WorldWideScience

Sample records for drug release studies

  1. Drug Release Studies from Caesalpinia pulcherrima Seed Polysaccharide.

    Science.gov (United States)

    Jeevanandham, Somasundaram; Dhachinamoorthi, Duraiswamy; Bannoth Chandra Sekhar, Kothapalli

    2011-01-01

    This study examines the controlled release behavior of both water-soluble (acetaminophen, caffeine, theophylline and salicylic acid) and water insoluble (indomethacin) drugs derived from Caesalpinia pulcherrima seed Gum isolated from Caesalpinia pulcherrima kernel powder. It further investigates the effect of incorporating diluents such as microcrystalline cellulose and lactose on caffeine release. In addition the effect the gum's (polysaccharide) partial cross-linking had on release of acetaminophen was examined. Applying the exponential equation, the soluble drugs mechanism of release was found to be anomalous. The insoluble drugs showed a near case II or zero order release mechanism. The rate of release in descending order was caffeine, acetaminophen, theophylline, salicylic acid and indomethacin. An increase in the release kinetics of the drug was observed on blending with diluents. However, the rate of release varied with the type and amount of blend within the matrix. The mechanism of release due to effect of diluents was found to be anomalous. The rate of drug release decreased upon partial cross-linking and the mechanism of release was found to be of super case II.

  2. Drug Release Studies from Caesalpinia pulcherrima Seed Polysaccharide

    OpenAIRE

    Jeevanandham, Somasundaram; Dhachinamoorthi, Duraiswamy; Bannoth Chandra Sekhar, Kothapalli

    2011-01-01

    This study examines the controlled release behavior of both water-soluble (acetaminophen, caffeine, theophylline and salicylic acid) and water insoluble (indomethacin) drugs derived from Caesalpinia pulcherrima seed Gum isolated from Caesalpinia pulcherrima kernel powder. It further investigates the effect of incorporating diluents such as microcrystalline cellulose and lactose on caffeine release. In addition the effect the gum?s (polysaccharide) partial cross-linking had on release of aceta...

  3. Fabrication of drug eluting implants: study of drug release mechanism from titanium dioxide nanotubes

    International Nuclear Information System (INIS)

    Hamlekhan, Azhang; Shokuhfar, Tolou; Sinha-Ray, Suman; Yarin, Alexander L; Takoudis, Christos; Mathew, Mathew T; Sukotjo, Cortino

    2015-01-01

    Formation of titanium dioxide nanotubes (TNTs) on a titanium surface holds great potential for promoting desirable cellular response. However, prolongation of drug release from these nano-reservoirs remains to be a challenge. In our previous work TNTs were successfully loaded with a drug. In this study the effect of TNTs dimensions on prolongation of drug release is quantified aiming at the introduction of a simple novel technique which overcomes complications of previously introduced methods. Different groups of TNTs with different lengths and diameters are fabricated. Samples are loaded with a model drug and rate of drug release over time is monitored. The relation of the drug release rate to the TNT dimensions (diameter, length, aspect ratio and volume) is established. The results show that an increase in any of these parameters increases the duration of the release process. However, the strongest parameter affecting the drug release is the aspect ratio. In fact, TNTs with higher aspect ratios release drug slower. It is revealed that drug release from TNT is a diffusion-limited process. Assuming that diffusion of drug in (Phosphate-Buffered Saline) PBS follows one-dimensional Fick’s law, the theoretical predictions for drug release profile is compatible with our experimental data for release from a single TNT. (paper)

  4. Polymeric nanoparticles containing diazepam: preparation, optimization, characterization, in-vitro drug release and release kinetic study

    Science.gov (United States)

    Bohrey, Sarvesh; Chourasiya, Vibha; Pandey, Archna

    2016-03-01

    Nanoparticles formulated from biodegradable polymers like poly(lactic-co-glycolic acid) (PLGA) are being extensively investigated as drug delivery systems due to their two important properties such as biocompatibility and controlled drug release characteristics. The aim of this work to formulated diazepam loaded PLGA nanoparticles by using emulsion solvent evaporation technique. Polyvinyl alcohol (PVA) is used as stabilizing agent. Diazepam is a benzodiazepine derivative drug, and widely used as an anticonvulsant in the treatment of various types of epilepsy, insomnia and anxiety. This work investigates the effects of some preparation variables on the size and shape of nanoparticles prepared by emulsion solvent evaporation method. These nanoparticles were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM). Zeta potential study was also performed to understand the surface charge of nanoparticles. The drug release from drug loaded nanoparticles was studied by dialysis bag method and the in vitro drug release data was also studied by various kinetic models. The results show that sonication time, polymer content, surfactant concentration, ratio of organic to aqueous phase volume, and the amount of drug have an important effect on the size of nanoparticles. Hopefully we produced spherical shape Diazepam loaded PLGA nanoparticles with a size range under 250 nm with zeta potential -23.3 mV. The in vitro drug release analysis shows sustained release of drug from nanoparticles and follow Korsmeyer-Peppas model.

  5. A study on programmed drug release from tablets

    NARCIS (Netherlands)

    Veen, Jacoba van der

    1993-01-01

    This thesis shows the extension of the applicability of the megaloporous system for drugs with different physico-chemical properties, like solubility and pK.. Procaine HC1, a highly soluble drug, can successfully be formulated in the programmed release megaloporous system, by using Carnauba wax,

  6. Application of drug selective electrode in the drug release study of pH-responsive microgels.

    Science.gov (United States)

    Tan, Jeremy P K; Tam, Kam C

    2007-03-12

    The colloidal phenomenon of soft particles is becoming an important field of research due to the growing interest in using polymeric system in drug delivery. Previous studies have focused on techniques that require intermediate process step such as dialysis or centrifugation, which introduces additional errors in obtaining the diffusion kinetic data. In this study, a drug selective electrode was used to directly measure the concentration of procaine hydrochloride (PrHy) released from methacrylic acid-ethyl acrylate (MAA-EA) microgel, thereby eliminating the intermediate process step. PrHy selective membrane constructed using a modified poly (vinyl chloride) (PVC) membrane and poly (ethylene-co-vinyl acetate-co-carbon monoxide) as plasticizer exhibited excellent reproducibility and stability. The response was reproducible at pH of between 3 to 8.5 and the selectivity coefficients against various organic and inorganic cations were evaluated. Drug release was conducted using the drug electrode under different pHs and the release rate increased with pH. The release behavior of the system under different pH exhibited obvious gradient release characteristics.

  7. The drug release study of ceftriaxone from porous hydroxyapatite scaffolds.

    Science.gov (United States)

    Al-Sokanee, Zeki N; Toabi, Abedl Amer H; Al-Assadi, Mohammed J; Alassadi, Erfan A S

    2009-01-01

    Hydroxyapatite (HAP) is an important biomedical material that is used for grafting osseous defects. It has an excellent bioactivity and biocompatibility properties. To isolate hydroxyapatite, pieces of cleaned cattle's bone were heated at different temperature range from 400 degrees C up to 1,200 degrees C. A reasonable yield of 60.32% w/w HAP was obtained at temperature range from 1,000 degrees C to 1,200 degrees C. Fourier transform infrared spectra and the thermogravimetric measurement showed a clear removal of organic at 600 degrees C as well as an excellent isolation of HAP from the bones which was achieved at 1,000-1,200 degrees C. This was also confirmed from X-ray diffraction of bone sample heated at 1,200 degrees C. The concentration ions were found to be sodium, potassium, lithium, zinc, copper, iron, calcium, magnesium, and phosphate present in bones within the acceptable limits for its role in the bioactivity property of HAP. Glucose powder was used as a porosifier. Glucose was novel and excellent as porogen where it was completely removed by heating, giving an efficient porosity in the used scaffolds. The results exhibited that the ceftriaxone drug release was increased with increasing the porosity. It was found that a faster, higher, and more regular drug release was obtained from the scaffold with a porosity of 10%.

  8. Drug Release from ß-Cyclodextrin Complexes and Drug Transfer into Model Membranes Studied by Affinity Capillary Electrophoresis.

    Science.gov (United States)

    Darwish, Kinda A; Mrestani, Yahya; Rüttinger, Hans-Hermann; Neubert, Reinhard H H

    2016-05-01

    Is to characterize the drug release from the ß-cyclodextrin (ß-CD) cavity and the drug transfer into model membranes by affinity capillary electrophoresis. Phospholipid liposomes with and without cholesterol were used to mimic the natural biological membrane. The interaction of cationic and anionic drugs with ß-CD and the interaction of the drugs with liposomes were detected separately by measuring the drug mobility in ß-CD containing buffer and liposome containing buffer; respectively. Moreover, the kinetics of drug release from ß-CD and its transfer into liposomes with or without cholesterol was studied by investigation of changes in the migration behaviours of the drugs in samples, contained drug, ß-CD and liposome, at 1:1:1 molar ratio at different time intervals; zero time, 30 min, 1, 2, 4, 6, 8, 10 and 24 h. Lipophilic drugs such as propranolol and ibuprofen were chosen for this study, because they form complexes with ß-CD. The mobility of the both drug liposome mixtures changed with time to a final state. For samples of liposomal membranes with cholesterol the final state was faster reached than without cholesterol. The study confirmed that the drug release from the CD cavity and its transfer into the model membrane was more enhanced by the competitive displacement of the drug from the ß-CD cavity by cholesterol, the membrane component. The ACE method here developed can be used to optimize the drug release from CD complexes and the drug transfer into model membranes.

  9. 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.

  10. Microstructural effects in drug release by solid and cellular polymeric dosage forms: A comparative study.

    Science.gov (United States)

    Blaesi, Aron H; Saka, Nannaji

    2017-11-01

    In recent studies, we have introduced melt-processed polymeric cellular dosage forms to achieve both immediate drug release and predictable manufacture. Dosage forms ranging from minimally-porous solids to highly porous, open-cell and thin-walled structures were prepared, and the drug release characteristics investigated as the volume fraction of cells and the excipient molecular weight were varied. In the present study, both minimally-porous solid and cellular dosage forms consisting of various weight fractions of Acetaminophen drug and polyethylene glycol (PEG) excipient are prepared and analyzed. Microstructures of the solid forms and the cell walls range from single-phase solid solutions of the excipient and a small amount of drug molecules to two-phase composites of the excipient and tightly packed drug particles. Results of dissolution experiments show that the minimally-porous solid forms disintegrate and release drug by slow surface erosion. The erosion rate decreases as the drug weight fraction is increased. By contrast, the open-cell structures disintegrate rapidly by viscous exfoliation, and the disintegration time is independent of drug weight fraction. Drug release models suggest that the solid forms erode by convective mass transfer of the faster-eroding excipient if the drug volume fraction is small. At larger drug volume fractions, however, the slower-eroding drug particles hinder access of the free-flowing fluid to the excipient, thus slowing down erosion of the composite. Conversely, the disintegration rate of the cellular forms is limited by diffusion of the dissolution fluid into the excipient phase of the thin cell walls. Because the wall thickness is of the order of the drug particle size, and the particles are enveloped by the excipient during melt-processing, the drug particles cannot hinder diffusion through the excipient across the walls. Thus the disintegration time of the cellular forms is mostly unaffected by the volume fraction of drug

  11. Functionalized mesoporous materials for adsorption and release of different drug molecules: A comparative study

    International Nuclear Information System (INIS)

    Wang Gang; Otuonye, Amy N.; Blair, Elizabeth A.; Denton, Kelley; Tao Zhimin; Asefa, Tewodros

    2009-01-01

    The adsorption capacity and release properties of mesoporous materials for drug molecules can be improved by functionalizing their surfaces with judiciously chosen organic groups. Functionalized ordered mesoporous materials containing various types of organic groups via a co-condensation synthetic method from 15% organosilane and by post-grafting organosilanes onto a pre-made mesoporous silica were synthesized. Comparative studies of their adsorption and release properties for various model drug molecules were then conducted. Functional groups including 3-aminopropyl, 3-mercaptopropyl, vinyl, and secondary amine groups were used to functionalize the mesoporous materials while rhodamine 6G and ibuprofen were utilized to investigate the materials' relative adsorption and release properties. The self-assembly of the mesoporous materials was carried out in the presence of cetyltrimethylammonium bromide (CTAB) surfactant, which produced MCM-41 type materials with pore diameters of ∼2.7-3.3 nm and moderate to high surface areas up to ∼1000 m 2 /g. The different functional groups introduced into the materials dictated their adsorption capacity and release properties. While mercaptopropyl and vinyl functionalized samples showed high adsorption capacity for rhodamine 6G, amine functionalized samples exhibited higher adsorption capacity for ibuprofen. While the diffusional release of ibuprofen was fitted on the Fickian diffusion model, the release of rhodamine 6G followed Super Case-II transport model. - Graphical abstract: The adsorption capacity and release properties of mesoporous materials for various drug molecules are tuned by functionalizing the surfaces of the materials with judiciously chosen organic groups. This work reports comparative studies of the adsorption and release properties of functionalized ordered mesoporous materials containing different hydrophobic and hydrophilic groups that are synthesized via a co-condensation and post-grafting methods for

  12. A new scleroglucan/borax hydrogel: swelling and drug release studies.

    Science.gov (United States)

    Coviello, Tommasina; Grassi, Mario; Palleschi, Antonio; Bocchinfuso, Gianfranco; Coluzzi, Gina; Banishoeib, Fateme; Alhaique, Franco

    2005-01-31

    The aim of the work was the characterization of a new polysaccharidic physical hydrogel, obtained from Scleroglucan (Sclg) and borax, following water uptake and dimension variations during the swelling process. Furthermore, the release of molecules of different size (Theophylline (TPH), Vitamin B12 (Vit. B12) and Myoglobin (MGB)) from the gel and from the dried system used as a matrix for tablets was studied. The increase of weight of the tablets with and without the loaded drugs was followed together with the relative variation of the dimensions. The dry matrix, in the form of tablets was capable, during the swelling process, to incorporate a relevant amount of solvent (ca. 20 g water/g dried matrix), without dissolving in the medium, leading to a surprisingly noticeable anisotropic swelling that can be correlated with a peculiar supramolecular structure of the system induced by compression. Obtained results indicate that the new hydrogel can be suitable for sustained drug release formulations. The delivery from the matrix is deeply dependent on the size of the tested model drugs. The experimental release data obtained from the gel were satisfactorily fitted by an appropriate theoretical approach and the relative drug diffusion coefficients in the hydrogel were estimated. The release profiles of TPH, Vit. B12 and MGB from the tablets have been analyzed in terms of a new mathematical approach that allows calculating of permeability values of the loaded drugs.

  13. Incorporation of ciprofloxacin/laponite in polycaprolactone electrospun nanofibers: drug release and antibacterial studies

    Science.gov (United States)

    Kalwar, Kaleemullah; Zhang, Xuan; Aqeel Bhutto, Muhammad; Dali, Li; Shan, Dan

    2017-12-01

    Electrospun nanofibers with sustained drug release are a challenge but it can be improved by using hydrophobic polymer. Polycaprolactone (PCL) is a hydrophobic and biocompatible polymer. In this work, we have proposed a drug release mechanism by preparation of ciprofloxacin (Cip)/Laponite (LAP) complex and then incorporation in PCL nanofibers through electrospinning technique. In addition, drug incorporation was confirmed by FTIR and morphology of electrospun nanofibers was revealed by SEM. Drug loading was measured by using spectrophotometer. PCL/LAP/Cip NFs proved sustained drug release as compared to PCL NFs and PCL/Cip NFs. Furthermore, PCL/LAP/Cip NFs were used as antimicrobial agent and higher effect measured.

  14. Study of drug release and tablet characteristics of silicone adhesive matrix tablets.

    Science.gov (United States)

    Tolia, Gaurav; Li, S Kevin

    2012-11-01

    Matrix tablets of a model drug acetaminophen (APAP) were prepared using a highly compressible low glass transition temperature (T(g)) polymer silicone pressure sensitive adhesive (PSA) at various binary mixtures of silicone PSA/APAP ratios. Matrix tablets of a rigid high T(g) matrix forming polymer ethyl cellulose (EC) were the reference for comparison. Drug release study was carried out using USP Apparatus 1 (basket), and the relationship between the release kinetic parameters of APAP and polymer/APAP ratio was determined to estimate the excipient percolation threshold. The critical points attributed to both silicone PSA and EC tablet percolation thresholds were found to be between 2.5% and 5% w/w. For silicone PSA tablets, satisfactory mechanical properties were obtained above the polymer percolation threshold; no cracking or chipping of the tablet was observed above this threshold. Rigid EC APAP tablets showed low tensile strength and high friability. These results suggest that silicone PSA could eliminate issues related to drug compressibility in the formulation of directly compressed oral controlled release tablets of poorly compressible drug powder such as APAP. No routinely used excipients such as binders, granulating agents, glidants, or lubricants were required for making an acceptable tablet matrix of APAP using silicone PSA. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Sustained Release Drug Delivery Applications of Polyurethanes

    Directory of Open Access Journals (Sweden)

    Michael B. Lowinger

    2018-05-01

    Full Text Available Since their introduction over 50 years ago, polyurethanes have been applied to nearly every industry. This review describes applications of polyurethanes to the development of modified release drug delivery. Although drug delivery research leveraging polyurethanes has been ongoing for decades, there has been renewed and substantial interest in the field in recent years. The chemistry of polyurethanes and the mechanisms of drug release from sustained release dosage forms are briefly reviewed. Studies to assess the impact of intrinsic drug properties on release from polyurethane-based formulations are considered. The impact of hydrophilic water swelling polyurethanes on drug diffusivity and release rate is discussed. The role of pore formers in modulating drug release rate is examined. Finally, the value of assessing mechanical properties of the dosage form and approaches taken in the literature are described.

  16. Tunable thermo-responsive hydrogels: synthesis, structural analysis and drug release studies.

    Science.gov (United States)

    Cirillo, Giuseppe; Spataro, Tania; Curcio, Manuela; Spizzirri, U Gianfranco; Nicoletta, Fiore Pasquale; Picci, Nevio; Iemma, Francesca

    2015-03-01

    Thermo-responsive hydrogel films, synthesized by UV-initiated radical polymerization, are proposed as delivery devices for non-steroidal anti-inflammatory drugs (Diclofenac sodium and Naproxen). N-isopropylacrylamide and N,N'-ethylenebisacrylamide were chosen as thermo-sensitive monomer and crosslinker, respectively. Infrared spectroscopy was used to assess the incorporation of monomers into the network, and the network density of hydrogel films was found to strictly depend on both feed composition and film thickness. Calorimetric analyses showed negative thermo-responsive behaviour with shrinking/swelling transition values in the range 32.8-36.1°C. Equilibrium swelling studies around the LCST allowed the correlation between the structural changes and the temperature variations. The mesh size, indeed, rapidly changed from a collapsed to a swollen state, with beneficial effects in applications such as size-selective permeation or controlled drug delivery, while the crosslinking degree, the film thickness, and the loading method deeply influenced the drug release profiles at 25 and 40°C. The analysis of both 3D-network structure, release kinetics and diffusional constraints at different temperatures was evaluated by mathematical modelling. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. 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.

  18. Computational Studies of Drug Release, Transport and Absorption in the Human Intestines

    Science.gov (United States)

    Behafarid, Farhad; Brasseur, J. G.; Vijayakumar, G.; Jayaraman, B.; Wang, Y.

    2016-11-01

    Following disintegration of a drug tablet, a cloud of particles 10-200 μm in diameter enters the small intestine where drug molecules are absorbed into the blood. Drug release rate depends on particle size, solubility and hydrodynamic enhancements driven by gut motility. To quantify the interrelationships among dissolution, transport and wall permeability, we apply lattice Boltzmann method to simulate the drug concentration field in the 3D gut released from polydisperse distributions of drug particles in the "fasting" vs. "fed" motility states. Generalized boundary conditions allow for both solubility and gut wall permeability to be systematically varied. We apply a local 'quasi-steady state' approximation for drug dissolution using a mathematical model generalized for hydrodynamic enhancements and heterogeneity in drug release rate. We observe fundamental differences resulting from the interplay among release, transport and absorption in relationship to particle size distribution, luminal volume, motility, solubility and permeability. For example, whereas smaller volume encourages higher bulk concentrations and reduced release rate, it also encourages higher absorption rate, making it difficult to generalize predictions. Supported by FDA.

  19. Using ion-selective electrodes to study the drug release from porous cellulose matrices

    DEFF Research Database (Denmark)

    Vakili, Hossein; Genina, Natalja; Ehlers, Henrik

    2012-01-01

    -polymer solutions were prepared with the model drugs, using different blend ratios of ethylcellulose (EC) and hydroxypropyl cellulose (HPC). Two different solid dosage forms were used. Polymer films were produced by solvent casting method and drug containing porous cellulose samples were prepared by depositing...... the drug-polymer solutions onto filter paper substrates. The quality of the electrodes and the release profile of Pr+ and Ld+ were investigated with \\r\

  20. Hybrid nanostructured drug carrier with tunable and controlled drug release

    International Nuclear Information System (INIS)

    Depan, D.; Misra, R.D.K.

    2012-01-01

    We describe here a transformative approach to synthesize a hybrid nanostructured drug carrier that exhibits the characteristics of controlled drug release. The synthesis of the nanohybrid architecture involved two steps. The first step involved direct crystallization of biocompatible copolymer along the long axis of the carbon nanotubes (CNTs), followed by the second step of attachment of drug molecule to the polymer via hydrogen bonding. The extraordinary inorganic–organic hybrid architecture exhibited high drug loading ability and is physically stable even under extreme conditions of acidic media and ultrasonic irradiation. The temperature and pH sensitive characteristics of the hybrid drug carrier and high drug loading ability merit its consideration as a promising carrier and utilization of the fundamental aspects used for synthesis of other promising drug carriers. The higher drug release response during the application of ultrasonic frequency is ascribed to a cavitation-type process in which the acoustic bubbles nucleate and collapse releasing the drug. Furthermore, the study underscores the potential of uniquely combining CNTs and biopolymers for drug delivery. - Graphical abstract: Block-copolymer crystallized on carbon nanotubes (CNTs). Nanohybrid drug carrier synthesized by attaching doxorubicin (DOX) to polymer crystallized CNTs. Crystallized polymer on CNTs provide mechanical stability. Triggered release of DOX. Highlights: ► The novel synthesis of a hybrid nanostructured drug carrier is described. ► The drug carrier exhibits high drug loading ability and is physically stable. ► The high drug release is ascribed to a cavitation-type process.

  1. Experimental study of PLLA/INH slow release implant fabricated by three dimensional printing technique and drug release characteristics in vitro.

    Science.gov (United States)

    Wu, Gui; Wu, Weigang; Zheng, Qixin; Li, Jingfeng; Zhou, Jianbo; Hu, Zhilei

    2014-07-19

    Local slow release implant provided long term and stable drug release in the lesion. The objective of this study was to fabricate biodegradable slow release INH/PLLA tablet via 3 dimensional printing technique (3DP) and to compare the drug release characteristics of three different structured tablets in vitro. Three different drug delivery systems (columnar-shaped tablet (CST), doughnut-shaped tablet (DST) and multilayer doughnut-shaped tablet (MDST)) were manufactured by the three dimensional printing machine and isoniazid was loaded into the implant. Dynamic soaking method was used to study the drug release characteristics of the three implants. MTT cytotoxicity test and direct contact test were utilized to study the biocompatibility of the implant. The microstructures of the implants' surfaces were observed with electron microscope. The PLLA powder in the tablet could be excellently combined through 3DP without disintegration. Electron microscope observations showed that INH distributed evenly on the surface of the tablet in a "nest-shaped" way, while the surface of the barrier layer in the multilayer doughnut shaped tablet was compact and did not contain INH. The concentration of INH in all of the three tablets were still higher than the effective bacteriostasis concentration (Isoniazid: 0.025 ~ 0.05 μg/ml) after 30 day's release in vitro. All of the tablets showed initial burst release of the INH in the early period. Drug concentration of MDST became stable and had little fluctuation starting from the 6th day of the release. Drug concentration of DST and CST decreased gradually and the rate of decrease in concentration was faster in DST than CST. MTT cytotoxicity test and direct contact test indicated that the INH-PLLA tablet had low cytotoxicity and favorable biocompatibility. Three dimensional printing technique was a reliable technique to fabricate complicated implants. Drug release pattern in MDST was the most stable among the three implants. It was

  2. Drug release into hydrogel-based subcutaneous surrogates studied by UV imaging

    DEFF Research Database (Denmark)

    Ye, Fengbin; Larsen, Susan Weng; Yaghmur, Anan

    2012-01-01

    of the performance of drug delivery systems based on in vitro experiments. The objective of this study was to evaluate a UV imaging-based method for real-time characterization of the release and transport of piroxicam in hydrogel-based subcutaneous tissue mimics/surrogates. Piroxicam partitioning from medium chain...... upon the injection of aqueous or MCT solutions into an agarose-based hydrogel were investigated by UV imaging. The spatial distribution of piroxicam around the injection site in the gel matrix was monitored in real-time. The disappearance profiles of piroxicam from the injected aqueous solution were...... obtained. This study shows that the UV imaging methodology has considerable potential for characterizing transport properties in hydrogels, including monitoring the real-time spatial concentration distribution in vitro after administration by injection....

