of AD skin lesions, altered immunoglobulin production, dampened Th2 cellular response, and boosted Treg infiltrates, without significant side effects; whereas SCIT (10 μg) or placebo subsets failed to show any effects. Based on the favorable safety and efficacy profiles demonstrated in mice by MNIT in the current study, we believe that MNIT may serve as a new SIT modality. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. On Teaching Methods: The Personal Experiences of Teachers of English

    Science.gov (United States)

    Kong, Melinda L. F.

    2017-01-01

    With the globalization and internationalization of education, many teachers from Asian countries pursue their professional development in English-speaking settings. However, there seems to be scarce research on these teachers' expectations, lived experiences and identities in these contexts, and how their personal experiences influence their views…

  14. Formulation and in vitro/in vivo evaluation of levodopa transdermal delivery systems.

    Science.gov (United States)

    Lee, Kyung Eun; Choi, Yun Jung; Oh, Byu Ree; Chun, In Koo; Gwak, Hye Sun

    2013-11-18

    This study aims to investigate the feasibility of Levodopa transdermal delivery systems (TDSs). Levodopa TDSs were formulated using various vehicles and permeation enhancers, and in vitro permeation and in vivo pharmacokinetic studies were carried out. In the in vitro study, ester-type vehicles showed relatively high enhancing effects; propylene glycol monocaprylate and propylene glycol monolaurate showed the highest permeation fluxes from both solution and pressure sensitive adhesive (PSA) TDS formulations. Lag time was dramatically shortened with PSA TDS formulations as compared with solution formulations. In the in vivo study, the addition of fatty acids increased blood drug concentrations regardless of the kind or concentration of fatty acid; the AUCinf increased up to 8.7 times as compared with propylene glycol (PG) alone. PSA TDS containing 10% linoleic acid exhibited prolonged Tmax as compared with oral form. Total clearance of L-dopa from PSA TDSs was significantly lower than from oral form (up to 86.8 times). Especially, PSA TDS containing 10% linoleic acid (LOA) revealed 76.2 fold higher AUCinf than oral administration. Based on our results, the L-dopa PSA TDS containing PG with 10% LOA could be used as a good adjuvant therapy for Parkinson's disease patients who experience symptom fluctuation by L-dopa oral administration. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Methods of RVD object pose estimation and experiments

    Science.gov (United States)

    Shang, Yang; He, Yan; Wang, Weihua; Yu, Qifeng

    2007-11-01

    Methods of measuring a RVD (rendezvous and docking) cooperative object's pose from monocular and binocular images respectively are presented. The methods solve the initial values first and optimize the object pose parameters by bundle adjustment. In the disturbance-rejecting binocular method, chosen measurement system parameters of one camera's exterior parameters are modified simultaneously. The methods need three or more cooperative target points to measure the object's pose accurately. Experimental data show that the methods converge quickly and stably, provide accurate results and do not need accurate initial values. Even when the chosen measurement system parameters are subjected to some amount of disturbance, the binocular method manages to provide fairly accurate results.

  16. Corticosteroid transdermal delivery to target swelling, edema and inflammation following facial rejuvenation procedures

    Directory of Open Access Journals (Sweden)

    Iannitti T

    2013-09-01

    Full Text Available T Iannitti,1,2 V Rottigni,2,3 B Palmieri2,31School of Biomedical Sciences, University of Leeds, Leeds, UK; 2Poliambulatorio del Secondo Parere, Modena, Italy; 3Department of General Surgery and Surgical Specialties, University of Modena and Reggio Emilia Medical School, Surgical Clinic, Modena, ItalyBackground and aim: The use of transdermal therapeutic systems has spread worldwide since they allow effective local drug delivery. In the present study, we investigated the efficacy and safety of a new betamethasone valerate medicated plaster (Betesil® to manage facial swelling, edema, inflammation, ecchymosis, and hematoma, when applied immediately after a facial rejuvenation procedure.Materials and methods: We applied the plaster to the skin of 20 healthy patients for 12 hours immediately after hyaluronic acid-based procedure performed with the aim of erasing facial wrinkles of perioral and nasolabial folds and improving chin and eye contour. A further 20 patients underwent the same cosmetic procedure, but they were treated with an aescin 10% cream (applied immediately after the procedure, in the evening, and the morning after and served as control group.Results: Betesil® application resulted in a significant improvement in swelling/edema/inflammation score, if compared with aescin 10% cream (P < 0.01. As for facial ecchymosis and hematoma around the needle injection track, only two patients in the active treatment group displayed minimal ecchymosis and hematoma. In the control group, two patients presented minimal ecchymosis and three slight hematoma. However, using the ecchymosis/hematoma score, no significant difference between Betesil® and aescin 10% cream groups was observed. Patients’ satisfaction was significantly higher among subjects receiving Betesil®, if compared to patients receiving aescin 10% cream (P < 0.01.Conclusion: The present study supports the use of Betesil® plaster immediately after facial cosmetic procedures in order

  17. Postoperative pain management with transdermal fentanyl after forefoot surgery: a randomized, placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Merivirta R

    2015-01-01

    Full Text Available Riika Merivirta,1 Mikko Pitkänen,2 Jouko Alanen,3 Elina Haapoja,1 Mari Koivisto,4 Kristiina Kuusniemi11Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine of Turku University Hospital and University of Turku, Turku, 2Department of Anaesthesia, Hospital Orton, Invalid Foundation, Helsinki, 3Terveystalo Clinic Hospital, Helsinki, 4Department of Biostatistics, University of Turku, Turku, FinlandBackground: Quality of life is decreased in patients with hallux valgus deformity, mainly because of pain. Significant improvement is usually achieved by surgery. However, postoperative pain can be moderate to severe for 2–3 days. The aim of the present study was to evaluate the use of transdermal fentanyl for postoperative pain management after forefoot surgery.Methods: Sixty patients undergoing hallux valgus or hallux rigidus surgery were allocated to receive a patch delivering either fentanyl 12 µg/hour or placebo for postoperative pain. The consumption of rescue opioid oxycodone, the primary outcome measure, was evaluated daily until the fourth postoperative day. Total consumption of oxycodone during the study period was also assessed. Pain scores and possible adverse effects were evaluated every 6 hours during the first 24 hours and on the fourth postoperative day.Results: The use of rescue opioid was low in both groups, the median (range consumption of oxycodone being 10 (0–50 mg on the day of surgery (no difference between the groups, P=0.31 and 0 (0–35 mg thereafter. The total combined consumption was 10 (0–105 mg in the fentanyl group and 20 (0–70 mg in the placebo group (P=0.23. There were no statistically significant differences in pain scores or adverse effects between the groups.Conclusion: As a part of multimodal analgesia with ibuprofen and acetaminophen, a patch delivering fentanyl 12 µg/hour did not significantly decrease the consumption of rescue opioid or pain scores after forefoot surgery

  18. Development of matrix type transdermal patches of lercanidipine hydrochloride: physicochemical and in-vitro characterization

    Directory of Open Access Journals (Sweden)

    T Mamatha

    2010-03-01

    Full Text Available Background and the purpose of the study: Lercanidipine hydrochloride (LRDP is used in the treatment of hypertension because of its selectivity and specificity on the smooth vascular cells. The pharmacokinetic parameters make LRDP a suitable candidate for transdermal delivery. The purpose of the study was to select a suitable formulation for the development of transdermal drug-delivery system (TDDS of LRDP and to determine the effect of penetration enhancer, limonene on drug permeation. Methods: The matrix type TDDS of LRDP were prepared by solvent evaporation technique. Formulations A1, A2, A3, A4, A5 and A6 were composed of Eudragit RL100 (ERL and hydroxypropyl methyl cellulose (HPMC in 1.5:8.5, 3:7, 4:6, 6:4, 7:3 and 8.5:1.5 ratios respectively. All the six formulations carried 10 mg of LRDP/patch area, 8 % v/w of d-limonene as a penetration enhancer, 20 % v/w of propylene glycol as plasticizer in methanol and dichloromethane as solvent system. The prepared TDDS were evaluated for physicochemical characteristics, in-vitro release, ex-vivo permeation and skin irritation. The ex-vivo permeation studies were carried out across excised rat skin using Franz diffusion cell. Results: All the formulations exhibited satisfactory physicochemical characteristics. Cumulative percentage of the drug released in 24 hrs from the six formulations were 82.0 %, 74.9 %, 63.2 %, 63.5 %, 59.8 % and 53.5 % respectively. Corresponding values for the cumulative amounts of the drug permeated across the rat skin for the above matrix films were 2644.5, 2347.2, 2249.5, 1933.4, 2021.5 and 1663.4 µg/cm2 respectively. By fitting the data into zero order, first order and Higuchi model, it was concluded that drug release from matrix films followed Higuchi model and the mechanism of the drug release was diffusion mediated. The patches were seemingly free of potentially hazardous skin irritation.  Conclusions: The patches composed of ERL, HPMC (1.5:8.5 with 8 % v/w limonene as

  19. Recent Advances in Skin Penetration Enhancers for Transdermal Gene and Drug Delivery.

    Science.gov (United States)

    Amjadi, Morteza; Mostaghaci, Babak; Sitti, Metin

    2017-01-01

    There is a growing interest in transdermal delivery systems because of their noninvasive, targeted, and on-demand delivery of gene and drugs. However, efficient penetration of therapeutic compounds into the skin is still challenging largely due to the impermeability of the outermost layer of the skin, known as stratum corneum. Recently, there have been major research activities to enhance the skin penetration depth of pharmacological agents. This article reviews recent advances in the development of various strategies for skin penetration enhancement. We show that approaches such as ultrasound waves, laser, and microneedle patches have successfully been employed to physically disrupt the stratum corneum structure for enhanced transdermal delivery. Rather than physical approaches, several non-physical route have also been utilized for efficient transdermal delivery across the skin barrier. Finally, we discuss some clinical applications of transdermal delivery systems for gene and drug delivery. This paper shows that transdermal delivery devices can potentially function for diverse healthcare and medical applications while further investigations are still necessary for more efficient skin penetration of gene and drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Systemic delivery of β-blockers via transdermal route for hypertension

    Science.gov (United States)

    Ahad, Abdul; Al-Jenoobi, Fahad I.; Al-Mohizea, Abdullah M.; Akhtar, Naseem; Raish, Mohammad; Aqil, Mohd.

    2014-01-01

    Hypertension is the most common cardiovascular disease worldwide. Moreover, management of hypertension requires long-term treatment that may result in poor patient compliance with conventional dosage forms due to greater frequency of drug administration. Although there is availability of a plethora of therapeutically effective antihypertensive molecules, inadequate patient welfare is observed; this arguably presents an opportunity to deliver antihypertensive agents through a different route. Ever since the transdermal drug delivery came into existence, it has offered great advantages including non-invasiveness, prolonged therapeutic effect, reduced side effects, improved bioavailability, better patient compliance and easy termination of drug therapy. Attempts were made to develop the transdermal therapeutic system for various antihypertensive agents, including β-blockers, an important antihypertensive class. β-blockers are potent, highly effective in the management of hypertension and other heart ailments by blocking the effects of normal amounts of adrenaline in the heart and blood vessels. The shortcomings associated with β-blockers such as more frequent dose administration, extensive first pass metabolism and variable bioavailability, make them an ideal candidate for transdermal therapeutic systems. The present article gives a brief view of different β-blockers formulated as transdermal therapeutic system in detail to enhance the bioavailability as well as to improve patient compliance. Constant improvement in this field holds promise for the long-term success in technologically advanced transdermal dosage forms being commercialized sooner rather than later. PMID:26702253

  1. Poly(lactic-co-glycolic) acid drug delivery systems through transdermal pathway: an overview.

    Science.gov (United States)

    Naves, Lucas; Dhand, Chetna; Almeida, Luis; Rajamani, Lakshminarayanan; Ramakrishna, Seeram; Soares, Graça

    2017-05-01

    In past few decades, scientists have made tremendous advancement in the field of drug delivery systems (DDS), through transdermal pathway, as the skin represents a ready and large surface area for delivering drugs. Efforts are in progress to design efficient transdermal DDS that support sustained drug release at the targeted area for longer duration in the recommended therapeutic window without producing side-effects. Poly(lactic-co-glycolic acid) (PLGA) is one of the most promising Food and Drug Administration approved synthetic polymers in designing versatile drug delivery carriers for different drug administration routes, including transdermal drug delivery. The present review provides a brief introduction over the transdermal drug delivery and PLGA as a material in context to its role in designing drug delivery vehicles. Attempts are made to compile literatures over PLGA-based drug delivery vehicles, including microneedles, nanoparticles, and nanofibers and their role in transdermal drug delivery of different therapeutic agents. Different nanostructure evaluation techniques with their working principles are briefly explained.

  2. Transport efficiency in transdermal drug delivery: What is the role of fluid microstructure?

    Science.gov (United States)

    Liuzzi, Roberta; Carciati, Antonio; Guido, Stefano; Caserta, Sergio

    2016-03-01

    Interaction of microstructured fluids with skin is ubiquitous in everyday life, from the use of cosmetics, lotions, and drugs, to personal care with detergents or soaps. The formulation of microstructured fluids is crucial for the control of the transdermal transport. In biomedical applications transdermal delivery is an efficient approach, alternative to traditional routes like oral and parenteral administration, for local release of drugs. Poor skin permeability, mainly due to its outer layer, which acts as the first barrier against the entry of external compounds, greatly limits the applicability of transdermal delivery. In this review, we focus on recent studies on the improvement of skin transport efficiency by using microemulsions (ME). Quantitative techniques, which are able to investigate both skin morphology and penetration processes, are also reviewed. ME are increasingly used as transdermal systems due to their low preparation cost, stability and high bioavailability. ME may act as penetration enhancers for many active principles, but ME microstructure should be chosen appropriately considering several factors such as ratio and type of ingredients and physic-chemical properties of the active components. ME microstructure is strongly affected by the flow conditions applied during processing, or during spreading and rubbing onto skin. Although the role played by ME microstructure has been generally recognized, the skin transport mechanisms associated with different ME microstructures are still to be elucidated and further investigations are required to fully exploit the potential of ME in transdermal delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Nanoemulsions as vehicles for transdermal delivery of glycyrrhizin

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    Ranjit Kumar Harwansh

    2011-12-01

    Full Text Available The present investigation aims to evaluate an isotropic and thermodynamically stable nanoemulsion formulation for transdermal delivery of glycyrrhizin (GZ, with minimum surfactant and cosurfactant (Smix concentrations that could improve its solubility, permeation enhancement, and stability. Pseudo-ternary phase diagrams were developed and various nanoemulsion formulations were prepared using soyabean oil as oil, Span 80, Brij 35 as a surfactant and isopropyl alcohol as a cosurfactant. Nanoemulsion formulations that passed the thermodynamic stability tests were characterized for pH, viscosity and droplet size using a transmission electron microscopy. The transdermal ability of glycyrrhizin through human cadaver skin was determined using Franz diffusion cells. The in vitro skin permeation profile of the optimized nanoemulsion formulation (NE2 was compared to that of conventional gel. A significant increase in permeability parameters such as steady-state flux (Jss and permeability coefficient (Kp was observed in the optimized nanoemulsion formulation (NE2, which consisted of 1% wt/wt of mono ammonium glycyrrhizinate (MAG, 32.4% Span 80, 3.7% Brij 35, 10% isopropyl alcohol, 46.5% soyabean oil and 6.4% distilled water. No obvious skin irritation was observed for the studied nanoemulsion formulation (NE2 or the gel. The results indicated that nanoemulsions are promising vehicles for transdermal delivery of glycyrrhizin through human cadaver skin, without the use of additional permeation enhancers, because excipients of nanoemulsions act as permeation enhancers themselves.O objetivo da investigação é avaliar uma nanoemulsão isotrópica termodinamicamente estável para a administração transdérmica da glicirrizina (GZ, com concentrações mínimas de tensoativo e co-tensoativo (Smix, que poderiam melhorar a sua solubilidade, a permeação e a estabilidade. Os diagramas pseudo-ternários de fase foram desenvolvidos e diversas nanoemulsões foram

  4. Effects of user experience and method in the inflation of ...

    African Journals Online (AJOL)

    Context: Endotracheal tube cuff pressure (ETCP) is recommended to be maintained between 20.30 cmH2O limits. While insufficient inflation of ETC may cause aspirations, over.inflation of it may lead to damage in tracheal epithelium. Aims: We planned to investigate the effects of user experience and cuff pressure inflation ...

  5. Evaluation of Mechanical Properties of Nonsteroidal Anti-Inflammatory Matrix Type Transdermal Therapeutic Systems

    Directory of Open Access Journals (Sweden)

    Antonoaea Paula

    2017-06-01

    Full Text Available Objective: Transdermal therapeutic systems (TTSs represent an intensely studied alternative to oral delivery of non-steroid anti-inflammatory drugs (NSAIDs in the treatment of rheumatic diseases due to its ability of avoiding the side effects of the oral route. This study aims to present the evaluation of the mechanical properties of three NSAIDs (meloxicam, tenoxicam and indomethacin individually included in four type of polymeric matrixes, as part of new formulations development process. Methods: 12 products in form of TTS matrixes were prepared by solvent casting evaporation technique, using hydroxypropyl methylcellulose (HPMC 15000, HPMC E5 and/or ethylcellulose as matrix-forming polymers. Each of the resulted products was evaluated by determining the water vapor absorption, desorption or transmission in controlled atmosphere humidity (evaluation of porosity; the elongation capacity, tensile strength and bioadhesiveness (evaluation of mechanical properties. Results: The analysis of three groups of the experimental data expressed as averages on each group was necessary, in order to identify the parameters which statistically are critically influenced by the ingredients associated in the TTSs matrix compositions. Analysis by normality tests, variance and correlation tests (Anova, Pearson enabled evaluation of the effect of NSAID type vs. the effect of polymer matrix type on the parameters of the NSAID TTS matrix. Conclusions: Meloxicam incorporated in the structure of HPMC 15000 polymeric matrix favors its viscoelastic structure. Ethylcellulose functions as plasticizer and supports the matrix bioadhesiveness. HPMC E5 does not meet the requirements for TTS preparation in the used experimental conditions.

  6. ATRP-based synthesis and characterization of light-responsive coatings for transdermal delivery systems

    Science.gov (United States)

    Pauly, Anja C.; Schöller, Katrin; Baumann, Lukas; Rossi, René M.; Dustmann, Kathrin; Ziener, Ulrich; de Courten, Damien; Wolf, Martin; Boesel, Luciano F.; Scherer, Lukas J.

    2015-06-01

    The grafting of poly(hydroxyethylmethacrylate) on polymeric porous membranes via atom transfer radical polymerization (ATRP) and subsequent modification with a photo-responsive spiropyran derivative is described. This method leads to photo-responsive membranes with desirable properties such as light-controlled permeability changes, exceptional photo-stability and repeatability of the photo-responsive switching. Conventional track etched polyester membranes were first treated with plasma polymer coating introducing anchoring groups, which allowed the attachment of ATRP-initiator molecules on the membrane surface. Surface initiated ARGET-ATRP of hydroxyethylmethacrylate (where ARGET stands for activator regenerated by electron transfer) leads to a membrane covered with a polymer layer, whereas the controlled polymerization procedure allows good control over the thickness of the polymer layer in respect to the polymerization conditions. Therefore, the final permeability of the membranes could be tailored by choice of pore diameter of the initial membranes, applied monomer concentration or polymerization time. Moreover a remarkable switch in permeability (more than 1000%) upon irradiation with UV-light could be achieved. These properties enable possible applications in the field of transdermal drug delivery, filtration, or sensing.

  7. A Computational Procedure for Assessing the Dynamic Performance of Diffusion-Controlled Transdermal Delivery Devices

    Directory of Open Access Journals (Sweden)

    Laurent Simon

    2011-08-01

    Full Text Available Abstract: The dynamic performances of two different controlled-release systems were analyzed. In a reservoir-type drug-delivery patch, the transdermal flux is influenced by the properties of the membrane. A constant thermodynamic drug activity is preserved in the donor compartment. Monolithic matrices are among the most inexpensive systems used to direct drug delivery. In these structures, the active pharmaceutical ingredients are encapsulated within a polymeric material. Despite the popularity of these two devices, to tailor the properties of the polymer and additives to specific transient behaviors can be challenging and time-consuming. The heuristic approaches often considered to select the vehicle formulation provide limited insight into key permeation mechanisms making it difficult to predict the device performance. In this contribution, a method to calculate the flux response time in a system consisting of a reservoir and a polymeric membrane was proposed and confirmed. Nearly 8.60 h passed before the metoprolol delivery rate reached ninety-eight percent of its final value. An expression was derived for the time it took to transport the active pharmaceutical ingredient out of the polymer. Ninety-eight percent of alpha-tocopherol acetate was released in 461.4 h following application to the skin. The effective time constant can be computed to help develop optimum design strategies.

  8. Applications and limitations of lipid nanoparticles in dermal and transdermal drug delivery via the follicular route.

    Science.gov (United States)

    Lauterbach, Andreas; Müller-Goymann, Christel C

    2015-11-01

    Lipid nanoparticles (LN) such as solid lipid nanoparticles (SLN) and nanolipid carriers (NLC) feature several claimed benefits for topical drug therapy including biocompatible ingredients, drug release modification, adhesion to the skin, and film formation with subsequent hydration of the superficial skin layers. However, penetration and permeation into and across deeper skin layers are restricted due to the barrier function of the stratum corneum (SC). As different kinds of nanoparticles provide the potential for penetration into hair follicles (HF) LN are applicable drug delivery systems (DDS) for this route in order to enhance the dermal and transdermal bioavailability of active pharmaceutical ingredients (API). Therefore, this review addresses the HF as application site, published formulations of LN which showed follicular penetration (FP), and characterization methods in order to identify and quantify the accumulation of API delivered by the LN in the HF. Since LN are based on lipids that appear in human sebum which is the predominant medium in HF an increased localization of the colloidal carriers as well as a promoted drug release may be assumed. Therefore, sebum-like lipid material and a size of less or equal 640 nm are appropriate specifications for FP of particulate formulations. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Enhancing topical analgesic administration: review and prospect for transdermal and transbuccal drug delivery systems.

    Science.gov (United States)

    Sanz, Roser; Calpena, Ana C; Mallandrich, Mireia; Clares, Beatriz

    2015-01-01

    Topical administration is an appealing method for drug delivery due to its non-invasiveness, self-controlled application, avoidance of first-pass metabolism in the liver and reduction of systemic side effects compared to other conventional routes such as oral and parenteral. However, topical administration must overcome the permeable barriers that skin and mucosa represent for the drug to achieve its desired therapeutic effect. Penetration of drugs through human skin is mainly impaired by the stratum corneum- the uppermost keratinized skin layer. In contrast, the stratified squamous epithelium (a nonkeratinized tissue) represents the major physical barrier for transbuccal drug administration in humans. Different technologies have been studied to enhance the bioavailability or local effects of drugs administered through skin and buccal mucosa. Those technologies involve the use of physical or chemical enhancers and new dosage forms such as vesicles, cyclodextrins, nanoparticles and other complex systems. Combinations of these technologies may further increase drug delivery in some cases. As analgesia is one of the main therapeutic effects sought through topical administration, this paper focuses on the review of drug delivery systems to improve the topical and transdermal/transbuccal drug delivery of substances with known analgesic action. A discussion of their possibilities and limitations is also included.

  10. Effect of Transdermal Tulobuterol Added to Inhaled Corticosteroids in Asthma Patients

    Directory of Open Access Journals (Sweden)

    Gen Tamura

    2005-01-01

    Methods: A randomized, double-blind, double-dummy, parallel-group, multicenter trial was conducted. Male and female patients with a diagnosis of asthma requiring inhaled short-acting β2-agonists despite treatment with inhaled corticosteroids took tulobuterol tape (1 mg or 2 mg and corresponding placebo tapes for 4 weeks. Results: Mean morning peak expiratory flows (PEF in the 1 and 2 mg/day groups were significantly increased from the baseline value by 23.8 and 35.9 L/min at week 4, respectively. The increase in mean morning PEF in the 2 mg/day group was significantly higher than that in the 1 mg/day group. The mean evening PEF was significantly increased in both treatment groups compared with baseline values. Although the increase in mean evening PEF in the 2 mg/day group was greater than that in the 1 mg/day group, the difference between groups was statistically significant only at week 1. The safety profiles of the two treatments were similar. Conclusions: In patients with persistent asthma who require inhaled short-acting β2-agonists while receiving inhaled corticosteroids, transdermal tulobuterol significantly improved PEF in a dose-dependent manner, i.e., greater effect with 2 mg than with 1 mg per day.

  11. ATRP-based synthesis and characterization of light-responsive coatings for transdermal delivery systems

    International Nuclear Information System (INIS)

    Pauly, Anja C; Schöller, Katrin; Baumann, Lukas; Rossi, René M; Dustmann, Kathrin; Boesel, Luciano F; Scherer, Lukas J; Ziener, Ulrich; De Courten, Damien; Wolf, Martin

    2015-01-01

    The grafting of poly(hydroxyethylmethacrylate) on polymeric porous membranes via atom transfer radical polymerization (ATRP) and subsequent modification with a photo-responsive spiropyran derivative is described. This method leads to photo-responsive membranes with desirable properties such as light-controlled permeability changes, exceptional photo-stability and repeatability of the photo-responsive switching. Conventional track etched polyester membranes were first treated with plasma polymer coating introducing anchoring groups, which allowed the attachment of ATRP-initiator molecules on the membrane surface. Surface initiated ARGET–ATRP of hydroxyethylmethacrylate (where ARGET stands for activator regenerated by electron transfer) leads to a membrane covered with a polymer layer, whereas the controlled polymerization procedure allows good control over the thickness of the polymer layer in respect to the polymerization conditions. Therefore, the final permeability of the membranes could be tailored by choice of pore diameter of the initial membranes, applied monomer concentration or polymerization time. Moreover a remarkable switch in permeability (more than 1000%) upon irradiation with UV-light could be achieved. These properties enable possible applications in the field of transdermal drug delivery, filtration, or sensing. (focus issue paper)

  12. Preparation, characterization and permeation studies of a nanovesicular system containing diclofenac for transdermal delivery.

