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Sample records for transdermal permeation enhancers

  1. 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.

  2. 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.

  3. 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.

  4. Evaluations of imidazolium ionic liquids as novel skin permeation enhancers for drug transdermal delivery.

    Science.gov (United States)

    Zhang, Ding; Wang, Huai-Ji; Cui, Xiu-Ming; Wang, Cheng-Xiao

    2017-06-01

    In this work, imidazolium ionic liquids (imidazolium ILs) were employed as the novel chemical permeation enhancers (CPEs) and their performances and mechanisms of action were deeply investigated. Testosterone was used as a model drug to investigate the transdermal delivery enhancement of twenty imdidazolium ILs. The results suggested that the promotion activity connected to the structure and composition of the ILs. The quantitative structure-activity relationship (QSAR) model revealed a good linearity between the electronic properties of ILs and their enhancements. Furthermore, the transepidermal water loss (TEWL) and scanning laser confocal microscope (CLSM) examinations showed the strong improvement of ILs on skin barrier permeability, which were well correlated with the drug penetration profiles. The total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and atomic force microscope (AFM) evaluations of skins indicated that the ILs can disrupt the regular and compact arrangements of the corneocytes, change the surface properties of stratum corneum, and make the skin structure more permeable. Our work demonstrated the significant skin permeation promotion profiles of the imidazolium ILs, which are of great potential in transdermal drug delivery systems.

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

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    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.

  6. 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.

  7. 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.

  8. Permeation enhancer dedocyl 6-(dimethylamino)hexanoate increases transdermal and topical delivery of adefovir: Influence of pH, ion-pairing and skin species

    Czech Academy of Sciences Publication Activity Database

    Vávrová, K.; Lorencová, K.; Novotný, J.; Holý, Antonín; Hrabálek, A.

    2008-01-01

    Roč. 70, č. 3 (2008), s. 901-907 ISSN 0939-6411 R&D Projects: GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z40550506 Keywords : adefovir * acyclic nucleoside phosphonates * antiviral * transdermal drug delivery * permeation enhancer Subject RIV: CC - Organic Chemistry Impact factor: 3.344, year: 2008

  9. Skin Permeation Enhancers and their Effects on Narcotic Transdermal Drug Delivery Systems through Response Surface Experimental Design

    Directory of Open Access Journals (Sweden)

    A. Moghimi

    2014-02-01

    Full Text Available Drug delivery through skin is often obstructed by low permeability of skin towards most drugs; however, such problem would be solved by application of skin penetration enhancers in the formulations. In the present study, a drug in adhesive patch with buprenorphine as active ingredient was prepared. Drug-in-adhesive transdermal drug delivery systems with different chemical penetration enhancers were designed. For this purpose a response-surface experimental design was used. Response surface methodology based on a three-level, three-variable Box–Behnken design was used to evaluate the interactive effects of dependent variables such as: the rate of skin permeation and adhesion properties including peel strength and tack value. The parameters such as drug release and adhesion were used as independent variables. Levulinic acid, lauryl alcohol and Tween 80 were used as penetration enhancers. In order to prepare samples, buprenorphine with constant concentration was incorporated into acrylic pressure sensitive adhesive with carboxylic functionality and this mixture was added to chemical penetration enhancer with different concentrations. The results show that the cumulative amount of drug release in presence of Tween 80 is 462.9 ± 0.006 μg so it is higher than cumulative amount of drug release in presence of levulinic acid (357.9 ± 0.005 μg and lauryl alcohol (269.5 ± 0.001 μg. Results of adhesion properties such as peel strength and tack reveal that using levulinic acid and lauryl alcohol will increase peel strength while Tween 80 will decrease it. Besides, the results show that all these permeation enhancers have increased tack values.

  10. 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.

  11. Transdermal delivery of carvedilol containing glycyrrhizin and chitosan as permeation enhancers: biochemical, biophysical, microscopic and pharmacodynamic evaluation.

    Science.gov (United States)

    Sapra, Bharti; Jain, Subheet; Tiwary, A K

    2008-09-01

    The present study was aimed at unveiling the influence of glycyrrhizin and chitosan on rat epidermis and to correlate these effects with percutaneous permeation characteristics of carvedilol. The permeation of carvedilol across excised rat epidermis was significantly higher (p vehicle as compared to propylene glycol:ethanol (7:3) mixture. Epidermis obtained after 12 hr treatment of viable rat skin with a glycyrrhizin-chitosan mixture showed significantly higher (p space, disordered lipid structure and corneocyte detachment as observed in SEM and TEM suggests great potential of glycyrrhizin for use as a percutaneous permeation enhancer.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

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

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    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.

  18. Enhanced transdermal delivery of ondansetron using nanovesicular systems: Fabrication, characterization, optimization and ex-vivo permeation study-Box-Cox transformation practical example.

    Science.gov (United States)

    Habib, Basant A; Sayed, Sinar; Elsayed, Ghada M

    2018-03-30

    This study aimed to formulate suitable nanovesicles (NVs) for transdermal delivery of Ondansetron. It also illustrated a practical example for the importance of Box-Cox transformation. A 2 3 full factorial design was used to enable testing transfersomes, ethosomes, and transethosomes of Ondansetron simultaneously. The independent variables (IVs) studied were sodium taurocholate amount, ethanol volume in hydration medium and sonication time. The studied dependent variables (DVs) were: particle size (PS), zeta potential (ZP) and entrapment efficiency (EE). Polynomial equations were used to study the influence of IVs on each DV. Numerical multiple response optimization was applied to select an optimized formula (OF) with the goals of minimizing PS and maximizing ZP absolute value and EE. Box-Cox transformation was adopted to enable modeling PS raised to the power of 1.2 with an excellent prediction R 2 of 1.000. ZP and EE were adequately represented directly with prediction R 2 of 0.9549 and 0.9892 respectively. Response surface plots helped in explaining the influence of IVs on each DV. Two-sided 95% prediction interval test and percent deviation of actual values from predicted ones proved the validity of the elucidated models. The OF was a transfersomal formula with desirability of 0.866 and showed promising results in ex-vivo permeation study. Copyright © 2018 Elsevier B.V. All rights reserved.

  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. 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.

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

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    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. 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

  3. In Vitro Skin Permeation Enhancement of Sumatriptan by Microneedle Application.

    Science.gov (United States)

    Nalluri, Buchi N; Anusha, Sai Sri V; Bramhini, Sri R; Amulya, J; Sultana, Ashraf S K; Teja, Chandra U; Das, Diganta B

    2015-01-01

    Different dimensions of commercially available microneedle devices, namely, Admin- Patch(®) microneedle arrays (MN) (0.6, 0.9, 1.2 and 1.5 mm lengths) and Dermaroller(®) microneedle rollers (DR) (0.5 and 1mm lengths) were evaluated for their relative efficiency in enhancement of transdermal permeation of Sumatriptan (SMT). Solubility assessment of SMT was carried out using propylene glycol (PG), polyethylene glycol (PEG) in combination with saline (S) at different ratios and the order of solubility was found to be 70:30 > 80:20 > 90:10 %v/v in both PG:S and PEG:S. In vitro skin permeation studies were performed using PG:S (70:30 %v/v) as donor vehicle. A significant increase in cumulative amount of SMT permeated, steady state flux, permeability coefficient and diffusion coefficient values were observed after microneedle treatment, and the values were in the order of 1.5mm MN >1.2mm MN >0.9mm MN >1mm DR >0.6mm MN >0.5mm DR > passive permeation. Lag times were significantly shorter after longer microneedle application (0.24h for 1.5mm MN). Arrays were found to be superior to rollers with similar microneedle lengths in enhancing SMT permeation and may be attributed to higher density of microneedles and force of application onto skin. The in vitro flux values revealed that 2.5cm(2) area patch is sufficient for effective therapy after treatment of skin with 1.5mm MN. It may be inferred that microneedle application significantly enhances the transdermal penetration of SMT and that it may be feasible to deliver clinically relevant therapeutic levels of SMT using microneedle assisted transdermal delivery systems.

  4. 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.

  5. Superiority of liquid crystalline cubic nanocarriers as hormonal transdermal vehicle: comparative human skin permeation-supported evidence.

    Science.gov (United States)

    Mohyeldin, Salma M; Mehanna, Mohammed M; Elgindy, Nazik A

    2016-08-01

    The aim of this investigation was to explore the feasibility of various nanocarriers to enhance progesterone penetration via the human abdominal skin. Four progesterone-loaded nanocarriers; cubosomes, nanoliposomes, nanoemulsions and nanomicelles were formulated and characterized regarding particle size, zeta potential, % drug encapsulation and in vitro release. Structural elucidation of each nanoplatform was performed using transmission electron microscopy. Ex vivo skin permeation, deposition ability and histopathological examination were evaluated using Franz diffusion cells. Each nanocarrier was fabricated with a negative surface, nanometric size (≤ 270 nm), narrow size distribution and reasonable encapsulation efficiency. In vitro progesterone release showed a sustained release pattern for 24 h following a non-Fickian transport diffusion mechanism. All nanocarriers exhibited higher transdermal flux relative to free progesterone. Cubosomes revealed a higher skin penetration with transdermal steady flux of 48.57.10(-2) ± 0.7 µg/cm(2) h. Nanoliposomes offered a higher percentage of skin progesterone deposition compared to other nanocarriers. Based on the histopathological examination, cubosomes and nanoliposomes were found to be biocompatible for transdermal application. Confocal laser scanning microscopy confirmed the ability of fluoro-labeled cubosomes to penetrate through the whole skin layers. The elaborated cubosomes proved to be a promising non-invasive nanocarrier for transdermal hormonal delivery.

  6. Skin permeation of D-limonene-based nanoemulsions as a transdermal carrier prepared by ultrasonic emulsification.

    Science.gov (United States)

    Lu, Wen-Chien; Chiang, Been-Huang; Huang, Da-Wei; Li, Po-Hsien

    2014-03-01

    Nanoemulsions can be used for transporting pharmaceutical phytochemicals in skin-care products because of their stability and rapid permeation properties. However, droplet size may be a critical factor aiding permeation through skin and transdermal delivery efficiency. We prepared D-limonene nanoemulsions with various droplet sizes by ultrasonic emulsification using mixed surfactants of sorbitane trioleate and polyoxyethylene (20) oleyl ether under different hydrophilic-lipophilic balance (HLB) values. Droplet size decreased with increasing HLB value. With HLB 12, the droplet size was 23 nm, and the encapsulated ratio peaked at 92.3%. Transmission electron microscopy revealed spherical droplets and the gray parts were D-limonene precipitation incorporated in spherical droplets of the emulsion system. Franz diffusion cell was used to evaluate the permeation of D-limonene nanoemulsion through rat abdominal skin; the permeation rate depended on droplet size. The emulsion with the lowest droplet size (54 nm) achieved the maximum permeation rate. The concentration of D-limonene in the skin was 40.11 μL/cm(2) at the end of 360 min. Histopathology revealed no distinct voids or empty spaces in the epidermal region of permeated rat skin, so the D-limonene nanoemulsion may be a safe carrier for transdermal drug delivery. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. 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

  8. 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

  9. 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

  10. Promotores de permeação para a liberação transdérmica de fármacos: uma nova aplicação para as ciclodextrinas Permeation enhancers in transdermal drug delivery systems: a new application of cyclodextrins

    Directory of Open Access Journals (Sweden)

    Maria Rita Fernandes Morais Martins

    2002-03-01

    Full Text Available No presente trabalho é feita uma breve revisão sobre promotores de permeação cutânea, descrevendo-se os seus mecanismos de ação e alguns exemplos. Abordam-se as vias de permeação de fármacos através da pele e liberação transdérmica. São também focadas as ciclodextrinas e seus derivados, a sua estrutura e propriedades físico-químicas, formação de complexos de inclusão e o seu papel como excipientes em sistemas transdérmicos. As ciclodextrinas constituem um grupo de excipientes que têm um papel de grande importância em formulação farmacêutica. Uma das mais extraordinárias propriedades destas moléculas é a sua capacidade de incrementar a liberação de fármacos através da pele sem, no entanto, afetar a sua função barreira.The present work is a short revision about transdermal permeation enhancers, their mechanism of action including some examples. Routes of permeation across the skin and transdermal delivery are also described. We focus cyclodextrins and their derivatives, structure, chemical properties, formation of inclusion complexes and their action as excipients in transdermal drug delivery systems. Cyclodextrins are a very important group of excipients used in pharmaceutical technology. One of the most extraordinary properties of cyclodextrins is their ability to increase transdermal drug delivery without affecting the barrier function of the skin.

  11. 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.

  12. 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.

  13. 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

  14. 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...

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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. 

  3. 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

  4. Enhanced delivery of hydrophilic peptides in vitro by transdermal microneedle pretreatment.

    Science.gov (United States)

    Zhang, Suohui; Qiu, Yuqin; Gao, Yunhua

    2014-02-01

    The aims of this study were to investigate the utility of solid microneedle arrays (150 µm in length) in enhancing transdermal delivery of peptides and to examine the relationship between peptide permeation rates and D2O flux. Four model peptides were used (Gly-Gln-Pro-Arg [tetrapeptide-3, 456.6 Da], Val-Gly-Val-Ala-Pro-Gly [hexapeptide, 498.6 Da], AC-Glu-Glu-Met-Gln-Arg-Arg-NH2 [acetyl hexapeptide-3, 889 Da] and Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly-NH2 [oxytocin, 1007.2 Da]). The influence of microneedle pretreatment on skin permeation was evaluated using porcine ear skin with Franze diffusion cell. Peptide permeation across the skin was significantly enhanced by microneedle pretreatment, and permeation rates were dependent on peptide molecular weights. A positive correlation between D2O flux and acetyl hexapeptide-3 clearances suggests that convective solvent flow contributes to the enhanced transdermal peptide delivery. It is concluded that solid microneedle arrays are effective devices to enhance skin delivery of peptides.

  5. Enhanced delivery of hydrophilic peptides in vitro by transdermal microneedle pretreatment

    Directory of Open Access Journals (Sweden)

    Suohui Zhang

    2014-02-01

    Full Text Available The aims of this study were to investigate the utility of solid microneedle arrays (150 µm in length in enhancing transdermal delivery of peptides and to examine the relationship between peptide permeation rates and D2O flux. Four model peptides were used (Gly–Gln–Pro–Arg [tetrapeptide-3, 456.6 Da], Val–Gly–Val–Ala–Pro–Gly [hexapeptide, 498.6 Da], AC–Glu–Glu–Met–Gln–Arg–Arg–NH2 [acetyl hexapeptide-3, 889 Da] and Cys–Tyr–Ile–Gln–Asn–Cys–Pro–Leu–Gly–NH2 [oxytocin, 1007.2 Da]. The influence of microneedle pretreatment on skin permeation was evaluated using porcine ear skin with Franze diffusion cell. Peptide permeation across the skin was significantly enhanced by microneedle pretreatment, and permeation rates were dependent on peptide molecular weights. A positive correlation between D2O flux and acetyl hexapeptide-3 clearances suggests that convective solvent flow contributes to the enhanced transdermal peptide delivery. It is concluded that solid microneedle arrays are effective devices to enhance skin delivery of peptides.

  6. Effect of permeation enhancers on the penetration mechanism of transfersomal gel of ketoconazole

    Directory of Open Access Journals (Sweden)

    Reshmy Rajan

    2012-01-01

    Full Text Available The aim of the present research work was to investigate the potential of transfersome formulations for transdermal delivery of Ketoconazole (KTZ. KTZ is a broad-spectrum antifungal agent that is active against a wide variety of fungi and yeasts. It is readily but incompletely absorbed after oral dosing and is highly variable. The transfersomes were formulated by lipid film hydration technique using Rotary vacuum Evaporator. The prepared transfersomes were converted into suitable gel formulation and is evaluated for their gel characteristics like pH, viscosity, spreadability, extrudability, homogeneity, drug content, etc. Suitable essential oils acting as natural permeation enhancers were added to the transfersomal formulation of KTZ for their release studies. Studies proved that addition of suitable permeation enhancers to the transfersomal formulation improved the release and permeation of KTZ, which showed that the permeation enhancers modify the barrier to penetration present in skin without itself undergoing any change. From the various essential oils which are used as permeation enhancers, the formulation containing Eucalyptus oil showed better in vitro release and permeation as compared with other formulations containing different permeation enhancers.

  7. 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.

  8. 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.

  9. Nanoethosomes for transdermal delivery of tropisetron HCl: multi-factorial predictive modeling, characterization, and ex vivo skin permeation.

    Science.gov (United States)

    Abdel Messih, Hanaa A; Ishak, Rania A H; Geneidi, Ahmed S; Mansour, Samar

    2017-06-01

    The aim of the present work is to exclusively optimize and model the effect of phospholipid type either egg phosphatidylcholine (EPC) or soybean phosphatidylcholine (SPC), together with other formulation variables, on the development of nano-ethosomal systems for transdermal delivery of a water-soluble antiemetic drug. Tropisetron HCl (TRO) is available as hard gelatin capsules and IV injections. The transdermal delivery of TRO is considered as a novel alternative route supposing to improve BAV as well as patient convenience. TRO-loaded ethanolic vesicular systems were prepared by hot technique. The effect of formulation variables were optimized through a response surface methodology using 3 × 2 2 -level full factorial design. The concentrations of both PC (A) and ethanol (B) and PC type (C) were the factors, while entrapment efficiency (Y 1 ), vesicle size (Y 2 ), polydispersity index (Y 3 ), and zeta potential (Y 4 ) were the responses. The drug permeation across rat skin from selected formulae was studied. Particle morphology, drug-excipient interactions, and vesicle stability were also investigated. The results proved the critical role of all formulation variables on ethosomal characteristics. The suggested models for all responses showed good predictability. Only the concentration of phospholipid, irrespective to PC type, had a significant effect on the transdermal flux (p transdermal TRO delivery.

  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. 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.

  12. Effects of Vehicles and Enhancers on the Skin Permeation of Phytoestrogenic Diarylheptanoids from Curcuma comosa.

    Science.gov (United States)

    Tuntiyasawasdikul, Sarunya; Limpongsa, Ekapol; Jaipakdee, Napaphak; Sripanidkulchai, Bungorn

    2017-04-01

    Curcuma comosa (C. comosa) is widely used in traditional medicine as a dietary supplement for health promotion in postmenopausal women in Thailand. It contains several diarylheptanoids, which are considered to be a novel class of phytoestrogens. However, the diarylheptanoids isolated from the plant rhizome are shown to have low oral bioavailability and faster elimination characteristics. The aim of this study was to investigate the permeation behavior of the active compounds of diarylheptanoids. The effects of binary vehicle systems and permeation enhancers on diarylheptanoids permeation and accumulation within the skin were studied using side-by-side diffusion cells through the porcine ear skin. Among the tested binary vehicle systems, the ethanol/water vehicle appeared to be the most effective system for diarylheptanoids permeation with the highest flux and shortest lag time. The presence of transcutol in the vehicle system significantly increased diarylheptanoid's permeation and accumulation within the skin in a concentration-dependent manner. Although the presence of terpenes in formulation decreased the flux of diarylheptanoids, it raised the amount of diarylheptanoids retained within the skin substantially. Based on the feasibility of diarylheptanoid permeation, C. comosa extract should be further developed into an effective transdermal product for health benefits and hormone replacement therapy.

  13. Effect of Permeation Enhancers on the Release Behavior and ...

    African Journals Online (AJOL)

    Purpose: The aim of this research work was to formulate, characterize and evaluate the in vitro permeation behavior of tramadol lotion containing propylene glycol (PG) and polyethylene glycol (PEG) as permeation enhancers. Methods: The permeation experiments were conducted in vitro using full thickness rabbit skin in ...

  14. Skin Delivery of EGCG and Silibinin: Potential of Peptide Dendrimers for Enhanced Skin Permeation and Deposition.

    Science.gov (United States)

    Shetty, Pallavi Krishna; Manikkath, Jyothsna; Tupally, Karnaker; Kokil, Ganesh; Hegde, Aswathi R; Raut, Sushil Y; Parekh, Harendra S; Mutalik, Srinivas

    2017-08-01

    The aim of the present study was to evaluate the ability of the peptide dendrimers to facilitate transdermal delivery of antioxidants, silibinin, and epigallocatechin-3-gallate (EGCG). Drug-peptide dendrimer complexes were prepared and evaluated for their ability to permeate across the skin. The data revealed the ready formation of complexes between drug and peptide dendrimer in a molar ratio of 1:1. In vitro permeation studies using excised rat skin and drug-peptide dendrimer complexes showed highest values for cumulative drug permeation at the end of 12 h (Q 12 ), with corresponding permeability coefficient (Kp) and enhancement ratio values also determined at this time point. With silibinin, 3.96-, 1.81-, and 1.06-fold increase in skin permeation was observed from silibinin-peptide dendrimer complex, simultaneous application of silibinin + peptide dendrimer, and pretreatment of skin with peptide dendrimer, respectively, in comparison with passive diffusion. With EGCG, 9.82-, 2.04-, and 1.72-fold increase in skin permeation was observed from EGCG-peptide dendrimer complex, simultaneous application of EGCG + peptide dendrimer, and pretreatment of skin with peptide dendrimer, respectively, in comparison with passive diffusion. The present study demonstrates the application of peptide dendrimers in effectively delivering antioxidants such as EGCG and silibinin into the skin, thus offering the potential to provide antioxidant effects when delivered via appropriately formulated topical preparations.

  15. 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

  16. Effects of Carbopol® 934 proportion on nanoemulsion gel for topical and transdermal drug delivery: a skin permeation study

    Directory of Open Access Journals (Sweden)

    Zheng Y

    2016-11-01

    Full Text Available Yin Zheng,1 Wu-Qing Ouyang,1 Yun-Peng Wei,1 Shahid Faraz Syed,2,3 Chao-Shuang Hao,1 Bo-Zhen Wang,4 Yan-Hong Shang1,5 1Department of Basic Veterinary Sciences, College of Veterinary Medicine, 2Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi; 3Faculty of Veterinary and Animal Sciences, Lasbella University of Agriculture Water and Marine Sciences, Uthal Baluchistan, Pakistan; 4College of Animal Science and Technology, Shihezi University, Shihezi, Xinjiang, 5College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan, China Abstract: Nanoemulsions (NEs are used as transdermal drug delivery systems for systematic therapeutic purposes. We hypothesized that the skin permeation profile of an NE could be modulated by incorporating it into a hydrogel containing differing proportions of thickening agent. The objectives of this study were as follows: 1 to determine the stability and skin irritability of NE gels (NGs containing 1%, 2%, and 3% (w/w Carbopol® 934 (CP934 (termed NG1, NG2, and NG3, respectively; 2 to compare the skin permeation profiles and drug deposition patterns of the NGs; and 3 to visualize the drug delivery routes of the NGs. Terbinafine and citral were incorporated into the NGs as model drugs. Ex vivo skin permeation tests indicated that the percutaneous flux rates of terbinafine decreased in the order NE (215 µg/cm2 > NG1 (213 µg/cm2 > NG2 (123 µg/cm2 > NG3 (74.3 µg/cm2. The flux rates of citral decreased in the order NE (1,026 µg/cm2 > NG1 (1,021 µg/cm2 > NG2 (541 µg/cm2 > NG3 (353 µg/cm2. The NGs accumulated greater amounts of the drugs in the stratum corneum and less in the epidermis/dermis than did the NE (P<0.05 over a period of 12 h. Laser scanning confocal microscopy indicated that the NGs altered the main drug delivery routes from skin appendages to intercellular paths. Histological images suggested

  17. Effects of Carbopol® 934 proportion on nanoemulsion gel for topical and transdermal drug delivery: a skin permeation study.

    Science.gov (United States)

    Zheng, Yin; Ouyang, Wu-Qing; Wei, Yun-Peng; Syed, Shahid Faraz; Hao, Chao-Shuang; Wang, Bo-Zhen; Shang, Yan-Hong

    Nanoemulsions (NEs) are used as transdermal drug delivery systems for systematic therapeutic purposes. We hypothesized that the skin permeation profile of an NE could be modulated by incorporating it into a hydrogel containing differing proportions of thickening agent. The objectives of this study were as follows: 1) to determine the stability and skin irritability of NE gels (NGs) containing 1%, 2%, and 3% (w/w) Carbopol ® 934 (CP934) (termed NG1, NG2, and NG3, respectively); 2) to compare the skin permeation profiles and drug deposition patterns of the NGs; and 3) to visualize the drug delivery routes of the NGs. Terbinafine and citral were incorporated into the NGs as model drugs. Ex vivo skin permeation tests indicated that the percutaneous flux rates of terbinafine decreased in the order NE (215 μg/cm 2 ) > NG1 (213 μg/cm 2 ) > NG2 (123 μg/cm 2 ) > NG3 (74.3 μg/cm 2 ). The flux rates of citral decreased in the order NE (1,026 μg/cm 2 ) > NG1 (1,021 μg/cm 2 ) > NG2 (541 μg/cm 2 ) > NG3 (353 μg/cm 2 ). The NGs accumulated greater amounts of the drugs in the stratum corneum and less in the epidermis/dermis than did the NE ( P drug delivery routes from skin appendages to intercellular paths. Histological images suggested that perturbations to the skin structure, specifically the size of the epidermal intercellular spaces and the separation distance of dermal collagen bundles, could be significantly minimized by increasing the proportion of CP934. These results suggest that adjustments of the CP934 proportions can be used to modulate the skin permeation profiles of NGs for specific therapeutic purposes.

  18. 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.

  19. 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.

  20. 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.

  1. Enhanced transdermal bioavailability of testosterone propionate via surfactant-modified ethosomes

    Directory of Open Access Journals (Sweden)

    Meng S

    2013-08-01

    Full Text Available Shu Meng,1 Zaixing Chen,2 Liqun Yang,1 Wei Zhang,1 Danhua Liu,1 Jing Guo,1 Yanmin Guan,1 Jianxin Li11Liaoning Research Institute of Family Planning, Shenyang, Liaoning Province, People's Republic of China; 2School of Pharmacy, China Medical University, Shenyang, Liaoning Province, People's Republic of ChinaAbstract: The current investigation aimed to evaluate the transdermal potential of novel testosterone propionate (TP ethosomes and liposomes prepared by surfactant modification. The effect of hexadecyl trimethyl ammonium bromide and cremophor EL-35 on the particle size and zeta potential of the prepared vesicles was investigated. The entrapment efficiency and stability, as well as in vitro and in vivo skin permeation, were studied with the various techniques, such as differential scanning calorimetry, confocal laser scanning microscopy, transmission electron microscopy, dynamic light scattering, and so on. The results indicated that the ethosomes were defined as spherical, unilamellar structures with low polydispersity (0.100 ± 0.015 and nanometric size (156.5 ± 3.5 nm. The entrapment efficiency of TP in ethosomal and liposomal carriers was 92.7% ± 3.7% and 64.7% ± 2.1%, respectively. The stability profile of the prepared TP ethosomal system assessed for 120 days revealed very low aggregation and very low growth in vesicular size. TP ethosomes also provided an enhanced transdermal flux of 37.85 ± 2.8 µg/cm2/hour and a decreased lag time of 0.18 hours across mouse skin. The skin permeation efficiency of the TP ethosomes as further assessed by confocal laser scanning microscopy revealed enhanced permeation of rhodamine red-loaded formulations to the deeper layers of the skin (260 µm than that of the liposomal formation (120 µm.Keywords: testosterone propionate, surfactant-modified ethosomes, liposomes, confocal laser scanning microscopy

  2. Liquid crystalline systems for transdermal delivery of celecoxib: in vitro drug release and skin permeation studies.

    Science.gov (United States)

    Estracanholli, Eder André; Praça, Fabíola Silva Garcia; Cintra, Ana Beatriz; Pierre, Maria Bernadete Riemma; Lara, Marilisa Guimarães

    2014-12-01

    Liquid crystalline systems of monoolein/water could be a promising approach for the delivery of celecoxib (CXB) to the skin because these systems can sustain drug release, improve drug penetration into the skin layers and minimize side effects. This study evaluated the potential of these systems for the delivery of CXB into the skin based on in vitro drug release and skin permeation studies. The amount of CXB that permeated into and/or was retained in the skin was assayed using an HPLC method. Polarizing light microscopy studies showed that liquid crystalline systems of monoolein/water were formed in the presence of CXB, without any changes in the mesophases. The liquid crystalline systems decreased drug release when compared to control solution. Drug release was independent of the initial water content of the systems and CXB was released from cubic phase systems, irrespective of the initial water content. The systems released the CXB following zero-order release kinetics. In vitro drug permeation studies showed that cubic phase systems allowed drug permeation and retention in the skin layers. Cubic phase systems of monoolein/water may be promising vehicles for the delivery of CXB in/through the skin because it improved CXB skin permeation compared with the control solution.

  3. Transdermal delivery of diclofenac using water-in-oil microemulsion: formulation and mechanistic approach of drug skin permeation.

    Science.gov (United States)

    Thakkar, Priyanka J; Madan, Parshotam; Lin, Senshang

    2014-05-01

    The objective of the present investigation was to enhance skin permeation of diclofenac using water-in-oil microemulsion and to elucidate its skin permeation mechanism. The w/o microemulsion formulations were selected based on constructed pseudoternary phase diagrams depending on water solubilization capacity and thermodynamic stability. These formulations were also subjected to physical characterization based on droplet size, viscosity, pH and conductivity. Permeation of diclofenac across rat skin using side-by-side permeation cells from selected w/o microemulsion formulations were evaluated and compared with control formulations. The selected w/o microemulsion formulations were thermodynamically stable, and incorporation of diclofenac sodium into microemulsion did not affect the phase behavior of system. All microemulsion formulations had very low viscosity (11-17 cps) and droplet size range of 30-160 nm. Microemulsion formulations exhibited statistically significant increase in diclofenac permeation compared to oily solution, aqueous solution and oil-Smix solution. Higher skin permeation of diclofenac was observed with low Smix concentration and smaller droplet size. Increase in diclofenac loading in aqueous phase decreased the partition of diclofenac. Diclofenac from the oil phase of microemulsion could directly partition into skin, while diclofenac from the aqueous droplets was carried through skin by carrier effect.

  4. 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. ...

  5. 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

  6. Alteration of skin hydration and its barrier function by vehicle and permeation enhancers: a study using TGA, FTIR, TEWL and drug permeation as markers.

    Science.gov (United States)

    Shah, D K; Khandavilli, S; Panchagnula, R

    2008-09-01

    Vehicles and permeation enhancers (PEs) used in transdermal drug delivery (TDD) of a drug can affect skin hydration, integrity and permeation of the solute administered. This investigation was designed to study the effect of the most commonly used vehicles and PEs on rat skin hydration, barrier function and permeation of an amphiphilic drug, imipramine hydrochloride (IMH). An array of well-established techniques were used to confirm the findings of the study. Thermogravimetric analysis (TGA) and Fourier transform infrared (FTIR) spectroscopy were used to determine changes in skin hydration. Alteration of the stratum corneum (SC) structure was investigated using FTIR studies. To monitor the barrier function alteration, transepidermal water loss (TEWL) measurement and permeation studies were performed. Our findings indicate that with hydration, there was an increase in the bound water content of the skin, and pseudoequilibrium of hydration (a drastic decrease in hydration rate) was achieved at around 12 h. Hydration increased the ratio between amide-I and amide-II peaks in FTIR and reduced the C-H stretching peak area. Both propylene glycol (PG) and ethanol (EtOH) dehydrated skin, with the latter showing a predominant effect. Furthermore, it was confirmed that PG and EtOH decreased the bound water content due to alteration in the protein domains and extraction of SC lipids, respectively. The effect of hydration on the SC was found to be similar to that reported for temperature. Permeation studies revealed that the dehydration caused by vehicles decreased IMH flux, whereas the flux was enhanced by PEs. The role of partition was predominant for the permeation of IMH through dehydrated skin. A synergistic effect was observed for PG and menthol in the enhancement of IMH. Further findings provided strong evidence that PG affects protein domains and EtOH extracts lipids from the bilayer. Both PG and EtOH, with or without PEs, increased TEWL. Initial TEWL was well

  7. Essential oil from Zanthoxylum bungeanum Maxim. and its main components used as transdermal penetration enhancers: a comparative study.

    Science.gov (United States)

    Lan, Yi; Li, Hui; Chen, Yan-yan; Zhang, Ye-wen; Liu, Na; Zhang, Qing; Wu, Qing

    2014-11-01

    Our previous studies had confirmed that the essential oil from Zanthoxylum bungeanum Maxim. (Z. bungeanum oil) could effectively enhance the percutaneous permeation of drug molecules as a natural transdermal penetration enhancer. The aim of the present study is to investigate and compare the skin penetration enhancement effect of Z. bungeanum oil and its main components on traditional Chinese medicine (TCM) active components. Toxicities of Z. bungeanum oil and three selected terpene compounds (terpinen-4-ol, 1,8-cineole, and limonene) in epidermal keratinocytes (HaCaT) and dermal fibroblast (CCC-ESF-1) cell lines were measured using an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Five model drugs in TCM external preparations, namely osthole (OT), tetramethylpyrazine (TMP), ferulic acid (FA), puerarin (PR), and geniposide (GP), which were selected based on their lipophilicity denoted by logKo/w, were tested using in vitro permeation studies in which vertical Franz diffusion cells and rat abdominal skin were employed. The secondary structure changes of skin stratum corneum (SC) and drug thermodynamic activities were investigated to understand their mechanisms of action using Fourier transform infrared (FTIR) spectroscopy and saturation solubility studies, respectively. It was found that Z. bungeanum oil showed lower toxicities in both HaCaT cells and CCC-ESF-1 cells compared with three terpene compounds used alone. The enhancement permeation capacities by all tested agents were in the following increasing order: terpinen-4-ol≈1,8-cineolepermeation enhancement suggested that these enhancers promoted the skin permeation of drugs mainly by affecting SC lipids. These results indicated that Z. bungeanum oil exhibited better performance in enhancing the skin permeation of active components in TCM preparations.

  8. Development of Lecithin Nanoemulsion Based Organogels for Permeation Enhancement of Metoprolol through Rat Skin

    Directory of Open Access Journals (Sweden)

    J. Varshosaz

    2013-01-01

    Full Text Available Background. Drugs with low oral bioavailability due to the first pass metabolism are good candidates for transdermal delivery. Objectives. The aim of this work was preparation of transdermal nanoemulsion of metoprolol which has high first pass metabolism. Methods. Three commercially available types of lecithin (200, 100p, and 170, three short chain alcohol (n-butanol, isopropyl alcohol, and n-propanol, and isopropyl myristate (IPM were used as surfactant, cosurfactant, and oil phase, respectively. The aqueous phase was composed of metoprolol tartrate. Nanoemulsions with different surfactant/cosurfactant weight ratio, various amounts of drug, and different types of alcohol were prepared, and their phase diagrams were studied. Drug release, permeability, and diffusion coefficient of the drug were studied using hairless rat skin. Results. A significant increase in drug solution rate was observed with increasing the metoprolol content in the nanoemulsions, while it decreased when lecithin concentration increased from 40% to 60%. Increasing the water content resulted in a significant increase in metoprolol release. N-butanol enhanced the drug flux from nanoemulsions more than n-propanol and isopropyl alcohol. The o/w nanoemulsions of metoprolol showed high flux and permeability through the skin. Conclusion. Both w/o and o/w nanoemulsions of metoprolol could enhance permeation and diffusion of metoprolol through rat skin.

  9. A statistical experimental design approach to evaluate the influence of various penetration enhancers on transdermal drug delivery of buprenorphine

    Directory of Open Access Journals (Sweden)

    S.Mojtaba Taghizadeh

    2015-03-01

    Full Text Available A series of drug-in-adhesive transdermal drug delivery systems (patch with different chemical penetration enhancers were designed to deliver drug through the skin as a site of application. The objective of our effort was to study the influence of various chemical penetration enhancers on skin permeation rate and adhesion properties of a transdermal drug delivery system using Box–Behnken experimental design. The response surface methodology based on a three-level, three-variable Box–Behnken design was used to evaluate the interactive effects on dependent variables including, the rate of skin permeation and adhesion properties, namely peel strength and tack value. Levulinic acid, lauryl alcohol, and Tween 80 were used as penetration enhancers (patch formulations, containing 0–8% of each chemical penetration enhancer. Buprenorphine was used as a model penetrant drug. The results showed that incorporation of 20% chemical penetration enhancer into the mixture led to maximum skin permeation flux of buprenorphine from abdominal rat skin while the adhesion properties decreased. Also that skin flux in presence of levulinic acid (1.594 μg/cm2 h was higher than Tween 80 (1.473 μg/cm2 h and lauryl alcohol (0.843 μg/cm2 h, and in mixing these enhancers together, an additional effect was observed. Moreover, it was found that each enhancer increased the tack value, while levulinic acid and lauryl alcohol improved the peel strength but Tween 80 reduced it. These findings indicated that the best chemical skin penetration enhancer for buprenorphine patch was levulinic acid. Among the designed formulations, the one which contained 12% (wt/wt enhancers exhibited the highest efficiency.

  10. A statistical experimental design approach to evaluate the influence of various penetration enhancers on transdermal drug delivery of buprenorphine.

    Science.gov (United States)

    Taghizadeh, S Mojtaba; Moghimi-Ardakani, Ali; Mohamadnia, Fatemeh

    2015-03-01

    A series of drug-in-adhesive transdermal drug delivery systems (patch) with different chemical penetration enhancers were designed to deliver drug through the skin as a site of application. The objective of our effort was to study the influence of various chemical penetration enhancers on skin permeation rate and adhesion properties of a transdermal drug delivery system using Box-Behnken experimental design. The response surface methodology based on a three-level, three-variable Box-Behnken design was used to evaluate the interactive effects on dependent variables including, the rate of skin permeation and adhesion properties, namely peel strength and tack value. Levulinic acid, lauryl alcohol, and Tween 80 were used as penetration enhancers (patch formulations, containing 0-8% of each chemical penetration enhancer). Buprenorphine was used as a model penetrant drug. The results showed that incorporation of 20% chemical penetration enhancer into the mixture led to maximum skin permeation flux of buprenorphine from abdominal rat skin while the adhesion properties decreased. Also that skin flux in presence of levulinic acid (1.594 μg/cm(2) h) was higher than Tween 80 (1.473 μg/cm(2) h) and lauryl alcohol (0.843 μg/cm(2) h), and in mixing these enhancers together, an additional effect was observed. Moreover, it was found that each enhancer increased the tack value, while levulinic acid and lauryl alcohol improved the peel strength but Tween 80 reduced it. These findings indicated that the best chemical skin penetration enhancer for buprenorphine patch was levulinic acid. Among the designed formulations, the one which contained 12% (wt/wt) enhancers exhibited the highest efficiency.

  11. Skin permeation enhancement effects of the gel and whole-leaf materials of Aloe vera, Aloe marlothii and Aloe ferox.

    Science.gov (United States)

    Fox, Lizelle T; Gerber, Minja; du Preez, Jan L; du Plessis, Jeanetta; Hamman, Josias H

    2015-01-01

    The aim of this study was to investigate the in-vitro permeation enhancement effects of the gel and whole-leaf materials of Aloe vera, Aloe marlothii and Aloe ferox using ketoprofen as a marker compound. The permeation studies were conducted across excised female abdominal skin in Franz diffusion cells, and the delivery of ketoprofen into the stratum corneum-epidermis and epidermis-dermis layers of the skin was investigated using a tape-stripping technique. A. vera gel showed the highest permeation-enhancing effect on ketoprofen (enhancement ratio or ER = 2.551) when compared with the control group, followed by A. marlothii gel (ER = 1.590) and A. ferox whole-leaf material (ER = 1.520). Non-linear curve fitting calculations indicated that the drug permeation-enhancing effect of A. vera gel can be attributed to an increased partitioning of the drug into the skin, while A. ferox whole leaf modified the diffusion characteristics of the skin for ketoprofen. The tape stripping results indicated that A. marlothii whole leaf delivered the highest concentration of the ketoprofen into the different skin layers. Of the selected aloe species investigated, A. vera gel material showed the highest potential as transdermal drug penetration enhancer across human skin. © 2014 Royal Pharmaceutical Society.

  12. 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.

  13. Development and Evaluation of Naproxen Sodium Gel Using Piper cubeba for Enhanced Transdermal Drug Delivery and Therapeutic Facilitation.