  3. Understanding Drug Release Data through Thermodynamic Analysis

    Directory of Open Access Journals (Sweden)

    Marjorie Caroline Liberato Cavalcanti Freire

    2017-06-01

    Full Text Available Understanding the factors that can modify the drug release profile of a drug from a Drug-Delivery-System (DDS is a mandatory step to determine the effectiveness of new therapies. The aim of this study was to assess the Amphotericin-B (AmB kinetic release profiles from polymeric systems with different compositions and geometries and to correlate these profiles with the thermodynamic parameters through mathematical modeling. Film casting and electrospinning techniques were used to compare behavior of films and fibers, respectively. Release profiles from the DDSs were performed, and the mathematical modeling of the data was carried out. Activation energy, enthalpy, entropy and Gibbs free energy of the drug release process were determined. AmB release profiles showed that the relationship to overcome the enthalpic barrier was PVA-fiber > PVA-film > PLA-fiber > PLA-film. Drug release kinetics from the fibers and the films were better fitted on the Peppas–Sahlin and Higuchi models, respectively. The thermodynamic parameters corroborate these findings, revealing that the AmB release from the evaluated systems was an endothermic and non-spontaneous process. Thermodynamic parameters can be used to explain the drug kinetic release profiles. Such an approach is of utmost importance for DDS containing insoluble compounds, such as AmB, which is associated with an erratic bioavailability.

  4. Understanding Drug Release Data through Thermodynamic Analysis

    Science.gov (United States)

    Freire, Marjorie Caroline Liberato Cavalcanti; Alexandrino, Francisco; Marcelino, Henrique Rodrigues; Picciani, Paulo Henrique de Souza; Silva, Kattya Gyselle de Holanda e; Genre, Julieta; de Oliveira, Anselmo Gomes; do Egito, Eryvaldo Sócrates Tabosa

    2017-01-01

    Understanding the factors that can modify the drug release profile of a drug from a Drug-Delivery-System (DDS) is a mandatory step to determine the effectiveness of new therapies. The aim of this study was to assess the Amphotericin-B (AmB) kinetic release profiles from polymeric systems with different compositions and geometries and to correlate these profiles with the thermodynamic parameters through mathematical modeling. Film casting and electrospinning techniques were used to compare behavior of films and fibers, respectively. Release profiles from the DDSs were performed, and the mathematical modeling of the data was carried out. Activation energy, enthalpy, entropy and Gibbs free energy of the drug release process were determined. AmB release profiles showed that the relationship to overcome the enthalpic barrier was PVA-fiber > PVA-film > PLA-fiber > PLA-film. Drug release kinetics from the fibers and the films were better fitted on the Peppas–Sahlin and Higuchi models, respectively. The thermodynamic parameters corroborate these findings, revealing that the AmB release from the evaluated systems was an endothermic and non-spontaneous process. Thermodynamic parameters can be used to explain the drug kinetic release profiles. Such an approach is of utmost importance for DDS containing insoluble compounds, such as AmB, which is associated with an erratic bioavailability. PMID:28773009

  5. Understanding Drug Release Data through Thermodynamic Analysis.

    Science.gov (United States)

    Freire, Marjorie Caroline Liberato Cavalcanti; Alexandrino, Francisco; Marcelino, Henrique Rodrigues; Picciani, Paulo Henrique de Souza; Silva, Kattya Gyselle de Holanda E; Genre, Julieta; Oliveira, Anselmo Gomes de; Egito, Eryvaldo Sócrates Tabosa do

    2017-06-13

    Understanding the factors that can modify the drug release profile of a drug from a Drug-Delivery-System (DDS) is a mandatory step to determine the effectiveness of new therapies. The aim of this study was to assess the Amphotericin-B (AmB) kinetic release profiles from polymeric systems with different compositions and geometries and to correlate these profiles with the thermodynamic parameters through mathematical modeling. Film casting and electrospinning techniques were used to compare behavior of films and fibers, respectively. Release profiles from the DDSs were performed, and the mathematical modeling of the data was carried out. Activation energy, enthalpy, entropy and Gibbs free energy of the drug release process were determined. AmB release profiles showed that the relationship to overcome the enthalpic barrier was PVA-fiber > PVA-film > PLA-fiber > PLA-film. Drug release kinetics from the fibers and the films were better fitted on the Peppas-Sahlin and Higuchi models, respectively. The thermodynamic parameters corroborate these findings, revealing that the AmB release from the evaluated systems was an endothermic and non-spontaneous process. Thermodynamic parameters can be used to explain the drug kinetic release profiles. Such an approach is of utmost importance for DDS containing insoluble compounds, such as AmB, which is associated with an erratic bioavailability.

  6. Preparation, characterization, drug release and computational modelling studies of antibiotics loaded amorphous chitin nanoparticles.

    Science.gov (United States)

    Gayathri, N K; Aparna, V; Maya, S; Biswas, Raja; Jayakumar, R; Mohan, C Gopi

    2017-12-01

    We present a computational investigation of binding affinity of different types of drugs with chitin nanocarriers. Understanding the chitn polymer-drug interaction is important to design and optimize the chitin based drug delivery systems. The binding affinity of three different types of anti-bacterial drugs Ethionamide (ETA) Methacycline (MET) and Rifampicin (RIF) with amorphous chitin nanoparticles (AC-NPs) were studied by integrating computational and experimental techniques. The binding energies (BE) of hydrophobic ETA, hydrophilic MET and hydrophobic RIF were -7.3kcal/mol, -5.1kcal/mol and -8.1kcal/mol respectively, with respect to AC-NPs, using molecular docking studies. This theoretical result was in good correlation with the experimental studies of AC-drug loading and drug entrapment efficiencies of MET (3.5±0.1 and 25± 2%), ETA (5.6±0.02 and 45±4%) and RIF (8.9±0.20 and 53±5%) drugs respectively. Stability studies of the drug encapsulated nanoparticles showed stable values of size, zeta and polydispersity index at 6°C temperature. The correlation between computational BE and experimental drug entrapment efficiencies of RIF, ETA and MET drugs with four AC-NPs strands were 0.999 respectively, while that of the drug loading efficiencies were 0.854 respectively. Further, the molecular docking results predict the atomic level details derived from the electrostatic, hydrogen bonding and hydrophobic interactions of the drug and nanoparticle for its encapsulation and loading in the chitin-based host-guest nanosystems. The present results thus revealed the drug loading and drug delivery insights and has the potential of reducing the time and cost of processing new antibiotic drug delivery nanosystem optimization, development and discovery. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Microwave Activation of Drug Release

    DEFF Research Database (Denmark)

    Jónasson, Sævar Þór

    Due to current limitations in control of pharmaceutical drug release in the body along with increasing medicine use, methods of externally-controlled drug release are of high interest. In this thesis, the use of microwaves is proposed as a technique with the purpose of externally activating...... setup, called the microwave activation system has been developed and tested on a body phantom that emulates the human torso. The system presented in this thesis, operates unobtrusively, i.e. without physically interfering with the target (patient). The torso phantom is a simple dual-layered cylindrical...... the phantom is of interest for disclosing essential information about the limitations of the concept, the phantom and the system. For these purposes, a twofold operation of the microwave activation system was performed, which are reciprocal of each other. In the first operation phase, named mapping...

  8. Analysis of drug effects on neurotransmitter release

    International Nuclear Information System (INIS)

    Rowell, P.; Garner, A.

    1986-01-01

    The release of neurotransmitter is routinely studied in a superfusion system in which serial samples are collected and the effects of drugs or other treatments on the amount of material in the superfusate is determined. With frequent sampling interval, this procedure provides a mechanism for dynamically characterizing the release process itself. Using automated data collection in conjunction with polyexponential computer analysis, the equation which describes the release process in each experiment is determined. Analysis of the data during the nontreated phase of the experiment allows an internal control to be used for accurately assessing any changes in neurotransmitter release which may occur during a subsequent treatment phase. The use of internal controls greatly improves the signal to noise ratio and allows determinations of very low concentrations of drugs on small amounts of tissue to be made. In this presentation, the effects of 10 μM nicotine on 3 H-dopamine release in rat nucleus accumbens is described. The time course, potency and efficacy of the drug treatment is characterized using this system. Determinations of the exponential order of the release as well as the rate constants allow one to study the mechanism of the release process. A description of 3 H-dopamine release in normal as well as Ca ++ -free medium is presented

  9. Functionalized silica nanoparticles as a carrier for Betamethasone Sodium Phosphate: Drug release study and statistical optimization of drug loading by response surface method.

    Science.gov (United States)

    Ghasemnejad, M; Ahmadi, E; Mohamadnia, Z; Doustgani, A; Hashemikia, S

    2015-11-01

    Mesoporous silica nanoparticles with a hexagonal structure (SBA-15) were synthesized and modified with (3-aminopropyl) triethoxysilane (APTES), and their performance as a carrier for drug delivery system was studied. Chemical structure and morphology of the synthesized and modified SBA-15 were characterized by SEM, BET, TEM, FT-IR and CHN technique. Betamethasone Sodium Phosphate (BSP) as a water soluble drug was loaded on the mesoporous silica particle for the first time. The response surface method was employed to obtain the optimum conditions for the drug/silica nanoparticle preparation, by using Design-Expert software. The effect of time, pH of preparative media, and drug/silica ratio on the drug loading efficiency was investigated by the software. The maximum loading (33.69%) was achieved under optimized condition (pH: 1.8, time: 3.54 (h) and drug/silica ratio: 1.7). The in vitro release behavior of drug loaded particles under various pH values was evaluated. Finally, the release kinetic of the drug was investigated using the Higuchi and Korsmeyer-Peppas models. Cell culture and cytotoxicity assays revealed the synthesized product doesn't have any cytotoxicity against human bladder cell line 5637. Accordingly, the produced drug-loaded nanostructures can be applied via different routes, such as implantation and topical or oral administration. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. pH- and thermo-responsive microcontainers as potential drug delivery systems: Morphological characteristic, release and cytotoxicity studies.

    Science.gov (United States)

    Efthimiadou, Eleni K; Tapeinos, Christos; Tziveleka, Leto-Aikaterini; Boukos, Nikos; Kordas, George

    2014-04-01

    Polymeric pH- and thermo-sensitive microcontainers (MCs) were developed as a potential drug delivery system for cancer therapy. It is well known that cancer cells exhibit notable characteristics such as acidic pH due to glycolytic cycle and higher temperature due to their higher proliferation rate. Based on these characteristics, we constructed a dual pH- and thermo-sensitive material for specific drug release on the pathological tissue. The MC's fabrication is based on a two-step procedure, in which, the first step involves the core synthesis and the second one is related to the shell formation. The core consists of poly(methyl methacrylate (PMMA), while the shell consists of PMMA, poly(isopropylacrylamide), poly(acrylic acid) and poly(divinylbenzene). Three different types of MCs were synthesized based on the seed polymerization method. The synthesized MCs were characterized structurally by Fourier transform infrared and morphologically by scanning electron microscopy. Dynamic light scattering was also used to study their behavior in aqueous solution under different pH and temperature conditions. For the loading and release study, the anthracycline drug daunorubicin (DNR) was used as a model drug, and its release properties were evaluated under different pH and thermo-conditions. Cytotoxicity studies were also carried out against MCF-7 breast cancer and 3T3 mouse embryonic fibroblast cells. According to our results, the synthesized microcontainers present desired pH and thermo behavior and can be applied in drug delivery systems. It is worth mentioning that the synthesized microcontainers which incorporated the drug DNR exhibit higher toxicity than the free drug. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. A targeted liposome delivery system for combretastatin A4: formulation optimization through drug loading and in vitro release studies.

    Science.gov (United States)

    Nallamothu, Ramakrishna; Wood, George C; Kiani, Mohammad F; Moore, Bob M; Horton, Frank P; Thoma, Laura A

    2006-01-01

    Efficient liposomal therapeutics require high drug loading and low leakage. The objective of this study is to develop a targeted liposome delivery system for combretastatin A4 (CA4), a novel antivascular agent, with high loading and stable drug encapsulation. Liposomes composed of hydrogenated soybean phosphatidylcholine (HSPC), cholesterol, and distearoyl phosphoethanolamine-PEG-2000 conjugate (DSPE-PEG) were prepared by the lipid film hydration and extrusion process. Cyclic arginine-glycine-aspartic acid (RGD) peptides with affinity for alphav beta3-integrins overexpressed on tumor vascular endothelial cells were coupled to the distal end of polyethylene glycol (PEG) on the liposomes sterically stabilized with PEG (non-targeted liposomes; LCLs). Effect of lipid concentration, drug-to-lipid ratio, cholesterol, and DSPE-PEG content in the formulation on CA4 loading and its release from the liposomes was studied. Total liposomal CA4 levels obtained increased with increasing lipid concentration in the formulation. As the drug-to-lipid ratio increased from 10:100 to 20:100, total drug in the liposome formulation increased from 1.05+/-0.11 mg/mL to 1.55+/-0.13 mg/mL, respectively. When the drug-to-lipid ratio was further raised to 40:100, the total drug in liposome formulation did not increase, but the amount of free drug increased significantly, thereby decreasing the percent of entrapped drug. Increasing cholesterol content in the formulation decreased drug loading. In vitro drug leakage from the liposomes increased with increase in drug-to-lipid ratio or DSPE-PEG content in the formulation; whereas increasing cholesterol content of the formulation up to 30 mol-percent, decreased CA4 leakage from the liposomes. Ligand coupling to the liposome surface increased drug leakage as a function of ligand density. Optimized liposome formulation with 100 mM lipid concentration, 20:100 drug-to-lipid ratio, 30 mol-percent cholesterol, 4 mol-percent DSPE-PEG, and 1 mol

  12. Assessment of Aprotinin Loaded Microemulsion Formulations for Parenteral Drug Delivery: Preparation, Characterization, in vitro Release and Cytotoxicity Studies.

    Science.gov (United States)

    Okur, Neslihan Üstündağ; Özdemir, Derya İlem; Kahyaoğlu, Şennur Görgülü; Şenyiğit, Zeynep Ay; Aşıkoğlu, Makbule; Genç, Lütfi; Karasulu, H Yeşim

    2015-01-01

    The object of the current study was to prepare novel microemulsion formulations of aprotinin for parenteral delivery and to compare in vitro characteristics and release behaviour of different Technetium-99m ((99m)Tc)-Aprotinin loaded microemulsion formulations. In addition, cytotoxicity of microemulsion formulation was evaluated with cell culture studies on human immortalized pancreatic duct epithelial-like cells. For this aim, firstly, pseudo-ternary phase diagrams were plotted to detect the formulation region and optimal microemulsions were characterized for their thermodynamic stability, conductivity, particle size, zeta potential, viscosity, pH and in vitro release properties. For in vitro release studies aprotinin was labelled with (99m)Tc and labelling efficiency, radiochemical purity and stability of the radiolabeled complex were determined by several chromatography techniques. Radiolabeling efficiency of (99m)Tc-Aprotinin was found over than 90% without any significant changes up to 6 hours after labelling at room temperature. After that, in vitro release studies of (99m)Tc-Aprotinin loaded microemulsions were performed with two different methods; dissolution from diffusion cells and dialysis bags. Both methods showed that release rate of (99m)Tc- Aprotinin from microemulsion could be controlled by microemulsion formulations. Drug release from the optimized microemulsion formulations was found lower compared to drug solution at the end of six hours. According to stability studies, the optimized formulation was found to be stable over a period of 12 months. Also, human immortalized pancreatic duct epithelial-like cells were used to evaluate the cytotoxicity of optimum formulation. Developed microemulsion did not reveal cytotoxicity. In conclusion the present study indicated that the M1-APT microemulsion is appropriate for intravenous application of aprotinin.

  13. Drug Release Mechanism of Slightly Soluble Drug from ...

    African Journals Online (AJOL)

    theophylline (THP) as drug in drug to clay ratios of 1:2, 3:4 and 1:1. The formulations were characterized for drug release and loading. Dependent and independent kinetic models were employed to analyze the drug release data. Fourier transform infrared spectroscopy (FTIR) was used for the structural characterization of ...

  14. Parameters to be Considered in the Simulation of Drug Release ...

    African Journals Online (AJOL)

    Purpose: Drug microparticles may be microencapsulated with water-insoluble polymers to obtain controlled release, which may be further determined by the particle distribution. The purpose of this study was to determine the drug release parameters needed for the theoretical prediction of the release profiles of single ...

  15. Studies on dissolution enhancement and mathematical modeling of drug release of a poorly water-soluble drug using water-soluble carriers.

    Science.gov (United States)

    Ahuja, Naveen; Katare, Om Prakash; Singh, Bhupinder

    2007-01-01

    Role of various water-soluble carriers was studied for dissolution enhancement of a poorly soluble model drug, rofecoxib, using solid dispersion approach. Diverse carriers viz. polyethylene glycols (PEG 4000 and 6000), polyglycolized fatty acid ester (Gelucire 44/14), polyvinylpyrollidone K25 (PVP), poloxamers (Lutrol F127 and F68), polyols (mannitol, sorbitol), organic acid (citric acid) and hydrotropes (urea, nicotinamide) were investigated for the purpose. Phase-solubility studies revealed AL type of curves for each carrier, indicating linear increase in drug solubility with carrier concentration. The sign and magnitude of the thermodynamic parameter, Gibbs free energy of transfer, indicated spontaneity of solubilization process. All the solid dispersions showed dissolution improvement vis-à-vis pure drug to varying degrees, with citric acid, PVP and poloxamers as the most promising carriers. Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer-Peppas model and the drug release kinetics primarily as Fickian diffusion. Solid state characterization of the drug-poloxamer binary system using XRD, FTIR, DSC and SEM techniques revealed distinct loss of drug crystallinity in the formulation, ostensibly accounting for enhancement in dissolution rate.

  16. Controlled drug release from bifunctionalized mesoporous silica

    Science.gov (United States)

    Xu, Wujun; Gao, Qiang; Xu, Yao; Wu, Dong; Sun, Yuhan; Shen, Wanling; Deng, Feng

    2008-10-01

    Serial of trimethylsilyl-carboxyl bifunctionalized SBA-15 (TMS/COOH/SBA-15) have been studied as carriers for controlled release of drug famotidine (Famo). To load Famo with large capacity, SBA-15 with high content of carboxyl groups was successfully synthesized by one-pot synthesis under the assistance of KCl. The mesostructure of carboxyl functionalized SBA-15 (COOH/SBA-15) could still be kept even though the content of carboxyl groups was up to 57.2%. Increasing carboxyl content could effectively enhance the loading capacity of Famo. Compared with pure SBA-15, into which Famo could be hardly adsorbed, the largest drug loading capacity of COOH/SBA-15 could achieve 396.9 mg/g. The release of Famo from mesoporous silica was studied in simulated intestine fluid (SIF, pH=7.4). For COOH/SBA-15, the release rate of Famo decreased with narrowing pore size. After grafting TMS groups on the surface of COOH/SBA-15 with hexamethyldisilazane, the release of Famo was greatly delayed with the increasing content of TMS groups.

  17. Effects of HPMC substituent pattern on water up-take, polymer and drug release: An experimental and modelling study.

    Science.gov (United States)

    Caccavo, Diego; Lamberti, Gaetano; Barba, Anna Angela; Abrahmsén-Alami, Susanna; Viridén, Anna; Larsson, Anette

    2017-08-07

    The purpose of this study was to investigate the hydration behavior of two matrix formulations containing the cellulose derivative hydroxypropyl methylcellulose (HPMC). The two HPMC batches investigated had different substitution pattern along the backbone; the first one is referred to as heterogeneous and the second as homogenous. The release of both the drug molecule theophylline and the polymer was determined. Additionally, the water concentrations at different positions in the swollen gel layers were determined by Magnetic Resonance Imaging. The experimental data was compared to predicted values obtained by the extension of a mechanistic Fickian based model. The hydration of tablets containing the more homogenous HPMC batch showed a gradual water concentration gradient in the gel layer and could be well predicted. The hydration process for the more heterogeneous batch showed a very abrupt step change in the water concentration in the gel layer and could not be well predicted. Based on the comparison between the experimental and predicted data this study suggests, for the first time, that formulations with HPMC of different heterogeneities form gels in different ways. The homogeneous HPMC batch exhibits a water sorption behavior ascribable to a Ficḱs law for the diffusion process whereas the more heterogeneous HPMC batches does not. This conclusion is important in the future development of simulation models and in the understanding of drug release mechanism from hydrophilic matrices. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. In-vitro release and permeation studies of ketoconazole from optimized dermatological vehicles using powder, nanoparticles and solid dispersion forms of drug

    Science.gov (United States)

    Mohammed, Irfan A.

    To optimize the clinical efficacy of Ketoconazole from an externally applied product, this project was undertaken to evaluate the drug release/permeation profile from various dermatological vehicles using regular powder, nanoparticles and solid dispersion forms with reduced level of drug. Nanoparticles of drug were prepared by wet media milling method using Polyvinylpyrrolidone (PVP-10K) as a stabilizer. The nanoparticles were in the size range of 250-300nm. Solid dispersion was prepared by solvent evaporation method using drug to PVP-10K at a weight ratio of (1:2). Formulations containing 1% w/w drug were developed using HPMC gel, Carbomer gel and a cationic cream as the vehicles. Penetration enhancers including propylene glycol (PG), dimethylsulfoxide (DMSO) and polyethylene glycol 400 (PEG-400) at various levels were evaluated. A commercial 2% w/w ketoconazole product was included as a control for comparison. Studies were carried out with Franz Diffusion Cells using cellulose membrane and human cadaver skin for two and six hour studies. Among the formulations evaluated, the general rank order of the drug release through the cellulose membrane was observed to be: HPMC gel base > Anionic gel base > Cationic gel base > Commercial product. The addition of penetration enhancers showed variable effects in all samples evaluated. However, the HPMC gel-based vehicle showed significant effect in enhancing the drug release in the presence of DMSO. The formulation containing 1% w/w ketoconazole and 20% w/w DMSO gave a maximum drug release of 20.21% when compared to only 1.60% from the commercial product. This represents a twelve fold increase in the release of ketoconazole from the formulation. Furthermore, when the optimum gel-based formulation containing 1% w/w ketoconazole was studied over an extended period of 6 hours, it gave 36.01% drug release from the sample formulation compared to only 2.00% from the commercial product. Finally, this formulation was selected to

  19. Effect of HPMC and mannitol on drug release and bioadhesion behavior of buccal discs of buspirone hydrochloride: In-vitro and in-vivo pharmacokinetic studies

    OpenAIRE

    Jaipal, A.; Pandey, M.M.; Charde, S.Y.; Raut, P.P.; Prasanth, K.V.; Prasad, R.G.

    2015-01-01

    Delivery of orally compromised therapeutic drug molecules to the systemic circulation via buccal route has gained a significant interest in recent past. Bioadhesive polymers play a major role in designing such buccal dosage forms, as they help in adhesion of designed delivery system to mucosal membrane and also prolong release of drug from delivery system. In the present study, HPMC (release retarding polymer) and mannitol (diluent and pore former) were used to prepare bioadhesive and control...

  20. Study of split-ring resonators for use on a pharmaceutical drug capsule for microwave activated drug release

    DEFF Research Database (Denmark)

    Jónasson, Sævar Þór; Jensen, Brian Sveistrup; Johansen, Tom Keinicke

    2012-01-01

    In this paper, a novel method for externally activating a pharmaceutical drug capsule by use of split-ring resonators (SRR) is introduced. To this end, the effect of the orientation of the SRRs on the ability to activate the capsules is examined. A coplanar waveguide is used to excite an identical...... pair of SRRs fabricated on a substrate, representing an enlarged lid for a pharmaceutical drug capsule. Orientations where the electric field component of a quasi-TEM wave lies across the gap of the SRRs provides the largest response. The optimal case is when the electric field component lies across...... the gap simultaneously with the magnetic field component normal to the SRRs. Furthermore, an analysis of the optimal conductivity and relative permittivity for enhanced temperature rise in the lid is performed. Conductivity of 0.09 S/m and relative permittivity of 12 shows the highest temperature rise....