    Science.gov (United States)

    Gaur, Praveen Kumar; Purohit, Suresh; Kumar, Yatendra; Mishra, Shikha; Bhandari, Anil

    2014-02-01

    Transdermal formulations contain permeation enhancer which causes skin damage. Ceramide 2 is natural lipid found in stratum corneum (SC). Drug-loaded nanovesicles of ceramide-2, cholesterol, palmitic acid, cholesteryl sulfate were formulated and analyzed for physical and biological properties. Diclofenac was used as a model drug. The vesicles were prepared using the film hydration method and characterized for physical parameters, in vitro drug release, accelerated stability studies and formulated into gel. Respective gels were compared with a commercial formulation (CEG) and plain carbopol gel (CG) containing drug for ex vivo, in vivo drug permeation and anti-inflammatory activity. The vesicles were stable with optimum physical parameters. DCG-1 showed 92.89% in vitro drug release. Ceramide vesicles showed drug release between 18 and 25 μg/cm(2) whereas CG and CEG released 0.33 and 1.35 μg/cm(2) drug, respectively. DCG-1 and CEG showed corresponding Cmax at 6 and 4 h, respectively. DCG-1 showed six times AUC than CEG. DCG-1 inhibited edema by 86.37% by 4th hour of application. The presence of ceramide 2 specifically promotes the drug permeation through SC and dermis and also contribute towards stability and non-irritancy. The composition of the nanovesicle played an important role in physical properties and drug permeation.

  13. Potential of Essential Oils as Penetration Enhancers for Transdermal Administration of Ibuprofen to Treat Dysmenorrhoea

    Directory of Open Access Journals (Sweden)

    Jun Chen

    2015-10-01

    Full Text Available The present study was conducted to evaluate and compare five essential oils (EOs as penetration enhancers (PEs to improve the transdermal drug delivery (TDD of ibuprofen to treat dysmenorrhoea. The EOs were prepared using the steam distillation method and their chemical compositions were identified by GC-MS. The corresponding cytotoxicities were evaluated in epidermal keartinocyte HaCaT cell lines by an MTT assay. Furthermore, the percutaneous permeation studies were carried out to compare the permeation enhancement effect of EOs. Then the therapeutic efficacy of ibuprofen with EOs was evaluated using dysmenorrheal model mice. The data supports a decreasing trend of skin cell viability in which Clove oil >Angelica oil > Chuanxiong oil > Cyperus oil > Cinnamon oil >> Azone. Chuanxiong oil and Angelica oil had been proved to possess a significant permeation enhancement for TDD of ibuprofen. More importantly, the pain inhibitory intensity of ibuprofen hydrogel was demonstrated to be greater with Chuanxiong oil when compared to ibuprofen without EOs (p < 0.05. The contents of calcium ion and nitric oxide (NO were also significantly changed after the addition of Chuanxiong oil (p < 0.05. In summary, we suggest that Chuanxiong oil should be viewed as the best PE for TDD of ibuprofen to treat dysmenorrhea.

  14. Experiment in Application of Methods of Programmed Instruction.

    Science.gov (United States)

    Fradkin, S. L.

    In a document translated from the Russian, an analysis is made of various forms and methods of programed learning. The primary developments in the introduction of programed learning methods are: creation of programed teaching aids; use of existing textbooks for programed lectures with feedback; and use of both teaching machines and machineless…

  15. Enhancement of Permeation in Transdermal Drug Delivery System by 6μm Wavelength Area Using an MIR-FEL

    Science.gov (United States)

    Uchizono, T.; Ishii, K.; Iwao, Y.; Itou, Y.; Maruo, H.; Hori, M.; Awazu, K.

    2005-03-01

    Ablation of the stratum corneum (SC) by pulsed-laser irradiation is one method of enhancing transdermal drug delivery (TD). For non-invasive laser TD treatment, we have tried to enhance TD without ablation of the SC using an MIR-FEL (6-μm wavelength) (FEL : free electron laser). Lidocaine was used as the drug in this study. The enhancement of TD was measured by HPLC. It was found that the lidocaine TD of the sample irradiated by MIR-FEL was enhanced 10 fold faster than the non-irradiated sample with a flux at 0.5 μg/cm2/h, measured by HPLC. We have demonstrated the effectiveness of TD enhancement by an MIR-FEL (6-μm wavelength) irradiation.

  16. Experiences with leak rate calculations methods for LBB application

    International Nuclear Information System (INIS)

    Grebner, H.; Kastner, W.; Hoefler, A.; Maussner, G.

    1997-01-01

    In this paper, three leak rate computer programs for the application of leak before break analysis are described and compared. The programs are compared to each other and to results of an HDR Reactor experiment and two real crack cases. The programs analyzed are PIPELEAK, FLORA, and PICEP. Generally, the different leak rate models are in agreement. To obtain reasonable agreement between measured and calculated leak rates, it was necessary to also use data from detailed crack investigations

  17. Experiences with leak rate calculations methods for LBB application

    Energy Technology Data Exchange (ETDEWEB)

    Grebner, H.; Kastner, W.; Hoefler, A.; Maussner, G. [and others

    1997-04-01

    In this paper, three leak rate computer programs for the application of leak before break analysis are described and compared. The programs are compared to each other and to results of an HDR Reactor experiment and two real crack cases. The programs analyzed are PIPELEAK, FLORA, and PICEP. Generally, the different leak rate models are in agreement. To obtain reasonable agreement between measured and calculated leak rates, it was necessary to also use data from detailed crack investigations.

  18. Quality of experience advanced concepts, applications and methods

    CERN Document Server

    Raake, Alexander

    2014-01-01

    This pioneering book develops definitions and concepts related to Quality of Experience in the context of multimedia- and telecommunications-related applications, systems and services, and applies these to various fields of communication and media technologies. The editors bring together numerous key-protagonists of the new discipline “Quality of Experience” and combine the state-of-the-art knowledge in one single volume. 

  19. Experiment of decontamination of radioactive liquid by a biological method

    International Nuclear Information System (INIS)

    Wormser, G.

    1962-01-01

    The author reports experiments of treatment of radioactive liquid effluents by percolation on a bacterial bed like the one used for the treatment of sewer wastewaters. He also reports results obtained in other countries in terms of reduction of effluent radioactivity for various radioactive ions. The installation is described and results are presented in terms of variation of contamination of an effluent with respect to its recycling on a bacterial bed [fr

  20. Electron beam processed transdermal delivery system for administration of an anti-anginal agent

    Science.gov (United States)

    Kotiyan, P. N.; Vavia, P. R.; Bharadwaj, Y. K.; Sabarwal, S.; Majali, A. B.

    2002-12-01

    Electron beam irradiation was used to synthesize a matrix type transdermal system of isosorbide dinitrate, an effective anti-anginal agent. The drug was dissolved in two monomeric systems, 2-ethylhexyl acrylate (EHA) and 2-ethylhexyl acrylate : methyl methacrylate (9 : 1). The solutions were then directly irradiated on a backing membrane (Scotchpak ®1006) at different doses to get transdermal patches. The developed systems were evaluated for residual monomer content, equilibrium weight swelling ratio, weight uniformity, thickness uniformity, drug content, peel strength, in vitro release and skin permeation kinetics. They possessed excellent tack and adhesive properties. In the case of isosorbide dinitrate-EHA systems, an increase in the peel strength values with respect to the skin was observed with increasing radiation doses. The systems exhibited promising skin permeation kinetics favorable for transdermal drug delivery. The radiation stability of the drug in the pure solid state form was also assessed.

  1. Nanoparticle enabled transdermal drug delivery systems for enhanced dose control and tissue targeting

    Science.gov (United States)

    Palmer, Brian C.; DeLouise, Lisa A.

    2017-01-01

    Transdermal drug delivery systems have been around for decades, and current technologies (e.g. patches, ointments, and creams) enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases. PMID:27983701

  2. Nanoparticle-Enabled Transdermal Drug Delivery Systems for Enhanced Dose Control and Tissue Targeting.

    Science.gov (United States)

    Palmer, Brian C; DeLouise, Lisa A

    2016-12-15

    Transdermal drug delivery systems have been around for decades, and current technologies (e.g., patches, ointments, and creams) enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases.

  3. Transdermal and transbuccal drug delivery systems: enhancement using iontophoretic and chemical approaches.

    Science.gov (United States)

    Hu, Longsheng; Silva, Sérgio M C; Damaj, Bassam B; Martin, Richard; Michniak-Kohn, Bozena B

    2011-12-12

    We investigated the enhancement effect of chemical enhancers and iontophoresis on the in vitro transdermal and transbuccal delivery of lidocaine HCl (LHCl), nicotine hydrogen tartrate (NHT), and diltiazem HCl (DHCl) using porcine skin and buccal tissues. Dodecyl 2-(N,N-dimethylamino) propionate (DDAIP), dodecyl-2-(N,N-dimethylamino) propionate hydrochloride (DDAIP HCl), N-(4-bromobenzoyl)-S,S-dimethyliminosulfurane (Br-iminosulfurane), and azone (laurocapram) were used as chemical enhancers. The study results showed that the application of iontophoresis at either 0.1 mA or 0.3 mA significantly enhanced transdermal and transmucosal delivery of LHCl, NHT and DHCl. It was also demonstrated that iontophoresis had a more pronounced enhancement effect on transdermal delivery than on transbuccal delivery of LHCl, NHT and DHCl. In addition, DDAIP HCl was found to be the most effective enhancer for transbuccal delivery of LHCl and NHT. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Synthesis and characterization of modified starch/polybutadiene as novel transdermal drug delivery system.

    Science.gov (United States)

    Saboktakin, Mohammad Reza; Akhyari, Shahab; Nasirov, Fizuli A

    2014-08-01

    Transdermal drug delivery systems are topically administered medicaments in the form of patches that deliver drugs for systemic effects at a predetermined and controlled rate. It works very simply in which drug is applied inside the patch and it is worn on skin for long period of time. Polymer matrix, drug, permeation enhancers are the main components of transdermal drug delivery systems. The objective of the present study was to develop the modified starch and 1,4-cis polybutadiene nanoparticles as novel polymer matrix system. We have been studied the properties of a novel transdermal drug delivery system with clonidine as drug model. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Electron beam processed transdermal delivery system for administration of an anti-anginal agent

    Energy Technology Data Exchange (ETDEWEB)

    Kotiyan, P.N. E-mail: pramila-kotiyan@uiowa.edu; Vavia, P.R.; Bharadwaj, Y.K.; Sabarwal, S.; Majali, A.B

    2002-12-01

    Electron beam irradiation was used to synthesize a matrix type transdermal system of isosorbide dinitrate, an effective anti-anginal agent. The drug was dissolved in two monomeric systems, 2-ethylhexyl acrylate (EHA) and 2-ethylhexyl acrylate : methyl methacrylate (9 : 1). The solutions were then directly irradiated on a backing membrane (Scotchpak[reg]1006) at different doses to get transdermal patches. The developed systems were evaluated for residual monomer content, equilibrium weight swelling ratio, weight uniformity, thickness uniformity, drug content, peel strength, in vitro release and skin permeation kinetics. They possessed excellent tack and adhesive properties. In the case of isosorbide dinitrate-EHA systems, an increase in the peel strength values with respect to the skin was observed with increasing radiation doses. The systems exhibited promising skin permeation kinetics favorable for transdermal drug delivery. The radiation stability of the drug in the pure solid state form was also assessed.

  6. Nanoparticle-Enabled Transdermal Drug Delivery Systems for Enhanced Dose Control and Tissue Targeting

    Directory of Open Access Journals (Sweden)

    Brian C. Palmer

    2016-12-01

    Full Text Available Transdermal drug delivery systems have been around for decades, and current technologies (e.g., patches, ointments, and creams enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases.

  7. Optimization of Biopolymer Based Transdermal Films of Metoclopramide as an Alternative Delivery Approach

    Directory of Open Access Journals (Sweden)

    Betül Aktar

    2014-05-01

    Full Text Available The objectives of this study were to develop and to characterize sodium alginate based matrix-type transdermal films of metoclopramide hydrochloride (MTC in order to improve patient compliance to treatment. The suitability of sodium alginate was shown to be a natural film former in terms of the physicochemical, mechanical, and bioadhesive features of the MTC loaded transdermal films. Terpinolene provided the highest drug release among the different terpenes (nerolidol, eucalyptol, dl-limonene, or terpinolene assessed as enhancer. Attenuated Total Reflectance Infrared (ATR-FTIR spectroscopy analysis performed to evaluate the effect of the transdermal films on skin barrier confirmed enhancer induced lipid bilayer disruption in stratum corneum, indicating its permeation enhancement effect.

  8. Electron beam processed transdermal delivery system for administration of an anti-anginal agent

    International Nuclear Information System (INIS)

    Kotiyan, P.N.; Vavia, P.R.; Bharadwaj, Y.K.; Sabarwal, S.; Majali, A.B.

    2002-01-01

    Electron beam irradiation was used to synthesize a matrix type transdermal system of isosorbide dinitrate, an effective anti-anginal agent. The drug was dissolved in two monomeric systems, 2-ethylhexyl acrylate (EHA) and 2-ethylhexyl acrylate : methyl methacrylate (9 : 1). The solutions were then directly irradiated on a backing membrane (Scotchpak[reg]1006) at different doses to get transdermal patches. The developed systems were evaluated for residual monomer content, equilibrium weight swelling ratio, weight uniformity, thickness uniformity, drug content, peel strength, in vitro release and skin permeation kinetics. They possessed excellent tack and adhesive properties. In the case of isosorbide dinitrate-EHA systems, an increase in the peel strength values with respect to the skin was observed with increasing radiation doses. The systems exhibited promising skin permeation kinetics favorable for transdermal drug delivery. The radiation stability of the drug in the pure solid state form was also assessed

  9. Mathematical methods for mechanics a handbook with Matlab experiments

    CERN Document Server

    Gekeler, Eckart W

    2008-01-01

    This book introduces all the mathematical tools necessary for solving complex problems in the field of mechanics. It also contains various applications of mathematical and numerical methods for modeling comprehensive mechanical-technical practical problems.

  10. Emergency First Responders' Experience with Colorimetric Detection Methods

    Energy Technology Data Exchange (ETDEWEB)

    Sandra L. Fox; Keith A. Daum; Carla J. Miller; Marnie M. Cortez

    2007-10-01

    Nationwide, first responders from state and federal support teams respond to hazardous materials incidents, industrial chemical spills, and potential weapons of mass destruction (WMD) attacks. Although first responders have sophisticated chemical, biological, radiological, and explosive detectors available for assessment of the incident scene, simple colorimetric detectors have a role in response actions. The large number of colorimetric chemical detection methods available on the market can make the selection of the proper methods difficult. Although each detector has unique aspects to provide qualitative or quantitative data about the unknown chemicals present, not all detectors provide consistent, accurate, and reliable results. Included here, in a consumer-report-style format, we provide “boots on the ground” information directly from first responders about how well colorimetric chemical detection methods meet their needs in the field and how they procure these methods.

  11. Iontophoresis: A Potential Emergence of a Transdermal Drug Delivery System

    Science.gov (United States)

    Dhote, Vinod; Bhatnagar, Punit; Mishra, Pradyumna K.; Mahajan, Suresh C.; Mishra, Dinesh K.

    2012-01-01

    The delivery of drugs into systemic circulation via skin has generated much attention during the last decade. Transdermal therapeutic systems propound controlled release of active ingredients through the skin and into the systemic circulation in a predictive manner. Drugs administered through these systems escape first-pass metabolism and maintain a steady state scenario similar to a continuous intravenous infusion for up to several days. However, the excellent impervious nature of the skin offers the greatest challenge for successful delivery of drug molecules by utilizing the concepts of iontophoresis. The present review deals with the principles and the recent innovations in the field of iontophoretic drug delivery system together with factors affecting the system. This delivery system utilizes electric current as a driving force for permeation of ionic and non-ionic medications. The rationale behind using this technique is to reversibly alter the barrier properties of skin, which could possibly improve the penetration of drugs such as proteins, peptides and other macromolecules to increase the systemic delivery of high molecular weight compounds with controlled input kinetics and minimum inter-subject variability. Although iontophoresis seems to be an ideal candidate to overcome the limitations associated with the delivery of ionic drugs, further extrapolation of this technique is imperative for translational utility and mass human application. PMID:22396901

  12. Photoinduced disaggregation of TiO₂ nanoparticles enables transdermal penetration.

    Directory of Open Access Journals (Sweden)

    Samuel W Bennett

    Full Text Available Under many aqueous conditions, metal oxide nanoparticles attract other nanoparticles and grow into fractal aggregates as the result of a balance between electrostatic and Van Der Waals interactions. Although particle coagulation has been studied for over a century, the effect of light on the state of aggregation is not well understood. Since nanoparticle mobility and toxicity have been shown to be a function of aggregate size, and generally increase as size decreases, photo-induced disaggregation may have significant effects. We show that ambient light and other light sources can partially disaggregate nanoparticles from the aggregates and increase the dermal transport of nanoparticles, such that small nanoparticle clusters can readily diffuse into and through the dermal profile, likely via the interstitial spaces. The discovery of photoinduced disaggregation presents a new phenomenon that has not been previously reported or considered in coagulation theory or transdermal toxicological paradigms. Our results show that after just a few minutes of light, the hydrodynamic diameter of TiO(2 aggregates is reduced from ∼280 nm to ∼230 nm. We exposed pigskin to the nanoparticle suspension and found 200 mg kg(-1 of TiO(2 for skin that was exposed to nanoparticles in the presence of natural sunlight and only 75 mg kg(-1 for skin exposed to dark conditions, indicating the influence of light on NP penetration. These results suggest that photoinduced disaggregation may have important health implications.

  13. Rapidly Dissolving Microneedle Patches for Transdermal Iron Replenishment Therapy.

    Science.gov (United States)

    Maurya, Abhijeet; Nanjappa, Shivakumar H; Honnavar, Swati; Salwa, M; Murthy, S Narasimha

    2018-02-17

    The prevalence of iron deficiency anemia (IDA) is predominant in women and children especially in developing countries. The disorder affects cognitive functions and physical activity. Although oral iron supplementation and parenteral therapy remains the preferred choice of treatment, gastric side effects and risk of iron overload decreases adherence to therapy. Transdermal route is an established approach, which circumvents the side effects associated with conventional therapy. In this project, an attempt was made to investigate the use of rapidly dissolving microneedles loaded with ferric pyrophosphate (FPP) as a potential therapeutic approach for management of IDA. Microneedle array patches were made using the micromolding technique and tested in vitro using rat skin to check the duration required for dissolution/disappearance of needles. The ability of FPP-loaded microneedles to replenish iron was investigated in anemic rats. Rats were fed iron-deficient diet for 5 weeks to induce IDA following which microneedle treatment was initiated. Recovery of rats from anemic state was monitored by measuring hematological and biochemical parameters. Results from in vivo study displayed significant improvements in hemoglobin and serum iron levels after 2-week treatment with FPP-loaded microneedles. The study effectively demonstrated the potential of microneedle-mediated iron replenishment for treatment of IDA. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  14. Transdermal nitroglycerine enhances postoperative analgesia of intrathecal neostigmine following abdominal hysterectomies

    Directory of Open Access Journals (Sweden)

    Fareed Ahmed

    2010-01-01

    Full Text Available This study was carried out to assess the effect of nitroglycerine (transdermal on intrathecal neostigmine with bupivacaine on postoperative analgesia and note the incidence of adverse effects, if any. After taking informed consent, 120 patients of ASA Grade I and II were systematically randomised into four groups of 30 each. Patients were premedicated with midazolam 0.05 mg/kg intravenously and hydration with Ringer′s lactate solution 10ml/kg preoperatively in the holding room. Group I patients received Intrathecal injection of 15 mg bupivacaine with 1ml of normal saline and transdermal placebo patch. Group II patients received Intrathecal injection of 15 mg bupivacaine with 5 mcg of neostigmine and transdermal placebo patch. Group III patients received Intrathecal injection of 15 mg bupivacaine with 1ml of normal saline with transdermal nitroglycerine patch (5 mg/24 hours. Group IV patients received Intrathecal injection of 15 mg bupivacaine with 5mcg of neostigmine and transdermal nitroglycerine patch (5 mg/24 hours, applied on a non anaesthetised area after 20 minutes. Groups were demographically similar and did not differ in intraoperative characteristics like sensory block, motor block, haemodynamic parameters and SpO 2 . The mean duration of analgesia was 202.17 minutes, 407.20 minutes, 207.53 minutes and 581.63 minutes in control group (I, neostigmine group (II, nitroglycerine group (III and nitroglycerine neostigmine group (IV respectively (P< 0.01. To conclude, our results show that transdermal nitroglycerine itself does not show any analgesic potential but it enhances the analgesic potential of intrathecal neostigmine.

  15. Transdermal rivastigmine: management of cutaneous adverse events and review of the literature.

    Science.gov (United States)

    Greenspoon, Jill; Herrmann, Nathan; Adam, David N

    2011-07-01

    Alzheimer's disease is a chronic neurodegenerative disorder resulting in part from the degeneration of cholinergic neurons in the brain. Rivastigmine, a cholinesterase inhibitor, is commonly used as a treatment for dementia due to its ability to moderate cholinergic neurotransmission; however, treatment with oral rivastigmine can lead to gastrointestinal adverse effects such as nausea and vomiting. Transdermal administration of rivastigmine can minimize these adverse effects by providing continuous delivery of the medication, while maintaining the effectiveness of the oral treatment. While the transdermal form of rivastigmine has been found to have fewer systemic adverse effects compared with the oral form, cutaneous reactions, such as contact dermatitis, can lead to discontinuation of the drug in its transdermal form. Lack of patient compliance with regard to applying the patch to the designated site, applying the patch for the correct length of time or rotating patch application sites increases the risk of cutaneous adverse reactions. This article outlines the diagnosis and management of irritant contact dermatitis and allergic contact dermatitis secondary to transdermal rivastigmine. The large majority of reactions to transdermal patches are of an irritant type, which can be diagnosed clinically by the presence of a pruritic, erythematous, eczematous plaque strictly confined to the borders of the patch. In contrast, an allergic reaction can be differentiated by the presence of vesicles and/or oedema, erythema beyond the boundaries of the transdermal patch and lack of improvement of the lesion 48 hours after removal of the offending treatment. By encouraging the patient to follow a regular rotation schedule for the patch, and using lipid-based emollients for irritant dermatitis and pre- and post-treatment topical corticosteroids for allergic dermatitis, cutaneous reactions can often be alleviated and patients can continue with their medication regimen. Other

  16. Factors influencing the contraceptive method choice: a university hospital experience

    Science.gov (United States)

    Kahraman, Korhan; Göç, Göksu; Taşkın, Salih; Haznedar, Pınar; Karagözlü, Selen; Kale, Burak; Kurtipek, Zeynep; Özmen, Batuhan

    2012-01-01

    Objective To analyze the factors influencing behavior of women in choosing contraceptive methods. Material and Methods A total of 4022 women who were admitted to our clinic in a year, were the subjects in this current study for contraception choices. Relationship between the current contraceptive choice and the age, marital status, educational level, gravidity and induced abortions were evaluated. Results Current users of any contraceptive methods were found to make up thirty-three percent of the entire study population. The most preferred method of contraception was an intrauterine device (46.4%), followed by, condom (19.2%), coitus interruptus (16.4%), tubal sterilization (11%), oral contraceptives (5.7%) and lastly the “other methods” that consisted of depot injectables and implants (1.2%). Among other contraceptive methods, the condom was found to be used mostly by the younger age group (OR:0.956, 95% CI:0.936–0.976, p<0.001), while tubal sterilization was preferred mainly by the elderly population (p<0.001, OR:1.091, 95% CI:1.062–1.122). Women that have a higher educational level, were found to use OC (76.3%, OR:5.970, 95% CI:3.233–11.022), tubal sterilization (59.6%, OR:4.110, 95% CI:2.694–6.271) and other methods (62.5%, OR:3.279, 95% CI:1.033–10.402) more commonly than the low educational group (p<0.001). Conclusion These results demonstrated that the rates of both contraception utilization and the usage of more effective methods of contraception need to be increased by providing better family planning systems and counselling opportunities. PMID:24592017

  17. Bangladesh Midlife Women's Health Study (BMWHS): methods, challenges and experiences.

    Science.gov (United States)

    Islam, Rakibul M; Bell, Robin J; Hossain, Mohammad B; Davis, Susan R

    2015-01-01

    To understand the challenges and experiences encountered during data collection for Bangladesh Midlife Women's Health Study (BMWHS) that investigated the low uptake of cervical cancer (CCa) screening barriers, understanding of breast cancer (BCa) knowledge and practices, the prevalence of urinary and fecal incontinence and menopausal symptoms. A multistage cluster sampling technique was used to recruit women from the 32 districts of Bangladesh that had offered CCa screening. Female interviewers were trained to undertake structured face-to-face interviews that incorporated both non-validated and several validated questionnaires, such as Question for Urinary Incontinence Diagnosis, Pelvic Organ Prolapse Distress Inventory, Colorectal-Anal Distress Inventory and Menopause-Specific Quality of Life. We completed surveys of 1590 women, estimated age 30-59 years, between September 2013 and March 2014. We implemented several strategies to deal with low literacy and used the temporal relationship between marriage and childbirth, and the average age of onset of menarche, to estimate age. Cultural and religious sensitivities and personal security were managed by engaging community leaders, limiting activities to daylight hours, adopting local codes of dress, such as the wearing of head scarves. Our major challenges and experiences included difficulties in age determination, selection of and access to households, interview privacy, lack of basic and health literacy, transportation, political unrest and security of the interviewers. By anticipating challenges, we have been able to comprehensively survey a representative sample of Bangladeshi women. Disseminating information about the field challenges and experiences from the BMWHS should assist other researchers planning to conduct surveys about women's health issues in similar context. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Methods of evaluating market transformation programmes: experience in Sweden

    International Nuclear Information System (INIS)

    Neij, L.