    Science.gov (United States)

    Patwardhan, Sunetra; Patil, Manohar; Sockalingam, Anbazhagan

    2017-01-01

    The absorption of drug through skin avoids many side effects of oral route like gastric irritation, nausea, systemic toxicity etc and thus improves patient compliance. Naproxen sodium (NPRS) is one of the potent NSAID agents. The present study was aimed to develop and evaluate the gel formulation containing NPRS for transdermal drug delivery reducing the side effects and improving patient compliance. The patents on topical delivery of NSAIDS (US 9012402 B1, US 9072659 B2, US 20150258196 A1) and patents indicating use of herbal penetration enhancers (US 20100273746A1, WO 2005009510 A2, US 6004969 A) helped in selecting the drug, excipients. Current protocol employs various extracts of Piper cubeba fruit to evaluate its role in absorption of NPRS. Various batches containing 1% NPRS and varying concentrations of synthetic permeation enhancers or the extracts were formulated in carbopol gel. Gel was evaluated for parameters like organoleptic parameters, pH, viscosity and spreadability. An ex-vivo percutaneous absorption of NPRS from gel was investigated and compared with best performing synthetic enhancer, transcutol P (TP). The batch containing 2% n-hexane extract (NHE) of Piper cubeba showed higher permeation than TP and Chloroform (CE), Methanolic (ME) and aqueous (AE) extracts as well. It showed improved % cumulative release (85.09%) and flux (278.61μg/cm2.h), as compared to TP and other extracts. Histopathology indicated the formulation safer as compared to that with synthetic enhancer. It suggests P. cubeba as effective and safer tool for transdermal delivery and acts as therapeutic facilitator for naproxen. GC-MS analysis indicates lignans & terpenes in NHE to which this permeation enhancement activity may be attributed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. Effect of various enhancers on transdermal penetration of indomethacin and urea, and relationship between penetration parameters and enhancement factors.

    Science.gov (United States)

    Ogiso, T; Iwaki, M; Paku, T

    1995-04-01

    The enhancing capacity of various chemicals, which are widely recognized as enhancers, for the transdermal penetration into full-thickness rat skin of a model lipophilic drug [indomethacin (IND)] and a hydrophilic permeant (urea) was estimated by an in vitro technique. In addition, the fluidity of the stratum corneum lipids, the partitioning of IND into skin, the lipid (ceramides) extraction from the stratum corneum by enhancers, and the IND solubility in enhancer vehicle were measured and related to the enhancing capacity. In vitro permeation experiments with hairless rat skin unequivocally revealed that the enhancers varied in abilities to enhance the fluxes of both agents. Laurocapram, isopropylmyristate (IPM), sodium oleate, and cineol increased fluxes of both agents to a great extent, but N-methyl-2-pyrrolidone (NMP), N,N-diethyl-m-tolamide (DEET), and oleyl oleate were less effective acclerants. Many enhancers increased the fluidity of the lipids [with a threshold of approximately 0.6-0.8 ns at 37 degrees C in the rotational correlation time (tau c)], the skin partitioning of IND, the extraction of ceramides from the cornified cells, and the thermodynamic activity of IND in vehicle (calculated from the solubility) to varying extents. A good correlation was observed between the increase in the fluidity of stratum corneum lipids and the partitioning of IND into skin, between the increase in the fluidity and the flux or the decrease in lag time for IND, between the removal of ceramides and the skin partitioning of IND, and between the removal of ceramides and the flux of urea (p < 0.05 in all cases).(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Effect of permeation enhancers on the iontophoretic transport of metoprolol tartrate and the drug retention in skin.

    Science.gov (United States)

    Nair, Anroop; Vyas, Hiral; Shah, Jigar; Kumar, Ashok

    2011-01-01

    Utilization of chemical penetration enhancers in conjunction with iontophoresis is regarded as the most effective method to enhance the passage of molecules across the skin barrier. A systematic approach to enhance the transdermal delivery of metoprolol tartrate and the subsequent release of the drug depot in the skin was investigated. Gel formulations with proximate viscosity were prepared and assessed for the effect of polymers (carbopol, hydroxypropyl methyl cellulose, and methyl cellulose), permeation enhancers (5% w/w, sodium lauryl sulfate (SLS), dimethyl formamide, n-methyl-2-pyrrolidone, and polyethylene glycol 400), and the combination approach (permeation enhancers with iontophoresis-0.5 mA/cm² on the drug delivery. The flux values observed in passive (4.59-5.89 µg/cm²/h) and iontophoresis (37.99-41.57 µg/cm²/h) processes revealed that the permeation of metoprolol was not influenced by the polymers studied, under similar conditions, and further studies were carried out using carbopol gel as a representative polymer. Appreciable enhancement (~5-fold) in drug delivery was observed with SLS in the passive process while the optimum iontophoretic delivery condition ensured better delivery (~7-fold). Combination of iontophoresis with SLS further enhanced the drug delivery (~9-fold) and leads to noticeable drug retention in the skin as well. Moreover, the drug retained in the cutaneous layer of the skin eventually released over a period of time (5 days) and followed a near first order profile. This study concludes that the combination of iontophoresis with SLS augmented the metoprolol delivery and rendered skin drug depot, which eventually released over a period of time.

  1. 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.

  2. 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.

  3. 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.

  4. Dry Gel Containing Optimized Felodipine-Loaded Transferosomes: a Promising Transdermal Delivery System to Enhance Drug Bioavailability.

    Science.gov (United States)

    Kassem, Mohammed Ali; Aboul-Einien, Mona Hassan; El Taweel, Mai Magdy

    2018-04-30

    Felodipine has a very low bioavailability due to first-pass metabolism. The aim of this study was to enhance its bioavailability by transdermal application. Felodipine-loaded transferosomes were prepared by thin-film hydration using different formulation variables. An optimized formula was designed using statistical experimental design. The independent variables were the used edge activator, its molar ratio to phosphatidylcholine, and presence or absence of cholesterol. The responses were entrapment efficiency of transferosomes, their size, polydispersity index, zeta potential, and percent drug released after 8 h. The optimized formula was subjected to differential scanning calorimetry studies and its stability on storage at 4°C for 6 months was estimated. This formula was improved by incorporation of different permeation enhancers where ex vivo drug flux through mice skin was estimated and the best improved formula was formulated in a gel and lyophilized. The prepared gel was subjected to in vivo study using Plendil® tablets as a reference. According to the calculated desirability, the optimized transferosome formula was that containing sodium deoxycholate as edge activator at 5:1 M ratio to phosphatidylcholine and no cholesterol. The thermograms of this formula indicated the incorporation of felodipine inside the prepared vesicles. None of the tested parameters differed significantly on storage. The lyophilized gel of labrasol-containing formula was chosen for in vivo study. The relative bioavailability of felodipine from the designed gel was 1.7. In conclusion, topically applied lyophilized gel containing felodipine-loaded transferosomes is a promising transdermal delivery system to enhance its bioavailability.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Enhanced Transdermal Delivery of Diclofenac Sodium via Conventional Liposomes, Ethosomes, and Transfersomes

    Directory of Open Access Journals (Sweden)

    Saeed Ghanbarzadeh

    2013-01-01

    Full Text Available The aim of this study was to improve the transdermal permeation of Diclofenac sodium, a poorly water-soluble drug, employing conventional liposomes, ethosomes, and transfersomes. The prepared formulations had been characterized for the loaded drug amount and vesicle size. The prepared vesicular systems were incorporated into 1% Carbopol 914 gel, and a survey of in vitro drug release and drug retention into rat skin has been done on them using a modified Franz diffusion cell. The cumulative amount of drug permeated after 24 h, flux, and permeability coefficient were assessed. Stability studies were performed for three months. The size of vesicles ranged from 145 to 202 nm, and the encapsulation efficiency of the Diclofenac sodium was obtained between 42.61% and 51.72%. The transfersomes and ethosomes provided a significantly higher amount of cumulative permeation, steady state flux, permeability coefficient, and residual drug into skin compared to the conventional liposomes, conventional gel, or hydroethanolic solution. The in vitro release data of all vesicular systems were well fit into Higuchi model (RSD > 0.99. Stability tests indicated that the vesicular formulations were stable over three months. Results revealed that both ethosome and transfersome formulations can act as drug reservoir in skin and extend the pharmacologic effects of Diclofenac sodium.

  13. 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.

  14. 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.

  15. 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.

  16. Enhanced skin permeation of naltrexone by pulsed electromagnetic fields in human skin in vitro.

    Science.gov (United States)

    Krishnan, Gayathri; Edwards, Jeffrey; Chen, Yan; Benson, Heather A E

    2010-06-01

    The aim of the present study was to evaluate the skin permeation of naltrexone (NTX) under the influence of a pulsed electromagnetic field (PEMF). The permeation of NTX across human epidermis and a silicone membrane in vitro was monitored during and after application of the PEMF and compared to passive application. Enhancement ratios of NTX human epidermis permeation by PEMF over passive diffusion, calculated based on the AUC of cumulative NTX permeation to the receptor compartment verses time for 0-4 h, 4-8 h, and over the entire experiment (0-8 h) were 6.52, 5.25, and 5.66, respectively. Observation of the curve indicated an initial enhancement of NTX permeation compared to passive delivery whilst the PEMF was active (0-4 h). This was followed by a secondary phase after termination of PEMF energy (4-8 h) in which there was a steady increase in NTX permeation. No significant enhancement of NTX penetration across silicone membrane occurred with PEMF application in comparison to passively applied NTX. In a preliminary experiment PEMF enhanced the penetration of 10 nm gold nanoparticles through the stratum corneum as visualized by multiphoton microscopy. This suggests that the channels through which the nanoparticles move must be larger than the 10 nm diameter of these rigid particles. (c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association

  17. 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

  18. Differential permeation of piroxicam-loaded PLGA micro/nanoparticles and their in vitro enhancement

    International Nuclear Information System (INIS)

    Shankarayan, Raju; Kumar, Sumit; Mishra, Prashant

    2013-01-01

    Piroxicam is a non-steroidal anti-inflammatory drug used for the treatment of musculoskeletal pain. The main problem encountered when piroxicam is administered orally is its gastric side-effect (ulcer, bleeding and holes in the stomach). Transmucosal delivery and encapsulation of piroxicam in biodegradable particles offer potential advantages over conventional oral delivery. The present study was aimed to develop an alternative to piroxicam-delivery which could overcome the direct contact of the drug at the mucosal membrane and its permeation through the mucosal membrane was studied. To achieve this, the piroxicam was encapsulated in Poly (lactide-co-glycolide) (PLGA) microparticles (size 1–4 μm, encapsulation efficiency 80–85 %) and nanoparticles (size 151.6 ± 28.6 nm, encapsulation efficiency 92.17 ± 3.08 %). Various formulation process parameters were optimised for the preparation of piroxicam-loaded PLGA nanoparticles of optimal size and encapsulation efficiency. Transmucosal permeability of piroxicam-loaded PLGA micro- and nanoparticles through the porcine oesophageal mucosa was studied. Using fluorescently labelled PLGA micro- and nanoparticles, size-dependent permeation was demonstrated. Furthermore, the effect of different permeation enhancers on the flux rate and permeability coefficient for the permeation of nanoparticles was investigated. The results suggested that amongst the permeation enhancers used the most efficient enhancement of permeation was observed with 10 mM sodium dodecyl sulphate.

  19. Differential permeation of piroxicam-loaded PLGA micro/nanoparticles and their in vitro enhancement

    Energy Technology Data Exchange (ETDEWEB)

    Shankarayan, Raju; Kumar, Sumit; Mishra, Prashant, E-mail: pmishra@dbeb.iitd.ac.in [Indian Institute of Technology Delhi, Department of Biochemical Engineering and Biotechnology (India)

    2013-03-15

    Piroxicam is a non-steroidal anti-inflammatory drug used for the treatment of musculoskeletal pain. The main problem encountered when piroxicam is administered orally is its gastric side-effect (ulcer, bleeding and holes in the stomach). Transmucosal delivery and encapsulation of piroxicam in biodegradable particles offer potential advantages over conventional oral delivery. The present study was aimed to develop an alternative to piroxicam-delivery which could overcome the direct contact of the drug at the mucosal membrane and its permeation through the mucosal membrane was studied. To achieve this, the piroxicam was encapsulated in Poly (lactide-co-glycolide) (PLGA) microparticles (size 1-4 {mu}m, encapsulation efficiency 80-85 %) and nanoparticles (size 151.6 {+-} 28.6 nm, encapsulation efficiency 92.17 {+-} 3.08 %). Various formulation process parameters were optimised for the preparation of piroxicam-loaded PLGA nanoparticles of optimal size and encapsulation efficiency. Transmucosal permeability of piroxicam-loaded PLGA micro- and nanoparticles through the porcine oesophageal mucosa was studied. Using fluorescently labelled PLGA micro- and nanoparticles, size-dependent permeation was demonstrated. Furthermore, the effect of different permeation enhancers on the flux rate and permeability coefficient for the permeation of nanoparticles was investigated. The results suggested that amongst the permeation enhancers used the most efficient enhancement of permeation was observed with 10 mM sodium dodecyl sulphate.

  20. Differential permeation of piroxicam-loaded PLGA micro/nanoparticles and their in vitro enhancement

    Science.gov (United States)

    Shankarayan, Raju; Kumar, Sumit; Mishra, Prashant

    2013-03-01

    Piroxicam is a non-steroidal anti-inflammatory drug used for the treatment of musculoskeletal pain. The main problem encountered when piroxicam is administered orally is its gastric side-effect (ulcer, bleeding and holes in the stomach). Transmucosal delivery and encapsulation of piroxicam in biodegradable particles offer potential advantages over conventional oral delivery. The present study was aimed to develop an alternative to piroxicam-delivery which could overcome the direct contact of the drug at the mucosal membrane and its permeation through the mucosal membrane was studied. To achieve this, the piroxicam was encapsulated in Poly (lactide- co-glycolide) (PLGA) microparticles (size 1-4 μm, encapsulation efficiency 80-85 %) and nanoparticles (size 151.6 ± 28.6 nm, encapsulation efficiency 92.17 ± 3.08 %). Various formulation process parameters were optimised for the preparation of piroxicam-loaded PLGA nanoparticles of optimal size and encapsulation efficiency. Transmucosal permeability of piroxicam-loaded PLGA micro- and nanoparticles through the porcine oesophageal mucosa was studied. Using fluorescently labelled PLGA micro- and nanoparticles, size-dependent permeation was demonstrated. Furthermore, the effect of different permeation enhancers on the flux rate and permeability coefficient for the permeation of nanoparticles was investigated. The results suggested that amongst the permeation enhancers used the most efficient enhancement of permeation was observed with 10 mM sodium dodecyl sulphate.

  1. Impacts of chemical enhancers on skin permeation and deposition of terbinafine.

    Science.gov (United States)

    Erdal, Meryem Sedef; Peköz, Ayca Yıldız; Aksu, Buket; Araman, Ahmet

    2014-08-01

    The addition of chemical enhancers into formulations is the most commonly employed approach to overcome the skin barrier. The objective of this work was to evaluate the effect of vehicle and chemical enhancers on the skin permeation and accumulation of terbinafine, an allylamine antifungal drug. Terbinafine (1% w/w) was formulated as a Carbopol 934 P gel formulation in presence and absence of three chemical enhancers, nerolidol, dl-limonene and urea. Terbinafine distribution and deposition in stratum corneum (SC) and skin following 8-h ex vivo permeation study was determined using a sequential tape stripping procedure. The conformational order of SC lipids was investigated by ATR-FTIR spectroscopy. Nerolidol containing gel formulation produced significantly higher enhancement in terbinafine permeation through skin and its skin accumulation was increased. ATR-FTIR results showed enhancer induced lipid bilayer disruption in SC. Urea resulted in enhanced permeation of terbinafine across the skin and a balanced distribution to the SC was achieved. But, dl-limonene could not minimize the accumulation of terbinafine in the upper SC. Nerolidol dramatically improved the skin permeation and deposition of terbinafine in the skin that might help to optimize targeting of the drug to the epidermal sites as required for both of superficial and deep cutaneous fungal infections.

  2. 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...

  3. Metabolic approaches to enhance transdermal drug delivery. 1. Effect of lipid synthesis inhibitors.

    Science.gov (United States)

    Tsai, J C; Guy, R H; Thornfeldt, C R; Gao, W N; Feingold, K R; Elias, P M

    1996-06-01

    The intercellular domains of the stratum corneum, which contain a mixture of cholesterol, free fatty acids, and ceramides, mediate both the epidermal permeability barrier and the transdermal delivery of both lipophilic and hydrophilic molecules. Prior studies have shown that each of the three key lipid classes is required for normal barrier function. For example, selective inhibition of either cholesterol, fatty acid, or ceramide synthesis in the epidermis delays barrier recovery rates after barrier perturbation of hairless mouse skin in vivo. In this study, we investigated the potential of certain inhibitors of lipid synthesis to enhance the transdermal delivery of lidocaine or caffeine as a result of their capacity to perturb barrier homeostasis. After acetone disruption of the barrier, the extent of lidocaine delivery and the degree of altered barrier function paralleled each other. Moreover, the further alteration in barrier function produced by either the fatty acid synthesis inhibitor 5-(tetradecyloxy)-2-furancarboxylic acid (TOFA), the cholesterol synthesis inhibitor fluvastatin (FLU), or cholesterol sulfate (CS) resulted in a further increase in lidocaine absorption. Furthermore, coapplications of TOFA and CS together caused an additive increase in lidocaine uptake. Finally, a comparable increase in drug delivery occurred when the barrier was disrupted initially with DMSO instead of acetone; coapplications of TOFA and FLU together again delayed barrier recovery and increased drug delivery by about 8-fold vs delivery from a standard enhancing vehicle. Whereas these metabolic inhibitors also variably increased the octanol/water partitioning of the drugs studied (perhaps via complexion or pH alterations), physicochemical effects of the inhibitors alone did not alter drug uptake in intact skin; i.e., passive mechanisms alone cannot account for the net increase in drug delivery. Our results show that modulations of epidermal lipid biosynthesis, following

  4. Drug Release and Skin Permeation from Lipid Liquid Crystalline Phases

    Science.gov (United States)

    Costa-Balogh, F. O.; Sparr, E.; Sousa, J. J. S.; Pais, A. A. C. C.

    We have studied drug release and skin permeation from several different liquid crystalline lipid formulations that may be used to control the respective release rates. We have studied the release and permeation through human skin of a water-soluble and amphiphilic drug, propranolol hydrochloride, from several formulations prepared with monoolein and phytantriol as permeation enhancers and controlled release excipients. Diolein and cineol were added to selected formulations. We observed that viscosity decreases with drug load, wich is compatible with the occurrence of phase changes. Diolein stabilizes the bicontinuous cubic phases leading to an increase in viscosity and sustained release of the drug. The slowest release was found for the cubic phases with higher viscosity. Studies on skin permeation showed that these latter formulations also presented lower permeability than the less viscous monoolein lamellar phases. Formulations containing cineol originated higher permeability with higher enhancement ratios. Thus, the various formulations are adapted to different circumstances and delivery routes. While a slow release is usually desired for drug sustained delivery, the transdermal route may require a faster release. Lamellar phases, which are less viscous, are more adapted to transdermal applications. Thus, systems involving lamellar phases of monoolein and cineol are good candidates to be used as skin permeation enhancers for propranolol hydrochloride.

  5. Analysis of skin permeation-enhancing mechanism of iontophoresis using hydrodynamic pore theory.

    Science.gov (United States)

    Manabe, E; Numajiri, S; Sugibayashi, K; Morimoto, Y

    2000-05-15

    The effects of constant DC iontophoresis (0-1.5 mA/0.966 cm(2)) on the permeation of three hydrophilic compounds, antipyrine (ANP, M.W. 188.23), sucrose (SR, M.W. 342.30) and 1-kestose (KT, M.W. 506.73), through excised hairless rat skin were evaluated using hydrodynamic pore theory. The electro-osmotic flow caused by iontophoresis was measured using deuterium oxide (D(2)O). The penetration-enhancing mechanism of iontophoresis was found to increase solvent flow through electro-osmosis and pore enlargement and/or new pore production in the skin barrier, together with enhancement of electrochemical potential difference across the skin. These effects were closely related to the strength of the current applied. The electro-osmotic flow of D(2)O (J(D(2)O)) greatly enhanced the skin permeation clearance of all hydrophilic penetrants (CL(drug)). Pore production was classified into reversible and irreversible processes, which resulted from lower (0-0.5 mA/0.966 cm(2)) and higher (0.5-1. 5 mA/0.966 cm(2)) currents, respectively. Thus, the enhancing effects of iontophoresis on skin permeation of nonionic hydrophilic compounds can be explained by increase in pore size and higher solvent flow.

  6. Electro-Conductive Membranes for Permeation Enhancement and Fouling Mitigation: A Short Review.

    Science.gov (United States)

    Formoso, Patrizia; Pantuso, Elvira; De Filpo, Giovanni; Nicoletta, Fiore Pasquale

    2017-07-28

    The research on electro-conductive membranes has expanded in recent years. These membranes have strong prospective as key components in next generation water treatment plants because they are engineered in order to enhance their performance in terms of separation, flux, fouling potential, and permselectivity. The present review summarizes recent developments in the preparation of electro-conductive membranes and the mechanisms of their response to external electric voltages in order to obtain an improvement in permeation and mitigation in the fouling growth. In particular, this paper deals with the properties of electro-conductive polymers and the preparation of electro-conductive polymer membranes with a focus on responsive membranes based on polyaniline, polypyrrole and carbon nanotubes. Then, some examples of electro-conductive membranes for permeation enhancement and fouling mitigation by electrostatic repulsion, hydrogen peroxide generation and electrochemical oxidation will be presented.

  7. Electro-Conductive Membranes for Permeation Enhancement and Fouling Mitigation: A Short Review

    Directory of Open Access Journals (Sweden)

    Patrizia Formoso

    2017-07-01

    Full Text Available The research on electro-conductive membranes has expanded in recent years. These membranes have strong prospective as key components in next generation water treatment plants because they are engineered in order to enhance their performance in terms of separation, flux, fouling potential, and permselectivity. The present review summarizes recent developments in the preparation of electro-conductive membranes and the mechanisms of their response to external electric voltages in order to obtain an improvement in permeation and mitigation in the fouling growth. In particular, this paper deals with the properties of electro-conductive polymers and the preparation of electro-conductive polymer membranes with a focus on responsive membranes based on polyaniline, polypyrrole and carbon nanotubes. Then, some examples of electro-conductive membranes for permeation enhancement and fouling mitigation by electrostatic repulsion, hydrogen peroxide generation and electrochemical oxidation will be presented.

  8. 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.

  9. Permeation enhancing polymers in oral delivery of hydrophilic macromolecules: thiomer/GSH systems.

    Science.gov (United States)

    Bernkop-Schnürch, A; Kast, C E; Guggi, D

    2003-12-05

    Thiolated polymers (= thiomers) in combination with reduced glutathione (GSH) were shown to improve the uptake of hydrophilic macromolecules from the GI tract. The mechanism responsible for this permeation enhancing effect seems to be based on the thiol groups of the polymer. These groups inhibit protein tyrosine phosphatase, being involved in the closing process of tight junctions, via a GSH-mediated mechanism. The strong permeation enhancing effect of various thiomer/GSH systems such as poly(acrylic acid)-cysteine/GSH or chitosan-4-thio-butylamidine (chitosan-TBA)/GSH could be shown via permeation studies on freshly excised intestinal mucosa in Ussing-type chambers. Furthermore, the efficacy of the system was also shown in vivo. By utilizing poly(acrylic acid)-cysteine/GSH as carrier matrix, an absolute oral bioavailability for low molecular weight heparin of 19.9 +/- 9.3% and a pharmacological efficacy--calculated on the basis of the areas under the reduction in serum glucose levels of the oral formulation versus subcutaneous (s.c.) injection-for orally given insulin of 7% could be achieved. The incorporation of salmon calcitonin in chitosan-TBA/GSH led on the other hand to a pharmacological efficacy based on the areas under the reduction in plasma calcium levels of the oral thiomer formulation versus intravenous (i.v.) injection of 1.3%. Because of this high efficacy (i), the possibility to combine thiomer/GSH systems with additional low molecular weight permeation enhancers acting in other ways (ii) and minimal toxicological risks as these polymers are not absorbed from the GI tract (iii), thiolated polymers represent a promising novel tool for the oral administration of hydrophilic macromolecules.

  10. 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.

  11. 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

  12. 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.

  13. Effect of chemical permeation enhancers on stratum corneum barrier lipid organizational structure and interferon alpha permeability.

    Science.gov (United States)

    Moghadam, Shadi H; Saliaj, Evi; Wettig, Shawn D; Dong, Chilbert; Ivanova, Marina V; Huzil, J Torin; Foldvari, Marianna

    2013-06-03

    The outermost layer of the skin, known as the stratum corneum (SC), is composed of dead corneocytes embedded in an intercellular lipid matrix consisting of ceramides, free fatty acids, and cholesterol. The high level of organization within this matrix protects the body by limiting the permeation of most compounds through the skin. While essential for its protective functions, the SC poses a significant barrier for the delivery of topically applied pharmaceutical agents. Chemical permeation enhancers (CPEs) can increase delivery of small drug compounds into the skin by interacting with the intercellular lipids through physical processes including extraction, fluidization, increased disorder, and phase separation. However, it is not clear whether these same mechanisms are involved in delivery of biotherapeutic macromolecules, such as proteins. Here we describe the effect of three categories of CPEs {solvents [ethanol, propylene glycol, diethylene glycol monoethyl ether (transcutol), oleic acid], terpenes [menthol, nerol, camphor, methyl salicylate], and surfactants [Tween 80, SDS, benzalkonium chloride, polyoxyl 40 hydrogenated castor oil (Cremophor RH40), didecyldimethylammonium bromide (DDAB), didecyltrimethylammonium bromide (DTAB)]} on the lipid organizational structure of human SC as determined by X-ray scattering studies. Small- and wide-angle X-ray scattering studies were conducted to correlate the degree of structural changes and hydrocarbon chain packing in SC lipids caused by these various classes of CPEs to the extent of permeation of interferon alpha-2b (IFNα), a 19 kDa protein drug, into human skin. With the exception of solvents, propylene glycol and ethanol, all classes of CPEs caused increased disordering of lamellar and lateral packing of lipids. We observed that the highest degree of SC lipid disordering was caused by surfactants (especially SDS, DDAB, and DTAB) followed by terpenes, such as nerol. Interestingly, in vitro skin permeation studies

  14. 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 ...

  15. Enhancing the in vivo transdermal delivery of gold nanoparticles using poly(ethylene glycol and its oleylamine conjugate

    Directory of Open Access Journals (Sweden)

    Hsiao PF

    2016-05-01

    Full Text Available Pa Fan Hsiao,1–3 Sydney Peng,4 Ting-Cheng Tang,4 Shuian-Yin Lin,5 Hsieh-Chih Tsai4 1Department of Dermatology, Mackay Memorial Hospital, 2Mackay Medicine, Nursing and Management College, 3Mackay Medical College, New Taipei City, 4Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei, 5National Applied Research Laboratories, Instrument Technology Research Center, Hsinchu, Taiwan Abstract: In this study, we investigated the effect of (ethylene glycol (PEG and PEG–oleylamine (OAm functionalization on the skin permeation property of gold nanoparticles (GNS in vivo. Chemisorption of polymers onto GNS was verified by a red shift in the ultraviolet–visible spectrum as well as by a change in the nanoparticle surface charge. The physicochemical properties of pristine and functionalized nanoparticles were analyzed by ultraviolet–visible spectroscopy, zeta potential analyzer, and transmission electron microscopy. Transmission electron microscopy revealed that the interparticle distance between nanoparticles increased after GNS functionalization. Comparing the skin permeation profile of pristine and functionalized GNS, the follicular deposition of GNS increased twofold after PEG–OAm functionalization. Moreover, PEG- and PEG–OAm-functionalized nanoparticles were able to overcome the skin barrier and deposit in the deeper subcutaneous adipose tissue. These findings demonstrate the potential of PEG- and PEG–OAm-functionalized GNS in serving a multitude of applications in transdermal pharmaceuticals. Keywords: skin penetration, amphiphilic copolymer, gold nanoparticle, oleylamine, poly(ethylene glycol

  16. Intestinal surfactant permeation enhancers and their interaction with enterocyte cell membranes in a mucosal explant system

    DEFF Research Database (Denmark)

    Danielsen, E Michael; Hansen, Gert H

    2017-01-01

    Intestinal permeation enhancers (PEs) are agents aimed to improve oral delivery of therapeutic drugs with poor bioavailability. The main permeability barrier for oral delivery is the intestinal epithelium, and PEs act to increase the paracellular and/or transcellular passage of drugs. Transcellular...... for the fluorescent polar tracer lucifer yellow, but surprisingly, they all also blocked both constitutive -and receptor-mediated pathways of endocytosis from the brush border, indicating a complete arrest of apical membrane trafficking. At the ultrastructural level, the PEs caused longitudinal fusion of brush border...

  17. Lyophilized phytosomal nanocarriers as platforms for enhanced diosmin delivery: optimization and ex vivo permeation

    Directory of Open Access Journals (Sweden)

    Freag MS

    2013-07-01

    Full Text Available May S Freag, Yosra SR Elnaggar, Ossama Y AbdallahDepartment of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, EgyptAbstract: Diosmin (DSN is an outstanding phlebotonic flavonoid with a tolerable potential for the treatment of colon and hepatocellular carcinoma. Being highly insoluble, DSN bioavailability suffers from high inter-subject variation due to variable degrees of permeation. This work endeavored to develop novel DSN loaded phytosomes in order to improve drug dissolution and intestinal permeability. Three preparation methods (solvent evaporation, salting out, and lyophilization were compared. Nanocarrier optimization encompassed different soybean phospholipid (SPC types, different solvents, and different DSN:SPC molar ratios (1:1, 1:2, and 1:4. In vitro appraisal encompassed differential scanning calorimetry, infrared spectroscopy, particle size, zeta potential, polydispersity index, transmission electron microscopy, drug content, and in vitro stability. Comparative dissolution studies were performed under sink versus non-sink conditions. Ex vivo intestinal permeation studies were performed on rats utilizing noneverted sac technique and high-performance liquid chromatography analysis. The results revealed lyophilization as the optimum preparation technique using SPC and solvent mixture (Dimethyl sulphoxide:t-butylalchol in a 1:2 ratio. Complex formation was contended by differential scanning calorimetry and infrared data. Optimal lyophilized phytosomal nanocarriers (LPNs exhibited the lowest particle size (316 nm, adequate zeta-potential (−27 mV, and good in vitro stability. Well formed, discrete vesicles were revealed by transmission electron microscopy, drug content, and in vitro stability. Comparative dissolution studies were performed. LPNs demonstrated significant enhancement in DSN dissolution compared to crude drug, physical mixture, and generic and brand DSN products. Permeation studies revealed 80% DSN

  18. 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.

  19. 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.

  20. Enhancing effect of negative polypropylene electret on in vitro transdermal delivery of cyclosporine A solution and its synergistic effect with ethyl oleate

    International Nuclear Information System (INIS)

    Cui, L L; Liu, H Y; Ma, L; Liang, Y Y; Guo, X; Jiang, J

    2013-01-01

    In this study, the corona charged electrets at voltages of −500 V, −1000 V and −2000 V were made from polypropylene (PP) film. The cyclosporine A (CsA) and 10% ethyl oleate were chosen as the model drug and chemical enhancer, respectively. The charge storage stability of the electrets and the in vitro transdermal behaviour of the model drug in solution under different conditions were studied. The results indicate that the external electrostatic field of the negative PP electrets could penetrate through the rat skin and enhance the transdermal delivery of cyclosporine A. A synergistic effect on enhancing the transdermal delivery of cyclosporine A was observed by combining different surface potential negative PP electrets with 10% ethyl oleate, and the amount of transdermal delivery of CsA was greatly increased comparing with only application of electrets. Therefore, the combination application of electret and chemical enhancer could be a feasible strategy in enhancing transdermal delivery of small peptide drugs or some large molecular drugs.

  1. 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...

  2. Enhancement of Skin Permeation and Skin Immunization of Ovalbumin Antigen via Microneedles.

    Science.gov (United States)

    Pamornpathomkul, Boonnada; Rojanarata, Theerasak; Opanasopit, Praneet; Ngawhirunpat, Tanasait

    2017-10-01

    The purpose of this study was to evaluate the use of different types of microneedles and doses of ovalbumin antigen for in vitro skin permeation and in vivo immunization. In vitro skin permeation experiments and confocal laser scanning microscopy revealed that hollow microneedles had a superior enhancing effect on skin permeation compared with a solid microneedle patch and untreated skin by efficiently delivering ovalbumin-fluorescein conjugate into the deep skin layers. The flux and cumulative amount of ovalbumin-fluorescein conjugate at 8 h after administering with various conditions could be ranked as follows: hollow MN; high dose > medium dose > low dose > MN patch; high dose > medium dose > low dose > untreated skin; high dose > medium dose > low dose > without ovalbumin-fluorescein conjugate. As the dose of ovalbumin-fluorescein conjugate was increased to 500 μg, the antigen accumulated in the skin to a greater extent, as evidenced by the increasing green fluorescence intensity. When the hollow microneedle was used for the delivery of ovalbumin into the skin of mice, it was capable of inducing a stronger immunoglobulin G immune response than conventional subcutaneous injection at the same antigen dose. Immunoglobulin G levels in the hollow MN group were 5.7, 11.6, and 13.3 times higher than those of the subcutaneous injection group for low, medium, and high doses, respectively. Furthermore, the mice immunized using the hollow microneedle showed no signs of skin infection or pinpoint bleeding. The results suggest that the hollow MN is an efficient device for delivering the optimal dose of antigen via the skin for successful immunization.

  3. 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.

  4. Effect of Enhancers on in vitro and in vivo Skin Permeation and Deposition of S-Methyl-L-Methionine.

    Science.gov (United States)

    Kim, Ki Taek; Kim, Ji Su; Kim, Min-Hwan; Park, Ju-Hwan; Lee, Jae-Young; Lee, WooIn; Min, Kyung Kuk; Song, Min Gyu; Choi, Choon-Young; Kim, Won-Serk; Oh, Hee Kyung; Kim, Dae-Duk

    2017-07-01

    S-methyl- L -methionine (SMM), also known as vitamin U, is commercially available as skin care cosmetic products for its wound healing and photoprotective effects. However, the low skin permeation expected of SMM due to its hydrophilic nature with a log P value of -3.3, has not been thoroughly addressed. The purpose of this study thus was to evaluate the effect of skin permeation enhancers on the skin permeation/deposition of SMM. Among the enhancers tested for the in vitro skin permeation and deposition of SMM, oleic acid showed the most significant enhancing effect. Moreover, the combination of oleic acid and ethanol further enhanced in vitro permeation and deposition of SMM through hairless mouse skin. Furthermore, the combination of oleic acid and ethanol significantly increased the in vivo deposition of SMM in the epidermis/dermis for 12 hr, which was high enough to exert a therapeutic effect. Therefore, based on the in vitro and in vivo studies, the combination of oleic acid and ethanol was shown to be effective in improving the topical skin delivery of SMM, which may be applied in the cosmetic production process for SMM.

  5. 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.

  6. Evaluation of Microemulsion and Lamellar Liquid Crystalline Systems for Transdermal Zidovudine Delivery.

    Science.gov (United States)

    Carvalho, André Luis Menezes; Silva, José Alexsandro da; Lira, Ana Amélia Moreira; Conceição, Tamara Matos Freire; Nunes, Rogéria de Souza; de Albuquerque Junior, Ricardo Luiz Cavalcanti; Sarmento, Victor Hugo Vitorino; Leal, Leila Bastos; de Santana, Davi Pereira

    2016-07-01

    This study proposed to investigate and to compare colloidal carrier systems containing Zidovudine (3'-azido-3'-deoxythymidine) (AZT) for transdermal administration and optimization of antiretroviral therapy. Microemulsion (ME) and lamellar phase (LP) liquid crystal were obtained and selected from pseudoternary diagrams previously developed. Small-angle X-ray scattering and rheology analysis confirmed the presence of typical ME and liquid crystalline structures with lamellar arrangement, respectively. Both colloidal carrier systems, ME, and LP remained stable, homogeneous, and isotropic after AZT addition. In vitro permeation study (using pig ear skin) showed that the amount of permeated drug was higher for ME compared to the control and LP, obtaining a permeation enhancing effect on the order of approximately 2-fold (p drug permeation without causing apparent skin irritation. On the order hand, LP functioned as a drug reservoir reducing AZT partitioning into the skin. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  7. Toward enhanced hydrogen generation from water using oxygen permeating LCF membranes

    KAUST Repository

    Wu, Xiao-Yu

    2015-01-01

    © the Owner Societies. Hydrogen production from water thermolysis can be enhanced by the use of perovskite-type mixed ionic and electronic conducting (MIEC) membranes, through which oxygen permeation is driven by a chemical potential gradient. In this work, water thermolysis experiments were performed using 0.9 mm thick La0.9Ca0.1FeO3-δ (LCF-91) perovskite membranes at 990 °C in a lab-scale button-cell reactor. We examined the effects of the operating conditions such as the gas species concentrations and flow rates on the feed and sweep sides on the water thermolysis rate and oxygen flux. A single step reaction mechanism is proposed for surface reactions, and three-resistance permeation models are derived. Results show that water thermolysis is facilitated by the LCF-91 membrane especially when a fuel is added to the sweep gas. Increasing the gas flow rate and water concentration on the feed side or the hydrogen concentration on the sweep side enhances the hydrogen production rate. In this work, hydrogen is used as the fuel by construction, so that a single-step surface reaction mechanism can be developed and water thermolysis rate parameters can be derived. Both surface reaction rate parameters for oxygen incorporation/dissociation and hydrogen-oxygen reactions are fitted at 990 °C. We compare the oxygen fluxes in water thermolysis and air separation experiments, and identify different limiting steps in the processes involving various oxygen sources and sweep gases for this 0.9 mm thick LCF-91 membrane. In the air feed-inert sweep case, the bulk diffusion and sweep side surface reaction are the two limiting steps. In the water feed-inert sweep case, surface reaction on the feed side dominates the oxygen permeation process. Yet in the water feed-fuel sweep case, surface reactions on both the feed and sweep sides are rate determining when hydrogen concentration in the sweep side is in the range of 1-5 vol%. Furthermore, long term studies show that the surface

  8. 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...

  9. 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.

  10. [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.

  11. 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

  12. Dual-directional regulation of drug permeating amount by combining the technique of ion-pair complexation with chemical enhancers for the synchronous permeation of indapamide and bisoprolol in their compound patch through rabbit skin.

    Science.gov (United States)

    Song, Wenting; Cun, Dongmei; Quan, Peng; Liu, Nannan; Chen, Yang; Cui, Hongxia; Xiang, Rongwu; Fang, Liang

    2015-04-01

    To achieve the synchronous skin permeation of indapamide (IND) and bisoprolol (BSP) in their compound patch, the techniques of ion-pair complexation and chemical enhancers were combined to dual-directionally regulate drug permeating amounts. Ion-pair complexes of BSP and various organic acids were formed by the technique of ion-pair complexation. Among the complexes formed, bisoprolol tartrate (BSP.T) down-regulated the permeating amount of BSP to the same extent as that of IND. Then, to simultaneously up-regulate the amounts of the two drugs, an enhancer combination of 15.8% Span80 (SP), 6.0% Azone (AZ) and 2.2% N-methyl pyrrolidone (NMP) was obtained by central composite design and exhibited an outstanding and simultaneous enhancement on IND and BSP with enhancing ratio (ER) of 4.52 and 3.49, respectively. The effect of the dual-directional regulation was evaluated by in vitro permeation experiments and in vivo pharmacokinetic studies. For IND and BSP, their observed permeation profiles were comparable and their MAT (mean absorption time) showed no significant difference, which both demonstrated these two drugs achieved the synchronous skin permeation in their compound patch by the dual-directional regulation strategy of combining the technique of ion-pair complexation with chemical enhancers. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. 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.

  14. Thiolated hydroxyethyl cellulose: design and in vitro evaluation of mucoadhesive and permeation enhancing nanoparticles.

    Science.gov (United States)

    Rahmat, Deni; Müller, Christiane; Barthelmes, Jan; Shahnaz, Gul; Martien, Ronny; Bernkop-Schnürch, Andreas

    2013-02-01

    Within this study, HEC-cysteamine nanoparticles with free thiol groups in the range of 117-1548 μmol/g were designed and characterized. Nanoparticles were generated via ionic gelation of the cationic polymer with tripolyphosphate (TPP) followed by covalent crosslinking via disulfide bond formation using H2O2 as oxidant. The mean diameter of the particles was in the range of 270-360 nm, and zeta potential was determined to be +4 to +10 mV. Nanoparticles were evaluated in terms of mucoadhesive, permeation enhancing, and biocompatible properties as well as biodegradability. The particles remained attached to porcine intestinal mucosa up to 70% after 3h of incubation. The more nanoparticles were oxidized; however, the less were their mucoadhesive properties. Nanoparticles applied in a concentration of 0.5% (m/v) with the highest content of free thiol groups improved the transport of fluorescein isothiocyanate dextran 4 (FD4) across Caco-2 cell monolayer 3.94-fold in comparison with control (buffer). In addition, the transport of FD4 was even 1.84-fold enhanced in the presence of 0.5% (m/v) nanoparticles with the lowest free thiol group content. The higher the disulfide bond content within nanoparticles was, to a lower degree nanoparticles were hydrolyzed by cellulase. None of these nanoparticles showed pronounced cytotoxicity. Accordingly, HEC-cysteamine could be a promising excipient for nanoparticulate delivery systems for poorly absorbed drugs. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. 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

  16. S-protected thiolated chitosan for oral delivery of hydrophilic macromolecules: evaluation of permeation enhancing and efflux pump inhibitory properties.