  1. Drug release kinetic analysis and prediction of release data via polymer molecular weight in sustained release diltiazem matrices.

    Science.gov (United States)

    Adibkia, K; Ghanbarzadeh, S; Mohammadi, G; Khiavi, H Z; Sabzevari, A; Barzegar-Jalali, M

    2014-03-01

    This study was conducted to investigate the effects of HPMC (K4M and K100M) as well as tragacanth on the drug release rate of diltiazem (DLTZ) from matrix tablets prepared by direct compression method.Mechanism of drug transport through the matrices was studied by fitting the release data to the 10 kinetic models. 3 model independent parameters; i. e., mean dissolution time (MDT), mean release rate (MRR) and release rate efficacy (RE) as well as 5 time point approaches were established to compare the dissolution profiles. To find correlation between fraction of drug released and polymer's molecular weight, dissolution data were fitted into two proposed equations.All polymers could sustain drug release up to 10 h. The release data were fitted best to Peppas and Higuchi square root kinetic models considering squared correlation coefficient and mean percent error (MPE). RE and MRR were decreased when polymer to drug ratio was increased. Conversely, t60% was increased with raising polymer /drug ratio. The fractions of drug released from the formulations prepared with tragacanth were more than those formulated using the same amount of HPMC K4M and HPMC K100M.Preparation of DLTZ matrices applying HPMCK4M, HPMC K100M and tragacanth could effectively extend the drug release. © Georg Thieme Verlag KG Stuttgart · New York.

  2. Effect of HPMC and mannitol on drug release and bioadhesion behavior of buccal discs of buspirone hydrochloride: In-vitro and in-vivo pharmacokinetic studies.

    Science.gov (United States)

    Jaipal, A; Pandey, M M; Charde, S Y; Raut, P P; Prasanth, K V; Prasad, R G

    2015-07-01

    Delivery of orally compromised therapeutic drug molecules to the systemic circulation via buccal route has gained a significant interest in recent past. Bioadhesive polymers play a major role in designing such buccal dosage forms, as they help in adhesion of designed delivery system to mucosal membrane and also prolong release of drug from delivery system. In the present study, HPMC (release retarding polymer) and mannitol (diluent and pore former) were used to prepare bioadhesive and controlled release buccal discs of buspirone hydrochloride (BS) by direct compression method. Compatibility of BS with various excipients used during the study was assessed using DSC and FTIR techniques. Effect of mannitol and HPMC on drug release and bioadhesive strength was studied using a 3(2) factorial design. The drug release rate from delivery system decreased with increasing levels of HPMC in formulations. However, bioadhesive strength of formulations increased with increasing proportion of HPMC in buccal discs. Increased levels of mannitol resulted in faster rate of drug release and rapid in vitro uptake of water due to the formation of channels in the matrix. Pharmacokinetic studies of designed bioadhesive buccal discs in rabbits demonstrated a 10-fold increase in bioavailability in comparison with oral bioavailability of buspirone reported.

  3. Study Drugs

    Science.gov (United States)

    ... to quit, they may have withdrawal symptoms like depression, thoughts of suicide, intense drug cravings, sleep problems, and fatigue. The health risks aren't the only downside to study drugs. Students caught with illegal prescription drugs may get suspended ...

  4. Controlled drug release for tissue engineering.

    Science.gov (United States)

    Rambhia, Kunal J; Ma, Peter X

    2015-12-10

    Tissue engineering is often referred to as a three-pronged discipline, with each prong corresponding to 1) a 3D material matrix (scaffold), 2) drugs that act on molecular signaling, and 3) regenerative living cells. Herein we focus on reviewing advances in controlled release of drugs from tissue engineering platforms. This review addresses advances in hydrogels and porous scaffolds that are synthesized from natural materials and synthetic polymers for the purposes of controlled release in tissue engineering. We pay special attention to efforts to reduce the burst release effect and to provide sustained and long-term release. Finally, novel approaches to controlled release are described, including devices that allow for pulsatile and sequential delivery. In addition to recent advances, limitations of current approaches and areas of further research are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. A stent for co-delivering paclitaxel and nitric oxide from abluminal and luminal surfaces: Preparation, surface characterization, and in vitro drug release studies

    Energy Technology Data Exchange (ETDEWEB)

    Gallo, Annemarie; Mani, Gopinath, E-mail: Gopinath.Mani@usd.edu

    2013-08-15

    Most drug-eluting stents currently available are coated with anti-proliferative drugs on both abluminal (toward blood vessel wall) and luminal (toward lumen) surfaces to prevent neointimal hyperplasia. While the abluminal delivery of anti-proliferative drugs is useful for controlling neointimal hyperplasia, the luminal delivery of such drugs impairs or prevents endothelialization which causes late stent thrombosis. This research is focused on developing a bidirectional dual drug-eluting stent to co-deliver an anti-proliferative agent (paclitaxel – PAT) and an endothelial cell promoting agent (nitric oxide – NO) from abluminal and luminal surfaces of the stent, respectively. Phosphonoacetic acid, a polymer-free drug delivery platform, was initially coated on the stents. Then, the PAT and NO donor drugs were co-coated on the abluminal and luminal stent surfaces, respectively. The co-coating of drugs was collectively confirmed by the surface characterization techniques such as Fourier transform infrared spectroscopy, scanning electron microscopy (SEM), 3D optical surface profilometry, and contact angle goniometry. SEM showed that the integrity of the co-coating of drugs was maintained without delamination or cracks formation occurring during the stent expansion experiments. In vitro drug release studies showed that the PAT was released from the abluminal stent surfaces in a biphasic manner, which is an initial burst followed by a slow and sustained release. The NO was burst released from the luminal stent surfaces. Thus, this study demonstrated the co-delivery of PAT and NO from abluminal and luminal stent surfaces, respectively. The stent developed in this study has potential applications in inhibiting neointimal hyperplasia as well as encouraging luminal endothelialization to prevent late stent thrombosis.

  6. A stent for co-delivering paclitaxel and nitric oxide from abluminal and luminal surfaces: Preparation, surface characterization, and in vitro drug release studies

    International Nuclear Information System (INIS)

    Gallo, Annemarie; Mani, Gopinath

    2013-01-01

    Most drug-eluting stents currently available are coated with anti-proliferative drugs on both abluminal (toward blood vessel wall) and luminal (toward lumen) surfaces to prevent neointimal hyperplasia. While the abluminal delivery of anti-proliferative drugs is useful for controlling neointimal hyperplasia, the luminal delivery of such drugs impairs or prevents endothelialization which causes late stent thrombosis. This research is focused on developing a bidirectional dual drug-eluting stent to co-deliver an anti-proliferative agent (paclitaxel – PAT) and an endothelial cell promoting agent (nitric oxide – NO) from abluminal and luminal surfaces of the stent, respectively. Phosphonoacetic acid, a polymer-free drug delivery platform, was initially coated on the stents. Then, the PAT and NO donor drugs were co-coated on the abluminal and luminal stent surfaces, respectively. The co-coating of drugs was collectively confirmed by the surface characterization techniques such as Fourier transform infrared spectroscopy, scanning electron microscopy (SEM), 3D optical surface profilometry, and contact angle goniometry. SEM showed that the integrity of the co-coating of drugs was maintained without delamination or cracks formation occurring during the stent expansion experiments. In vitro drug release studies showed that the PAT was released from the abluminal stent surfaces in a biphasic manner, which is an initial burst followed by a slow and sustained release. The NO was burst released from the luminal stent surfaces. Thus, this study demonstrated the co-delivery of PAT and NO from abluminal and luminal stent surfaces, respectively. The stent developed in this study has potential applications in inhibiting neointimal hyperplasia as well as encouraging luminal endothelialization to prevent late stent thrombosis.

  7. 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.

  8. In vitro dissolution study of acetylsalicylic acid solid dispersions. Tunable drug release allowed by the choice of polymer matrix

    Czech Academy of Sciences Publication Activity Database

    Policianová, Olivia; Brus, Jiří; Hrubý, Martin; Urbanová, Martina

    2015-01-01

    Roč. 20, č. 8 (2015), s. 935-940 ISSN 1083-7450 R&D Projects: GA ČR(CZ) GA14-03636S; GA ČR GPP106/11/P426 Grant - others:AV ČR(CZ) M200501201 Program:M Institutional support: RVO:61389013 Keywords : acetylsallicylic acid * controlled drug release * polymers Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.566, year: 2015

  9. Hydrophobic Drug-Loaded PEGylated Magnetic Liposomes for Drug-Controlled Release

    Science.gov (United States)

    Hardiansyah, Andri; Yang, Ming-Chien; Liu, Ting-Yu; Kuo, Chih-Yu; Huang, Li-Ying; Chan, Tzu-Yi

    2017-05-01

    Less targeted and limited solubility of hydrophobic-based drug are one of the serious obstacles in drug delivery system. Thus, new strategies to enhance the solubility of hydrophobic drug and controlled release behaviors would be developed. Herein, curcumin, a model of hydrophobic drug, has been loaded into PEGylated magnetic liposomes as a drug carrier platform for drug controlled release system. Inductive magnetic heating (hyperthermia)-stimulated drug release, in vitro cellular cytotoxicity assay of curcumin-loaded PEGylated magnetic liposomes and cellular internalization-induced by magnetic guidance would be investigated. The resultant of drug carriers could disperse homogeneously in aqueous solution, showing a superparamagnetic characteristic and could inductive magnetic heating with external high-frequency magnetic field (HFMF). In vitro curcumin release studies confirmed that the drug carriers exhibited no significant release at 37 °C, whereas exhibited rapid releasing at 45 °C. However, it would display enormous (three times higher) curcumin releasing under the HFMF exposure, compared with that without HFMF exposure at 45 °C. In vitro cytotoxicity test shows that curcumin-loaded PEGylated magnetic liposomes could efficiently kill MCF-7 cells in parallel with increasing curcumin concentration. Fluorescence microscopy observed that these drug carriers could internalize efficiently into the cellular compartment of MCF-7 cells. Thus, it would be anticipated that the novel hydrophobic drug-loaded PEGylated magnetic liposomes in combination with inductive magnetic heating are promising to apply in the combination of chemotherapy and thermotherapy for cancer therapy.

  10. A study of chitosan hydrogel with embedded mesoporous silica nanoparticles loaded by ibuprofen as a dual stimuli-responsive drug release system for surface coating of titanium implants.

    Science.gov (United States)

    Zhao, Pengkun; Liu, Hongyu; Deng, Hongbing; Xiao, Ling; Qin, Caiqin; Du, Yumin; Shi, Xiaowen

    2014-11-01

    In this study, the complex pH and electro responsive system made of chitosan hydrogel with embedded mesoporous silica nanoparticles (MSNs) was evaluated as a tunable drug release system. As a model drug, ibuprofen (IB) was used; its adsorption in MSNs was evidenced by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and thermogravimetric analysis (TG). In order to prepare the complex drug release system, the loaded particles IB-MSNs were dispersed in chitosan solution and then the complex IB-MSNs/chitosan film of 2mm thickness was deposited as a hydrogel on the titanium electrode. The codeposition of components was performed under a negative biasing of the titanium electrode at -0.75 mA/cm2 current density during 30 min. The IB release from the IB-MSNs/chitosan hydrogel film was studied as dependent on pH of the release media and electrical conditions applied to the titanium plate. When incubating the complex hydrogel film in buffers with different pH, the IB release followed a near zero-order profile, though its kinetics varied. Compared to the spontaneous IB release from the hydrogel in 0.9% NaCl solution (at 0 V), the application of negative biases to the coated titanium plate had profound effluences on the release behavior. The release was retarded when -1.0 V was applied, but a faster kinetics was observed at -5.0 V. These results imply that a rapid, mild and facile electrical process for covering titanium implants by complex IB-MSNs/chitosan hydrogel films can be used for controlled drug delivery applications. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Development and Optimization of controlled drug release ...

    African Journals Online (AJOL)

    The aim of this study is to develop and optimize an osmotically controlled drug delivery system of diclofenac sodium. Osmotically controlled oral drug delivery systems utilize osmotic pressure for controlled delivery of active drugs. Drug delivery from these systems, to a large extent, is independent of the physiological factors ...

  12. Modulatory effect of polymer type and composition on drug release ...

    African Journals Online (AJOL)

    The purpose of this study was to investigate the effects of polymer type and composition on drug release from the matrix of diclofenac sodium sustained release tablets formulated using three different granulation methods. Ten (10) batches of diclofenac sodium tablets (F01 - F10) were prepared by melt granulation, ...

  13. Investigating the in vitro drug release kinetics from controlled release diclofenac potassium-ethocel matrix tablets and the influence of co-excipients on drug release patterns.

    Science.gov (United States)

    Shah, Shefaat Ullah; Shah, Kifayat Ullah; Rehman, Asimur; Khan, Gul Majid

    2011-04-01

    The objective of the study was to formulate and evaluate controlled release polymeric tablets of Diclofenac Potassium for the release rate, release patterns and the mechanism involved in the release process of the drug. Formulations with different types and grades of Ethyl Cellulose Ether derivatives in several drug-to-polymer ratios (D:P) were compressed into tablets using the direct compression method. In vitro drug release studies were performed in phosphate buffer (pH 7.4) as dissolution medium by using USP Method-1 (Rotating Basket Method). Similarity factor f2 and dissimilarity factor f1 were applied for checking the similarities and dissimilarities of the release profiles of different formulations. For the determination of the release mechanism and drug release kinetics various mathematical/kinetic models were employed. It was found that all of the Ethocel polymers could significantly slow down the drug release rate with Ethocel FP polymers being the most efficient, especially at D:P ratios of 10:03 which lead towards the achievement of zero or near zero order release kinetics.

  14. Reinforcing the inner phase of the filled hydrogels with CNTs alters drug release properties and human keratinocyte morphology: A study on the gelatin- tamarind gum filled hydrogels.

    Science.gov (United States)

    Maharana, Vivek; Gaur, Deepanjali; Nayak, Suraj K; Singh, Vinay K; Chakraborty, Subhabrata; Banerjee, Indranil; Ray, Sirsendu S; Anis, Arfat; Pal, Kunal

    2017-11-01

    The study reports the synthesis and characterization of gelatin-tamarind gum (TG) based filled hydrogels for drug delivery applications. In this study, three different types of carbon nanotubes (CNTs) were incorporated within the dispersed TG phase of the filled hydrogels. The prepared hydrogels were thoroughly characterised using bright field microscope, FESEM, FTIR spectroscopy, differential scanning calorimeter, and mechanical tester. The swelling and the drug (salicylic acid) release properties of the filled hydrogels were also evaluated. The micrographs revealed the formation of biphasic systems. The internal phase appeared as agglomerates, and the CNTs were confined within the dispersed TG phase. FTIR and XRD studies revealed that CNTs promoted associative interactions among the components of the hydrogel, which promoted the formation of large crystallite size. The mechanical study indicated better resistance to the breakdown of the architecture of the CNT-containing filled hydrogels. Drug release studies, both passive and iontophoretic, suggested that the non-Fickian diffusion of the drug was prevalent during its release from hydrogel matrices. The prepared hydrogels were cytocompatible with human keratinocytes. The results suggested the probable use of such hydrogels in wound healing, tissue engineering and drug delivery applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Biodegradable hollow fibres for the controlled release of drugs

    NARCIS (Netherlands)

    Schakenraad, J.M.; Oosterbaan, J.A.; Nieuwenhuis, P.; Molenaar, I.; Olijslager, J.; Potman, W.; Eenink, M.J.D.; Feijen, Jan

    1988-01-01

    Biodegradable hollow fibres of poly-l-lactic acid (PLLA) filled with a suspension of the contraceptive hormone levonorgestrel in castor oil were implanted subcutaneously in rats to study the rate of drug release, rate of biodegradation and tissue reaction caused by the implant. The in vivo drug

  16. Thermosensitive liposomes entrapping iron oxide nanoparticles for controllable drug release

    International Nuclear Information System (INIS)

    Tai, L-A; Wang, Y-C; Wang, Y-J; Yang, C-S; Tsai, P-J; Lo, L-W

    2009-01-01

    Iron oxide nanoparticles can serve as a heating source upon alternative magnetic field (AMF) exposure. Iron oxide nanoparticles can be mixed with thermosensitive nanovehicles for hyperthermia-induced drug release, yet such a design and mechanism may not be suitable for controllable drug release applications in which the tissues are susceptible to environmental temperature change such as brain tissue. In the present study, iron oxide nanoparticles were entrapped inside of thermosensitive liposomes for AMF-induced drug release while the environmental temperature was maintained at a constant level. Carboxyfluorescein was co-entrapped with the iron oxide nanoparticles in the liposomes as a model compound for monitoring drug release and environmental temperature was maintained with a water circulator jacket. These experiments have been successfully performed in solution, in phantom and in anesthetized animals. Furthermore, the thermosensitive liposomes were administered into rat forearm skeletal muscle, and the release of carboxylfluorescein triggered by the external alternative magnetic field was monitored by an implanted microdialysis perfusion probe with an on-line laser-induced fluorescence detector. In the future such a device could be applied to simultaneous magnetic resonance imaging and non-invasive drug release in temperature-sensitive applications.

  17. POLYURETHANE COMPOSITES AS DRUG CARRIERS:: RELEASE PATTERNS

    Directory of Open Access Journals (Sweden)

    M. V. Grigoreva

    2013-10-01

    Full Text Available Biodegradable polyurethanes attract interest of those developing composite materials for biomedical applications. One of their features is their ability to serve as carriers, or matrixes, for medicines and other bioactive compounds to produce a therapeutic effect in body through targeted and/or prolonged delivery of these compounds in the process of their controlled release from matrix. The review presents polyurethane composites as matrices for a number of drugs. The relation between structure of the composites and their degradability both in vitro and in vivo and the dependence of drug release kinetics on physicochemical properties of polyurethane matrix are highlighted. The release of drugs (cefazolin, naltrexone and piroxicam from the composites based on cross-linked polyurethanes (synthesized from laprols, Mw between 1,500 and 2,000 Da and toluylene diisocyanate demonstrated more or less the same pattern (about 10 days in vitro and three to five days in vivo. In contrast, the composites with dioxydine based on a linear polyurethanes (synthesized from oligotetramethilene glycol, Mw 1,000 Da, diphenylmethane-4,4’-diisocyanate and 1,4-butanediol retained their antimicrobial activity at least 30 days. They also showed a significantly higher breaking strength as compared to that of the composites based on cross-linked polyurethanes.

  18. Electrostimulated Release of Neutral Drugs from Polythiophene Nanoparticles: Smart Regulation of Drug-Polymer Interactions.

    Science.gov (United States)

    Puiggalí-Jou, Anna; Micheletti, Paolo; Estrany, Francesc; Del Valle, Luis J; Alemán, Carlos

    2017-09-01

    Poly(3,4-ethylenedioxythiophene) (PEDOT) nanoparticles are loaded with curcumin and piperine by in situ emulsion polymerization using dodecyl benzene sulfonic acid both as a stabilizer and a doping agent. The loaded drugs affect the morphology, size, and colloidal stability of the nanoparticles. Furthermore, kinetics studies of nonstimulated drug release have evidenced that polymer···drug interactions are stronger for curcumin than for piperine. This observation suggests that drug delivery systems based on combination of the former drug with PEDOT are much appropriated to show an externally tailored release profile. This is demonstrated by comparing the release profiles obtained in presence and absence of electrical stimulus. Results indicate that controlled and time-programmed release of curcumin is achieved in a physiological medium by applying a negative voltage of -1.25 V to loaded PEDOT nanoparticles. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Fabrication of a microfluidic device for studying the in situ drug-loading/release behavior of graphene oxide-encapsulated hydrogel beads.

    Science.gov (United States)

    Veerla, Sarath Chandra; Kim, Da Reum; Yang, Sung Yun

    2018-01-01

    Controlled drug delivery system is highly important for not only prolonged the efficacy of drug but also cellular development for tissue engineering. A number of biopolymer composites and nanostructured carriers behave been used for the controlled drug delivery of therapeutics. Recently, in vitro microfluidic devices that mimic the human body have been developed for drug-delivery applications. A microfluidic channel was fabricated via a two-step process: (i) polydimethyl siloxane (PDMS) and curing agent were poured with a 10:2 mass ratio onto an acrylic mold with two steel pipes, and (ii) calcium alginate beads were synthesized using sodium alginate and calcium chloride solutions. Different amounts (10, 25, 50 μg) of graphene oxide (GO) were then added by Hummers method, and studies on the encapsulation and release of the model drug, risedronate (Ris), were performed using control hydrogel beads (pH 6.3), GO-containing beads (10GO, 25GO and 50GO), and different pH conditions. MC3T3 osteoblastic cells were cultured in a microchannel with Ris-loaded GO-hydrogel beads, and their proliferation, viability, attachment and spreading were assessed for a week. The spongy and textured morphology of pristine hydrogel beads was converted to flowery and rod-shaped structures in drug-loaded hydrogel beads at reduced pH (6.3) and at a lower concentration (10 μg) of GO. These latter 10GO drug-loaded beads rapidly released their cargo owing to the calcium phosphate deposited on the surface. Notably, beads containing a higher amount of GO (50GO) exhibited an extended drug-release profile. We further found that MC3T3 cells proliferated continuously in vitro in the microfluidic channel containing the GO-hydrogel system. MTT and live/dead assays showed similar proliferative potential of MC3T3 cells. Therefore, a microfluidic device with microchannels containing hydrogel beads formulated with different amounts of GO and tested under various pH conditions could be a promising system

  20. Effect of food on early drug exposure from extended-release stimulants: results from the Concerta, Adderall XR Food Evaluation (CAFE) Study.

    Science.gov (United States)

    Auiler, J F; Liu, K; Lynch, J M; Gelotte, C K

    2002-01-01

    Stimulant therapy is the mainstay of treatment for children, adolescents and adults with attention-deficit/hyperactivity disorder (ADHD). Once-daily, extended-release oral formulations offer long acting control of symptoms by modifying drug delivery and absorption. In particular, consistency in early drug exposure is important for symptom control during school or work hours. Because these once-daily formulations are usually taken in the morning, the timing of the doses with breakfast is important. This study compared the effect of a high-fat breakfast on early drug exposure from a morning dose of two extended-release stimulant formulations: the osmotic-controlled OROS tablet of methylphenidate HCI (CONCERTA) and the capsule containing extended-release beads of mixed amphetamine salts (ADDERALL XR). The study had a single-dose, open-label, randomised, four-treatment, crossover design in which healthy subjects received either 36 mg CONCERTA or 20 mg ADDERALL XR in the morning after an overnight fast or a high-fat breakfast. Serial blood samples were collected over 28h to determine plasma concentrations of methylphenidate and amphetamine. The food effect on early drug exposure and the pharmacokinetic profiles up to 8 h after dosing of the two extended-release stimulants were directly compared using partial area (AUC(p4h), AUC(p6h) and AUC(p8h)) fed/fasted ratios. Amphetamine concentrations were markedly lower when the subjects had eaten breakfast, resulting in lower early drug exposures (p food, for patients with ADHD.

  1. Externally controlled triggered-release of drug from PLGA micro and nanoparticles.

    Directory of Open Access Journals (Sweden)

    Xin Hua

    Full Text Available Biofilm infections are extremely hard to eradicate and controlled, triggered and controlled drug release properties may prolong drug release time. In this study, the ability to externally control drug release from micro and nanoparticles was investigated. We prepared micro/nanoparticles containing ciprofloxacin (CIP and magnetic nanoparticles encapsulated in poly (lactic-co-glycolic acid PLGA. Both micro/nanoparticles were observed to have narrow size distributions. We investigated and compared their passive and externally triggered drug release properties based on their different encapsulation structures for the nano and micro systems. In passive release studies, CIP demonstrated a fast rate of release in first 2 days which then slowed and sustained release for approximately 4 weeks. Significantly, magnetic nanoparticles containing systems all showed ability to have triggered drug release when exposed to an external oscillating magnetic field (OMF. An experiment where the OMF was turned on and off also confirmed the ability to control the drug release in a pulsatile manner. The magnetically triggered release resulted in a 2-fold drug release increase compared with normal passive release. To confirm drug integrity following release, the antibacterial activity of released drug was evaluated in Pseudomonas aeruginosa biofilms in vitro. CIP maintained its antimicrobial activity after encapsulation and triggered release.