    2001-01-01

    The evaluation of market transformation programmes requires the development of new methods, relative to methods used for the evaluation of traditional energy efficiency programmes. In this paper, a model for the evaluation of market transformation programmes is proposed, based in part on evaluation methods discussed in the literature. The proposed model entails an extensive evaluation process, including the evaluation of market transformation effects, the impact of these effects, and the evaluation of the outline of the programme. Furthermore, evaluations of Swedish market transformation programmes have been analysed in relation to the proposed model. The analysis shows that not all of the evaluations have been focused on market transformation, and those that have, are only partly consistent with the evaluation model proposed here. It is concluded that future evaluations of Swedish market transformation programmes should be extended and improved in accordance with the proposed model. (author)

  19. Advanced quantitative magnetic nondestructive evaluation methods - Theory and experiment

    Science.gov (United States)

    Barton, J. R.; Kusenberger, F. N.; Beissner, R. E.; Matzkanin, G. A.

    1979-01-01

    The paper reviews the scale of fatigue crack phenomena in relation to the size detection capabilities of nondestructive evaluation methods. An assessment of several features of fatigue in relation to the inspection of ball and roller bearings suggested the use of magnetic methods; magnetic domain phenomena including the interaction of domains and inclusions, and the influence of stress and magnetic field on domains are discussed. Experimental results indicate that simplified calculations can be used to predict many features of these results; the data predicted by analytic models which use finite element computer analysis predictions do not agree with respect to certain features. Experimental analyses obtained on rod-type fatigue specimens which show experimental magnetic measurements in relation to the crack opening displacement and volume and crack depth should provide methods for improved crack characterization in relation to fracture mechanics and life prediction.

  20. Effect of buprenorphine transdermal patch combined with patientcontrolled intravenous analgesia on the serum pain-related biochemical indexes in elderly patients with intertrochanteric fracture

    Directory of Open Access Journals (Sweden)

    Lei Xu

    2017-09-01

    Full Text Available Objective: To study the effect of buprenorphine transdermal patch combined with patientcontrolled intravenous analgesia on the serum pain-related biochemical indexes in elderly patients with intertrochanteric fracture. Methods: A total of 92 elderly patients with intertrochanteric fracture who received surgical treatment in the hospital between August 2014 and January 2017 were collected and divided into control group (n=46 and observation group (n=46 according to the random number table method. The control group received patient-controlled intravenous analgesia, and the observation group received buprenorphine transdermal patch combined with patient-controlled intravenous analgesia. Differences in serum levels of inflammatory factors, oxidative stress indexes and pain mediators of two groups of patients were measured before and 24h after surgery. Results: Differences in serum levels of inflammatory factors, oxidative stress indexes and pain mediators were not statistically significant between the two groups before surgery; 24 h after surgery, serum IL- 1β, IL-6, IL-8, TNF-α, MDA, SP, PGE2, 5-HT, HA and NPY levels of both groups of patients increased significantly while SOD, TAC and CAT levels decreased significantly, and serum IL-1β, IL-6, IL-8, TNF-α, MDA, SP, PGE2, 5-HT, HA and NPY levels of observation group were lower than those of control group while SOD, TAC and CAT levels were higher than those of control group. Conclusion: Buprenorphine transdermal patch combined with patient-controlled intravenous analgesia can effectively inhibit the expression of pain-related indexes and relieve early postoperative pain intensity in elderly patients with intertrochanteric fracture.

  1. Clinical experience with the objective symmetry detector method for gammaencephalography

    International Nuclear Information System (INIS)

    Sachs, C.; Ericson, K.; Lind, M.

    1982-01-01

    The objective symmetry detector method for gammaencephalography previously described has been further developed. A rapid micro-computerized automatic measuring device has been constructed and the method used in screening of neurologic patients. The previously chosen classification boundaries between normal and pathologic isotope distributions were not entirely satisfactory for clinical screening of patients with neurologic symptoms. By use of new classification boundaries, 87 per cent of patients with brain tumours could be separated from patients with neurologic symptoms but without gross brain lesions and from neurologically healthy subjects. (Auth.)

  2. Modular reservoir concept for MEMS-based transdermal drug delivery systems

    International Nuclear Information System (INIS)

    Cantwell, Cara T; Wei, Pinghung; Ziaie, Babak; Rao, Masaru P

    2014-01-01

    While MEMS-based transdermal drug delivery device development efforts have typically focused on tightly-integrated solutions, we propose an alternate conception based upon a novel, modular drug reservoir approach. By decoupling the drug storage functionality from the rest of the delivery system, this approach seeks to minimize cold chain storage volume, enhance compatibility with conventional pharmaceutical practices, and allow independent optimization of reservoir device design, materials, and fabrication. Herein, we report the design, fabrication, and preliminary characterization of modular reservoirs that demonstrate the virtue of this approach within the application context of transdermal insulin administration for diabetes management. (technical note)

  3. Modular reservoir concept for MEMS-based transdermal drug delivery systems

    Science.gov (United States)

    Cantwell, Cara T.; Wei, Pinghung; Ziaie, Babak; Rao, Masaru P.

    2014-11-01

    While MEMS-based transdermal drug delivery device development efforts have typically focused on tightly-integrated solutions, we propose an alternate conception based upon a novel, modular drug reservoir approach. By decoupling the drug storage functionality from the rest of the delivery system, this approach seeks to minimize cold chain storage volume, enhance compatibility with conventional pharmaceutical practices, and allow independent optimization of reservoir device design, materials, and fabrication. Herein, we report the design, fabrication, and preliminary characterization of modular reservoirs that demonstrate the virtue of this approach within the application context of transdermal insulin administration for diabetes management.

  4. METHODICAL APPROACHES TO THE CREATION MOOC (EXPERIENCE LAC

    Directory of Open Access Journals (Sweden)

    Larysa Nozdrina

    2016-03-01

    Full Text Available The article presents a number of problems, determining the current state of development of the domestic market of massive open online courses (MOOC. Considering the aim of the research, there is described national experience in this area, proposed and substantiated a number of the criteria and methodological approaches to the implementation of MOOC in higher education. The development of MOOC in the Lviv Academy of Commerce (LAC is reviewed as example. The main factors which determine the success of this educational innovation in the domestic market and are put under the research are software platforms, multimedia software for creating video lectures, course structure and support the learning process. The results of study which have been analyzed in this course can have a positive impact on the functioning of the market MOOC in Ukrainian universities. The article focuses on finding the ways of improving the process of developing and implementing MOOC in higher education in the example of LAC where Web-center on the MOODLE platform is used for e-learning. Further research should focus on the development of institutional mechanisms to ensure the effective design, implementation and operation of the MOOC in the universities in Ukraine. Particular attention during learning in massive open online course should be aimed at improving the educational process and to strengthen student's motivation in MOOC. Experience of MOOC's development in LAC can be useful at creating similar courses at other institutions of higher education in the different platforms, both MOODLE, and on the others

  5. Clearance gap flow: Simulations by discontinuous Galerkin method and experiments

    Czech Academy of Sciences Publication Activity Database

    Hála, Jindřich; Luxa, Martin; Bublík, O.; Prausová, H.; Vimmr, J.

    2016-01-01

    Roč. 92, May (2016), 02073-02073 ISSN 2100-014X. [EFM14 – Experimental Fluid Mechanics 2014. Český Krumlov, 18.11.2014-21.11.2014] Institutional support: RVO:61388998 Keywords : compressible fluid flow * narrow channel flow * discontinuous Galerkin finite element method Subject RIV: BK - Fluid Dynamics

  6. Statistical methods for quantitative mass spectrometry proteomic experiments with labeling

    Directory of Open Access Journals (Sweden)

    Oberg Ann L

    2012-11-01

    Full Text Available Abstract Mass Spectrometry utilizing labeling allows multiple specimens to be subjected to mass spectrometry simultaneously. As a result, between-experiment variability is reduced. Here we describe use of fundamental concepts of statistical experimental design in the labeling framework in order to minimize variability and avoid biases. We demonstrate how to export data in the format that is most efficient for statistical analysis. We demonstrate how to assess the need for normalization, perform normalization, and check whether it worked. We describe how to build a model explaining the observed values and test for differential protein abundance along with descriptive statistics and measures of reliability of the findings. Concepts are illustrated through the use of three case studies utilizing the iTRAQ 4-plex labeling protocol.

  7. Statistical methods for quantitative mass spectrometry proteomic experiments with labeling.

    Science.gov (United States)

    Oberg, Ann L; Mahoney, Douglas W

    2012-01-01

    Mass Spectrometry utilizing labeling allows multiple specimens to be subjected to mass spectrometry simultaneously. As a result, between-experiment variability is reduced. Here we describe use of fundamental concepts of statistical experimental design in the labeling framework in order to minimize variability and avoid biases. We demonstrate how to export data in the format that is most efficient for statistical analysis. We demonstrate how to assess the need for normalization, perform normalization, and check whether it worked. We describe how to build a model explaining the observed values and test for differential protein abundance along with descriptive statistics and measures of reliability of the findings. Concepts are illustrated through the use of three case studies utilizing the iTRAQ 4-plex labeling protocol.

  8. Methods for Factor Screening in Computer Simulation Experiments

    Science.gov (United States)

    1979-03-01

    of the dat-a In a-space, impacto the variable selection problem s ign if Lrast ly. S-arch-type variable selection methods include the all-po"sible...i.iv 41.1 ti * n wt- -iu’pt-v c C it st’vt’re mu It ico11 inear it v is pro-crtnt Lind. , ii;.qt4pai tlv * Iti’lt- c- j c. tic j icivnt, art, verv

  9. Capacity for work researching method in animal experiment

    International Nuclear Information System (INIS)

    Pul'nov, V.N.; Mashneva, N.I.

    1978-01-01

    The existing methods of examining the work capacity of animals are discussed with reference to extrapolation of animal data to man. A modified procedure for measuring maximal physical strength is proposed, whereby static endurance of animals at a given exercise rate can be measured. For an integrated evaluation of work capacity, a formula of absolute work capacity is suggested. The proposed procedure may be used to study the working capacity of animals exposed to unfavorable factors of radiation or nonradiation nature

  10. Ultrasound-mediated transdermal drug delivery of fluorescent nanoparticles and hyaluronic acid into porcine skin in vitro

    International Nuclear Information System (INIS)

    Wang Huan-Lei; Fan Peng-Fei; Guo Xia-Sheng; Tu Juan; Zhang Dong; Ma Yong

    2016-01-01

    Transdermal drug delivery (TDD) can effectively bypass the first-pass effect. In this paper, ultrasound-facilitated TDD on fresh porcine skin was studied under various acoustic parameters, including frequency, amplitude, and exposure time. The delivery of yellow–green fluorescent nanoparticles and high molecular weight hyaluronic acid (HA) in the skin samples was observed by laser confocal microscopy and ultraviolet spectrometry, respectively. The results showed that, with the application of ultrasound exposures, the permeability of the skin to these markers (e.g., their penetration depth and concentration) could be raised above its passive diffusion permeability. Moreover, ultrasound-facilitated TDD was also tested with/without the presence of ultrasound contrast agents (UCAs). When the ultrasound was applied without UCAs, low ultrasound frequency will give a better drug delivery effect than high frequency, but the penetration depth was less likely to exceed 200 μm. However, with the help of the ultrasound-induced microbubble cavitation effect, both the penetration depth and concentration in the skin were significantly enhanced even more. The best ultrasound-facilitated TDD could be achieved with a drug penetration depth of over 600 μm, and the penetration concentrations of fluorescent nanoparticles and HA increased up to about 4–5 folds. In order to get better understanding of ultrasound-facilitated TDD, scanning electron microscopy was used to examine the surface morphology of skin samples, which showed that the skin structure changed greatly under the treatment of ultrasound and UCA. The present work suggests that, for TDD applications (e.g., nanoparticle drug carriers, transdermal patches and cosmetics), protocols and methods presented in this paper are potentially useful. (special topic)

  11. Conducting organizational safety reviews - requirements, methods and experience

    International Nuclear Information System (INIS)

    Reiman, T.; Oedewald, P.; Wahlstroem, B.; Rollenhagen, C.; Kahlbom, U.

    2008-03-01

    Organizational safety reviews are part of the safety management process of power plants. They are typically performed after major reorganizations, significant incidents or according to specified review programs. Organizational reviews can also be a part of a benchmarking between organizations that aims to improve work practices. Thus, they are important instruments in proactive safety management and safety culture. Most methods that have been used for organizational reviews are based more on practical considerations than a sound scientific theory of how various organizational or technical issues influence safety. Review practices and methods also vary considerably. The objective of this research is to promote understanding on approaches used in organizational safety reviews as well as to initiate discussion on criteria and methods of organizational assessment. The research identified a set of issues that need to be taken into account when planning and conducting organizational safety reviews. Examples of the issues are definition of appropriate criteria for evaluation, the expertise needed in the assessment and the organizational motivation for conducting the assessment. The study indicates that organizational safety assessments involve plenty of issues and situations where choices have to be made regarding what is considered valid information and a balance has to be struck between focus on various organizational phenomena. It is very important that these choices are based on a sound theoretical framework and that these choices can later be evaluated together with the assessment findings. The research concludes that at its best, the organizational safety reviews can be utilised as a source of information concerning the changing vulnerabilities and the actual safety performance of the organization. In order to do this, certain basic organizational phenomena and assessment issues have to be acknowledged and considered. The research concludes with recommendations on

  12. Conducting organizational safety reviews - requirements, methods and experience

    Energy Technology Data Exchange (ETDEWEB)

    Reiman, T.; Oedewald, P.; Wahlstroem, B. [Technical Research Centre of Finland, VTT (Finland); Rollenhagen, C. [Royal Institute of Technology, KTH, (Sweden); Kahlbom, U. [RiskPilot (Sweden)

    2008-03-15

    Organizational safety reviews are part of the safety management process of power plants. They are typically performed after major reorganizations, significant incidents or according to specified review programs. Organizational reviews can also be a part of a benchmarking between organizations that aims to improve work practices. Thus, they are important instruments in proactive safety management and safety culture. Most methods that have been used for organizational reviews are based more on practical considerations than a sound scientific theory of how various organizational or technical issues influence safety. Review practices and methods also vary considerably. The objective of this research is to promote understanding on approaches used in organizational safety reviews as well as to initiate discussion on criteria and methods of organizational assessment. The research identified a set of issues that need to be taken into account when planning and conducting organizational safety reviews. Examples of the issues are definition of appropriate criteria for evaluation, the expertise needed in the assessment and the organizational motivation for conducting the assessment. The study indicates that organizational safety assessments involve plenty of issues and situations where choices have to be made regarding what is considered valid information and a balance has to be struck between focus on various organizational phenomena. It is very important that these choices are based on a sound theoretical framework and that these choices can later be evaluated together with the assessment findings. The research concludes that at its best, the organizational safety reviews can be utilised as a source of information concerning the changing vulnerabilities and the actual safety performance of the organization. In order to do this, certain basic organizational phenomena and assessment issues have to be acknowledged and considered. The research concludes with recommendations on

  13. A gas trapping method for high-throughput metabolic experiments.

    Science.gov (United States)

    Krycer, James R; Diskin, Ciana; Nelson, Marin E; Zeng, Xiao-Yi; Fazakerley, Daniel J; James, David E

    2018-01-01

    Research into cellular metabolism has become more high-throughput, with typical cell-culture experiments being performed in multiwell plates (microplates). This format presents a challenge when trying to collect gaseous products, such as carbon dioxide (CO2), which requires a sealed environment and a vessel separate from the biological sample. To address this limitation, we developed a gas trapping protocol using perforated plastic lids in sealed cell-culture multiwell plates. We used this trap design to measure CO2 production from glucose and fatty acid metabolism, as well as hydrogen sulfide production from cysteine-treated cells. Our data clearly show that this gas trap can be applied to liquid and solid gas-collection media and can be used to study gaseous product generation by both adherent cells and cells in suspension. Since our gas traps can be adapted to multiwell plates of various sizes, they present a convenient, cost-effective solution that can accommodate the trend toward high-throughput measurements in metabolic research.

  14. An open-label, two-period comparative study on pharmacokinetics and safety of a combined ethinylestradiol/gestodene transdermal contraceptive patch

    Directory of Open Access Journals (Sweden)

    Zhang C

    2017-03-01

    Full Text Available Chao Zhang,1 Haiyan Li,2 Xin Xiong,1 Suodi Zhai,1 Yudong Wei,2 Shuang Zhang,2 Yuanyuan Zhang,1 Lin Xu,2 Li Liu1 1Department of Pharmacy, 2Institute of Clinical Trial, Peking University Third Hospital, Beijing, People’s Republic of China Abstract: We investigated the pharmacokinetics and safety profiles of a newly developed combined ethinylestradiol (EE/gestodene (GSD transdermal contraceptive patch after a single-dose administration and compared with the market available tablet formulation in healthy adult subjects. An open-label, two-period comparative study was conducted in 12 healthy women volunteers. A single dose of the study combined EE/GE transdermal contraceptive patch and oral tablet (Milunet® were administered. Blood samples at different time points after dose were collected, and concentrations were analyzed. A reliable, highly sensitive and accurate high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC/MS/MS assay method was developed in this study to determine the plasma concentrations of EE and GSD. Compared to the tablet, the study patch had a significantly decreased maximum plasma concentration (Cmax, extended time to reach the Cmax and half-life, as well as increased clearance and apparent volume of distribution. The half-lives of EE and GSD of the patch were 3.3 and 2.2 times, respectively, than the half-life of the tablet. The areas under the plasma concentration–time curve (AUCs of EE and GSD of the patch were 8.0 and 16.2 times, respectively, than the AUC of the tablet. No severe adverse event was observed during the whole study, and the general safety was acceptable. In conclusion, compared to the oral tablet Milunet, the study contraceptive patch was well tolerated and showed potent drug exposure, significant extended half-life and stable drug concentrations. Keywords: pharmacokinetics, safety, ethinylestradiol/gestodene, transdermal contraceptive patch

  15. Novel non-ionic surfactant proniosomes for transdermal delivery of lacidipine: optimization using 2(3) factorial design and in vivo evaluation in rabbits.

    Science.gov (United States)

    Soliman, Sara M; Abdelmalak, Nevine S; El-Gazayerly, Omaima N; Abdelaziz, Nabaweya

    2016-06-01

    Proniosomes offer a versatile vesicle drug delivery concept with potential for delivery of drugs via transdermal route. To develop proniosomal gel using cremophor RH 40 as non-ionic surfactant containing the antihypertensive drug lacidipine for transdermal delivery so as to avoid its extensive first pass metabolism and to improve its permeation through the skin. Proniosomes containing 1% lacidipine were prepared by the coacervation phase separation method, characterized, and optimized using a 2(3) full factorial design to define the optimum conditions to produce proniosomes with high entrapment efficiency, minimal vesicle size, and high-percentage release efficiency. The amount of cholesterol (X1), the amount of soya lecithin (X2), and the amount of cremophor RH 40 (X3) were selected as three independent variables. The system F4 was found to fulfill the maximum requisite of an optimum system because it had minimum vesicle size, maximum EE, maximum release efficiency, and maximum desirability. The optimized system (F4) was then converted to proniosomal gel using carbopol 940 (1% w/w). In vitro permeation through excised rabbit skin study revealed higher flux (6.48 ± 0.45) for lacidipine from the optimized proniosomal gel when compared with the corresponding emulgel (3.04 ± 0.13) mg/cm(2)/h. The optimized formulation was evaluated for its bioavailability compared with commercial product. Statistical analysis revealed significant increase in AUC (0 - α) 464.17 ± 113.15 ng h/ml compared with 209.02 ± 47.35 ng h/ml for commercial tablet. Skin irritancy and histopathological investigation of rat skin revealed its safety. Cremophor RH 40 proniosomal gel could be considered as very promising nanocarriers for transdermal delivery of lacidipine.

  16. Enhanced transdermal delivery with less irritation by magainin pore-forming peptide with a N-lauroylsarcosine and sorbitan monolaurate mixture.

    Science.gov (United States)

    Lee, Haerin; Park, Juhyun; Kim, Yeu-Chun

    2018-02-01

    Transdermal drug delivery is advantageous over other conventional drug administration routes. However, it can be inefficient because of the natural barrier of the stratum corneum which is the uppermost layer of the skin. A previous study verified that the treatment of magainin pore-forming peptide with N-lauroylsarcosine (NLS) on human skin can increase skin permeability by 47-fold. However, NLS is well known as a potential skin irritant. The irritation potential of NLS is known to decrease when mixed with sorbitan monolaurate (S20). Encouraged by these results, we combined S20 with magainin-NLS to enhance transdermal drug transport with less skin irritation. In this study, nine groups with magainin and NLS:S20 mixtures at different concentrations and weight fractions were screened to maximize their synergistic effect. To quantify the efficacy to toxicity ratio of each formulation, we defined the ratio as the "enhancement ratio/irritation potential (ER/IP)." The ER was observed by Franz cell diffusion of the target drug fluorescein, and the IP was measured by the cytotoxicity of the NIH/3T3 mouse fibroblast cell line. As a result, the magainin with the NLS:S20 mixture increased the permeability of porcine skin as well as decreased the toxicity. Among the various combinations, a formulation of 2% (w/v) NLS:S20 with a weight fraction of 0.6:0.4 had the largest ER/IP. ATR-FTIR spectroscopy of the formulations and skin was done to analyze the interactions in the formulations themselves and between the formulations and the skin. Both the intercellular lipidic route and transcellular route through the stratum corneum protein were involved in the delivery of fluorescein. This study turned pore-forming peptides into an efficient and safe penetration enhancer by combining them with other chemical penetration enhancers. Moreover, this discovery could be a possible method for enabling the transdermal delivery of macromolecules.

  17. Methods in carbon K-edge NEXAFS: Experiment and analysis

    International Nuclear Information System (INIS)

    Watts, B.; Thomsen, L.; Dastoor, P.C.

    2006-01-01

    Near-edge X-ray absorption spectroscopy (NEXAFS) is widely used to probe the chemistry and structure of surface layers. Moreover, using ultra-high brilliance polarised synchrotron light sources, it is possible to determine the molecular alignment of ultra-thin surface films. However, the quantitative analysis of NEXAFS data is complicated by many experimental factors and, historically, the essential methods of calibration, normalisation and artefact removal are presented in the literature in a somewhat fragmented manner, thus hindering their integrated implementation as well as their further development. This paper outlines a unified, systematic approach to the collection and quantitative analysis of NEXAFS data with a particular focus upon carbon K-edge spectra. As a consequence, we show that current methods neglect several important aspects of the data analysis process, which we address with a combination of novel and adapted techniques. We discuss multiple approaches in solving the issues commonly encountered in the analysis of NEXAFS data, revealing the inherent assumptions of each approach and providing guidelines for assessing their appropriateness in a broad range of experimental situations

  18. [Teaching quantitative methods in public health: the EHESP experience].

    Science.gov (United States)

    Grimaud, Olivier; Astagneau, Pascal; Desvarieux, Moïse; Chambaud, Laurent

    2014-01-01

    Many scientific disciplines, including epidemiology and biostatistics, are used in the field of public health. These quantitative sciences are fundamental tools necessary for the practice of future professionals. What then should be the minimum quantitative sciences training, common to all future public health professionals? By comparing the teaching models developed in Columbia University and those in the National School of Public Health in France, the authors recognize the need to adapt teaching to the specific competencies required for each profession. They insist that all public health professionals, whatever their future career, should be familiar with quantitative methods in order to ensure that decision-making is based on a reflective and critical use of quantitative analysis.

  19. 'Odontologic dosimetric card' experiments and simulations using Monte Carlo methods

    International Nuclear Information System (INIS)

    Menezes, C.J.M.; Lima, R. de A.; Peixoto, J.E.; Vieira, J.W.

    2008-01-01

    The techniques for data processing, combined with the development of fast and more powerful computers, makes the Monte Carlo methods one of the most widely used tools in the radiation transport simulation. For applications in diagnostic radiology, this method generally uses anthropomorphic phantoms to evaluate the absorbed dose to patients during exposure. In this paper, some Monte Carlo techniques were used to simulation of a testing device designed for intra-oral X-ray equipment performance evaluation called Odontologic Dosimetric Card (CDO of 'Cartao Dosimetrico Odontologico' in Portuguese) for different thermoluminescent detectors. This paper used two computational models of exposition RXD/EGS4 and CDO/EGS4. In the first model, the simulation results are compared with experimental data obtained in the similar conditions. The second model, it presents the same characteristics of the testing device studied (CDO). For the irradiations, the X-ray spectra were generated by the IPEM report number 78, spectrum processor. The attenuated spectrum was obtained for IEC 61267 qualities and various additional filters for a Pantak 320 X-ray industrial equipment. The results obtained for the study of the copper filters used in the determination of the kVp were compared with experimental data, validating the model proposed for the characterization of the CDO. The results shower of the CDO will be utilized in quality assurance programs in order to guarantee that the equipment fulfill the requirements of the Norm SVS No. 453/98 MS (Brazil) 'Directives of Radiation Protection in Medical and Dental Radiodiagnostic'. We conclude that the EGS4 is a suitable code Monte Carlo to simulate thermoluminescent dosimeters and experimental procedures employed in the routine of the quality control laboratory in diagnostic radiology. (author)

  20. VHTRC experiment for verification test of H{infinity} reactivity estimation method

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, Yoshio; Suzuki, Katsuo; Akino, Fujiyoshi; Yamane, Tsuyoshi; Fujisaki, Shingo; Takeuchi, Motoyoshi; Ono, Toshihiko [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1996-02-01

    This experiment was performed at VHTRC to acquire the data for verifying the H{infinity} reactivity estimation method. In this report, the experimental method, the measuring circuits and data processing softwares are described in details. (author).