    Science.gov (United States)

    Dünnhaupt, Sarah; Barthelmes, Jan; Rahmat, Deni; Leithner, Katharina; Thurner, Clemens C; Friedl, Heike; Bernkop-Schnürch, Andreas

    2012-05-07

    The objective of this study was the investigation of permeation enhancing and P-glycoprotein (P-gp) inhibition effects of a novel thiolated chitosan, the so-named S-protected thiolated chitosan. Mediated by a carbodiimide, increasing amounts of thioglycolic acid (TGA) were covalently bound to chitosan (CS) in the first step of modification. In the second step, these thiol groups of thiolated chitosan were protected by disulfide bond formation with the thiolated aromatic residue 6-mercaptonicotinamide (6-MNA). Mucoadhesive properties of all conjugates were evaluated in vitro on porcine intestinal mucosa based on tensile strength investigations. Permeation enhancing effects were evaluated ex vivo using rat intestinal mucosa and in vitro via Caco-2 cells using the hydrophilic macromolecule FD(4) as the model drug. Caco-2 cells were further used to show P-gp inhibition effects by using Rho-123 as P-gp substrate. Apparent permeability coefficients (P(app)) were calculated and compared to values obtained from each buffer control. Three different thiolated chitosans were generated in the first step of modification, which displayed increasing amounts of covalently attached free thiol groups on the polymer backbone. In the second modification step, more than 50% of these free thiol groups were covalently linked with 6-MNA. Within 3 h of permeation studies on excised rat intestine, P(app) values of all S-protected chitosans were at least 1.3-fold higher compared to those of corresponding thiomers and more than twice as high as that of unmodified chitosan. Additional permeation studies on Caco-2 cells confirmed these results. Because of the chemical modification and higher amount of reactive thiol groups, all S-protected thiolated chitosans exhibit at least 1.4-fold pronounced P-gp inhibition effects in contrast to their corresponding thiomers. These features approve S-protected thiolated chitosan as a promising excipient for various drug delivery systems providing improved

  17. Photokinetic Drug Delivery: Light-Enhanced Permeation in an In Vitro Eye Model.

    Science.gov (United States)

    Godley, Bernard F; Kraft, Edward R; Giannos, Steven A; Zhao, Zhen-Yang; Haag, Anthony M; Wen, Julie W

    2015-12-01

    To investigate light-enhanced molecular movement as a potential technology for drug delivery. To do this, we developed an in vitro eye model while representing similar concentration gradient conditions and compositions found in the eye. The eye model unit was fabricated by inserting a cross-linked type I collagen membrane in a spectrophotometer cuvette with 1% hyaluronic acid as the drug recipient medium. Photokinetic delivery was studied by illuminating 1 mg/mL methotrexate (MTX) placed in the drug donor compartment on top of the membrane, with noncoherent 450 nm light at 8.2 mW from an LED source pulsed at 25 cycles per second, placed in contact with the solution. A modified UV-visual spectrophotometer was employed to rapidly determine the concentration of MTX, at progressive 1 mm distances away from the membrane, within the viscous recipient medium of the model eye after 1 h. A defined, progressive concentration gradient was observed within the nonagitated drug recipient media, diminishing with greater distances from the membrane. Transport of MTX through the membrane was significantly enhanced (ranging from 2 to 3 times, P < 0.05 to P ≤ 0.001) by photokinetic methods compared with control conditions by determining drug concentrations at 4 defined distances from the membrane. According to scanning electron microscopy images, no structural damage or shunts were created on the surface of the cross-linked gelatin membrane. The application of pulsed noncoherent visible light significantly enhances the permeation of MTX through a cross-linked collagen membrane and hyaluronic acid recipient medium without causing structural damage to the membrane.

  18. Safety concerns over the use of intestinal permeation enhancers: A mini-review.

    Science.gov (United States)

    McCartney, Fiona; Gleeson, John P; Brayden, David J

    2016-01-01

    Intestinal permeation enhancers (PEs) are key components in ∼12 oral peptide formulations in clinical trials for a range of molecules, primarily insulin and glucagon-like-peptide 1 (GLP-1) analogs. The main PEs comprise medium chain fatty acid-based systems (sodium caprate, sodium caprylate, and N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC)), bile salts, acyl carnitines, and EDTA. Their mechanism of action is complex with subtle differences between the different molecules. With the exception of SNAC and EDTA, most PEs fluidize the plasma membrane causing plasma membrane perturbation, as well as enzymatic and intracellular mediator changes that lead to alteration of intestinal epithelial tight junction protein expression. The question arises as to whether PEs can cause irreversible epithelial damage and tight junction openings sufficient to permit co-absorption of payloads with bystander pathogens, lipopolysaccharides and its fragment, or exo- and endotoxins that may be associated with sepsis, inflammation and autoimmune conditions. Most PEs seem to cause membrane perturbation to varying extents that is rapidly reversible, and overall evidence of pathogen co-absorption is generally lacking. It is unknown however, whether the intestinal epithelial damage-repair cycle is sustained during repeat-dosing regimens for chronic therapy.

  19. Toward enhanced hydrogen generation from water using oxygen permeating LCF membranes

    KAUST Repository

    Wu, Xiao-Yu; Chang, Le; Uddi, Mruthunjaya; Kirchen, Patrick; Ghoniem, Ahmed F.

    2015-01-01

    and flow rates on the feed and sweep sides on the water thermolysis rate and oxygen flux. A single step reaction mechanism is proposed for surface reactions, and three-resistance permeation models are derived. Results show that water thermolysis

  20. 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.

  1. 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.

  2. SAMPA: A free software tool for skin and membrane permeation data analysis.

    Science.gov (United States)

    Bezrouk, Aleš; Fiala, Zdeněk; Kotingová, Lenka; Krulichová, Iva Selke; Kopečná, Monika; Vávrová, Kateřina

    2017-10-01

    Skin and membrane permeation experiments comprise an important step in the development of a transdermal or topical formulation or toxicological risk assessment. The standard method for analyzing these data relies on the linear part of a permeation profile. However, it is difficult to objectively determine when the profile becomes linear, or the experiment duration may be insufficient to reach a maximum or steady state. Here, we present a software tool for Skin And Membrane Permeation data Analysis, SAMPA, that is easy to use and overcomes several of these difficulties. The SAMPA method and software have been validated on in vitro and in vivo permeation data on human, pig and rat skin and model stratum corneum lipid membranes using compounds that range from highly lipophilic polycyclic aromatic hydrocarbons to highly hydrophilic antiviral drug, with and without two permeation enhancers. The SAMPA performance was compared with the standard method using a linear part of the permeation profile and a complex mathematical model. SAMPA is a user-friendly, open-source software tool for analyzing the data obtained from skin and membrane permeation experiments. It runs on a Microsoft Windows platform and is freely available as a Supporting file to this article. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. An optimized probucol microencapsulated formulation integrating a secondary bile acid (deoxycholic acid as a permeation enhancer

    Directory of Open Access Journals (Sweden)

    Mooranian A

    2014-09-01

    Full Text Available Armin Mooranian,1 Rebecca Negrulj,1 Nigel Chen-Tan,2 Gerald F Watts,3 Frank Arfuso,4 Hani Al-Salami11Biotechnology and Drug Development Research Laboratory, School of Pharmacy, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Curtin University, 2Faculty of Science and Engineering, Curtin University, 3School of Medicine and Pharmacology, Royal Perth Hospital, University of Western Australia, 4School of Biomedical Science, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Curtin University, Perth, AustraliaAbstract: The authors have previously designed, developed, and characterized a novel microencapsulated formulation as a platform for the targeted delivery of therapeutics in an animal model of type 2 diabetes, using the drug probucol (PB. The aim of this study was to optimize PB microcapsules by incorporating the bile acid deoxycholic acid (DCA, which has good permeation-enhancing properties, and to examine its effect on microcapsules’ morphology, rheology, structural and surface characteristics, and excipients’ chemical and thermal compatibilities. Microencapsulation was carried out using a BÜCHI-based microencapsulating system established in the authors’ laboratory. Using the polymer sodium alginate (SA, two microencapsulated formulations were prepared: PB-SA (control and PB-DCA-SA (test at a constant ratio (1:30 and 1:3:30, respectively. Complete characterization of the microcapsules was carried out. The incorporation of DCA resulted in better structural and surface characteristics, uniform morphology, and stable chemical and thermal profiles, while size and rheological parameters remained similar to control. In addition, PB-DCA-SA microcapsules showed good excipients’ compatibilities, which were supported by data from differential scanning calorimetry, Fourier transform infrared spectroscopy, scanning electron microscopy, and energy dispersive X-ray studies, suggesting

  4. 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.

  5. 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

  6. 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.

  7. Glycerol monooleate/solvents systems for progesterone transdermal delivery: In vitro permeation and microscopic studies Sistemas monoleína/solventes para a liberação transdérmica da progesterona: estudos de permeação cutânea e microscópicos

    Directory of Open Access Journals (Sweden)

    Gislaine R Pereira

    2002-03-01

    Full Text Available Transdermal delivery of most drugs is precluded by the barrier characteristics of the stratum corneum (SC. Chemical penetration enhancers are capable of interacting with SC constituents, inducing a temporary reversible increase in the skin permeability. The aim of this work was to assess the influence of glycerol monooleate (GMO/solvents systems on percutaneous absorption across hairless mouse SC of a lipophilic drug, progesterone (PG, as well as its effect on the SC structural characteristics, by scanning electron microscopy (SEM and confocal laser scanning microscopy (CLSM. The morphological changes observed in the hairless mouse SC suggest a GMO effect on the skin barrier. In addition, the increase in the In vitro PG flux and in vivo penetration of a fluorescent label point towards GMO as a potential absorption enhancer. The results obtained showed that GMO/solvents systems provoked changes in the SC that could be causing increased permeation of PG across hairless mouse skin, optimising in this way the transdermal delivery of this drug.A liberação transdérmica de muitos fármacos é dificultada pelas características de barreira do estrato córneo. Promotores químicos de absorção cutânea são capazes de interagir com os constituintes do estrato córneo, induzindo aumento temporário e reversível na permeabilidade da pele. O objetivo deste trabalho foi avaliar a influência de sistemas monoleína (monoleato de glicerol/solventes na absorção percutânea de um fármaco lipofílico (a progesterona, através do estrato córneo de camundongos sem pelo, bem como o efeito da monoleína nas características estruturais do estrato córneo, por meio de microscopia eletrônica de varredura (SEM e microscopia de varredura confocal a laser (CLSM. As alterações morfológicas observadas no estrato córneo de camundongos sem pelo sugerem efeito da monoleína na barreira da pele. E, ainda, o aumento no fluxo In vitro da progesterona, bem como na

  8. 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

  9. 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.

  10. Long time effects in radiation enhanced permeation of H2 through stainless steel tubes

    International Nuclear Information System (INIS)

    Schwarzinger, G.; Dobrozemsky, R.

    1982-01-01

    The aim of this research is to give the particulars of influences of penetrating radiation on permeation and diffusion processes of hydrogen isotopes in stainless steel. Short time as well as long time effects have been investigated. Such processes are not only of interest for the fuel inventory of fusion reactors, but also for environmental aspects (tritium release). (Author)

  11. 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.

  12. Pluronic lecithin organogel (PLO) of diltiazem hydrochloride: effect of solvents/penetration enhancers on ex vivo permeation.

    Science.gov (United States)

    Parhi, Rabinarayan; Suresh, Podilam; Pattnaik, Subasini

    2016-06-01

    In the present study, pluronic lecithin organogel (PLO) of diltiazem hydrochloride (DZH) was developed by taking different ratios of organic phase to aqueous phase (1:3, 1:4, and 1:5) with varying concentration of soya lecithin (20, 30, and 40 % w/w) in organic phase (isopropyl myristate, IPM) and pluronic (20, 25, and 30 % w/w) in aqueous phase, respectively, and characterized for in vitro parameters and ex vivo permeation study. The results of in vitro parameters were found to be within permissible limit and all the PLOs were physically stable at refrigeration and ambient temperature. The influence of phase ratio and different concentrations of soya lecithin on DZH release from the PLOs was found to be significant (p < 0.05), whereas the influences of different concentrations of pluronic were insignificant. The effect of different solvents/penetration enhancers viz. IPM, propylene glycol (PG), dimethyl sulphoxide (DMSO), and D-limonene, in combination and alone, on the permeation of DZH across the dorsal skin of rat was studied. Among all, formulation containing IPM (PLO6) exhibited highest flux of 147.317 μg/cm(2)/h. Furthermore, histopathology section of treated skin sample illustrated that lipid bilayer disruption was the mechanism for the DZH permeation. The above results indicated that PLO6 may serve as a promising alternative delivery system for DZH in the effective treatment of hypertension.

  13. 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

  14. 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.

  15. In silico modelling of permeation enhancement potency in Caco-2 monolayers based on molecular descriptors and random forest

    DEFF Research Database (Denmark)

    Welling, Søren Havelund; Clemmensen, Line Katrine Harder; Buckley, Stephen T.

    2015-01-01

    has been developed.The random forest-QSAR model was based upon Caco-2 data for 41 surfactant-like permeation enhancers from Whitehead et al. (2008) and molecular descriptors calculated from their structure.The QSAR model was validated by two test-sets: (i) an eleven compound experimental set with Caco......-2 data and (ii) nine compounds with Caco-2 data from literature. Feature contributions, a recent developed diagnostic tool, was applied to elucidate the contribution of individual molecular descriptors to the predicted potency. Feature contributions provided easy interpretable suggestions...

  16. Efficacious Intestinal Permeation Enhancement Induced by the Sodium Salt of 10-undecylenic Acid, A Medium Chain Fatty Acid Derivative

    OpenAIRE

    Brayden, David J.; Walsh, Edwin

    2014-01-01

    10-undecylenic acid (UA) is an OTC antifungal therapy and a nutritional supplement. It is an unsaturated medium chain fatty acid (MCFA) derivative, so our hypothesis was that its 11-mer sodium salt, uC11, would improve intestinal permeation similar to the established enhancer, sodium caprate (C10), but without the toxicity of the parent saturated MCFA, decylenic acid (C11). MTT assay and high-content screening (HCS) confirmed a cytotoxicity ranking in Caco-2 cells: C11 > C10 = uC11. Five to t...

  17. Synthesis and Characterization of a Gd-DOTA-D-Permeation Peptide for Magnetic Resonance Relaxation Enhancement of Intracellular Targets

    Directory of Open Access Journals (Sweden)

    Andrew M. Prantner

    2003-10-01

    Full Text Available Many MR contrast agents have been developed and proven effective for extracellular nontargeted applications, but exploitation of intracellular MR contrast agents has been elusive due to the permeability barrier of the plasma membrane. Peptide transduction domains can circumvent this permeability barrier and deliver cargo molecules to the cell interior. Based upon enhanced cellular uptake of permeation peptides with D-amino acid residues, an all-D Tat basic domain peptide was conjugated to DOTA and chelated to gadolinium. Gd-DOTA-D-Tat peptide in serum at room temperature showed a relaxivity of 7.94 ± 0.11 mM−1 sec−1 at 4.7 T. The peptide complex displayed no significant binding to serum proteins, was efficiently internalized by human Jurkat leukemia cells resulting in intracellular T1 relaxation enhancement, and in preliminary T1-weighted MRI experiments, significantly enhanced liver, kidney, and mesenteric signals.

  18. Gel in core carbosomes as novel ophthalmic vehicles with enhanced corneal permeation and residence.

    Science.gov (United States)

    Moustafa, Mona A; El-Refaie, Wessam M; Elnaggar, Yosra S R; Abdallah, Ossama Y

    2018-05-17

    Carbopol is a good bio-adhesive polymer that increases the residence time in the eye. However, the effect of blinking and lacrimation still reduce the amount of polymer and the incorporated drug available for bioadhesion. Gel-core liposomes are advanced systems offering benefits making it a good tool for improved ocular drug delivery and residence time. Incorporation of carbopol in gel-core liposomes and their potential in ocular delivery have not so far been investigated. Fluconazole (FLZ) was selected as a challenging important ocular antifungal suffering from poor corneal permeation and short residence time. In this study, gel-core carbosomes have been elaborated as novel carbopol-based ophthalmic vehicles to solve ocular delivery obstacles of FLZ and to sustain its effect. Full in vitro appraisal was performed considering gel-core structure, entrapment efficiency, particle size and stability of the vesicles as quality attributes. Structure elucidation of the nanocarrier was performed using optical, polarizing and transmission electron microscopy before and after Triton-X100 addition. Ex-vivo ocular permeation and in vivo performance were investigated on male albino rabbits. Optimized formulation (CBS5) showed gel-core structure, nanosize (339.00 ± 5.50 nm) and not defined before (62.00% ± 1.73) entrapment efficiency. Cumulative amount of CBS5 permeated ex-vivo after 6 h, was 2.43 and 3.43 folds higher than that of conventional liposomes and FLZ suspension, respectively. In-vivo corneal permeation of CBS5 showed significantly higher AUC0-24 h (487.12 ± 74.80) compared to that of FLZ suspension (204.34 ± 7.46) with longer residence time in the eye lasts for more than 18 h. In conclusion, novel gel-core carbosomes could successfully be used as a promising delivery system for chronic ocular diseases. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Development and characterisation of electrospun timolol maleate-loaded polymeric contact lens coatings containing various permeation enhancers.

    Science.gov (United States)

    Mehta, Prina; Al-Kinani, Ali A; Arshad, Muhammad Sohail; Chang, Ming-Wei; Alany, Raid G; Ahmad, Zeeshan

    2017-10-30

    Despite exponential growth in research relating to sustained and controlled ocular drug delivery, anatomical and chemical barriers of the eye still pose formulation challenges. Nanotechnology integration into the pharmaceutical industry has aided efforts in potential ocular drug device development. Here, the integration and in vitro effect of four different permeation enhancers (PEs) on the release of anti-glaucoma drug timolol maleate (TM) from polymeric nanofiber formulations is explored. Electrohydrodynamic (EHD) engineering, more specifically electrospinning, was used to engineer nanofibers (NFs) which coated the exterior of contact lenses. Parameters used for engineering included flow rates ranging from 8 to 15μL/min and a novel EHD deposition system was used; capable of hosting four lenses, masked template and a ground electrode to direct charged atomised structures. SEM analysis of the electrospun structures confirmed the presence of smooth nano-fibers; whilst thermal analysis confirmed the stability of all formulations. In vitro release studies demonstrated a triphasic release; initial burst release with two subsequent sustained release phases with most of the drug being released after 24h (86.7%) Biological evaluation studies confirmed the tolerability of all formulations tested with release kinetics modelling results showing drug release was via quasi-Fickian or Fickian diffusion. There were evident differences (p<0.05) in TM release dependant on permeation enhancer. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  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. Effect of Asparagus racemosus extract on transdermal delivery of carvedilol: a mechanistic study.

    Science.gov (United States)

    Sapra, Bharti; Jain, Subheet; Tiwary, Ashok K

    2009-01-01

    This study was designed for investigating the effect of Asparagus racemosus (AR) extract and chitosan (CTN) in facilitating the permeation of carvedilol (CDL) across rat epidermis. Transdermal flux of carvedilol through heat-separated rat epidermis was investigated in vitro using vertical Keshary-Chien diffusion cells. Biophysical and microscopic manifestations of epidermis treated with AR extract, CTN, and AR extract-CTN mixture were investigated by using differential scanning calorimetry, transepidermal water loss, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Biochemical estimations of cholesterol, sphingosine, and triglycerides were carried out for treated excised as well as viable rat epidermis. The antihypertensive activity of the patches in comparison with that of oral carvedilol was studied in deoxycorticosterone acetate-induced hypertensive rats. The permeation of carvedilol across excised rat epidermis was significantly higher (p vehicle as compared to propylene glycol/ethanol (7:3) mixture. Epidermis obtained after 12 h treatment of viable rat skin with AR extract-CTN mixture showed significantly higher (p space, disordered lipid structure, and corneocyte detachment as observed in SEM and TEM suggested great potential of AR extract for use as percutaneous permeation enhancer. The developed transdermal patches of CDL containing AR extract-CTN mixture exhibited better performance as compared to oral administration in controlling hypertension in rats.

  2. Effects of Chemical and Physical Enhancement Techniques on Transdermal Delivery of Cyanocobalamin (Vitamin B12 In Vitro

    Directory of Open Access Journals (Sweden)

    Ajay K. Banga

    2011-08-01

    Full Text Available Vitamin B12 deficiency, which may result in anemia and nerve damage if left untreated, is currently treated by administration of cyanocobalamin via oral or intramuscular routes. However, these routes are associated with absorption and compliance issues which have prompted us to investigate skin as an alternative site of administration. Delivery through skin, however, is restricted to small and moderately lipophilic molecules due to the outermost barrier, the stratum corneum (SC. In this study, we have investigated the effect of different enhancement techniques, chemical enhancers (ethanol, oleic acid, propylene glycol, iontophoresis (anodal iontophoresis and microneedles (soluble maltose microneedles, which may overcome this barrier and improve cyanocobalamin delivery. Studies with different chemical enhancer formulations indicated that ethanol and oleic acid decreased the lag time while propylene glycol based formulations increased the lag time. The formulation with ethanol (50%, oleic acid (10% and propylene glycol (40% showed the maximum improvement in delivery. Iontophoresis and microneedle treatments resulted in enhanced permeation levels compared to passive controls. These enhancement approaches can be explored further to develop alternative treatment regimens.

  3. Efficacious intestinal permeation enhancement induced by the sodium salt of 10-undecylenic acid, a medium chain fatty acid derivative.

    Science.gov (United States)

    Brayden, David J; Walsh, Edwin

    2014-09-01

    10-undecylenic acid (UA) is an OTC antifungal therapy and a nutritional supplement. It is an unsaturated medium chain fatty acid (MCFA) derivative, so our hypothesis was that its 11-mer sodium salt, uC11, would improve intestinal permeation similar to the established enhancer, sodium caprate (C10), but without the toxicity of the parent saturated MCFA, decylenic acid (C11). MTT assay and high-content screening (HCS) confirmed a cytotoxicity ranking in Caco-2 cells: C11 > C10 = uC11. Five to ten millimolars of the three agents reduced TEER and increased the Papp of [(14)C]-mannitol across Caco-2 monolayers and rat intestinal mucosae, a concentration that matched increases in plasma membrane permeability seen in HCS. Although C11 was the most efficacious enhancer in vitro, it damaged monolayers and tissue mucosae more than the other two agents at similar concentrations and exposure times and was therefore not pursued further. Rat jejunal and colonic in situ intestinal instillations of 100 mM C10 or uC11 with FITC-dextran 4000 (FD4) solutions yielded comparable regional enhancement ratios of ~10 and 30%, respectively, for each agent with acceptable tissue histology. Mini-tablets of uC11 and FD4 however delivered more FD4 compared to C10-FD-4 mini-tablets in both regions, as reflected by a statistically higher AUC, and with no evidence of membrane perturbation. The unsaturated bond in uC11 therefore confers a reduction in lipophilicity and cytotoxicity compared to C11, and the resulting permeation enhancement is on a par with or superior to that of C10, a key component of formulations in current phase II oral peptide clinical trials.

  4. 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.

  5. Enhancing Skin Permeation of Biphenylacetic Acid (BPA) Using Salt Formation with Organic and Alkali Metal Bases.

    Science.gov (United States)

    Pawar, Vijay; Naik, Prashant; Giridhar, Rajani; Yadav, Mange Ram

    2015-01-01

    In the present study, a series of organic and alkali metal salts of biphenylacetic acid (BPA) have been prepared and evaluated in vitro for percutaneous drug delivery. The physicochemical properties of BPA salts were determined using solubility measurements, DSC, and IR. The DSC thermogram and FTIR spectra confirmed the salt formation with organic and alkali metal bases. Among the series, salts with organic amines (ethanolamine, diethanolamine, triethanolamine, and diethylamine) had lowered melting points while the alkali metal salt (sodium) had a higher melting point than BPA. The in vitro study showed that salt formation improves the physicochemical properties of BPA, leading to improved permeability through the skin. Amongst all the prepared salts, ethanolamine salt (1b) showed 7.2- and 5.4-fold higher skin permeation than the parent drug at pH 7.4 and 5.0, respectively, using rat skin.

  6. Laboratory validation of a new gas-enhanced dentine liquid permeation evaluation system.

    Science.gov (United States)

    Al-Jadaa, Anas; Attin, Thomas; Peltomäki, Timo; Heumann, Christian; Schmidlin, Patrick R

    2014-12-01

    To validate a new automated dentine permeability testing platform based on pressure change measurements. A split chamber was designed allowing for concomitant measurement of fluid permeation and pressure difference. In a first test, system reliability was assessed by interposing a solid metal disk, embedded composite resin disks, or teeth by consecutively measuring eight times under standardized conditions. Secondly, the repeatability and applicability of the method was tested in a dentine wound model by using intact third molars: Class I (2 × 5 mm) and a full occlusal preparation as well a ceramic restoration were consecutively performed and repeatedly measured eight times each. In the last test, the system detection limit as well correlation between gas pressure difference and liquid permeation were evaluated: Again, third molars were used and occlusal preparations of increasing size (2 × 5, 3 × 5, 4 × 5, and 5 × 5 mm and full occlusal preparations, respectively) were made. Data was analyzed for the linearity of measurement, and R (2) values were calculated. The embedding procedure allowed for perfect separation of the two chambers, and no significant variation in repeated measurements of evaluated samples for the respective treatments (p = 0.05) was found. The detection was 0.002 hPa/min for the pressure slope and 0.0225 μl/min for the fluid infiltration, respectively. The saline volume was highly correlating to the gas pressure changes (R (2) = 0.996, p < 0.0001). The presented method is a reliable and exact tool to assess dentine permeability by nondestructive and repeatable measurements. This method is suitable for measurements and comparison of the effectiveness of dentine wounds sealing materials.

  7. 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

  8. Transdermal agomelatine microemulsion gel: pyramidal screening, statistical optimization and in vivo bioavailability.

    Science.gov (United States)

    Said, Mayada; Elsayed, Ibrahim; Aboelwafa, Ahmed A; Elshafeey, Ahmed H

    2017-11-01

    Agomelatine is a new antidepressant having very low oral drug bioavailability less than 5% due to being liable to extensive hepatic 1st pass effect. This study aimed to deliver agomelatine by transdermal route through formulation and optimization of microemulsion gel. Pyramidal screening was performed to select the most suitable ingredients combinations and then, the design expert software was utilized to optimize the microemulsion formulations. The independent variables of the employed mixture design were the percentages of capryol 90 as an oily phase (X 1 ), Cremophor RH40 and Transcutol HP in a ratio of (1:2) as surfactant/cosurfactant mixture 'S mix ' (X 2 ) and water (X 3 ). The dependent variables were globule size, optical clarity, cumulative amount permeated after 1 and 24 h, respectively (Q1 and Q 24 ) and enhancement ratio (ER). The optimized formula was composed of 5% oil, 45% S mix and 50% water. The optimized microemulsion formula was converted into carbopol-based gel to improve its retention on the skin. It enhanced the drug permeation through rat skin with an enhancement ratio of 37.30 when compared to the drug hydrogel. The optimum ME gel formula was found to have significantly higher C max , AUC 0-24 h and AUC 0-∞ than that of the reference agomelatine hydrogel and oral solution. This could reveal the prosperity of the optimized microemulsion gel formula to augment the transdermal bioavailability of agomelatine.

  9. Enhanced Ungual Permeation of Terbinafine HCl Delivered Through Liposome-Loaded Nail Lacquer Formulation Optimized by QbD Approach.

    Science.gov (United States)

    Shah, Viral H; Jobanputra, Amee

    2018-01-01

    The present investigation focused on developing, optimizing, and evaluating a novel liposome-loaded nail lacquer formulation for increasing the transungual permeation flux of terbinafine HCl for efficient treatment of onychomycosis. A three-factor, three-level, Box-Behnken design was employed for optimizing process and formulation parameters of liposomal formulation. Liposomes were formulated by thin film hydration technique followed by sonication. Drug to lipid ratio, sonication amplitude, and sonication time were screened as independent variables while particle size, PDI, entrapment efficiency, and zeta potential were selected as quality attributes for liposomal formulation. Multiple regression analysis was employed to construct a second-order quadratic polynomial equation and contour plots. Design space (overlay plot) was generated to optimize a liposomal system, with software-suggested levels of independent variables that could be transformed to desired responses. The optimized liposome formulation was characterized and dispersed in nail lacquer which was further evaluated for different parameters. Results depicted that the optimized terbinafine HCl-loaded liposome formulation exhibited particle size of 182 nm, PDI of 0.175, zeta potential of -26.8 mV, and entrapment efficiency of 80%. Transungual permeability flux of terbinafine HCl through liposome-dispersed nail lacquer formulation was observed to be significantly higher in comparison to nail lacquer with a permeation enhancer. The developed formulation was also observed to be as efficient as pure drug dispersion in its antifungal activity. Thus, it was concluded that the developed formulation can serve as an efficient tool for enhancing the permeability of terbinafine HCl across human nail plate thereby improving its therapeutic efficiency.

  10. 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.

  11. 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

  12. 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

  13. Permeation of sumatriptan succinate across human skin using multiple types of self-dissolving microneedle arrays fabricated from sodium hyaluronate.

    Science.gov (United States)

    Wu, Dan; Katsumi, Hidemasa; Quan, Ying-Shu; Kamiyama, Fumio; Kusamori, Kosuke; Sakane, Toshiyasu; Yamamoto, Akira

    2016-09-01

    Available formulations of sumatriptan succinate (SS) have low bioavailability or are associated with site reactions. We developed various types of self-dissolving microneedle arrays (MNs) fabricated from sodium hyaluronate as a new delivery system for SS and evaluated their skin permeation and irritation in terms of clinical application. In vitro permeation studies with human skin, physicochemical properties (needle length, thickness and density), and penetration enhancers (glycerin, sodium dodecyl sulfate and lauric acid diethanolamide) were investigated. SS-loaded high-density MNs of 800 µm in length were the optimal formulation and met clinical therapeutic requirements. Penetration enhancers did not significantly affect permeation of SS from MNs. Optical coherence tomography images demonstrated that SS-loaded high-density MNs (800 µm) uniformly created drug permeation pathways for the delivery of SS into the skin. SS-loaded high-density MNs induced moderate primary skin irritations in rats, but the skin recovered within 72 h of removal of the MNs. These findings suggest that high-density MNs of 800 µm in length are an effective and promising formulation for transdermal delivery of SS. To our knowledge, this is the first report of SS permeation across human skin using self-dissolving MNs.

  14. Enhanced transbuccal salmon calcitonin (sCT) delivery: effect of chemical enhancers and electrical assistance on in vitro sCT buccal permeation.

    Science.gov (United States)

    Oh, Dong-Ho; Chun, Kyeung-Hwa; Jeon, Sang-Ok; Kang, Jeong-Won; Lee, Sangkil

    2011-10-01

    This study investigates the combined effect of absorption enhancers and electrical assistance on transbuccal salmon calcitonin (sCT) delivery, using fresh swine buccal tissue. We placed 200 IU (40 μg/mL) of each sCT formulation--containing various concentrations of ethanol, N-acetyl-L-cysteine (NAC), and sodium deoxyglycocholate (SDGC)--onto the donor part of a Franz diffusion cell. Then, 0.5 mA/cm(2) of fixed anodal current was applied alone or combined with chemical enhancers. The amount of permeated sCT was analyzed using an ELISA kit, and biophysical changes of the buccal mucosa were investigated using FT-IR spectroscopy, and hematoxylin-eosin staining methods were used to evaluate histological alteration of the buccal tissues. The flux (J(s)) of sCT increased with the addition of absorption enhancer groups, but it was significantly enhanced by the application of anodal iontophoresis (ITP). FT-IR study revealed that all groups caused an increase in lipid fluidity but only the groups containing SDGC showed statistically significant difference. Although the histological data of SDGC groups showed a possibility for tissue damage, the present enhancing methods appear to be safe. In conclusion, the combination of absorption enhancers and electrical assistance is a potential strategy for the enhancement of transbuccal sCT delivery. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Development of w/o microemulsion for transdermal delivery of iodide ions.

    Science.gov (United States)

    Lou, Hao; Qiu, Ni; Crill, Catherine; Helms, Richard; Almoazen, Hassan

    2013-03-01

    The objective of this study was to develop a water-in-oil (w/o) microemulsion which can be utilized as a transdermal delivery for iodide ions. Several w/o microemulsion formulations were prepared utilizing Span 20, ethanol, Capryol 90®, and water. The selected formulations had 5%, 10%, 15%, 20%, and a maximum of 23% w/w water content. Potassium iodide (KI) was incorporated in all formulations at 5% w/v. Physicochemical characterizations were conducted to evaluate the structure and stability. These studies included: mean droplet size, pH, viscosity, conductivity, and chemical stability tests. In vitro human skin permeation studies were conducted to evaluate the diffusion of the iodide ion through human skin. The w/o microemulsion formulations were stable and compatible with iodide ions with water content ranging from 5% to 23% w/w. The addition of KI influenced the physicochemical properties of microemulsion as compared to blank microemulsion formulations. In vitro human skin permeation studies indicated that selected formulations improved iodide ion diffusion significantly as compared to control (KI solution; P valuemicroemulsion. Span 20, ethanol and Capryol 90 protected the iodide ions against oxidation and formed a stable microemulsion. It is worth to note that according to Hofmeister series, iodide ions tend to lower the interfacial tension between water and oil and consequently enhance overall stability. This work illustrates that microemulsion system can be utilized as a vehicle for the transdermal administration of iodide.

  16. Influence of electrical and chemical factors on transdermal iontophoretic delivery of three diclofenac salts.

    Science.gov (United States)

    Fang, J Y; Wang, R J; Huang, Y B; Wu, P C; Tsai, Y H

    2001-04-01

    The aim of this present study was to investigate the in vitro transdermal iontophoretic delivery of three diclofenac salts--diclofenac sodium (DFS), diclofenac potassium (DFP), and diclofenac diethylammonium (DFD). A series of physicochemical and electrical variables which might affect iontophoretic permeation of diclofenac salts was studied. Application of 0.3 mA/cm2 current density significantly increased the transdermal flux of diclofenac salts as compared to passive transport. The iontophoretic enhancement increased in the order of DFS>DFP>DFD. The permeability coefficient of diclofenac salts all decreased with increasing donor concentration during iontophoresis. The addition of buffer ions and salt ions such as NaCl, KCl, and C4H12ClN reduced the permeation of diclofenac salts due to competition. However, this effect was lesser for DFD than for DFS and DFP. Comparing the various application modes of iontophoresis, the discontinuous on/off mode showed lower but more constant flux than the continuous mode.

  17. Influence of cellulose derivative and ethylene glycol on optimization of lornoxicam transdermal formulation.

    Science.gov (United States)

    Shahzad, Yasser; Khan, Qalandar; Hussain, Talib; Shah, Syed Nisar Hussain

    2013-10-01

    Lornoxicam containing topically applied lotions were formulated and optimized with the aim to deliver it transdermally. The formulated lotions were evaluated for pH, viscosity and in vitro permeation studies through silicone membrane using Franz diffusion cells. Data were fitted to linear, quadratic and cubic models and best fit model was selected to investigate the influence of variables, namely hydroxypropyl methylcellulose (HPMC) and ethylene glycol (EG) on permeation of lornoxicam from topically applied lotion formulations. The best fit quadratic model revealed that low level of HPMC and intermediate level of EG in the formulation was optimum for enhancing the drug flux across silicone membrane. FT-IR analysis confirmed absence of drug-polymer interactions. Selected optimized lotion formulation was then subjected to accelerated stability testing, sensatory perception testing and in vitro permeation across rabbit skin. The drug flux from the optimized lotion across rabbit skin was significantly better that that from the control formulation. Furthermore, sensatory perception test rated a higher acceptability while lotion was stable over stability testing period. Therefore, use of Box-Wilson statistical design successfully elaborated the influence of formulation variables on permeation of lornoxicam form topical formulations, thus, helped in optimization of the lotion formulation. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. 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

  19. 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.

  20. Skin deposition and permeation of finasteride in vitro: effects of propylene glycol, ethanol and sodium lauryl sulfate.

    Science.gov (United States)

    Limpongsa, Ekapol; Jaipakdee, Napaphak; Pongjanyakul, Thaned

    2014-08-27

    Abstract The objective of this study was to investigate the effects of propylene glycol (PG), ethanol (EtOH) and sodium lauryl sulfate (SLS) on the in vitro deposition and permeation of finasteride (FNS). A side-by-side diffusion cell mounted with a pig ear skin and a saturated solution of FNS in PG (10, 20% v/v), EtOH (10, 20% v/v) or SLS (0.5, 1% w/v) vehicles were used. Incorporation of PG, EtOH or SLS caused a significant increase in FNS solubility both in the solution and on the skin with SLS > EtOH > PG. The results obtained from skin deposition studies showed that the FNS deposition rate and time increased in the same order as that of the solubility. The deposition kinetics of FNS solubilized in PG, EtOH and SLS vehicles followed either zero-order, square-root-of-time or pseudo-first-order kinetic models depending on the type and concentration of the enhancer. The permeation studies demonstrated that FNS permeation fluxes were enhanced only by EtOH vehicles. These results suggest that PG and SLS could be used as deposition enhancers, while EtOH could be the effective permeation enhancer of FNS. The obtained results can be used as the considerable insights for formulating the topical and transdermal products of FNS.

  1. Statistically optimized fast dissolving microneedle transdermal patch of meloxicam: A patient friendly approach to manage arthritis.

    Science.gov (United States)

    Amodwala, Sejal; Kumar, Praveen; Thakkar, Hetal P

    2017-06-15

    The long term administration of Meloxicam for the management of arthritis, a chronic disorder, results in gastrointestinal disturbances leading to poor patient compliance. Considering the favorable molecular weight, therapeutic dose, biological half-life and log P value of meloxicam for transdermal delivery, its fast dissolving microneedle patch, with an ability to breach the stratum corneum and efficiently deliver the cargo to deeper skin layers, were developed. Microneedle patch of low molecular weight polyvinyl alcohol and polyvinylpyrrolidone was prepared using Polydimethylsiloxane micromolds. The ratio of polyvinyl alcohol to polyvinyl pyrrolidone and solid content of matrix solution was optimized to achieve maximum needle strength. The optimized batch was extensively evaluated for in vitro dissolution, drug release, stability, ex vivo skin permeation/deposition, histopathology and in vivo pharmacodynamic study. The patch containing 9:1 polyvinyl alcohol to polyvinylpyrrolidone ratio with 50% solid content had shown maximum axial needle fracture force (0.9N) suitable for penetrating the skin. The optimized batch was found to be fast dissolving and released almost 100% drug in 60min following dissolution controlled kinetics. The formulation showed a significant drug deposition within skin (63.37%) and an improved transdermal flux (1.60μg/cm 2 /h) with a 2.58 fold enhancement in permeation as compared to plain drug solution. The formulation showed a comparable anti-inflammatory activity in rats when compared to its existing approved marketed oral tablet. Histopathology and stability evaluations demonstrated acceptable safety and shelf-life of the developed formulation. The successful verification of safety, efficacy and stability of microneedle patch advocated the suitability of the formulation for transdermal use. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Nanoemulsions as vehicles for transdermal delivery of glycyrrhizin

    Directory of Open Access Journals (Sweden)

    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

  3. Topical Niosome Gel of Zingiber cassumunar Roxb. Extract for Anti-inflammatory Activity Enhanced Skin Permeation and Stability of Compound D.

    Science.gov (United States)

    Priprem, Aroonsri; Janpim, Khwanhatai; Nualkaew, Somsak; Mahakunakorn, Pramote

    2016-06-01

    An extract of Zingiber cassumunar Roxb. (ZC) was encapsulated in niosomes of which a topical gel was formed. (E)-4-(3',4'-dimethoxyphenyl)but-3-en-1-ol or compound D detected by a gradient HPLC was employed as the marker and its degradation determined to follow zero-order kinetics. Niosomes significantly retarded thermal-accelerated decomposition of compound D in the gel (p D. Niosomes enhanced in vitro permeation rate of compound D from the gel. Topical applications of ZC noisome gel gave a faster change in tail flick latency than piroxicam gel and hydrocortisone cream (p anti-inflammatory activity up to 6 h using croton oil-induced ear edema model in mice (p > 0.05). Thus, encapsulation of ZC extract in niosomes enhanced chemical stability and skin permeation with comparable topical anti-inflammatory effects to steroid and NSAID.