  2. Externally controlled triggered-release of drug from PLGA micro and nanoparticles.

    Science.gov (United States)

    Hua, Xin; Tan, Shengnan; Bandara, H M H N; Fu, Yujie; Liu, Siguo; Smyth, Hugh D C

    2014-01-01

    Biofilm infections are extremely hard to eradicate and controlled, triggered and controlled drug release properties may prolong drug release time. In this study, the ability to externally control drug release from micro and nanoparticles was investigated. We prepared micro/nanoparticles containing ciprofloxacin (CIP) and magnetic nanoparticles encapsulated in poly (lactic-co-glycolic acid) PLGA. Both micro/nanoparticles were observed to have narrow size distributions. We investigated and compared their passive and externally triggered drug release properties based on their different encapsulation structures for the nano and micro systems. In passive release studies, CIP demonstrated a fast rate of release in first 2 days which then slowed and sustained release for approximately 4 weeks. Significantly, magnetic nanoparticles containing systems all showed ability to have triggered drug release when exposed to an external oscillating magnetic field (OMF). An experiment where the OMF was turned on and off also confirmed the ability to control the drug release in a pulsatile manner. The magnetically triggered release resulted in a 2-fold drug release increase compared with normal passive release. To confirm drug integrity following release, the antibacterial activity of released drug was evaluated in Pseudomonas aeruginosa biofilms in vitro. CIP maintained its antimicrobial activity after encapsulation and triggered release.

  3. Dissolution stability studies of suspensions of prolonged-release diclofenac microcapsules prepared by the Wurster process: I. Eudragit-based formulation and possible drug-excipient interaction.

    Science.gov (United States)

    Adeyeye, M C; Mwangi, E; Katondo, B; Jain, A; Ichikawa, H; Fukumori, Y

    2005-06-01

    The aim was to evaluate possible interaction in solid and liquid state of the drug with formulation excipients consequent to very fast drug release of diclofenac-Eudragit prolonged release microcapsules. The microcapsules were prepared by drug layering on calcium carbonate cores and coated with Eudragit RS 30D and L30D-55 as previously reported. Suspension of the microcapsules was prepared using microcrystalline cellulose/sodium carboxymethyl cellulose (Avicel CL-611) as medium. In vitro dissolution testing of the suspension was done, and, based on the dissolution results, possible interaction between diclofenac and Eudragit and Avicel in the medium was studied. Powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) analyses were performed using 1:1 binary, 1:1:1 ternary mixtures and a ratio equivalent to that in the formulation. The mixtures were prepared by mixing the dispersions--Eudragit RS 30D or L30D-55 with the drug or other components, followed by drying at 60 degrees C for 48 h. Dry mixing was done using the powder equivalents of the polymers, Eudragit RS PO and L100-55, Avicel and calcium carbonate. In vitro dissolution of the suspended microcapsules showed a very fast release after 48 h (T50 = microcapsules (T50 = 6 h). DSC curves of the formulation components or microcapsules did not show the characteristic endothermic peak of diclofenac at 287 degrees C. Powder X-ray diffraction of the binary or ternary mixtures of diclofenac and Eudragit polymers indicated reduction, shift or modification of the crystalline peaks of the drug or excipients at 2theta of 12 degrees and 18 degrees , suggestive of interaction. Some changes in drug peak characteristics at 18 degrees and 23 degrees were observed for Avicel/drug mixture, though not significant. The DSC curves of the binary mixture of diclofenac co-dried with liquid forms of Eudragit (i.e. RS 30D or L30D-55) revealed greater interaction compared to the curves of drug and powdered forms of

  4. Study Drugs

    OpenAIRE

    Lam, Stephanie Phuong; Roosta, Natalie; Nielsen, Mikkel Fuhr; Meyer, Maria Holmgaard; Friis, Katrine Birk

    2016-01-01

    In recent years, students around the world, started to use preparations as Ritalin and Modafinil,also known as study drugs, to improve their cognitive abilities1. It is a common use among thestudents in United States of America, but it is a new tendency in Denmark. Our main focus is tolocate whether study drugs needs to be legalized in Denmark or not. To investigate this ourstarting point is to understand central ethical arguments in the debate. We have chosen twoarguments from Nick Bostrom a...

  5. Mathematical modeling of drug release from lipid dosage forms.

    Science.gov (United States)

    Siepmann, J; Siepmann, F

    2011-10-10

    Lipid dosage forms provide an interesting potential for controlled drug delivery. In contrast to frequently used poly(ester) based devices for parenteral administration, they do not lead to acidification upon degradation and potential drug inactivation, especially in the case of protein drugs and other acid-labile active agents. The aim of this article is to give an overview on the current state of the art of mathematical modeling of drug release from this type of advanced drug delivery systems. Empirical and semi-empirical models are described as well as mechanistic theories, considering diffusional mass transport, potentially limited drug solubility and the leaching of other, water-soluble excipients into the surrounding bulk fluid. Various practical examples are given, including lipid microparticles, beads and implants, which can successfully be used to control the release of an incorporated drug during periods ranging from a few hours up to several years. The great benefit of mechanistic mathematical theories is the possibility to quantitatively predict the effects of different formulation parameters and device dimensions on the resulting drug release kinetics. Thus, in silico simulations can significantly speed up product optimization. This is particularly useful if long release periods (e.g., several months) are targeted, since experimental trial-and-error studies are highly time-consuming in these cases. In the future it would be highly desirable to combine mechanistic theories with the quantitative description of the drug fate in vivo, ideally including the pharmacodynamic efficacy of the treatments. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Development of novel small molecules for imaging and drug release

    Science.gov (United States)

    Cao, Yanting

    Small organic molecules, including small molecule based fluorescent probes, small molecule based drugs or prodrugs, and smart multifunctional fluorescent drug delivery systems play important roles in biological research, drug discovery, and clinical practices. Despite the significant progress made in these fields, the development of novel and diverse small molecules is needed to meet various demands for research and clinical applications. My Ph.D study focuses on the development of novel functional molecules for recognition, imaging and drug release. In the first part, a turn-on fluorescent probe is developed for the detection of intracellular adenosine-5'-triphosphate (ATP) levels based on multiplexing recognitions. Considering the unique and complicated structure of ATP molecules, a fluorescent probe has been implemented with improved sensitivity and selectivity due to two synergistic binding recognitions by incorporating of 2, 2'-dipicolylamine (Dpa)-Zn(II) for targeting of phospho anions and phenylboronic acid group for cis-diol moiety. The novel probe is able to detect intracellular ATP levels in SH-SY5Y cells. Meanwhile, the advantages of multiplexing recognition design concept have been demonstrated using two control molecules. In the second part, a prodrug system is developed to deliver multiple drugs within one small molecule entity. The prodrug is designed by using 1-(2-nitrophenyl)ethyl (NPE) as phototrigger, and biphenol biquaternary ammonium as the prodrug. With controlled photo activation, both DNA cross-linking agents mechlorethamine and o-quinone methide are delivered and released at the preferred site, leading to efficient DNA cross-links formation and cell death. The prodrug shows negligible cytotoxicity towards normal skin cells (Hekn cells) with and without UV activation, but displays potent activity towards cancer cells (HeLa cells) upon UV activation. The multiple drug release system may hold a great potential for practical application. In the

  7. Encapsulation of methotrexate loaded magnetic microcapsules for magnetic drug targeting and controlled drug release

    Energy Technology Data Exchange (ETDEWEB)

    Chakkarapani, Prabu [Department of Pharmaceutical Technology & Centre for Excellence in Nanobio Translational Research, Anna University, Bharathidasan Institute of Technology Campus, Tiruchirappalli 620024, Tamil Nadu (India); Subbiah, Latha, E-mail: lathasuba2010@gmail.com [Department of Pharmaceutical Technology & Centre for Excellence in Nanobio Translational Research, Anna University, Bharathidasan Institute of Technology Campus, Tiruchirappalli 620024, Tamil Nadu (India); Palanisamy, Selvamani; Bibiana, Arputha [Department of Pharmaceutical Technology & Centre for Excellence in Nanobio Translational Research, Anna University, Bharathidasan Institute of Technology Campus, Tiruchirappalli 620024, Tamil Nadu (India); Ahrentorp, Fredrik; Jonasson, Christian; Johansson, Christer [Acreo Swedish ICT AB, Arvid Hedvalls backe 4, SE-411 33 Göteborg (Sweden)

    2015-04-15

    We report on the development and evaluation of methotrexate magnetic microcapsules (MMC) for targeted rheumatoid arthritis therapy. Methotrexate was loaded into CaCO{sub 3}-PSS (poly (sodium 4-styrenesulfonate)) doped microparticles that were coated successively with poly (allylamine hydrochloride) and poly (sodium 4-styrenesulfonate) by layer-by-layer technique. Ferrofluid was incorporated between the polyelectrolyte layers. CaCO{sub 3}-PSS core was etched by incubation with EDTA yielding spherical MMC. The MMC were evaluated for various physicochemical, pharmaceutical parameters and magnetic properties. Surface morphology, crystallinity, particle size, zeta potential, encapsulation efficiency, loading capacity, drug release pattern, release kinetics and AC susceptibility studies revealed spherical particles of ~3 µm size were obtained with a net zeta potential of +24.5 mV, 56% encapsulation and 18.6% drug loading capacity, 96% of cumulative drug release obeyed Hixson-Crowell model release kinetics. Drug excipient interaction, surface area, thermal and storage stability studies for the prepared MMC was also evaluated. The developed MMC offer a promising mode of targeted and sustained release drug delivery for rheumatoid arthritis therapy. - Highlights: • Development of methotrexate magnetic microcapsules (MMC) by layer-by-layer method. • Characterization of physicochemical, pharmaceutical and magnetic properties of MMC. • Multiple layers of alternative polyelectrolytes prolongs methotrexate release time. • MMC is capable for targeted and sustained release rheumatoid arthritis therapy.

  8. Mössbauer, XRD and TEM Study on the Intercalation and the Release of Drugs in/from Layered Double Hydroxides

    Directory of Open Access Journals (Sweden)

    E. Kuzmann

    2015-12-01

    Full Text Available Layered double hydroxides (LDHs are one of the very important nano-carriers for drug delivery, due to their many advantageous features, such as the ease and low-cost of preparation, low cytotoxicity, good biocompatibility, protection for the intercalated drugs, and the capacity to facilitate the uptake of the loaded drug in the cells. In our previous studies, Mössbauer spectroscopy was applied to monitor structural changes occurring during the incorporation of Fe(III in MgFe- and CaFe-LDHs, and the intercalation of various organic compounds in anionic form. Recently, we have successfully elaborated a protocol for the intercalation and release of indol-2-carboxylate and L-cysteinate in CaFe-LDH. The corresponding structural changes in the LDH samples were studied by XRD, HR-TEM and 57Fe Mössbauer spectroscopy. The Mössbauer spectra reflected small but significant changes upon both the intercalation and the release of drugs. The changes in the basal distances could be followed by XRD measurements, and HR-TEM images made these changes visible.

  9. Multicompartment Drug Release System for Dynamic Modulation of Tissue Responses.

    Science.gov (United States)

    Morris, Aaron H; Mahal, Rajwant S; Udell, Jillian; Wu, Michelle; Kyriakides, Themis R

    2017-10-01

    Pharmacological modulation of responses to injury is complicated by the need to deliver multiple drugs with spatiotemporal resolution. Here, a novel controlled delivery system containing three separate compartments with each releasing its contents over different timescales is fabricated. Core-shell electrospun fibers create two of the compartments in the system, while electrosprayed spheres create the third. Utility is demonstrated by targeting the foreign body response to implants because it is a dynamic process resulting in implant failure. Sequential delivery of a drug targeting nuclear factor-κB (NF-κB) and an antifibrotic is characterized in in vitro experiments. Specifically, macrophage fusion and p65 nuclear translocation in the presence of releasate or with macrophages cultured on the surfaces of the constructs are evaluated. In addition, releasate from pirfenidone scaffolds is shown to reduce transforming growth factor-β (TGF-β)-induced pSMAD3 nuclear localization in fibroblasts. In vivo, drug eluting constructs successfully mitigate macrophage fusion at one week and fibrotic encapsulation in a dose-dependent manner at four weeks, demonstrating effective release of both drugs over different timescales. Future studies can employ this system to improve and prolong implant lifetimes, or load it with other drugs to modulate other dynamic processes. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Modeling Drug-Carrier Interaction in the Drug Release from Nanocarriers

    Directory of Open Access Journals (Sweden)

    Like Zeng

    2011-01-01

    Full Text Available Numerous nanocarriers of various compositions and geometries have been developed for the delivery and release of therapeutic and imaging agents. Due to the high specific surface areas of nanocarriers, different mechanisms such as ion pairing and hydrophobic interaction need to be explored for achieving sustained release. Recently, we developed a three-parameter model that considers reversible drug-carrier interaction and first-order drug release from liposomes. A closed-form analytical solution was obtained. Here, we further explore the ability of the model to capture the release of bioactive molecules such as drugs and growth factors from various nanocarriers. A parameter study demonstrates that the model is capable of resembling major categories of drug release kinetics. We further fit the model to 60 sets of experimental data from various drug release systems, including nanoparticles, hollow particles, fibers, and hollow fibers. Additionally, bootstrapping is used to evaluate the accuracy of parameter determination and validate the model in selected cases. The simplicity and universality of the model and the clear physical meanings of each model parameter render the model useful for the design and development of new drug delivery systems.

  11. Prodigiosin release from an implantable biomedical device: kinetics of localized cancer drug release

    Energy Technology Data Exchange (ETDEWEB)

    Danyuo, Y.; Obayemi, J.D.; Dozie-Nwachukwu, S. [Department of Materials Science and Engineering, African University of Science and Technology (AUST), Abuja, Federal Capital Territory (Nigeria); Ani, C.J. [Department of Theoretical Physics, African University of Science and Technology (AUST), Abuja, Federal Capital Territory (Nigeria); Odusanya, O.S. [Biotechnology and Genetic Engineering Advanced Laboratory, Sheda Science and Technology Complex (SHESTCO), Abuja, Federal Capital Territory (Nigeria); Oni, Y. [Department of Chemistry, Bronx Community College, New York, NY (United States); Anuku, N. [Department of Chemistry, Bronx Community College, New York, NY (United States); Princeton Institute for the Science and Technology of Materials (PRISM), 70 Prospect Street, Princeton, NJ 08544 (United States); Malatesta, K. [Department of Chemistry, Bronx Community College, New York, NY (United States); Soboyejo, W.O., E-mail: soboyejo@princeton.edu [Department of Materials Science and Engineering, African University of Science and Technology (AUST), Abuja, Federal Capital Territory (Nigeria); Princeton Institute for the Science and Technology of Materials (PRISM), 70 Prospect Street, Princeton, NJ 08544 (United States); Department of Mechanical and Aerospace Engineering 1 Olden Street, Princeton, NJ 08544 (United States)

    2014-09-01

    This paper presents an implantable encapsulated structure that can deliver localized heating (hyperthermia) and controlled concentrations of prodigiosin (a cancer drug) synthesized by bacteria (Serratia marcesce (subsp. marcescens)). Prototypical Poly-di-methyl-siloxane (PDMS) packages, containing well-controlled micro-channels and drug storage compartments, were fabricated along with a drug-storing polymer produced by free radical polymerization of Poly(N-isopropylacrylamide)(PNIPA) co-monomers of Acrylamide (AM) and Butyl-methacrylate (BMA). The mechanisms of drug diffusion of PNIPA-base gels were elucidated. Scanning Electron Microscopy (SEM) was also used to study the heterogeneous porous structure of the PNIPA-based gels. The release exponents, n, of the gels were found to between 0.5 and 0.7. This is in the range expected for Fickian (n = 0.5). Deviation from Fickian diffusion was also observed (n > 0.5) diffusion. The gel diffusion coefficients were shown to vary between 2.1 × 10{sup −12} m{sup 2}/s and 4.8 × 10{sup −6} m{sup 2}/s. The implications of the results are then discussed for the localized treatment of cancer via hyperthermia and the controlled delivery of prodigiosin from encapsulated PNIPA-based devices. - Highlights: • Fabricated thermo-sensitive hydrogels for localized drug release from an implantable biomedical device. • Determined the cancer drug diffusion mechanisms of PNIPA-co-AM copolymer hydrogel. • Encapsulated PNIPA-based hydrogels in PDMS capsules for controlled drug delivery. • Established the kinetics of drug release from gels and channels in an implantable biomedical device. • Demonstrated the potential for the controlled release of prodigiosin (PG) as an anticancer drug.

  12. Prodigiosin release from an implantable biomedical device: kinetics of localized cancer drug release

    International Nuclear Information System (INIS)

    Danyuo, Y.; Obayemi, J.D.; Dozie-Nwachukwu, S.; Ani, C.J.; Odusanya, O.S.; Oni, Y.; Anuku, N.; Malatesta, K.; Soboyejo, W.O.

    2014-01-01

    This paper presents an implantable encapsulated structure that can deliver localized heating (hyperthermia) and controlled concentrations of prodigiosin (a cancer drug) synthesized by bacteria (Serratia marcesce (subsp. marcescens)). Prototypical Poly-di-methyl-siloxane (PDMS) packages, containing well-controlled micro-channels and drug storage compartments, were fabricated along with a drug-storing polymer produced by free radical polymerization of Poly(N-isopropylacrylamide)(PNIPA) co-monomers of Acrylamide (AM) and Butyl-methacrylate (BMA). The mechanisms of drug diffusion of PNIPA-base gels were elucidated. Scanning Electron Microscopy (SEM) was also used to study the heterogeneous porous structure of the PNIPA-based gels. The release exponents, n, of the gels were found to between 0.5 and 0.7. This is in the range expected for Fickian (n = 0.5). Deviation from Fickian diffusion was also observed (n > 0.5) diffusion. The gel diffusion coefficients were shown to vary between 2.1 × 10 −12 m 2 /s and 4.8 × 10 −6 m 2 /s. The implications of the results are then discussed for the localized treatment of cancer via hyperthermia and the controlled delivery of prodigiosin from encapsulated PNIPA-based devices. - Highlights: • Fabricated thermo-sensitive hydrogels for localized drug release from an implantable biomedical device. • Determined the cancer drug diffusion mechanisms of PNIPA-co-AM copolymer hydrogel. • Encapsulated PNIPA-based hydrogels in PDMS capsules for controlled drug delivery. • Established the kinetics of drug release from gels and channels in an implantable biomedical device. • Demonstrated the potential for the controlled release of prodigiosin (PG) as an anticancer drug

  13. Kinetics of drug release from ointments: Role of transient-boundary layer.

    Science.gov (United States)

    Xu, Xiaoming; Al-Ghabeish, Manar; Krishnaiah, Yellela S R; Rahman, Ziyaur; Khan, Mansoor A

    2015-10-15

    In the current work, an in vitro release testing method suitable for ointment formulations was developed using acyclovir as a model drug. Release studies were carried out using enhancer cells on acyclovir ointments prepared with oleaginous, absorption, and water-soluble bases. Kinetics and mechanism of drug release was found to be highly dependent on the type of ointment bases. In oleaginous bases, drug release followed a unique logarithmic-time dependent profile; in both absorption and water-soluble bases, drug release exhibited linearity with respect to square root of time (Higuchi model) albeit differences in the overall release profile. To help understand the underlying cause of logarithmic-time dependency of drug release, a novel transient-boundary hypothesis was proposed, verified, and compared to Higuchi theory. Furthermore, impact of drug solubility (under various pH conditions) and temperature on drug release were assessed. Additionally, conditions under which deviations from logarithmic-time drug release kinetics occur were determined using in situ UV fiber-optics. Overall, the results suggest that for oleaginous ointments containing dispersed drug particles, kinetics and mechanism of drug release is controlled by expansion of transient boundary layer, and drug release increases linearly with respect to logarithmic time. Published by Elsevier B.V.

  14. Mechanism and kinetics of the loss of poorly soluble drugs from liposomal carriers studied by a novel flow field-flow fractionation-based drug release-/transfer-assay

    DEFF Research Database (Denmark)

    Hinna, Askell Hvid; Hupfeld, Stefan; Kuntsche, Judith

    2016-01-01

    Liposomes represent a versatile drug formulation approach e.g. for improving the water-solubility of poorly soluble drugs but also to achieve drug targeting and controlled release. For the latter applications it is essential that the drug remains associated with the liposomal carrier during transit...... in the vascular bed. A range of in vitro test methods has been suggested over the years for prediction of the release of drug from liposomal carriers. The majority of these fail to give a realistic prediction for poorly water-soluble drugs due to the intrinsic tendency of such compounds to remain associated...... the amount of drug remaining associated with the liposomal drug carrier as well as that transferred to the acceptor liposomes at distinct times of incubation, boththe kinetics of drug transfer and release to the water phase could be established for the model drug p-THPP (5,10,15,20-tetrakis(4-hydroxyphenyl...

  15. Sustained Release of a Water-Soluble Drug from Directly ...

    African Journals Online (AJOL)

    Okra gum was evaluated as a controlled-release agent in modified release matrices in comparison with sodium carboxymethylcellulose (NaCMC) using aspirin as the model drug. Tablets were produced by direct compression and the in vitro drug release was assessed under conditions similar to those in the gastrointestinal ...

  16. FACTORS AFFECTING THE RELEASE RATE OF A HIGHLY SOLUBLE DRUG FROM A PROGRAMMED RELEASE MEGALOPOROUS SYSTEM

    NARCIS (Netherlands)

    VANDERVEEN, C; MENGER, NR; LERK, CF

    The present study reports on the successful incorporation of a highly soluble drug, procaine HCl, in a programmed-release megaloporous system. This solid two-phase system is composed of housing phase matrix granules (HMG), controlling liquid penetration into the system, and of restraining phase

  17. Dual-controlled release system of drugs for bone regeneration.

    Science.gov (United States)

    Kim, Yang-Hee; Tabata, Yasuhiko

    2015-11-01

    Controlled release systems have been noted to allow drugs to enhance their ability for bone regeneration. To this end, various biomaterials have been used as the release carriers of drugs, such as low-molecular-weight drugs, growth factors, and others. The drugs are released from the release carriers in a controlled fashion to maintain their actions for a long time period. Most research has been focused on the controlled release of single drugs to demonstrate the therapeutic feasibility. Controlled release of two combined drugs, so-called dual release systems, are promising and important for tissue regeneration. This is because the tissue regeneration process of bone formation is generally achieved by multiple bioactive molecules, which are produced from cells by other molecules. If two types of bioactive molecules, (i.e., drugs), are supplied in an appropriate fashion, the regeneration process of living bodies will be efficiently promoted. This review focuses on the bone regeneration induced by dual-controlled release of drugs. In this paper, various dual-controlled release systems of drugs aiming at bone regeneration are overviewed explaining the type of drugs and their release materials. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Programmable release of multiple protein drugs from aptamer-functionalized hydrogels via nucleic acid hybridization.

    Science.gov (United States)

    Battig, Mark R; Soontornworajit, Boonchoy; Wang, Yong

    2012-08-01

    Polymeric delivery systems have been extensively studied to achieve localized and controlled release of protein drugs. However, it is still challenging to control the release of multiple protein drugs in distinct stages according to the progress of disease or treatment. This study successfully demonstrates that multiple protein drugs can be released from aptamer-functionalized hydrogels with adjustable release rates at predetermined time points using complementary sequences (CSs) as biomolecular triggers. Because both aptamer-protein interactions and aptamer-CS hybridization are sequence-specific, aptamer-functionalized hydrogels constitute a promising polymeric delivery system for the programmable release of multiple protein drugs to treat complex human diseases.