  1. Pharmacokinetics and repolarization effects of intravenous and transdermal granisetron.

    Science.gov (United States)

    Mason, Jay W; Selness, Daniel S; Moon, Thomas E; O'Mahony, Bridget; Donachie, Peter; Howell, Julian

    2012-05-15

    The need for greater clarity about the effects of 5-HT(3) receptor antagonists on cardiac repolarization is apparent in the changing product labeling across this therapeutic class. This study assessed the repolarization effects of granisetron, a 5-HT(3) receptor antagonist antiemetic, administered intravenously and by a granisetron transdermal system (GTDS). In a parallel four-arm study, healthy subjects were randomized to receive intravenous granisetron, GTDS, placebo, or oral moxifloxacin (active control). The primary endpoint was difference in change from baseline in mean Fridericia-corrected QT interval (QTcF) between GTDS and placebo (ddQTcF) on days 3 and 5. A total of 240 subjects were enrolled, 60 in each group. Adequate sensitivity for detection of QTc change was shown by a 5.75 ms lower bound of the 90% confidence interval (CI) for moxifloxacin versus placebo at 2 hours postdose on day 3. Day 3 ddQTcF values varied between 0.2 and 1.9 ms for GTDS (maximum upper bound of 90% CI, 6.88 ms), between -1.2 and 1.6 ms for i.v. granisetron (maximum upper bound of 90% CI, 5.86 ms), and between -3.4 and 4.7 ms for moxifloxacin (maximum upper bound of 90% CI, 13.45 ms). Day 5 findings were similar. Pharmacokinetic-ddQTcF modeling showed a minimally positive slope of 0.157 ms/(ng/mL), but a very low correlation (r = 0.090). GTDS was not associated with statistically or clinically significant effects on QTcF or other electrocardiographic variables. This study provides useful clarification on the effect of granisetron delivered by GTDS on cardiac repolarization. ©2012 AACR.

  2. Granisetron transdermal system improves refractory nausea and vomiting in gastroparesis.

    Science.gov (United States)

    Simmons, Kellie; Parkman, Henry P

    2014-06-01

    Symptoms of gastroparesis include nausea and vomiting, which can markedly diminish quality of life. Nausea and vomiting can also make treatment with oral antiemetics problematic. Our aim was to determine whether treatment-resistant nausea and vomiting in patients with gastroparesis improve after granisetron transdermal patch (GTP) therapy. In an open-label pilot study, patients with gastroparesis and symptoms of nausea and vomiting refractory to conventional treatment were treated with GTP. After 2 weeks, patients were asked to assess their therapeutic response using the Clinical Patient Grading Assessment Scale (CPGAS; +7 = completely better; 0 = no change; -7 = very considerably worse). Responders were defined as CPGAS score >0, non-responders as ≤0. Patients (n = 36) were treated with GTP. Of these 36 patients, one patient discontinued treatment due to the GTP not adhering to the skin. Of the remaining 35 patients, 18 improved, 15 remained the same, and two worsened. The average CPGAS score was +1.8 ± 0.4 (SEM) (P < 0.05 vs 0). Of the 18 patients with improvement, the average CPGAS score was +3.7 ± 0.3 (SEM), corresponding to "somewhat" to "moderately better" improvement in nausea/vomiting. Side effects occurred in nine patients: four developed constipation, three patients had skin rash, and two reported headaches. GTP was moderately effective in reducing refractory symptoms of nausea and/or vomiting from gastroparesis in 50% of patients. Mild side effects were reported by 25% of patients. GTP may be an effective treatment for nausea and vomiting in gastroparesis, and further study is warranted.

  3. Transdermal nicotine absorption handling e-cigarette refill liquids.

    Science.gov (United States)

    Maina, Giovanni; Castagnoli, Carlotta; Passini, Valter; Crosera, Matteo; Adami, Gianpiero; Mauro, Marcella; Filon, Francesca Larese

    2016-02-01

    The concentrated nicotine in e-cigarette refill liquids can be toxic if inadvertently ingested or absorbed through the skin. Reports of poisonings due to accidental ingestion of nicotine on refill liquids are rapidly increasing, while the evaluation of nicotine dermally absorbed still lacks. For that reason we studied transdermal nicotine absorption after the skin contamination with e-liquid. Donor chambers of eight Franz diffusion cells were filled with 1 mL of 0.8 mg/mL nicotine e-liquid for 24 h. The concentration of nicotine in the receiving phase was determined by high-performance liquid chromatography (LOD:0.1 μg/mL). Nicotine was detectable in receiving solution 2 h after the start of exposure and increased progressively. The medium flux calculated was 4.82 ± 1.05 μg/cm(2)/h with a lag time of 3.9 ± 0.1 h. After 24 h, the nicotine concentration in the receiving compartment was 101.02 ± 22.35 μg/cm(2) corresponding to 3.04 mg of absorbed nicotine after contamination of a skin surface of 100 cm(2). Skin contamination with e-liquid can cause nicotine skin absorption: caution must be paid when handling refill e-liquids. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Simple and cost-effective fabrication of solid biodegradable polymer microneedle arrays with adjustable aspect ratio for transdermal drug delivery using acupuncture microneedles

    International Nuclear Information System (INIS)

    Cha, Kyoung Je; Kim, Taewan; Park, Sung Jea; Kim, Dong Sung

    2014-01-01

    Polymer microneedle arrays (MNAs) have received much attention for their use in transdermal drug delivery and microneedle therapy systems due to the advantages they offer, such as low cost, good mechanical properties, and a versatile choice of materials. Here, we present a simple and cost-effective method for the fabrication of a biodegradable polymer MNA in which the aspect ratio of each microneedle is adjustable using commercially available acupuncture microneedles. In our process, a master template with acupuncture microneedles, whose shape will be the final MNA, was carefully prepared by fixing them onto a plastic substrate with selectively drilled holes which, in turn, determine the aspect ratios of the microneedles. A polylactic acid (PLA; a biodegradable polymer) MNA was fabricated by a micromolding process with a polydimethylsiloxane (PDMS) mold containing the cavity of the microneedles, which was obtained by the PDMS replica molding against the master template. The mechanical force and degradation behavior of the replicated PLA MNA were characterized with the help of a compression test and an accelerated degradation test, respectively. Finally, the transdermal drug delivery performance of the PLA MNA was successfully simulated by two different methods of penetration and staining, using the skin of a pig cadaver. These results indicated that the proposed method can be effectively used for the fabrication of polymer MNAs which can be used in various microneedle applications. (paper)

  5. Simple and cost-effective fabrication of solid biodegradable polymer microneedle arrays with adjustable aspect ratio for transdermal drug delivery using acupuncture microneedles

    Science.gov (United States)

    Cha, Kyoung Je; Kim, Taewan; Jea Park, Sung; Kim, Dong Sung

    2014-11-01

    Polymer microneedle arrays (MNAs) have received much attention for their use in transdermal drug delivery and microneedle therapy systems due to the advantages they offer, such as low cost, good mechanical properties, and a versatile choice of materials. Here, we present a simple and cost-effective method for the fabrication of a biodegradable polymer MNA in which the aspect ratio of each microneedle is adjustable using commercially available acupuncture microneedles. In our process, a master template with acupuncture microneedles, whose shape will be the final MNA, was carefully prepared by fixing them onto a plastic substrate with selectively drilled holes which, in turn, determine the aspect ratios of the microneedles. A polylactic acid (PLA; a biodegradable polymer) MNA was fabricated by a micromolding process with a polydimethylsiloxane (PDMS) mold containing the cavity of the microneedles, which was obtained by the PDMS replica molding against the master template. The mechanical force and degradation behavior of the replicated PLA MNA were characterized with the help of a compression test and an accelerated degradation test, respectively. Finally, the transdermal drug delivery performance of the PLA MNA was successfully simulated by two different methods of penetration and staining, using the skin of a pig cadaver. These results indicated that the proposed method can be effectively used for the fabrication of polymer MNAs which can be used in various microneedle applications.

  6. Some experience of shielding calculations by combinatorial method

    International Nuclear Information System (INIS)

    Korobejnikov, V.V.; Oussanov, V.I.

    1996-01-01

    Some aspects of the compound systems shielding calculations by a combinatorial approach are discussed. The effectiveness of such an approach is based on the fundamental characteristic of a compound system: if some element of the system have in itself mathematical or physical properties favorable for calculation, these properties may be used in a combinatorial approach and are lost when the system is being calculated in the whole by a direct approach. The combinatorial technique applied is well known. A compound system are being splitting for two or more auxiliary subsystems (so that calculation each of them is a more simple problem than calculation of the original problem (or at last is a soluble problem if original one is not). Calculation of every subsystem are carried out by suitable method and code, the coupling being made through boundary conditions or boundary source. The special consideration in the paper is given to a fast reactor shielding combinatorial analysis and to the testing of the results received. (author)

  7. A review of experiment data processing method for uranium mining and metallurgy in BRICEM

    International Nuclear Information System (INIS)

    Ye Guoqiang; Lu Kehong; Wang Congying

    1997-01-01

    The authors investigates the methods of experiment data processing in Beijing Research Institute of Chemical Engineering and Metallurgy (BRICEM). It turns out that error analysis method is used to process experiment data, single-factor transformation and orthogonal test design method are adopted for arranging test, and regression analysis and mathematical process simulation are applied to process mathematical model for uranium mining and metallurgy. The methods above-mentioned lay a foundation for the utilization of mathematical statistics in our subject

  8. External individual monitoring: experiments and simulations using Monte Carlo Method

    International Nuclear Information System (INIS)

    Guimaraes, Carla da Costa

    2005-01-01

    In this work, we have evaluated the possibility of applying the Monte Carlo simulation technique in photon dosimetry of external individual monitoring. The GEANT4 toolkit was employed to simulate experiments with radiation monitors containing TLD-100 and CaF 2 :NaCl thermoluminescent detectors. As a first step, X ray spectra were generated impinging electrons on a tungsten target. Then, the produced photon beam was filtered in a beryllium window and additional filters to obtain the radiation with desired qualities. This procedure, used to simulate radiation fields produced by a X ray tube, was validated by comparing characteristics such as half value layer, which was also experimentally measured, mean photon energy and the spectral resolution of simulated spectra with that of reference spectra established by international standards. In the construction of thermoluminescent dosimeter, two approaches for improvements have. been introduced. The first one was the inclusion of 6% of air in the composition of the CaF 2 :NaCl detector due to the difference between measured and calculated values of its density. Also, comparison between simulated and experimental results showed that the self-attenuation of emitted light in the readout process of the fluorite dosimeter must be taken into account. Then, in the second approach, the light attenuation coefficient of CaF 2 :NaCl compound estimated by simulation to be 2,20(25) mm -1 was introduced. Conversion coefficients C p from air kerma to personal dose equivalent were calculated using a slab water phantom with polymethyl-metacrilate (PMMA) walls, for reference narrow and wide X ray spectrum series [ISO 4037-1], and also for the wide spectra implanted and used in routine at Laboratorio de Dosimetria. Simulations of backscattered radiations by PMMA slab water phantom and slab phantom of ICRU tissue-equivalent material produced very similar results. Therefore, the PMMA slab water phantom that can be easily constructed with low

  9. Foetal Fentanyl Exposure and Ion Trapping after Intravenous and Transdermal Administration to the Ewe.

    Science.gov (United States)

    Heikkinen, Emma M; Kokki, Hannu; Heikkinen, Aki; Ranta, Veli-Pekka; Räsänen, Juha; Voipio, Hanna-Marja; Kokki, Merja

    2017-02-01

    Opioids given to pregnant and parturient women are relatively freely transferred across the placenta. Spinal, epidural and intravenous fentanyl has been studied in pregnant women and neonates, but foetal safety of fentanyl dosing with transdermal patch during pregnancy and labour is not sufficiently studied. Foetal pH is physiologically lower than maternal pH, and thus, opioids, which are weak bases, are ionized and may cumulate to foetus. Foetal asphyxia may further worsen acidosis, and ion trapping induced by low pH is assumed to increase the foetal exposure to opioids. Here, we show that no correlation between foetal acidosis and ion trapping of fentanyl could be found. In three experiments, 29 pregnant sheep were administered fentanyl with 2 μg/kg/h patch supplemented with IV boluses/infusion. Foetal exposure to fentanyl was extensive, median 0.34 ng/ml (quartiles 0.21, 0.42), yet drug accumulation to foetus was not observed, and median of foetal/maternal concentration (F/M) ratio was 0.63 (0.43, 0.75) during the first hours after the fentanyl administration. Low foetal pH and pH difference between ewe and the foetus did not correlate with fentanyl concentration in the foetus or F/M ratio. At steady-state during the second patch worn, foetal plasma fentanyl was low, 0.13 ng/ml, and the median of F/M ratio was 0.69. Our results demonstrate that drug accumulation to foetus caused by ion trapping seen with some weak base opioids may not be that significant with fentanyl. These results have a clinical relevance when fentanyl is dosed to pregnant woman and the foetus is acidemic. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  10. Synthesis of conjugated chitosan and its effect on drug permeation from transdermal patches.

    Science.gov (United States)

    Satheeshababu, B K; Shivakumar, K L

    2013-03-01

    The aim of this study was to synthesis the conjugated chitosan by covalent attachment of thiol moieties to the cationic polymer, mediated by a carbodiimide to improve permeation properties of chitosan. Thioglycolic acid was covalently attached to chitosan by the formation of amide bonds between the primary amino groups of the polymer and the carboxylic acid groups of thioglycolic acid. Hence, these polymers are called as thiomers or thiolated polymers. Conjugation of chitosan was confirmed by Fourier transform-infrared and differential scanning calorimetric analysis. Matrix type transdermal patches of carvedilol were prepared using the different proportions of chitosan and chitosan-thioglycolic acid conjugates (2:0, 1.7:0.3, 1.4:0.6, 1:1, 0.6:1.4 and 0.3:1.7) by solvent casting technique. Prepared matrix type patches were evaluated for their physicochemical characterization followed by in vitro evaluation. Selected formulations were subjected for their ex vivo studies on Wistar albino rat skin and human cadaver skin using the modified Franz diffusion cell. As the proportion of conjugated chitosan increased, the transdermal patches showed increased drug permeation. The mechanism of drug release was found to be nonFickian profiles. The present study concludes that the transdermal patches of carvedilol using conjugated chitosan with different proportions of chitosan were successfully developed to provide improved drug permeation. The transdermal patches can be a good approach to improve drug bioavailability by bypassing the extensive hepatic first-pass metabolism of the drug.

  11. Dodecyl Amino Glucoside Enhances Transdermal and Topical Drug Delivery via Reversible Interaction with Skin Barrier Lipids

    Czech Academy of Sciences Publication Activity Database

    Kopečná, M.; Macháček, M.; Prchalová, Eva; Štěpánek, P.; Drašar, P.; Kotora, Martin; Vávrová, K.

    2017-01-01

    Roč. 34, č. 3 (2017), s. 640-653 ISSN 0724-8741 Institutional support: RVO:61388963 Keywords : penetration enhancers * sugar * topical drug delivery * transdermal drug delivery Subject RIV: FR - Pharmacology ; Medidal Chemistry OBOR OECD: Pharmacology and pharmacy Impact factor: 3.002, year: 2016

  12. Use and cardiovascular safety of transdermal and other granisetron preparations in cancer management

    International Nuclear Information System (INIS)

    Mason, Jay W; Moon, Thomas E

    2013-01-01

    5-HT 3 antagonists have been available as oral and intravenous preparations for decades. The availability more recently of transdermal granisetron and the anticipated availability of a subcutaneous granisetron preparation have provided helpful alternatives to patients, and these preparations have been shown to have less potential to prolong QT than other drugs in the class

  13. Enhanced Transdermal Permeability via Constructing the Porous Structure of Poloxamer-Based Hydrogel

    Directory of Open Access Journals (Sweden)

    Wen-Yi Wang

    2016-11-01

    Full Text Available A major concern for transdermal drug delivery systems is the low bioavailability of targeted drugs primarily caused by the skin’s barrier function. The resistance to the carrier matrix for the diffusion and transport of drugs, however, is routinely ignored. This study reports a promising and attractive approach to reducing the resistance to drug transport in the carrier matrix, to enhance drug permeability and bioavailability via enhanced concentration-gradient of the driving force for transdermal purposes. This approach simply optimizes and reconstructs the porous channel structure of the carrier matrix, namely, poloxamer 407 (P407-based hydrogel matrix blended with carboxymethyl cellulose sodium (CMCs. Addition of CMCs was found to distinctly improve the porous structure of the P407 matrix. The pore size approximated to normal distribution as CMCs were added and the fraction of pore number was increased by over tenfold. Transdermal studies showed that P407/CMCs saw a significant increase in drug permeability across the skin. This suggests that P407/CMC with improved porous structure exhibits a feasible and promising way for the development of transdermal therapy with high permeability and bioavailability, thereby avoiding or reducing use of any chemical enhancers.

  14. Anti-cancer vaccination by transdermal delivery of antigen peptide-loaded nanogels via iontophoresis.

    Science.gov (United States)

    Toyoda, Mao; Hama, Susumu; Ikeda, Yutaka; Nagasaki, Yukio; Kogure, Kentaro

    2015-04-10

    Transdermal vaccination with cancer antigens is expected to become a useful anti-cancer therapy. However, it is difficult to accumulate enough antigen in the epidermis for effective exposure to Langerhans cells because of diffusion into the skin and muscle. Carriers, such as liposomes and nanoparticles, may be useful for the prevention of antigen diffusion. Iontophoresis, via application of a small electric current, is a noninvasive and efficient technology for transdermal drug delivery. Previously, we succeeded in the iontophoretic transdermal delivery of liposomes encapsulating insulin, and accumulation of polymer-based nanoparticle nanogels in the stratum corneum of the skin. Therefore, in the present study, we examined the use of iontophoresis with cancer antigen gp-100 peptide KVPRNQDWL-loaded nanogels for anti-cancer vaccination. Iontophoresis resulted in the accumulation of gp-100 peptide and nanogels in the epidermis, and subsequent increase in the number of Langerhans cells in the epidermis. Moreover, tumor growth was significantly suppressed by iontophoresis of the antigen peptide-loaded nanogels. Thus, iontophoresis of the antigen peptide-loaded nanogels may serve as an effective transdermal delivery system for anti-cancer vaccination. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Inefficacy of high-dose transdermal fentanyl in a patient with neuropathic pain, a case report.

    NARCIS (Netherlands)

    Bleeker, C.P.; Bremer, R.; Dongelmans, D.A.; Dongen, R.T.M. van; Crul, B.J.P.

    2001-01-01

    Pain partially responsive to opioids can lead to rapid escalating dosages due to tolerance development. In this report the case of a 58-year-old female with neuropathic pain using increasing transdermal (TTS) fentanyl dosages to a maximum dose of 3400 microg/h resulting in fentanyl plasma levels of

  16. Treatment with subcutaneous and transdermal fentanyl: results from a population pharmacokinetic study in cancer patients

    NARCIS (Netherlands)

    Oosten, A.W.; Abrantes, J.A.; Jonsson, S.; Bruijn, P. de; Kuip, E.J.M.; Falcao, A.; Rijt, C.C. van der; Mathijssen, R.H.

    2016-01-01

    PURPOSE: Transdermal fentanyl is effective for the treatment of moderate to severe cancer-related pain but is unsuitable for fast titration. In this setting, continuous subcutaneous fentanyl may be used. As data on the pharmacokinetics of continuous subcutaneous fentanyl are lacking, we studied the

  17. Treatment with subcutaneous and transdermal fentanyl: Results from a population pharmacokinetic study in cancer patients

    NARCIS (Netherlands)

    A.W. Oosten (Astrid); J.A. Abrantes (João A.); S. Jönsson (Siv); P. de Bruijn (Peter); E.J.M. Kuip (Evelien); A. Falcão (Amílcar); C.C.D. van der Rijt (Carin); A.H.J. Mathijssen (Ron)

    2016-01-01

    textabstractPurpose: Transdermal fentanyl is effective for the treatment of moderate to severe cancer-related pain but is unsuitable for fast titration. In this setting, continuous subcutaneous fentanyl may be used. As data on the pharmacokinetics of continuous subcutaneous fentanyl are lacking, we

  18. Efficacy of a single dose of a transdermal diclofenac patch as pre ...

    African Journals Online (AJOL)

    2012-01-25

    Jan 25, 2012 ... When the side-effects were compared between the groups using a test of proportions, it was not significant. Discussion. The results of our study suggest that when applied at the beginning of surgery, a transdermal patch of diclofenac is as effective as intramuscular diclofenac in prolonging the requirement ...

  19. Functionalization of Cotton Fabrics with Polycaprolactone Nanoparticles for Transdermal Release of Melatonin

    Directory of Open Access Journals (Sweden)

    Daniele Massella

    2017-12-01

    Full Text Available Drug delivery by means of transdermal patches raised great interest as a non-invasive and sustained therapy. The present research aimed to design a patch for transdermal delivery of melatonin, which was encapsulated in polycaprolactone (PCL nanoparticles (NPs by employing flash nanoprecipitation (FNP technique. Melatonin-loaded PCL nanoparticles were successfully prepared with precise control of the particle size by effectively tuning process parameters. The effect of process parameters on the particle size was assessed by dynamic light scattering for producing particles with suitable size for transdermal applications. Quantification of encapsulated melatonin was performed by mean of UV spectrophotometry, obtaining the estimation of encapsulation efficiency (EE% and loading capacity (LC%. An EE% higher than 80% was obtained. Differential scanning calorimetry (DSC analysis of NPs was performed to confirm effective encapsulation in the solid phase. Cotton fabrics, functionalized by imbibition with the nano-suspension, were analyzed by scanning electron microscopy to check morphology, adhesion and distribution of the NPs on the surface; melatonin transdermal release from the functionalized fabric was performed via Franz’s cells by using a synthetic membrane. NPs were uniformly distributed on cotton fibres, as confirmed by SEM observations; the release test showed a continuous and controlled release whose kinetics were satisfactorily described by Baker–Lonsdale model.

  20. Transdermal Delivery and Cutaneous Targeting of Antivirals using a Penetration Enhancer and Lysolipid Prodrugs

    Czech Academy of Sciences Publication Activity Database

    Diblíková, D.; Kopečná, M.; Školová, B.; Krečmerová, Marcela; Roh, J.; Hrabálek, A.; Vávrová, K.

    2014-01-01

    Roč. 31, č. 4 (2014), s. 1071-1081 ISSN 0724-8741 Grant - others:GA ČR(CZ) GAP207/11/0365 Institutional support: RVO:61388963 Keywords : acyclic nucleoside phosphonate antivirals * lysolipid prodrug * penetration enhancer * skin absorption * transdermal drug delivery Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 3.420, year: 2014

  1. Novel diffusion cell for in vitro transdermal permeation, compatible with automated dynamic sampling

    NARCIS (Netherlands)

    Bosman, I.J; Lawant, A.L; Avegaart, S.R.; Ensing, K; de Zeeuw, R.A

    The development of a new diffusion cell for in vitro transdermal permeation is described. The so-called Kelder cells were used in combination with the ASPEC system (Automatic Sample Preparation with Extraction Columns), which is designed for the automation of solid-phase extractions (SPE). Instead

  2. In vitro human skin permeation of endoxifen: potential for local transdermal therapy for primary prevention and carcinoma in situ of the breast

    Directory of Open Access Journals (Sweden)

    Lee O

    2011-07-01

    Full Text Available Oukseub Lee1, David Ivancic1, Robert T Chatterton Jr2, Alfred W Rademaker3, Seema A Khan11Department of Surgery, 2Department of Obstetrics/Gynecology, 3Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USAPurpose: Oral tamoxifen, a triphenylethylene (TPE, is useful for breast cancer prevention, but its adverse effects limit acceptance by women. Tamoxifen efficacy is related to its major metabolites 4-hydroxytamoxifen (4-OHT and N-desmethyl-4-hydroxytamoxifen (endoxifen [ENX]. Transdermal delivery of these to the breast may avert the toxicity of oral tamoxifen while maintaining efficacy. We evaluated the relative efficiency of skin permeation of 4-OHT and ENX in vitro, and tested oleic acid (OA as a permeation-enhancer.Methods: 4-OHT, ENX, and estradiol (E2 (0.2 mg/mL of 0.5 µCi 3H/mg were dissolved in 60% ethanol-phosphate buffer, ±OA (0.1%–5%. Permeation through EpiDermTM (Matek Corp, Ashland, MA and split-thickness human skin was calculated based on the amount of the agents recovered from the receiver fluid and skin using liquid scintillation counting over 24 hours.Results: In the EpiDerm model, the absorption of 4-OHT and ENX was 10%–11%; total penetration (TP was 26%–29% at 24 hours and was decreased by OA. In normal human skin, the absorption of 4-OHT and ENX was 0.3%; TP was 2%–4% at 24 hours. The addition of 1% OA improved the permeation of ENX significantly more than that of 4-OHT (P < 0.004; further titration of OA at 0.25%–0.5% further improved the permeation of ENX to a level similar to that of estradiol.Conclusion: The addition of OA to ENX results in a favorable rapid delivery equivalent to that of estradiol, a widely used transdermal hormone. The transdermal delivery of ENX to the breast should be further developed in preclinical and clinical studies.Keywords: endoxifen, breast cancer prevention, human skin, transdermal, oleic acid

  3. Student Teachers' Emotional Teaching Experiences in Relation to Different Teaching Methods

    Science.gov (United States)

    Timoštšuk, I.; Kikas, E.; Normak, M.

    2016-01-01

    The role of emotional experiences in teacher training is acknowledged, but the role of emotions during first experiences of classroom teaching has not been examined in large samples. This study examines the teaching methods used by student teachers in early teaching practice and the relationship between these methods and emotions experienced. We…

  4. Thai Undergraduate Chemistry Practical Learning Experiences Using the Jigsaw IV Method

    Science.gov (United States)

    Jansoon, Ninna; Somsook, Ekasith; Coll, Richard K.

    2008-01-01

    The research reported in this study consisted of an investigation of student learning experiences in Thai chemistry laboratories using the Jigsaw IV method. A hands-on experiment based on the Jigsaw IV method using a real life example based on green tea beverage was designed to improve student affective variables for studying topics related to…

  5. An Enzymatic Clinical Chemistry Laboratory Experiment Incorporating an Introduction to Mathematical Method Comparison Techniques

    Science.gov (United States)

    Duxbury, Mark

    2004-01-01

    An enzymatic laboratory experiment based on the analysis of serum is described that is suitable for students of clinical chemistry. The experiment incorporates an introduction to mathematical method-comparison techniques in which three different clinical glucose analysis methods are compared using linear regression and Bland-Altman difference…

  6. Experiences from introduction of peer-to-peer teaching methods in Advanced Biochemistry E2010

    DEFF Research Database (Denmark)

    Brodersen, Ditlev; Etzerodt, Michael; Rasmussen, Jan Trige

    2012-01-01

    During the autumn semester 2010, we experimented with a range of active teaching methods on the course, Advanced Biochemistry, at the Department of Molecular Biology and Genetics.......During the autumn semester 2010, we experimented with a range of active teaching methods on the course, Advanced Biochemistry, at the Department of Molecular Biology and Genetics....