  4. 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.

  5. Permeation of Ionic Liquids through the skin

    Directory of Open Access Journals (Sweden)

    Ana Júlio

    2017-12-01

    Full Text Available Alternative forms of drug delivery such as delivery through the skin, have been developed to explore other routes. However, the incorporation of poorly soluble or partially insoluble drugs into these delivery systems represents a major problem. Ionic liquids (ILs may be incorporated in aqueous, oily or hydroalcoholic solutions and thus, may be used as excipients in drug delivery systems to increase/improve the topical and transdermal drug delivery. However, it is fundamental to consider the cytotoxicity of these salts and it is also crucial to evaluate if these compounds permeate through the skin. Herein, three imidazole-based ILs: [C2mim][Br], [C4mim][Br] and [C6mim][Br], were synthesized and each IL was incorporated within caffeine saturated solutions. Permeation studies of the active (caffeine in these solutions were performed to evaluate the amount of IL that permeated through the porcine ear skin in the presence of the active. To achieve this, gravimetric studies of the receptor compartment were performed. Results showed that the more lipophilic IL [C6mim][Br] presented the highest permeation through the skin. The permeation is dependent upon the size of the alkyl chain of the IL, and as more than 60% of the ILs permeate is it vital to consider the cytotoxicity of these salts when considering their incorporation in topical systems.

  6. 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.

  7. Penetration enhancer-containing vesicles (PEVs) as carriers for cutaneous delivery of minoxidil: in vitro evaluation of drug permeation by infrared spectroscopy.

    Science.gov (United States)

    Mura, Simona; Manconi, Maria; Fadda, Anna Maria; Sala, Maria Chiara; Perricci, Jacopo; Pini, Elena; Sinico, Chiara

    2013-01-01

    Recently, we carried out a research on new liposomal systems prepared by using in their composition a few penetration enhancers which differ for chemical structure and physicochemical properties. The penetration enhancer-containing vesicles (PEVs) were prepared by using soy lecithin and different amounts of three penetration enhancers, 2-(2-ethoxyethoxy) ethanol (Transcutol(®)), capryl-caproyl macrogol 8-glyceride (Labrasol(®)), and cineole.To study the influence of the PEVs on (trans)dermal delivery of minoxidil, in vitro diffusion experiments were performed through new born pig skin and the results were compared with that obtained applying the vesicular system without enhancer (control) after pretreatment of the skin with the various enhancers. In this study, Fourier transform infrared spectroscopy (FTIR), attenuated total reflectance FTIR (ATR-FTIR) and FTIR imaging were used to evaluate the effective penetration of minoxidil in the skin layers and to discover the influence of the enhancer on the drug topical delivery. These analytical studies allowed us to characterize the drug formulations and to evaluate the vesicle distribution into the skin. Recorded spectra confirmed that the vesicle formulations with penetration enhancers promoted drug deposition into the skin.

  8. 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 ...

  9. Optimization and evaluation of pluronic lecithin organogels as a transdermal delivery vehicle for sinomenine.

    Science.gov (United States)

    Ba, Wenqiang; Li, Zhou; Wang, Lisheng; Wang, Ding; Liao, Weiguo; Fan, Wentao; Wu, Yinai; Liao, Fengyun; Yu, Jianye

    2016-08-01

    The purpose of the present study was to prepare and optimize sinomenine (SIN) pluronic lecithin organogels system (PLO), and to evaluate the permeability of the optimized PLO in vitro and in vivo. Box-Behnken design was used to optimize the PLO and the optimized formulation was pluronic F127 of 19.61%, lecithin of 3.60% and SIN of 1.27%. The formulation was evaluated its skin permeation and drug deposition both in vitro and in vivo compared with gel. Permeation and deposition studies of PLO were carried out with Franz diffusion cells in vitro and with microdialysis in vivo. In vitro studies, permeation rate (Jss) of SIN from PLO was 146.55 ± 2.93 μg/cm(2)/h, significantly higher than that of gel (120.39 μg/cm(2)/h) and the amount of SIN deposited in skin from the PLO was 10.08 ± 0.86 μg/cm(2), significantly larger than that from gel (6.01 ± 0.04 μg/cm(2)). In vivo skin microdialysis studies showed that the maximum concentration (Cmax) of SIN from PLO in "permeation study" and "drug-deposition study" were 150.27 ± 20.85 μg/ml and 67.95 μg/ml, respectively, both significantly higher than that of SIN from gel (29.66 and 6.73 μg/ml). The results recommend that PLO can be used as an advantageous transdermal delivery vehicle to enhance the permeation and skin deposition of SIN.

  10. 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

  11. Enhanced transdermal permeability of Terbinafine through novel nanoemulgel formulation; Development, in vitro and in vivo characterization

    Directory of Open Access Journals (Sweden)

    Maha E. Elmataeeshy

    2018-06-01

    Full Text Available Terbinafine Hcl (TB is a poorly water soluble antifungal drug. Topical nanoemulsion based gel containing TB was prepared with a view to improve its solubility and antifungal activity. In preparation of the nanoemulsion (NE, excipients were selected based on the solubility study. Peceol was optimized as the oil phase. Tween 80 and propanol were optimized as the surfactant and co-solvent respectively, and were mixed (Smix in different weight ratios (1:1, 1:2, 1:3, 1:4, 4:1, 3:1 and 2:1, respectively. Pseudoternary phase diagrams were developed and Pecol and Smix were mixed in different weight ratios ranging from 1:9 to 9:1. Based on the NE region of each diagram, the formulae were selected. The formulated nanoemulsions were characterized and evaluated for in vitro drug release and thermodynamic stability. The optimum nanoemulsion formulae containing 10 or 15% w/w oil, 45% w/w Smix (1:2/1:3 and 45-40% w/w aqueous phase were incorporated into Carbopol 940 gel bases forming three different TB nanoemulsion based emulgel formulae (F1-F3 which were examined for ex vivo drug permeation and in vivo antifungal activity compared to the marketed product; Lamisil® emulgel. The results showed that TB skin permeation from all the prepared nanoemulsion based gel formulae was significantly (p < 0.05 improved in relation to the commercial emulgel. F3 exhibited a superior in vivo antifungal activity over the marketed emulgel for the treatment of Candida infection. Keywords: Terbinafine nanoemulsion, Pseudoternary phase diagrams, Permeation study

  12. 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.

  13. Transdermal nicotine mixed natural rubber-hydroxypropylmethylcellulose film forming systems for smoking cessation: in vitro evaluations.

    Science.gov (United States)

    Pichayakorn, Wiwat; Suksaeree, Jirapornchai; Boonme, Prapaporn; Taweepreda, Wirach; Amnuaikit, Thanaporn; Ritthidej, Garnpimol C

    2014-08-27

    Abstract Novel film forming polymeric dispersions for transdermal nicotine delivery were prepared from deproteinized natural rubber latex (DNRL) blended with hydroxypropylmethylcellulose (HPMC) and dibutyl phthalate (DBP) or glycerin (GLY) as plasticizer. The preliminary molecular compatibility of ingredients was observed by Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffractometry characterizations. All film forming polymeric dispersions were elegant in appearance and smooth in texture without agglomeration. Their pH was 7-8. In addition, their viscosity and spreadability showed good characteristics depended on HPMC and plasticizers blended. The transparent in situ dry films with good strength and elasticity were also confirmed by peeling-off. The nicotine release from them revealed an initial fast release that was similar to the release from a concentrated nicotine solution, and followed by slow release pattern from the in situ films. GLY blended formulation produced a higher amount of nicotine permeation through the in vitro pig skin than DBP blends. Ethanol mixing also enhanced nicotine permeation, but it affected the integrity of in situ films. The nicotine release and skin permeation kinetics were by a diffusion mechanism that was confirmed by the Higuchi's model. These formulations were safe without producing any severe skin irritation. However, for the stability they needed to be stored at 4 °C in tightly sealed containers.

  14. Design, formulation and optimization of novel soft nano-carriers for transdermal olmesartan medoxomil delivery: In vitro characterization and in vivo pharmacokinetic assessment.

    Science.gov (United States)

    Kamran, Mohd; Ahad, Abdul; Aqil, Mohd; Imam, Syed Sarim; Sultana, Yasmin; Ali, Asgar

    2016-05-30

    Olmesartan is a hydrophobic antihypertensive drug with a short biological half-life, and low bioavailability, presents a challenge with respect to its oral administration. The objective of the work was to formulate, optimize and evaluate the transdermal potential of novel vesicular nano-invasomes, containing above anti-hypertensive agent. To achieve the above purpose, soft carriers (viz. nano-invasomes) of olmesartan with β-citronellene as potential permeation enhancer were developed and optimized using Box-Behnken design. The physicochemical characteristics e.g., vesicle size, shape, entrapment efficiency and skin permeability of the nano-invasomes formulations were evaluated. The optimized formulation was further evaluated for in vitro drug release, confocal microscopy and in vivo pharmacokinetic study. The optimum nano-invasomes formulation showed vesicles size of 83.35±3.25nm, entrapment efficiency of 65.21±2.25% and transdermal flux of 32.78±0.703 (μg/cm(2)/h) which were found in agreement with the predicted value generated by Box-Behnken design. Confocal laser microscopy of rat skin showed that optimized formulation was eventually distributed and permeated deep into the skin. The pharmacokinetic study presented that transdermal nano-invasomes formulation showed 1.15 times improvement in bioavailability of olmesartan with respect to the control formulation in Wistar rats. It was concluded that the response surfaces estimated by Design Expert(®) illustrated obvious relationship between formulation factors and response variables and nano-invasomes were found to be a proficient carrier system for transdermal delivery of olmesartan. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. 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.

  16. 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.

  17. 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

  18. Drug Delivery Through the Skin: Molecular Simulations of Barrier Lipids to Design more Effective Noninvasive Dermal and Transdermal Delivery Systems for Small Molecules Biologics and Cosmetics

    Energy Technology Data Exchange (ETDEWEB)

    J Torin Huzil; S Sivaloganathan; M Kohandel; M Foldvari

    2011-12-31

    The delivery of drugs through the skin provides a convenient route of administration that is often preferable to injection because it is noninvasive and can typically be self-administered. These two factors alone result in a significant reduction of medical complications and improvement in patient compliance. Unfortunately, a significant obstacle to dermal and transdermal drug delivery alike is the resilient barrier that the epidermal layers of the skin, primarily the stratum corneum, presents for the diffusion of exogenous chemical agents. Further advancement of transdermal drug delivery requires the development of novel delivery systems that are suitable for modern, macromolecular protein and nucleotide therapeutic agents. Significant effort has already been devoted to obtain a functional understanding of the physical barrier properties imparted by the epidermis, specifically the membrane structures of the stratum corneum. However, structural observations of membrane systems are often hindered by low resolutions, making it difficult to resolve the molecular mechanisms related to interactions between lipids found within the stratum corneum. Several models describing the molecular diffusion of drug molecules through the stratum corneum have now been postulated, where chemical permeation enhancers are thought to disrupt the underlying lipid structure, resulting in enhanced permeability. Recent investigations using biphasic vesicles also suggested a possibility for novel mechanisms involving the formation of complex polymorphic lipid phases. In this review, we discuss the advantages and limitations of permeation-enhancing strategies and how computational simulations, at the atomic scale, coupled with physical observations can provide insight into the mechanisms of diffusion through the stratum corneum.

  19. 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-...

  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. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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...

  6. Liquid crystalline systems containing Vitamin E TPGS for the controlled transdermal nicotine delivery

    Directory of Open Access Journals (Sweden)

    Lívia Neves Borgheti-Cardoso

    Full Text Available ABSTRACT Transdermal nicotine patches have been used in smoking cessation therapy, suggested for the treatment of skin disorders with eosinophilic infiltration and have been found to improve attention performance in patients with Alzheimer's disease and age-associated memory impairment. However, skin irritation with extended patch use is still a problem. The aim of this work was to develop a simple to prepare liquid crystalline system containing vitamin E TPGS that would be able to control nicotine delivery and reduce irritation and sensitization problems. The liquid crystalline phases were macroscopically characterized by visual analysis and examined microscopically under a polarized light microscope. Topical and transdermal delivery of nicotine were investigated in vitro using porcine ear skin mounted on a Franz diffusion cell. Nicotine skin permeation from the developed cubic phase followed zero-order kinetics (r = 0.993 and was significantly enhanced after 12 h when compared to the control formulation (nicotine solution (p < 0.05 (138.86 ± 20.44 and 64.91 ± 4.06 μg/cm2, respectively. Cubic phase was also able to target viable skin layers in comparison to control solution (8.18 ± 1.89 and 2.63 ± 2.51 μg/cm2, respectively. Further studies to evaluate skin sensitization and irritation are now necessary.

  7. Development of gellan gum containing formulations for transdermal drug delivery: Component evaluation and controlled drug release using temperature responsive nanogels.

    Science.gov (United States)

    Carmona-Moran, Carlos A; Zavgorodnya, Oleksandra; Penman, Andrew D; Kharlampieva, Eugenia; Bridges, S Louis; Hergenrother, Robert W; Singh, Jasvinder A; Wick, Timothy M

    2016-07-25

    Enhancing skin permeation is important for development of new transdermal drug delivery formulations. This is particularly relevant for non-steroidal anti-inflammatory drugs (NSAIDs). To address this, semisolid gel and solid hydrogel film formulations containing gellan gum as a gelling agent were developed and the effects of penetration enhancers (dimethyl sulfoxide, isopropyl alcohol and propylene glycol) on transport of the NSAID diclofenac sodium was quantified. A transwell diffusion system was used to accelerate formulation development. After 4h, diclofenac flux from a superior formulation of the semisolid gel or the solid hydrogel film was 130±11μg/cm(2)h and 108±7μg/cm(2)h, respectively, and significantly greater than that measured for a currently available diclofenac sodium topical gel (30±4μg/cm(2)h, ptransdermal drug formulations with adjustable drug transport kinetics. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. On Diffusion and Permeation

    KAUST Repository

    Peppin, Stephen S. L.

    2009-01-01

    concentrations they form a nearly rigid porous glass through which the fluid permeates. The theoretically determined pressure drop is nonlinear in the diffusion regime and linear in the permeation regime, in quantitative agreement with experimental measurements

  9. 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.

  10. 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.

  11. 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

  12. Preparation and physicochemical evaluation of transdermal ...

    African Journals Online (AJOL)

    permeation enhancers presented higher rates of skin penetration compared to control formulations. .... Drug release, in the presence of lower amounts of PVP ... Amorphous drugs are in a high energy state that causes increased solubility and.

  13. 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...

  14. Transdermal therapeutic system of narcotic analgesics using nonporous membrane (I) : Effect of the ethanol permeability on vinylacetate content of EVA membrane

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, H.; Song, H.Y. [Chungnam National University, Taejon (Korea); Khang, G.S. [Chonbuk National University, Chonju (Korea); Lee, H.B. [Korea Research Institute of Chemical Technology, Taejon (Korea)

    1999-05-01

    The fundamental properties of transdermal therapeutic patch as narcotic analgesics agent has been investigated. From the study of drug and ethanol release patterns from the fentanyl base (FB) patches through diffusion cell and hairless mouse skin, it was observed that the FB release patterns were largely affected by the content of vinyl acetate (VA) of ethylene-co-vinyl acetate (EVA) membrane, and volume fraction of ethanolic solution. Additionally, a variety of control membrane as a function of VA content were examined for swelling following equilibration with ethanolic solutions. Generally, ethanol was incorporated into a transdermal therapeutic device to enable the controlled delivery of enhancer and drug to the skin surface. In vitro skin permeation analysis of the control membrane showed that ethanol flux was linearly related to the ethanol volume fraction. This result was shown that drug permeability increased with increasing as the content of VA. But, the FB flux from saturated aqueous ethanol solutions increases until 80% ethanol volume fraction. Over 80% ethanol volume fraction, the FB flux through skin samples is independent of ethanol volume. These results showed that the decrease in skin permeation due to dehydration nis the dominant effect. 26 refs., 8 figs.

  15. Dissolution and permeation characteristics of artemether tablets ...

    African Journals Online (AJOL)

    characterized by delayed drug release but enhanced permeation of the released drug. Keywords: ... and prosopis gum as binders and to consider the relationship between ..... higher tensile strength and higher brittle fracture index compared ...

  16. 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.

  17. Transdermal glimepiride delivery system based on optimized ethosomal nano-vesicles: Preparation, characterization, in vitro, ex vivo and clinical evaluation.

    Science.gov (United States)

    Ahmed, Tarek A; El-Say, Khalid M; Aljaeid, Bader M; Fahmy, Usama A; Abd-Allah, Fathy I

    2016-03-16

    This work aimed to develop an optimized ethosomal formulation of glimepiride then loading into transdermal films to offer lower drug side effect, extended release behavior and avoid first pass effect. Four formulation factors were optimized for their effects on vesicle size (Y1), entrapment efficiency (Y2) and vesicle flexibility (Y3). Optimum desirability was identified and, an optimized formulation was prepared, characterized and loaded into transdermal films. Ex-vivo permeation study for the prepared films was conducted and, the permeation parameters and drug permeation mechanism were identified. Penetration through rat skin was studied using confocal laser microscope. In-vivo study was performed following transdermal application on human volunteers. The percent of alcohol was significantly affecting all the studied responses while the other factors and their interaction effects were varied on their effects on each response. The optimized ethosomal formulation showed observed values for Y1, Y2 and Y3 of 61 nm, 97.12% and 54.03, respectively. Ex-vivo permeation of films loaded with optimized ethosomal formulation was superior to that of the corresponding pure drug transdermal films and this finding was also confirmed after confocal laser microscope study. Permeation of glimepiride from the prepared films was in favor of Higushi-diffusion model and exhibited non-Fickian or anomalous release mechanism. In-vivo study revealed extended drug release behavior and lower maximum drug plasma level from transdermal films loaded with drug ethosomal formulation. So, the ethosomal formulation could be considered a suitable drug delivery system especially when loaded into transdermal vehicle with possible reduction in side effects and controlling the drug release. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. 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

  19. 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.

  20. 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).

  1. 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.

  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. Permeation through graphene ripples

    Science.gov (United States)

    Liang, Tao; He, Guangyu; Wu, Xu; Ren, Jindong; Guo, Hongxuan; Kong, Yuhan; Iwai, Hideo; Fujita, Daisuke; Gao, Hongjun; Guo, Haiming; Liu, Yingchun; Xu, Mingsheng

    2017-06-01

    Real graphene sheets show limited anti-permeation performance deviating from the ideally flat honeycomb carbon lattice that is impermeable to gases. Ripples in graphene are prevalent and they could significantly influence carrier transport. However, little attention has been paid to the role of ripples in the permeation properties of graphene. Here, we report that gases can permeate through graphene ripples at room temperature. The feasibility of gas permeation through graphene ripples is determined by detecting the initial oxidation sites of Cu surface covered with isolated graphene domain. Nudged elastic band (NEB) calculations demonstrate that the oxygen atom permeation occurs via the formation of C-O-C bond, in which process the energy barrier through the rippled graphene lattice is much smaller than that through a flat graphene lattice, rendering permeation through ripples more favorable. Combining with the recent advances in atoms intercalation between graphene and metal substrate for transfer-free and electrically insulated graphene, this discovery provides new perspectives regarding graphene’s limited anti-permeation performance and evokes for rational design of graphene-based encapsulation for barrier and selective gas separation applications through ripple engineering.

  4. [Effects of Frankincense and Myrrh essential oil on transdermal absorption in vitro of Chuanxiong and penetration mechanism of skin blood flow].

    Science.gov (United States)

    Zhu, Xiao-Fang; Luo, Jing; Guan, Yong-Mei; Yu, Ya-Ting; Jin, Chen; Zhu, Wei-Feng; Liu, Hong-Ning

    2017-02-01

    The aim of this paper was to explore the effects of Frankincense and Myrrh essential oil on transdermal absorption in vitro of Chuanxiong, and to investigate the possible penetration mechanism of their essential oil from the perspective of skin blood perfusion changes. Transdermal tests were performed in vitro with excised mice skin by improved Franz diffusion cells. The cumulative penetration amounts of ferulic acid in Chuanxiong were determined by HPLC to investigate the effects of Frankincense and Myrrh essential oil on transdermal permeation properties of Chuanxiong. Simultaneously, the skin blood flows were determined by laser flow doppler. The results showed that the cumulative penetration amount of ferulic acid in Chuanxiong was (8.13±0.76) μg•cm⁻² in 24 h, and was (48.91±4.87), (57.80±2.86), (63.34±4.56), (54.17±4.40), (62.52±7.79) μg•cm⁻² respectively in Azone group, Frankincense essential oil group, Myrrh essential oil, frankincense and myrrh singly extracted essential oil mixture group, and frankincense and myrrh mixed extraction essential oil group. The enhancement ratios of each essential oil groups were 7.68, 8.26, 7.26, 8.28, which were slightly greater than 6.55 in Azone group. In addition, as compared with the conditions before treatment, there were significant differences and obvious increasing trend in blood flow of rats in Frankincense essential oil group, Myrrh essential oil group, frankincense and myrrh singly extracted essential oil mixture group, and frankincense and myrrh mixed extraction essential oil group when were dosed at 10, 20, 30, 10 min respectively, indicating that the skin blood flows were increased under the effects of Frankincense and Myrrh essential oil to a certain extent. Thus, Frankincense and Myrrh essential oil had certain effect on promoting permeability of Chuanxiong both before and after drug combination, and may promote the elimination of drugs from epidermis to dermal capillaries through increase of

  5. Thiolated quaternary ammonium-chitosan conjugates for enhanced precorneal retention, transcorneal permeation and intraocular absorption of dexamethasone.

    Science.gov (United States)

    Zambito, Ylenia; Di Colo, Giacomo

    2010-06-01

    Previously, a quaternary ammonium (N(+))-chitosan (Ch) conjugate (N(+)(60)-Ch) characterized by short pendant chains, made of 1.7+/-0.1 adjacent diethyl-dimethylene-ammonium groups, substituted onto the primary amino group of the chitosan repeating units (degree of substitution, 59.2+/-4.5%) was used to synthesize a multifunctional non-cytotoxic thiomer (N(+)(60)-Ch-SH(5)), carrying 4.5+/-0.7% thiol-bearing 3-mercaptopropionamide besides quaternary ammonium groups. The present work was aimed at evaluating the potential of N(+)(60)-Ch-SH(5) and N(+)(60)-Ch as bioactive excipients for dexamethasone (DMS) eyedrops. The DMS permeability across excised rabbit cornea was enhanced over the control value by the thiomer and the parent polymer to about the same extent (3.8 vs. 4.1 times). The mean precorneal retention time and AUC in the aqueous of DMS instilled in rabbit eyes via eyedrops were enhanced by the thiomer (MRT=77.96+/-3.57 min, AUC=33.19+/-6.96 microg ml(-1) min) more than the parent polymer (MRT=65.74+/-4.91 min, AUC=21.48+/-3.81 microg ml(-1) min) over the control (MRT=5.07+/-0.25 min, AUC=6.25+/-0.65 microg ml(-1) min). The quaternary ammonium ions were responsible for both permeabilization of corneal epithelium and polymer adhesion to precorneal mucus, while the thiols increased the latter. This synergistic action is the basis of the higher thiomer bioactivity in vivo. A good ocular tolerability of the chitosan derivatives resulted from in vivo experiments. Copyright 2010 Elsevier B.V. All rights reserved.

  6. Cell Permeating Nano-Complexes of Amphiphilic Polyelectrolytes Enhance Solubility, Stability, and Anti-Cancer Efficacy of Curcumin.

    Science.gov (United States)

    Fatima, Munazza T; Chanchal, Abhishek; Yavvari, Prabhu S; Bhagat, Somnath D; Gujrati, Mansi; Mishra, Ram K; Srivastava, Aasheesh

    2016-07-11

    Many hydrophobic drugs encounter severe bioavailability issues owing to their low aqueous solubility and limited cellular uptake. We have designed a series of amphiphilic polyaspartamide polyelectrolytes (PEs) that solubilize such hydrophobic drugs in aqueous medium and enhance their cellular uptake. These PEs were synthesized through controlled (∼20 mol %) derivatization of polysuccinimide (PSI) precursor polymer with hydrophobic amines (of varying alkyl chain lengths, viz. hexyl, octyl, dodecyl, and oleyl), while the remaining succinimide residues of PSI were opened using a protonable and hydrophilic amine, 2-(2-amino-ethyl amino) ethanol (AE). Curcumin (Cur) was employed as a representative hydrophobic drug to explore the drug-delivery potential of the resulting PEs. Unprecedented enhancement in the aqueous solubility of Cur was achieved by employing these PEs through a rather simple protocol. In the case of PEs containing oleyl/dodecyl residues, up to >65000× increment in the solubility of Cur in aqueous medium could be achieved without requiring any organic solvent at all. The resulting suspensions were physically and chemically stable for at least 2 weeks. Stable nanosized polyelectrolyte complexes (PECs) with average hydrodynamic diameters (DH) of 150-170 nm (without Cur) and 220-270 nm (after Cur loading) were obtained by using submolar sodium polyaspartate (SPA) counter polyelectrolyte. The zeta potential of these PECs ranged from +36 to +43 mV. The PEC-formation significantly improved the cytocompatibility of the PEs while affording reconstitutable nanoformulations having up to 40 wt % drug-loading. The Cur-loaded PECs were readily internalized by mammalian cells (HEK-293T, MDA-MB-231, and U2OS), majorly through clathrin-mediated endocytosis (CME). Cellular uptake of Cur was directly correlated with the length of the alkyl chain present in the PECs. Further, the PECs significantly improved nuclear transport of Cur in cancer cells, resulting in their

  7. Development of surface stabilized candesartan cilexetil nanocrystals with enhanced dissolution rate, permeation rate across CaCo-2, and oral bioavailability.

    Science.gov (United States)

    Jain, Sanyog; Reddy, Venkata Appa; Arora, Sumit; Patel, Kamlesh

    2016-10-01

    Candesartan cilexetil (CC), an ester prodrug of candesartan, is BCS class II drug with extremely low aqueous solubility limiting its oral bioavailability. The present research aimed to develop a nanocrystalline formulation of CC with improved saturation solubility in gastrointestinal fluids and thereby, exhibiting enhanced oral bioavailability. CC nanocrystals were prepared using a low energy antisolvent precipitation methodology. A combination of hydroxypropyl methylcellulose (HPMC) and Pluronic® F 127 (50:50 w/w) was found to be optimum for the preparation of CC nanocrystals. The particle size, polydispersity index (PDI), and zeta potential of optimized formulation was found to be 159 ± 8.1 nm, 0.177 ± 0.043, and -23.7 ± 1.02 mV, respectively. Optimized formulation was found to possess irregular, plate-like morphology as evaluated by scanning electron microscopy and crystalline as evaluated by differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD). A significant increase in saturation solubility and dissolution rate of the optimized nanosuspension was observed at all the tested pH conditions. Optimized CC nanocrystals exhibited a storage stability of more than 3 months when stored under cold and room temperature conditions. In vitro Caco-2 permeability further revealed that CC nanocrystals exhibited nearly 4-fold increase in permeation rate compared to the free CC. In vivo oral bioavailability studies of optimized CC nanocrystals in murine model revealed 3.8-fold increase in the oral bioavailability and twice the C max as compared with the free CC when administered orally. In conclusion, this study has established a crystalline nanosuspension formulation of CC with improved oral bioavailability in murine model. Graphical Abstract Antisolvent precipitation methodology for the preparation of Candesartan Cilexetil nanocrystals for enhanced solubility and oral bioavailability.

  8. Enhanced delivery of cosmeceuticals by microdermabrasion.

    Science.gov (United States)

    Zhou, Yingcong; Banga, Ajay K

    2011-09-01

    Microdermabrasion (MDA) is one of the top five nonsurgical cosmetic procedures performed. It is a well-established technology with widespread applications in the cosmetic industry. To investigate the effects of MDA on skin and delivery of cosmeceuticals. The alternation of skin structure post-MDA was examined by histological sectioning and transepidermal water loss measurements. The effect of MDA treatment on skin permeation profiles of hydrophilic and lipophilic molecules was investigated by laser scanning confocal microscopy and in vitro permeation studies. Confocal images indicated different absorption profiles and permeation depths for hydrophilic and lipophilic molecules. Microdermabrasion enhanced the transdermal delivery of nicotinamide, the model hydrophilic compound employed. On the other hand, permeation of retinol, the model lipophilic compound, did not improve after treatment with MDA. When treated with 20 passes, the skin recovered from MDA induced changes in 4 days. Permeation of cosmeceuticals into skin was found to be affected by their lipophilicity. Application of skin care products post-MDA therapy may be promising to improve their dermal uptake. © 2011 Wiley Periodicals, Inc.

  9. Enhanced paracellular and transcellular paclitaxel permeation by chitosan-vitamin E succinate- N-acetyl- l-cysteine copolymer on Caco-2 cell monolayer

    Science.gov (United States)

    Lian, He; Zhang, Tianhong; Sun, Jin; Pu, Xiaohui; Tang, Yilin; Zhang, Youxi; He, Zhonggui

    2014-04-01

    The aim of this study was to evaluate the underlying mechanism of enhanced oral absorption of paclitaxel (PTX)-loaded chitosan-vitamin E succinate- N-acetyl- l-cysteine (CS-VES-NAC) nanomicelles from the cellular level. In aqueous solution, CS-VES-NAC copolymer self-assembled into the polymeric nanomicelles, with the size ranging from 190 to 240 nm and the drug loading content as high as 20.5 %. Cytotoxicity results showed that the PTX-loaded nanomicelles exhibited the similar effect to PTX solution (PTX-Sol) on Caco-2 cells, but no toxicity observed for blank CS-VES-NAC nanomicelles. The cellular uptake of PTX was significantly increased by CS-VES-NAC nanomicelles, compared with that of PTX-Sol, due to the possible escapement of P-glycoprotein (P-gp) efflux pumps by endocytosis pathway. Confocal laser scanning microscope (CLSM) images also confirmed CS-VES-NAC nanomicelles could be effectively internalized by Caco-2 cells. More importantly, P app value of PTX-loaded CS-VES-NAC nanomicelles was 2.3-fold higher than that of PTX-Sol, and the efflux ratio decreased by more than 10.8-fold for the nanomicelles. As a consequence of opening of tight junctions and P-gp inhibition induced by free CS-VES-NAC copolymer, the P app value of PTX was almost increased up to 19.5-fold. All the results indicate that CS-VES-NAC copolymer hold great promises as nanocarrier for antitumor drug oral delivery by improving paracellular and transcellular permeation.

  10. 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.

  11. 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.

  12. Microemulsion Transdermal Formulation for Simultaneous Delivery of Valsartan and Nifedipine: Formulation by Design.

    Science.gov (United States)

    Sood, Jatin; Sapra, Bharti; Tiwary, Ashok K

    2017-08-01

    The objective of the study was to optimize the proportion of different components for formulating oil in water microemulsion formulation meant for simultaneous transdermal delivery of two poorly soluble antihypertensive drugs. Surface response methodology of Box-Behnken design was utilized to evaluate the effect of two oils (Captex 500 - x1 and Capmul MCM - x2) and surfactant (Acrysol EL135 - x3) on response y1 (particle size), y2 (solubility of valsartan), and y3 (solubility of nifedipine). The important factors which significantly affected the responses were identified and validated using ANOVA. The model was diagnosed using normal plot of residuals and Box-Cox plot. The design revealed an inverse correlation between particle size and concentration of Capmul MCM and Acrysol EL 135. However, an increase in concentration of Captex 500 led to an increase in particle size of microemulsion. Solubility of valsartan decreased while that of nifedipine increased with increase in concentration of Captex 500. Capmul MCM played a significant role in increasing the solubility of valsartan. The effect of Acrysol EL 135 on solubility of both drugs, although significant, was only marginal as compared to that of Captex 500 and Capmul MCM. The optimized microemulsion was able to provide an enhancement ratio of 27.21 and 63.57-fold for valsartan and nifedipine, respectively, with respect to drug dispersion in aqueous surfactant system when evaluated for permeation studies. The current studies candidly suggest the scope of microemulsion systems for solubilizing as well as promoting the transport of both drugs across rat skin at an enhanced permeation rate.

  13. Tritium permeation through iron

    International Nuclear Information System (INIS)

    Hagi, Hideki; Hayashi, Yasunori

    1989-01-01

    An experimental method for measuring diffusion coefficients and permeation rates of tritium in metals around room temperature has been established, and their values in iron have been obtained by using the method. Permeation rates of tritium and hydrogen through iron were measured by the electrochemical method in which a tritiated aqueous solution was used as a cathodic electrolyte. Tritium and hydrogen were introduced from one side of a membrane specimen by cathodic polarization, while at the other side of the specimen the permeating tritium and hydrogen were extracted by potentiostatical ionization. The amount of permeated hydrogen was obtained by integrating the anodic current, and that of tritium was determined by measuring the radioactivity of the electrolyte sampled from the extraction side. Diffusion coefficients of tritium (D T ) and hydrogen (D H ) were determined from the time lag of tritium and hydrogen permeation. D T =9x10 -10 m 2 /s and D H =4x10 -9 m 2 /s at 286 K for annealed iron specimens. These values of D T and D H were compared with the previous data of the diffusion coefficients of hydrogen and deuterium, and the isotope effect in diffusion was discussed. (orig.)

  14. Long-term stable water vapor permeation barrier properties of SiN/SiCN/SiN nanolaminated multilayers grown by plasma-enhanced chemical vapor deposition at extremely low pressures

    International Nuclear Information System (INIS)

    Choi, Bum Ho; Lee, Jong Ho

    2014-01-01

    We investigated the water vapor permeation barrier properties of 30-nm-thick SiN/SiCN/SiN nanolaminated multilayer structures grown by plasma enhanced chemical vapor deposition at 7 mTorr. The derived water vapor transmission rate was 1.12 × 10 −6 g/(m 2 day) at 85 °C and 85% relative humidity, and this value was maintained up to 15 000 h of aging time. The X-ray diffraction patterns revealed that the nanolaminated film was composed of an amorphous phase. A mixed phase was observed upon performing high resolution transmission electron microscope analysis, which indicated that a thermodynamically stable structure was formed. It was revealed amorphous SiN/SiCN/SiN multilayer structures that are free from intermixed interface defects effectively block water vapor permeation into active layer

  15. Characterization and In Vitro Skin Permeation of Meloxicam-Loaded Liposomes versus Transfersomes

    Directory of Open Access Journals (Sweden)

    Sureewan Duangjit

    2011-01-01

    Full Text Available The goal of this study was to develop and evaluate the potential use of liposome and transfersome vesicles in the transdermal drug delivery of meloxicam (MX. MX-loaded vesicles were prepared and evaluated for particle size, zeta potential, entrapment efficiency (%EE, loading efficiency, stability, and in vitro skin permeation. The vesicles were spherical in structure, 90 to 140 nm in size, and negatively charged (−23 to −43 mV. The %EE of MX in the vesicles ranged from 40 to 70%. Transfersomes provided a significantly higher skin permeation of MX compared to liposomes. Fourier Transform Infrared Spectroscopy (FT-IR and Differential Scanning Calorimetry (DSC analysis indicated that the application of transfersomes significantly disrupted the stratum corneum lipid. Our research suggests that MX-loaded transfersomes can be potentially used as a transdermal drug delivery system.

  16. On Diffusion and Permeation

    KAUST Repository

    Peppin, Stephen S. L.

    2009-01-01

    Diffusion and permeation are discussed within the context of irreversible thermodynamics. A new expression for the generalized Stokes-Einstein equation is obtained which links the permeability to the diffusivity of a two-component solution and contains the poroelastic Biot-Willis coefficient. The theory is illustrated by predicting the concentration and pressure profiles during the filtration of a protein solution. At low concentrations the proteins diffuse independently while at higher concentrations they form a nearly rigid porous glass through which the fluid permeates. The theoretically determined pressure drop is nonlinear in the diffusion regime and linear in the permeation regime, in quantitative agreement with experimental measurements. © 2009 Walter de Gruyter, Berlin, New York.

  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. Enhanced skin delivery of vismodegib by microneedle treatment.

    Science.gov (United States)

    Nguyen, Hiep X; Banga, Ajay K

    2015-08-01

    The present study investigated the effects of microneedle treatment (maltose microneedles, Admin Pen™ 1200, and Admin Pen™ 1500) on in vitro transdermal delivery of vismodegib with different needle lengths, skin equilibration times, and microneedle insertion durations. The influence of microneedle treatment on the dimensions of microchannels (dye binding, calcein imaging, histology, and confocal microscopy studies), transepidermal water loss, and skin permeability of vismodegib was also evaluated. Skin viscoelasticity was assessed using a rheometer, and microneedle geometry was characterized by scanning electron microscopy. Permeation studies of vismodegib through dermatomed porcine ear skin were conducted using vertical Franz diffusion cells. Skin irritation potential of vismodegib formulation was assessed using an in vitro reconstructed human epidermis model. Results of the in vitro permeation studies revealed significant enhancement in permeation of vismodegib through microneedle-treated skin. As the needle length increased from 500 to 1100 and 1400 μm, drug delivery increased from 14.50 ± 2.35 to 32.38 ± 3.33 and 74.40 ± 15.86 μg/cm(2), respectively. Positive correlation between drug permeability and microneedle treatment duration was observed. The equilibration time was also found to affect the delivery of vismodegib. Thus, changes in microneedle length, equilibration time, and duration of treatment altered transdermal delivery of vismodegib.

  19. [Effects of Frankincense and Myrrh essential oil on transdermal absorption of ferulic acid in Chuanxiong].

    Science.gov (United States)

    Guan, Yong-Mei; Tao, Ling; Zhu, Xiao-Fang; Zang, Zhen-Zhong; Jin, Chen; Chen, Li-Hua

    2017-09-01

    The aim of this paper was to explore the effects of Frankincense and Myrrh essential oil on transdermal absorption, and investigate the mechanism of permeation on the microstructure and molecular structure of stratum corneum. Through the determination of stratum corneum/medium partition coefficient of ferulicacid in Chuanxiong influenced by Frankincense and Myrrh essential oil, the effects of volatile oil of frankincense and Myrrh on the the microscopic and molecular structure of stratum corneum were explored by observation of skin stratum corneum structure under scanning electron microscopy, and investigation of frankincense and myrrh essential oil effects on the molecular structure of keratin and lipids in stratum corneum under Fourier transform infrared spectroscopy. The results showed that the oil could enhance the distribution of ferulic acid in the stratum corneum and medium, and to a certain extent damaged the imbricate structure of stratum corneum which was originally regularly, neatly, and closely arranged; some epidermal scales turned upward, with local peeling phenomenon. In addition, frankincense and myrrh essential oil caused the relative displacement of CH2 stretching vibration peak of stratum corneum lipids and amide stretching vibration peak of stratum corneum keratin, indicating that frankincense and myrrh essential oil may change the conformation of lipid and keratin in the stratum corneum, increase the bilayer liquidity of the stratum corneum lipid, and change the orderly and compact structure to increase the skin permeability and reduce the effect of barrier function. It can be concluded that Frankincense and Myrrh essential oil can promote the permeation effect by increasing the distribution of drugs in the stratum corneum and changing the structure of the stratum corneum. Copyright© by the Chinese Pharmaceutical Association.

  20. Comparison of the effect of fatty alcohols on the permeation of melatonin between porcine and human skin.

    Science.gov (United States)

    Andega, S; Kanikkannan, N; Singh, M

    2001-11-09

    Melatonin (MT) is a hormone secreted by the pineal gland that plays an important role in the regulation of the circadian sleep-wake cycle. It would be advantageous to administer MT using a transdermal delivery system for the treatment of sleep disorders such as delayed sleep syndrome, jet lag in travelers, cosmonauts and shift workers. The porcine skin has been found to have similar morphological and functional characteristics as human skin. The elastic fibres in the dermis, enzyme pattern of the epidermis, epidermal tissue turnover time, keratinous proteins and thickness of epidermis of porcine skin are similar to human skin. However, the fat deposition and vascularisation of the cutaneous glands of porcine skin are different from human skin. In addition, porcine skin has been found to have a close permeability character to human skin. However, the comparative effect of chemical penetration enhancers on the permeation of drugs between porcine and human skin has not been reported. The purpose of this study was to compare the effect of fatty alcohols on the permeability of porcine and human skin using MT as a model compound. The effect of saturated fatty alcohols (octanol, nonanol, decanol, undecanol, lauryl alcohol, tridecanol, myristyl alcohol) and unsaturated fatty alcohols (oleyl alcohol, linoleyl alcohol, linolenyl alcohol) at 5% concentration was tested across dermatomed porcine and human skin. Our studies showed a parabolic relationship between the carbon chain length of saturated fatty alcohols and permeation enhancement of MT with both porcine and human skin. Maximum permeation of MT was observed when fatty alcohol carbon chain length was 10. In general, as the level of unsaturation increased from one to two double bonds, there was an increase in the permeation of MT both in porcine and human skin. However, a decrease in the permeation was observed with three double bonds. Regression analysis using the steady state flux data showed a significant positive

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  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

    ..., and enhancement and measurement of skin permeation. The book provides pharmaceutical scientists, skin product development experts, and those in the cosmetic and personal care industry with practical knowledge and insight into future product...