  19. Synthesis, characterization, drug release and transdentinal delivery studies of magnetic nanocubes coated with biodegradable poly(2-(dimethyl amino)ethyl methacrylate)

    Energy Technology Data Exchange (ETDEWEB)

    Ajkidkarn, Phranot [Petrochemistry and Polymer Science Program, Faculty of Science, Chulalongkorn University, Bangkok 10330 (Thailand); Ritprajak, Patcharee [Department of Microbiology and RU in Oral Microbiology and Immunology, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330 (Thailand); Injumpa, Wishulada [Departmen of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330 (Thailand); Porntaveetus, Thantrira [Department of Physiology, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330 (Thailand); STAR on Craniofacial and Skeletal Disorders, Chulalongkorn University, Bangkok 10330 (Thailand); Insin, Numpon, E-mail: Numpon.I@chula.ac.th [Departmen of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330 (Thailand)

    2017-04-01

    Nanotechnology on magnetism and magnetic materials has been developed and studied extensively for the recent decades. Magnetic nanoparticles were applied in magnetic targeting, magnetic drug carriers, and diagnostic materials. In this work, the development of magnetic nanocomposites and their applications as drug carriers for dentistry were investigated. Well-defined ferromagnetic magnetite nanocubes (FMNCs) with the diameter of around 60 nm were synthesized using a thermal decomposition method at 290 °C with iron-oleate complexes as starting materials resulting in nanostructure with high saturation magnetization. The FMNCs were then coated with poly(2-(dimethyl amino)ethyl methacrylate) (PDMAEMA), a water-soluble, biodegradable, and pH-responsive polymer, in order to become good drug carriers with excellent dispersity in biological buffer, low cytotoxicity, and controllable drug release. The polymer coating was performed using atom transfer radical polymerization (ATRP). By using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, FMNCs/PDMAEMA showed the high compatibility in fibroblast and macrophage cell line with the cell viability of more than 80% after incubation with the highest nanocomposites concentration of 100 μg/mL for 24 h. Furthermore, the FMNCs/PDMAEMA subsequently demonstrated the anti-inflammatory effect on macrophages by suppression of pro-inflammatory cytokines, IL-6 and TNF-α production in a dose-dependent manner. The behavior of model drug alkaline hyperchlorite released from the FMNCs/PDMAEMA indicated that the drug release could be controlled by altering pH of the environment. As a result of successfully synthesized FMCNs/PDMAEMA, dentine infiltration of FMNCs/PDMAEMA was performed. It was observed that FMNCs/PDMAEMA could significantly infiltrate the dentine within 30 min under an external magnetic field. Our findings indicated the therapeutic potential of the FMNCs/PDMAEMA as transdentinal drug carriers with its

  20. Electrically controlled drug release from nanostructured polypyrrole coated on titanium

    International Nuclear Information System (INIS)

    Sirivisoot, Sirinrath; Pareta, Rajesh; Webster, Thomas J

    2011-01-01

    Previous studies have demonstrated that multi-walled carbon nanotubes grown out of anodized nanotubular titanium (MWNT-Ti) can be used as a sensing electrode for various biomedical applications; such sensors detected the redox reactions of certain molecules, specifically proteins deposited by osteoblasts during extracellular matrix bone formation. Since it is known that polypyrrole (PPy) can release drugs upon electrical stimulation, in this study antibiotics (penicillin/streptomycin, P/S) or an anti-inflammatory drug (dexamethasone, Dex), termed PPy[P/S] or PPy[Dex], respectively, were electrodeposited in PPy on titanium. The objective of the present study was to determine if such drugs can be released from PPy on demand and (by applying a voltage) control cellular behavior important for orthopedic applications. Results showed that PPy films possessed nanometer-scale roughness as analyzed by atomic force microscopy. X-ray photoelectron spectroscopy confirmed the presence of P/S and Dex encapsulated within the PPy films. Results from cyclic voltammetry showed that 80% of the drugs were released on demand when sweep voltages were applied for five cycles at a scan rate of 0.1 V s -1 . Furthermore, osteoblast (bone-forming cells) and fibroblast (fibrous tissue-forming cells) adhesion were determined on the PPy films. Results showed that PPy[Dex] enhanced osteoblast adhesion after 4 h of culture compared to plain Ti. PPy-Ti (with or without anionic drug doping) inhibited fibroblast adhesion compared to plain Ti. These in vitro results confirmed that electrodeposited PPy[P/S] and PPy[Dex] can release drugs on demand to potentially fight bacterial infection, reduce inflammation, promote bone growth or reduce fibroblast functions, further implicating the use of such materials as implant sensors.

  1. Electrically controlled drug release from nanostructured polypyrrole coated on titanium

    Science.gov (United States)

    Sirivisoot, Sirinrath; Pareta, Rajesh; Webster, Thomas J.

    2011-02-01

    Previous studies have demonstrated that multi-walled carbon nanotubes grown out of anodized nanotubular titanium (MWNT-Ti) can be used as a sensing electrode for various biomedical applications; such sensors detected the redox reactions of certain molecules, specifically proteins deposited by osteoblasts during extracellular matrix bone formation. Since it is known that polypyrrole (PPy) can release drugs upon electrical stimulation, in this study antibiotics (penicillin/streptomycin, P/S) or an anti-inflammatory drug (dexamethasone, Dex), termed PPy[P/S] or PPy[Dex], respectively, were electrodeposited in PPy on titanium. The objective of the present study was to determine if such drugs can be released from PPy on demand and (by applying a voltage) control cellular behavior important for orthopedic applications. Results showed that PPy films possessed nanometer-scale roughness as analyzed by atomic force microscopy. X-ray photoelectron spectroscopy confirmed the presence of P/S and Dex encapsulated within the PPy films. Results from cyclic voltammetry showed that 80% of the drugs were released on demand when sweep voltages were applied for five cycles at a scan rate of 0.1 V s - 1. Furthermore, osteoblast (bone-forming cells) and fibroblast (fibrous tissue-forming cells) adhesion were determined on the PPy films. Results showed that PPy[Dex] enhanced osteoblast adhesion after 4 h of culture compared to plain Ti. PPy-Ti (with or without anionic drug doping) inhibited fibroblast adhesion compared to plain Ti. These in vitro results confirmed that electrodeposited PPy[P/S] and PPy[Dex] can release drugs on demand to potentially fight bacterial infection, reduce inflammation, promote bone growth or reduce fibroblast functions, further implicating the use of such materials as implant sensors.

  2. Electrically controlled drug release from nanostructured polypyrrole coated on titanium

    Energy Technology Data Exchange (ETDEWEB)

    Sirivisoot, Sirinrath; Pareta, Rajesh; Webster, Thomas J, E-mail: Thomas_Webster@Brown.edu [School of Engineering, Brown University, Providence, RI 02912 (United States)

    2011-02-25

    Previous studies have demonstrated that multi-walled carbon nanotubes grown out of anodized nanotubular titanium (MWNT-Ti) can be used as a sensing electrode for various biomedical applications; such sensors detected the redox reactions of certain molecules, specifically proteins deposited by osteoblasts during extracellular matrix bone formation. Since it is known that polypyrrole (PPy) can release drugs upon electrical stimulation, in this study antibiotics (penicillin/streptomycin, P/S) or an anti-inflammatory drug (dexamethasone, Dex), termed PPy[P/S] or PPy[Dex], respectively, were electrodeposited in PPy on titanium. The objective of the present study was to determine if such drugs can be released from PPy on demand and (by applying a voltage) control cellular behavior important for orthopedic applications. Results showed that PPy films possessed nanometer-scale roughness as analyzed by atomic force microscopy. X-ray photoelectron spectroscopy confirmed the presence of P/S and Dex encapsulated within the PPy films. Results from cyclic voltammetry showed that 80% of the drugs were released on demand when sweep voltages were applied for five cycles at a scan rate of 0.1 V s{sup -1}. Furthermore, osteoblast (bone-forming cells) and fibroblast (fibrous tissue-forming cells) adhesion were determined on the PPy films. Results showed that PPy[Dex] enhanced osteoblast adhesion after 4 h of culture compared to plain Ti. PPy-Ti (with or without anionic drug doping) inhibited fibroblast adhesion compared to plain Ti. These in vitro results confirmed that electrodeposited PPy[P/S] and PPy[Dex] can release drugs on demand to potentially fight bacterial infection, reduce inflammation, promote bone growth or reduce fibroblast functions, further implicating the use of such materials as implant sensors.

  3. A comparative study on the effects of amphiphilic and hydrophilic polymers on the release profiles of a poorly water-soluble drug.

    Science.gov (United States)

    Irwan, Anastasia W; Berania, Jacqueline E; Liu, Xueming

    2016-03-01

    This paper reports the use of two crystalline polymers, an amphiphilic Pluronic® F-127 (PF-127) and a hydrophilic poly(ethylene glycol) (PEG6000) as drug delivery carriers for improving the drug release of a poorly water-soluble drug, fenofibrate (FEN), via micelle formation and formation of a solid dispersion (SD). In 10% PF-127 (aq.), FEN showed an equilibrium solubility of ca. 0.6 mg/mL, due to micelle formation. In contrast, in 10% PEG6000 (aq.), FEN only exhibited an equilibrium solubility of 0.0037 mg/mL. FEN-loaded micelles in PF-127 were prepared by direct dissolution and membrane dialysis. Both methods only yielded a highest drug loading (DL) of 0.5%. SDs of FEN in PF-127 and PEG6000, at DLs of 5-80%, were prepared by solvent evaporation. In-vitro dissolution testing showed that both micelles and SDs significantly improved FEN's release rate. The SDs of FEN in PF-127 showed significantly faster release than crystalline FEN, when the DL was as high as 50%, whereas SDs of PEG6000 showed similar enhancement in the release rate when the DL was not more than 20%. The DSC thermograms of SDs of PF-127 exhibited a single phase transition peak at ca. 55-57 °C when the DL was not more than 50%, whereas those in PEG6000 exhibited a similar peak at ca. 61-63 °C when the DL was not more than 35%. When the DL exceeded 50% for SDs of PF-127 and 35% for SDs of PEG6000, DSC thermograms showed two melting peaks for the carrier polymer and FEN, respectively. FT-IR studies revealed that PF-127 has a stronger hydrophobic-hydrophobic interaction with FEN than PEG6000. It is likely that both dispersion and micelle formation contributed to the stronger effect of PF-127 on enhancing the release rate of FEN in its SDs.

  4. Development and evaluation of accelerated drug release testing methods for a matrix-type intravaginal ring.

    Science.gov (United States)

    Externbrink, Anna; Eggenreich, Karin; Eder, Simone; Mohr, Stefan; Nickisch, Klaus; Klein, Sandra

    2017-01-01

    Accelerated drug release testing is a valuable quality control tool for long-acting non-oral extended release formulations. Currently, several intravaginal ring candidates designed for the long-term delivery of steroids or anti-infective drugs are being in the developing pipeline. The present article addresses the demand for accelerated drug release methods for these formulations. We describe the development and evaluation of accelerated release methods for a steroid releasing matrix-type intravaginal ring. The drug release properties of the formulation were evaluated under real-time and accelerated test conditions. Under real-time test conditions drug release from the intravaginal ring was strongly affected by the steroid solubility in the release medium. Under sufficient sink conditions that were provided in release media containing surfactants drug release was Fickian diffusion driven. Both temperature and hydro-organic dissolution media were successfully employed to accelerate drug release from the formulation. Drug release could be further increased by combining the temperature effect with the application of a hydro-organic release medium. The formulation continued to exhibit a diffusion controlled release kinetic under the investigated accelerated conditions. Moreover, the accelerated methods were able to differentiate between different prototypes of the intravaginal ring that exhibited different release profiles under real-time test conditions. Overall, the results of the present study indicate that both temperature and hydro-organic release media are valid parameters for accelerating drug release from the intravaginal ring. Variation of either a single or both parameters yielded release profiles that correlated well with real-time release. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Colloid electrochemistry of conducting polymer: towards potential-induced in-situ drug release

    International Nuclear Information System (INIS)

    Sankoh, Supannee; Vagin, Mikhail Yu.; Sekretaryova, Alina N.; Thavarungkul, Panote; Kanatharana, Proespichaya; Mak, Wing Cheung

    2017-01-01

    Highlights: • Pulsed electrode potential induced an in-situ drug release from dispersion of conducting polymer microcapsules. • Fast detection of the released drug within the colloid microenvironment. • Improved the efficiency of localized drug release at the electrode interface. - Abstract: Over the past decades, controlled drug delivery system remains as one of the most important area in medicine for various diseases. We have developed a new electrochemically controlled drug release system by combining colloid electrochemistry and electro-responsive microcapsules. The pulsed electrode potential modulation led to the appearance of two processes available for the time-resolved registration in colloid microenvironment: change of the electronic charge of microparticles (from 0.5 ms to 0.1 s) followed by the drug release associated with ionic equilibration (1–10 s). The dynamic electrochemical measurements allow the distinction of drug release associated with ionic relaxation and the change of electronic charge of conducting polymer colloid microparticles. The amount of released drug (methylene blue) could be controlled by modulating the applied potential. Our study demonstrated a surface-potential driven controlled drug release of dispersion of conducting polymer carrier at the electrode interfaces, while the bulk colloids dispersion away from the electrode remains as a reservoir to improve the efficiency of localized drug release. The developed new methodology creates a model platform for the investigations of surface potential-induced in-situ electrochemical drug release mechanism.

  6. A REVIEW ON CONTROLLED DRUG RELEASE FORMULATION: SPANSULES

    OpenAIRE

    Rinky Maurya; Dr. Pramod Kumar Sharma; Rishabha Malviya

    2014-01-01

    Spansules are a dosage form which was considered as one of the Advanced Drug Delivery System. Multidrug preparations can be delivered easily by spansules or granules in capsule technology. This type of delivery system designed to release a drug or a medicament at two or more different rates or in different span of time. A quick/slow release system provides an initial release of drug followed by a constant rate of drug release over a extended period or a defined period of time and in slow/quic...

  7. Effect of Anionic Polymers on Drug Loading and Release from ...

    African Journals Online (AJOL)

    Purpose: To develop and characterize solid lipid nanoparticle (SLN) systems containing dextran sulfate or sodium ... SLNs. Drug release from SLNs is also dependent on the polymer type. ..... nanoparticles for parenteral drug delivery. Adv.

  8. The enzyme-sensitive release of prodigiosin grafted β-cyclodextrin and chitosan magnetic nanoparticles as an anticancer drug delivery system: Synthesis, characterization and cytotoxicity studies.

    Science.gov (United States)

    Rastegari, Banafsheh; Karbalaei-Heidari, Hamid Reza; Zeinali, Sedigheh; Sheardown, Heather

    2017-10-01

    In present investigation, two glucose based smart tumor-targeted drug delivery systems coupled with enzyme-sensitive release strategy are introduced. Magnetic nanoparticles (Fe 3 O 4 ) were grafted with carboxymethyl chitosan (CS) and β-cyclodextrin (β-CD) as carriers. Prodigiosin (PG) was used as the model anti-tumor drug, targeting aggressive tumor cells. The morphology, properties and composition and grafting process were characterized by transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FT-IR), vibration sample magnetometer (VSM), X-ray diffraction (XRD) analysis. The results revealed that the core crystal size of the nanoparticles synthesized were 14.2±2.1 and 9.8±1.4nm for β-CD and CS-MNPs respectively when measured using TEM; while dynamic light scattering (DLS) gave diameters of 121.1 and 38.2nm. The saturation magnetization (Ms) of bare magnetic nanoparticles is 50.10emucm -3 , while modification with β-CD and CS gave values of 37.48 and 65.01emucm -3 , respectively. The anticancer compound, prodigiosin (PG) was loaded into the NPs with an encapsulation efficiency of approximately 81% for the β-CD-MNPs, and 92% for the CS-MNPs. This translates to a drug loading capacity of 56.17 and 59.17mg/100mg MNPs, respectively. Measurement of in vitro release of prodigiosin from the loaded nanocarriers in the presence of the hydrolytic enzymes, alpha-amylase and chitosanase showed that 58.1 and 44.6% of the drug was released after one-hour of incubation. Cytotoxicity studies of PG-loaded nanocarriers on two cancer cell lines, MCF-7 and HepG2, and on a non-cancerous control, NIH/3T3 cells, revealed that the drug loaded nanoparticles had greater efficacy on the cancer cell lines. The selective index (SI) for free PG on MCF-7 and HepG2 cells was 1.54 and 4.42 respectively. This parameter was reduced for PG-loaded β-CD-MNPs to 1.27 and 1.85, while the SI for CS-MNPs improved considerably to 7.03 on MCF-7 cells. Complementary studies

  9. Encapsulation of boswellic acid with β- and hydroxypropyl-β-cyclodextrin: Synthesis, characterization, in vitro drug release and molecular modelling studies

    Science.gov (United States)

    Tambe, Amruta; Pandita, Nancy; Kharkar, Prashant; Sahu, Niteshkumar

    2018-02-01

    Boswellic acids (BAs) are a group of pentacyclic triterpenes present in gum-resin of Boswellia serrata. They are well known for their anti-inflammatory, hypolipidemic, immunomodulatory and anti-tumor activity, but they have poor aqueous solubility and limited bioavailability. In order to enhance their aqueous solubility, inclusion complexes of BAs with β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) were synthesized and their drug release profiles were studied. Molecular associations of β-CD and HP-β-CD with BAs were investigated by phase solubility studies. The stability constants were found to be 380.2 and 145.9 M-1 for BA: β-CD and BA: HP-β-CD inclusion complexes, respectively with AN- type curve. BA: β-CD and BA: HP-β-CD inclusion complexes were synthesized using kneading (KN), co-precipitation (CP) and solvent evaporation (SE) methods in 1:1 as well as 1:2 ratios. Further these were characterized by Fourier transform infrared (FTIR) spectrophotometry, Powder X-ray Diffraction (P-XRD) and Differential scanning calorimetric (DSC) analysis. FTIR analysis showed shifting of frequencies in complexes as compared to CDs and BAs. P-XRD data obtained for BA: β-CD complexes synthesized by CP and SE methods showed amorphous pattern. Also, DSC analysis showed a change in thermal behaviour for synthesized complexes. In vitro drug release studies of BA: β-CD complexes showed enhanced release with 1:2 complexes than 1:1 complexes at pH 1.2 and pH 6.8. Similarly, drug release enhancement was observed more with BA: HP-β-CD complexes in 1:2 ratio than 1:1. To understand the interaction of BAs with CD cavity molecular modelling studies were performed which favored 1:2 complex formation over 1:1 complexes. The study thus highlights that CDs can be used for solubility and dissolution enhancement of BAs.

  10. Injectable In-Situ Gelling Controlled Release Drug Delivery System

    OpenAIRE

    Kulwant Singh; S. L. HariKumar

    2012-01-01

    The administration of poorly bioavailable drug through parenteral route is regarded the most efficient for drug delivery. Parenteral delivery provides rapid onset even for the drug with narrow therapeutic window, but to maintain the systemic drug level repeated installation are required which cause the patient discomfort. This can be overcome by designing the drug into a system, which control the drug release even through parenteral delivery, which improve patient compliance as well as pharma...

  11. Tailored sequential drug release from bilayered calcium sulfate composites

    International Nuclear Information System (INIS)

    Orellana, Bryan R.; Puleo, David A.

    2014-01-01

    The current standard for treating infected bony defects, such as those caused by periodontal disease, requires multiple time-consuming steps and often multiple procedures to fight the infection and recover lost tissue. Releasing an antibiotic followed by an osteogenic agent from a synthetic bone graft substitute could allow for a streamlined treatment, reducing the need for multiple surgeries and thereby shortening recovery time. Tailorable bilayered calcium sulfate (CS) bone graft substitutes were developed with the ability to sequentially release multiple therapeutic agents. Bilayered composite samples having a shell and core geometry were fabricated with varying amounts (1 or 10 wt.%) of metronidazole-loaded poly(lactic-co-glycolic acid) (PLGA) particles embedded in the shell and simvastatin directly loaded into either the shell, core, or both. Microcomputed tomography showed the overall layered geometry as well as the uniform distribution of PLGA within the shells. Dissolution studies demonstrated that the amount of PLGA particles (i.e., 1 vs. 10 wt.%) had a small but significant effect on the erosion rate (3% vs. 3.4%/d). Mechanical testing determined that introducing a layered geometry had a significant effect on the compressive strength, with an average reduction of 35%, but properties were comparable to those of mandibular trabecular bone. Sustained release of simvastatin directly loaded into CS demonstrated that changing the shell to core volume ratio dictates the duration of drug release from each layer. When loaded together in the shell or in separate layers, sequential release of metronidazole and simvastatin was achieved. By introducing a tunable, layered geometry capable of releasing multiple drugs, CS-based bone graft substitutes could be tailored in order to help streamline the multiple steps needed to regenerate tissue in infected defects. - Highlights: • Bilayered CS composites were fabricated as potential bone graft substitutes. • The shell

  12. Tailored sequential drug release from bilayered calcium sulfate composites

    Energy Technology Data Exchange (ETDEWEB)

    Orellana, Bryan R.; Puleo, David A., E-mail: puleo@uky.edu

    2014-10-01

    The current standard for treating infected bony defects, such as those caused by periodontal disease, requires multiple time-consuming steps and often multiple procedures to fight the infection and recover lost tissue. Releasing an antibiotic followed by an osteogenic agent from a synthetic bone graft substitute could allow for a streamlined treatment, reducing the need for multiple surgeries and thereby shortening recovery time. Tailorable bilayered calcium sulfate (CS) bone graft substitutes were developed with the ability to sequentially release multiple therapeutic agents. Bilayered composite samples having a shell and core geometry were fabricated with varying amounts (1 or 10 wt.%) of metronidazole-loaded poly(lactic-co-glycolic acid) (PLGA) particles embedded in the shell and simvastatin directly loaded into either the shell, core, or both. Microcomputed tomography showed the overall layered geometry as well as the uniform distribution of PLGA within the shells. Dissolution studies demonstrated that the amount of PLGA particles (i.e., 1 vs. 10 wt.%) had a small but significant effect on the erosion rate (3% vs. 3.4%/d). Mechanical testing determined that introducing a layered geometry had a significant effect on the compressive strength, with an average reduction of 35%, but properties were comparable to those of mandibular trabecular bone. Sustained release of simvastatin directly loaded into CS demonstrated that changing the shell to core volume ratio dictates the duration of drug release from each layer. When loaded together in the shell or in separate layers, sequential release of metronidazole and simvastatin was achieved. By introducing a tunable, layered geometry capable of releasing multiple drugs, CS-based bone graft substitutes could be tailored in order to help streamline the multiple steps needed to regenerate tissue in infected defects. - Highlights: • Bilayered CS composites were fabricated as potential bone graft substitutes. • The shell

  13. SU-F-19A-08: Optimal Time Release Schedule of In-Situ Drug Release During Permanent Prostate Brachytherapy

    International Nuclear Information System (INIS)

    Cormack, R; Ngwa, W; Makrigiorgos, G; Tangutoori, S; Rajiv, K; Sridhar, S

    2014-01-01

    Purpose: Permanent prostate brachytherapy spacers can be used to deliver sustained doses of radiosentitizing drug directly to the target, in order to enhance the radiation effect. Implantable nanoplatforms for chemo-radiation therapy (INCeRTs) have a maximum drug capacity and can be engineered to control the drug release schedule. The optimal schedule for sensitization during continuous low dose rate irradiation is unknown. This work studies the optimal release schedule of drug for both traditional sensitizers, and those that work by suppressing DNA repair processes. Methods: Six brachytherapy treatment plans were used to model the anatomy, implant geometry and calculate the spatial distribution of radiation dose and drug concentrations for a range of drug diffusion parameters. Three state partial differential equations (cells healthy, damaged or dead) modeled the effect of continuous radiation (radiosensitivities α,β) and cellular repair (time tr) on a cell population. Radiosensitization was modeled as concentration dependent change in α,β or tr which with variable duration under the constraint of fixed total drug release. Average cell kill was used to measure effectiveness. Sensitization by means of both enhanced damage and reduced repair were studied. Results: Optimal release duration is dependent on the concentration of radiosensitizer compared to the saturation concentration (csat) above which additional sensitization does not occur. Long duration drug release when enhancing α or β maximizes cell death when drug concentrations are generally over csat. Short term release is optimal for concentrations below saturation. Sensitization by suppressing repair has a similar though less distinct trend that is more affected by the radiation dose distribution. Conclusion: Models of sustained local radiosensitization show potential to increase the effectiveness of radiation in permanent prostate brachytherapy. INCeRTs with high drug capacity produce the greatest

  14. EQCM verification of the concept of drug immobilization and release from conducting polymer matrix

    International Nuclear Information System (INIS)

    Krukiewicz, Katarzyna; Bednarczyk-Cwynar, Barbara; Turczyn, Roman; Zak, Jerzy K.