  7. Computational Experience with Globally Convergent Descent Methods for Large Sparse Systems of Nonlinear Equations

    Czech Academy of Sciences Publication Activity Database

    Lukšan, Ladislav; Vlček, Jan

    1998-01-01

    Roč. 8, č. 3-4 (1998), s. 201-223 ISSN 1055-6788 R&D Projects: GA ČR GA201/96/0918 Keywords : nonlinear equations * Armijo-type descent methods * Newton-like methods * truncated methods * global convergence * nonsymmetric linear systems * conjugate gradient -type methods * residual smoothing * computational experiments Subject RIV: BB - Applied Statistics, Operational Research

  8. Evaluation of transdermal delivery of nanoemulsions in ex vivo porcine skin using two-photon microscopy and confocal laser-scanning microscopy

    Science.gov (United States)

    Choi, Sanghoon; Kim, Jin Woong; Lee, Yong Joong; Delmas, Thomas; Kim, Changhwan; Park, Soyeun; Lee, Ho

    2014-10-01

    This study experimentally evaluates the self-targeting ability of asiaticoside-loaded nanoemulsions compared with nontargeted nanoemulsions in ex vivo experiments with porcine skin samples. Homebuilt two-photon and confocal laser-scanning microscopes were employed to noninvasively examine the transdermal delivery of two distinct nanoemulsions. Prior to the application of nanoemulsions, we noninvasively observed the morphology of porcine skin using two-photon microscopy. We have successfully visualized the distributions of the targeted and nontargeted nanoemulsions absorbed into the porcine skin samples. Asiaticoside-loaded nanoemulsions showed an improved ex vivo transdermal delivery through the stratum corneum compared with nonloaded nanoemulsions. As a secondary measure, nanoemulsions-applied samples were sliced in the depth direction with a surgical knife in order to obtain the complete depth-direction distribution profile of Nile red fluorescence. XZ images demonstrated that asiaticoside-loaded nanoemulsion penetrated deeper into the skin compared with nontargeted nanoemulsions. The basal layer boundary is clearly visible in the case of the asiaticoside-loaded skin sample. These results reaffirm the feasibility of using self-targeting ligands to improve permeation through the skin barrier for cosmetics and topical drug applications.

  9. Accuracy of the improved quasistatic space-time method checked with experiment

    International Nuclear Information System (INIS)

    Kugler, G.; Dastur, A.R.

    1976-10-01

    Recent experiments performed at the Savannah River Laboratory have made it possible to check the accuracy of numerical methods developed to simulate space-dependent neutron transients. The experiments were specifically designed to emphasize delayed neutron holdback. The CERBERUS code using the IQS (Improved Quasistatic) method has been developed to provide a practical yet accurate tool for spatial kinetics calculations of CANDU reactors. The code was tested on the Savannah River experiments and excellent agreement was obtained. (author)

  10. Preparation and characterization of metoprolol tartrate containing matrix type transdermal drug delivery system.

    Science.gov (United States)

    Malipeddi, Venkata Ramana; Awasthi, Rajendra; Ghisleni, Daniela Dal Molim; de Souza Braga, Marina; Kikuchi, Irene Satiko; de Jesus Andreoli Pinto, Terezinha; Dua, Kamal

    2017-02-01

    The present study aimed to develop matrix-type transdermal drug delivery system (TDDS) of metoprolol tartrate using polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA). The transdermal films were evaluated for physical parameters, Fourier transform infrared spectroscopy analysis (FTIR), differential scanning calorimetry (DSC), in vitro drug release, in vitro skin permeability, skin irritation test and stability studies. The films were found to be tough, non-sticky, easily moldable and possess good tensile strength. As the concentration of PVA was increased, the tensile strength of the films was also increased. Results of FTIR spectroscopy and DSC revealed the absence of any drug-polymer interactions. In vitro release of metoprolol followed zero-order kinetics and the mechanism of release was found to be diffusion rate controlled. In vitro release studies of metoprolol using Keshary-Chein (vertical diffusion cell) indicated 65.5 % drug was released in 24 h. In vitro skin permeation of metoprolol transdermal films showed 58.13 % of the drug was released after 24 h. In vitro skin permeation of metoprolol followed zero-order kinetics in selected formulations. The mechanism of release was found to be diffusion rate controlled. In a 22-day skin irritation test, tested formulation of transdermal films did not exhibit any allergic reactions, inflammation, or contact dermatitis. The transdermal films showed good stability in the 180-day stability study. It can be concluded that the TDDS of MPT can help in bypassing the first-pass effect and will provide patient improved compliance, without sacrificing the therapeutic advantages of the drugs.

  11. Transdermal delivery and cutaneous targeting of antivirals using a penetration enhancer and lysolipid prodrugs.

    Science.gov (United States)

    Diblíková, Denisa; Kopečná, Monika; Školová, Barbora; Krečmerová, Marcela; Roh, Jaroslav; Hrabálek, Alexandr; Vávrová, Kateřina

    2014-04-01

    In this work, we investigate prodrug and enhancer approaches for transdermal and topical delivery of antiviral drugs belonging to the 2,6-diaminopurine acyclic nucleoside phosphonate (ANP) group. Our question was whether we can differentiate between transdermal and topical delivery, i.e., to control the delivery of a given drug towards either systemic absorption or retention in the skin. The in vitro transdermal delivery and skin concentrations of seven antivirals, including (R)- and (S)-9-[2-(phosphonomethoxy)propyl]-2,6-diaminopurine (PMPDAP), (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]-2,6-diaminopurine ((S)-HPMPDAP), its 8-aza analog, and their cyclic and hexadecyloxypropyl (HDP) prodrugs, was investigated with and without the penetration enhancer dodecyl-6-(dimethylamino)hexanoate (DDAK) using human skin. The ability of ANPs to cross the human skin barrier was very low (0.5-1.4 nmol/cm(2)/h), and the majority of the compounds were found in the stratum corneum, the uppermost skin layer. The combination of antivirals and the penetration enhancer DDAK proved to be a viable approach for transdermal delivery, especially in case of (R)-PMPDAP, an anti-HIV effective drug (30.2 ± 2.3 nmol/cm(2)/h). On the other hand, lysophospholipid-like HDP prodrugs, e.g., HDP-(S)-HPMPDAP, reached high concentrations in viable epidermis without significant systemic absorption. By using penetration enhancers or lysolipid prodrugs, it is possible to effectively target systemic diseases by the transdermal route or to target cutaneous pathologies by topical delivery.

  12. Transdermal delivery of isoniazid and rifampin in guinea pigs by electro-phonophoresis.

    Science.gov (United States)

    Chen, Suting; Han, Yi; Yu, Daping; Huo, Fengmin; Wang, Fen; Li, Yunxu; Dong, Lingling; Liu, Zhidong; Huang, Hairong

    2017-11-01

    Electro-phonophoresis (EP) has been used as a drug delivery approach in clinical fields. The objective of the present study is to evaluate the skin permeability of isoniazid and rifampin in guinea pigs by EP to provide reference basis for clinical applications of such transdermal delivery system in the treatment of patients with superficial tuberculosis. Isoniazid and rifampin solutions were delivered transdermally with or without EP in health guinea pigs for 0.5 h. Local skin and blood samples were collected serially at 0, 1/2, 1, 2, 4, 6 and 24 h after dosing. Drug concentrations in local skin and blood were evaluated by high-performance liquid chromatography. Isoniazid concentrations in local skin of guinea pigs receiving isoniazid through EP transdermal delivery were significantly higher than in animals receiving only isoniazid with transdermal patch. However, for rifampin, patches alone group presented almost uniform concentration versus time curve with that of EP group, and both groups had concentrations much higher than the therapeutic concentration of the drug over sustainable time. After EP transdermal delivery, the mean peak concentrations of isoniazid and rifampin in skin were 771.0 ± 163.4 μg/mL and 81.2 ± 17.3 μg/mL respectively. Neither isoniazid nor rifampin concentration in blood could be detected (below the lower detection limit of 1 μg/mL) at any time point. The present study showed that application of EP significantly enhanced INH penetration through skin in guinea pigs, while RIF patch alone obtained therapeutic concentration in local skin. Our work suggests several possible medication approaches for efficient treatment of superficial tuberculosis.

  13. Therapeutic serum phenobarbital concentrations obtained using chronic transdermal administration of phenobarbital in healthy cats.

    Science.gov (United States)

    Delamaide Gasper, Joy A; Barnes Heller, Heidi L; Robertson, Michelle; Trepanier, Lauren A

    2015-04-01

    Seizures are a common cause of neurologic disease, and phenobarbital (PB) is the most commonly used antiepileptic drug. Chronic oral dosing can be challenging for cat owners, leading to poor compliance. The purpose of this study was to determine if the transdermal administration of PB could achieve serum PB concentrations of between 15 and 45 μg/ml in healthy cats. Nineteen healthy cats were enrolled in three groups. Transdermal PB in pluronic lecithin organogel (PLO) was applied to the pinnae for 14 days at a dosage of 3 mg/kg q12h in group 1 (n = 6 cats) and 9 mg/kg q12h in group 2 (n = 7 cats). Transdermal PB in Lipoderm Activemax was similarly applied at 9 mg/kg q12h for 14 days in group 3 (n = 6 cats). Steady-state serum PB concentrations were measured at trough, and at 2, 4 and 6 h after the morning dose on day 15. In group 1, median concentrations ranged from 6.0-7.5 μg/ml throughout the day (observed range 0-11 μg/ml). Group 2 median concentrations were 26.0 μg/ml (observed range 18.0-37.0 μg/ml). For group 3, median concentrations ranged from 15.0-17.0 μg/ml throughout the day (range 5-29 μg/ml). Side effects were mild. One cat was withdrawn from group 2 owing to ataxia and sedation. These results show therapeutic serum PB concentrations can be achieved in cats following chronic transdermal administration of PB in PLO at a dosage of 9 mg/kg q12h. More individual variation was noted using Lipoderm Activemax. Transdermal administration may be an alternative for cats that are difficult to medicate orally. © ISFM and AAFP 2014.

  14. Genetic, pathological and physiological determinants of transdermal fentanyl pharmacokinetics in 620 cancer patients of the EPOS study

    DEFF Research Database (Denmark)

    Barratt, Daniel T; Bandak, Benedikte; Klepstad, Pål

    2014-01-01

    This study aimed to investigate whether CYP3A4/5 genetic variants, together with clinical and patient factors, influence serum fentanyl and norfentanyl concentrations and their ratio in cancer pain patients receiving transdermal fentanyl....

  15. The Effectiveness of Transdermal Opioid in the Management Multiple Rib Fractures: Randomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    Okan Solak

    2013-09-01

    Full Text Available Background: The most commonly observed pathology in chest traumas is rib fracture, and the most important clinical symptom is severe pain. Aims: To investigate the effectiveness of intramuscular opioid (IMO, intravenous patient-controlled analgesia (IVPCA and the Fentanyl transdermal therapeutic system (TTS in the management of rib fracture pain. Study Design: Prospective randomized clinical trial. Methods: In our prospective and randomised study, we included 45 patients with a diagnosis of multiple rib fractures. There were three groups and intercostal nerve blockage (ICB in the first day and oral paracetamol for five days was administered to each group as standard. In Group IMO (n=15, 4x40 mg pethidine HCl was administered to the patients, while in Group IVPCA (n=15 this was 5 µg/mL continuous intravenous fentanyl and was 50 µg fentanyl TTS in Group TTS (n=15. The demographics, injury data and vital signs of the patients were recorded. Pain was scored using Visual Analogue Scale (VAS. The pain during lying down (VASl and mobilisation (VASm was detected. Results: There were no differences between the three groups regarding age, sex, the trauma pattern, the number and distribution of costal fracture localisations, the presence of additional pathology, complications, thoracal catheter and the duration of thoracal catheter. No significant difference between the groups regarding systolic and diastolic arterial tension, number of breaths and beats in a minute was observed (p>0.05. We observed an improvement in the mean VAS score after treatment in all three groups. The mean VASl score significantly decreased after treatment in each group (p0.05. Conclusion: In the analgesia of patients with multiple rib fractures, TTS administration with ICB showed similar effectiveness with IVPCA administration with ICB. In the management of pain due to multiple rib fractures, TTS administration is a safe, non-invasive and effective procedure.

  16. Economies of using seismic experience data qualification methods at Department of Energy facilities

    International Nuclear Information System (INIS)

    Loceff, F.; Antaki, G.; Goen, L.

    1995-01-01

    This paper summarizes the implementation of the seismic qualification of existing equipment using experience data techniques. The emphasis is on the economies of this approach compared with standard qualification methods of analysis and testing or replacement with qualified equipment. Seismic qualification of existing equipment using experience data is a technical necessity and is the most economically attractive of the options. Representative costs for seismic qualification at two facilities show costs are substantially lower than the costs for qualification using conventional methods. Because of the experience to date, the authors recommend that the Department of Energy continue to sponsor the Existing Facilities Program for applying qualification using experience data techniques at DOE facilities

  17. Assay of 6-gingerol in CO2 supercritical fluid extracts of ginger and evaluation of its sustained release from a transdermal delivery system across rat skin.

    Science.gov (United States)

    Chen, Yan; Zhang, Cuiping; Zhang, Mei; Fu, Xiaobing

    2014-07-01

    Ginger has been widely used as healthy food condiment as well as traditional Chinese medicine since antiquity. Multiple potentials of ginger for treatment of various ailments have been revealed. However, the biological half-life of 6-gingerol (a principal pungent ingredient of ginger) is only 7.23 minutes while taken orally. Delivery of ginger compositions by routes other than oral have scarcely been reported. Therefore, we studied a noninvasive transdermal drug delivery system (TDDS) of ginger to bypass hepatic first pass metabolism, avoid gastrointestinal degradation and achieve long persistent release of effective compositions. After establishment of a HPLC analysis method of 6-gingerol, assays of 6-gingerol were performed to compare two kinds of ginger extracts. Then, the characteristics of transdermal delivery of 6-gingerol in TDDS were exhibited. The results showed that the contents of 6-gingerol in two kinds of ginger extracts were significantly different. The maximal delivery percentage of 6-gingerol across rat skin at 20 h was more than 40% in different TDDS formulations. TDDS may provide long-lasting delivery of ginger compounds.

  18. In vitro efficacy and release study with anti-inflammatory drugs incorporated in adhesive transdermal drug delivery systems.

    Science.gov (United States)

    Meyer, Stefanie; Peters, Nils; Mann, Tobias; Wolber, Rainer; Pörtner, Ralf; Nierle, Jens

    2014-04-01

    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.

  19. How Sensitive Are Transdermal Transport Predictions by Microscopic Stratum Corneum Models to Geometric and Transport Parameter Input?

    Science.gov (United States)

    Wen, Jessica; Koo, Soh Myoung; Lape, Nancy

    2018-02-01

    While predictive models of transdermal transport have the potential to reduce human and animal testing, microscopic stratum corneum (SC) model output is highly dependent on idealized SC geometry, transport pathway (transcellular vs. intercellular), and penetrant transport parameters (e.g., compound diffusivity in lipids). Most microscopic models are limited to a simple rectangular brick-and-mortar SC geometry and do not account for variability across delivery sites, hydration levels, and populations. In addition, these models rely on transport parameters obtained from pure theory, parameter fitting to match in vivo experiments, and time-intensive diffusion experiments for each compound. In this work, we develop a microscopic finite element model that allows us to probe model sensitivity to variations in geometry, transport pathway, and hydration level. Given the dearth of experimentally-validated transport data and the wide range in theoretically-predicted transport parameters, we examine the model's response to a variety of transport parameters reported in the literature. Results show that model predictions are strongly dependent on all aforementioned variations, resulting in order-of-magnitude differences in lag times and permeabilities for distinct structure, hydration, and parameter combinations. This work demonstrates that universally predictive models cannot fully succeed without employing experimentally verified transport parameters and individualized SC structures. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  20. Evaluation Methods for Assessing Users' Psychological Experiences of Web-Based Psychosocial Interventions: A Systematic Review.

    Science.gov (United States)

    Feather, Jacqueline Susan; Howson, Moira; Ritchie, Linda; Carter, Philip D; Parry, David Tudor; Koziol-McLain, Jane

    2016-06-30

    The use of Web-based interventions to deliver mental health and behavior change programs is increasingly popular. They are cost-effective, accessible, and generally effective. Often these interventions concern psychologically sensitive and challenging issues, such as depression or anxiety. The process by which a person receives and experiences therapy is important to understanding therapeutic process and outcomes. While the experience of the patient or client in traditional face-to-face therapy has been evaluated in a number of ways, there appeared to be a gap in the evaluation of patient experiences of therapeutic interventions delivered online. Evaluation of Web-based artifacts has focused either on evaluation of experience from a computer Web-design perspective through usability testing or on evaluation of treatment effectiveness. Neither of these methods focuses on the psychological experience of the person while engaged in the therapeutic process. This study aimed to investigate what methods, if any, have been used to evaluate the in situ psychological experience of users of Web-based self-help psychosocial interventions. A systematic literature review was undertaken of interdisciplinary databases with a focus on health and computer sciences. Studies that met a predetermined search protocol were included. Among 21 studies identified that examined psychological experience of the user, only 1 study collected user experience in situ. The most common method of understanding users' experience was through semistructured interviews conducted posttreatment or questionnaires administrated at the end of an intervention session. The questionnaires were usually based on standardized tools used to assess user experience with traditional face-to-face treatment. There is a lack of methods specified in the literature to evaluate the interface between Web-based mental health or behavior change artifacts and users. Main limitations in the research were the nascency of the topic

  1. Dynamics of psychological crisis experience with psychological consulting by gestalt therapy methods.

    Science.gov (United States)

    Fahrutdinova, Liliya Raifovna; Nugmanova, Dzhamilia Renatovna

    2015-01-01

    Dynamics of experience as such and its corporeal, emotional and cognitive elements in the situation of psychological consulting provisioning is covered. The aim of research was to study psychological crisis experience dynamics in the situation when psychological consulting by gestalt therapy methods is provided. Theoretical analysis of the problem of crisis situations, phenomenon and structural, and dynamic organization of experience of the subject of consulting have been carried out. To fulfill research project test subjects experience crisis situation have been selected, studied in the situation when they provided psychological consulting by methods of gestalt therapy, and methodology of study of crisis situations experience has been prepared. Specifics of psychological crisis experience have been revealed and its elements in different stages of psychological consulting by gestalt therapy methods. Dynamics of experience of psychological crisis and its structural elements have been revealed and reliable changes in it have been revealed. Dynamics of psychological crisis experience and its structural elements have been revealed and reliable changes in it have been revealed. "Desiccation" of experience is being observed, releasing its substantiality of negative impression to the end of consulting and development of the new experience of control over crisis situation. Interrelations of structural elements of experience in the process of psychological consulting have been shown. Effecting one structure causes reliable changes in all others structural elements of experience. Giving actual psychological help to clients in crisis situation by methods of gestalt therapy is possible as it was shown in psychological consulting sessions. Structure of client's request has been revealed - problems of personal sense are fixed as the most frequent cause of clients' applications, as well as absence of choices, obtrusiveness of negative thoughts, tend to getting stuck on events

  2. Design and analysis methods for fish survival experiments based on release-recapture

    National Research Council Canada - National Science Library

    Burnham, Kenneth P

    1987-01-01

    .... The application of the methods developed here is more general, however, as it includes experiments to estimate survival of fish as they pass over spillways or through bypass systems and several dams...

  3. Notification: Notification Memo for Evaluation of Management Controls for Alternative Asbestos Control Method Experiments

    Science.gov (United States)

    Project #OPE-FY12-0011, February 27, 2012. This memorandum is to notify you that the Office of Inspector General (OIG) is initiating an evaluation on the Alternative Asbestos Control Method (AACM) experiments.

  4. Simulating experiments using a Comsol application for teaching scientific research methods

    NARCIS (Netherlands)

    Schijndel, van A.W.M.

    2015-01-01

    For universities it is important to teach the principles of scientific methods as soon as possible. However, in case of performing experiments, students need to have some knowledge and skills before start doing measurements. In this case, Comsol can be helpfully by simulating the experiments before

  5. Experience in Use of Project Method during Technology Lessons in Secondary Schools of the USA

    Science.gov (United States)

    Sheludko, Inna

    2015-01-01

    The article examines the opportunities and prospects for the use of experience of project method during "technology lessons" in US secondary schools, since the value of project technology implementation experience into the educational process in the USA for ensuring holistic development of children, preparing them for adult life, in…

  6. Genetic Risk by Experience Interaction for Childhood Internalizing Problems: Converging Evidence across Multiple Methods

    Science.gov (United States)

    Vendlinski, Matthew K.; Lemery-Chalfant, Kathryn; Essex, Marilyn J.; Goldsmith, H. Hill

    2011-01-01

    Background: Identifying how genetic risk interacts with experience to predict psychopathology is an important step toward understanding the etiology of mental health problems. Few studies have examined genetic risk by experience interaction (GxE) in the development of childhood psychopathology. Methods: We used both co-twin and parent mental…

  7. Experience-Sampling Research Methods and Their Potential for Education Research

    Science.gov (United States)

    Zirkel, Sabrina; Garcia, Julie A.; Murphy, Mary C.

    2015-01-01

    Experience-sampling methods (ESM) enable us to learn about individuals' lives in context by measuring participants' feelings, thoughts, actions, context, and/or activities as they go about their daily lives. By capturing experience, affect, and action "in the moment" and with repeated measures, ESM approaches allow researchers…

  8. Exploring Reticence in Research Methods: The Experience of Studying Psychological Research Methods in Higher Education

    Science.gov (United States)

    Kingsley, Barbara E.; Robertson, Julia M.

    2017-01-01

    As a fundamental element of any psychology degree, the teaching and learning of research methods is repeatedly brought into sharp focus, and it is often regarded as a real challenge by undergraduate students. The reasons for this are complex, but frequently attributed to an aversion of maths. To gain a more detailed understanding of students'…

  9. The integrated circuit IC EMP transient state disturbance effect experiment method investigates

    International Nuclear Information System (INIS)

    Li Xiaowei

    2004-01-01

    Transient state disturbance characteristic study on the integrated circuit, IC, need from its coupling path outset. Through cable (aerial) coupling, EMP converts to an pulse current voltage and results in the impact to the integrated circuit I/O orifice passing the cable. Aiming at the armament system construction feature, EMP effect to the integrated circuit, IC inside the system is analyzed. The integrated circuit, IC EMP effect experiment current injection method is investigated and a few experiments method is given. (authors)

  10. Diclofenac Potassium Transdermal Patches Using Natural Rubber Latex Biomembranes as Carrier

    Directory of Open Access Journals (Sweden)

    Natan Roberto de Barros

    2015-01-01

    Full Text Available The aim of this study was to design a compound transdermal patch containing diclofenac potassium (Dic-K using natural rubber latex (NRL biomembrane. The NRL from Hevea brasiliensis is easily manipulated and low cost and presents high mechanical resistance. It is a biocompatible material which can stimulate natural angiogenesis and is capable of adhering cells on its surface. Recent researches have used the NRL for Transdermal Drug Delivery Systems (TDDSs. Dic-K is used for the treatment of rheumatoid arthritis and osteoarthritis and pain relief for postoperative and posttraumatic cases, as well as inflammation and edema. Results showed that the biomembrane can release Dic-K for up to 216 hours. The kinetics of the Dic-K release could be fitted with double exponential function. X-ray diffraction and Fourier Transform Infrared (FTIR spectroscopy show some interaction by hydrogen bound. The results indicated the potential of the compound patch.

  11. Expanding the domain of drug delivery for HIV prevention: exploration of the transdermal route.

    Science.gov (United States)

    Puri, Ashana; Sivaraman, Arunprasad; Zhang, Wei; Clark, Meredith R; Banga, Ajay K

    2017-01-01

    Constant efforts for HIV prevention using antiretroviral drugs, pre- and postexposure prophylactic agents, and microbicides are being made by researchers. Drug-delivery systems such as oral tablets and coitally dependent vaginal gels are short acting, require daily application, and are associated with user adherence issues, whereas the coitally independent systems such as injectables and biodegradable implants are long acting, lasting several months, during which time the termination of prophylaxis is impractical in case of adverse effects. An effective drug-delivery system to be used for an intermediate duration, if available, would be an attractive alternative option for users in terms of adherence. Transdermal delivery systems, overcoming most of the limitations of the other routes of administration and aiming to provide sustained delivery of drugs through skin, may be explored for HIV prevention. Passive and physical enhancement techniques may be designed strategically to improve the transdermal delivery of HIV preventive agents.

  12. Current and emerging lipid-based systems for transdermal drug delivery.

    Science.gov (United States)

    Singla, Sumeet K; Sachdeva, Vishal

    2015-01-01

    Developing a transdermal drug delivery system is a challenging task considering the selective permeability of the skin and the physicochemical properties the drug must possess to permeate through the skin. Lipid-based drug delivery systems have contributed a great deal in this direction in the last few decades, and thereby have helped to expand the range of therapeutic molecules that can be delivered through the skin in a safe and effective manner. Additionally, vesicular delivery systems such as nanoparticles and emulsions have also played important roles in providing alternative novel approaches for drug delivery. In this article, we will discuss some of the current and future lipid-based systems for transdermal drug delivery along with the associated challenges.

  13. Acute Intoxication by Transdermal Opium Application in Infants: Two Case Reports

    Directory of Open Access Journals (Sweden)

    Iraj Sedighi

    2012-05-01

    Full Text Available Background: Acute opium intoxication is one of the most common causes of poisoning in children in Iran. Although most cases are accidental, traditional misuse of opium for symptomatic therapy of various childhood diseases also contributes to high rate of opium intoxication in Iran. Cases: Here, we report two cases of opium intoxication in infants resulted from transdermal application of opium on burned skin. To our knowledge this is the first case report of intoxication from transdermal misuse of opium. Conclusion: Health care providers should be aware about signs and symptoms of opium intoxication in children. Opium intoxication should be suspected in each child with history of a recent burn injury that presented with decreased level of consciousness.