  6. Simplified tritium permeation model

    International Nuclear Information System (INIS)

    Longhurst, G.R.

    1993-01-01

    In this model I seek to provide a simplified approach to solving permeation problems addressed by TMAP4. I will assume that there are m one-dimensional segments with thickness L i , i = 1, 2, hor-ellipsis, m, joined in series with an implantation flux, J i , implanting at the single depth, δ, in the first segment. From material properties and heat transfer considerations, I calculate temperatures at each face of each segment, and from those temperatures I find local diffusivities and solubilities. I assume recombination coefficients K r1 and K r2 are known at the upstream and downstream faces, respectively, but the model will generate Baskes recombination coefficient values on demand. Here I first develop the steady-state concentration equations and then show how trapping considerations can lead to good estimates of permeation transient times

  7. 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.

  8. 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.

  9. 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.

  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. Using transdermal iontophoresis to increase granisetron delivery across skin in vitro and in vivo: effect of experimental conditions and a comparison with other enhancement strategies.

    Science.gov (United States)

    Cázares-Delgadillo, Jennyfer; Ganem-Rondero, Adriana; Quintanar-Guerrero, David; López-Castellano, Alicia C; Merino, Virginia; Kalia, Yogeshvar N

    2010-03-18

    The objectives of the study were (i) to investigate the effect of experimental parameters on the iontophoretic transport of granisetron, (ii) to identify the relative contributions of electromigration (EM) and electroosmosis (EO), (iii) to determine the feasibility of delivering therapeutic amounts of drug for the treatment of chemotherapy-induced nausea and vomiting and (iv) to test the in vitro results in a simple animal model in vivo. Preliminary in vitro studies using aqueous granisetron formulations investigating the effect of drug concentration (5, 10, 20 and 40 mM) and current density (0.1, 0.2, 0.3 mA cm(-2)) were performed using porcine ear skin. As expected, cumulative delivery in vitro at the 20 and 40 mM concentrations was significantly greater than that at 5 and 10mM, which were not statistically different (pgranisetron concentration of 40 mM, the transport rate was 2.93+/-0.62 microg cm(-2)min(-1)). Co-iontophoresis of acetaminophen was used to show that EM was the predominant transport mechanism accounting for 71-86% of total granisetron delivery. In vivo studies in Wistar rats (40 mM granisetron; application of 0.3 mA cm(-2) for 5h with Ag/AgCl electrodes and salt bridges) showed an average iontophoretic input rate (k(input)) of 0.83+/-0.26 microg min(-1) and a maximum plasma concentration (C(max)) of 0.092+/-0.004 microg ml(-1). Based on these results and given the known pharmacokinetics, transdermal iontophoresis could achieve therapeutic drug levels for the management of chemotherapy-induced emesis using a reasonably sized (4-6 cm(2)) patch. Copyright 2010 Elsevier B.V. All rights reserved.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Enhancement of In Vitro Skin Transport and In Vivo Hypoglycemic ...

    African Journals Online (AJOL)

    ... (PVP) for the enhancement of the transdermal delivery of glimepiride (GMD). Methods: Matrix-type transdermal patches containing GMD, drug coprecipitate ... evaluation of the formulations was conducted using automated diffusion system.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Tritium permeation and recovery

    International Nuclear Information System (INIS)

    Bond, R.A.; Hamilton, A.M.

    1987-01-01

    The paper is an appendix to a study of the reactor relevance of the NET design concept. The latter study examines whether the technologies and design principles proposed for NET can be directly extrapolated to a demonstration (DEMO) reactor. In this appendix, tritium transport in the DEMO breeding blanket is considered with emphasis on the permeation rate from the lithium-lead breeder into the coolant. A computational model used to calculate the tritium transport in the breeder blanket is described. Results are reported for the tritium transport in the NET/INTOR type blanket as well as the DEMO blanket in order to provide a comparison. In addition, results are presented for the helium coolant tritium extraction analysis. (U.K.)

  5. Reemission and permeation of deuterium implanted into metals

    International Nuclear Information System (INIS)

    Tanabe, T.; Furuyama, Y.; Imoto, S.

    1984-01-01

    Focusing on the marked depression of deuterium permeation rate during the deuteron bombardment, implantation experiments coupled with gaseous permeation experiments are performed on pure Ni and Ni with evaporated MnO. It is concluded that the reemission of implanted deuterium is initially depressed, but it soon becomes enhanced with increase of fluence leading to a rapid decrease of permeation rate at the intermediate temperatures 600-1000 K, which is attributed to the formation of short diffusion paths from the projected range to the front surface. (orig.)

  6. Design of a Dissolving Microneedle Platform for Transdermal Delivery of a Fixed-Dose Combination of Cardiovascular Drugs.

    Science.gov (United States)

    Quinn, Helen L; Bonham, Louise; Hughes, Carmel M; Donnelly, Ryan F

    2015-10-01

    Microneedles (MNs) are a minimally invasive drug delivery platform, designed to enhance transdermal drug delivery by breaching the stratum corneum. For the first time, this study describes the simultaneous delivery of a combination of three drugs using a dissolving polymeric MN system. In the present study, aspirin, lisinopril dihydrate, and atorvastatin calcium trihydrate were used as exemplar cardiovascular drugs and formulated into MN arrays using two biocompatible polymers, poly(vinylpyrrollidone) and poly(methylvinylether/maleic acid). Following fabrication, dissolution, mechanical testing, and determination of drug recovery from the MN arrays, in vitro drug delivery studies were undertaken, followed by HPLC analysis. All three drugs were successfully delivered in vitro across neonatal porcine skin, with similar permeation profiles achieved from both polymer formulations. An average of 126.3 ± 18.1 μg of atorvastatin calcium trihydrate was delivered, notably lower than the 687.9 ± 101.3 μg of lisinopril and 3924 ± 1011 μg of aspirin, because of the hydrophobic nature of the atorvastatin molecule and hence poor dissolution from the array. Polymer deposition into the skin may be an issue with repeat application of such a MN array, hence future work will consider more appropriate MN systems for continuous use, alongside tailoring delivery to less hydrophilic compounds. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  7. Formulation Optimization and Ex Vivo and In Vivo Evaluation of Celecoxib Microemulsion-Based Gel for Transdermal Delivery.

    Science.gov (United States)

    Cao, Mengyuan; Ren, Lili; Chen, Guoguang

    2017-08-01

    Celecoxib (CXB) is a poorly aqueous solubility sulfonamide non-steroidal anti-inflammatory drug (NSAID). Hence, the formulation of CXB was selected for solubilization and bioavailability. To find out suitable formulation for microemulsion, the solubility of CXB in triacetin (oil phase), Tween 80 (surfactant), and Transcutol-P (co-surfactant) was screened respectively and optimized by using orthogonal experimental design. The Km value and concentration of oil, S mix , and water were confirmed by pseudo-ternary phase diagram studies and central composite design. One percent carbopol 934 was added to form CXB microemulsion-based gel. The final formulation was evaluated for its appearance, pH, viscosity, stability, drug content determination, globule size, and zeta potential. Its ex vivo drug permeation and the in vivo pharmacokinetic was investigated. Further research was performed to ensure the safety and validity by skin irritation study and in vivo anti-inflammatory activity study. Ex vivo permeation study in mice was designed to compare permeation and transdermal ability between microemulsion formulation and conventional gel. The results revealed that optimized microemulsion-based gel gained higher permeation based on smaller globule size and high drug loading of microemulsion. Transdermal ability was also greatly improved. Bioavailability was compared to market Celebrex® by the in vivo pharmacokinetic study in rabbits. The results indicated that CXB microemulsion-based gel had better bioavailability than Celebrex®.

  8. An extended model based on the modified Nernst-Planck equation for describing transdermal iontophoresis of weak electrolytes.

    Science.gov (United States)

    Imanidis, Georgios; Luetolf, Peter

    2006-07-01

    An extended model for iontophoretic enhancement of transdermal drug permeation under constant voltage is described based on the previously modified Nernst-Planck equation, which included the effect of convective solvent flow. This model resulted in an analytical expression for the enhancement factor as a function of applied voltage, convective flow velocity due to electroosmosis, ratio of lipid to aqueous pathway passive permeability, and weighted average net ionic valence of the permeant in the aqueous epidermis domain. The shift of pH in the epidermis compared to bulk caused by the electrical double layer at the lipid-aqueous domain interface was evaluated using the Poisson-Boltzmann equation. This was solved numerically for representative surface charge densities and yielded pH differences between bulk and epidermal aqueous domain between 0.05 and 0.4 pH units. The developed model was used to analyze the experimental enhancement of an amphoteric weak electrolyte measured in vitro using human cadaver epidermis and a voltage of 250 mV at different pH values. Parameter values characterizing the involved factors were determined that yielded the experimental enhancement factors and passive permeability coefficients at all pH values. The model provided a very good agreement between experimental and calculated enhancement and passive permeability. The deduced parameters showed (i) that the pH shift in the aqueous permeation pathway had a notable effect on the ionic valence and the partitioning of the drug in this domain for a high surface charge density and depending on the pK(a) and pI of the drug in relation to the bulk pH; (ii) the magnitude and the direction of convective transport due to electroosmosis typically reflected the density and sign, respectively, of surface charge of the tissue and its effect on enhancement was substantial for bulk pH values differing from the pI of epidermal tissue; (iii) the aqueous pathway predominantly determined passive

  9. Impact of Humidity on In Vitro Human Skin Permeation Experiments for Predicting In Vivo Permeability.

    Science.gov (United States)

    Ishida, Masahiro; Takeuchi, Hiroyuki; Endo, Hiromi; Yamaguchi, Jun-Ichi

    2015-12-01

    In vitro skin permeation studies have been commonly conducted to predict in vivo permeability for the development of transdermal therapeutic systems (TTSs). We clarified the impact of humidity on in vitro human skin permeation of two TTSs having different breathability and then elucidated the predictability of in vivo permeability based on in vitro experimental data. Nicotinell(®) TTS(®) 20 and Frandol(®) tape 40mg were used as model TTSs in this study. The in vitro human skin permeation experiments were conducted under humidity levels similar to those used in clinical trials (approximately 50%) as well as under higher humidity levels (approximately 95%). The skin permeability values of drugs at 95% humidity were higher than those at 50% humidity. The time profiles of the human plasma concentrations after TTS application fitted well with the clinical data when predicted based on the in vitro permeation parameters at 50% humidity. On the other hand, those profiles predicted based on the parameters at 95% humidity were overestimated. The impact of humidity was higher for the more breathable TTS; Frandol(®) tape 40mg. These results show that in vitro human skin permeation experiments should be investigated under realistic clinical humidity levels especially for breathable TTSs. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  10. Comparative study of silver nanoparticle permeation using Side-Bi-Side and Franz diffusion cells

    Science.gov (United States)

    Trbojevich, Raul A.; Fernandez, Avelina; Watanabe, Fumiya; Mustafa, Thikra; Bryant, Matthew S.

    2016-03-01

    Better understanding the mechanisms of nanoparticle permeation through membranes and packaging polymers has important implications for the evaluation of drug transdermal uptake, in food safety and the environmental implications of nanotechnology. In this study, permeation of 21 nm diameter silver nanoparticles (AgNPs) was tested using Side-Bi-Side and Franz static diffusion cells through hydrophilic 0.1 and 0.05 µm pore diameter 125 µm thick synthetic cellulose membranes, and 16 and 120 µm thick low-density polyethylene (LDPE) films. Experiments performed with LDPE films discarded permeation of AgNPs or Ag ions over the investigated time-frame in both diffusion systems. But controlled release of AgNPs has been quantified using semipermeable hydrophilic membranes. The permeation followed a quasi-linear time-dependent model during the experimental time-frame, which represents surface reaction-limited permeation. Diffusive flux, diffusion coefficients, and membrane permeability were determined as a function of pore size and diffusion model. Concentration gradient and pore size were key to understand mass transfer phenomena in the diffusion systems.

  11. Comparative study of silver nanoparticle permeation using Side-Bi-Side and Franz diffusion cells

    International Nuclear Information System (INIS)

    Trbojevich, Raul A.; Fernandez, Avelina; Watanabe, Fumiya; Mustafa, Thikra; Bryant, Matthew S.

    2016-01-01

    Better understanding the mechanisms of nanoparticle permeation through membranes and packaging polymers has important implications for the evaluation of drug transdermal uptake, in food safety and the environmental implications of nanotechnology. In this study, permeation of 21 nm diameter silver nanoparticles (AgNPs) was tested using Side-Bi-Side and Franz static diffusion cells through hydrophilic 0.1 and 0.05 µm pore diameter 125 µm thick synthetic cellulose membranes, and 16 and 120 µm thick low-density polyethylene (LDPE) films. Experiments performed with LDPE films discarded permeation of AgNPs or Ag ions over the investigated time-frame in both diffusion systems. But controlled release of AgNPs has been quantified using semipermeable hydrophilic membranes. The permeation followed a quasi-linear time-dependent model during the experimental time-frame, which represents surface reaction-limited permeation. Diffusive flux, diffusion coefficients, and membrane permeability were determined as a function of pore size and diffusion model. Concentration gradient and pore size were key to understand mass transfer phenomena in the diffusion systems.Graphical Abstract

  12. Comparative study of silver nanoparticle permeation using Side-Bi-Side and Franz diffusion cells

    Energy Technology Data Exchange (ETDEWEB)

    Trbojevich, Raul A. [U.S. Food and Drug Administration, Division of Biochemical Toxicology, National Center for Toxicological Research (United States); Fernandez, Avelina, E-mail: velifdez@ific.uv.es [Consejo Superior de Investigaciones Científicas-Universitat de València, Parc Científic, Instituto de Física Corpuscular (Spain); Watanabe, Fumiya; Mustafa, Thikra [University Arkansas at Little Rock, Center for Integrative Nanotechnology Sciences (United States); Bryant, Matthew S. [U.S. Food and Drug Administration, Division of Biochemical Toxicology, National Center for Toxicological Research (United States)

    2016-03-15

    Better understanding the mechanisms of nanoparticle permeation through membranes and packaging polymers has important implications for the evaluation of drug transdermal uptake, in food safety and the environmental implications of nanotechnology. In this study, permeation of 21 nm diameter silver nanoparticles (AgNPs) was tested using Side-Bi-Side and Franz static diffusion cells through hydrophilic 0.1 and 0.05 µm pore diameter 125 µm thick synthetic cellulose membranes, and 16 and 120 µm thick low-density polyethylene (LDPE) films. Experiments performed with LDPE films discarded permeation of AgNPs or Ag ions over the investigated time-frame in both diffusion systems. But controlled release of AgNPs has been quantified using semipermeable hydrophilic membranes. The permeation followed a quasi-linear time-dependent model during the experimental time-frame, which represents surface reaction-limited permeation. Diffusive flux, diffusion coefficients, and membrane permeability were determined as a function of pore size and diffusion model. Concentration gradient and pore size were key to understand mass transfer phenomena in the diffusion systems.Graphical Abstract.

  13. Effect of stratum corneum heterogeneity, anisotropy, asymmetry and follicular pathway on transdermal penetration.

    Science.gov (United States)

    Barbero, Ana M; Frasch, H Frederick

    2017-08-28

    The impact of the complex structure of the stratum corneum on transdermal penetration is not yet fully described by existing models. A quantitative and thorough study of skin permeation is essential for chemical exposure assessment and transdermal delivery of drugs. The objective of this study is to analyze the effects of heterogeneity, anisotropy, asymmetry, follicular diffusion, and location of the main barrier of diffusion on percutaneous permeation. In the current study, the solution of the transient diffusion through a two-dimensional-anisotropic brick-and-mortar geometry of the stratum corneum is obtained using the commercial finite element program COMSOL Multiphysics. First, analytical solutions of an equivalent multilayer geometry are used to determine whether the lipids or corneocytes constitute the main permeation barrier. Also these analytical solutions are applied for validations of the finite element solutions. Three illustrative compounds are analyzed in these sections: diethyl phthalate, caffeine and nicotine. Then, asymmetry with depth and follicular diffusion are studied using caffeine as an illustrative compound. The following findings are drawn from this study: the main permeation barrier is located in the lipid layers; the flux and lag time of diffusion through a brick-and-mortar geometry are almost identical to the values corresponding to a multilayer geometry; the flux and lag time are affected when the lipid transbilayer diffusivity or the partition coefficients vary with depth, but are not affected by depth-dependent corneocyte diffusivity; and the follicular contribution has significance for low transbilayer lipid diffusivity, especially when flux between the follicle and the surrounding stratum corneum is involved. This study demonstrates that the diffusion is primarily transcellular and the main barrier is located in the lipid layers. Published by Elsevier B.V.

  14. In Vitro Drug Transfer Due to Drug Retention in Human Epidermis Pretreated with Application of Marketed Estradiol Transdermal Systems.

    Science.gov (United States)

    Krishnaiah, Yellela S R; Pavurala, Naresh; Yang, Yang; Manda, Prashanth; Katragadda, Usha; Yang, Yongsheng; Shah, Rakhi; Fang, Guodong; Khan, Mansoor A

    2017-08-01

    Study objective was to assess skin-to-skin drug transfer potential that may occur due to drug retention in human epidermis (DRE) pretreated with application of estradiol transdermal drug delivery systems (TDDS) and other estradiol transdermal dosage forms (gels and sprays). TDDS (products-A, B, and C) with varying formulation design and composition, and other estradiol transdermal products (gel and spray) were applied to heat separated human epidermis (HSE) and subjected to in vitro drug permeation study. Amounts of DRE were quantified after 24 h. The DRE with product-B was significantly (P  0.05) amounts of DRE. A separate in vitro permeation study was carried out to determine amounts of drug transferred from drug-retaining epidermis to untreated HSE. The amounts of drug transferred, due to DRE after 8 h, with product-C were significantly (P drug transfer due to the DRE after labeled period of using estradiol TDDS, though the clinical relevance of these findings is yet to be determined.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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)

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. Development and evaluation of ibuprofen transdermal gel formulations

    African Journals Online (AJOL)

    A commercial ibuprofen gel product (Ibutop®) was used as a reference. Results: The formulations containing 5 % of either menthol or glycerol as permeation enhancers gave drug release patterns comparable to that of the reference product. Propanol increased the apparent viscosity of the test gels to the same extent as that ...

  5. 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

  6. Co-delivery of evodiamine and rutaecarpine in a microemulsion-based hyaluronic acid hydrogel for enhanced analgesic effects on mouse pain models.

    Science.gov (United States)

    Zhang, Yong-Tai; Li, Zhe; Zhang, Kai; Zhang, Hong-Yu; He, Ze-Hui; Xia, Qing; Zhao, Ji-Hui; Feng, Nian-Ping

    2017-08-07

    The aim of this study was to improve the analgesic effect of evodiamine and rutaecarpine, using a microemulsion-based hydrogel (ME-Gel) as the transdermal co-delivery vehicle, and to assess hyaluronic acid as a hydrogel matrix for microemulsion entrapment. A microemulsion was formulated with ethyl oleate as the oil core to improve the solubility of the alkaloids and was loaded into a hyaluronic acid-structured hydrogel. Permeation-enhancing effects of the microemulsion enabled evodiamine and rutaecarpine in ME-Gel to achieve 2.60- and 2.59-fold higher transdermal fluxes compared with hydrogel control (pmicroemulsion exhibited good skin biocompatibility, whereas effective ME-Gel co-delivery of evodiamine and rutaecarpine through the skin enhanced the analgesic effect in mouse pain models compared with hydrogel. Notably, evodiamine and rutaecarpine administered using ME-Gel effectively down-regulated serum levels of prostaglandin E 2 , interleukin 6, and tumor necrosis factor α in formaldehyde-induced mouse pain models, possibly reflecting the improved transdermal permeability of ME-Gel co-delivered evodiamine and rutaecarpine, particularly with hyaluronic acid as the hydrogel matrix. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. What Is the Mechanism Behind Increased Permeation Rate of a Poorly Soluble Drug from Aqueous Dispersions of an Amorphous Solid Dispersion?

    DEFF Research Database (Denmark)

    Frank, K. J.; Westedt, U.; Rosenblatt, K. M.

    2014-01-01

    of amorphous microparticles present in aqueous dispersions induces lasting supersaturation maintaining enhanced permeation. The hypothesis is supported by a slower drug permeation when the microparticles were removed. (c) 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci...

  8. 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.

  9. Enhanced transdermal delivery of ketobemidone with prodrugs

    DEFF Research Database (Denmark)

    Hansen, L.B.; Fullerton, A.; Christrup, Lona Louring

    1992-01-01

    were observed for the ketobemidone esters from 20% w/v solutions in ethanol and ethanol-water (3:1 and 1:1 v/v) vehicles. The esters were rapidly hydrolyzed to the parent drug in the presence of skin enzymes and only from ketobemidone was detected in the receptor phase. The study demonstrates...

  10. 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,.

  11. 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.

  12. Enhancement techniques for improving 5-aminolevulinic acid delivery through the skin

    Directory of Open Access Journals (Sweden)

    Li-Wen Zhang

    2011-03-01

    Full Text Available Photodynamic therapy (PDT is a popular technique for skin cancer treatment. Protoporphyrin IX, which is a photosensitizing agent, converted enzymatically from the prodrug 5-aminolevulinic acid (ALA, is used as a photosensitizer in PDT for cancer. However, ALA penetrates with difficulty through intact skin; therefore, improving delivery systems for ALA in the skin will play an important role in ALA-PDT. Enhancement of ALA skin penetration can be achieved by physical methods, such as iontophoresis, laser, microneedles, ultrasound, and by adding chemical penetration enhancers, such as, dimethyl sulfoxide, oleic acid, and others, whereas some researches used lipophilic ALA derivatives and different vehicles to improve the transdermal delivery of ALA. This review introduces several enhancement techniques for increasing ALA permeation through the skin.

  13. In-pile tritium permeation experiment

    International Nuclear Information System (INIS)

    Longhurst, G.R.; Miller, L.G.; Watts, K.D.; Kershner, C.J.; Rogers, M.L.

    1982-01-01

    The experiments in progress are examining various aspects of the permeation of hydrogen isotopes through fusion materials. Of particular importance will be the measurement of permeation due to ion implantation in the presence of a neutron radiation field. Theoretical and early experimental results for these experiments have suggested that sufficient tritium will permeate fusion reactor interior structures that development of a permeation barrier will be needed. (orig.)

  14. In-pile tritium permeation experiment

    Energy Technology Data Exchange (ETDEWEB)

    Longhurst, G.R.; Miller, L.G.; Watts, K.D. (Idaho National Engineering Lab., Idaho Falls (USA)); Kershner, C.J.; Rogers, M.L. (Monsanto Research Corp., Miamisburg, OH (USA). Mound Facility)

    The experiments in progress are examining various aspects of the permeation of hydrogen isotopes through fusion materials. Of particular importance will be the measurement of permeation due to ion implantation in the presence of a neutron radiation field. Theoretical and early experimental results for these experiments have suggested that sufficient tritium will permeate fusion reactor interior structures that development of a permeation barrier will be needed.

  15. 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

  16. Lidocaine self-sacrificially improves the skin permeation of the acidic and poorly water-soluble drug etodolac via its transformation into an ionic liquid.

    Science.gov (United States)

    Miwa, Yasushi; Hamamoto, Hidetoshi; Ishida, Tatsuhiro

    2016-05-01

    Poor transdermal penetration of active pharmaceutical ingredients (APIs) impairs both bioavailability and therapeutic benefits and is a major challenge in the development of transdermal drug delivery systems. Here, we transformed a poorly water-soluble drug, etodolac, into an ionic liquid in order to improve its hydrophobicity, hydrophilicity and skin permeability. The ionic liquid was prepared by mixing etodolac with lidocaine (1:1, mol/mol). Both the free drug and the transformed ionic liquid were characterized by differential scanning colorimetry (DSC), infrared spectroscopy (IR), and saturation concentration measurements. In addition, in vitro skin-permeation testing was carried out via an ionic liquid-containing patch (Etoreat patch). The lidocaine and etodolac in ionic liquid form led to a relatively lower melting point than either lidocaine or etodolac alone, and this improved the lipophilicity/hydrophilicity of etodolac. In vitro skin-permeation testing demonstrated that the Etoreat patch significantly increased the skin permeation of etodolac (9.3-fold) compared with an etodolac alone patch, although an Etoreat patch did not increase the skin permeation of lidocaine, which was consistent with the results when using a lidocaine alone patch. Lidocaine appeared to self-sacrificially improve the skin permeation of etodolac via its transformation into an ionic liquid. The data suggest that ionic liquids composed of approved drugs may substantially expand the formulation preparation method to meet the challenges of drugs which are characterized by poor rates of transdermal absorption. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  17. 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.

  18. 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.

  19. 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.

  20. Hydrogen permeation preventive structural materials

    International Nuclear Information System (INIS)

    Fukushima, Kimichika; Nakahigashi, Shigeo; Imura, Masashi; Terasawa, Michitaka; Ebisawa, Katsuyuki.

    1986-01-01

    Purpose: To provide highly practical wall materials for use in thermonuclear reactors capable of effectively preventing the permeation of hydrogen isotopes such as tritium thereby preventing the contamination of coolants. Constitution: Helium gas is injected into or at the surface of base materials comprising stainless steel plates to form a helium gas region. Alternatively, boron, nitrogen or the compound thereof having a greater helium forming nuclear reaction cross section than that of the base materials is mixed or injected into the base material to form the helium gas region through (n,α) reaction under neutron irradiation. Since the helium gas region constitutes a diffusion barrier for the tritium as the hydrogen isotope, the permeation amount of tritium is significantly suppressed. Helium gas bubbles or lattice defects are formed in the helium gas region under the neutron irradiation, by which the hydrogen isotope capturing effect can also be effected. In this way, permeation of the hydrogen isotope, contamination of the coolants, etc. can be prevented to provide great practical effectives. (Kawakami, Y.)

  1. Prediction of Human Pharmacokinetic Profile After Transdermal Drug Application Using Excised Human Skin.

    Science.gov (United States)

    Yamamoto, Syunsuke; Karashima, Masatoshi; Arai, Yuta; Tohyama, Kimio; Amano, Nobuyuki

    2017-09-01

    Although several mathematical models have been reported for the estimation of human plasma concentration profiles of drug substances after dermal application, the successful cases that can predict human pharmacokinetic profiles are limited. Therefore, the aim of this study is to investigate the prediction of human plasma concentrations after dermal application using in vitro permeation parameters obtained from excised human skin. The in vitro skin permeability of 7 marketed drug products was evaluated. The plasma concentration-time profiles of the drug substances in humans after their dermal application were simulated using compartment models and the clinical pharmacokinetic parameters. The transdermal process was simulated using the in vitro skin permeation rate and lag time assuming a zero-order absorption. These simulated plasma concentration profiles were compared with the clinical data. The result revealed that the steady-state plasma concentration of diclofenac and the maximum concentrations of nicotine, bisoprolol, rivastigmine, and lidocaine after topical application were within 2-fold of the clinical data. Furthermore, the simulated concentration profiles of bisoprolol, nicotine, and rivastigmine reproduced the decrease in absorption due to drug depletion from the formulation. In conclusion, this simple compartment model using in vitro human skin permeation parameters as zero-order absorption predicted the human plasma concentrations accurately. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  2. Deuterium permeation through Flibe facing materials

    International Nuclear Information System (INIS)

    Fukada, S.; Anderl, R.A.; Smolik, G.R.

    2004-01-01

    Experiment of deuterium permeation through Ni facing with purified Flibe is being carried out under the Japan-US joint research project (JUPITER-II). The experiment has been proceeding in the following phases; (i) fabrication and assembly of a dual-probe permeation apparatus, (ii) a single-probe Ni/D 2 , permeation experiment without Flibe, (iii) a dual-probe Ar/Ni/D 2 permeation experiment without Flibe, (iv) Flibe chemical purification by HF/H 2 gas bubbling, (v) physical purification by Flibe transport through a porous Ni filter, (vi) Ar/Ni/Flibe/Ni/D 2 permeation experiment using the dual Ni probe, and (vii) Ar/Ni/Flibe/Ni/HT permeation experiment. The present paper describe results until the Ar/Ni/Flibe/Ni/D 2 permeation experiment in detail. (author)

  3. Design and characterization of submicron formulation for a poorly soluble drug: the effect of Vitamin E TPGS and other solubilizers on skin permeability enhancement.

    Science.gov (United States)

    Ghosh, Indrajit; Michniak-Kohn, Bozena

    2012-09-15

    In transdermal drug delivery systems (TDDS), it is a challenge to achieve stable and prolonged high permeation rates across the skin since the concentrations of the drug dissolved in the matrix have to be high in order to maintain zero order release kinetics. Several attempts have been reported to improve the permeability of poorly soluble drug compounds using supersaturated systems, however, due to thermodynamic challenges, there was a high tendency for the drug to nucleate immediately after formulating or even during storage. The present study focuses on the efficiency of drug crystals at the submicron/nano range in presence of different solubilizers to improve the permeation rate. Effect of several solubilizers, e.g. Pluronic F-127, Vitamin E TPGS, propylene glycol were studied on the submicron suspension systems of ibuprofen as a model drug. Various stabilizers such as hydroxylpropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP) were examined to evaluate their crystal inhibitory effects on particle growth of the drug compound at submicron range. The overall permeation enhancement process through the skin seems to be influenced by the presence of solubilizers and also the presence of submicron drug crystal. The most promising stable formulation was developed with Vitamin E TPGS+HPMC submicron suspension, which produced higher permeation rate compared to other vehicles. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Permeation behavior of deuterium implanted into beryllium

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Hirofumi; Hayashi, Takumi; O' hira, Shigeru; Nishi, Masataka [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    2001-09-01

    Study on Implantation Driven Permeation (IDP) behavior of deuterium through pure beryllium was investigated as a part of the research to predict the tritium permeation through the first wall components ITER (International Thermonuclear Experimental Reactor). The permeation experiments were carried out with two beryllium specimens, one was an unannealed specimen and the other was that annealed at 1173 K. The permeation flux was measured as a function of specimen temperature and incident ion flux. Surface analysis of specimen was also carried out after the permeation experiment. Permeation was observed only with the annealed specimen and no significant permeation was observed with unannealed specimen under the present experimental condition (maximum temperature: 685 K, detection limit: 1x10{sup 13} D atoms/m{sup 2}s). It could be attributed that the intrinsic lattice defects, which act as diffusion preventing site, decreased with the specimen annealing. Based on the result of steady and transient permeation behavior and surface analysis, it was estimated that the deuterium permeation implanted into annealed beryllium was controlled by surface recombination due to the oxide layer on the surface of the permeated side. (author)

  5. Quantitative characterization of chitosan in the skin by Fourier-transform infrared spectroscopic imaging and ninhydrin assay: application in transdermal sciences.

    Science.gov (United States)

    Nawaz, A; Wong, T W

    2016-07-01

    The chitosan has been used as the primary excipient in transdermal particulate dosage form design. Its distribution pattern across the epidermis and dermis is not easily accessible through chemical assay and limited to radiolabelled molecules via quantitative autoradiography. This study explored Fourier-transform infrared spectroscopy imaging technique with built-in microscope as the means to examine chitosan molecular distribution over epidermis and dermis with the aid of histology operation. Fourier-transform infrared spectroscopy skin imaging was conducted using chitosan of varying molecular weights, deacetylation degrees, particle sizes and zeta potentials, obtained via microwave ligation of polymer chains at solution state. Both skin permeation and retention characteristics of chitosan increased with the use of smaller chitosan molecules with reduced acetyl content and size, and increased positive charge density. The ratio of epidermal to dermal chitosan content decreased with the use of these chitosan molecules as their accumulation in dermis (3.90% to 18.22%) was raised to a greater extent than epidermis (0.62% to 1.92%). A larger dermal chitosan accumulation nonetheless did not promote the transdermal polymer passage more than the epidermal chitosan. A small increase in epidermal chitosan content apparently could fluidize the stratum corneum and was more essential to dictate molecular permeation into dermis and systemic circulation. The histology technique aided Fourier-transform infrared spectroscopy imaging approach introduces a new dimension to the mechanistic aspect of chitosan in transdermal delivery. © 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.

  6. Hydrogen permeation through metallic foils

    International Nuclear Information System (INIS)

    Bernardi, M.I.B.; Rodrigues, J.A.

    1987-01-01

    The process of electrolytic permeation of hydrogen through metallic foils is studied. A double electrolytic cell, in glass, in which the two compartments of reaction are separated by a metallic foil to be studied, was built. As direct result, the hydrogen diffusion coefficient in the metal is obtained. The hydrogen diffusion coefficients in the palladium and, in austenitic stainless steels 304 and 304 L, used in the Angra-1 reactor, were obtained. Samples of stainless steels with and without welding, were used. (Author) [pt

  7. A multicenter, open-label, long-term safety and tolerability study of DFN-02, an intranasal spray of sumatriptan 10 mg plus permeation enhancer DDM, for the acute treatment of episodic migraine.

    Science.gov (United States)

    Munjal, Sagar; Brand-Schieber, Elimor; Allenby, Kent; Spierings, Egilius L H; Cady, Roger K; Rapoport, Alan M

    2017-12-01

    DFN-02 is a novel intranasal spray formulation composed of sumatriptan 10 mg and a permeation-enhancing excipient comprised of 0.2% 1-O-n-Dodecyl-β-D-Maltopyranoside (DDM). This composition of DFN-02 allows sumatriptan to be rapidly absorbed into the systemic circulation and exhibit pharmacokinetics comparable to subcutaneously administered sumatriptan. Rapid rate of absorption is suggested to be important for optimal efficacy. The objective of this study was to evaluate the safety and tolerability of DFN-02 (10 mg) in the acute treatment of episodic migraine with and without aura over a 6-month period based on the incidence of treatment-emergent adverse events and the evaluation of results of clinical laboratory tests, vital signs, physical examination, and electrocardiograms. This was a multi-center, open-label, repeat-dose safety study in adults with episodic migraine with and without aura. Subjects diagnosed with migraine with or without aura according to the criteria set forth in the International Classification of Headache Disorders, 2nd edition, who experienced 2 to 6 attacks per month with fewer than 15 headache days per month and at least 48 headache-free hours between attacks, used DFN-02 to treat their migraine attacks acutely over the course of 6 months. A total of 173 subjects was enrolled, 167 (96.5%) subjects used at least 1 dose of study medication and were evaluable for safety, and 134 (77.5%) subjects completed the 6-month study. A total of 2211 migraine attacks was reported, and 3292 doses of DFN-02 were administered; mean per subject monthly use of DFN-02 was 3.6 doses. Adverse events were those expected for triptans, as well as for nasally administered compounds. No new safety signals emerged. Dysgeusia and application site pain were the most commonly reported treatment-emergent adverse events over 6 months (21% and 30.5%, respectively). Most of the treatment-emergent adverse events were mild. There were 5 serious adverse events, all

  8. 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

  9. 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

  10. Nanoscaffold matrices for size-controlled, pulsatile transdermal testosterone delivery: nanosize effects on the time dimension

    International Nuclear Information System (INIS)

    Malik, Ritu; Misra, Amit; Tondwal, Shailesh; Venkatesh, K S

    2008-01-01

    Pulsatile transdermal testosterone (T) has applications in hormone supplementation and male contraception. Pulsatile T delivery was achieved by assembling crystalline and nanoparticulate T in nucleation-inhibiting polymer matrices of controlled porosity. Different interference patterns observed from various polymeric films containing T were due to the various particle sizes of T present in the polymer matrices. Scanning electron microscopy was used to determine the size and shape of T crystals. Skin-adherent films containing T nanoparticles of any size between 10-500 nm could be prepared using pharmaceutically acceptable vinylic polymers. Drug release and skin permeation profiles were studied. The dissolution-diffusion behavior of nanoparticles differed from crystalline and molecular states. Nanosize may thus be used to engineer chronopharmacologically relevant drug delivery.

  11. Nanoscaffold matrices for size-controlled, pulsatile transdermal testosterone delivery: nanosize effects on the time dimension

    Science.gov (United States)

    Malik, Ritu; Tondwal, Shailesh; Venkatesh, K. S.; Misra, Amit

    2008-10-01

    Pulsatile transdermal testosterone (T) has applications in hormone supplementation and male contraception. Pulsatile T delivery was achieved by assembling crystalline and nanoparticulate T in nucleation-inhibiting polymer matrices of controlled porosity. Different interference patterns observed from various polymeric films containing T were due to the various particle sizes of T present in the polymer matrices. Scanning electron microscopy was used to determine the size and shape of T crystals. Skin-adherent films containing T nanoparticles of any size between 10-500 nm could be prepared using pharmaceutically acceptable vinylic polymers. Drug release and skin permeation profiles were studied. The dissolution-diffusion behavior of nanoparticles differed from crystalline and molecular states. Nanosize may thus be used to engineer chronopharmacologically relevant drug delivery.

  12. 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.

  13. In vitro and in vivo transdermal delivery capacity of quantum dots through mouse skin

    International Nuclear Information System (INIS)

    Chu Maoquan; Wu Qiang; Wang Jiaxu; Hou Shengke; Miao Yi; Peng Jinliang; Sun Ye

    2007-01-01

    CdTe quantum dots (QDs) with red fluorescence have been used to study their transdermal delivery capacity through mouse skin. The results showed that the QDs could permeate through skin, either separated from or still attached to live mice. Although the fluorescence emitted by the QDs could only be found in the skin and muscle cells located under the mouse skins coated with QDs, an inductive coupled plasma atomic emission spectrometry (ICP-AES) study indicated that the main organs, such as the heart, liver, spleen, lung, kidney and brain, all contained a significant quantity of Cd atoms. Moreover, these Cd atoms could remain in vivo for at least one week. As a control, the concentration of Cd atoms in normal mice not coated with QDs was very low

  14. Tritium permeation in fusion reactors: INTOR

    International Nuclear Information System (INIS)

    Baskes, M.I.; Bauer, W.; Kerst, R.A.; Swansiger, W.A.; Wilson, K.L.

    1981-12-01

    Tritium permeation through the first wall of advanced fusion reactors is examined. A fraction of the D-T which bombards the first wall as charge exchange neutral particles will permeate through the first wall and enter the coolant. Calculations of the steady state permeation rate for the US INTOR Tokamak design result in values of less than or equal to 0.002 grams of tritium per day under the most favorable conditions. For unfavorable surface conditions the rate is greater than or equal to 0.1 g/day. The magnitude of these permeation rates is critically dependent on the temperatures and surface conditions of the wall. The introduction of permeation barriers at the wall-coolant interface can significantly reduce permeation rates and hence may be desirable for reactor applications

  15. 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.

  16. 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.

  17. Water permeation through anion exchange membranes

    Science.gov (United States)

    Luo, Xiaoyan; Wright, Andrew; Weissbach, Thomas; Holdcroft, Steven

    2018-01-01

    An understanding of water permeation through solid polymer electrolyte (SPE) membranes is crucial to offset the unbalanced water activity within SPE fuel cells. We examine water permeation through an emerging class of anion exchange membranes, hexamethyl-p-terphenyl poly (dimethylbenzimidazolium) (HMT-PMBI), and compare it against series of membrane thickness for a commercial anion exchange membrane (AEM), Fumapem® FAA-3, and a series of proton exchange membranes, Nafion®. The HMT-PMBI membrane is found to possess higher water permeabilities than Fumapem® FAA-3 and comparable permeability than Nafion (H+). By measuring water permeation through membranes of different thicknesses, we are able to decouple, for the first time, internal and interfacial water permeation resistances through anion exchange membranes. Permeation resistances on liquid/membrane interface is found to be negligible compared to that for vapor/membrane for both series of AEMs. Correspondingly, the resistance of liquid water permeation is found to be one order of magnitude smaller compared to that of vapor water permeation. HMT-PMBI possesses larger effective internal water permeation coefficient than both Fumapem® FAA-3 and Nafion® membranes (60 and 18% larger, respectively). In contrast, the effective interfacial permeation coefficient of HMT-PMBI is found to be similar to Fumapem® (±5%) but smaller than Nafion®(H+) (by 14%).

  18. 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...