    2016-01-01

    Highlights: • Disuccinyl derivative of anti-cancer drug, betulin, was immobilized in PEDOT matrix. • EQCM was used to monitor the processes of drug immobilization and release. • SEM, EDS and IR confirmed the presence of drug in polymer matrix. • The release of drug was performed with and without application of external potential. • Potentiodynamic stimulation was more efficient that potentiostatic release. - Abstract: Local drug delivery based on conducting polymer carriers is an innovative approach of medical treatment joining the concept of regional release of biomolecules with ion-exchange properties of conjugated polymers. In this study, we have applied electrochemical quartz crystal microbalance (EQCM) to monitor the process of three-step immobilization and release of anti-cancer drug, disuccinyl derivative of betulin, in PEDOT matrix. Each step of this process has been carefully investigated, i.e. electrochemical polymerization of monomer in the absence of drug, removal of primary dopant during the process of matrix reduction and drug incorporation during the process of matrix oxidation. The release of drug from PEDOT matrix has been performed via three paths, i.e. spontaneous release with no application of external potential, active release under potentiostatic conditions and active release under potentiodynamic conditions. EDS elemental analysis, scanning electron microscopy, IR and Raman spectroscopies, have been used to analyze structural and surface properties of drug-loaded PEDOT matrices.

  15. Development of controlled drug release systems based on thiolated polymers.

    Science.gov (United States)

    Bernkop-Schnürch, A; Scholler, S; Biebel, R G

    2000-05-03

    The purpose of the present study was to generate mucoadhesive matrix-tablets based on thiolated polymers. Mediated by a carbodiimide, L-cysteine was thereby covalently linked to polycarbophil (PCP) and sodium carboxymethylcellulose (CMC). The resulting thiolated polymers displayed 100+/-8 and 1280+/-84 micromol thiol groups per gram, respectively (means+/-S.D.; n=6-8). In aqueous solutions these modified polymers were capable of forming inter- and/or intramolecular disulfide bonds. The velocity of this process augmented with increase of the polymer- and decrease of the proton-concentration. The oxidation proceeded more rapidly within thiolated PCP than within thiolated CMC. Due to the formation of disulfide bonds within thiol-containing polymers, the stability of matrix-tablets based on such polymers could be strongly improved. Whereas tablets based on the corresponding unmodified polymer disintegrated within 2 h, the swollen carrier matrix of thiolated CMC and PCP remained stable for 6.2 h (mean, n=4) and more than 48 h, respectively. Release studies of the model drug rifampicin demonstrated that a controlled release can be provided by thiolated polymer tablets. The combination of high stability, controlled drug release and mucoadhesive properties renders matrix-tablets based on thiolated polymers useful as novel drug delivery systems.

  16. Modelling of drug release from ensembles of aspirin microcapsules ...

    African Journals Online (AJOL)

    Purpose: In order to determine the drug release profile of an ensemble of aspirin crystals or microcapsules from its particle distribution a mathematical model that considered the individual release characteristics of the component single particles was developed. The model assumed that under sink conditions the release ...

  17. Elucidation of release characteristics of highly soluble drug trimetazidine hydrochloride from chitosan-carrageenan matrix tablets.

    Science.gov (United States)

    Li, Liang; Wang, Linlin; Shao, Yang; Tian, Ye; Li, Conghao; Li, Ying; Mao, Shirui

    2013-08-01

    The aim of this study was to better understand the underlying drug release characteristics from matrix tablets based on the combination of chitosan (CS) and different types of carrageenans [kappa (κ)-CG, iota (ι)-CG, and lambda (λ)-CG]. Highly soluble trimetazidine hydrochloride (TH) was used as a model drug. First, characteristics of drug release from different formulations were investigated, and then in situ complexation capacity of CG with TH and CS was studied by differential scanning calorimetry and Fourier transform infrared spectroscopy. Erosion and swelling of matrix were also characterized to better understand the drug-release mechanisms. Effects of pH and ionic strength on drug release were also studied. It was found that not only ι-CG and λ-CG could reduce the burst release of TH by the effect of TH-CG interaction, CS-ι-CG- and CS-λ-CG-based polyelectrolyte film could further modify the controlled-release behavior, but not CS-κ-CG. High pH and high ionic strength resulted in faster drug release from CS-κ-CG- and CS-ι-CG-based matrix, but drug release from CS-λ-CG-based matrix was less sensitive to pH and ionic strength. In conclusion, CS-λ-CG-based matrix tablets are quite promising as controlled-release drug carrier based on multiple mechanisms. Copyright © 2013 Wiley Periodicals, Inc.

  18. Magnetothermal release of payload from iron oxide/silica drug delivery agents

    Energy Technology Data Exchange (ETDEWEB)

    Luong, T.T., E-mail: thientai.luong@chem.kuleuven.be [KU Leuven, Department of Chemistry, Celestijnenlaan 200D, Heverlee 3001 (Belgium); Hanoi National University of Education, Faculty of Chemistry, Xuan Thuy 136, Cau Giay, Hanoi (Viet Nam); Knoppe, S.; Bloemen, M.; Brullot, W.; Strobbe, R. [KU Leuven, Department of Chemistry, Celestijnenlaan 200D, Heverlee 3001 (Belgium); Locquet, J.-P. [KU Leuven, Department of Physics, Celestijnenlaan 200D, Heverlee 3001 (Belgium); Verbiest, T. [KU Leuven, Department of Chemistry, Celestijnenlaan 200D, Heverlee 3001 (Belgium)

    2016-10-15

    The release of covalently bound Rhodamine B from iron oxide/mesoporous silica core/shell nanoparticles under magnetically induced heating was studied. The system acts as a model to study drug delivery and payload release under magnetothermal heating. - Graphical abstract: The release of covalently bound Rhodamine B from iron oxide/mesoporous silica core/shell nanoparticles under magnetically induced heating was studied. - Highlights: • Iron oxide/mesoporous-SiO{sub 2} core-shell NPs were synthesized. • The dye was covalently bound to SiO{sub 2} shells. • The release of dye under magnetothermal heating was studied. • The results are relevant for controlled drug release.

  19. Imaging neurotransmitter release by drugs of abuse.

    Science.gov (United States)

    Martinez, Diana; Narendran, Rajesh

    2010-01-01

    Previous studies have shown that imaging with positron emission tomography (PET) and single photon emission computed tomography (SPECT) radiotracers that are specific for brain dopamine receptors can be used to indirectly image the change in the levels of neurotransmitters within the brain. Most of the studies in addiction have focused on dopamine, since the dopamine neurons that project to the striatum have been shown to play a critical role in mediating addictive behavior. These imaging studies have shown that increased extracellular dopamine produced by psychostimulants can be measured with PET and SPECT. However, there are some technical issues associated with imaging changes in dopamine, and these are reviewed in this chapter. Among these are the loss of sensitivity, the time course of dopamine pulse relative to PET and SPECT imaging, and the question of affinity state of the receptor. In addition, animal studies have shown that most drugs of abuse increase extracellular dopamine in the striatum, yet not all produce a change in neurotransmitter that can be measured. As a result, imaging with a psychostimulant has become the preferred method for imaging presynaptic dopamine transmission, and this method has been used in studies of addiction. The results of these studies suggest that cocaine and alcohol addiction are associated with a loss of dopamine transmission, and a number of studies show that this loss correlates with severity of disease.

  20. Production and Investigation of Controlled Drug Release Properties of Tamoxifen Loaded Alginate-Gum Arabic Microbeads

    Directory of Open Access Journals (Sweden)

    Rukiye Yavaşer

    2016-08-01

    Full Text Available The entrapment of tamoxifen onto alginate-gum arabic beads and the production of controlled drug release was investigated in this study. The polymeric system that would provide the controlled release of tamoxifen was formed using alginate and gum arabic. In the first phase of the study, the optimization of the alginate-gum arabic beads production was conducted; then the study continued with drug entrapment experiments. Tamoxifen entrapment yield was found to be approximately 90% of initial tamoxifen concentration. In vitro drug release experiments were performed in simulated gastric juice and intestinal fluid where the tamoxifen release was 20% and 53% of the initial drug present, respectively. As a result of this study, it is expected that a valuable contribution to the field of controlled drug release system production is realized.

  1. Microchips and controlled-release drug reservoirs.

    Science.gov (United States)

    Staples, Mark

    2010-01-01

    This review summarizes and updates the development of implantable microchip-containing devices that control dosing from drug reservoirs integrated with the devices. As the expense and risk of new drug development continues to increase, technologies that make the best use of existing therapeutics may add significant value. Trends of future medical care that may require advanced drug delivery systems include individualized therapy and the capability to automate drug delivery. Implantable drug delivery devices that promise to address these anticipated needs have been constructed in a variety of ways using micro- and nanoelectromechanical systems (MEMS or NEMS)-based technology. These devices expand treatment options for addressing unmet medical needs related to dosing. Within the last few years, advances in several technologies (MEMS or NEMS fabrication, materials science, polymer chemistry, and data management) have converged to enable the construction of miniaturized implantable devices for controlled delivery of therapeutic agents from one or more reservoirs. Suboptimal performance of conventional dosing methods in terms of safety, efficacy, pain, or convenience can be improved with advanced delivery devices. Microchip-based implantable drug delivery devices allow localized delivery by direct placement of the device at the treatment site, delivery on demand (emergency administration, pulsatile, or adjustable continuous dosing), programmable dosing cycles, automated delivery of multiple drugs, and dosing in response to physiological and diagnostic feedback. In addition, innovative drug-medical device combinations may protect labile active ingredients within hermetically sealed reservoirs. Copyright (c) 2010 John Wiley & Sons, Inc.

  2. Controlled drug release on amine functionalized spherical MCM-41

    Energy Technology Data Exchange (ETDEWEB)

    Szegedi, Agnes, E-mail: szegedi@chemres.hu [Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, 1025 Budapest, Pusztaszeri ut 59-67 (Hungary); Popova, Margarita; Goshev, Ivan [Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Sofia (Bulgaria); Klebert, Szilvia [Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, 1025 Budapest, Pusztaszeri ut 59-67 (Hungary); Mihaly, Judit [Institute of Molecular Pharmacology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, 1025 Budapest, Pusztaszeri ut 59-67 (Hungary)

    2012-10-15

    MCM-41 silica with spherical morphology and small particle sizes (100 nm) was synthesized and modified by post-synthesis method with different amounts of 3-aminopropyltriethoxysilane (APTES). A comparative study of the adsorption and release of a model drug, ibuprofen, was carried out. The modified and drug loaded mesoporous materials were characterized by XRD, TEM, N{sub 2} physisorption, elemental analysis, thermal analysis and FT-IR spectroscopy. A new method was developed for the quantitative determination of amino groups in surface modified mesoporous materials by the ninhydrin reaction. Good correlation was found between the amino content of the MCM-41 materials determined by the ninhydrin method and their ibuprofen adsorption capacity. Amino modification resulted in high degree of ibuprofen loading and slow release rate in comparison to the parent non-modified MCM-41. - Graphical abstract: Determination of surface amino groups by ninhidrin method. Highlights: Black-Right-Pointing-Pointer Spherical MCM-41 modified by different amounts of APTES was studied. Black-Right-Pointing-Pointer Ibuprofen (IBU) adsorption and release characteristics was tested. Black-Right-Pointing-Pointer The ninhydrin reaction was used for the quantitative determination of amino groups. Black-Right-Pointing-Pointer Stoichiometric amount of APTES is enough for totally covering the surface with amino groups. Black-Right-Pointing-Pointer Good correlation was found between the amino content and IBU adsorption capacity.

  3. Controlled drug release on amine functionalized spherical MCM-41

    International Nuclear Information System (INIS)

    Szegedi, Agnes; Popova, Margarita; Goshev, Ivan; Klébert, Szilvia; Mihály, Judit

    2012-01-01

    MCM-41 silica with spherical morphology and small particle sizes (100 nm) was synthesized and modified by post-synthesis method with different amounts of 3-aminopropyltriethoxysilane (APTES). A comparative study of the adsorption and release of a model drug, ibuprofen, was carried out. The modified and drug loaded mesoporous materials were characterized by XRD, TEM, N 2 physisorption, elemental analysis, thermal analysis and FT-IR spectroscopy. A new method was developed for the quantitative determination of amino groups in surface modified mesoporous materials by the ninhydrin reaction. Good correlation was found between the amino content of the MCM-41 materials determined by the ninhydrin method and their ibuprofen adsorption capacity. Amino modification resulted in high degree of ibuprofen loading and slow release rate in comparison to the parent non-modified MCM-41. - Graphical abstract: Determination of surface amino groups by ninhidrin method. Highlights: ► Spherical MCM-41 modified by different amounts of APTES was studied. ► Ibuprofen (IBU) adsorption and release characteristics was tested. ► The ninhydrin reaction was used for the quantitative determination of amino groups. ► Stoichiometric amount of APTES is enough for totally covering the surface with amino groups. ► Good correlation was found between the amino content and IBU adsorption capacity.

  4. Cyclodextrin Controlled Release of Poorly Water-Soluble Drugs from Hydrogels

    DEFF Research Database (Denmark)

    Woldum, Henriette Sie; Madsen, Flemming; Larsen, Kim Lambertsen

    2008-01-01

    The effect of 2-hydroxypropyl- -cyclodextrin and -cyclodextrin on the release of ibuprofen, ketoprofen and prednisolone was studied. Stability constants calculated for inclusion complexes show size dependence for complexes with both cyclodextrins. Hydrogels were prepared by ultraviolet irradiation...... and release of each model drug was studied. For drugs formulated using cyclodextrins an increase in the achievable concentration and in the release from hydrogels was obtained due to increased solubility, although the solubility of all -cyclodextrin complexes was limited. The load also was increased...

  5. THE STUDY ON THE EFFECT OF FORMULATION VARIABLES ON IN VITRO FLOATING TIME AND THE RELEASE PROPERTIES OF A FLOATING DRUG DELIVERY SYSTEM BY A STATISTICAL OPTIMIZATION TECHNIQUE

    Directory of Open Access Journals (Sweden)

    C. NARENDRA

    2008-03-01

    Full Text Available The present investigation concerns the evaluation of the effect of formulation variables on in vitro floating time and the release properties in developing a floating drug delivery system (FDDS containing a highly water soluble drug metoprolol tartrate (MT in the presence of a gas generating agent. A 32 full factorial design was employed in formulating the FDDS containing hydroxyl propylmethylcellulose (HPMC K4M and sodium carboxymethylcellulose (NaCMC as swellable polymers. Drug-to-polymer ratio and polymer-to-polymer ratio were included as independent variables. The main effect and the interaction terms were quantitatively evaluated by a quadratic model to predict formulations with the floating time desired, and the release properties. It was found that only drug-to-polymer ratio and its quadratic term were found to be significantly affective for all the response variables. Non-Fickian transport was confirmed as a release mechanism from the optimized formulations. The desirability function was used to optimize the response variables, each having a different target, and the observed responses were highly agreed with experimental values. The results demonstrate the feasibility of the model in the development of FDDS containing a highly water-soluble drug MT.

  6. Ultrasound enhanced release of therapeutics from drug-releasing implants based on titania nanotube arrays.

    Science.gov (United States)

    Aw, Moom Sinn; Losic, Dusan

    2013-02-25

    A non-invasive and external stimulus-driven local drug delivery system (DDS) based on titania nanotube (TNT) arrays loaded with drug encapsulated polymeric micelles as drug carriers and ultrasound generator is described. Ultrasound waves (USW) generated by a pulsating sonication probe (Sonotrode) in phosphate buffered saline (PBS) at pH 7.2 as the medium for transmitting pressure waves, were used to release drug-loaded nano-carriers from the TNT arrays. It was demonstrated that a very rapid release in pulsatile mode can be achieved, controlled by several parameters on the ultrasonic generator. This includes pulse length, time, amplitude and power intensity. By optimization of these parameters, an immediate drug-micelles release of 100% that spans a desirable time of 5-50 min was achieved. It was shown that stimulated release can be generated and reproduced at any time throughout the TNT-Ti implant life, suggesting considerable potential of this approach as a feasible and tunable ultrasound-mediated drug delivery system in situ via drug-releasing implants. It is expected that this concept can be translated from an in vitro to in vivo regime for therapeutic applications using drug-releasing implants in orthopedic and coronary stents. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  7. Biodegradable drug-eluting nanofiber-enveloped implants for sustained release of high bactericidal concentrations of vancomycin and ceftazidime: in vitro and in vivo studies

    Directory of Open Access Journals (Sweden)

    Hsu YH

    2014-09-01

    Full Text Available Yung-Heng Hsu,1,2 Dave Wei-Chih Chen,1 Chun-Der Tai,3 Ying-Chao Chou,1,2 Shih-Jung Liu,2 Steve Wen-Neng Ueng,1 Err-Cheng Chan4 1Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Guishan Township, 2Department of Mechanical Engineering, Chang Gung University, Guishan Township, 3Graduate Institute of Medical Mechatronics, Chang Gung University, Guishan Township, 4School of Medical Technology, Chang Gung University, Guishan Township, Taiwan Abstract: We developed biodegradable drug-eluting nanofiber-enveloped implants that provided sustained release of vancomycin and ceftazidime. To prepare the biodegradable nanofibrous membranes, poly(D,L-lactide-co-glycolide and the antibiotics were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. They were electrospun into biodegradable drug-eluting membranes, which were then enveloped on the surface of stainless plates. An elution method and a high-performance liquid chromatography assay were employed to characterize the in vivo and in vitro release rates of the antibiotics from the nanofiber-enveloped plates. The results showed that the biodegradable nanofiber-enveloped plates released high concentrations of vancomycin and ceftazidime (well above the minimum inhibitory concentration for more than 3 and 8 weeks in vitro and in vivo, respectively. A bacterial inhibition test was carried out to determine the relative activity of the released antibiotics. The bioactivity ranged from 25% to 100%. In addition, the serum creatinine level remained within the normal range, suggesting that the high vancomycin concentration did not affect renal function. By adopting the electrospinning technique, we will be able to manufacture biodegradable drug-eluting implants for the long-term drug delivery of different antibiotics. Keywords: biodegradable nanofiber-enveloped plates, electrospinning, antibiotics, release characteristics

  8. Modulating drug release from gastric-floating microcapsules through spray-coating layers.

    Directory of Open Access Journals (Sweden)

    Wei Li Lee

    Full Text Available Floating dosage forms with prolonged gastric residence time have garnered much interest in the field of oral delivery. However, studies had shown that slow and incomplete release of hydrophobic drugs during gastric residence period would reduce drug absorption and cause drug wastage. Herein, a spray-coated floating microcapsule system was developed to encapsulate fenofibrate and piroxicam, as model hydrophobic drugs, into the coating layers with the aim of enhancing and tuning drug release rates. Incorporating fenofibrate into rubbery poly(caprolactone (PCL coating layer resulted in a complete and sustained release for up to 8 h, with outermost non-drug-holding PCL coating layer serving as a rate-controlling membrane. To realize a multidrug-loaded system, both hydrophilic metformin HCl and hydrophobic fenofibrate were simultaneously incorporated into these spray-coated microcapsules, with metformin HCl and fenofibrate localized within the hollow cavity of the capsule and coating layer, respectively. Both drugs were observed to be completely released from these coated microcapsules in a sustained manner. Through specific tailoring of coating polymers and their configurations, piroxicam loaded in both the outer polyethylene glycol and inner PCL coating layers was released in a double-profile manner (i.e. an immediate burst release as the loading dose, followed by a sustained release as the maintenance dose. The fabricated microcapsules exhibited excellent buoyancy in simulated gastric fluid, and provided controlled and sustained release, thus revealing its potential as a rate-controlled oral drug delivery system.

  9. The influence of granulating solvents on drug release from tablets ...

    African Journals Online (AJOL)

    ... significantly lower than the other wet granulated tablets, but higher than the matrix tablets. The granulating solvent influenced the release of drug which increased with increase in the water content. Key Words: Grewia gum: Granulating solvents; Release mechanisms. Journal of Pharmacy and Bioresources Vol.1(1) 2004: ...

  10. Pharmaceutical properties of two ethenzamide-gentisic acid cocrystal polymorphs: Drug release profiles, spectroscopic studies and theoretical calculations.

    Science.gov (United States)

    Sokal, Agnieszka; Pindelska, Edyta; Szeleszczuk, Lukasz; Kolodziejski, Waclaw

    2017-04-30

    The aim of this study was to evaluate the stability and solubility of the polymorphic forms of the ethenzamide (ET) - gentisic acid (GA) cocrystals during standard technological processes leading to tablet formation, such as compression and excipient addition. In this work two polymorphic forms of pharmaceutical cocrystals (ETGA) were characterized by 13 C and 15 N solid-state nuclear magnetic resonance and Fourier transformed infrared spectroscopy. Spectroscopic studies were supported by gauge including projector augmented wave (GIPAW) calculations of chemical shielding constants.Polymorphs of cocrystals were easily identified and characterized on the basis of solid-state spectroscopic studies. ETGA cocrystals behaviour during direct compressionand tabletting with excipient addition were tested. In order to choose the best tablet composition with suitable properties for the pharmaceutical industry dissolution profile studies of tablets containing polymorphic forms of cocrystals with selected excipients were carried out. Copyright © 2017. Published by Elsevier B.V.

  11. Grafting amino drugs to poly(styrene-alt-maleic anhydride) as a potential method for drug release

    Energy Technology Data Exchange (ETDEWEB)

    Khazaei, Ardeshir; Saednia, Shahnaz; Saien, Javad; Abbasi, Fatemeh, E-mail: Khazaei_1326@yahoo.com, E-mail: ssaednia@gmail.com [Faculty of Chemistry, Bu-Ali Sina University, Hamedan (Iran, Islamic Republic of); Kazem-Rostami, Masoud [Young Researchers Club and Elite, Takestan Branch, Islamic Azad University, Takestan (Iran, Islamic Republic of); Sadeghpour, Mahdieh [Department of Chemistry, Takestan Branch, Islamic Azad University, Takestan (Iran, Islamic Republic of); Borazjani, Maryam Kiani [Faculty of Science, Department of Chemistry, Bushehr Payame Noor University (PNU), Bushehr (Iran, Islamic Republic of)

    2013-07-15

    Drug delivery systems based on polymer-drug conjugates give an improved treatment with lower toxicity or side effects and be used for the treatment of different diseases. Conjugates of biodegradable poly(styrene-alt-maleic anhydride) (PSMA), with a therapeutic agents such as amantadine hydrochloride, amlodipine, gabapentin, zonisamide and mesalamine, were afforded by the formation of the amide bonds of the amino drugs that reacted with the PSMA anhydride groups. The amounts of covalently conjugated drugs were determined by a {sup 1}H NMR spectroscopic method, and the in vitro release rate in buffer solution (pH 1.3) was studied at body temperature 37 Degree-Sign C. In kinetic studies, different dissolution models were examined to obtain drug release data and the collected data were well-fitted to the Korsmeyer-Peppas equation, revealing a dominant Fickian diffusion mechanism for drug release under the in vitro conditions. (author)

  12. Development of Bilayer Tablets with Modified Release of Selected Incompatible Drugs.

    Science.gov (United States)

    Dhiman, Neha; Awasthi, Rajendra; Jindal, Shammy; Khatri, Smriti; Dua, Kamal

    2016-01-01

    The oral route is considered to be the most convenient and commonly-employed route for drug delivery. When two incompatible drugs need to be administered at the same time and in a single formulation, bilayer tablets are the most appropriate dosage form to administer such incompatible drugs in a single dose. The aim of the present investigation was to develop bilayered tablets of two incompatible drugs; telmisartan and simvastatin. The bilayer tablets were prepared containing telmisartan in a conventional release layer using croscarmellose sodium as a super disintegrant and simvastatin in a slow-release layer using HPMC K15M, Carbopol 934P and PVP K 30 as matrix forming polymers. The tablets were evaluated for various physical properties, drug-excipient interactions using FTIR spectroscopy and in vitro drug release using 0.1M HCl (pH 1.2) for the first hour and phosphate buffer (pH 6.8) for the remaining period of time. The release kinetics of simvastatin from the slow release layer were evaluated using the zero order, first order, Higuchi equation and Peppas equation. All the physical parameters (such as hardness, thickness, disintegration, friability and layer separation tests) were found to be satisfactory. The FTIR studies indicated the absence of interactions between the components within the individual layers, suggesting drug-excipient compatibility in all the formulations. No drug release from the slow-release layer was observed during the first hour of the dissolution study in 0.1M HCl. The release-controlling polymers had a significant effect on the release of simvastatin from the slow-release layer. Thus, the formulated bilayer tablets avoided incompatibility issues and proved the conventional release of telmisartan (85% in 45 min) and slow release of simvastatin (80% in 8 h). Stable and compatible bilayer tablets containing telmisartan and simvastatin were developed with better patient compliance as an alternative to existing conventional dosage forms.

  13. Studies on Gastroselective Famotidine Floating Tablets for Gastric Ulcers and Effect of Polymeric Excipients on Drug Release.