  14. Flexible and Stretchable Microneedle Patches with Integrated Rigid Stainless Steel Microneedles for Transdermal Biointerfacing.

    Science.gov (United States)

    Rajabi, Mina; Roxhed, Niclas; Shafagh, Reza Zandi; Haraldson, Tommy; Fischer, Andreas Christin; Wijngaart, Wouter van der; Stemme, Göran; Niklaus, Frank

    2016-01-01

    This paper demonstrates flexible and stretchable microneedle patches that combine soft and flexible base substrates with hard and sharp stainless steel microneedles. An elastomeric polymer base enables conformal contact between the microneedle patch and the complex topography and texture of the underlying skin, while robust and sharp stainless steel microneedles reliably pierce the outer layers of the skin. The flexible microneedle patches have been realized by magnetically assembling short stainless steel microneedles into a flexible polymer supporting base. In our experimental investigation, the microneedle patches were applied to human skin and an excellent adaptation of the patch to the wrinkles and deformations of the skin was verified, while at the same time the microneedles reliably penetrate the surface of the skin. The unobtrusive flexible and stretchable microneedle patches have great potential for transdermal biointerfacing in a variety of emerging applications such as transdermal drug delivery, bioelectric treatments and wearable bio-electronics for health and fitness monitoring.

  15. A comparative study on the transdermal penetration effect of gaseous and aqueous plasma reactive species

    Science.gov (United States)

    Liu, Xin; Gan, Lu; Ma, Mingyu; Zhang, Song; Liu, Jingjing; Chen, Hongxiang; Liu, Dawei; Lu, Xinpei

    2018-02-01

    To improve the depth of plasma active species in the skin, it is very important to develop skin disease treatment using plasma. In this article, an air plasma source was used to work directly with the skin of a mouse. A tortuous pathway, hair follicles, electroporation and a microneedle do not aid the transdermal delivery of gaseous plasma active species, therefore these gaseous plasma active species cannot penetrate mouse skin with a thickness of ~0.75 mm. The plasma activated water (PAW) produced by the air plasma source was used to study the transdermal penetration of the aqueous plasma activated species. This aqueous plasma activated species can penetrate the skin through hair follicles, intercellular and transcellular routes. The pH of the PAW did not affect the penetration efficiency of the aqueous plasma active species.

  16. Unconventional Consumption Methods and Enjoying Things Consumed: Recapturing the "First-Time" Experience.

    Science.gov (United States)

    O'Brien, Ed; Smith, Robert W

    2018-06-01

    People commonly lament the inability to re-experience familiar things as they were first experienced. Four experiments suggest that consuming familiar things in new ways can disrupt adaptation and revitalize enjoyment. Participants better enjoyed the same familiar food (Experiment 1), drink (Experiment 2), and video (Experiments 3a-3b) simply when re-experiencing the entity via unusual means (e.g., eating popcorn using chopsticks vs. hands). This occurs because unconventional methods invite an immersive "first-time" perspective on the consumption object: boosts in enjoyment were mediated by revitalized immersion into the consumption experience and were moderated by time such that they were strongest when using unconventional methods for the first time (Experiments 1-2); likewise, unconventional methods that actively disrupted immersion did not elicit the boost, despite being novel (Experiments 3a-3b). Before abandoning once-enjoyable entities, knowing to consume old things in new ways (vs. attaining new things altogether) might temporarily restore enjoyment and postpone wasteful replacement.

  17. TRANSDERMAL PERMEABILITY OF ESTRADIOL THROUGH THE HUMAN SKIN OF DIFFERENT BODY REGIONS IN VITRO

    Institute of Scientific and Technical Information of China (English)

    CHENGuo-Shen; GONGSai-Jun; DUJie; MARun-Zhen; ZHOURong-Rong; LIULiang-Chu

    1989-01-01

    Transdermal permeability of estradiol was carried out by using Valia-Chien double compartment permeation cells for the following regions of intact skin and skin without stratum corncum: chest, abdomen, hip, upper arm, thigh and back. The estradiol permeation rates and accumulative amounts within 72h in vitro were examined by HPLC. The results showed that the permeation rates of intact skin from different regions of the body

  18. A Transdermal Drug Delivery System Based on LIGA Technology and Soft Lithography

    Science.gov (United States)

    Matteucci, Marco; Perennes, Frederic; Marmiroli, Benedetta; Di Fabrizio, Enzo

    2007-01-01

    This report presents a transdermal drug delivery system based on LIGA fabricated microparts. It is a portable device combining a magnetically actuated micro gear pump with a microneedle array. The fluidic behaviour of the system is analyzed in order to predict its performance according to the dimension of the microparts and then compared to experimental data. The manufacturing process of both micropump and microneedle array are described.

  19. Effect of electron beam irradiation on bacterial cellulose membranes used as transdermal drug delivery systems

    Energy Technology Data Exchange (ETDEWEB)

    Stoica-Guzun, Anicuta [Department of Chemical Engineering, ' Politehnica' University Bucharest, 313 Splaiul Independentei, 060042 Bucharest (Romania)], E-mail: astoica@mt.pub.ro; Stroescu, Marta; Tache, Florin [Department of Chemical Engineering, ' Politehnica' University Bucharest, 313 Splaiul Independentei, 060042 Bucharest (Romania); Zaharescu, Traian [Advanced Research Institute for Electrical Engineering, 313 Splaiul Unirii, 030138 Bucharest (Romania)], E-mail: zaharescut@icpe-ca.ro; Grosu, Elena [Department of Chemical Engineering, ' Politehnica' University Bucharest, 313 Splaiul Independentei, 060042 Bucharest (Romania)

    2007-12-15

    Ionizing radiation is an effective energetic source for polymer surfaces modification in order to obtain transdermal systems with different controlled release properties. In this work, gamma rays have been applied to induce changes in bacterial cellulose membranes. Permeation of drug (tetracycline) was theoretically and experimentally investigated starting from the effect of {gamma}-irradiation on membranes permeability. Release and permeation of drug from irradiated and non-irradiated membranes have been performed using a diffusion cell.

  20. Effect of electron beam irradiation on bacterial cellulose membranes used as transdermal drug delivery systems

    International Nuclear Information System (INIS)

    Stoica-Guzun, Anicuta; Stroescu, Marta; Tache, Florin; Zaharescu, Traian; Grosu, Elena

    2007-01-01

    Ionizing radiation is an effective energetic source for polymer surfaces modification in order to obtain transdermal systems with different controlled release properties. In this work, gamma rays have been applied to induce changes in bacterial cellulose membranes. Permeation of drug (tetracycline) was theoretically and experimentally investigated starting from the effect of γ-irradiation on membranes permeability. Release and permeation of drug from irradiated and non-irradiated membranes have been performed using a diffusion cell

  1. Effect of electron beam irradiation on bacterial cellulose membranes used as transdermal drug delivery systems

    Science.gov (United States)

    Stoica-Guzun, Anicuta; Stroescu, Marta; Tache, Florin; Zaharescu, Traian; Grosu, Elena

    2007-12-01

    Ionizing radiation is an effective energetic source for polymer surfaces modification in order to obtain transdermal systems with different controlled release properties. In this work, gamma rays have been applied to induce changes in bacterial cellulose membranes. Permeation of drug (tetracycline) was theoretically and experimentally investigated starting from the effect of γ-irradiation on membranes permeability. Release and permeation of drug from irradiated and non-irradiated membranes have been performed using a diffusion cell.

  2. Nanoethosomal transdermal delivery of vardenafil for treatment of erectile dysfunction: optimization, characterization, and in vivo evaluation

    Directory of Open Access Journals (Sweden)

    Fahmy UA

    2015-11-01

    Full Text Available Usama A Fahmy Department of Pharmaceutics & Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia Abstract: Vesicular drug delivery systems have recently gained attention as a way of improving dosing accuracy for drugs with poor transdermal permeation. The current study focuses on utilization of the natural biocompatible vesicles to formulate vardenafil nanoethosomes (VRD-NE, for the enhancement of their transdermal permeation and bioavailability. Fifteen formulations were prepared by thin-layer evaporation technique according to Box–Behnken design to optimize formulation variables. The effects of lipid composition, sonication time, and ethanol concentration on particle size and encapsulation efficiency were studied. The diffusion of vardenafil (VRD from the prepared nanoethosomes specified by the design was carried out using automated Franz diffusion cell apparatus. The optimized formula was investigated for in vivo pharmacokinetic parameters compared with oral VRD suspension. Confocal laser scanning microscopy images were used to confirm enhanced diffusion release of VRD in rat skin. The results showed that the optimized formula produced nanoethosomes with an average size of 128 nm and an entrapment efficiency of 76.23%. VRD-NE provided a significant improvement in permeation with an enhancement ratio of 3.05-fold for a film made with optimally formulated VRD-NE compared with a film made with VRD powder. The transdermal bioavailability of VRD from the nanoethosome film was approximately twofold higher than the oral bioavailability from an aqueous suspension. VRD-NE thus provide a promising transdermal drug delivery system. As a result, management of impotence for a longer duration could be achieved with a reduced dosage rate that improves patient tolerability and compliance for the treatment of erectile dysfunction.Keywords: Box–Behnken design, impotence, vesicles, nanoparticles

  3. Preparation and the in vitro evaluation of nanoemulsion system for the transdermal delivery of granisetron hydrochloride.

    Science.gov (United States)

    Zheng, Wen-wu; Zhao, Ling; Wei, Yu-meng; Ye, Yun; Xiao, Shun-han

    2010-08-01

    The objective of this study was to develop and evaluate nanoemulsion system for transdermal delivery of granisetron hydrochloride. Pseudo-ternary phase diagram was constructed to ascertain the concentration range of components of nanoemulsion composed of isopropyl myristate (IPM) as an oil phase, tween 85 as surfactant, ethanol as cosurfactant, water as aqueous phase. The effects of the content of IPM as an oil phase and n-methyl pyrrolidone (NMP) as transdermal enhancer on rat skin permeation of granisetron hydrochloride nanoemulsion were studied in vitro. The results showed that the mean particle size of nanoemulsion ranged from 50.4+/-1.5 to 82.4+/-0.9 nm with homogeneous size distribution. The resulted optimum formulation composed of 2.5% granisetron hydrochloride, 4% IPM, 40% tween 85/ethanol (1 : 1) and 10% NMP showed that the skin permeation rate was the highest (85.39+/-2.90 microg/cm(2)/h) and enhancement of drug permeability was 4.1-fold for transdermal delivery of granisetron hydrochloridein comparison with the control group (20% of tween 85 and 20% of ethanol micelle solution containing 2.5% of granisetron hydrochloride without IPM), and cumulative permeation amount was the highest (891.8+/-2.86 microg/cm(2)) with the shortest lag time (0.11+/-0.02 h) and was stable for at least 12 months. Therefore, the nanoemulsion system developed in this study offers a promising vehicle for the transdermal delivery system of granisetron hydrochloride, which may be as effective as oral or intravenous dosage forms and avoid some difficulties associated with these dosage forms.

  4. Use and cardiovascular safety of transdermal and other granisetron preparations in cancer management

    OpenAIRE

    Mason, Jay W; Moon, Thomas E

    2013-01-01

    Jay W Mason,1 Thomas E Moon2 1School of Medicine, University of Utah, Salt Lake City, UT, 2Tarizona eHealth Services, Inc, Emeryville, CA, USA Abstract: 5-HT3 antagonists have been available as oral and intravenous preparations for decades. The availability more recently of transdermal granisetron and the anticipated availability of a subcutaneous granisetron preparation have provided helpful alternatives to patients, and these preparations have been shown to have less potential to prolong Q...

  5. Microdose transdermal estrogen therapy for relief of vulvovaginal symptoms in postmenopausal women.

    Science.gov (United States)

    Bachmann, Gloria A; Schaefers, Matthias; Uddin, Alkaz; Utian, Wulf H

    2009-01-01

    The aim of this study was to investigate the effectiveness of microdose transdermal 17beta-estradiol (E2) therapy in postmenopausal women with moderate to severe vulvovaginal symptoms. This report is based on a subset of 121 women who reported most bothersome moderate or severe vulvovaginal symptoms at baseline, from a previous randomized, double-blind, placebo-controlled, multicenter study of 425 healthy, symptomatic, postmenopausal women. Recruits had experienced at least 7 moderate or severe hot flushes daily for at least 1 week or at least 50 moderate or severe hot flushes per week for at least 1 week. Effects on coprimary efficacy variables have been reported previously. Participants received low-dose transdermal E2 plus levonorgestrel (n = 43; nominal delivery 0.023 mg/d E2/0.0075 mg/d levonorgestrel), microdose E2 (n = 42; nominal delivery 0.014 mg/d), or placebo (n = 36) for 12 weeks. Secondary efficacy variables reported herein include mean change from baseline in vaginal pH and vaginal maturation index, the proportion of women with symptoms of vulvar and vaginal atrophy at baseline and week 12, and the proportion of women with moderate-to-severe symptoms of vulvar and vaginal atrophy. Microdose transdermal E2 treatment was associated with a consistent benefit versus placebo in women with vulvovaginal atrophy. There was a statistically significant difference between both E2 versus placebo for changes in vaginal pH and vaginal maturation index. Microdose transdermal E2 offers a useful addition to the therapeutic armamentarium for postmenopausal women in whom vulvovaginal symptoms are particularly troublesome.

  6. Enhanced Topical and Transdermal Delivery of Antineoplastic and Antiviral Acyclic Nucleoside Phosphonate cPr-PMEDAP

    Czech Academy of Sciences Publication Activity Database

    Vávrová, K.; Kovaříková, P.; Školová, B.; Líbalová, M.; Roh, J.; Čáp, R.; Holý, Antonín; Hrabálek, A.

    2011-01-01

    Roč. 28, č. 12 (2011), s. 3105-3115 ISSN 0724-8741 R&D Projects: GA MŠk 1M0508 Grant - others:GA ČR(CZ) GAP207/11/0365 Institutional research plan: CEZ:AV0Z40550506 Keywords : acyclic nucleoside phosphonates * antivirals * antineoplastics * permeation enhancer * topical skin application * transdermal delivery Subject RIV: CC - Organic Chemistry Impact factor: 4.093, year: 2011

  7. Sustained transdermal release of diltiazem hydrochloride through electron beam irradiated different PVA hydrogel membranes

    Energy Technology Data Exchange (ETDEWEB)

    Bhunia, Tridib [Department of Polymer Science and Technology, University of Calcutta, 92 A.P.C. Road, Calcutta 700009 (India); Goswami, Luna [KIIT School of Biotechnology, KIIT University Campus XI, Patia, Bhubaneswar 751024, Orissa (India); Chattopadhyay, Dipankar [Department of Polymer Science and Technology, University of Calcutta, 92 A.P.C. Road, Calcutta 700009 (India); Bandyopadhyay, Abhijit, E-mail: abpoly@caluniv.ac.in [Department of Polymer Science and Technology, University of Calcutta, 92 A.P.C. Road, Calcutta 700009 (India)

    2011-08-15

    Extremely fast release of diltiazem hydrochloride (water soluble, anti anginal drug used to treat chest pain) together with its faster erosion has been the primary problem in conventional oral therapy. It has been addressed in this paper by encapsulating the drug in electron beam irradiated various poly (vinyl alcohol) hydrogel membranes and delivering it through transdermal route. Results show excellent control over the release of diltiazem hydrochloride through these membranes subject to their physico-mechanicals.

  8. Sustained transdermal release of diltiazem hydrochloride through electron beam irradiated different PVA hydrogel membranes

    Science.gov (United States)

    Bhunia, Tridib; Goswami, Luna; Chattopadhyay, Dipankar; Bandyopadhyay, Abhijit

    2011-08-01

    Extremely fast release of diltiazem hydrochloride (water soluble, anti anginal drug used to treat chest pain) together with its faster erosion has been the primary problem in conventional oral therapy. It has been addressed in this paper by encapsulating the drug in electron beam irradiated various poly (vinyl alcohol) hydrogel membranes and delivering it through transdermal route. Results show excellent control over the release of diltiazem hydrochloride through these membranes subject to their physico-mechanicals.

  9. Sustained transdermal release of diltiazem hydrochloride through electron beam irradiated different PVA hydrogel membranes

    International Nuclear Information System (INIS)

    Bhunia, Tridib; Goswami, Luna; Chattopadhyay, Dipankar; Bandyopadhyay, Abhijit

    2011-01-01

    Extremely fast release of diltiazem hydrochloride (water soluble, anti anginal drug used to treat chest pain) together with its faster erosion has been the primary problem in conventional oral therapy. It has been addressed in this paper by encapsulating the drug in electron beam irradiated various poly (vinyl alcohol) hydrogel membranes and delivering it through transdermal route. Results show excellent control over the release of diltiazem hydrochloride through these membranes subject to their physico-mechanicals.

  10. Development of Tat-Conjugated Dendrimer for Transdermal DNA Vaccine Delivery.

    Science.gov (United States)

    Bahadoran, Azadeh; Moeini, Hassan; Bejo, Mohd Hair; Hussein, Mohd Zobir; Omar, Abdul Rahman

    In order to enhance cellular uptake and to facilitate transdermal delivery of DNA vaccine, polyamidoamine (PAMAM) dendrimers conjugated with HIV transactivator of transcription (TAT) was developed. First, the plasmid DNA (pIRES-H5/GFP) nanoparticle was formulated using PAMAM dendrimer and TAT peptide and then characterized for surface charge, particle size, DNA encapsulation and protection of the pIRES-H5/GFP DNA plasmid to enzymatic digestion. Subsequently, the potency of the TAT-conjugated dendrimer for gene delivery was evaluated through in vitro transfection into Vero cells followed by gene expression analysis including western blotting, fluorescent microscopy and PCR. The effect of the TAT peptide on cellular uptake of DNA vaccine was studied by qRT-PCR and flow cytometry. Finally, the ability of TAT-conjugated PAMAM dendrimer for transdermal delivery of the DNA plasmid was assessed through artificial membranes followed by qRT-PCR and flow cytometry. TAT-conjugated PAMAM dendrimer showed the ability to form a compact and nanometre-sized polyplexes with the plasmid DNA, having the size range of 105 to 115 nm and a positive charge of +42 to +45 mV over the N/P ratio of 6:1(+/-).  In vitro transfection analysis into Vero cells confirms the high potency of TAT-conjugated PAMAM dendrimer to enhance the cellular uptake of DNA vaccine.  The permeability value assay through artificial membranes reveals that TAT-conjugated PAMAM has more capacity for transdermal delivery of the DNA compared to unmodified PAMAM dendrimer (Pdendrimer is a promising non-viral vector for transdermal use.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

  11. In vitro transdermal delivery of caffeine, theobromine, theophylline and catechin from extract of Guarana, Paullinia Cupana.

    Science.gov (United States)

    Heard, Charles M; Johnson, Sarah; Moss, Gary; Thomas, Chris P

    2006-07-06

    Extracts of guarana (Paullinia cupana) feature as putatively stimulating ingredients in a number of foods, drinks and dietary/herbal supplements. The objective of this work was to investigate in vitro the transdermal delivery of the major pharmacologically active compounds contained in guarana extract. Saturated solutions of guarana were prepared in polyethylene glycol 400 (PEG400), propylene glycol (PG) and H(2)O at 32 degrees C. Guarana extract was also formulated in Duro-tak 2287 transdermal adhesive in a range of concentrations and the diffusional release was determined in addition to adhesive properties. Transdermal delivery across full thickness pig ear skin was investigated in vitro using Franz-type diffusion cells, with reverse-phase HPLC being used for the quantification of the permeation of theobromine (TB), theophylline (TP), (+)-catechin (C) and caffeine (CF). Based upon a combination of release and adhesive property data a patch containing 5.55 mg guarana extract cm(-2) was deemed optimal. The general trend for the delivery of the 4 analytes was: water >5.55 mg cm(-2) patch approximately PG>PEG400. For CF the greatest steady state flux was obtained from the water vehicle: 19 microg cm(-2)h(-1), with approximately 420 microg cm(-2) permeating after 24h. This was some 6x times more than from the drug-in-adhesive patch and 10x greater than PG, a well-known penetration enhancer, and 50x that of the 'regular' excipient PEG400. A water vehicle also provided the greatest delivery of TB (0.45 microg cm(-2) h(-1)), TP (0.022 microg cm(-2) h(-1)), and C (0.10 microg cm(-2) h(-1)). An inverse relationship was noted between lipophilicity and k(p) in each vehicle. The simultaneous transdermal delivery of the major actives of guarana was established, with permeation rates being highly concentration and vehicle dependent.

  12. The Influence of Solid Microneedles on the Transdermal Delivery of Selected Antiepileptic Drugs

    Directory of Open Access Journals (Sweden)

    Julia Nguyen

    2016-11-01

    Full Text Available The aim of this project was to examine the effect of microneedle rollers on the percutaneous penetration of tiagabine hydrochloride and carbamazepine across porcine skin in vitro. Liquid chromatography-mass spectrometric analysis was carried out using an Agilent 1200 Series HPLC system coupled to an Agilent G1969A TOF-MS system. Transdermal flux values of the drugs were determined from the steady-state portion of the cumulative amount versus time curves. Following twelve hours of microneedle roller application, there was a 6.74-fold increase in the percutaneous penetration of tiagabine hydrochloride (86.42 ± 25.66 µg/cm2/h compared to passive delivery (12.83 ± 6.30 µg/cm2/h. For carbamazepine in 20% ethanol, passive transdermal flux of 7.85 ± 0.60 µg/cm2/h was observed compared to 10.85 ± 0.11 µg/cm2/h after microneedle treatment. Carbamazepine reconstituted in 30% ethanol resulted in only a 1.19-fold increase in drug permeation across porcine skin (36.73 ± 1.83 µg/cm2/h versus 30.74 ± 1.32 µg/cm2/h. Differences in flux values of untreated and microneedle-treated porcine skin using solid microneedles for the transdermal delivery of tiagabine were statistically significant. Although there were 1.38- and 1.19-fold increases in transdermal flux values of carbamazepine when applied as 20% and 30% ethanol solutions across microneedle-treated porcine skin, respectively, the increases were not statistically significant.

  13. Transdermal delivery of scopolamine by natural submicron injectors: in-vivo study in pig.

    Directory of Open Access Journals (Sweden)

    Esther Shaoul

    Full Text Available Transdermal drug delivery has made a notable contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. While transdermal delivery systems would appear to provide an attractive solution for local and systemic drug delivery, only a limited number of drugs can be delivered through the outer layer of the skin. The most difficult to deliver in this way are hydrophilic drugs. The aquatic phylum Cnidaria, which includes sea anemones, corals, jellyfish and hydra, is one of the most ancient multicellular phyla that possess stinging cells containing organelles (cnidocysts, comprising a sophisticated injection system. The apparatus is folded within collagenous microcapsules and upon activation injects a thin tubule that immediately penetrates the prey and delivers its contents. Here we show that this natural microscopic injection system can be adapted for systemic transdermal drug delivery once it is isolated from the cells and uploaded with the drug. Using a topically applied gel containing isolated natural sea anemone injectors and the muscarinic receptor antagonist scopolamine, we found that the formulated injectors could penetrate porcine skin and immediately deliver this hydrophilic drug. An in-vivo study in pigs demonstrated, for the first time, rapid systemic delivery of scopolamine, with T(max of 30 minutes and C(max 5 times higher than in controls treated topically with a scopolamine-containing gel without cnidocysts. The ability of the formulated natural injection system to penetrate a barrier as thick as the skin and systemically deliver an exogenous compound presents an intriguing and attractive alternative for hydrophilic transdermal drug delivery.

  14. Transdermal delivery of naltrexol and skin permeability lifetime after microneedle treatment in hairless guinea pigs

    OpenAIRE

    Banks, Stan L.; Pinninti, Raghotham R.; Gill, Harvinder S.; Paudel, Kalpana S.; Crooks, Peter A.; Brogden, Nicole K.; Prausnitz, Mark R.; Stinchcomb, Audra L.

    2010-01-01

    Controlled-release delivery of 6-β-naltrexol (NTXOL), the major active metabolite of naltrexone, via a transdermal patch is desirable for treatment of alcoholism. Unfortunately, NTXOL does not diffuse across skin at a therapeutic rate. Therefore, the focus of this study was to evaluate microneedle (MN) skin permeation enhancement of NTXOL's hydrochloride salt in hairless guinea pigs. Specifically, these studies were designed to determine the lifetime of MN-created aqueous pore pathways. Micro...