  19. Mechanisms of oxygen permeation through plastic films and barrier coatings

    Science.gov (United States)

    Wilski, Stefan; Wipperfürth, Jens; Jaritz, Montgomery; Kirchheim, Dennis; Mitschker, Felix; Awakowicz, Peter; Dahlmann, Rainer; Hopmann, Christian

    2017-10-01

    Oxygen and water vapour permeation through plastic films in food packaging or other applications with high demands on permeation are prevented by inorganic barrier films. Most of the permeation occurs through small defects (visualized by etching with reactive oxygen in a capacitively coupled plasma and subsequent SEM imaging. In this work, defects in SiO x -coatings deposited by plasma-enhanced chemical vapour deposition on polyethylene terephthalate (PET) are investigated and the mass transport through the polymer is simulated in a 3D approach. Calculations of single defects showed that there is no linear correlation between the defect area and the resulting permeability. The influence of adjacent defects in different distances was observed and led to flow reduction functions depending on the defect spacing and defect area. A critical defect spacing where no interaction between defects occurs was found and compared to other findings. According to the superposition principle, the permeability of single defects was added up and compared to experimentally determined oxygen permeation. The results showed the same trend of decreasing permeability with decreasing defect densities.

  20. Mechanisms of oxygen permeation through plastic films and barrier coatings

    International Nuclear Information System (INIS)

    Wilski, Stefan; Wipperfürth, Jens; Jaritz, Montgomery; Kirchheim, Dennis; Dahlmann, Rainer; Hopmann, Christian; Mitschker, Felix; Awakowicz, Peter

    2017-01-01

    Oxygen and water vapour permeation through plastic films in food packaging or other applications with high demands on permeation are prevented by inorganic barrier films. Most of the permeation occurs through small defects (<3 µ m) in the barrier coating. The defects were visualized by etching with reactive oxygen in a capacitively coupled plasma and subsequent SEM imaging. In this work, defects in SiO x -coatings deposited by plasma-enhanced chemical vapour deposition on polyethylene terephthalate (PET) are investigated and the mass transport through the polymer is simulated in a 3D approach. Calculations of single defects showed that there is no linear correlation between the defect area and the resulting permeability. The influence of adjacent defects in different distances was observed and led to flow reduction functions depending on the defect spacing and defect area. A critical defect spacing where no interaction between defects occurs was found and compared to other findings. According to the superposition principle, the permeability of single defects was added up and compared to experimentally determined oxygen permeation. The results showed the same trend of decreasing permeability with decreasing defect densities. (paper)

  1. 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.

  2. Effect of pressure sensitive adhesive and vehicles on permeation of terbinafine across porcine hoof membrane.

    Science.gov (United States)

    Ahn, Tai Sang; Lee, Jung-Phil; Kim, Juhyun; Oh, Seaung Youl; Chun, Myung-Kwan; Choi, Hoo-Kyun

    2013-11-01

    The purpose of this study was to investigate characteristics of transungual drug delivery and the feasibility of developing a drug-in-adhesive formulation of terbinafine. The permeation of terbinafine from a PSA matrix across porcine hoof membrane was determined using a plate containing poloxamer gel. The permeation rate of terbinafine across hairless mouse skin was evaluated using a flow-through diffusion cell system. The permeation of terbinafine across the hoof membranes was the highest from the silicone adhesive matrix, followed by PIB, and most of the acrylic adhesives, SIS, and SBS. The rank order of permeation rate across mice skin was different from the rank order across porcine hooves. The amount of terbinafine permeated across the porcine hoof membranes poorly correlated with the amount of terbinafine remaining inside the hooves after 20 days, however, the ratio between rate of terbinafine partitioning into the hoof membrane and its rate of diffusion across the membrane was relatively constant within the same type of PSA. For influence of various vehicles in enhancing permeation of terbinafine across the hoof membrane, all vehicles except Labrasol(®) showed tendency to improve permeation rate. However, the enhancement ratio of a given vehicle differed from one adhesive to another with a moderate correlation between them. The infrared spectrum of the hoof treated with NMP, PPG 400 or PEG 200 indicated that the conformation of keratin changed from a non-helical to a helical structure.

  3. Implanted-tritium permeation experiments

    International Nuclear Information System (INIS)

    Longhurst, G.R.; Holland, D.F.; Casper, L.A.; Hsu, P.Y.; Miller, L.G.; Schmunk, R.E.; Watts, K.D.; Wilson, C.J.; Kershner, C.J.; Rogers, M.L.

    1982-04-01

    In fusion reactors, charge exchange neutral atoms of tritium coming from the plasma will be implanted into the first wall and other interior structures. EG and G Idaho is conducting two experiments to determine the magnitude of permeation into the coolant streams and the retention of tritium in those structures. One experiment uses an ion gun to implant deuterium. The ion gun will permit measurements to be made for a variety of implantation energies and fluxes. The second experiment utilizes a fission reactor to generate a tritium implantation flux by the 3 He(n,p) 3 H reaction. This experiment will simulate the fusion reactor radiation environment. We also plan to verify a supporting analytical code development program, in progress, by these experiments

  4. Practical experience of backwashing with SWRO permeate for UF fouling control

    KAUST Repository

    Li, Sheng; Heijman, Sebastiaan G J; Verberk, J. Q J C; Amy, Gary L.; Van Dijk, Johannis C.

    2013-01-01

    Effectiveness of seawater reverse osmosis (SWRO) permeate backwash on fouling control of seawater ultrafiltration was investigated at a pilot scale. A standard membrane module was used in this pilot to represent full-scale desalination plants. Results of the pilot show a good reproducibility. When the UF permeate was used for backwash, the frequency of chemically enhanced backwash (CEB) was around once per day. However, results of the pilot show that SWRO permeate backwashing could significantly reduce the CEB frequency. © 2013 Desalination Publications.

  5. Permeation Tests on Polypropylene Fiber Materials

    Science.gov (United States)

    2018-03-16

    Permeation Tests on Polypropylene Fiber Materials Brandy J. White Martin H. Moore Brian J. Melde Laboratory for the Study of Molecular Interfacial...ABSTRACT Permeation Tests on Polypropylene Fiber Materials Brandy J. White, Martin H. Moore, Brian J. Melde Center for Bio/Molecular Science

  6. 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

  7. 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...

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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...

  13. 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.

  14. A novel lipid nanoemulsion system for improved permeation of granisetron.

    Science.gov (United States)

    Doh, Hea-Jeong; Jung, Yunjin; Balakrishnan, Prabagar; Cho, Hyun-Jong; Kim, Dae-Duk

    2013-01-01

    A new lipid nanoemulsion (LNE) system containing granisetron (GRN) was developed and its in vitro permeation-enhancing effect was evaluated using Caco-2 cell monolayers. Particle size, polydispersity index (PI) and stability of the prepared GRN-loaded LNE systems were also characterized. The mean diameters of prepared LNEs were around 50 nm with PI<0.2. Developed LNEs were stable at 4°C in the dark place over a period of 12 weeks. In vitro drug dissolution and cytotoxicity studies of GRN-loaded LNEs were performed. GRN-loaded LNEs exhibited significantly higher drug dissolution than GRN suspension at pH 6.8 for 2h (P<0.05). In vitro permeation study in Caco-2 cell monolayers showed that the LNEs significantly enhanced the drug permeation compared to GRN powder. The in vivo toxicity study in the rat jejunum revealed that the prepared GRN-loaded LNE was as safe as the commercial formulation (Kytril). These results suggest that LNE could be used as a potential oral liquid formulation of GRN for anti-emetic treatment on the post-operative and chemotherapeutic patients. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. 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.

  16. Permeation of hydrogen through metal membranes

    International Nuclear Information System (INIS)

    Wienhold, P.; Rota, E.; Waelbroeck, F.; Winter, J.; Banno, Tatsuya.

    1986-08-01

    Experiments show that the permeant flux of hydrogen through a metal membrane at low driving pressures ( r is introduced into the model as a new material constant and the rate equations are given. After the description of the wall pump effect, a variety of different limiting cases are discussed for a symmetrical permeation membrane. This is modified to the asymmetric case and to the influence of particle implantation. The permeation number W turns out to be a dimensionless quantity which characterizes the permeation range and predicts the permeant flux in steady state. (orig.)

  17. Formulation and in Vitro, ex Vivo and in Vivo Evaluation of Elastic Liposomes for Transdermal Delivery of Ketorolac Tromethamine

    Directory of Open Access Journals (Sweden)

    Néstor Mendoza

    2011-12-01

    Full Text Available The objective of the current study was to formulate ketorolac tromethamine-loaded elastic liposomes and evaluate their in vitro drug release and their ex vivo and in vivo transdermal delivery. Ketorolac tromethamine (KT, which is a potent analgesic, was formulated in elastic liposomes using Tween 80 as an edge activator. The elastic vesicles were prepared by film hydration after optimizing the sonication time and number of extrusions. The vesicles exhibited an entrapment efficiency of 73 ± 11%, vesicle size of 127.8 ± 3.4 nm and a zeta potential of −12 mV. In vitro drug release was analyzed from liposomes and an aqueous solution, using Franz diffusion cells and a cellophane dialysis membrane with molecular weight cut-off of 8000 Da. Ex vivo permeation of KT across pig ear skin was studied using a Franz diffusion cell, with phosphate buffer (pH 7.4 at 32 °C as receptor solution. An in vivo drug permeation study was conducted on healthy human volunteers using a tape-stripping technique. The in vitro results showed (i a delayed release when KT was included in elastic liposomes, compared to an aqueous solution of the drug; (ii a flux of 0.278 mg/cm2h and a lag time of about 10 h for ex vivo permeation studies, which may indicate that KT remains in the skin (with the possibility of exerting a local effect before reaching the receptor medium; (iii a good correlation between the total amount permeated, the penetration distance (both determined by tape stripping and transepidermal water loss (TEWL measured during the in vivo permeation studies. Elastic liposomes have the potential to transport the drug through the skin, keep their size and drug charge, and release the drug into deep skin layers. Therefore, elastic liposomes hold promise for the effective topical delivery of KT.

  18. Effect of microemulsions on transdermal delivery of citalopram: optimization studies using mixture design and response surface methodology

    Directory of Open Access Journals (Sweden)

    Huang CT

    2013-06-01

    Full Text Available Chi-Te Huang,1 Ming-Jun Tsai,2,3 Yu-Hsuan Lin,1 Yaw-Sya Fu,4 Yaw-Bin Huang,5 Yi-Hung Tsai,5 Pao-Chu Wu11School of Pharmacy, Kaohsiung Medical University, Kaohsiung City, 2Department of Neurology, China Medical University Hospital, Taichung, 3School of Medicine, Medical College, China Medical University, Taichung, 4Faculty of Biomedical Science and Environmental Biology, 5Graduate Institute of Clinical Pharmacy, Kaohsiung Medical University, Kaohsiung City, Taiwan, Republic of ChinaAbstract: The aim of this study was to evaluate the potential of microemulsions as a drug vehicle for transdermal delivery of citalopram. A computerized statistical technique of response surface methodology with mixture design was used to investigate and optimize the influence of the formulation compositions including a mixture of Brij 30/Brij 35 surfactants (at a ratio of 4:1, 20%–30%, isopropyl alcohol (20%–30%, and distilled water (40%–50% on the properties of the drug-loaded microemulsions, including permeation rate (flux and lag time. When microemulsions were used as a vehicle, the drug permeation rate increased significantly and the lag time shortened significantly when compared with the aqueous control of 40% isopropyl alcohol solution containing 3% citalopram, demonstrating that microemulsions are a promising vehicle for transdermal application. With regard to the pharmacokinetic parameters of citalopram, the flux required for the transdermal delivery system was about 1280 µg per hour. The microemulsions loaded with citalopram 3% and 10% showed respective flux rates of 179.6 µg/cm2 and 513.8 µg/cm2 per hour, indicating that the study formulation could provide effective therapeutic concentrations over a practical application area. The animal study showed that the optimized formulation (F15 containing 3% citalopram with an application area of 3.46 cm2 is able to reach a minimum effective therapeutic concentration with no erythematous reaction

  19. Permeation of deuterium implanted into vanadium alloys

    International Nuclear Information System (INIS)

    Anderl, R.A.; Longhurst, G.R.; Struttmann, D.A.

    1986-05-01

    Permeation of deuterium through the vanadium alloy, V-15Cr-5Ti, was investigated using 3-keV, D 3 + ion beams from a small accelerator. The experiments consisted of measurements of the deuterium reemission and permeation rates as a function of implantation fluence for 0.5-mm thick specimens heated to tempertures from 623 to 823 0 K. Implantation-side surface characterization was made by simultaneous measurements of sputtered ions with a secondary ion mass spectrometer (SIMS). Analyses of these measurements indicate that for the experimental conditions used, the steady-state deuterium permeation flux in V-15Cr-5Ti is approximately 18% of the implantation flux. This corresponds to approximately 1000 times that seen in the ferritic steel, HT-9, under comparable conditions. Measurement of deuterium diffusivity in V-15Cr-5Ti using permeation break-through times indicates D = 1.4 x 10 -8 exp(-.11 eV/kT) (m 2 /s)

  20. Proton permeation of lipid bilayers.

    Science.gov (United States)

    Deamer, D W

    1987-10-01

    Proton permeation of the lipid bilayer barrier has two unique features. First, permeability coefficients measured at neutral pH ranges are six to seven orders of magnitude greater than expected from knowledge of other monovalent cations. Second, proton conductance across planar lipid bilayers varies at most by a factor of 10 when pH is varied from near 1 to near 11. Two mechanisms have been proposed to account for this anomalous behavior: proton conductance related to contaminants of lipid bilayers, and proton translocation along transient hydrogen-bonded chains (tHBC) of associated water molecules in the membrane. The weight of evidence suggests that trace contaminants may contribute to proton conductance across planar lipid membranes at certain pH ranges, but cannot account for the anomalous proton flux in liposome systems. Two new results will be reported here which were designed to test the tHBC model. These include measurements of relative proton/potassium permeability in the gramicidin channel, and plots of proton flux against the magnitude of pH gradients. (1) The relative permeabilities of protons and potassium through the gramicidin channel, which contains a single strand of hydrogen-bonded water molecules, were found to differ by at least four orders of magnitude when measured at neutral pH ranges. This result demonstrates that a hydrogen-bonded chain of water molecules can provide substantial discrimination between protons and other cations. It was also possible to calculate that if approximately 7% of bilayer water was present in a transient configuration similar to that of the gramicidin channel, it could account for the measured proton flux. (2) The plot of proton conductance against pH gradient across liposome membranes was superlinear, a result that is consistent with one of three alternative tHBC models for proton conductance described by Nagle elsewhere in this volume.

  1. 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

  2. Ex vivo and in vivo evaluation of microemulsion based transdermal delivery of E. coli specific T4 bacteriophage: A rationale approach to treat bacterial infection.

    Science.gov (United States)

    Rastogi, Vaibhav; Yadav, Pragya; Verma, Anurag; Pandit, Jayanta K

    2017-09-30

    This study is focused on the development and evaluation of transdermal delivery of E. coli-specific T4 bacteriophages both ex-vivo and in-vivo using microemulsion as delivery carrier in eradicating the infection caused by E. coli. Microemulsions were prepared by mixing selected oil, surfactants and aqueous phase containing bacteriophages. The formulations were subjected to physicochemical characterization, ex-vivo and in-vivo permeation, stability studies, histological and immunofluorescence examination. The colloidal system exhibits a uniform size distribution, of finite size (150-320nm). Transmission electron microscopy revealed the encapsulation of bacteriophage in the aqueous globule. Ex-vivo permeation across skin was successfully achieved as 6×10 6 PFU/mL and 6.7×10 6 PFU/mL of T4 permeated from ME 6% and 10%, respectively. ME 6% was found to be thermodynamically stable and in-vivo permeation resulted in 5.49×10 5 PFU/mL of bacteriophages in the blood of the E. coli challenged rats, while 2.48×10 5 PFU/mL was detected in germ free rats, at the end of the study. Infected rats that were treated with bacteriophage were survived while significant mortality was observed in others. Histological and IL-6 immunofluorescence examination of the tissues revealed the efficacy/safety of the therapy. The microemulsion-based transdermal delivery of bacteriophage could be a promising approach to treat the infections caused by antibiotic-resistant bacteria. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Interactions between oxygen permeation and homogeneous-phase fuel conversion on the sweep side of an ion transport membrane

    KAUST Repository

    Hong, Jongsup; Kirchen, Patrick; Ghoniem, Ahmed F.

    2013-01-01

    concentration enhances oxygen permeation substantially. This is accomplished through promoting oxidation reactions (oxygen consumption) and the transport of the products and reaction heat towards the membrane, which lowers the oxygen concentration and increases

  4. Investigating the sonophoresis effect on the permeation of diclofenac sodium using 3D skin equivalent.

    Science.gov (United States)

    Aldwaikat, Mai; Alarjah, Mohammed

    2015-01-01

    Ultrasound temporally increases skin permeability by altering stratum corneum SC function (sonophoresis). The objective of this study was to evaluate the effect of variable ultrasound conditions on the permeation of diclofenac sodium DS with range of physicochemical properties through EpiDerm™. Permeation studies were carried out in vitro using Franz diffusion cell. HPLC method was used for the determination of the concentration of diclofenac sodium in receiving compartment. Parameters like ultrasound frequency, application time, amplitude, and mode of sonication and distance of ultrasound horn from skin were investigated, and the conditions where the maximum enhancement rate obtained were determined. Application of ultrasound enhanced permeation of diclofenac sodium across EpiDerm™ by fivefolds. The most effective enhancing parameters were power sonication of 20kHz frequency, 20% amplitude at continuous mode for 5min. Copyright © 2014. Published by Elsevier B.V.

  5. Evaluation of whey, milk, and delactosed permeates as salt substitutes.

    Science.gov (United States)

    Smith, S T; Metzger, L; Drake, M A

    2016-11-01

    Whey and milk permeates are by-products of high-protein dairy powder manufacture. Previous work has shown that these permeates contribute to salty taste without contributing significantly to sodium content. The objective of this study was to explore the sensory characteristics and compositional analysis of permeates from different milk and whey streams and a low-sodium product application made from them. Skim milk, Cheddar, cottage, and Mozzarella cheese whey permeates were manufactured in triplicate, and delactosed whey permeate was obtained in triplicate. Composition (protein, fat, solids, minerals) was conducted on permeates. Organic acid composition was determined using HPLC. Volatile compounds were extracted from permeates by solid phase microextraction with gas chromatography-mass spectrometry. A trained sensory panel documented sensory attributes of permeates and cream of broccoli soups with and without salt or permeates followed by consumer acceptance testing (n=105) on the soups. Cottage cheese whey permeate contained a higher lactic acid content than other permeates, which has been shown to contribute to a higher salty taste. Cottage cheese whey permeate also contained potato or brothy and caramel flavors and sour and salty tastes, whereas delactosed whey permeate had high intensities of cardboard and beefy or brothy flavors and salty taste. Milk, Cheddar, and Mozzarella cheese whey permeates were characterized by sweet taste and cooked milky flavor. Permeates with higher cardboard flavor had higher levels of aldehydes. All permeates contributed to salty taste and to salty taste perception in soups; although the control soup with added salt was perceived as saltier and was preferred by consumers over permeate soups. Soup with permeate from cottage cheese was the least liked of all soups, likely due to its sour taste. All other permeate soups scored at parity for liking. These results demonstrate the potential for milk, whey, and delactosed permeates from

  6. Tritium permeation barriers for fusion technology

    International Nuclear Information System (INIS)

    Perujo, A.; Forcey, K.

    1994-01-01

    An important issue concerning the safety, feasibility and fueling (i.e., tritium breeding ratio and recovery from the breeding blanket) of a fusion reactor is the possible tritium leakages through the structural materials and in particular through those operating at high temperatures. The control of tritium permeation could be a critical factor in determining the viability of a future fusion power reactor. The formation of tritium permeation barriers to prevent the loss of tritium to the coolant by diffusion though the structural material seems to be the most practical method to minimize such losses. Many authors have discussed the formation of permeation barriers to reduce the leakage of hydrogen isotopes through proposed first wall and structural materials. In general, there are two routes for the formation of such a barrier, namely: the growth of oxide layers (e.g., Cr 2 O 3 , Al 2 O 3 , etc.) or the application of surface coatings. Non-metals are the most promising materials from the point of view of the formation of permeation barriers. Oxides such as Al 2 O 3 or Cr 2 O 3 or carbides such as SiC or TiC have been proposed. Amongst the metals only tungsten or gold are sufficiently less permeable than steel to warrant investigation as candidate materials for permeation barriers. It is of course possible to grow oxide layers on steel directly by heating in the atmosphere or under a variety of conditions (first route above). The direct oxidizing is normally done in an environment of open-quotes wet hydrogenclose quotes to promote the growth of chromia on, for example, nickel steels or ternary oxides on 316L to prevent corrosion. The application of surface layers (second route above), offers a greater range of materials for the formation of permeation barriers. In addition to reducing permeation, such layers should be adhesive, resistant to attack by corrosive breeder materials and should not crack during thermal cycling

  7. 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

  8. A comparison of implantation-driven permeation characteristics of fusion reactor structural materials

    Science.gov (United States)

    Longhurst, G. R.; Anderl, R. A.; Struttmann, D. A.

    1986-11-01

    Implantation-driven permeation experiments have been conducted on samples of the ferritic steel HT-9, the austenitic Primary Candidate Alloy (PCA) and the vanadium alloy V-15Cr-5Ti using D 3+ ions under conditions that simulate charge-exchange neutral loading on a fusion reactor first wall. The steels all exhibited an initially intense permeation "spike" followed by an exponential decrease to low steady-state values. That spike was not evident in the V-15Cr-5Ti experiments. Steady-state permeation was highest in the vanadium alloy and lowest in the austenitic steel. Though permeation rates in the HT-9 were lower than those in V-15Cr-5Ti, permeation transients were much faster in HT-9 than in other materials tested. Sputtering of the steel surface resulted in enhanced reemission, whereas in the vanadium tests, recombination and diffusivity both appeared to diminish as the deuterium concentration rose. We conclude that for conditions comparable to those of these experiments, tritium retention and permeation loss in first wall structures made of steels will be less than in structures made of V-15Cr-5Ti.

  9. Comparison on implantation-driven permeation characteristics of fusion reactor structural materials

    Energy Technology Data Exchange (ETDEWEB)

    Longhurst, G.R.; Anderl, R.A.; Struttmann, D.A. (Idaho National Engineering Lab., Idaho Falls)

    Implantation-driven permeation experiments have been conducted on samples of the ferritic steel HT-9, the austenitic Primary Candidate Alloy (PCA) and the vanadium alloy V-15Cr-5Ti using D{sub 3}{sup +} ions under conditions that simulate charge-exchange neutral loading on a fusion reactor first wall. The steels all exhibited an initially intense permeation spike followed by an exponential decrease to low steady-state values. That spike was not evident in the V-15Cr-5Ti experiments. Steady-state permeation was highest in the vanadium alloy and lowest in the austenitic steel. Though permeation rates in the HT-9 were lower than those in V-15Cr-5Ti, permeation transients were much faster in HT-9 than in other materials tested. Sputtering of the steel surface resulted in enhanced reemission, whereas in the vanadium tests, recombination and diffusivity both appeared to diminish as the deuterium concentration rose. We conclude that for conditions comparable to those of these experiments, tritium retention and permeation loss in first wall structures made of steels will be less than in structures made of V-15Cr-5Ti.

  10. 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

  11. ATR-FTIR and Raman spectroscopic investigation of the electroporation-mediated transdermal delivery of a nanocarrier system containing an antitumour drug.

    Science.gov (United States)

    Balázs, Boglárka; Sipos, Péter; Danciu, Corina; Avram, Stefana; Soica, Codruta; Dehelean, Cristina; Varju, Gábor; Erős, Gábor; Budai-Szűcs, Mária; Berkó, Szilvia; Csányi, Erzsébet

    2016-01-01

    The aim of the present work was the optimization of the transdermal delivery of a lyotropic liquid crystal genistein-based formulation (LLC-GEN). LLC was chosen as medium in view of the poor solubility of GEN in water. Membrane diffusion and penetration studies were carried out with a Franz diffusion cell, through a synthetic membrane in vitro, a chick chorioallantoic membrane ex ovo, and ex vivo excised human epidermis. Thereafter, LLC-GEN was combined with electroporation (EP) to enhance the transdermal drug delivery. The synergistic effect of EP was verified by in vivo ATR-FTIR and ex vivo Raman spectroscopy on hairless mouse skin.

  12. Feasibility of permeation grouting for constructing subsurface barriers

    International Nuclear Information System (INIS)

    Dwyer, B.P.

    1994-03-01

    The technical feasibility of emplacing a barrier beneath a waste site using directionally drilled boreholes and permeation grouting was investigated. The benefits of this emplacement system are: (1) Directionally drilled boreholes provide access beneath a waste site without disturbing the waste; (2) interim containment of contaminants allows time for the development of remediation options; (3) in the interim, the volume of waste remains fixed; (4) barriers may enhance the effectiveness of in situ remediation actions; and (5) barrier systems may provide permanent waste containment

  13. 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.

  14. 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- ...

  15. 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

  16. 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.

  17. Permeation barrier for lightweight liquid hydrogen tanks

    Energy Technology Data Exchange (ETDEWEB)

    Schultheiss, D.

    2007-04-16

    For the future usage of hydrogen as an automotive fuel, its on-board storage is crucial. One approach is the storage of liquid hydrogen (LH2, 20 K) in double-walled, vacuum insulated tanks. The introduction of carbon fiber reinforced plastics (CFRP) as structural material enables a high potential of reducing the weight in comparison to the state-of-the-art stainless steel tanks. The generally high permeability of hydrogen through plastics, however, can lead to long-term degradation of the insulating vacuum. The derived objective of this dissertation was to find and apply an adequate permeation barrier (liner) on CFRP. The investigated liners were either foils adhered on CFRP specimens or coatings deposited on CFRP specimens. The coatings were produced by means of thermal spraying, metal plating or physical vapor deposition (PVD). The materials of the liners included Al, Au, Cu, Ni and Sn as well as stainless steel and diamond-like carbon. The produced liners were tested for their permeation behavior, thermal shock resistance and adherence to the CFRP substrate. Additionally, SEM micrographs were used to characterize and qualify the liners. The foils, although being a good permeation barrier, adhered weakly to the substrate. Furthermore, leak-free joining of foil segments is a challenge still to be solved. The metal plating liners exhibited the best properties. For instance, no permeation could be detected through a 50 {mu}m thick Cu coating within the accuracy of the measuring apparatus. This corresponds to a reduction of the permeation gas flow by more than factor 7400 compared to uncoated CFRP. In addition, the metal platings revealed a high adherence and thermal shock resistance. The coatings produced by means of thermal spraying and PVD did not show a sufficient permeation barrier effect. After having investigated the specimens, a 170 liter CFRP tank was fully coated with 50 {mu}m Cu by means of metal plating. (orig.)

  18. 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.

  19. Permeation of Comite through protective gloves.

    Science.gov (United States)

    Zainal, Hanaa; Que Hee, Shane S

    2006-09-01

    The goal of the study was to assess how protective disposable (Safeskin) and chemical protective (Sol-Vex) nitrile gloves were against Comite emulsifiable concentrate formulation containing propargite (PROP) as active pesticidal ingredient, because there were no explicit recommendations for the gloves that should be worn for hand protection. The glove material was exposed in ASTM-type I-PTC-600 permeation cells at 30.0+/-0.5 degrees C, and gas chromatography-mass spectrometry used for PROP analysis. Aqueous solutions of Comite at 40.4 mg/mL permeated both Safeskin and Sol-Vex nitrile by 8h. Safeskin showed a mean PROP mass permeated of 176+/-27 microg after 8h compared with a mean mass permeated for Sol-Vex of 3.17+/-4.08 microg. Thus, Sol-Vex was about 56 times more protective than Safeskin for an 8-h exposure. However, the kinetics of the permeation revealed that Safeskin can be worn for at least 200 min before disposal. When undiluted Comite challenged both types of nitrile, much faster permeation was observed. Safeskin gloves showed two steady state periods. The first had lag times (t(l)) values of about 1h, although normalized breakthrough times (t(b)) were gloves exposed continuously to undiluted Comite permeated above the normalized breakthrough threshold beyond 2.7h. A risk assessment revealed that the PROP skin permeation rate of 7.1 ng cm(-2)h(-1) was much slower than the first steady state Safeskin glove P(s) of 62,000 ng cm(-2)h(-1). Infrared analysis showed that the glove surfaces were not degraded by the Comite challenge. The chemically protective Sol-Vex gloves protected adequately against undiluted formulation for about 2.7h, whereas they provided protection for nearly 8h when the formulation was diluted with water to the highest concentration for field application. In contrast, the disposable Safeskin gloves did not protect at all for the undiluted formulation, but did for 200 min when the formulation was diluted with water to the highest

  20. In-site coatings to reduce H and Tr permeation

    International Nuclear Information System (INIS)

    Stoever, D.; Buchkremer, H.P.; Hecker, R.; Jonas, H.; Schaefer, J.; Zink, U.; Forsyth, N.; Thiele, W.

    1982-01-01

    The main goal of this project is the development of protective coatings to reduce or prevent Tr and H permeation through the heat exchanger walls of HTR components. The tasks of the project are: Measurement of the permeation inhibition efficiency of oxidic coatings on the high-temperature- resistant heat exchanger walls; establishing the parameters influencing permeation by variation of the process gas and steam parameters, temperature and mechanical stress; characterisation of coatings and correlation of coating characteristics with permeation measurements; investigation of permeation and corrosion mechanisms; quantitative description of H and Tr permeation by means of mathematical/physical models. (orig./IHOE) [de

  1. Combined use of bile acids and aminoacids to improve permeation properties of acyclovir.

    Science.gov (United States)

    Cirri, M; Maestrelli, F; Mennini, N; Mura, P

    2015-07-25

    The aim of this work was to develop a topical formulation with improved permeation properties of acyclovir. Ursodeoxycholic (UDC) and dehydrocholic (DHC) acids were tested as potential enhancers, alone or in combination with different aminoacids. Equimolar binary and ternary systems of acyclovir with cholic acids and basic, hydrophilic or hydrophobic aminoacids were prepared by co-grinding in a high vibrational micromill. Differential scanning calorimetry (DSC) was used to characterize the solid state of these systems, while their permeation properties were evaluated in vitro through a lipophilic artificial membrane. UDC was more than 2 times more effective than DHC in improving drug AUC and permeation rate. As for the ternary systems drug-UDC-aminoacid, only the combined use of l-lysine with UDC acid produced an evident synergistic effect in enhancing drug permeation properties, enabling an almost 3 and 8 times AUC increase compared to the binary UDC system or the pure drug, respectively. The best systems were selected for the development of topical cream formulations, adequately characterized and tested for in vitro drug permeation properties and stability on storage. The better performance revealed by acyclovir-UDC-l-lysine was mainly attributed to the formation of a more permeable activated system induced by the multicomponent co-grinding process. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. 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.

  3. 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.

  4. [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.

  5. Preparation of Silica Nanoparticles Loaded with Nootropics and Their In Vivo Permeation through Blood-Brain Barrier

    OpenAIRE

    Jampilek, Josef; Zaruba, Kamil; Oravec, Michal; Kunes, Martin; Babula, Petr; Ulbrich, Pavel; Brezaniova, Ingrid; Opatrilova, Radka; Triska, Jan; Suchy, Pavel

    2015-01-01

    The blood-brain barrier prevents the passage of many drugs that target the central nervous system. This paper presents the preparation and characterization of silica-based nanocarriers loaded with piracetam, pentoxifylline, and pyridoxine (drugs from the class of nootropics), which are designed to enhance the permeation of the drugs from the circulatory system through the blood-brain barrier. Their permeation was compared with non-nanoparticle drug substances (bulk materials) by means of an i...

  6. On the intrinsic moisture permeation rate of remote microwave plasma-deposited silicon nitride layers

    NARCIS (Netherlands)

    van Assche, F. J. H.; Unnikrishnan, S.; Michels, J. J.; van Mol, A. M. B.; van de Weijer, P.; M. C. M. van de Sanden,; Creatore, M.

    2014-01-01

    We report on a low substrate temperature (110 °C) remote microwave plasma-enhanced chemical vapor deposition (PECVD) process of silicon nitride barrier layers against moisture permeation for organic light emitting diodes (OLEDs) and other moisture sensitive devices such as organic

  7. Effect of Bile Salt on Permeation Characteristics of the Oral Mucosal ...

    African Journals Online (AJOL)

    An attempt was made to study the effect of bile salt [sodium glycocholate (SG)] as a permeation enhancer on mucoadhesive buccal patches of diltiazem hydrochloride (anti-anginal drug) using various polymers like hydroxypropyl methyl cellulosee (HPMC), Eudragit RL100, ethyl cellulose alone and in combination with PVP.

  8. LIBRETTO-3: modelling tritium extraction/permeation and evaluation of permeation barriers under irradiation

    International Nuclear Information System (INIS)

    Sedano, L.A.; Fuetterer, M.A.; Viola, R.; Dies, X.

    1996-01-01

    Permeation barriers are required in order to limit the size and cost of the detritiation plants for future fusion reactor blankets of the water-cooled Pb-17Li type. The LIBRETTO irradiations were performed to evaluate the efficiency of permeation barriers under high flux reactor (HFR) conditions. Tritium extraction and permeation characteristics from Pb-17Li under variable temperatures 553-723 K, H 2 doping (0-1 vol%) and purge gas flow rates 20-100 scc/min were tested in LIBRETTO-3. An external TiC coating, an internal (TiC+Al 2 O 3 ), both produced by chemical vapour deposition (CVD), and an internal Al 2 O 3 produced by pack cementation (PC) on AISI 316L steel were tested as permeation barriers. The release mechanisms, experimental uncertainties and method for permeation barriers qualification are presented. As a result permeation reduction factors (PRF) at 0.1 dpa of 17 and 34 were obtained for the CVD-Al 2 O 3 at 498 K and for the PC-Al 2 O 3 at 508 K, respectively. These values were confirmed by a residence time analysis and are higher than in a preliminary analysis. (orig.)

  9. 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.

  10. 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.

  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. Fabrication of a Ti porous microneedle array by metal injection molding for transdermal drug delivery.

    Science.gov (United States)

    Li, Jiyu; Liu, Bin; Zhou, Yingying; Chen, Zhipeng; Jiang, Lelun; Yuan, Wei; Liang, Liang

    2017-01-01

    Microneedle arrays (MA) have been extensively investigated in recent decades for transdermal drug delivery due to their pain-free delivery, minimal skin trauma, and reduced risk of infection. However, porous MA received relatively less attention due to their complex fabrication process and ease of fracturing. Here, we present a titanium porous microneedle array (TPMA) fabricated by modified metal injection molding (MIM) technology. The sintering process is simple and suitable for mass production. TPMA was sintered at a sintering temperature of 1250°C for 2 h. The porosity of TPMA was approximately 30.1% and its average pore diameter was about 1.3 μm. The elements distributed on the surface of TPMA were only Ti and O, which may guarantee the biocompatibility of TPMA. TPMA could easily penetrate the skin of a human forearm without fracture. TPMA could diffuse dry Rhodamine B stored in micropores into rabbit skin. The cumulative permeated flux of calcein across TPMA with punctured skin was 27 times greater than that across intact skin. Thus, TPMA can continually and efficiently deliver a liquid drug through open micropores in skin.

  13. Fabrication of a Ti porous microneedle array by metal injection molding for transdermal drug delivery.

    Directory of Open Access Journals (Sweden)

    Jiyu Li

    Full Text Available Microneedle arrays (MA have been extensively investigated in recent decades for transdermal drug delivery due to their pain-free delivery, minimal skin trauma, and reduced risk of infection. However, porous MA received relatively less attention due to their complex fabrication process and ease of fracturing. Here, we present a titanium porous microneedle array (TPMA fabricated by modified metal injection molding (MIM technology. The sintering process is simple and suitable for mass production. TPMA was sintered at a sintering temperature of 1250°C for 2 h. The porosity of TPMA was approximately 30.1% and its average pore diameter was about 1.3 μm. The elements distributed on the surface of TPMA were only Ti and O, which may guarantee the biocompatibility of TPMA. TPMA could easily penetrate the skin of a human forearm without fracture. TPMA could diffuse dry Rhodamine B stored in micropores into rabbit skin. The cumulative permeated flux of calcein across TPMA with punctured skin was 27 times greater than that across intact skin. Thus, TPMA can continually and efficiently deliver a liquid drug through open micropores in skin.

  14. Permeation of antigen protein-conjugated nanoparticles and live bacteria through microneedle-treated mouse skin

    Directory of Open Access Journals (Sweden)

    Kumar A

    2011-06-01

    Full Text Available Amit Kumar, Xinran Li, Michael A Sandoval, B Leticia Rodriguez, Brian R Sloat, Zhengrong CuiUniversity of Texas at Austin, College of Pharmacy, Pharmaceutics Division, Austin, TX, USABackground: The present study was designed to evaluate the extent to which pretreatment with microneedles can enhance skin permeation of nanoparticles in vitro and in vivo. Permeation of live bacteria, which are physically nanoparticles or microparticles, through mouse skin pretreated with microneedles was also studied to evaluate the potential risk of microbial infection.Methods and results: It was found that pretreatment of mouse skin with microneedles allowed permeation of solid lipid nanoparticles, size 230 nm, with ovalbumin conjugated on their surface. Transcutaneous immunization in a mouse skin area pretreated with microneedles with ovalbumin nanoparticles induced a stronger antiovalbumin antibody response than using ovalbumin alone. The dose of ovalbumin antigen determined whether microneedle-mediated transcutaneous immunization with ovalbumin nanoparticles induced a stronger immune response than subcutaneous injection of the same ovalbumin nanoparticles. Microneedle treatment permitted skin permeation of live Escherichia coli, but the extent of the permeation was not greater than that enabled by hypodermic injection.Conclusion: Transcutaneous immunization on a microneedle-treated skin area with antigens carried by nanoparticles can potentially induce a strong immune response, and the risk of bacterial infection associated with microneedle treatment is no greater than that with a hypodermic injection.Keywords: antibody responses, safety of microneedles, transepidermal water loss

  15. Permeation of antigen protein-conjugated nanoparticles and live bacteria through microneedle-treated mouse skin

    Science.gov (United States)

    Kumar, Amit; Li, Xinran; Sandoval, Michael A; Rodriguez, B Leticia; Sloat, Brian R; Cui, Zhengrong

    2011-01-01

    Background: The present study was designed to evaluate the extent to which pretreatment with microneedles can enhance skin permeation of nanoparticles in vitro and in vivo. Permeation of live bacteria, which are physically nanoparticles or microparticles, through mouse skin pretreated with microneedles was also studied to evaluate the potential risk of microbial infection. Methods and results: It was found that pretreatment of mouse skin with microneedles allowed permeation of solid lipid nanoparticles, size 230 nm, with ovalbumin conjugated on their surface. Transcutaneous immunization in a mouse skin area pretreated with microneedles with ovalbumin nanoparticles induced a stronger antiovalbumin antibody response than using ovalbumin alone. The dose of ovalbumin antigen determined whether microneedle-mediated transcutaneous immunization with ovalbumin nanoparticles induced a stronger immune response than subcutaneous injection of the same ovalbumin nanoparticles. Microneedle treatment permitted skin permeation of live Escherichia coli, but the extent of the permeation was not greater than that enabled by hypodermic injection. Conclusion: Transcutaneous immunization on a microneedle-treated skin area with antigens carried by nanoparticles can potentially induce a strong immune response, and the risk of bacterial infection associated with microneedle treatment is no greater than that with a hypodermic injection. PMID:21753877

  16. Comparison of implantation-driven permeation characteristics of fusion reactor structural materials

    International Nuclear Information System (INIS)

    Longhurst, G.R.; Anderl, R.A.; Struttmann, D.A.

    1986-01-01

    Implantation-driven permeation experiments have been conducted on samples of the ferritic steel HT-9, the austenitic Primary Candidate Alloy (PCA) and the vanadium alloy V-15Cr-5Ti using D 3 + ions under conditions that simulate charge-exchange neutral loading on a fusion reactor first wall. The steels all exhibited an initially intense permeation ''spike'' followed by an exponential decrease to low steady-state values. That spike was not evident in the V-15Cr-5Ti experiments. Steady-state permeation was highest in the vanadium alloy and lowest in the austenitic steel. Though permeation rates in the HT-9 were lower than those in V-15Cr-5Ti, permeation transients were much faster in HT-9 than in other materials tested. Ion-beam sputtering of the surface in the steel experiments resulted in enhanced remission at the front surface, whereas in the vanadium tests, recombination and diffusivity both appeared to diminish as the deuterium concentration rose. This may be due to a phase change in the material. We conclude that for conditions comparable to those of these experiments, tritium retention and loss in first wall structures made of steels will be less than in structures made of V-15Cr-5Ti

  17. Implications of recent implantation-driven permeation experiments for fusion reactor safety

    International Nuclear Information System (INIS)

    Longhurst, G.R.; Anderl, R.A.; Struttmann, D.A.