    OpenAIRE

    Putta Rajesh Kumar

    2012-01-01

    The present investigation was planned to formulate effervescent floating, gastroretentive guar gum tablets containing famotidine, which can be useful in the treatment of gastric ulcer. The investigations carried out on various formulations resulted in totally four formulations obeying zero order kinetics. The study on rheological characteristics of powder bed indicated that, all the granules were freely flowing and compressible; density of all the tablets was less than 1, thereby assisting in...

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

    Directory of Open Access Journals (Sweden)

    Rachel Shet Hui Wong

    2017-07-01

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

  15. Ultrasound-triggered local release of lipophilic drugs from a novel polymeric ultrasound contrast agent

    NARCIS (Netherlands)

    Kooiman, K.; Böhmer, M.R.; Emmer, M.; Vos, Hendrik J.; Chlon, C.; Foppen-Harteveld, M.; Versluis, Michel; de Jong, N.; van Wamel, A.; Hennink, W.E.; Feijen, J.; Sam, A.P.

    2008-01-01

    The advantage of ultrasound contrast agents (UCAs) as drug delivery systems is the ability to non-invasively control the local and triggered release of a drug or gene. In this study we designed and characterized a novel UCA-based drug delivery system, based on polymer-shelled microcapsules filled

  16. Formulation of 3D Printed Tablet for Rapid Drug Release by Fused Deposition Modeling: Screening Polymers for Drug Release, Drug-Polymer Miscibility and Printability.

    Science.gov (United States)

    Solanki, Nayan G; Tahsin, Md; Shah, Ankita V; Serajuddin, Abu T M

    2018-01-01

    The primary aim of this study was to identify pharmaceutically acceptable amorphous polymers for producing 3D printed tablets of a model drug, haloperidol, for rapid release by fused deposition modeling. Filaments for 3D printing were prepared by hot melt extrusion at 150°C with 10% and 20% w/w of haloperidol using Kollidon ® VA64, Kollicoat ® IR, Affinsiol ™ 15 cP, and HPMCAS either individually or as binary blends (Kollidon ® VA64 + Affinisol ™ 15 cP, 1:1; Kollidon ® VA64 + HPMCAS, 1:1). Dissolution of crushed extrudates was studied at pH 2 and 6.8, and formulations demonstrating rapid dissolution rates were then analyzed for drug-polymer, polymer-polymer and drug-polymer-polymer miscibility by film casting. Polymer-polymer (1:1) and drug-polymer-polymer (1:5:5 and 2:5:5) mixtures were found to be miscible. Tablets with 100% and 60% infill were printed using MakerBot printer at 210°C, and dissolution tests of tablets were conducted at pH 2 and 6.8. Extruded filaments of Kollidon ® VA64-Affinisol ™ 15 cP mixtures were flexible and had optimum mechanical strength for 3D printing. Tablets containing 10% drug with 60% and 100% infill showed complete drug release at pH 2 in 45 and 120 min, respectively. Relatively high dissolution rates were also observed at pH 6.8. The 1:1-mixture of Kollidon ® VA64 and Affinisol ™ 15 cP was thus identified as a suitable polymer system for 3D printing and rapid drug release. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  17. Local drug delivery - the early Berlin experience: single drug administration versus sustained release.

    Science.gov (United States)

    Speck, Ulrich; Scheller, Bruno; Rutsch, Wolfgang; Laule, Michael; Stangl, Verena

    2011-05-01

    Our initial investigations into restenosis inhibition by local drug delivery were prompted by reports on an improved outcome of coronary interventions, including a lower rate of target lesion revascularisation, when the intervention was performed with an ionic instead of non-ionic contrast medium. Although this was not confirmed in an animal study, the short exposure of the vessel wall to paclitaxel dissolved in contrast agent or coated on balloons proved to be efficacious. A study comparing three methods of local drug delivery to the coronary artery in pigs indicated the following order of efficacy in inhibiting neointimal proliferation: paclitaxel-coated balloons > sirolimus-eluting stents, sustained drug release > paclitaxel in contrast medium. Cell culture experiments confirmed that cell proliferation can be inhibited by very short exposure to the drug. Shorter exposure times require higher drug concentrations. Effective paclitaxel concentrations in porcine arteries are achieved when the drug is dissolved in contrast medium or coated on balloons. Paclitaxel is an exceptional drug in that it stays in the treated tissue for a long time. This may explain the long-lasting efficacy of paclitaxel-coated balloons, but does not disprove the hypothesis that the agent blocks a process initiating long-lasting excessive neointimal proliferation, which occurs early after vessel injury.

  18. Investigating the feasibility of temperature-controlled accelerated drug release testing for an intravaginal ring.

    Science.gov (United States)

    Externbrink, Anna; Clark, Meredith R; Friend, David R; Klein, Sandra

    2013-11-01

    The objective of the present study was to investigate if temperature can be utilized to accelerate drug release from Nuvaring®, a reservoir type intravaginal ring based on polyethylene vinyl acetate copolymer that releases a constant dose of contraceptive steroids over a duration of 3 weeks. The reciprocating holder apparatus (USP 7) was utilized to determine real-time and accelerated etonogestrel release from ring segments. It was demonstrated that drug release increased with increasing temperature which can be attributed to enhanced drug diffusion. An Arrhenius relationship of the zero-order release constants was established, indicating that temperature is a valid parameter to accelerate drug release from this dosage form and that the release mechanism is maintained under these accelerated test conditions. Accelerated release tests are particularly useful for routine quality control to assist during batch release of extended release formulations that typically release the active over several weeks, months or even years, since they can increase the product shelf life. The accelerated method should therefore be able to discriminate between formulations with different release characteristics that can result from normal manufacturing variance. In the case of Nuvaring®, it is well known that the process parameters during the extrusion process strongly influence the polymeric structure. These changes in the polymeric structure can affect the permeability which, in turn, is reflected in the release properties. Results from this study indicate that changes in the polymeric structure can lead to a different temperature dependence of the release rate, and as a consequence, the accelerated method can become less sensitive to detect changes in the release properties. When the accelerated method is utilized during batch release, it is therefore important to take this possible restriction into account and to evaluate the accelerated method with samples from non

  19. Drug loading and release on tumor cells using silk fibroin–albumin nanoparticles as carriers

    International Nuclear Information System (INIS)

    Subia, B; Kundu, S C

    2013-01-01

    Polymeric and biodegradable nanoparticles are frequently used in drug delivery systems. In this study silk fibroin–albumin blended nanoparticles were prepared using the desolvation method without any surfactant. These nanoparticles are easily internalized by the cells, reside within perinuclear spaces and act as carriers for delivery of the model drug methotrexate. Methotrexate loaded nanoparticles have better encapsulation efficiency, drug loading ability and less toxicity. The in vitro release behavior of methotrexate from the nanoparticles suggests that about 85% of the drug gets released after 12 days. The encapsulation and loading of a drug would depend on factors such as size, charge and hydrophobicity, which affect drug release. MTT assay and conjugation of particles with FITC demonstrate that the silk fibroin–albumin nanoparticles do not affect the viability and biocompatibility of cells. This blended nanoparticle, therefore, could be a promising nanocarrier for the delivery of drugs and other bioactive molecules. (paper)

  20. Ingenious pH-sensitive dextran/mesoporous silica nanoparticles based drug delivery systems for controlled intracellular drug release.

    Science.gov (United States)

    Zhang, Min; Liu, Jia; Kuang, Ying; Li, Qilin; Zheng, Di-Wei; Song, Qiongfang; Chen, Hui; Chen, Xueqin; Xu, Yanglin; Li, Cao; Jiang, Bingbing

    2017-05-01

    In this work, dextran, a polysaccharide with excellent biocompatibility, is applied as the "gatekeeper" to fabricate the pH-sensitive dextran/mesoporous silica nanoparticles (MSNs) based drug delivery systems for controlled intracellular drug release. Dextran encapsulating on the surface of MSNs is oxidized by NaIO 4 to obtain three kinds of dextran dialdehydes (PADs), which are then coupled with MSNs via pH-sensitive hydrazone bond to fabricate three kinds of drug carriers. At pH 7.4, PADs block the pores to prevent premature release of anti-cancer drug doxorubicin hydrochloride (DOX). However, in the weakly acidic intracellular environment (pH∼5.5) the hydrazone can be ruptured; and the drug can be released from the carriers. The drug loading capacity, entrapment efficiency and release rates of the drug carriers can be adjusted by the amount of NaIO 4 applied in the oxidation reaction. And from which DOX@MSN-NH-N=C-PAD 10 is chosen as the most satisfactory one for the further in vitro cytotoxicity studies and cellular uptake studies. The results demonstrate that DOX@MSN-NH-N=C-PAD 10 with an excellent pH-sensitivity can enter HeLa cells to release DOX intracellular due to the weakly acidic pH intracellular and kill the cells. In our opinion, the ingenious pH-sensitive drug delivery systems have application potentials for cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Effect of ingested lipids on drug dissolution and release with concurrent digestion: a modeling approach

    Science.gov (United States)

    Buyukozturk, Fulden; Di Maio, Selena; Budil, David E.; Carrier, Rebecca L.

    2014-01-01

    Purpose To mechanistically study and model the effect of lipids, either from food or self-emulsifying drug delivery systems (SEDDS), on drug transport in the intestinal lumen. Methods Simultaneous lipid digestion, dissolution/release, and drug partitioning were experimentally studied and modeled for two dosing scenarios: solid drug with a food-associated lipid (soybean oil) and drug solubilized in a model SEDDS (soybean oil and Tween 80 at 1:1 ratio). Rate constants for digestion, permeability of emulsion droplets, and partition coefficients in micellar and oil phases were measured, and used to numerically solve the developed model. Results Strong influence of lipid digestion on drug release from SEDDS and solid drug dissolution into food-associated lipid emulsion were observed and predicted by the developed model. 90 minutes after introduction of SEDDS, there was 9% and 70% drug release in the absence and presence of digestion, respectively. However, overall drug dissolution in the presence of food-associated lipids occurred over a longer period than without digestion. Conclusion A systems-based mechanistic model incorporating simultaneous dynamic processes occurring upon dosing of drug with lipids enabled prediction of aqueous drug concentration profile. This model, once incorporated with a pharmacokinetic model considering processes of drug absorption and drug lymphatic transport in the presence of lipids, could be highly useful for quantitative prediction of impact of lipids on bioavailability of drugs. PMID:24234918

  2. Structural and morphological studies on poly(3-hydroxybutyrate acid) (PHB)/chitosan drug releasing microspheres prepared by both single and double emulsion processes

    Energy Technology Data Exchange (ETDEWEB)

    Shih, W.-J. [Department of Materials Science and Engineering, National Cheng Kung University, 1 Ta-Hsueh Road, Tainan 70101, Taiwan (China); Chen, Y.-H. [Department of Mechanical Engineering, National Kaohsiung University of Applied Sciences, 415 Chien-kung Road, Kaohsiung 80782, Taiwan (China); Shih, C.-J. [Faculty of Fragrance and Cosmetics, Kaohsiung Medical University, No. 100, Shih-Chuang 1st Rd., Sanmin District, Kaohsiung 80708, Taiwan (China); Hon, M.-H. [Department of Materials Science and Engineering, National Cheng Kung University, 1 Ta-Hsueh Road, Tainan 70101, Taiwan (China); Dayeh University, 112 Shan-Jiau Road, Da-Tsuen, Changhua 515, Taiwan (China); Wang, M.-C. [Department of Mechanical Engineering, National Kaohsiung University of Applied Sciences, 415 Chien-kung Road, Kaohsiung 80782, Taiwan (China) and Department of Materials Science and Engineering, National United University, 1 Lien-Da Road, Kung-ching Li, Miao Li 360, Taiwan (China)]. E-mail: mcwang@cc.kuas.edu.tw

    2007-05-31

    Drug releasing microspheres of poly(3-hydroxybutyric acid)/chitosan (PHB/CTS) with various compositions have been synthesized by both single and double emulsion methods, and collected by a freeze-drying process. In this study, gentamicin was used as an antibacterial medicine coated with PHB. The PHB/CTS microspheres of various compositions prepared by a single emulsion process (SEP) were identified as the major PHB phase together with a minor unknown Phase X by X-ray diffraction (XRD) and FT-IR. However, in the microspheres prepared using a double emulsion process (DEP) the dominant Phase was X and the minor phase was PHB. The size of the PHB/CTS microspheres prepared by SEP increased with the PHB/CTS ratio from 1 {mu}m for 1:1 to 2 {mu}m for 5:1. However, the size of the PHB/CTS microspheres prepared by DEP decreased with the PHB/CTS ratio from 1 {mu}m for 1:1 to 800 nm for 5:1.

  3. Structural and morphological studies on poly(3-hydroxybutyrate acid) (PHB)/chitosan drug releasing microspheres prepared by both single and double emulsion processes

    International Nuclear Information System (INIS)

    Shih, W.-J.; Chen, Y.-H.; Shih, C.-J.; Hon, M.-H.; Wang, M.-C.

    2007-01-01

    Drug releasing microspheres of poly(3-hydroxybutyric acid)/chitosan (PHB/CTS) with various compositions have been synthesized by both single and double emulsion methods, and collected by a freeze-drying process. In this study, gentamicin was used as an antibacterial medicine coated with PHB. The PHB/CTS microspheres of various compositions prepared by a single emulsion process (SEP) were identified as the major PHB phase together with a minor unknown Phase X by X-ray diffraction (XRD) and FT-IR. However, in the microspheres prepared using a double emulsion process (DEP) the dominant Phase was X and the minor phase was PHB. The size of the PHB/CTS microspheres prepared by SEP increased with the PHB/CTS ratio from 1 μm for 1:1 to 2 μm for 5:1. However, the size of the PHB/CTS microspheres prepared by DEP decreased with the PHB/CTS ratio from 1 μm for 1:1 to 800 nm for 5:1

  4. Sol-gel encapsulation for controlled drug release and biosensing

    Science.gov (United States)

    Fang, Jonathan

    The main focus of this dissertation is to investigate the use of sol-gel encapsulation of biomolecules for controlled drug release and biosensing. Controlled drug release has advantages over conventional therapies in that it maintains a constant, therapeutic drug level in the body for prolonged periods of time. The anti-hypertensive drug Captopril was encapsulated in sol-gel materials of various forms, such as silica xerogels and nanoparticles. The primary objective was to show that sol-gel silica materials are promising drug carriers for controlled release by releasing Captopril at a release rate that is within a therapeutic range. We were able to demonstrate desired release for over a week from Captopril-doped silica xerogels and overall release from Captopril-doped silica nanoparticles. As an aside, the antibiotic Vancomycin was also encapsulated in these porous silica nanoparticles and desired release was obtained for several days in-vitro. The second part of the dissertation focuses on immobilizing antibodies and proteins in sol-gel to detect various analytes, such as hormones and amino acids. Sol-gel competitive immunoassays on antibody-doped silica xerogels were used for hormone detection. Calibration for insulin and C-peptide in standard solutions was obtained in the nM range. In addition, NASA-Ames is also interested in developing a reagentless biosensor using bacterial periplasmic binding proteins (bPBPs) to detect specific biomarkers, such as amino acids and phosphate. These bPBPs were doubly labeled with two different fluorophores and encapsulated in silica xerogels. Ligand-binding experiments were performed on the bPBPs in solution and in sol-gel. Ligand-binding was monitored by fluorescence resonance energy transfer (FRET) between the two fluorophores on the bPBP. Titration data show that one bPBP has retained its ligand-binding properties in sol-gel.

  5. Mechanism and kinetics of the loss of poorly soluble drugs from liposomal carriers studied by a novel flow field-flow fractionation-based drug release-/transfer-assay.

    Science.gov (United States)

    Hinna, Askell Hvid; Hupfeld, Stefan; Kuntsche, Judith; Bauer-Brandl, Annette; Brandl, Martin

    2016-06-28

    Liposomes represent a versatile drug formulation approach e.g. for improving the water-solubility of poorly soluble drugs but also to achieve drug targeting and controlled release. For the latter applications it is essential that the drug remains associated with the liposomal carrier during transit in the vascular bed. A range of in vitro test methods has been suggested over the years for prediction of the release of drug from liposomal carriers. The majority of these fail to give a realistic prediction for poorly water-soluble drugs due to the intrinsic tendency of such compounds to remain associated with liposome bilayers even upon extensive dilution. Upon i.v. injection, in contrast, rapid drug loss often occurs due to drug transfer from the liposomal carriers to endogenous lipophilic sinks such as lipoproteins, plasma proteins or membranes of red blood cells and endothelial cells. Here we report on the application of a recently introduced in vitro predictive drug transfer assay based on incubation of the liposomal drug carrier with large multilamellar liposomes, the latter serving as a biomimetic model sink, using flow field-flow fractionation as a tool to separate the two types of liposomes. By quantifying the amount of drug remaining associated with the liposomal drug carrier as well as that transferred to the acceptor liposomes at distinct times of incubation, both the kinetics of drug transfer and release to the water phase could be established for the model drug p-THPP (5,10,15,20-tetrakis(4-hydroxyphenyl)21H,23H-porphine). p-THPP is structurally similar to temoporfin, a photosensitizer which is under clinical evaluation in a liposomal formulation. Mechanistic insights were gained by varying the donor-to-acceptor lipid mass ratio, size and lamellarity of the liposomes. Drug transfer kinetics from one liposome to another was found rate determining as compared to redistribution from the outermost to the inner concentric bilayers, such that the overall

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

    Directory of Open Access Journals (Sweden)

    Bing Cai

    2012-01-01

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

  7. Effects of process variables on micromeritic properties and drug release of non-degradable microparticles

    Directory of Open Access Journals (Sweden)

    Mitra Jelvehgari

    2011-06-01

    Full Text Available Introduction: The purpose of this investigation was to evaluate microencapsulated controlled release preparation of theophylline using Eudragit RS 100 as the retardant material with high entrapment efficiency. Methods: Microspheres were prepared by the emulsion-solvent evaporation method. A mixed solvent system consisting of methanol and acetone and light liquid paraffin as oily phase were chosen. Sucrose stearate was used as the surfactant to stabilize the emulsification process. The prepared microspheres were characterized by drug loading, Fourier-transform infrared spectroscopy (FTIR, differential scanning colorimetry (DSC and scanning electron microscopy (SEM. The in vitro release studies were performed at pH 1.2 and 7.4 aqueous medium. Results: Increasing the concentration of emulsifier, sucrose fatty acid ester F-70, decreased the particle size which contributed to increased drug release rate. The drug loading microparticle Eudragit RS100 (1:6 showed 60-75% of entrapment and mean particle size 205.93-352.76 µm. The results showed that, an increase in the ratio of polymer: drug (F5, 6: 1 resulted in a reduction in the release rate of the drug which may be attributed to the hydrophobic nature of the polymer. Conclusion: The release of theophylline is influenced by the drug to polymer ratio and particle size. Drug release is controlled by diffusion and the best-fit release kinetic is Higuchi model.

  8. Effects of process variables on micromeritic properties and drug release of non-degradable microparticles.

    Science.gov (United States)

    Jelvehgari, Mitra; Barar, Jaleh; Nokhodchi, Ali; Shadrou, Sanam; Valizadeh, Hadi

    2011-01-01

    The purpose of this investigation was to evaluate microencapsulated controlled release preparation of theophylline using Eudragit RS 100 as the retardant material with high entrapment efficiency. Microspheres were prepared by the emulsion-solvent evaporation method. A mixed solvent system consisting of methanol and acetone and light liquid paraffin as oily phase were chosen. Sucrose stearate was used as the surfactant to stabilize the emulsification process. The prepared microspheres were characterized by drug loading, Fourier-transform infrared spectroscopy (FTIR), differential scanning colorimetry (DSC) and scanning electron microscopy (SEM). The in vitro release studies were performed at pH 1.2 and 7.4 aqueous medium. Increasing the concentration of emulsifier, sucrose fatty acid ester F-70, decreased the particle size which contributed to increased drug release rate. The drug loading microparticle Eudragit RS100(1:6) showed 60-75% of entrapment and mean particle size 205.93-352.76 μm.The results showed that, an increase in the ratio of polymer: drug (F5, 6: 1) resulted in a reduction in the release rate of the drug which may be attributed to the hydrophobic nature of the polymer. The release of theophylline is influenced by the drug to polymer ratio and particle size. Drug release is controlled by diffusion and the best-fit release kinetic is Higuchi model.

  9. INCREASE IN DOPAMINE RELEASE FROM THE NUCLEUS-ACCUMBENS IN RESPONSE TO FEEDING - A MODEL TO STUDY INTERACTIONS BETWEEN DRUGS AND NATURALLY ACTIVATED DOPAMINERGIC-NEURONS IN THE RAT-BRAIN

    NARCIS (Netherlands)

    WESTERINK, BHC; TEISMAN, A; DEVRIES, JB

    The aim of the present study was to investigate the interactions between the in vivo release of dopamine and certain drugs, during conditions of increased dopaminergic activity. Dopaminergic neurons in the nucleus accumbens were activated by feeding hungry rats. 48-96 h after implantation of a

  10. Chitosan nanoparticles as a modified diclofenac drug release system

    Science.gov (United States)

    Duarte Junior, Anivaldo Pereira; Tavares, Eraldo José Madureira; Alves, Taís Vanessa Gabbay; de Moura, Márcia Regina; da Costa, Carlos Emmerson Ferreira; Silva Júnior, José Otávio Carréra; Ribeiro Costa, Roseane Maria

    2017-08-01

    This study evaluated a modified nanostructured release system employing diclofenac as a drug model. Biodegradable chitosan nanoparticles were prepared with chitosan concentrations between 0.5 and 0.8% ( w/ v) by template polymerization method using methacrylic acid in aqueous solution. Chitosan-poly(methacrylic acid) (CS-PMAA) nanoparticles showed uniform size around 50-100 nm, homogeneous morphology, and spherical shape. Raw material and chitosan nanoparticles were characterized by thermal analysis, Fourier transform infrared spectroscopy (FT-IR), and transmission electron microscopy (TEM), confirming the interaction between chitosan and methacrylic acid during nanoparticles preparation. Diclofenac sorption on the chitosan nanoparticles surface was achieved by incubation in water/ethanol (1:1) drug solution in concentrations of 0.5 and 0.8 mg/mL. The diclofenac amount sorbed per gram of CS-PMAA nanoparticles, when in a 0.5 mg/mL sodium diclofenac solution, was as follows: 12.93, 15, 20.87, and 29.63 mg/g for CS-PMAA nanoparticles 0.5, 0.6, 0.7, and 0.8% ( w/ v), respectively. When a 0.8 mg/mL sodium diclofenac solution was used, higher sorption efficiencies were obtained: For CS-PMAA nanoparticles with chitosan concentrations of 0.5, 0.6, 0.7, and 0.8% ( w/ v), the sorption efficiencies were 33.39, 49.58, 55.23, and 67.2 mg/g, respectively. Diclofenac sorption kinetics followed a second-order kinetics. Drug release from nanoparticles occurred in a period of up to 48 h and obeyed Korsmeyer-Peppas model, which was characterized mainly by Fickian diffusion transport. [Figure not available: see fulltext.

  11. Plasticisation of amylodextrin by moisture : Consequences for drug release from tablets

    NARCIS (Netherlands)

    Steendam, Rob; Eissens, Anco C.E.; Frijlink, Henderik W.; Lerk, Coenraad F.

    2000-01-01

    Moisture influences the consolidation behaviour of amylodextrin powders and the porosity and mechanical strength of compacts thereof. The aim of this study is to relate moisture content and compact properties to drug release characteristics of amylodextrin tablets. Therefore, amylodextrin tablets

  12. Model for Microcapsule Drug Release with Ultrasound-Activated Enhancement.

    Science.gov (United States)

    Tsao, Nadia H; Hall, Elizabeth A H

    2017-11-14

    Microbubbles and microcapsules of silane-polycaprolactone (SiPCL) have been filled with a fluorescent acridium salt (lucigenin) as a model for a drug-loaded delivery vehicle. The uptake and delivery were studied and compared with similar microbubbles and microcapsules of silica/mercaptosilica (S/M/S). Positively charged lucigenin was encapsulated through an electrostatic mechanism, following a Type I Langmuir isotherm as expected, but with an additional multilayer uptake that leads to a much higher loading for the SiPCL system (∼280 μg/2.4 × 10 9 microcapsules compared with ∼135 μg/2.4 × 10 9 microcapsules for S/M/S). Whereas the lucigenin release from the S/M/S bubbles and capsules loaded below the solubility limit is consistent with diffusion from a monolithic structure, the SiPCL structures show distinct release patterns; the Weibull function predicts a general trend for diffusion from normal Euclidean space at short times tending toward diffusion out of fractal spaces with increasing time. As a slow release system, the dissolution time (T d ) increases from 1 to 2 days for the S/M/S and for the low concentration, loaded SiPCl vehicles to ∼10 days for the high loaded microcapsules. However, T d can be reduced on insonation to 2 days, indicating the potential to gain control over the local enhanced release with ultrasound. This was tested for a docetaxel model and its effect on C4-2B prostate cancer cells, showing improved cell toxicity for concentrations below the normal EC 50 in solution.