  15. The Effect of Transdermal Scopolamine for the Prevention of Postoperative Nausea and Vomiting

    Directory of Open Access Journals (Sweden)

    Maria A. Antor

    2014-04-01

    Full Text Available Postoperative nausea and vomiting is one of the most common and undesirable complaints recorded in as many as 70%-80% of high-risk surgical patients. The current prophylactic therapy recommendations for PONV management stated in the Society of Ambulatory Anesthesia guidelines should start with monotherapy and patients at moderate to high risk, a combination of antiemetic medication should be considered. Consequently, if rescue medication is required, the antiemetic drug chosen should be from a different therapeutic class and administration mode than the drug used for prophylaxis. The guidelines restrict the use of dexamethasone, transdermal scopolamine, aprepitant, and palonosetron as rescue medication 6 hours after surgery. In an effort to find a safer and reliable therapy for postoperative nausea and vomiting, new drugs with antiemetic properties and minimal side effects are needed, and scopolamine may be considered an effective alternative. Scopolamine is a belladonna alkaloid, α-(hydroxymethyl benzene acetic acid 9-methyl-3-oxa-9-azatricyclo non-7-yl ester, acting as a nonselective muscarinic antagonist and producing both peripheral antimuscarinic and central sedative, antiemetic, and amnestic effects. The empirical formula is C17H21NO4 and its structural formula is a tertiary amine L-(2-scopolamine (tropic acid ester with scopine; MW = 303.4. Scopolamine became the first drug commercially available as a transdermal therapeutic system used for extended continuous drug delivery during 72 hours. Clinical trials with transdermal scopolamine have consistently demonstrated its safety and efficacy in postoperative nausea and vomiting. Thus, scopolamine is a promising candidate for the management of postoperative nausea and vomiting in adults as a first line monotherapy or in combination with other drugs. In addition, transdermal scopolamine might be helpful in preventing postoperative discharge nausea and vomiting owing to its long

  16. Natural oils as skin permeation enhancers for transdermal delivery of olanzapine: in vitro and in vivo evaluation.

    Science.gov (United States)

    Aggarwal, Geeta; Dhawan, Sanju; HariKumar, S L

    2012-03-01

    The feasibility of development of transdermal delivery system of olanzapine utilizing natural oils as permeation enhancers was investigated. Penetration enhancing potential of corn (maize) oil, groundnut oil and jojoba oil on in vitro permeation of olanzapine across rat skin was studied. The magnitude of flux enhancement factor with corn oil, groundnut oil and jojoba oil was 7.06, 5.31 and 1.9 respectively at 5mg/ml concentration in solvent system. On the basis of in vitro permeation studies, eudragit based matrix type transdermal patches of olanzapine were fabricated using optimized concentrations of natural oils as permeation enhancers. All transdermal patches were found to be uniform with respect to physical characteristics. The interaction studies carried out by comparing the results of ultraviolet, HPLC and FTIR analyses for the pure drug, polymers and mixture of drug and polymers indicated no chemical interaction between the drug and excipients. Corn oil containing unsaturated fatty acids was found to be promising natural permeation enhancer for transdermal delivery of olanzapine with greatest cumulative amount of drug permeated (1010.68 μg/cm²/h) up to 24 h and caused no skin irritation. The fabricated transdermal patches were found to be stable. The pharmacokinetic characteristics of the final optimized matrix patch (T2) were determined after transdermal application to rabbits. The calculated relative bioavailability of TDDS was 113.6 % as compared to oral administration of olanzapine. The therapeutic effectiveness of optimized transdermal system was confirmed by tranquillizing activity in rotarod and grip mice model.

  17. Young Dutch people’s everyday experiences of romance and sexuality : A mixed-method approach

    NARCIS (Netherlands)

    Dalenberg, Wieke G.; Timmerman, Margaretha C.; van Geert, Paul L.C.; Kunnen, Elske S.

    2016-01-01

    Objectives: This exploratory study assessed young Dutch people’s emerging sexual experiences in everyday life, in addition to examine the feasibility of a mixed-methods diary study. Methods: Using one-week diaries, 12- –17-year-olds recorded qualitative reports of their everyday romantic and sexual

  18. Learning Practice-Based Research Methods: Capturing the Experiences of MSW Students

    Science.gov (United States)

    Natland, Sidsel; Weissinger, Erika; Graaf, Genevieve; Carnochan, Sarah

    2016-01-01

    The literature on teaching research methods to social work students identifies many challenges, such as dealing with the tensions related to producing research relevant to practice, access to data to teach practice-based research, and limited student interest in learning research methods. This is an exploratory study of the learning experiences of…

  19. Formulation Design and Development of a Unani Transdermal Patch for Antiemetic Therapy and Its Pharmaceutical Evaluation

    Directory of Open Access Journals (Sweden)

    Mohd Nauman Saleem

    2016-01-01

    Full Text Available The Transdermal Drug Delivery System (TDDS is one of the novel routes for systemic delivery of drugs through intact skin. A transdermal patch (TP is a medicated patch that is placed on skin for delivery of medication through skin into the blood stream. The aim of present study was to formulate and evaluate a Unani transdermal patch that could be used for antiemetic therapy. The incorporation of Unani ingredients, namely, Khardal (Brassica nigra, Zanjabeel (Zingiber officinale, Podina (Mentha arvensis, and Sirka (Vinegar were envisaged. The TP was prepared by solvent evaporation technique and was evaluated for organoleptic characteristics and other physicochemical properties, such as thickness, weight uniformity, folding endurance, moisture content, drug content, and tolerability and acceptability of patch. The in vitro permeation study of the patch was carried out through Franz diffusion cell using egg shell membrane as barrier membrane. Phosphate buffer pH 7.4 was used as dissolution medium and the temperature was maintained at 37 ± 1°C. The in vitro permeation study of the prepared TP indicated a time dependent increase in drug release throughout the study. The percentage of cumulative drug release was found to be 77.38% in 24 hours. The study shows a new approach to work in Unani pharmaceutics.

  20. Dendrimer-coupled sonophoresis-mediated transdermal drug-delivery system for diclofenac.

    Science.gov (United States)

    Huang, Bin; Dong, Wei-Jiang; Yang, Gao-Yi; Wang, Wei; Ji, Cong-Hua; Zhou, Fei-Ni

    2015-01-01

    The purpose of the present study was to develop a novel transdermal drug-delivery system comprising a polyamidoamine dendrimer coupled with sonophoresis to enhance the permeation of diclofenac (DF) through the skin. The novel transdermal drug-delivery system was developed by using a statistical Plackett-Burman design. Hairless male Wistar rat skin was used for the DF-permeation study. Coupling media concentration, ultrasound-application time, duty cycle, distance from probe to skin, and a third-generation polyamidoamine-dendrimer concentration were selected as independent variables, while in vitro drug release was selected as a dependent variable. Independent variables were found to be statistically significant (Pdelivery, run 13) showed 56.69 µg/cm(2) cumulative drug permeated through the skin, while the DF-dendrimer gel without sonophoresis treatment (run 14) showed 257.3 µg/cm(2) cumulative drug permeated through the skin after 24 hours. However, when the same gel was applied to sonophoresis-treated skin, drastic permeation enhancement was observed. In the case of run 3, the cumulative drug that permeated through the skin was 935.21 µg/cm(2). It was concluded that dendrimer-coupled sonophoresis-mediated transdermal drug delivery system has the potential to enhance the permeation of DF through the skin.

  1. A New Combination of Testosterone and Nestorone Transdermal Gels for Male Hormonal Contraception

    Science.gov (United States)

    Ilani, Niloufar; Roth, Mara Y.; Amory, John K.; Swerdloff, Ronald S.; Dart, Clint; Page, Stephanie T.; Bremner, William J.; Sitruk-Ware, Regine; Kumar, Narender; Blithe, Diana L.

    2012-01-01

    Context: Combinations of testosterone (T) and nestorone (NES; a nonandrogenic progestin) transdermal gels may suppress spermatogenesis and prove appealing to men for contraception. Objective: The objective of the study was to determine the effectiveness of T gel alone or combined with NES gel in suppressing spermatogenesis. Design and Setting: This was a randomized, double-blind, comparator clinical trial conducted at two academic medical centers. Participants: Ninety-nine healthy male volunteers participated in the study. Interventions: Volunteers were randomized to one of three treatment groups applying daily transdermal gels (group 1: T gel 10 g + NES 0 mg/placebo gel; group 2: T gel 10 g + NES gel 8 mg; group 3: T gel 10 g + NES gel 12 mg). Main Outcome Variable: The main outcome variable of the study was the percentage of men whose sperm concentration was suppressed to 1 million/ml or less by 20–24 wk of treatment. Results: Efficacy data analyses were performed on 56 subjects who adhered to the protocol and completed at least 20 wk of treatment. The percentage of men whose sperm concentration was 1 million/ml or less was significantly higher for T + NES 8 mg (89%, P male range throughout the treatment period. Adverse effects were minimal in all groups. Conclusion: A combination of daily NES + T gels suppressed sperm concentration to 1 million/ml or less in 88.5% of men, with minimal adverse effects, and may be further studied as a male transdermal hormonal contraceptive. PMID:22791756

  2. [{sup 11}C]diclofenac sodium: synthesis and PET assessment of transdermal penetration

    Energy Technology Data Exchange (ETDEWEB)

    Petroni, Debora, E-mail: debora.petroni@ifc.cnr.i [CNR Institute of Clinical Physiology, Via Moruzzi 1, 56124 Pisa (Italy); Menichetti, Luca; Sorace, Oreste; Poli, Michela [CNR Institute of Clinical Physiology, Via Moruzzi 1, 56124 Pisa (Italy); Vanasia, Massimo [Gienne Pharma, Via Lorenteggio 270/A, 20152 Milan (Italy); Salvadori, Piero A. [CNR Institute of Clinical Physiology, Via Moruzzi 1, 56124 Pisa (Italy)

    2011-02-15

    The aim of this work was to study the feasibility of using Positron Emission Tomography (PET) imaging as a new tool to detect transdermal penetration of topical drugs in human subjects. The compound used in the study is sodium 2-[(2,6-dichlorophenyl)amino]phenyl]acetate, better known as diclofenac sodium. This molecule belongs to the family of non-steroidal anti-inflammatory drugs and is considered one of the first choices among non-steroidal anti-inflammatory drugs for the treatment of inflammatory diseases; it is widely used and commercially present in a large number of pharmaceutical forms and formulations. {sup 11}C-labeled diclofenac has been synthesized and coformulated, as an internal indicator, with a proprietary preparation based on the use of a sprayer. The radiolabeled preparation was topically administered to healthy volunteers, and PET imaging was used to evaluate transdermal penetration. Results obtained have demonstrated the efficacy of PET and radiolabeled tracers for the evaluation of transdermal penetration of active pharmaceutical ingredients as topical formulations.

  3. [11C]diclofenac sodium: synthesis and PET assessment of transdermal penetration

    International Nuclear Information System (INIS)

    Petroni, Debora; Menichetti, Luca; Sorace, Oreste; Poli, Michela; Vanasia, Massimo; Salvadori, Piero A.

    2011-01-01

    The aim of this work was to study the feasibility of using Positron Emission Tomography (PET) imaging as a new tool to detect transdermal penetration of topical drugs in human subjects. The compound used in the study is sodium 2-[(2,6-dichlorophenyl)amino]phenyl]acetate, better known as diclofenac sodium. This molecule belongs to the family of non-steroidal anti-inflammatory drugs and is considered one of the first choices among non-steroidal anti-inflammatory drugs for the treatment of inflammatory diseases; it is widely used and commercially present in a large number of pharmaceutical forms and formulations. 11 C-labeled diclofenac has been synthesized and coformulated, as an internal indicator, with a proprietary preparation based on the use of a sprayer. The radiolabeled preparation was topically administered to healthy volunteers, and PET imaging was used to evaluate transdermal penetration. Results obtained have demonstrated the efficacy of PET and radiolabeled tracers for the evaluation of transdermal penetration of active pharmaceutical ingredients as topical formulations.

  4. Exposure to Fentanyl After Transdermal Patch Administration for Cancer Pain Management.

    Science.gov (United States)

    Bista, Sudeep R; Haywood, Alison; Hardy, Janet; Norris, Ross; Hennig, Stefanie

    2016-06-01

    This study aimed to describe exposure after fentanyl transdermal patch administration in patients with advanced cancer to quantify variability around the exposure. Patients (n  =  56) with advanced cancer who received transdermal fentanyl (Durogesic®; median dose, 50 μg/h; range, 12-200 μg/h) provided venous blood samples (n  =  163) at various times (0.5-72 hours) during several patch application intervals. Plasma fentanyl concentration was determined (median, 0.9 μg/L; range, 0.04-9.7 μg/L) by high-performance liquid chromatography coupled to tandem mass spectrometry. Pharmacokinetic analysis was performed using nonlinear mixed-effects modeling with NONMEM. A 1-compartment distribution model with first-order absorption and elimination described fentanyl exposure after transdermal patch administration. Fentanyl apparent clearance (between-subject variability [BSV], %) was estimated at 122 L/h/70 kg and 38.5%, respectively. The absorption rate constant was 0.013 h(-1) . Between-occasion variability on apparent clearance was 22.0%, which was lower than BSV, suggesting predictable exposure within the same patient and justifying therapeutic drug monitoring. Except for weight-based dosing, no other patient characteristic could be identified to guide initial fentanyl dose selection in patients with advanced cancer. © 2015, The American College of Clinical Pharmacology.

  5. A self-adherent, bullet-shaped microneedle patch for controlled transdermal delivery of insulin.

    Science.gov (United States)

    Seong, Keum-Yong; Seo, Min-Soo; Hwang, Dae Youn; O'Cearbhaill, Eoin D; Sreenan, Seamus; Karp, Jeffrey M; Yang, Seung Yun

    2017-11-10

    Proteins are important biologic therapeutics used for the treatment of various diseases. However, owing to low bioavailability and poor skin permeability, transdermal delivery of protein therapeutics poses a significant challenge. Here, we present a new approach for transdermal protein delivery using bullet-shaped double-layered microneedle (MN) arrays with water-swellable tips. This design enabled the MNs to mechanically interlock with soft tissues by selective distal swelling after skin insertion. Additionally, prolonged release of loaded proteins by passive diffusion through the swollen tips was obtained. The bullet-shaped MNs provided an optimal geometry for mechanical interlocking, thereby achieving significant adhesion strength (~1.6Ncm -2 ) with rat skin. By harnessing the MN's reversible swelling/deswelling property, insulin, a model protein drug, was loaded in the swellable tips using a mild drop/dry procedure. The insulin-loaded MN patch released 60% of insulin when immersed in saline over the course of 12h and approximately 70% of the released insulin appeared to have preserved structural integrity. An in vivo pilot study showed a prolonged release of insulin from swellable MN patches, leading to a gradual decrease in blood glucose levels. This self-adherent transdermal MN platform can be applied to a variety of protein drugs requiring sustained release kinetics. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Transdermal delivery of naltrexol and skin permeability lifetime after microneedle treatment in hairless guinea pigs.

    Science.gov (United States)

    Banks, Stan L; Pinninti, Raghotham R; Gill, Harvinder S; Paudel, Kalpana S; Crooks, Peter A; Brogden, Nicole K; Prausnitz, Mark R; Stinchcomb, Audra L

    2010-07-01

    Controlled-release delivery of 6-beta-naltrexol (NTXOL), the major active metabolite of naltrexone, via a transdermal patch is desirable for treatment of alcoholism. Unfortunately, NTXOL does not diffuse across skin at a therapeutic rate. Therefore, the focus of this study was to evaluate microneedle (MN) skin permeation enhancement of NTXOL's hydrochloride salt in hairless guinea pigs. Specifically, these studies were designed to determine the lifetime of MN-created aqueous pore pathways. MN pore lifetime was estimated by pharmacokinetic evaluation, transepidermal water loss (TEWL) and visualization of MN-treated skin pore diameters using light microscopy. A 3.6-fold enhancement in steady-state plasma concentration was observed in vivo with MN treated skin with NTXOL.HCl, as compared to NTXOL base. TEWL measurements and microscopic evaluation of stained MN-treated guinea pig skin indicated the presence of pores, suggesting a feasible nonlipid bilayer pathway for enhanced transdermal delivery. Overall, MN-assisted transdermal delivery appears viable for at least 48 h after MN-application. (c) 2010 Wiley-Liss, Inc. and the American Pharmacists Association

  7. Application of the Monte Carlo method to the problem of expensive experiment planning

    International Nuclear Information System (INIS)

    Aleksandrov, V.M.; Sanina, S.B.

    1989-01-01

    Numerical method for determination of the optimal experiment plan by the criterion of maximizing the information worth is suggested. The method is based on statistical mathematical simulation of possible outcomes of the experiment and on the analysis of efficiency of subsequent solutions. It is shown that results of conducted statistical simulation contain the data, enabling to determine the direction of plan correction, which provides the increase of its efficiency. A major advantages of the method are that it enables to interpret evidently all its stages and can be used in many-dimensional problems

  8. SUGGESTOPEDIA AS THE METHOD OF THE MUSIC EXPERIENCE FORMATION OF PRE-SCHOOL CHILDREN

    OpenAIRE

    Natalya T. Таgiltseva; Filip D. Shavov

    2015-01-01

    The article aims to consider the possibility of suggestopedia methods use that are successfully practiced in foreign language teaching, pedagogy of music education of preschool children, in starting schools; to find out the degree of methods efficiency of suggestopedia in shaping the musical experience of preschool children in various activities at music lessons. Methods. The theoretical foundations of the article are views and concepts of the Bulgarian researcher, teacher and psychologist, G...

  9. New radionuclide method for determination of gastric content proteolytic activity. (Experiments)

    International Nuclear Information System (INIS)

    Sergienko, V.B.; Popova, L.V.; Khodarev, N.N.; Astashenkova, K.Yu.

    1988-01-01

    A possibility of the use of a radionuclide tubeless rapid method for measuring gastric content proteolytic activity (GCPA) with the help of a protein (gelatin) RP containing capsule was demonstrated in experiments in vitro. There was correlation between the time of dissolution of RP containing capsules and GCPA determined after Mett's method. Reference time intervals were established for normal, raised and lowered proteolytic activity. The method was shown to be physiological, simple and timesaving

  10. Evaluation Methods for Assessing Users’ Psychological Experiences of Web-Based Psychosocial Interventions: A Systematic Review

    Science.gov (United States)

    Howson, Moira; Ritchie, Linda; Carter, Philip D; Parry, David Tudor; Koziol-McLain, Jane

    2016-01-01

    Background The use of Web-based interventions to deliver mental health and behavior change programs is increasingly popular. They are cost-effective, accessible, and generally effective. Often these interventions concern psychologically sensitive and challenging issues, such as depression or anxiety. The process by which a person receives and experiences therapy is important to understanding therapeutic process and outcomes. While the experience of the patient or client in traditional face-to-face therapy has been evaluated in a number of ways, there appeared to be a gap in the evaluation of patient experiences of therapeutic interventions delivered online. Evaluation of Web-based artifacts has focused either on evaluation of experience from a computer Web-design perspective through usability testing or on evaluation of treatment effectiveness. Neither of these methods focuses on the psychological experience of the person while engaged in the therapeutic process. Objective This study aimed to investigate what methods, if any, have been used to evaluate the in situ psychological experience of users of Web-based self-help psychosocial interventions. Methods A systematic literature review was undertaken of interdisciplinary databases with a focus on health and computer sciences. Studies that met a predetermined search protocol were included. Results Among 21 studies identified that examined psychological experience of the user, only 1 study collected user experience in situ. The most common method of understanding users’ experience was through semistructured interviews conducted posttreatment or questionnaires administrated at the end of an intervention session. The questionnaires were usually based on standardized tools used to assess user experience with traditional face-to-face treatment. Conclusions There is a lack of methods specified in the literature to evaluate the interface between Web-based mental health or behavior change artifacts and users. Main

  11. Transdermal thiol-acrylate polyethylene glycol hydrogel synthesis using near infrared light

    Science.gov (United States)

    Chung, Solchan; Lee, Hwangjae; Kim, Hyung-Seok; Kim, Min-Gon; Lee, Luke P.; Lee, Jae Young

    2016-07-01

    Light-induced polymerization has been widely applied for hydrogel synthesis, which conventionally involves the use of ultraviolet or visible light to activate a photoinitiator for polymerization. However, with these light sources, transdermal gelation is not efficient and feasible due to their substantial interactions with biological systems, and thus a high power is required. In this study, we used biocompatible and tissue-penetrating near infrared (NIR) light to remotely trigger a thiol-acrylate reaction for efficient in vivo gelation with good controllability. Our gelation system includes gold nanorods as a photothermal agent, a thermal initiator, diacrylate polyethylene glycol (PEG), and thiolated PEG. Irradiation with a low-power NIR laser (0.3 W cm-2) could induce gelation via a mixed-mode reaction with a small increase in temperature (~5 °C) under the optimized conditions. We also achieved successful transdermal gelation via the NIR-assisted photothermal thiol-acryl reactions. This new type of NIR-assisted thiol-acrylate polymerization provides new opportunities for in situ hydrogel formation for injectable hydrogels and delivery of drugs/cells for various biomedical applications.Light-induced polymerization has been widely applied for hydrogel synthesis, which conventionally involves the use of ultraviolet or visible light to activate a photoinitiator for polymerization. However, with these light sources, transdermal gelation is not efficient and feasible due to their substantial interactions with biological systems, and thus a high power is required. In this study, we used biocompatible and tissue-penetrating near infrared (NIR) light to remotely trigger a thiol-acrylate reaction for efficient in vivo gelation with good controllability. Our gelation system includes gold nanorods as a photothermal agent, a thermal initiator, diacrylate polyethylene glycol (PEG), and thiolated PEG. Irradiation with a low-power NIR laser (0.3 W cm-2) could induce gelation

  12. Pharmacodynamics of transdermal granisetron in women with nausea and vomiting of pregnancy.

    Science.gov (United States)

    Caritis, Steve; Zhao, Yang; Chen, Hui-Jun; Venkataramanan, Raman

    2016-07-01

    Limited options exist for women with nausea and vomiting of pregnancy (NVP) who cannot tolerate oral intake. Transdermal delivery of granisetron, a 5-hydroxytryptamine-3 receptor antagonist, provides an effective alternative for such patients. The objective of this study was to evaluate the pharmacodynamics of granisetron administered intravenously (IV) and as a sustained release transdermal patch in women with NVP. We recruited 16 women with singleton gestation between 12 0/7-18 6/7 weeks who were receiving treatment for NVP and had a Pregnancy Unique Quantification of Emesis and Nausea (PUQE) score of ≥6. All consenting subjects received 1 mg of granisetron as an IV infusion over 5 minutes and blood was obtained prior to the infusion and at 10, 20, 30, and 60 minutes and at 2, 4, 6, 8, 12, and 24 hours after the start of the infusion. After a minimum washout of 48 hours after initiation of IV granisetron, a 52-cm(2) granisetron patch (34.3 mg) was placed on the upper arm of all subjects for 7 days. Blood was drawn prior to patch placement and daily thereafter for 9 days. The subjects were evaluated daily. The PUQE score was obtained from these subjects prior to the IV infusion and daily for 2 days after and again prior to and daily for 9 days after patch placement. Complete data were available in 15 women after IV administration and 13 women after patch placement. One woman stopped participation during the IV infusion while data were not available in 2 additional women after patch placement due to noncompliance. Peak plasma granisetron concentrations after IV and transdermal administration were similar (∼10 ng/mL). Prior to IV administration of granisetron, the PUQE score was 8.6 ± 1.8 (mean ± SD). The PUQE scores were significantly reduced for the ensuing 2 days (P Granisetron significantly improved symptoms of nausea and vomiting as gauged by the PUQE score. After IV infusion the reduction in PUQE score was observed within 1 day. When granisetron was

  13. Experimental design and optimization of raloxifene hydrochloride loaded nanotransfersomes for transdermal application

    Directory of Open Access Journals (Sweden)

    Mahmood S

    2014-09-01

    Full Text Available Syed Mahmood, Muhammad Taher, Uttam Kumar Mandal Department of Pharmaceutical Technology, Kulliyyah of Pharmacy, International Islamic University Malaysia (IIUM, Pahang Darul Makmur, Malaysia Abstract: Raloxifene hydrochloride, a highly effective drug for the treatment of invasive breast cancer and osteoporosis in post-menopausal women, shows poor oral bioavailability of 2%. The aim of this study was to develop, statistically optimize, and characterize raloxifene hydrochloride-loaded transfersomes for transdermal delivery, in order to overcome the poor bioavailability issue with the drug. A response surface methodology experimental design was applied for the optimization of transfersomes, using Box-Behnken experimental design. Phospholipon® 90G, sodium deoxycholate, and sonication time, each at three levels, were selected as independent variables, while entrapment efficiency, vesicle size, and transdermal flux were identified as dependent variables. The formulation was characterized by surface morphology and shape, particle size, and zeta potential. Ex vivo transdermal flux was determined using a Hanson diffusion cell assembly, with rat skin as a barrier medium. Transfersomes from the optimized formulation were found to have spherical, unilamellar structures, with a ­homogeneous distribution and low polydispersity index (0.08. They had a particle size of 134±9 nM, with an entrapment efficiency of 91.00%±4.90%, and transdermal flux of 6.5±1.1 µg/cm2/hour. Raloxifene hydrochloride-loaded transfersomes proved significantly superior in terms of amount of drug permeated and deposited in the skin, with enhancement ratios of 6.25±1.50 and 9.25±2.40, respectively, when compared with drug-loaded conventional liposomes, and an ethanolic phosphate buffer saline. Differential scanning calorimetry study revealed a greater change in skin structure, compared with a control sample, during the ex vivo drug diffusion study. Further, confocal laser

  14. Use of granisetron transdermal system in the prevention of chemotherapy-induced nausea and vomiting: a review

    Directory of Open Access Journals (Sweden)

    Albert Tuca

    2009-12-01

    Full Text Available Albert TucaPalliative Care Hospital Team, Palliative Care Department, Institut Català d’Oncologia, L’Hospitalet de Llobregat, Barcelona, SpainAbstract: Until now only intravenous and oral formulations of 5HT3 receptor antagonists have been available. Recently a new formulation of a 5HT3 receptor antagonist, transdermal granisetron, has been developed, and approved by the FDA. Three phase I studies to evaluate its pharmacokinetic profile have shown that granisetron administered by a transdermal delivery system is absorbed by passive diffusion and maximal concentration is reached 48 hours after patch application. The patch of 52 cm2, which contains 34.3 mg of granisetron, releases 3.3 mg of the drug every day and maintains a stable average plasma concentration of 2.2 ng/mL over 6 days, similar to levels obtained with 2 mg of oral granisetron, administered every day during the same period of time. Two randomized as yet unpublished clinical trials (phase II/III have been conducted to evaluate the antiemetic efficacy of transdermal granisetron in chemotherapy-induced nausea and vomiting, in patients receiving moderately and highly emetogenic chemotherapy, compared with 2 mg of oral granisetron. More than 800 cancer patients were included in the trials. The rate of complete control of acute emesis was 49% for the phase II trial and 60% for the phase III trial. Neither trial showed a statistically significant difference between transdermal and oral granisetron. The control of delayed emesis was observed in 46% of patients, and there were no statistically significant differences between transdermal and oral granisetron. The most common adverse effects in both trials were constipation (<7% and headache (<1%; there were no statistically significant differences between transdermal and oral granisetron. These data show that transdermal granisetron is effective and safe in controlling acute emesis induced by chemotherapy with both moderate and high

  15. Use of granisetron transdermal system in the prevention of chemotherapy-induced nausea and vomiting: a review

    International Nuclear Information System (INIS)

    Tuca, Albert

    2009-01-01

    Until now only intravenous and oral formulations of 5HT 3 receptor antagonists have been available. Recently a new formulation of a 5HT 3 receptor antagonist, transdermal granisetron, has been developed, and approved by the FDA. Three phase I studies to evaluate its pharmacokinetic profile have shown that granisetron administered by a transdermal delivery system is absorbed by passive diffusion and maximal concentration is reached 48 hours after patch application. The patch of 52 cm 2 , which contains 34.3 mg of granisetron, releases 3.3 mg of the drug every day and maintains a stable average plasma concentration of 2.2 ng/mL over 6 days, similar to levels obtained with 2 mg of oral granisetron, administered every day during the same period of time. Two randomized as yet unpublished clinical trials (phase II/III) have been conducted to evaluate the antiemetic efficacy of transdermal granisetron in chemotherapy-induced nausea and vomiting, in patients receiving moderately and highly emetogenic chemotherapy, compared with 2 mg of oral granisetron. More than 800 cancer patients were included in the trials. The rate of complete control of acute emesis was 49% for the phase II trial and 60% for the phase III trial. Neither trial showed a statistically significant difference between transdermal and oral granisetron. The control of delayed emesis was observed in 46% of patients, and there were no statistically significant differences between transdermal and oral granisetron. The most common adverse effects in both trials were constipation (<7%) and headache (<1%); there were no statistically significant differences between transdermal and oral granisetron. These data show that transdermal granisetron is effective and safe in controlling acute emesis induced by chemotherapy with both moderate and high emetogenic potential. Efficacy and safety of transdermal granisetron are fully comparable with that of oral granisetron. More clinical trials using regimens of 2 or 3 drugs

  16. [Experience summary of professor WANG Fuchun's "Zhenjing Anshen" acupuncture method for insomnia].