    1986-01-01

    Metal structures exposed to the plasma in tritium-burning fusion reactors will be subject to implantation-driven permeation (IDP) of tritium. Permeation rates for IDP in fusion structural materials are usually high because the tritium atoms enter the material without having to go through the dissociation and solution steps required of tritium-bearing gas molecules. These surface processes, which may be rate limiting in PDP, actually enhance permeation in IDP by inhibiting the return of tritium to the plasma side of the structure. Experiments have been conducted at the Idaho National Engineering Laboratory (INEL) to investigate the nature of IDP by simulating conditions experienced by structures exposed to the plasma. These experiments have shown that surface conditions are important to tritium permeation in materials endothermic to hydrogen solution such as austenitic and ferritic steels. In reactive metals such as vanadium, surface processes appear to totally control the permeation. The purpose of this paper is to review the progress of those experiments and to discuss the implications that the results have regarding the tritium-related safety concerns of fusion reactors

  18. Compound antimalarial ethosomal cataplasm: preparation, evaluation, and mechanism of penetration enhancement.

    Science.gov (United States)

    Shen, Shuo; Liu, Shu-Zhi; Zhang, Yu-Shi; Du, Mao-Bo; Liang, Ai-Hua; Song, Li-Hua; Ye, Zu-Guang

    2015-01-01

    Malaria is still a serious public health problem in some parts of the world. The problems of recurrence and drug resistance are increasingly more serious. Thus, it is necessary to develop a novel antimalarial agent. The objectives of this study were to construct a novel compound antimalarial transdermal nanosystem-ethosomal cataplasm, to investigate its characteristics and efficiency, and to systematically explore the penetration-enhancing mechanisms of ethosomal cataplasm. Artesunate-loaded ethosomes and febrifugine-loaded ethosomes were prepared, and their characteristics were evaluated. Drug-loaded ethosomes were incorporated in the matrix of cataplasm to form the compound antimalarial ethosomal cataplasm. With the help of ethosomal technology, the accumulated permeation quantity of artesunate significantly increased at 8 hours after administration, which was 1.57 times as much as that of conventional cataplasm. Soon after administration, the ethosomal cataplasm could make a large quantity of antimalarial drug quickly penetrate through skin, then the remaining drug in the ethosomal cataplasm could be steadily released. These characteristics of ethosomal cataplasm are favorable for antimalarial drugs to kill Plasmodium spp. quickly and prevent the resurgence of Plasmodium spp. As expected, the ethosomal cataplasm showed good antimalarial efficiency in this experiment. The negative conversion rates were 100% and the recurrence rates were 0% at all dosages. The mechanism of penetration enhancement of the ethosomal cataplasm was systematically explored using an optics microscope, polarization microscope, and transmission electron microscopy. The microstructure, ultrastructure, and birefringent structure in skin were observed. Data obtained in this study showed that the application of ethosomal technology to antimalarial cataplasm could improve the transdermal delivery of drug, enhance the efficacy, and facilitate practical application in clinic.

  19. RF plasma-driven hydrogen permeation through a biased iron membrane

    International Nuclear Information System (INIS)

    Banno, T.; Waelbroeck, F.; Winter, J.

    1984-01-01

    The steady-state RF plasma-driven hydrogen permeation through an electrically biased iron membrane has been investigated as a function of the bias potential Vsub(M) for membrane temperatures in the range of 150-400 0 C. Vsub(M) has been gradually increased positively from the floating potential of the membrane. The permeation flux decreases when Vsub(M) increases at low voltages: positive hydrogen ions are repelled. The membrane temperature does not influence this effect measurably. The permeation flux starts to increase when Vsub(M) is raised higher, i.e. when energetic electrons strike the surface. This phenomenon shows a pronounced temperature dependence - the enhancement is largest for the lowest temperatures. The effect is interpreted in terms of an electron-induced dissociation of hydrogen molecules on the membrane surface. (orig.)

  20. In vitro permeation studies of nanoemulsions containing ketoprofen as a model drug.

    Science.gov (United States)

    Kim, Beom Su; Won, Myoung; Lee, Kang Min; Kim, Cheo Sang

    2008-09-01

    We prepared a nanoemulsion system with benzyl alcohol/ ethanol/Solutol/smash(R) HS 15 /water. Ketoprofen was used as a model drug in this study. The nanoemulsions of this system evidenced a high degree of stability. The droplet diameter did not change over a period of at least 3 months. The nanoemulsion containing 4% benzyl alcohol evidenced a permeation rate higher than was observed with the 1% and 2% nanoemulsions. Also the nanoemulsion containing 1% Solutol(R) HS 15 provided a permeation rate higher than was seen with the 2% and 4% nanoemulsions. All ketoprofen-loaded nanoemulsions enhanced the in vitro permeation rate through mouse skins as compared to the control.

  1. Oral and transdermal drug delivery systems: role of lipid-based lyotropic liquid crystals.

    Science.gov (United States)

    Rajabalaya, Rajan; Musa, Muhammad Nuh; Kifli, Nurolaini; David, Sheba R

    2017-01-01

    Liquid crystal (LC) dosage forms, particularly those using lipid-based lyotropic LCs (LLCs), have generated considerable interest as potential drug delivery systems. LCs have the physical properties of liquids but retain some of the structural characteristics of crystalline solids. They are compatible with hydrophobic and hydrophilic compounds of many different classes and can protect even biologicals and nucleic acids from degradation. This review, focused on research conducted over the past 5 years, discusses the structural evaluation of LCs and their effects in drug formulations. The structural classification of LLCs into lamellar, hexagonal and micellar cubic phases is described. The structures of these phases are influenced by the addition of surfactants, which include a variety of nontoxic, biodegradable lipids; these also enhance drug solubility. LLC structure influences drug localization, particle size and viscosity, which, in turn, determine drug delivery properties. Through several specific examples, we describe the applications of LLCs in oral and topical drug formulations, the latter including transdermal and ocular delivery. In oral LLC formulations, micelle compositions and the resulting LLC structures can determine drug solubilization and stability as well as intestinal transport and absorption. Similarly, in topical LLC formulations, composition can influence whether the drug is retained in the skin or delivered transdermally. Owing to their enhancement of drug stability and promotion of controlled drug delivery, LLCs are becoming increasingly popular in pharmaceutical formulations.

  2. A novel non-imaging optics based Raman spectroscopy device for transdermal blood analyte measurement

    Directory of Open Access Journals (Sweden)

    Chae-Ryon Kong

    2011-09-01

    Full Text Available Due to its high chemical specificity, Raman spectroscopy has been considered to be a promising technique for non-invasive disease diagnosis. However, during Raman excitation, less than one out of a million photons undergo spontaneous Raman scattering and such weakness in Raman scattered light often require highly efficient collection of Raman scattered light for the analysis of biological tissues. We present a novel non-imaging optics based portable Raman spectroscopy instrument designed for enhanced light collection. While the instrument was demonstrated on transdermal blood glucose measurement, it can also be used for detection of other clinically relevant blood analytes such as creatinine, urea and cholesterol, as well as other tissue diagnosis applications. For enhanced light collection, a non-imaging optical element called compound hyperbolic concentrator (CHC converts the wide angular range of scattered photons (numerical aperture (NA of 1.0 from the tissue into a limited range of angles accommodated by the acceptance angles of the collection system (e.g., an optical fiber with NA of 0.22. A CHC enables collimation of scattered light directions to within extremely narrow range of angles while also maintaining practical physical dimensions. Such a design allows for the development of a very efficient and compact spectroscopy system for analyzing highly scattering biological tissues. Using the CHC-based portable Raman instrument in a clinical research setting, we demonstrate successful transdermal blood glucose predictions in human subjects undergoing oral glucose tolerance tests.

  3. 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.

  4. Fluvastatin as a micropore lifetime enhancer for sustained delivery across microneedle-treated skin.

    Science.gov (United States)

    Ghosh, Priyanka; Brogden, Nicole K; Stinchcomb, Audra L

    2014-02-01

    Microneedles (MNs), a physical skin permeation enhancement technique, facilitate drug delivery across the skin, thus enhancing the number of drugs that can be delivered transdermally in therapeutically relevant concentrations. The micropores created in the skin by MNs reseal because of normal healing processes of the skin, thus limiting the duration of the drug delivery window. Pore lifetime enhancement strategies can increase the effectiveness of MNs as a drug delivery mechanism by prolonging the delivery window. Fluvastatin (FLU), a HMGCoA reductase inhibitor, was used in this study to enhance the pore lifetime by inhibiting the synthesis of cholesterol, a major component of the stratum corneum lipids. The study showed that using FLU as a pretreatment it is possible to enhance the pore lifetime of MN-treated skin and thus allow for sustained drug delivery. The skin recovered within a 30-45-min time period following the removal of occlusion, and there was no significant irritation observed due to the treatment compared to the control sites. Thus, it can be concluded that localized skin treatment with FLU can be used to extend micropore lifetime and deliver drugs for up to 7 days across MN-treated skin. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  5. Fermentation of lactose to ethanol in cheese whey permeate and concentrated permeate by engineered Escherichia coli.

    Science.gov (United States)

    Pasotti, Lorenzo; Zucca, Susanna; Casanova, Michela; Micoli, Giuseppina; Cusella De Angelis, Maria Gabriella; Magni, Paolo

    2017-06-02

    Whey permeate is a lactose-rich effluent remaining after protein extraction from milk-resulting cheese whey, an abundant dairy waste. The lactose to ethanol fermentation can complete whey valorization chain by decreasing dairy waste polluting potential, due to its nutritional load, and producing a biofuel from renewable source at the same time. Wild type and engineered microorganisms have been proposed as fermentation biocatalysts. However, they present different drawbacks (e.g., nutritional supplements requirement, high transcriptional demand of recombinant genes, precise oxygen level, and substrate inhibition) which limit the industrial attractiveness of such conversion process. In this work, we aim to engineer a new bacterial biocatalyst, specific for dairy waste fermentation. We metabolically engineered eight Escherichia coli strains via a new expression plasmid with the pyruvate-to-ethanol conversion genes, and we carried out the selection of the best strain among the candidates, in terms of growth in permeate, lactose consumption and ethanol formation. We finally showed that the selected engineered microbe (W strain) is able to efficiently ferment permeate and concentrated permeate, without nutritional supplements, in pH-controlled bioreactor. In the conditions tested in this work, the selected biocatalyst could complete the fermentation of permeate and concentrated permeate in about 50 and 85 h on average, producing up to 17 and 40 g/l of ethanol, respectively. To our knowledge, this is the first report showing efficient ethanol production from the lactose contained in whey permeate with engineered E. coli. The selected strain is amenable to further metabolic optimization and represents an advance towards efficient biofuel production from industrial waste stream.

  6. Improved permeation barriers for tritiated waste packaging

    International Nuclear Information System (INIS)

    Vassallo, G.; Van Den Bergh, R.; Forcey, K.S.; Perujo, A.

    1994-01-01

    High-density polyethylene (HDPE) is extensively used as flexible bagging or packaging for soft tritiated waste in the tritium community because of its low permeability to the more radiotoxic form of tritium, i.e., tritiated water (HTO). However, HDPE does not represent a perfect barrier to HTO nor does it effectively hinder the permeation of elemental tritium, i.e, HT. This latter drawback is particularly important considering that the elemental form may readily convert to HTO outside of the waste package. The possible use of a multilayer film as packing material for the conditioning of tritiated waste is assessed, and its capability to hinder the permeation of elemental tritium is measured and compared with that of bare HDPE. The material investigated is readily available from the food industry. 5 refs., 1 tab

  7. Modeling and experiments on tritium permeation in fusion reactor blankets

    Science.gov (United States)

    Holland, D. F.; Longhurst, G. R.

    The determination of tritium loss from helium-cooled fusion breeding blankets are discussed. The issues are: (1) applicability of present models to permeation at low tritium pressures; (2) effectiveness of oxide layers in reducing permeation; (3) effectiveness of hydrogen addition as a means to lower tritium permeation; and (4) effectiveness of conversion to tritiated water and subsequent trapping to reduce permeation. Theoretical models applicable to these issues are discussed, and results of experiments in two areas are presented; permeation of mixtures of hydrogen isotopes and conversion to tritiated water.

  8. Modeling and experiments on tritium permeation in fusion reactor blankets

    International Nuclear Information System (INIS)

    Holland, D.F.; Longhurst, G.R.

    1985-01-01

    Issues are discussed that are critical in determining tritium loss from helium-cooled fusion breeding blankets. These issues are: (a) applicability of present models to permeation at low tritium pressures, (b) effectiveness of oxide layers in reducing permeation, (c) effectiveness of hydrogen addition as a means to lower tritium permeation, and (d) effectiveness of conversion to tritiated water and subsequent trapping as a means to reduce permeation. The paper discusses theoretical models applicable to these issues, and presents results of experiments in two areas: permeation of mixtures of hydrogen isotopes and conversion to tritiated water

  9. Enzymatic hydrolysis of lactose of whey permeate

    Directory of Open Access Journals (Sweden)

    Karina Nascimento de Almeida

    2015-09-01

    Full Text Available The whey permeate is the residual of the concentration process of the whey proteins by ultrafiltration method. It contains important nutrients such as lactose, minerals and some proteins and lipids. It is without an ending industrial waste that causes serious damage to the environment. For its full use the lactose must be hydrolyzed to enable its consumption by intolerant people. The enzymatic hydrolysis by lactase (β-galactosidase of Kluyveromyces lactis yeast is a safe method that does not compromise the integrity of other nutrients, enabling further use of the permeate as a raw material. This study aimed to perform tests of enzymatic hydrolysis of lactose in whey permeate formulations in a concentration of 0.2%, 0.7% and 1% at 30, 60 and 90 minutes with pH 6.3 medium and 37 °C. The reactions were monitored by high performance liquid chromatography which showed that the enzyme concentration of 0.7% at time 30 minutes formulations became safe for consumption by lactose intolerant people, according to minimum levels established by law.

  10. Flibe-D2 Permeation Experiment and Analysis

    International Nuclear Information System (INIS)

    Fukada, S.; Anderl, R.A.; Pawelko, R.J.; Smolik, G.R.; Schuetz, S.T.; O'Brien, J.E.; Nishimura, H.; Hatano, Y.; Terai, T.; Petti, D.A.; Sze, D.-K.; Tanaka, S.

    2003-01-01

    Experiment of D 2 permeation through Ni facing with purified Flibe is being carried out under the Japan-US joint research project (JUPITER-II). The experiment is proceeding in the following phases; (i) fabrication and assembly of a dual-probe permeation apparatus, (ii) a single-probe Ni/D 2 permeation experiment without Flibe, (iii) a dual-probe Ni/D 2 permeation experiment without Flibe, (iv) Flibe chemical purification by HF/H 2 gas bubbling, (v) physical purification by Flibe transport through a porous Ni filter, (vi) Ni/Flibe/D 2 permeation experiment, and (vii) Ni/Flibe/HT permeation experiment. The present paper describes results of the single and dual Ni/D 2 permeation experiments in detail

  11. 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.

  12. 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

  13. 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.

  14. Hydrogen permeation resistant heat pipe for bi-modal reactors. Final report, October 1, 1994--September 30, 1995

    International Nuclear Information System (INIS)

    North, M.T.; Anderson, W.G.

    1995-01-01

    The principal objective of this program was to demonstrate technology that will make a sodium heat pipe tolerant of hydrogen permeation for a bimodal space reactor application. Special focus was placed on techniques which enhance the permeation of hydrogen out of the heat pipe. Specific objectives include: define the detailed requirements for the bimodal reactor application; design and fabricate a prototype heat pipe tolerant of hydrogen permeation; and test the prototype heat pipe and demonstrate that hydrogen which permeates into the heat pipe is removed or reduced to acceptable levels. The results of the program were fully successful. Analyses were performed on two different heat pipe designs and an experimental heat pipe was fabricated and tested. A model of the experimental heat pipe was developed to predict the enhancement in the hydrogen permeation rate out of the heat pipe. A significant improvement in the rate at which hydrogen permeates out of a heat pipe was predicted for the use of the special condenser geometry developed here. Agreement between the model and the experimental results was qualitatively good. Inclusion of the additional effects of fluid flow in the heat pipe are recommended for future work

  15. 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.

  16. Role of the Na(+)/K(+)-ATPase beta-subunit in peptide-mediated transdermal drug delivery.

    Science.gov (United States)

    Wang, Changli; Ruan, Renquan; Zhang, Li; Zhang, Yunjiao; Zhou, Wei; Lin, Jun; Ding, Weiping; Wen, Longping

    2015-04-06

    In this work, we discovered that the Na(+)/K(+)-ATPase beta-subunit (ATP1B1) on epidermal cells plays a key role in the peptide-mediated transdermal delivery of macromolecular drugs. First, using a yeast two-hybrid assay, we screened candidate proteins that have specific affinity for the short peptide TD1 (ACSSSPSKHCG) identified in our previous work. Then, we verified the specific binding of TD1 to ATP1B1 in yeast and mammalian cells by a pull-down ELISA and an immunoprecipitation assay. Finally, we confirmed that TD1 mainly interacted with the C-terminus of ATP1B1. Our results showed that the interaction between TD1 and ATP1B1 affected not only the expression and localization of ATP1B1, but also the epidermal structure. In addition, this interaction could be antagonized by the exogenous competitor ATP1B1 or be inhibited by ouabain, which results in the decreased delivery of macromolecular drugs across the skin. The discovery of a critical role of ATP1B1 in the peptide-mediated transdermal drug delivery is of great significance for the future development of new transdermal peptide enhancers.

  17. 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.

  18. Elastic vesicles for transdermal drug delivery of hydrophilic drugs: a comparison of important physicochemical characteristics of different vesicle types.

    Science.gov (United States)

    Ntimenou, Vassiliki; Fahr, Alfred; Antimisiaris, Sophia G

    2012-08-01

    The aim of this study is to evaluate the influence of different lipid vesicular systems on the skin permeation ability of hydrophilic molecules, and understand if and which vesicle physicochemical properties may be used as predictive tools. Calcein and carboxyfluorescein were used as hydrophilic drug models. All vesicles (conventional liposomes [CLs], transfersomes [TRs] and invasomes [INVs]), were characterized for particle size distribution, zeta-potential, vesicular shape and morphology, encapsulation efficiency, integrity, colloidal stability, elasticity and finally in vitro human skin permeation. Dynamic light scattering (DLS) and cryo-transmission electron microscopy (cryo-TEM) defined that almost all vesicles had spherical structure, low polydispersity (PI Elasticity values (measured by extrusion through membranes) were in the order INVs > TRs > CLs. Three vesicle types were selected (having different elasticity) and in vitro skin permeation experiments demonstrated that calcein permeation was minimal from an aqueous solution, slightly enhanced from CLs, and enhanced by 1.8 and 7.2 times from TRs and INVs, respectively. Permeation and elasticity values were correlated by rank order but not linearly, indicating that elasticity can be used as a crude predictive tool for enhancement of skin transport. Drug encapsulation efficiency was not found to be an important factor in the current study.

  19. 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.

  20. 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.

  1. 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.

  2. Compound antimalarial ethosomal cataplasm: preparation, evaluation, and mechanism of penetration enhancement

    Directory of Open Access Journals (Sweden)

    Shen S

    2015-06-01

    Full Text Available Shuo Shen, Shu-Zhi Liu, Yu-Shi Zhang, Mao-Bo Du, Ai-Hua Liang, Li-Hua Song, Zu-Guang Ye Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China Abstract: Malaria is still a serious public health problem in some parts of the world. The problems of recurrence and drug resistance are increasingly more serious. Thus, it is necessary to develop a novel antimalarial agent. The objectives of this study were to construct a novel compound antimalarial transdermal nanosystem–ethosomal cataplasm, to investigate its characteristics and efficiency, and to systematically explore the penetration-enhancing mechanisms of ethosomal cataplasm. Artesunate-loaded ethosomes and febrifugine-loaded ethosomes were prepared, and their characteristics were evaluated. Drug-loaded ethosomes were incorporated in the matrix of cataplasm to form the compound antimalarial ethosomal cataplasm. With the help of ethosomal technology, the accumulated permeation quantity of artesunate significantly increased at 8 hours after administration, which was 1.57 times as much as that of conventional cataplasm. Soon after administration, the ethosomal cataplasm could make a large quantity of antimalarial drug quickly penetrate through skin, then the remaining drug in the ethosomal cataplasm could be steadily released. These characteristics of ethosomal cataplasm are favorable for antimalarial drugs to kill Plasmodium spp. quickly and prevent the resurgence of Plasmodium spp. As expected, the ethosomal cataplasm showed good antimalarial efficiency in this experiment. The negative conversion rates were 100% and the recurrence rates were 0% at all dosages. The mechanism of penetration enhancement of the ethosomal cataplasm was systematically explored using an optics microscope, polarization microscope, and transmission electron microscopy. The microstructure, ultrastructure, and birefringent structure in skin were observed. Data

  3. Microstructural Study on Oxygen Permeated Arc Beads

    Directory of Open Access Journals (Sweden)

    Kuan-Heng Liu

    2015-01-01

    Full Text Available We simulated short circuit of loaded copper wire at ambient atmosphere and successfully identified various phases of the arc bead. A cuprous oxide flake was formed on the surface of the arc bead in the rapid solidification process, and there were two microstructural constituents, namely, Cu-κ eutectic structure and solutal dendrites. Due to the arc bead formed at atmosphere during the local equilibrium solidification process, the phase of arc bead has segregated to the cuprous oxide flake, Cu-κ eutectic, and Cu phase solutal dendrites, which are the fingerprints of the arc bead permeated by oxygen.

  4. Hydrogen isotope permeation in elastomeric materials

    International Nuclear Information System (INIS)

    Steinmeyer, R.H.; Braun, J.D.

    1976-01-01

    The permeabilities of elastomeric and polymeric materials to hydrogen isotopes were measured at room temperature. The technique for measuring permeation rates is based on the following constant-volume method: a fixed pressure of gas is applied to one side of the specimen to be studied and the permeability constant is determined from the observed rate of pressure increase in an initially evacuated volume on the other side of the specimen. Permeability constants for hydrogen, deuterium, and tritium were measured for Mylar, Teflon, Kapton, Saran, Buna-N, and latex rubber. Results were compared with literature values for hydrogen and deuterium where available and showed excellent agreement

  5. Organic fluid permeation through fluoropolymer membranes

    Science.gov (United States)

    Nemser, Stuart M.; Kosaraju, Praveen; Bowser, John

    2015-07-14

    Separation of the components of liquid mixtures is achieved by contacting a liquid mixture with a nonporous membrane having a fluoropolymer selectively permeable layer and imposing a pressure gradient across the membrane from feed side to permeate side. Unusually high transmembrane flux is obtained when the membrane is subjected to one or more process conditions prior to separation. These include (a) leaving some residual amount of membrane casting solvent in the membrane, and (b) contacting the membrane with a component of the mixture to be separated for a duration effective to saturate the membrane with the component.

  6. 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

  7. 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.

  8. 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

  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. 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 ...

  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. Transdermal delivery of relatively high molecular weight drugs using novel self-dissolving microneedle arrays fabricated from hyaluronic acid and their characteristics and safety after application to the skin.

    Science.gov (United States)

    Liu, Shu; Jin, Mei-na; Quan, Ying-shu; Kamiyama, Fumio; Kusamori, Kosuke; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

    2014-02-01

    The purpose of this study was to develop novel dissolving microneedle arrays fabricated from hyaluronic acid (HA) as a material and to improve the transdermal permeability of relatively high molecular weight drugs. In this study, fluorescein isothiocyanate-labeled dextran with an average molecular weight of 4kDa (FD4) was used as a model drug with a relatively high molecular weight. The microneedle arrays significantly increased transepidermal water loss (TEWL) and reduced transcutaneous electrical resistance (TER), indicating that they could puncture the skin and create drug permeation pathways successfully. Both TEWL and TER almost recovered to baseline levels in the microneedle array group, and relatively small pathways created by the microneedles rapidly recovered as compared with those created by a tape stripping treatment. These findings confirmed that the microneedle arrays were quite safe. Furthermore, we found that the transdermal permeability of FD4 using the microneedle arrays was much higher than that of the FD4 solution. Furthermore, we found that the microneedle arrays were much more effective for increasing the amount of FD4 accumulated in the skin. These findings indicated that using novel microneedle arrays fabricated from HA is a very useful and effective strategy to improve the transdermal delivery of drugs, especially relatively high molecular weight drugs without seriously damaging the skin. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Tritium permeation losses in HYLIFE-II heat exchanger tubes

    International Nuclear Information System (INIS)

    Longhurst, G.R.; Dolan, T.J.

    1990-01-01

    Tritium permeation through the intermediate heat exchanger of the HYLIFE-II inertial fusion design concept is evaluated for routine operating conditions. The permeation process is modelled using the Lewis analogy combined with surface recombination. It is demonstrated that at very low driving potentials, permeation becomes proportional to the first power of the driving potential. The model predicts that under anticipated conditions the primary cooling loop will pass about 6% of the tritium entering it to the intermediate coolant. Possible approached to reducing tritium permeation are explored. Permeation is limited by turbulent diffusion transport through the molten salt. Hence, surface barriers with impendance factors typical of present technology can do very little to reduce permeation. Low Flibe viscosity is desirable. An efficient tritium removal system operating on the Flibe before it gets to the intermediate heat exchanger is required. Needs for further research are highlighted. 9 refs., 2 figs., 1 tab

  14. Importance of the Direct Contact of Amorphous Solid Particles with the Surface of Monolayers for the Transepithelial Permeation of Curcumin.

    Science.gov (United States)

    Kimura, Shunsuke; Kasatani, Sachiha; Tanaka, Megumi; Araki, Kaeko; Enomura, Masakazu; Moriyama, Kei; Inoue, Daisuke; Furubayashi, Tomoyuki; Tanaka, Akiko; Kusamori, Kosuke; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

    2016-02-01

    The amorphization has been generally known to improve the absorption and permeation of poorly water-soluble drugs through the enhancement of the solubility. The present study focused on the direct contact of amorphous solid particles with the surface of the membrane using curcumin as a model for water-insoluble drugs. Amorphous nanoparticles of curcumin (ANC) were prepared with antisolvent crystallization method using a microreactor. The solubility of curcumin from ANC was two orders of magnitude higher than that of crystalline curcumin (CC). However, the permeation of curcumin from the saturated solution of ANC was negligible. The transepithelial permeation of curcumin from ANC suspension was significantly increased as compared to CC suspension, while the permeation was unlikely correlated with the solubility, and the increase in the permeation was dependent on the total concentration of curcumin in ANC suspension. The absorptive transport of curcumin (from apical to basal, A to B) from ANC suspension was much higher than the secretory transport (from basal to apical, B to A). In vitro transport of curcumin through air-interface monolayers is large from ANC but negligible from CC particles. These findings suggest that the direct contact of ANC with the absorptive membrane can play an important role in the transport of curcumin from ANC suspension. The results of the study suggest that amorphous particles may be directly involved in the transepithlial permeation of curcumin.

  15. Interactions between oxygen permeation and homogeneous-phase fuel conversion on the sweep side of an ion transport membrane

    KAUST Repository

    Hong, Jongsup

    2013-02-01

    The interactions between oxygen permeation and homogeneous fuel oxidation reactions on the sweep side of an ion transport membrane (ITM) are examined using a comprehensive model, which couples the dependency of the oxygen permeation rate on the membrane surface conditions and detailed chemistry and transport in the vicinity of the membrane. We assume that the membrane surface is not catalytic to hydrocarbon or syngas oxidation. Results show that increasing the sweep gas inlet temperature and fuel concentration enhances oxygen permeation substantially. This is accomplished through promoting oxidation reactions (oxygen consumption) and the transport of the products and reaction heat towards the membrane, which lowers the oxygen concentration and increases the gas temperature near the membrane. Faster reactions at higher fuel concentration and higher inlet gas temperature support substantial fuel conversion and lead to a higher oxygen permeation flux without the contribution of surface catalytic activity. Beyond a certain maximum in the fuel concentration, extensive heat loss to the membrane (and feed side) reduces the oxidation kinetic rates and limits oxygen permeation as the reaction front reaches the membrane. The sweep gas flow rate and channel height have moderate impacts on oxygen permeation and fuel conversion due to the residence time requirements for the chemical reactions and the location of the reaction zone relative to the membrane surface. © 2012 Elsevier B.V.

  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. Evaluation of in vitro percutaneous enhancement effect of papain and pequi oil on diclofenac sodium permeation through human skin Avaliação in vitro da papaína e do óleo de pequi como promotores de permeação cutânea para diclofenaco de sódio em pele humana

    Directory of Open Access Journals (Sweden)

    Patrícia Santos Lopes

    2008-06-01

    Full Text Available The purpose of this research was to determine the potential of papain and pequi oil as penetration enhancers for diclofenac sodium (DS across human skin in vitro. The permeation studies were conducted with vertical diffusion cells. The enhancers were associated or not in gels in different concentrations. In vitro studies reveled that papain 0.2% (w/v presented an elevated enhancer property for diclofenac sodium (J = 0.3369 mg/cm²x h. Pequi oil 10% (w/v generated a reduced flux value (J = 0.1848 mg/cm²x h and a combination of both enhancers presented a medium value of J = 0.2187 mg/cm²x h. Papain was found to be better enhancer than pequi oil.O objetivo desta pesquisa foi determinar in vitro o potencial da papaína e do óleo de pequi como promotores de penetração cutânea para o diclofenaco de sódio (DS através de pele humana. Os estudos de penetração foram conduzidos em células de difusão vertical. Os promotores foram associados ou não em géis em concentrações distintas. A avaliação in vitro revelou que a papaína 0,2% p/p apresentou propriedade promotora maior para o diclofenaco de sódio (J = 0,3369 mg/cm²x h. O óleo de pequi 10,0% p/v promoveu redução do fluxo (J = 0,1848 mg/cm²x h e a combinação de ambos os promotores apresentou valor mediano de fluxo de J = 0,2187 mg/cm²x h. A partir dos resultados, verificou-se que a papaína exerceu ação promotora de penetração cutânea melhor que o óleo de pequi.

  18. Hydrogen permeation measurement of the reduced activation ferritic steel F82H by the vacuum thermo-balance method

    International Nuclear Information System (INIS)

    Yoshida, Hajime; Enoeda, Mikio; Abe, Tetsuya; Akiba, Masato

    2005-03-01

    Hydrogen permeation fluxes of the reduced activation ferritic steel F82H were quantitatively measured by a newly proposed method, vacuum thermo-balance method, for a precise estimation of tritium leakage in a fusion reactor. We prepared sample capsules made of F82H, which enclosed hydrogen gas. The hydrogen in the capsules permeated through the capsule wall, and subsequently desorbed from the capsule surface during isothermal heating. The vacuum thermo-balance method allows simultaneous measurement of the hydrogen permeation flux by two independent methods, namely, the net weight reduction of the sample capsule and exhaust gas analysis. Thus the simultaneous measurements by two independent methods increase the reliability of the permeability measurement. When the gas pressure of enclosed hydrogen was 0.8 atm at the sample temperature of 673 K, the hydrogen permeation flux of F82H obtained by the net weight reduction and the exhaust gas analysis was 0.75x10 18 (H 2 /m 2 s) and 2.2x10 18 (H 2 /m 2 s), respectively. The ratio of the hydrogen permeation fluxes obtained by the net weight reduction to that measured by the exhaust gas analysis was in the range from 1/4 to 1/1 in this experiment. The temperature dependence of the estimated permeation flux was similar in both methods. Taking the uncertainties of both measurements into consideration, both results are supposed to be consistent. The enhancement of hydrogen permeation flux was observed from the sample of which outer surface was mechanically polished. Through the present experiments, it has been demonstrated that the vacuum thermo-balance method is effective for the measurement of hydrogen permeation rate of F82H. (author)

  19. Development of a Contact Permeation Test Fixture and Method

    Science.gov (United States)

    2013-04-01

    Permeation and Analytical Solutions Team Quality System documentation and the guidance found in the ISO 17025 standard. All permeation and...annular ring (left) and no pressure (right). 2.2.4 Quality Controls Analytical permeation testing was conducted in accordance with ISO 17025 quality...internal standard. This mixture was vortexed for 20–30 s then centrifuged at 15,000 rpm for 5 min in a Micromax microcentrifuge (Thermo IEC ; Needham

  20. Formulation optimization of transdermal meloxicam potassium-loaded mesomorphic phases containing ethanol, oleic acid and mixture surfactant using the statistical experimental design methodology.

    Science.gov (United States)

    Huang, Chi-Te; Tsai, Chia-Hsun; Tsou, Hsin-Yeh; Huang, Yaw-Bin; Tsai, Yi-Hung; Wu, Pao-Chu

    2011-01-01

    Response surface methodology (RSM) was used to develop and optimize the mesomorphic phase formulation for a meloxicam transdermal dosage form. A mixture design was applied to prepare formulations which consisted of three independent variables including oleic acid (X(1)), distilled water (X(2)) and ethanol (X(3)). The flux and lag time (LT) were selected as dependent variables. The result showed that using mesomorphic phases as vehicles can significantly increase flux and shorten LT of drug. The analysis of variance showed that the permeation parameters of meloxicam from formulations were significantly influenced by the independent variables and their interactions. The X(3) (ethanol) had the greatest potential influence on the flux and LT, followed by X(1) and X(2). A new formulation was prepared according to the independent levels provided by RSM. The observed responses were in close agreement with the predicted values, demonstrating that RSM could be successfully used to optimize mesomorphic phase formulations.

  1. 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.

  2. In situ measurement of tritium permeation through stainless steel

    Science.gov (United States)

    Luscher, Walter G.; Senor, David J.; Clayton, Kevin K.; Longhurst, Glen R.

    2013-06-01

    The TMIST-2 irradiation experiment was conducted in the Advanced Test Reactor at Idaho National Laboratory to evaluate tritium permeation through Type 316 stainless steel (316 SS). The interior of a 316 SS seamless tube specimen was exposed to a 4He carrier gas mixed with a specified quantity of tritium (T2) to yield partial pressures of 0.1, 5, and 50 Pa at 292 °C and 330 °C. In situ tritium permeation measurements were made by passing a He-Ne sweep gas over the outer surface of the specimen to carry the permeated tritium to a bubbler column for liquid scintillation counting. Results from in situ permeation measurements were compared with predictions based on an ex-reactor permeation correlation in the literature. In situ permeation data were also used to derive an in-reactor permeation correlation as a function of temperature and pressure over the ranges considered in this study. In addition, the triton recoil contribution to tritium permeation, which results from the transmutation of 3He to T, was also evaluated by introducing a 4He carrier gas mixed with 3He at a partial pressure of 1013 Pa at 330 °C. Less than 3% of the tritium resulting from 3He transmutation contributed to tritium permeation.

  3. Separation of aromatics by vapor permeation through solvent swollen membrane

    Energy Technology Data Exchange (ETDEWEB)

    Ito, A.; Adachi, K.; Feng, Y. [Niigata University, Niigata (Japan)

    1995-12-20

    A vapor permeation process for aromatics separation from a hydrocarbon mixture was studied by means of the simultaneous permeation of dimethylsulfoxide vapor as an agent for membrane swelling and preferential permeation of aromatics. The separation performance of the process was demonstrated by a polyvinylalcohol membrane for mixed vapors of benzene/cyclohexane, xylene/octane and a model gasoline. The aromatic vapors preferentially permeated from these mixed vapor feeds. The separation factor was over 10. The separation mechanism of the process mainly depends on the relative salability of the vapors between aromatics and other hydrocarbons in dimethylsulfoxide. 14 refs., 9 figs., 1 tab.

  4. Hydrogen permeation resistant layers for liquid metal reactors

    International Nuclear Information System (INIS)

    McGuire, J.C.

    1980-03-01

    Reviewing the literature in the tritium diffusion field one can readily see a wide divergence in results for both the response of permeation rate to pressure, and the effect of oxide layers on total permeation rates. The basic mechanism of protective oxide layers is discussed. Two coatings which are less hydrogen permeable than the best naturally occurring oxide are described. The work described is part of an HEDL-ANL cooperative research program on Tritium Permeation in Liquid Metal Cooled Reactors. This includes permeation work on hydrogen, deuterium, and tritium with the hydrogen-deuterium research leading to the developments presented

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

    African Journals Online (AJOL)

    1Department of Pain Medicine, 2Department of Gastroenterology, 3Department of Pathology, 4Department of Radiology,. 5Department of Orthopedic, Linzi People's ... not only drug flux but also analgesic and anti-inflammatory activities in rats. ... chronic pain and inflammation management in. SCI, arthritis and other related ...

  6. Utilization of prodrugs to enhance the transdermal absorption of morphine

    DEFF Research Database (Denmark)

    Drustrup, J.; Fullerton, A.; Christrup, Lona Louring

    1991-01-01

    . The esters showed generally a higher water and lipid solubility than morphine and were also much more lipophilic than the parent drug in terms of octanol-buffer partition coefficients. Diffusion experiments in vitro using human skin samples showed that whereas morphine did not penetrate the skin to any...

  7. 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.

  8. 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.

  9. Development and validation of in vitro-in vivo correlation (IVIVC) for estradiol transdermal drug delivery systems.

    Science.gov (United States)

    Yang, Yang; Manda, Prashanth; Pavurala, Naresh; Khan, Mansoor A; Krishnaiah, Yellela S R

    2015-07-28

    The objective of this study was to develop a level A in vitro-in vivo correlation (IVIVC) for drug-in-adhesive (DIA) type estradiol transdermal drug delivery systems (TDDS). In vitro drug permeation studies across human skin were carried out to obtain the percent of estradiol permeation from marketed products. The in vivo time versus plasma concentration data of three estradiol TDDS at drug loadings of 2.0, 3.8 and 7.6mg (delivery rates of 25, 50 and 100μg/day, respectively) was deconvoluted using Wagner-Nelson method to obtain percent of in vivo drug absorption in postmenopausal women. The IVIVC between the in vitro percent of drug permeation (X) and in vivo percent of drug absorption (Y) for these three estradiol TDDS was constructed using GastroPlus® software. There was a high correlation (R(2)=1.0) with a polynomial regression of Y=-0.227X(2)+0.331X-0.001. These three estradiol TDDS were used for internal validation whereas another two products of the same formulation design (with delivery rates of 60 and 100μg/day) were used for external validation. The predicted estradiol serum concentrations (convoluted from in vitro skin permeation data) were compared with the observed serum concentrations for the respective products. The developed IVIVC model passed both the internal and external validations as the prediction errors (%PE) for Cmax and AUC were less than 15%. When another marketed estradiol TDDS with a delivery rate of 100μg/day but with a slight variation in formulation design was chosen, it did not pass external validation indicating the product-specific nature of IVIVC model. Results suggest that the IVIVC model developed in this study can be used to successfully predict the in vivo performance of the same estradiol TDDS with in vivo delivery rates ranging from 25 to 100μg/day. Published by Elsevier B.V.

  10. In situ measurement of tritium permeation through stainless steel

    Energy Technology Data Exchange (ETDEWEB)

    Luscher, Walter G., E-mail: walter.luscher@pnnl.gov [Pacific Northwest National Laboratory, 902 Battelle Blvd, Richland, WA 99352 (United States); Senor, David J., E-mail: david.senor@pnnl.gov [Pacific Northwest National Laboratory, 902 Battelle Blvd, Richland, WA 99352 (United States); Clayton, Kevin K., E-mail: kevin.clayton@inl.gov [Idaho National Laboratory, 2525 Fremont Ave., Idaho Falls, ID 83415 (United States); Longhurst, Glen R., E-mail: glenlonghurst@suu.edu [Idaho National Laboratory, 2525 Fremont Ave., Idaho Falls, ID 83415 (United States)

    2013-06-15

    Highlights: ► In situ tritium permeation measurements collected over broad pressure range. ► Test conditions relevant to 316 SS in commercial light water reactors. ► Comparisons between in- and ex-reactor measurements provided. ► Correlation between tritium permeation, temperature, and pressure developed. -- Abstract: The TMIST-2 irradiation experiment was conducted in the Advanced Test Reactor at Idaho National Laboratory to evaluate tritium permeation through Type 316 stainless steel (316 SS). The interior of a 316 SS seamless tube specimen was exposed to a {sup 4}He carrier gas mixed with a specified quantity of tritium (T{sub 2}) to yield partial pressures of 0.1, 5, and 50 Pa at 292 °C and 330 °C. In situ tritium permeation measurements were made by passing a He–Ne sweep gas over the outer surface of the specimen to carry the permeated tritium to a bubbler column for liquid scintillation counting. Results from in situ permeation measurements were compared with predictions based on an ex-reactor permeation correlation in the literature. In situ permeation data were also used to derive an in-reactor permeation correlation as a function of temperature and pressure over the ranges considered in this study. In addition, the triton recoil contribution to tritium permeation, which results from the transmutation of {sup 3}He to T, was also evaluated by introducing a {sup 4}He carrier gas mixed with {sup 3}He at a partial pressure of 1013 Pa at 330 °C. Less than 3% of the tritium resulting from {sup 3}He transmutation contributed to tritium permeation.