    Science.gov (United States)

    Li, Tie; Ha, Lijuan; Cao, Fang; Zhi, Mujun; Wang, Fuchun

    2015-11-01

    The experience of "Zhenjing Anshen" acupuncture method originally created by professor WANG Fuchun for treatment of insomnia was introduced in this paper. From aspects of insomnia pathogenesis, theoretical foundation, characteristics of acupoint selection, needing methods, needing time, etc., the experience of Professor WANG Fuchun for treatment of insomnia was explained. The "Zhenjing Anshen" acupuncture method proposed, for the first time, "new three layers" method of acupoint selection, including Sishencong (EX-HN 1), Shenmen (HT 7), Sanyinjiao (SP 6). This method presents the principles of acupoint selection along meridian, acupoint selection based on essence-qi-spirit, harmony of yin and yang. The acupuncture manipulation is emphasized, and treating time (the period of the day from 3 pm to 5 pm) is focused on; acupoint selection is simple but essential, and acupoint combination is scientific, which receives notable therapeutic effect in clinic.

  17. On the evaluation of X-ray diffraction experiments by the regularization method

    Energy Technology Data Exchange (ETDEWEB)

    Trubin, V.A.; Szasz, A. (Lab. of Surface and Interface Physics, Eoetvoes Univ., Budapest (Hungary))

    1991-05-16

    The characteristic property of diffractometers as the presence of occasional and systematic errors in measured patterns requires such an evaluation which is as informative as possible. This circumstance gives rise to the problem of optimal planning of the experiment. The X-ray diffraction optimization problem with application of the regularization method is studied. The proposal permits to determine more accurately the unknown true characteristics of the X-ray diffraction experiment. (orig.).

  18. On the evaluation of X-ray diffraction experiments by the regularization method

    International Nuclear Information System (INIS)

    Trubin, V.A.; Szasz, A.

    1991-01-01

    The characteristic property of diffractometers as the presence of occasional and systematic errors in measured patterns requires such an evaluation which is as informative as possible. This circumstance gives rise to the problem of optimal planning of the experiment. The X-ray diffraction optimization problem with application of the regularization method is studied. The proposal permits to determine more accurately the unknown true characteristics of the X-ray diffraction experiment. (orig.)

  19. Study on reactor power transient characteristics (reactor training experiments). Control rod reactivity calibration by positive period method and other experiment

    International Nuclear Information System (INIS)

    Ozaki, Yoshihiko; Sunagawa, Takeyoshi

    2014-01-01

    In this paper, it is reported about some experiments that have been carried out in the reactor training that targets sophomore of the department of applied nuclear engineering, FUT. Reactor of Kinki University Atomic Energy Research Institute (UTR-KINKI) was used for reactor training. When each critical state was achieved at different reactor output respectively in reactor operating, it was confirmed that the control rod position at that time does not change. Further, control rod reactivity calibration experiments using positive Period method were carried out for shim safety rod and regulating rod, respectively. The results were obtained as reasonable values in comparison with the nominal value of the UTR-KINKI. The measurement of reactor power change after reactor scram was performed, and the presence of the delayed neutron precursor was confirmed by calculating the half-life. The spatial dose rate measurement experiment of neutrons and γ-rays in the reactor room in a reactor power 1W operating conditions were also performed. (author)

  20. Fabrication, appraisal, and transdermal permeation of sildenafil citrate-loaded nanostructured lipid carriers versus solid lipid nanoparticles

    Science.gov (United States)

    Elnaggar, Yosra SR; El-Massik, Magda A; Abdallah, Ossama Y

    2011-01-01

    Although sildenafil citrate (SC) is used extensively for erectile dysfunction, oral delivery of SC encounters many obstacles. Furthermore, the physicochemical characteristics of this amphoteric drug are challenging for delivery system formulation and transdermal permeation. This article concerns the assessment of the potential of nanomedicine for improving SC delivery and transdermal permeation. SC-loaded nanostructured lipid carriers (NLCs) and solid lipid nanoparticles (SLNs) were fabricated using a modified high-shear homogenization technique. Nanoparticle optimization steps included particle size analysis, entrapment efficiency (EE) determination, freeze-drying and reconstitution, differential scanning calorimetry, in vitro release, stability study and high-performance liquid chromatography analysis. Transdermal permeation of the nanocarriers compared with SC suspension across human skin was assessed using a modified Franz diffusion cell assembly. Results revealed that SLNs and NLCs could be optimized in the nanometric range (180 and 100 nm, respectively) with excellent EE (96.7% and 97.5%, respectively). Nanoparticles have significantly enhanced in vitro release and transdermal permeation of SC compared with its suspensions. Furthermore, transdermal permeation of SC exhibited higher initial release from both SLN and NLC formulations followed by controlled release, with promising implications for faster onset and longer drug duration. Nanomedicines prepared exhibited excellent physical stability for the study period. Solid nanoparticles optimized in this study successfully improved SC characteristics, paving the way for an efficient topical Viagra® product. PMID:22238508

  1. Measuring Patient Preferences: An Overview of Methods with a Focus on Discrete Choice Experiments.

    Science.gov (United States)

    Hazlewood, Glen S

    2018-05-01

    There is increasing recognition of the importance of patient preferences and methodologies to measure them. In this article, methods to quantify patient preferences are reviewed, with a focus on discrete choice experiments. In a discrete choice experiment, patients are asked to choose between 2 or more treatments. The results can be used to quantify the relative importance of treatment outcomes and/or other considerations relevant to medical decision making. Conducting and interpreting a discrete choice experiment requires multiple steps and an understanding of the potential biases that can arise, which we review in this article with examples in rheumatic diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Neutron reflection effect on total absorption detector method used in SWINPC neutron multiplication experiment for beryllium

    International Nuclear Information System (INIS)

    Tian Dongfeng; Ho Yukun; Yang Fujia

    2001-01-01

    The SWINPC integral experiment on neutron multiplication in bulk beryllium showed that there were marked discrepancies between experimental data and calculated values with the ENDF/B-VI data. The calculated values become higher than experimental ones as the sample thickness increases. Several works had been devoted to find problems existing in the experiment. This paper discusses the neutron reflection effect on the total absorption detector method which was used in the experiment to measure the neutron leakage from samples. One systematic correction is suggested to make the experimental values agree with the calculated ones with the ENDF/B-VI data within experimental errors. (author)

  3. New screening methodology for selection of polymeric materials for transdermal drug delivery devices

    Science.gov (United States)

    Falcone, Roberto P.

    As medical advances extend the human lifespan, the level of chronic illnesses will increase and thus straining the needs of the health care system that, as a result, governments will need to balance expenses without upsetting national budgets. Therefore, the selection of a precise and affordable drug delivery technology is seen as the most practical solution for governments, health care professionals, and consumers. Transdermal drug delivery patches (TDDP) are one of the best economical technologies that are favored by pharmaceutical companies and physicians alike because it offers fewer complications when compared to other delivery technologies. TDDP provides increased efficiency, safety and convenience for the patient. The TDDP segment within the US and Global drug delivery markets were valued at 5.6 and 12.7 billion respectively in 2009. TDDP is forecasted to reach $31.5 billion in 2015. The present TDDP technology involves the fabrication of a patch that consists of a drug embedded in a polymeric matrix. The diffusion coefficient is determined from the slope of the cumulative drug release versus time. It is a trial and error method that is time and labor consuming. With all the advantages that TDDPs can offer, the methodology used to achieve the so-called optimum design has resulted in several incidents where the safety and design have been put to question in recent times (e.g. Fentanyl). A more logical screening methodology is needed. This work shows the use of a modified Duda Zielinsky equation (DZE). Experimental release curves from commercial are evaluated. The experimental and theoretical Diffusion Coefficient values are found to be within the limits specified in the patent literature. One interesting finding is that the accuracy of the DZE is closer to experimental values when the type of Molecular Shape and Radius are used. This work shows that the modified DZE could be used as an excellent screening tool to determine the optimal polymeric matrices that

  4. Experiments to Evaluate and Implement Passive Tracer Gas Methods to Measure Ventilation Rates in Homes

    Energy Technology Data Exchange (ETDEWEB)

    Lunden, Melissa [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Faulkner, David [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Heredia, Elizabeth [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Cohn, Sebastian [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Dickerhoff, Darryl [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Noris, Federico [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Logue, Jennifer [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Hotchi, Toshifumi [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Singer, Brett [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Sherman, Max H. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2012-10-01

    This report documents experiments performed in three homes to assess the methodology used to determine air exchange rates using passive tracer techniques. The experiments used four different tracer gases emitted simultaneously but implemented with different spatial coverage in the home. Two different tracer gas sampling methods were used. The results characterize the factors of the execution and analysis of the passive tracer technique that affect the uncertainty in the calculated air exchange rates. These factors include uncertainties in tracer gas emission rates, differences in measured concentrations for different tracer gases, temporal and spatial variability of the concentrations, the comparison between different gas sampling methods, and the effect of different ventilation conditions.

  5. Intercomparison of diffusion coefficient derived from the through-diffusion experiment using different numerical methods

    International Nuclear Information System (INIS)

    Chih-Lung Chen; Institute of Nuclear Energy Research, Taoyuan, Taiwan; Tsing-Hai Wang; Shi-Ping Teng; Ching-Hor Lee

    2014-01-01

    Diffusion is a dominant mechanism regulating the transport of released nuclides. The through-diffusion method is typically applied to determine the diffusion coefficients (D). Depending on the design of the experiment, the concentrations in the source term [i.e., inlet reservoir (IR)] or the end term [i.e., outlet reservoir (OR)] can be fixed or vary. The combinations involve four distinct models (i.e., the CC-CC model, CC-VC model, VC-CC model, and the VC-VC model). Studies discussing the VC-CC model are scant. An analytical method considering the decay effect is required to accurately interpret the radioactive nuclide diffusion experiment results. Therefore, we developed a CC-CC model and a CC-VC model with a decay effect and the simplified formulas of these two models to determine the diffusion coefficient (i.e., the CC-CC method and CC-VC method). We also proposed two simplified methods using the VC-VC model to determine the diffusion coefficient straightforwardly based upon the concentration variation in IR and OR. More importantly, the best advantage of proposed method over others is that one can derive three diffusion coefficients based on one run of experiment. In addition, applying our CC-VC method to those data reported from Radiochemica Acta 96:111-117, 2008; and J Contam Hydrol 35:55-65, 1998, derived comparable diffusion coefficient lying in the identical order of magnitude. Furthermore, we proposed a formula to determine the conceptual critical time (Tc), which is particularly beneficial for the selection of using CC-VC or VC-VC method. Based on our proposed method, it becomes possible to calculate diffusion coefficient from a through-diffusion experiment in a shorter period of time. (author)

  6. Dual-functional transdermal drug delivery system with controllable drug loading based on thermosensitive poloxamer hydrogel for atopic dermatitis treatment

    Science.gov (United States)

    Wang, Wenyi; Wat, Elaine; Hui, Patrick C. L.; Chan, Ben; Ng, Frency S. F.; Kan, Chi-Wai; Wang, Xiaowen; Hu, Huawen; Wong, Eric C. W.; Lau, Clara B. S.; Leung, Ping-Chung

    2016-04-01

    The treatment of atopic dermatitis (AD) has long been viewed as a problematic issue by the medical profession. Although a wide variety of complementary therapies have been introduced, they fail to combine the skin moisturizing and drug supply for AD patients. This study reports the development of a thermo-sensitive Poloxamer 407/Carboxymethyl cellulose sodium (P407/CMCs) composite hydrogel formulation with twin functions of moisture and drug supply for AD treatment. It was found that the presence of CMCs can appreciably improve the physical properties of P407 hydrogel, which makes it more suitable for tailored drug loading. The fabricated P407/CMCs composite hydrogel was also characterized in terms of surface morphology by field emission scanning electron microscopy (FE-SEM), rheological properties by a rheometer, release profile in vitro by dialysis method and cytotoxicity test. More importantly, the findings from transdermal drug delivery behavior revealed that P407/CMCs showed desirable percutaneous performance. Additionally, analysis of cytotoxicity test suggested that P407/CMCs composite hydrogel is a high-security therapy for clinical trials and thus exhibits a promising way to treat AD with skin moisturizing and medication.

  7. Contraceptive efficacy, compliance and beyond: factors related to satisfaction with once-weekly transdermal compared with oral contraception.

    Science.gov (United States)

    Urdl, Wolfgang; Apter, Dan; Alperstein, Alan; Koll, Peter; Schönian, Siegfried; Bringer, Jacques; Fisher, Alan C; Preik, Michael

    2005-08-01

    To investigate contraceptive efficacy, compliance and user's satisfaction with transdermal versus oral contraception (OC). Randomized, open-label, parallel-group trial conducted at 65 centers in Europe and South Africa. One thousand four hundred and eighty-nine women received a contraceptive patch (n = 846) or an OC (n = 643) for 6 or 13 cycles. Overall/method-failure Pearl Indices were 0.88/0.66 with the patch and 0.56/0.28 with the OC (p = n.s.). Compliance was higher at all age groups with the patch compared to the OC. Significantly more users were very satisfied with the contraceptive patch than with the OC. The percentage of patch users being very satisfied increased with age whereas it did not in the OC group. Likewise, improvements of premenstrual symptoms as well as emotional and physical well-being increased with age in the patch-group in contrast to the OC group. Ratings of satisfaction with the study medication correlated weakly with emotional (r = 0.33) and physical well-being (r = 0.39) as well as premenstrual symptoms (r = 0.30; p Contraceptive efficacy of the patch is comparable to OC, but compliance is consistently better at all age groups. Higher satisfaction with the patch at increasing age may be attributed to improvements in emotional and physical well-being as well as reduction of premenstrual symptoms.

  8. A prospective study on the use of rivastigmine transdermal patch in Alzheimer's dementia in a routine clinical setting

    Directory of Open Access Journals (Sweden)

    Ejaz Nazir

    Full Text Available Abstract There is not much published literature on the use of rivastigmine patch in a "routine" clinical setting. Objectives: In this naturalistic longitudinal observational study we sought to evaluate the safety, tolerability and efficacy of the rivastigmine patch in patients with early and late onset moderate Alzheimer's disease in a routine clinical setting. Methods: Out of all routine clinical referrals, the first 30 patients with diagnosis of moderate Alzheimer's dementia who were started on rivastigmine patch were included in the study. Rivastigmine patch dose was titrated from 4.6 to 9.5 mg/ 24 hours as appropriate. The primary outcome measure was safety and tolerability, measured by the incidence of adverse events and discontinuation due to any reason. The secondary outcome measure was to examine improvement on global, functional and behavioral domains as demonstrated by the MMSE (Mini Mental State Examination score, BADLS (Bristol Activities of Daily Living Skills score, patient and carer feedback and clinical judgment. Results: Adverse events were reported in 20% of patients and 10% of total patients needed discontinuation of treatment. Improvement on global, functional and behavioral domains was observed in two thirds of patients whereas one third showed a relative decline. The most common side effect was skin irritation or erythema. Conclusions: The rivastigmine transdermal patch may provide a treatment option for those patients who require a change in their current oral cholinesterase inhibitor therapy due to safety or tolerability concerns.

  9. Particle generation methods applied in large-scale experiments on aerosol behaviour and source term studies

    International Nuclear Information System (INIS)

    Swiderska-Kowalczyk, M.; Gomez, F.J.; Martin, M.

    1997-01-01

    In aerosol research aerosols of known size, shape, and density are highly desirable because most aerosols properties depend strongly on particle size. However, such constant and reproducible generation of those aerosol particles whose size and concentration can be easily controlled, can be achieved only in laboratory-scale tests. In large scale experiments, different generation methods for various elements and compounds have been applied. This work presents, in a brief from, a review of applications of these methods used in large scale experiments on aerosol behaviour and source term. Description of generation method and generated aerosol transport conditions is followed by properties of obtained aerosol, aerosol instrumentation used, and the scheme of aerosol generation system-wherever it was available. An information concerning aerosol generation particular purposes and reference number(s) is given at the end of a particular case. These methods reviewed are: evaporation-condensation, using a furnace heating and using a plasma torch; atomization of liquid, using compressed air nebulizers, ultrasonic nebulizers and atomization of liquid suspension; and dispersion of powders. Among the projects included in this worked are: ACE, LACE, GE Experiments, EPRI Experiments, LACE-Spain. UKAEA Experiments, BNWL Experiments, ORNL Experiments, MARVIKEN, SPARTA and DEMONA. The aim chemical compounds studied are: Ba, Cs, CsOH, CsI, Ni, Cr, NaI, TeO 2 , UO 2 Al 2 O 3 , Al 2 SiO 5 , B 2 O 3 , Cd, CdO, Fe 2 O 3 , MnO, SiO 2 , AgO, SnO 2 , Te, U 3 O 8 , BaO, CsCl, CsNO 3 , Urania, RuO 2 , TiO 2 , Al(OH) 3 , BaSO 4 , Eu 2 O 3 and Sn. (Author)

  10. Experiments of Long-range Inspection Method in Straight Pipes using Ultrasonic Guided Waves

    International Nuclear Information System (INIS)

    Eom, H. S.; Lim, S. H.; Kim, J. H.; Joo, Y.S.

    2006-02-01

    This report describes experimental results of a long-range inspection method of pipes using ultrasonic guided waves. In chapter 2, theory of guided wave was reviewed. In chapter 3, equipment and procedures which were used in the experiments were described. Detailed specifications of the specimens described in chapter 4. In chapter 5, we analyzed characteristics of guided wave signals according to shapes and sizes of defects and presents results of various signal processing methods

  11. Mixture experiment methods in the development and optimization of microemulsion formulations.

    Science.gov (United States)

    Furlanetto, S; Cirri, M; Piepel, G; Mennini, N; Mura, P

    2011-06-25

    Microemulsion formulations represent an interesting delivery vehicle for lipophilic drugs, allowing for improving their solubility and dissolution properties. This work developed effective microemulsion formulations using glyburide (a very poorly-water-soluble hypoglycaemic agent) as a model drug. First, the area of stable microemulsion (ME) formations was identified using a new approach based on mixture experiment methods. A 13-run mixture design was carried out in an experimental region defined by constraints on three components: aqueous, oil and surfactant/cosurfactant. The transmittance percentage (at 550 nm) of ME formulations (indicative of their transparency and thus of their stability) was chosen as the response variable. The results obtained using the mixture experiment approach corresponded well with those obtained using the traditional approach based on pseudo-ternary phase diagrams. However, the mixture experiment approach required far less experimental effort than the traditional approach. A subsequent 13-run mixture experiment, in the region of stable MEs, was then performed to identify the optimal formulation (i.e., having the best glyburide dissolution properties). Percent drug dissolved and dissolution efficiency were selected as the responses to be maximized. The ME formulation optimized via the mixture experiment approach consisted of 78% surfactant/cosurfacant (a mixture of Tween 20 and Transcutol, 1:1, v/v), 5% oil (Labrafac Hydro) and 17% aqueous phase (water). The stable region of MEs was identified using mixture experiment methods for the first time. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. The role of transdermal estrogen sprays and estradiol topical emulsion in the management of menopause-associated vasomotor symptoms

    Directory of Open Access Journals (Sweden)

    Amy M Egras

    2010-05-01

    Full Text Available Amy M Egras, Elena M UmlandJefferson School of Pharmacy, Thomas Jefferson University, Philadelphia, PA, USAAbstract: Vasomotor symptoms (VMS are among the most bothersome complaints of postmenopausal women. To date, the most widely studied and effective treatment for VMS is hormone replacement therapy, consisting of estrogen (in women without a uterus or estrogen plus progestin (in women with a uterus. Traditionally, oral estrogens have been used for treatment. However, over the years, additional estrogen formulations have been developed including transdermal patches; vaginal rings, creams, and tablets; and injectable preparations. Two newer formulations are transdermal estrogen spray and estradiol topical emulsion. This review evaluates the current literature assessing the use of these two newer formulations for the treatment of VMS associated with menopause.Keywords: menopause, vasomotor symptoms, transdermal estrogen spray, estradiol topical emulsion

  13. Teaching Methods and Their Impact on Students' Emotions in Mathematics: An Experience-Sampling Approach

    Science.gov (United States)

    Bieg, Madeleine; Goetz, Thomas; Sticca, Fabio; Brunner, Esther; Becker, Eva; Morger, Vinzenz; Hubbard, Kyle

    2017-01-01

    Various theoretical approaches propose that emotions in the classroom are elicited by appraisal antecedents, with subjective experiences of control playing a crucial role in this context. Perceptions of control, in turn, are expected to be influenced by the classroom social environment, which can include the teaching methods being employed (e.g.,…

  14. Randomized Controlled Trial of Teaching Methods: Do Classroom Experiments Improve Economic Education in High Schools?

    Science.gov (United States)

    Eisenkopf, Gerald; Sulser, Pascal A.

    2016-01-01

    The authors present results from a comprehensive field experiment at Swiss high schools in which they compare the effectiveness of teaching methods in economics. They randomly assigned classes into an experimental and a conventional teaching group, or a control group that received no specific instruction. Both teaching treatments improve economic…

  15. Discrimination of Semi-Quantitative Models by Experiment Selection: Method Application in Population Biology

    NARCIS (Netherlands)

    Vatcheva, Ivayla; Bernard, Olivier; de Jong, Hidde; Gouze, Jean-Luc; Mars, Nicolaas; Nebel, B.

    2001-01-01

    Modeling an experimental system often results in a number of alternative models that are justified equally well by the experimental data. In order to discriminate between these models, additional experiments are needed. We present a method for the discrimination of models in the form of

  16. Using Grounded Theory Method to Capture and Analyze Health Care Experiences

    Science.gov (United States)

    Foley, Geraldine; Timonen, Virpi

    2015-01-01

    Objective Grounded theory (GT) is an established qualitative research method, but few papers have encapsulated the benefits, limits, and basic tenets of doing GT research on user and provider experiences of health care services. GT can be used to guide the entire study method, or it can be applied at the data analysis stage only. Methods We summarize key components of GT and common GT procedures used by qualitative researchers in health care research. We draw on our experience of conducting a GT study on amyotrophic lateral sclerosis patients’ experiences of health care services. Findings We discuss why some approaches in GT research may work better than others, particularly when the focus of study is hard-to-reach population groups. We highlight the flexibility of procedures in GT to build theory about how people engage with health care services. Conclusion GT enables researchers to capture and understand health care experiences. GT methods are particularly valuable when the topic of interest has not previously been studied. GT can be applied to bring structure and rigor to the analysis of qualitative data. PMID:25523315

  17. The effect of preference elicitation methods on the user experience of a recommender system

    NARCIS (Netherlands)

    Knijnenburg, B.P.; Willemsen, M.C.

    2010-01-01

    To increase the user experience, preference elicitation methods used by recommender systems can be adapted to individual differences such as the level of expertise. However, we will show that the satisfaction and perceived usefulness of a recommender system also depends strongly on subtle variations

  18. Diagnostic methods and interpretation of the experiments on microtarget compression in the Iskra-4 device

    International Nuclear Information System (INIS)

    Kochemasov, G.G.

    1992-01-01

    Studies on the problem of laser fusion, which is mainly based on experiments conducted in the Iskra-4 device are reviewed. Different approaches to solution of the problem of DT-fuel ignition, methods of diagnostics of characteristics of laser radiation and plasma, occurring on microtarget heating and compression, are considered

  19. Teaching Teachers: Methods and Experiences Used in Educating Doctoral Students to Prepare Preservice Music Educators

    Science.gov (United States)

    Kelly, Steven N.; VanWeelden, Kimberly

    2017-01-01

    This investigation addressed methods and experiences used to educate doctoral music education students to work as university college professors. Selected faculty representing every institution offering a Ph.D. in music education in the United States and Canada (N = 46) were sent an online questionnaire concerning (1) the extent respondents…

  20. Visual Research Methods: A Novel Approach To Understanding The Experiences of Compulsive Hoarders: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Satwant Singh

    2012-04-01

    Conclusion: The study concluded that the experience of hoarding is both psychologically and physically distressing with numerous impacts upon everyday living and relationships. The study also concluded that visual research methods may be particularly helpful when generating qualitative evidence within this specialist field. [JCBPR 2012; 1(1.000: 36-42