  11. 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].

  12. 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...

  13. Permeation studies of novel terbinafine formulations containing hydrophobins through human nails in vitro.

    Science.gov (United States)

    Vejnovic, Ivana; Huonder, Cornelia; Betz, Gabriele

    2010-09-15

    Existing treatments of onychomycosis are not satisfactory. Oral therapies have many side effects and topical formulations are not able to penetrate into the human nail plate and deliver therapeutical concentrations of active agent in situ. The purpose of the present study was to determine the amount of terbinafine, which permeates through the human nail plate, from liquid formulations containing enhancers, namely hydrophobins A-C in the concentration of 0.1% (w/v). The used reference solution contained 10% (w/v) of terbinafine in 60% (v/v) ethanol/water without enhancer. Permeability studies have been performed on cadaver nails using Franz diffusion cells modified to mount nail plates and filled with 60% (v/v) ethanol/water in the acceptor chamber. Terbinafine was quantitatively determined by HPLC. The amount of terbinafine remaining in the nail was extracted by 96% ethanol from pulverized nail material after permeation experiment and presented as percentage of the dry nail weight before the milling test. Permeability coefficient (PC) of terbinafine from reference solution was determined to be 1.52E-10 cm/s. Addition of hydrophobins improved PC in the range of 3E-10 to 2E-9 cm/s. Remaining terbinafine reservoir in the nail from reference solution was 0.83% (n=2). An increase of remaining terbinafine reservoir in the nail was observed in two out of three tested formulations containing hydrophobins compared to the reference. In all cases, known minimum inhibitory concentration of terbinafine for dermatophytes (0.003 microg/ml) has been exceeded in the acceptor chamber of the diffusion cells. All tested proteins (hydrophobins) facilitated terbinafine permeation after 10 days of permeation experiment, however one of them achieved an outstanding enhancement factor of 13.05 compared to the reference. Therefore, hydrophobins can be included in the list of potential enhancers for treatment of onychomycosis. Copyright 2010 Elsevier B.V. All rights reserved.

  14. Effect of alcohol on skin permeation and metabolism of an ester-type prodrug in Yucatan micropig skin.

    Science.gov (United States)

    Fujii, Makiko; Ohara, Rieko; Matsumi, Azusa; Ohura, Kayoko; Koizumi, Naoya; Imai, Teruko; Watanabe, Yoshiteru

    2017-11-15

    We studied the effect that three alcohols, ethanol (EA), propanol (PA), and isopropanol (IPA), have on the skin permeation of p-hydroxy benzoic acid methyl ester (HBM), a model ester-type prodrug. HBM was applied to Yucatan micropig skin in a saturated phosphate buffered solution with or without 10% alcohol, and HBM and related materials in receptor fluid and skin were determined with HPLC. In the absence of alcohol, p-hydroxy benzoic acid (HBA), a metabolite of HBM, permeated the skin the most. The three alcohols enhanced the penetration of HBM at almost the same extent. The addition of 10% EA or PA to the HBM solution led to trans-esterification into the ethyl ester or propyl ester of HBA, and these esters permeated skin as well as HBA and HBM did. In contrast, the addition of 10% IPA promoted very little trans-esterification. Both hydrolysis and trans-esterification in the skin S9 fraction were inhibited by BNPP, an inhibitor of carboxylesterase (CES). Western blot and native PAGE showed the abundant expression of CES in micropig skin. Both hydrolysis and trans-esterification was simultaneously catalyzed by CES during skin permeation. Our data indicate that the alcohol used in dermal drug preparations should be selected not only for its ability to enhance the solubility and permeation of the drug, but also for the effect on metabolism of the drug in the skin. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Permeation of Light Gases through Hexagonal Ice

    Directory of Open Access Journals (Sweden)

    Luis Gales

    2012-09-01

    Full Text Available Gas separation using porous solids have attracted great attention due to their energetic applications. There is an enormous economic and environmental interest in the development of improved technologies for relevant processes, such as H2 production, CO2 separation or O2 and N2 purification from air. New materials are needed for achieving major improvements. Crystalline materials, displaying unidirectional and single-sized pores, preferentially with low pore tortuosity and high pore density, are promising candidates for membrane synthesis. Herein, we study hexagonal ice crystals as an example of this class of materials. By slowly growing ice crystals inside capillary tubes we were able to measure the permeation of several gas species through ice crystals and investigate its relation with both the size of the guest molecules and temperature of the crystal.

  16. Electrical insulator assembly with oxygen permeation barrier

    Science.gov (United States)

    Van Der Beck, Roland R.; Bond, James A.

    1994-01-01

    A high-voltage electrical insulator (21) for electrically insulating a thermoelectric module (17) in a spacecraft from a niobium-1% zirconium alloy wall (11) of a heat exchanger (13) filled with liquid lithium (16) while providing good thermal conductivity between the heat exchanger and the thermoelectric module. The insulator (21) has a single crystal alumina layer (SxAl.sub.2 O.sub.3, sapphire) with a niobium foil layer (32) bonded thereto on the surface of the alumina crystal (26) facing the heat exchanger wall (11), and a molybdenum layer (31) bonded to the niobium layer (32) to act as an oxygen permeation barrier to preclude the oxygen depleting effects of the lithium from causing undesirable niobium-aluminum intermetallic layers near the alumina-niobium interface.

  17. Tritium permeation model for plasma facing components

    Science.gov (United States)

    Longhurst, G. R.

    1992-12-01

    This report documents the development of a simplified one-dimensional tritium permeation and retention model. The model makes use of the same physical mechanisms as more sophisticated, time-transient codes such as implantation, recombination, diffusion, trapping and thermal gradient effects. It takes advantage of a number of simplifications and approximations to solve the steady-state problem and then provides interpolating functions to make estimates of intermediate states based on the steady-state solution. The model is developed for solution using commercial spread-sheet software such as Lotus 123. Comparison calculations are provided with the verified and validated TMAP4 transient code with good agreement. Results of calculations for the ITER CDA diverter are also included.

  18. Tritium permeation model for plasma facing components

    International Nuclear Information System (INIS)

    Longhurst, G.R.

    1992-12-01

    This report documents the development of a simplified one-dimensional tritium permeation and retention model. The model makes use of the same physical mechanisms as more sophisticated, time-transient codes such as implantation, recombination, diffusion, trapping and thermal gradient effects. It takes advantage of a number of simplifications and approximations to solve the steady-state problem and then provides interpolating functions to make estimates of intermediate states based on the steady-state solution. The model is developed for solution using commercial spread-sheet software such as Lotus 123. Comparison calculations are provided with the verified and validated TMAP4 transient code with good agreement. Results of calculations for the ITER CDA diverter are also included

  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. Formulation of two-layer dissolving polymeric microneedle patches for insulin transdermal delivery in diabetic mice.

    Science.gov (United States)

    Lee, I-Chi; Lin, Wei-Ming; Shu, Jwu-Ching; Tsai, Shau-Wei; Chen, Chih-Hao; Tsai, Meng-Tsan

    2017-01-01

    Dissolving microneedles (MNs) display high efficiency in delivering poorly permeable drugs and vaccines. Here, two-layer dissolving polymeric MN patches composed of gelatin and sodium carboxymethyl cellulose (CMC) were fabricated with a two-step casting and centrifuging process to localize the insulin in the needle and achieve efficient transdermal delivery of insulin. In vitro skin insertion capability was determined by staining with tissue-marking dye after insertion, and the real-time penetration depth was monitored using optical coherence tomography. Confocal microscopy images revealed that the rhodamine 6G and fluorescein isothiocyanate-labeled insulin (insulin-FITC) can gradually diffuse from the puncture sites to deeper tissue. Ex vivo drug-release profiles showed that 50% of the insulin was released and penetrated across the skin after 1 h, and the cumulative permeation reached 80% after 5 h. In vivo and pharmacodynamic studies were then conducted to estimate the feasibility of the administration of insulin-loaded dissolving MN patches on diabetic mice for glucose regulation. The total area above the glucose level versus time curve as an index of hypoglycemic effect was 128.4 ± 28.3 (% h) at 0.25 IU/kg. The relative pharmacologic availability and relative bioavailability (RBA) of insulin from MN patches were 95.6 and 85.7%, respectively. This study verified that the use of gelatin/CMC MN patches for insulin delivery achieved a satisfactory RBA compared to traditional hypodermic injection and presented a promising device to deliver poorly permeable protein drugs for diabetic therapy. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 84-93, 2017. © 2016 Wiley Periodicals, Inc.

  1. Permeation of Telone EC through protective gloves.

    Science.gov (United States)

    Zainal, Hanaa; Que Hee, Shane S

    2005-09-30

    Telone is a potent fumigant that is based on the chlorinated unsaturated hydrocarbon, 1,3-dichloropropene (1,3-DCP). It is often applied without dilution and so poses severe inhalation and air pollution threats. Urinary metabolites of 1,3-DCP have been detected after Telone skin exposure, so that preventing dermal exposure is also important. The objective of the study was to assess if nitrile and multi-layer ("laminated") gloves provide adequate protection against Telone EC formulation. To accomplish this, disposable (Safeskin) and chemically resistant (Sol-Vex) nitrile and laminated (Barrier mark and Silver Shield) glove materials were challenged by Telone EC with hexane liquid collection in an ASTM-type I-PTC-600 permeation cell. Analyses of cis- and trans-1,3-DCP in the collection fluid at specified times were performed on a moderately polar capillary column by gas chromatography-electron capture detection. Telone EC caused microholes in both nitrile materials, though the chemically protective material was degraded slower than the disposable nitrile. The laminated gloves offered limited protection. Silver Shield protected best because 1.5-2.3 mg 1,3-DCP permeated by 8 h relative to 2.5-7.6 mg for Barrier, implying about 2.5 times more protection for 8 h. Even for Silver Shield, the extent of protection was inadequate as illustrated by a risk assessment of the skin exposure situation. The normalized breakthrough times for both types of laminated gloves varied between 27 and 60 min. It is recommended that Viton gloves still be worn for protection.

  2. A study on reverse osmosis permeating treatment for yarn dyeing ...

    African Journals Online (AJOL)

    This paper presents a fuzzy linear regression model for estimation of reverse osmosis permeating parameters conditions. The proposed model can effectively take on non-crisp, fuzzy and crisp data. This study model used for estimation of reverse osmosis permeating parameters data from Tirupur examines the variables that ...

  3. Effect of Nutrient Formulations on Permeation of Proteins and Lipids ...

    African Journals Online (AJOL)

    Purpose: To investigate the effect of nutrient formulations on the permeation of proteins and lipids through porcine intestine in vitro. Method: In vitro permeation studies of proteins and lipids of two peptide-based formulations, composed of various compounds and sources of hydrolyzed protein was carried out, and compared ...

  4. An unheated permeation device for calibrating atmospheric VOC measurements

    Directory of Open Access Journals (Sweden)

    J. Brito

    2011-10-01

    Full Text Available The development of an unpowered permeation device for continuous calibration of in-situ instruments measuring atmospheric volatile organic compounds (VOCs is described. Being lightweight and compact, and containing only negligible amounts of chemicals, the device is especially suited for field use such as on board aircraft. Its speciality is to maintain the permeation process in thermal equilibrium, so that the instantaneous permeation rate can be ascribed to a simple temperature measurement. This equilibrium state is maintained by a combination of three features: (i a thin PTFE membrane as permeation medium which guarantees short stabilization times, (ii a water bath as heat buffer, and (iii a vacuum-panel based insulation, in which features (ii and (iii minimize temperature drifts to ~30 mK h−1 per Kelvin temperature difference to the environment. The respective uncertainty of the permeation rate due to thermal non-equilibrium is kept below 1%. An extensive theory part details the major permeation processes of gases through porous polymers, being Fick's diffusion, Knudsen flow, and viscous flow. Both the measured stabilization time and the measured temperature dependence of the permeation rate independently indicate that the permeation can be described by a viscous flow model, where diffusion of the gas molecules in large pores (having a diameter of >0.05 μm dominates.

  5. Implantation driven permeation behavior of deuterium through pure tungsten

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Hirofumi E-mail: nakamura@tpl.tokai.jaeri.go.jp; Hayashi, Takumi; Nishi, Masataka; Arita, Makoto; Okuno, Kenji

    2001-09-01

    Implantation driven permeation behavior of deuterium through pure tungsten has been investigated to estimate the amount of tritium permeation through its barrier in a thermo-nuclear fusion device. The permeation experiments were performed on pure tungsten foil of 25 {mu}m thickness under conditions of incident flux of 1.9x10{sup 18}-1.1x10{sup 19} D{sup +}/m{sup 2}s, incident ion energy of 200-2000 eV, and specimen temperature of 512-660 K. As a result of this steady-state permeation experiment, the rate-determining process of deuterium permeation was found to be controlled by diffusion at both implanted and permeated sides. On the other hand, transient permeation was strongly affected by trap effect in the specimen. Simulation analysis using TMAP code on transient permeation behavior indicates the existence of a trap site with a trap energy of nearly 1eV and with a trap density of over several ten's ppm in tungsten.

  6. Implantation driven permeation behavior of deuterium through pure tungsten

    International Nuclear Information System (INIS)

    Nakamura, Hirofumi; Hayashi, Takumi; Nishi, Masataka; Arita, Makoto; Okuno, Kenji

    2001-01-01

    Implantation driven permeation behavior of deuterium through pure tungsten has been investigated to estimate the amount of tritium permeation through its barrier in a thermo-nuclear fusion device. The permeation experiments were performed on pure tungsten foil of 25 μm thickness under conditions of incident flux of 1.9x10 18 -1.1x10 19 D + /m 2 s, incident ion energy of 200-2000 eV, and specimen temperature of 512-660 K. As a result of this steady-state permeation experiment, the rate-determining process of deuterium permeation was found to be controlled by diffusion at both implanted and permeated sides. On the other hand, transient permeation was strongly affected by trap effect in the specimen. Simulation analysis using TMAP code on transient permeation behavior indicates the existence of a trap site with a trap energy of nearly 1eV and with a trap density of over several ten's ppm in tungsten

  7. Gastrointestinal behavior of nano- and microsized fenofibrate: In vivo evaluation in man and in vitro simulation by assessment of the permeation potential.

    Science.gov (United States)

    Hens, Bart; Brouwers, Joachim; Corsetti, Maura; Augustijns, Patrick

    2015-09-18

    The purpose of this study was (i) to evaluate the gastrointestinal behavior of micro- and nanosized fenofibrate in humans and (ii) to develop a simple yet qualitatively predictive in vitro setup that simulates the observed absorption-determining factors. Commercially available micro- and nanoparticles of fenofibrate (Lipanthyl® and Lipanthylnano®, respectively) were administered orally to five healthy volunteers in fasting and postprandial conditions. Intraluminal and systemic drug concentrations were determined as reference data for the development of a predictive in vitro setup. To capture the observed solubility/permeability interplay, in vitro dissolution testing was performed in the presence of a permeation bag with sink conditions. In fasting conditions, intake of nanosized fenofibrate generated increased duodenal concentrations compared to microsized fenofibrate, which was reflected in an improved systemic exposure. In postprandial conditions, duodenal concentrations were greatly enhanced for both formulations, however without an accompanying increase in systemic exposure. It appeared that micellar encapsulation of the highly lipohilic fenofibrate limited its potential to permeate from fed state intestinal fluids. To capture these in vivo observations in an in vitro setup, classic dissolution testing was combined with permeation assessment into a permeation bag with sink conditions. In case of fasting conditions, the dissolution/permeation approach allowed for an improved discriminative power between micro- and nanosized fenofibrate by better simulating the dynamic interplay of dissolution and absorption. In case of postprandial conditions, the observed solubility-permeability interplay could be simulated using the dissolution/permeation approach in combination with biorelevant media (FeSSGFFortimel and FeSSIF-V2) to mimic micellar entrapment and reduced permeation potential of fenofibrate. For the first time, reduced permeation of a lipophilic drug

  8. Pervaporation membrane bioreactor with permeate fractional condensation and mechanical vapor compression for energy efficient ethanol production

    International Nuclear Information System (INIS)

    Fan, Senqing; Xiao, Zeyi; Li, Minghai; Li, Sizhong

    2016-01-01

    Graphical abstract: Pervaporation membrane bioreactor with permeate partial condensation and mechanical vapor compression is developed for an energy efficient ethanol production. - Highlights: • PVMBR-MVC for energy efficient ethanol production. • Process separation factor of 20–44 for ethanol achieved by fractional condensation. • Energy production of 20.25 MJ and hourly energy production of 56.25 kJ/h achieved. • Over 50% of energy saved in PVMBR-MVC compared with PVMBR-LTC. • Integrated heat pump with COP of 7–9 for the energy recovery of the permeate. - Abstract: Improved process separation factor and heat integration are two key issues to increase the energy efficiency of ethanol production in a pervaporation membrane bioreactor (PVMBR). A PVMBR with permeate fractional condensation and mechanical vapor compression was developed for energy efficient ethanol production. A condensation model based on the mass balance and thermodynamic equilibrium in the partial vacuum condenser was developed for predicting the purification performance of the permeate vapor. Three runs of ethanol fermentation-pervaporation experiment were carried out and ethanol concentration of higher than 50 wt% could be achieved in the final condensate, with the separation factor of the process for ethanol increased to 20. Ethanol production could be enhanced in the bioreactor and 17.1 MJ of the energy could be produced in per liter of fermentation broth, owing to 27.0 MJ/kg heating value of the recovered ethanol. Compared with the traditional pervaporation process with low temperature condensation for ethanol production, 50% of the energy would be saved in the process. The energy consumption would be further reduced, if the available energy of the permeate vapor was utilized by integrating the mechanical vapor compression heat pump.

  9. Permeation of aromatic solvent mixtures through nitrile protective gloves.

    Science.gov (United States)

    Chao, Keh-Ping; Hsu, Ya-Ping; Chen, Su-Yi

    2008-05-30

    The permeation of binary and ternary mixtures of benzene, toluene, ethyl benzene and p-xylene through nitrile gloves were investigated using the ASTM F739 test cell. The more slowly permeating component of a mixture was accelerated to have a shorter breakthrough time than its pure form. The larger differences in solubility parameter between a solvent mixture and glove resulted in a lower permeation rate. Solubility parameter theory provides a potential approach to interpret the changes of permeation properties for BTEX mixtures through nitrile gloves. Using a one-dimensional diffusion model based on Fick's law, the permeation concentrations of ASTM F739 experiments were appropriately simulated by the estimated diffusion coefficient and solubility. This study will be a fundamental work for the risk assessment of the potential dermal exposure of workers wearing protective gloves.

  10. Oral and transdermal drug delivery systems: role of lipid-based lyotropic liquid crystals

    Directory of Open Access Journals (Sweden)

    Rajabalaya R

    2017-02-01

    Full Text Available Rajan Rajabalaya, Muhammad Nuh Musa, Nurolaini Kifli, Sheba R David PAPRSB Institute of Health Sciences, Universiti Brunei Darussalam, Brunei Darussalam Abstract: Liquid crystal (LC dosage forms, particularly those using lipid-based lyotropic LCs (LLCs, have generated considerable interest as potential drug delivery systems. LCs have the physical properties of liquids but retain some of the structural characteristics of crystalline solids. They are compatible with hydrophobic and hydrophilic compounds of many different classes and can protect even biologicals and nucleic acids from degradation. This review, focused on research conducted over the past 5 years, discusses the structural evaluation of LCs and their effects in drug formulations. The structural classification of LLCs into lamellar, hexagonal and micellar cubic phases is described. The structures of these phases are influenced by the addition of surfactants, which include a variety of nontoxic, biodegradable lipids; these also enhance drug solubility. LLC structure influences drug localization, particle size and viscosity, which, in turn, determine drug delivery properties. Through several specific examples, we describe the applications of LLCs in oral and topical drug formulations, the latter including transdermal and ocular delivery. In oral LLC formulations, micelle compositions and the resulting LLC structures can determine drug solubilization and stability as well as intestinal transport and absorption. Similarly, in topical LLC formulations, composition can influence whether the drug is retained in the skin or delivered transdermally. Owing to their enhancement of drug stability and promotion of controlled drug delivery, LLCs are becoming increasingly popular in pharmaceutical formulations. Keywords: liquid crystal, drug delivery, controlled release, lyotropic, surfactants, drug localization

  11. 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

  12. Effect of Permeation Enhancers on the Release Behavior and ...

    African Journals Online (AJOL)

    HP

    International Pharmaceutical Abstract, Chemical Abstracts, Embase, Index Copernicus, EBSCO, African. Index Medicus ... inhibition of norepinephrine and serotonin uptake. ..... structural organization and increase in their fluidity and partial ...

  13. 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.

  14. 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

  15. 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....

  16. 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.

  17. 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.

  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. A new approach for noninvasive transdermal determination of blood uric acid levels

    Directory of Open Access Journals (Sweden)

    Ching CTS

    2014-06-01

    Full Text Available Congo Tak-Shing Ching,1,2 Kok-Khun Yong,3 Yan-Dong Yao,4 Huan-Ting Shen,3 Shiu-Man Hsieh,5 Deng-Yun Jheng,1 Tai-Ping Sun,1,6 Hsiu-Li Shieh11Department of Electrical Engineering, National Chi Nan University, Nantou, 2Department of Photonics and Communication Engineering, Asia University, Taichung, 3Department of Internal Medicine, Puli Christian Hospital, Nantou, People’s Republic of China; 4Division of Science and Technology, Hong Kong Community College, Hong Kong; 5Department of Orthopedic Surgery, Puli Christian Hospital, 6Department of Electronic Engineering, Nan Kai University of Technology, Nantou, People’s Republic of ChinaAbstract: The aims of this study were to investigate the most effective combination of physical forces from laser, electroporation, and reverse iontophoresis for noninvasive transdermal extraction of uric acid, and to develop a highly sensitive uric acid biosensor (UAB for quantifying the uric acid extracted. It is believed that the combination of these physical forces has additional benefits for extraction of molecules other than uric acid from human skin. A diffusion cell with porcine skin was used to investigate the most effective combination of these physical forces. UABs coated with ZnO2 nanoparticles and constructed in an array configuration were developed in this study. The results showed that a combination of laser (0.7 W, electroporation (100 V/cm2, and reverse iontophoresis (0.5 mA/cm2 was the most effective and significantly enhanced transdermal extraction of uric acid. A custom-designed UAB coated with ZnO2 nanoparticles and constructed in a 1×3 array configuration (UAB-1×3-ZnO2 demonstrated enough sensitivity (9.4 µA/mM for quantifying uric acid extracted by the combined physical forces of laser, electroporation, and RI. A good linear relationship (R2=0.894 was demonstrated to exist between the concentration of uric acid (0.2–0.8 mM inside the diffusion cell and the current response of the

  20. Characterization and in vitro permeation study of microemulsions and liquid crystalline systems containing the anticholinesterase alkaloidal extract from Tabernaemontana divaricata

    DEFF Research Database (Denmark)

    Chaiyana, Wantida; Rades, Thomas; Okonogi, Siriporn

    2013-01-01

    The aims of the present study were to characterize the microstructure and study the skin permeation enhancement of formulations containing the alkaloidal extract from Tabernaemontana divaricata. The extract was loaded in the formulations composed of Zingiber cassumunar oil, Triton X-114, ethanol ...

  1. Vapour permeation for the recovery of organic solvents from waste air streams: separation capacities and process optimization

    NARCIS (Netherlands)

    Leemann, M.; Leemann, M.; Eigenberger, G.; Strathmann, H.

    1996-01-01

    Vapour permeation is a potentially suitable technology for the recovery of organic solvents from waste air streams. New solvent stable capillary membrane modules that are currently emerging on the market provide large membrane areas for an acceptable price and enhance the competitiveness of this

  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. Effect of Different Skin Penetration Promoters in Halobetasol Propionate Permeation and Retention in Human Skin

    Directory of Open Access Journals (Sweden)

    Paulina Carvajal-Vidal

    2017-11-01

    Full Text Available Halobetasol propionate (HB is a potent synthetic corticosteroid used against inflammatory skin diseases, such as dermatitis, eczema, and psoriasis, among others. The aim of this study is to define how the presence of different skin penetration enhancers (nonane, menthone, limonene, azone, carene, decanol, linoleic acid and cetiol affects the penetration and retention in skin of HB. To determine drug penetration through skin, 5% of each promoter was used in an ex vivo system with human skin on Franz cells. The results showed that the highest permeation occurs in the presence of menthone, followed by nonane. Permeation parameters were determined. The in vivo test was assessed, and the formulation containing HB-menthone presented better anti-inflammatory efficacy. These results are useful to generate a specific treatment according to each patient’s needs, and the inflammatory characteristics of the disease.

  6. 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.

  7. 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: ...

  8. 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

  9. Development of tritium permeation barriers on Al base in Europe

    Science.gov (United States)

    Benamati, G.; Chabrol, C.; Perujo, A.; Rigal, E.; Glasbrenner, H.

    The development of the water cooled lithium lead (WCLL) DEMO fusion reactor requires the production of a material capable of acting as a tritium permeation barrier (TPB). In the DEMO blanket reactor permeation barriers on the structural material are required to reduce the tritium permeation from the Pb-17Li or the plasma into the cooling water to acceptable levels (HIP) technology and spray (this one developed also for repair) deposition techniques. The final goal is to select a reference technique to be used in the blanket of the DEMO reactor and in the ITER test module fabrication. The activities performed in four European laboratories are summarised here.

  10. Solid Lipid Nanoparticles of Guggul Lipid as Drug Carrier for Transdermal Drug Delivery

    Directory of Open Access Journals (Sweden)

    Praveen Kumar Gaur

    2013-01-01

    Full Text Available Diclofenac sodium loaded solid lipid nanoparticles (SLNs were formulated using guggul lipid as major lipid component and analyzed for physical parameters, permeation profile, and anti-inflammatory activity. The SLNs were prepared using melt-emulsion sonication/low temperature-solidification method and characterized for physical parameters, in vitro drug release, and accelerated stability studies, and formulated into gel. Respective gels were compared with a commercial emulgel (CEG and plain carbopol gel containing drug (CG for ex vivo and in vivo drug permeation and anti-inflammatory activity. The SLNs were stable with optimum physical parameters. GMS nanoparticle 1 (GMN-1 and stearic acid nanoparticle 1 (SAN-1 gave the highest in vitro drug release. Guggul lipid nanoparticle gel 3 (GLNG-3 showed 104.68 times higher drug content than CEG in receptor fluid. The enhancement ratio of GLNG-3 was 39.43 with respect to CG. GLNG-3 showed almost 8.12 times higher Cmax than CEG at 4 hours. The AUC value of GLNG-3 was 15.28 times higher than the AUC of CEG. GLNG-3 showed edema inhibition up to 69.47% in the first hour. Physicochemical properties of major lipid component govern the properties of SLN. SLN made up of guggul lipid showed good physical properties with acceptable stability. Furthermore, it showed a controlled drug release profile along with a promising permeation profile.

  11. Radionuclide decorporation: matching the biokinetics of actinides by transdermal delivery of pro-chelators.

    Science.gov (United States)

    Zhang, Yong; Sadgrove, Matthew P; Mumper, Russell J; Jay, Michael

    2013-10-01

    The threat of nuclear terrorism by the deliberate detonation of a nuclear weapon or radiological dispersion device ("dirty bomb") has made emergency response planning a priority. The only FDA-approved treatments for contamination with isotopes of the transuranic elements Am, Pu, and Cm are the Ca and Zn salts of diethylenetriaminepentaacetic acid (DTPA). These injectable products are not well suited for use in a mass contamination scenario as they require skilled professionals for their administration and are rapidly cleared from the circulation. To overcome the mismatch in the pharmacokinetics of the DTPA and the biokinetics of these transuranic elements, which are slowly released from contamination sites, the penta-ethyl ester of DTPA (C2E5) was prepared and formulated in a nonaqueous gel for transdermal administration. When gels comprised of 40% C2E5, 40-45% Miglyol® 840, and 15-20% ethyl cellulose were spiked with [(14)C]-C2E5 and applied to rat skin; over 60% of the applied dose was absorbed within a 24-h period. Radioactivity was observed in urinary and fecal excretions for over 3 days after removal of the gel. Using an (241)Am wound contamination model, transdermal C2E5 gels were able to enhance total body elimination and reduce the liver and skeletal burden of (241)Am in a dose-dependent manner. The efficacy achieved by a single 1,000 mg/kg dose to contaminated rats was statistically comparable to intravenous Ca-DTPA at 14 mg/kg. The effectiveness of this treatment, favorable sustained release profile of pro-chelators, and ease of administration support its use following radiological emergencies and for its inclusion in the Strategic National Stockpile.

  12. Permeation rates for RTF metal hydride vessels

    International Nuclear Information System (INIS)

    Klein, J.E.

    1992-01-01

    Contamination rates have been estimated for the RTF nitrogen heating and cooling system (NH and CS) due to tritium permeation through the walls of metal hydride vessels. Tritium contamination of the NH and CS will be seen shortly after start-up of the RTF with the majority of it coming from the TCAP units. Contamination rates of the NH and CS are estimated to exceed 400 Ci/year after three years of operation and will elevate tritium concentrations in the NH and CS above 6 x 10 -3 μCi/cc. To reduce tritium activity in the NH and CS, a stripper or ''getter'' bed may need to be installed in the NH and CS. Increasing the purge rate of nitrogen from the NH and CS is shown to be an impractical method for reducing tritium activity due to the high purge rates required. Stripping of the NH and CS nitrogen in the glove box stripper system will give a temporary lowering of tritium activity in the NH and CS, but tritium activity will return to its previous level in approximately two weeks

  13. 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.

  14. Quality by design approach for formulation, evaluation and statistical optimization of diclofenac-loaded ethosomes via transdermal route.

    Science.gov (United States)

    Jain, Shashank; Patel, Niketkumar; Madan, Parshotam; Lin, Senshang

    2015-06-01

    The objective of this study was to fabricate and understand ethosomal formulations of diclofenac (DF) for enhanced anti-inflammatory activity using quality by design approach. DF-loaded ethosomal formulations were prepared using 4 × 5 full-factorial design with phosphatidylcholine:cholesterol (PC:CH) ratios ranging between 50:50 and 90:10, and ethanol concentration ranging between 0% and 30% as formulation variables. These formulations were characterized in terms of physicochemical properties and skin permeation kinetics. The interaction of formulation variables had a significant effect on both physicochemical properties and permeation kinetics. The results of multivariate regression analysis illustrated that vesicle size and elasticity of ethosomes were the dominating physicochemical properties affecting skin permeation, and could be suitably controlled by manipulation of formulation variables to optimize the formulation and enhance the skin permeation of DF-loaded ethosomes. The optimized formulation had ethanol concentration of 22.9% and PC:CH ratio of 88.4:11.6, with vesicle size of 144 ± 5 nm, zeta potential of -23.0 ± 3.76 mV, elasticity of 2.48 ± 0.75 and entrapment efficiency of 71 ± 4%. Permeation flux for the optimized formulation was 12.9 ± 1.0 µg/h cm(2), which was significantly higher than the drug-loaded conventional liposome, ethanolic or aqueous solution. The in vivo study indicated that optimized ethosomal hydrogel exhibited enhanced anti-inflammatory activity compared with liposomal and plain drug hydrogel formulations.

  15. Study of tritium permeation through Peach Bottom Steam Generator tubes

    International Nuclear Information System (INIS)

    Yang, L.; Baugh, W.A.; Baldwin, N.L.

    1977-06-01

    The report describes the equipment developed, samples tested, procedures used, and results obtained in the tritium permeation tests conducted on steam generator tubing samples which were removed from the Peach Bottom Unit No. 1 reactor

  16. Recent results on implantation and permeation into fusion reactor materials

    Science.gov (United States)

    Anderl, R. A.; Holland, D. F.; Longhurst, G. R.; Struttman, D. A.

    This paper reports on implantation-driven permeation experiments that have been made for primary candidate alloy (PCA) and the ferritic steel HT-9 using deuterium ion beams from an accelerator. The results include measurements of the implantation flux and fluence dependence of the deuterium reemission and permeation for specimens heated to approximately 430(0)C. Simultaneous measurements of the ions sputtered from the specimen front surface with a secondary ion mass spectrometer provided some characterization of the surface condition throughout an experiment. For both materials, the permeation rate was lowered by the implantation process. However, the steady state permeation rate for HT-9 was found to be at least a factor of 5 greater than that for PCA.

  17. Phase Change Permeation Technology for Environmental Control & Life Support Systems

    Data.gov (United States)

    National Aeronautics and Space Administration — NASA is evaluating Dutyion™, a phase change permeation membrane technology developed by Design Technology and Irrigation (DTI), for use in future advanced life...

  18. Effect of residual stresses on hydrogen permeation in iron

    International Nuclear Information System (INIS)

    Mouanga, M.; Bercot, P.; Takadoum, J.

    2010-01-01

    The effect of residual stresses on electrochemical permeation in iron membrane was investigated. Four thermal and mechanical treatments were chosen to obtain different surface states in relation to the residual stresses. Residual stresses were determined by X-ray diffraction (XRD) using the Macherauch and Mueller method. The results were completed by the microhardness measurements. For all iron membranes, compressive residual stresses were obtained. Electrochemical permeation experiments using a Devanathan and Stachurski cell were employed to determine the hydrogen permeation behaviour of the various iron membranes. The latter was charged with hydrogen by galvanostatic cathodic polarization in 0.1 M NaOH at 25 deg. C. The experimental results revealed that hydrogen permeation rate increases with increasing residual stresses introduced in iron membranes.

  19. Rationalizing the permeation of polar antibiotics into Gram-negative bacteria

    International Nuclear Information System (INIS)

    Scorciapino, Mariano Andrea; Acosta-Gutierrez, Silvia; Benkerrou, Dehbia; D’Agostino, Tommaso; Malloci, Giuliano; Samanta, Susruta; Bodrenko, Igor; Ceccarelli, Matteo

    2017-01-01

    -Translocation consortium. The synergistic combination of structural data, in vitro assays and computer simulations has proven to give new insights towards the identification and description of physico–chemical properties modulating permeation. Once similar general rules are identified, we believe that the use of virtual screening techniques will be very helpful in searching for new molecular scaffolds with enhanced permeation, and that molecular modeling will be of fundamental assistance to the optimization stage. (topical review)

  20. Rationalizing the permeation of polar antibiotics into Gram-negative bacteria

    Science.gov (United States)

    Scorciapino, Mariano Andrea; Acosta-Gutierrez, Silvia; Benkerrou, Dehbia; D'Agostino, Tommaso; Malloci, Giuliano; Samanta, Susruta; Bodrenko, Igor; Ceccarelli, Matteo

    2017-03-01

    -Translocation consortium. The synergistic combination of structural data, in vitro assays and computer simulations has proven to give new insights towards the identification and description of physico-chemical properties modulating permeation. Once similar general rules are identified, we believe that the use of virtual screening techniques will be very helpful in searching for new molecular scaffolds with enhanced permeation, and that molecular modeling will be of fundamental assistance to the optimization stage.

  1. Measurement of tritium permeation through resistant materials near room temperature

    International Nuclear Information System (INIS)

    Maienschein, J.; DuVal, V.; McMurphy, F.; Uribe, F.; Musket, R.; Brown, D.

    1985-01-01

    To measure tritium permeation through low-permeability materials at 50 to 170 0 C, we use highly-sensitive liquid scintillation counting to detect the permeating tritium. To validate our method, we conducted extensive experiments with copper, for which much data exists for comparison. We report permeability of tritium through copper at 50, 100, and 170 0 C, and discuss details of the experimental technique. Further plans are outlined. 15 refs., 5 figs., 1 tab

  2. Transdermal estrogen gel and oral aspirin combination therapy improves fertility prognosis via the promotion of endometrial receptivity in moderate to severe intrauterine adhesion

    Science.gov (United States)

    Chi, Yugang; He, Ping; Lei, Li; Lan, Yi; Hu, Jianguo; Meng, Ying; Hu, Lina

    2018-01-01

    Intrauterine adhesion (IUA) is one of the most common gynecological diseases in women of reproductive age. IUA, particularlyin moderate to severe forms, accounts for a large percentage of infertility cases. Clinically, the first-line treatment strategy for IUA is transcervical resection of adhesion (TCRA), followed by adjuvant postoperative treatment. Estrogen is one of the classic chemotherapies used following TCRA and contributes to preventing re-adhesion following surgery. However, estrogen has limited effects in promoting pregnancy, which is the ultimate goal for IUA management. In the present study, a transdermal estrogen gel and oral aspirin combination therapy was used in patients with IUA following TCRA. Compared with in the control group (transdermal estrogen only therapy), the combination therapy significantly increased endometrial receptivity marker (αvβ٣ and laminin) expression in endometrium tissues. Additionally, ultrasonic examination revealed the pulsatility index and resistant index of the uterine artery were lower in the combination therapy group. Combination therapy promoted angiogenesis and prevented fibrosis following TCRA more effectively than estrogen-only therapy. Collectively, the evaluation indices, including American Fertility Society score, endometrial parameters and pregnancy rate, indicated that patients with combination therapy had better prognoses in endometrial repair and pregnancy. In conclusion, postoperative combination therapy with transdermal estrogen gel and oral aspirin may be more efficacious in enhancing endometrial receptivity by increasing uterine blood and angiogenesis, contributing to improved fertility prognosis. The findings of the present study may provide novel guidance to the clinical treatment of IUA. PMID:29512784

  3. Increased cutaneous wound healing effect of biodegradable liposomes containing madecassoside: preparation optimization, in vitro dermal permeation, and in vivo bioevaluation.

    Science.gov (United States)

    Li, Zehao; Liu, Meifeng; Wang, Huijuan; Du, Song

    2016-01-01

    Madecassoside (MA) is highly potent in treating skin disorders such as wounds and psoriasis. However, the topical wound healing effect of MA was hampered by its poor membrane permeability. In order to overcome this shortcoming, MA liposomes were designed and prepared by a double-emulsion method to enhance transdermal and wound healing effects. In this study, response surface methodology was adopted to yield the optimal preparation conditions of MA double-emulsion liposomes with average particle size of 151 nm and encapsulation efficiency of 70.14%. Moreover, MA double-emulsion liposomes demonstrated superior stability and homogeneous appearance in 5 months; their leakage rate was healing of MA liposomal formulations were conducted for the first time to evaluate MA delivery efficiency and wound healing effect. The transdermal property and wound cure effect of MA double-emulsion liposomes were superior to those of MA film dispersion liposomes, and both the methods were endowed with an excellent performance by polyethylene glycol modification. In conclusion, double-emulsion liposome formulation was an applicable and promising pharmaceutical preparation for enhancing MA delivery toward wound healing effect and improving wound-healing progress.

  4. Buccal delivery of thiocolchicoside: in vitro and in vivo permeation studies.

    Science.gov (United States)

    Artusi, M; Santi, P; Colombo, P; Junginger, H E

    2003-01-02

    Thiocolchicoside, a muscle-relaxant agent, is administered by the oral, intra-muscular and topical route. After oral administration the extent of bioavailability compared with intra-muscular administration is low, due to a first pass effect. In this paper, the delivery of thiocolchicoside through oral mucosa is studied to improve the bioavailability. Thiocolchicoside in vitro permeation through porcine oral mucosa and in vivo buccal transport in humans were investigated. Two dosage forms, a bioadhesive disc and a fast dissolving disc for buccal and sublingual administration of thiocolchicoside, respectively, were designed. The in vitro permeation of thiocolchicoside through porcine buccal mucosa from these dosage forms was evaluated and compared with in vivo absorption. Results from in vitro studies demonstrated that thiocolchicoside is quite permeable across porcine buccal mucosa and that permeation enhancers, such as sodium taurocholate and sodium taurodeoxycholate, were not able to increase its flux. The in vivo thiocolchicoside absorption experiments, in which the drug loss from oral cavity was measured, indicated that both formulations could be useful for therapeutic application. The fast dissolving (sublingual) form resulted in a quick uptake of 0.5 mg of thiocolchicoside within 15 min whereas with the adhesive buccal form the same dose can be absorbed over an extended period of time.

  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. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. Electrochemical measurement of tritium and hydrogen permeation through iron membranes

    International Nuclear Information System (INIS)

    Hagi, Hideki; Hayashi, Yasunori

    1987-01-01

    Permeation rates of tritium and hydrogen through iron were measured by the electro-chemical method in which an aqueous solution containing 3.7 x 10 12 Bq/m 3 tritium was used as a cathodic electrolyte. Tritium and hydrogen were introduced from one side of a specimen by cathodic polarization