  13. Preparation and properties of a drug sustained-release hydrogel film

    International Nuclear Information System (INIS)

    Yue Ling; Yang Zhanshan; Yang Shuqin; Li Qinghua

    2009-01-01

    A hydrogel film of drug sustained-release was prepared to accelerate wound healing. The hydrogel films containing drug or not were prepared by the freezing and thawing process. Their properties such as the physicochemical property and the drug release behavior in vitro were studied. Effect of the freezing and thawing process on antimicrobial efficacy of the gentamicin was evaluated by diffusion method. The results indicate that swelling ratio of the hydrogel films freezed for 4h is 841.21% and their gel fraction, tensile strength and elongation at break is 96.10%, 0.222 MPa and 673.50% respectively. The antimicrobial efficacy of the gentamicin has no change. The hydrogel film contained gentamicin releases the antibiotic to peak during 6 h with the cumulative drug release rate of 59.57%. The drug releases continually up to the 5th day. The drug delivery conforms to Higuchi kinetic equation, and mechanism of the drug release is matrix diffusion. The results show that the hydrogel film prepared by the freezing and thawing process display satisfactory physicochemical properties and can be used as a drug delivery system. (authors)

  14. Tailored beads made of dissolved cellulose - Investigation of their drug release properties

    DEFF Research Database (Denmark)

    Yildir, Emrah; Kolakovic, Ruzica; Genina, Natalja

    2013-01-01

    In the frame of this work, we have investigated drug entrapping and release abilities of new type of porous cellulose beads (CBs) as a spherical matrix system for drug delivery. For that purpose, CBs prepared with three different methods were used as drug carriers and three compounds, anhydrous...... theophylline (Thp), riboflavin 5′-phosphate sodium (RSP) and lidocaine hydrochloride monohydrate (LiHCl) were used as model drug substances. The loading procedure was carried out by immersing swollen empty beads into the solutions of different concentrations of model drugs. The morphology of empty and loaded...... beads was examined using a field emission scanning electron microscopy (FE-SEM). Near-infrared (NIR) imaging was performed to identify the drug distributions on and within the loaded CBs. The drug amount incorporated into CBs was examined spectrophotometrically and in vitro drug release studies were...

  15. Release behavior of drugs from various natural gums and polymers.

    Science.gov (United States)

    Singh, Anupama; Sharma, Pramod Kumar; Malviya, Rishabha

    2011-01-01

    Polymers are the high molecular weight compounds of natural or synthetic origin, widely used in drug delivery of formulations. These polymers are further classified as hydrophilic or hydrophobic in nature. Depending upon this characteristic, polymers exhibit different release behavior in different media. This property plays an important role in the selection of polymers for controlled, sustained or immediate release formulations. The review highlights the literatures related to the research made on several polymers regarding the release kinetics which made them a novel approach for modifying the action of the particular formulation.

  16. Drug-releasing shape-memory polymers - the role of morphology, processing effects, and matrix degradation.

    Science.gov (United States)

    Wischke, Christian; Behl, Marc; Lendlein, Andreas

    2013-09-01

    Shape-memory polymers (SMPs) have gained interest for temporary drug-release systems that should be anchored in the body by self-sufficient active movements of the polymeric matrix. Based on the so far published scientific literature, this review highlights three aspects that require particular attention when combining SMPs with drug molecules: i) the defined polymer morphology as required for the shape-memory function, ii) the strong effects that processing conditions such as drug-loading methodologies can have on the drug-release pattern from SMPs, and iii) the independent control of drug release and degradation by their timely separation. The combination of SMPs with a drug-release functionality leads to multifunctional carriers that are an interesting technology for pharmaceutical sciences and can be further expanded by new materials such as thermoplastic SMPs or temperature-memory polymers. Experimental studies should include relevant molecules as (model) drugs and provide a thermomechanical characterization also in an aqueous environment, report on the potential effect of drug type and loading levels on the shape-memory functionality, and explore the potential correlation of polymer degradation and drug release.

  17. Molecular weight-dependent degradation and drug release of surface-eroding poly(ethylene carbonate)

    DEFF Research Database (Denmark)

    Bohr, Adam; Wang, Yingya; Harmankaya, Necati

    2017-01-01

    .7 macrophages) and in vivo (subcutaneous implantation in rats). All investigated samples degraded by means of surface erosion (mass loss, but constant molecular weight), which was accompanied by a predictable, erosion-controlled drug release pattern. Accordingly, the obtained in vitro degradation half......Poly(ethylene carbonate) (PEC) is a unique biomaterial showing significant potential for controlled drug delivery applications. The current study investigated the impact of the molecular weight on the biological performance of drug-loaded PEC films. Following the preparation and thorough...... to control the spatial and temporal on-demand degradation and drug release from the employed delivery system....

  18. Kinetic models for the release of the anticancer drug doxorubicin from biodegradable polylactide/metal oxide-based hybrids

    CSIR Research Space (South Africa)

    Mhlanga, N

    2015-01-01

    Full Text Available For decades, studies on drug-release kinetics have been an important topic in the field of drug delivery because they provide important insights into the mechanism of drug release from carriers. In this work, polylactide (PLA), doxorubicin (DOX...

  19. Organic Nano vesicular Cargoes for Sustained Drug Delivery: Synthesis, Vesicle Formation, Controlling “Pearling” States, and Terfenadine Loading/Release Studies

    International Nuclear Information System (INIS)

    Botcha, A.K.; Chandrasekar, R.; Dulla, B.; Reddy, E.R.; Rajadurai, M.S.; Chennubhotla, K.S.; Kulkarni, P.; Kulkarni, P.

    2014-01-01

    “Sustained drug delivery systems” which are designed to accomplish long-lasting therapeutic effect are one of the challenging topics in the area of nano medicine. We developed an innovative strategy to prepare nontoxic and polymer stabilized organic nano vesicles (diameter: 200 nm) from a novel bolaamphiphile, where two hydrogen bonding acetyl cytosine molecules connected to 4,4′′-positions of the 2,6-bispyrazolylpyridine through two flexible octyne chains. The nano vesicles behave like biological membrane by spontaneously self-assembling into “pearl-like” chains and subsequently forming long nano tubes (diameter: 150 nm), which further develop into various types of network-junctions through self-organization. For drug loading and delivery applications, the nano vesicles were externally protected with biocompatible poly(ethyleneglycol)-2000 to prevent them from fusion and ensuing tube formation. Nontoxic nature of the nano vesicles was demonstrated by zebra fish teratogenicity assay. Biocompatible nano vesicles were loaded with “terfenadine” drug and successfully utilized to transport and release drug in sustained manner (up to 72 h) in zebra fish larvae, which is recognized as an emerging in vivo model system Synthetic nano

  20. Controlled Release from Zein Matrices : Interplay of Drug Hydrophobicity and pH

    NARCIS (Netherlands)

    Bouman, Jacob; Belton, Peter; Venema, Paul; van der Linden, Erik; de Vries, Renko; Qi, Sheng

    In earlier studies, the corn protein zein is found to be suitable as a sustained release agent, yet the range of drugs for which zein has been studied remains small. Here, zein is used as a sole excipient for drugs differing in hydrophobicity and isoelectric point: indomethacin, paracetamol and

  1. Fabrication, characterization and in vitro drug release behavior of electrospun PLGA/chitosan nanofibrous scaffold

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Z.X.; Zheng, W.; Li, L. [Center for Biomedical Materials and Engineering, Harbin Engineering University, Harbin 150001 (China); Zheng, Y.F., E-mail: yfzheng@pku.edu.cn [Center for Biomedical Materials and Engineering, Harbin Engineering University, Harbin 150001 (China); Department of Advanced Materials and Nanotechnology, College of Engineering, Peking University, Beijing 100871 (China)

    2011-02-15

    Graphical abstract: The fenbufen loaded PLGA/chitosan nanofibrous scaffolds were fabricated by electrospinning. The hydrophilicity of nanofibrous scaffold was enhanced with the increase of chitosan content. The drug release also is accelerated with chitosan increasing because the higher hydrophilicity makes drug diffusing from scaffold more easily. Research highlights: {yields} The average diameter increased with the increase of chitosan content and then decreased. {yields} The release rate of fenbufen increased with the increase of chitosan. {yields} The aligned nanofibrous scaffold exhibits lower drug release rate. {yields} The drug release could be controlled by crosslinking in glutaraldehyde vapor. - Abstract: In this study both aligned and randomly oriented poly(D,L-lactide-co-glycolide) (PLGA)/chitosan nanofibrous scaffold have been prepared by electrospinning. The ratio of PLGA to chitosan was adjusted to get smooth nanofiber surface. Morphological characterization using scanning electron microscopy showed that the aligned nanofiber diameter distribution obtained by electrospinning of polymer blend increased with the increase of chitosan content which was similar to that of randomly oriented nanofibers. The release characteristic of model drug fenbufen (FBF) from the FBF-loaded aligned and randomly oriented PLGA and PLGA/chitosan nanofibrous scaffolds was investigated. The drug release rate increased with the increase of chitosan content because the addition of chitosan enhanced the hydrophilicity of the PLGA/chitosan composite scaffold. Moreover, for the aligned PLGA/chitosan nanofibrous scaffold the release rate was lower than that of randomly oriented PLGA/chitosan nanofibrous scaffold, which indicated that the nanofiber arrangement would influence the release behavior. In addition, crosslinking in glutaraldehyde vapor would decrease the burst release of FBF from FBF-loaded PLGA/chitosan nanofibrous scaffold with a PLGA/chitosan ratio less than 9/1, which

  2. Fabrication, characterization and in vitro drug release behavior of electrospun PLGA/chitosan nanofibrous scaffold

    International Nuclear Information System (INIS)

    Meng, Z.X.; Zheng, W.; Li, L.; Zheng, Y.F.

    2011-01-01

    Graphical abstract: The fenbufen loaded PLGA/chitosan nanofibrous scaffolds were fabricated by electrospinning. The hydrophilicity of nanofibrous scaffold was enhanced with the increase of chitosan content. The drug release also is accelerated with chitosan increasing because the higher hydrophilicity makes drug diffusing from scaffold more easily. Research highlights: → The average diameter increased with the increase of chitosan content and then decreased. → The release rate of fenbufen increased with the increase of chitosan. → The aligned nanofibrous scaffold exhibits lower drug release rate. → The drug release could be controlled by crosslinking in glutaraldehyde vapor. - Abstract: In this study both aligned and randomly oriented poly(D,L-lactide-co-glycolide) (PLGA)/chitosan nanofibrous scaffold have been prepared by electrospinning. The ratio of PLGA to chitosan was adjusted to get smooth nanofiber surface. Morphological characterization using scanning electron microscopy showed that the aligned nanofiber diameter distribution obtained by electrospinning of polymer blend increased with the increase of chitosan content which was similar to that of randomly oriented nanofibers. The release characteristic of model drug fenbufen (FBF) from the FBF-loaded aligned and randomly oriented PLGA and PLGA/chitosan nanofibrous scaffolds was investigated. The drug release rate increased with the increase of chitosan content because the addition of chitosan enhanced the hydrophilicity of the PLGA/chitosan composite scaffold. Moreover, for the aligned PLGA/chitosan nanofibrous scaffold the release rate was lower than that of randomly oriented PLGA/chitosan nanofibrous scaffold, which indicated that the nanofiber arrangement would influence the release behavior. In addition, crosslinking in glutaraldehyde vapor would decrease the burst release of FBF from FBF-loaded PLGA/chitosan nanofibrous scaffold with a PLGA/chitosan ratio less than 9/1, which would be beneficial

  3. Chitosan/alginate based multilayers to control drug release fromophthalmic lens

    OpenAIRE

    Silva, Diana; Pinto, Luís F. V.; Bozukova, Dimitriya; Santos, Luís F.; Serro, Ana Paula; Saramago, Benilde

    2016-01-01

    In this study we investigated the possibility of using layer-by-layer deposition, based in natural polymers (chitosan and alginate), to control the release of different ophthalmic drugs from three types of lens materials: a silicone-based hydrogel recently proposed by our group as drug releasing soft contact lens (SCL) material and two commercially available materials: CI26Y for intraocular lens (IOLs) and Definitive 50 for SCLs. The optimised coating, consisting in one double layer of (algin...

  4. Alginate microgels loaded with temperature sensitive liposomes for magnetic resonance imageable drug release and microgel visualization

    NARCIS (Netherlands)

    Van Elk, Merel; Lorenzato, Cyril; Ozbakir, Burcin; Oerlemans, Chris; Storm, Gert; Nijsen, Frank; Deckers, Roel; Vermonden, Tina; Hennink, Wim E.

    2015-01-01

    The objective of this study was to prepare and characterize alginate microgels loaded with temperature sensitive liposomes, which release their payload after mild hyperthermia. It is further aimed that by using these microgels both the drug release and the microgel deposition can be visualized by

  5. Floating solid cellulose nanofibre nanofoams for sustained release of the poorly soluble model drug furosemide

    DEFF Research Database (Denmark)

    Svagan, Anna Justina; Müllertz, Anette; Löbmann, Korbinian

    2017-01-01

    OBJECTIVES: This study aimed to prepare a furosemide-loaded sustained release cellulose nanofibre (CNF)-based nanofoams with buoyancy. METHODS: Dry foams consisting of CNF and the model drug furosemide at concentrations of 21% and 50% (w/w) have been prepared by simply foaming a CNF-drug suspension...... followed by drying. The resulting foams were characterized towards their morphology, solid state properties and dissolution kinetics. KEY FINDINGS: Solid state analysis of the resulting drug-loaded foams revealed that the drug was present as an amorphous sodium furosemide salt and in form of furosemide...... form I crystals embedded in the CNF foam cell walls. The foams could easily be shaped and were flexible, and during the drug release study, the foam pieces remained intact and were floating on the surface due to their positive buoyancy. Both foams showed a sustained furosemide release compared...

  6. Studies on the toxic effects of periodontal sustained release drug containing ornidazole and pefloxacin mesylate on early embryonic development of SD rat

    Directory of Open Access Journals (Sweden)

    Zheng-mou DONG

    2011-01-01

    Full Text Available Objective To evaluate the toxic effects of periodontal sustained release drug containing ornidazole and pefloxacin mesylate on early embryonic development of SD rats.Methods A total of 100female SD rats were randomly divided into negative control,low-,medium-,high-dose group and intervention group(20each.Rats in low-,medium-and high-dose group were fed daily with the sustained release drug at 1,4,and 8g/kg respectively;those in negative control group were fed daily with distilled water from the 14th day before mating to the 7th day of pregnancy continuously,and those in intervention group received cyclophosphamide(40mg/kgby intraperitoneal injection for 5successive days.During this period,the general status,mating,pregnancy,coefficient of ovary and uterus,the numbers of corpus luteum,nidation,live births,stillbirths,absorbed embryo,prenidatory and postnidatory mortality,serum testosterone(Tand estradiol(E2were determined respectively.Histopathologic examination of the ovary and uterus,immunohistochemical observation of ovaries for proliferating cell nuclear antigen(PCNAand Bcl-2associated X protein(Baxwere also performed respectively.Results The general status of those rats was good except one in the low-dose group and one in the intervention group died on the 14th day of administration,and one in negative control and one in high dose group died on the 5th day of pregnancy,respectively.The body weight of animals decreased significantly(P 0.05.The serum T level in medium-and high-dose group and the E2level in high-dose group declined compared to that in negative control group(P < 0.05.Conclusions Although the periodontal sustained release drug containing ornidazole and pefloxacin mesylate shows no toxicity to the early embryonic development of SD rats,the high dose drug has certain toxicity to ovary.Declined serum concentrations of T and E2,reduced expression of PCNA,and increased Bax may be the causes of the toxicity.

  7. Radiation crosslinked hydrogels as sustained release drug delivery systems

    International Nuclear Information System (INIS)

    Pekala, W.; Rosiak, J.; Rucinska-Rybus, A.; Burczak, K.; Galant, S.; Czolczynska, T.

    1986-01-01

    Radiation methods have been used for: i/modification of vascular prostheses, ii/ obtaining burn dressing materials enabling controlled drug release, iii/ the preparation of polymer ocular insert discs. The surface of polyester vascular prostheses, has been modified by deposition of acrylamide and inducing its polymerization in the solid state by γ-radiation. As a result of this treatment, tightness of the prosthesis walls and its surface hydrophilicity have been improved. Toxicological examinations and blood hemolysis studies of modified prostheses showed its good biocompatibility. Various burn dressings have been prepared and the most promising of all investigated turned to be composition consisting of a cotton gauze base and an active polyacrylamide hydrogel layer with addition of glycerin and immobilized Provital/protein preparation/. Preliminary clinical evaluations of this particular dressing showed that the process of burn healing is indeed fast and fully satisfactory. Ocular insert discs made of polymer and containing pilocarpin hydrochloride which is released at controlled rate have been prepared. It has been found that high hydrophilicity and good swelling properties of the ocular insert discs made possible to incorporate pilocarpin hydrochloride into hydrogel matrix. This work has been carried out under IAEA research contract RB 3379/R-1 POL. (author)

  8. Drug Release from Phase-Changeable Nanodroplets Triggered by Low-Intensity Focused Ultrasound

    Science.gov (United States)

    Cao, Yang; Chen, Yuli; Yu, Tao; Guo, Yuan; Liu, Fengqiu; Yao, Yuanzhi; Li, Pan; Wang, Dong; Wang, Zhigang; Chen, Yu; Ran, Haitao

    2018-01-01

    Background: As one of the most effective triggers with high tissue-penetrating capability and non-invasive feature, ultrasound shows great potential for controlling the drug release and enhancing the chemotherapeutic efficacy. In this study, we report, for the first time, construction of a phase-changeable drug-delivery nanosystem with programmable low-intensity focused ultrasound (LIFU) that could trigger drug-release and significantly enhance anticancer drug delivery. Methods: Liquid-gas phase-changeable perfluorocarbon (perfluoropentane) and an anticancer drug (doxorubicin) were simultaneously encapsulated in two kinds of nanodroplets. By triggering LIFU, the nanodroplets could be converted into microbubbles locally in tumor tissues for acoustic imaging and the loaded anticancer drug (doxorubicin) was released after the microbubble collapse. Based on the acoustic property of shell materials, such as shell stiffness, two types of nanodroplets (lipid-based nanodroplets and PLGA-based nanodroplets) were activated by different acoustic pressure levels. Ultrasound irradiation duration and power of LIFU were tested and selected to monitor and control the drug release from nanodroplets. Various ultrasound energies were introduced to induce the phase transition and microbubble collapse of nanodroplets in vitro (3 W/3 min for lipid nanodroplets; 8 W/3 min for PLGA nanodroplets). Results: We detected three steps in the drug-releasing profiles exhibiting the programmable patterns. Importantly, the intratumoral accumulation and distribution of the drug with LIFU exposure were significantly enhanced, and tumor proliferation was substantially inhibited. Co-delivery of two drug-loaded nanodroplets could overcome the physical barriers of tumor tissues during chemotherapy. Conclusion: Our study provides a new strategy for the efficient ultrasound-triggered chemotherapy by nanocarriers with programmable LIFU capable of achieving the on-demand drug release. PMID:29507623

  9. Release of Water Soluble Drugs from Dynamically Swelling POLY(2-HYDROXYETHYL Methacrylate - CO - Methacrylic Acid) Hydrogels.

    Science.gov (United States)

    Kou, Jim Hwai-Cher

    In this study, ionizable copolymers of HEMA and methacrylic acid (MA) are investigated for their potential use in developing pH dependent oral delivery systems. Because of the MA units, these gels swell extensively at high pH. Since solute diffusion in the hydrophilic polymers depends highly on the water content of the matrix, it is anticipated that the release rate will be modulated by this pH induced swelling. From a practical point of view, the advantage of the present system is that one can minimize drug loss in the stomach and achieve a programmed release in intestine. This approach is expected to improve delivery of acid labile drugs or drugs that cause severe gastrointestinal side effects. This work mainly focuses on the basic understanding of the mechanism involved in drug release from the poly(HEMA -co- MA) gels, especially under dynamic swelling conditions. Equilibrium swelling is first characterized since water content is the major determinant of transport properties in these gels. Phenylpropanolamine (PPA) is chosen as the model drug for the release study and its diffusion characteristics in the gel matrix determined. The data obtained show that the PPA diffusivity follows the free volume theory of Yasuda, which explains the accelerating effect of swelling on drug release. A mathematical model based on a diffusion mechanism has been developed to describe PPA release from the swelling gels. Based on this model, several significant conclusions can be drawn. First, the release rate can be modulated by the aspect ratio of the cylindrical geometry, and this has a practical implication in dosage form design. Second, the release rate can be lowered quite considerably if the dimensional increase due to swelling is significant. Consequently, it is the balance between the drug diffusivity increase and the gel dimensional growth that determines the release rate from the swelling matrix. Third, quasi-steady release kinetics, which are characteristic of swelling

  10. Preparation of microspheres for slow release drug by radiation-induced suspension polymerization and their properties

    International Nuclear Information System (INIS)

    Yoshida, Masaru; Asano, Masaharu; Kaetsu, Isao

    1982-01-01

    The polymer microspheres containing drugs as drug delivery system were made by means of suspension-polymerization by radiation at low temperature by using glass-forming monomers which have stable supercooling properties and large polymerizability at low temperature. The particle distribution depended on the kind of monomer. It was found that the entrapping yield of drug in polymer microspheres increased with increasing viscosity of monomer and that the maximum value on the particle size distribution curve was also shifted to large particle diameter side. In the case of trimethylolpropane trimethacrylate monomer (43 cps), TMPT, the entrapping yield of drug reached 74% and the maximum value in particle size distribution curve appeared in the neighborhood of 105 to 210 mu m ranges. On the other hand, those values in neopentyl glycol dimethacrylate monomer (4 cps) were 12% in former and 44 -- 105 mu m in the latter. The release phenomenon of drugs from polymer microspheres was investigated. for example, the cumulative amount of mitomycin C (water soluble drug) released from TMPT polymer microsphere was about 90% after 30-day dissolution, while in the case of water-insoluble drug such as testosterone the amount of release was about 49% after 40-day dissolution. In all cases, the release rate is constant during the experimental period. Therefore, it was concluded that the release of drugs from polymer microspheres obtained in this study is possible over the long periods. (author)

  11. Ibuprofen-loaded poly(lactic-co-glycolic acid films for controlled drug release

    Directory of Open Access Journals (Sweden)

    Pang JM

    2011-04-01

    Full Text Available Jianmei Pang1, Yuxia Luan1, Feifei Li1, Xiaoqing Cai1, Jimin Du2, Zhonghao Li31School of Pharmaceutical Science, Shandong University, Jinan, Shandong Province, PR China; 2School of Chemistry and Chemical Engineering, Anyang Normal University, Henan Province, PR China; 3School of Materials Science and Engineering, Shandong University, Jinan, Shandong Province, PR ChinaAbstract: Ibuprofen- (IBU loaded biocompatible poly(lactic-co-glycolic acid (PLGA films were prepared by spreading polymer/ibuprofen solution on the nonsolvent surface. By controlling the weight ratio of drug and polymer, different drug loading polymer films can be obtained. The synthesized ibuprofen-loaded PLGA films were characterized with scanning electron microscopy, powder X-ray diffraction, and differential scanning calorimetry. The drug release behavior of the as-prepared IBU-loaded PLGA films was studied to reveal their potential application in drug delivery systems. The results show the feasibility of the as-obtained films for controlling drug release. Furthermore, the drug release rate of the film could be controlled by the drug loading content and the release medium. The development of a biodegradable ibuprofen system, based on films, should be of great interest in drug delivery systems.Keywords: ibuprofen, controlled release, poly(lactic-co-glycolic acid, films

  12. Modeling the modified drug release from curved shape drug delivery systems - Dome Matrix®.

    Science.gov (United States)

    Caccavo, D; Barba, A A; d'Amore, M; De Piano, R; Lamberti, G; Rossi, A; Colombo, P

    2017-12-01

    The controlled drug release from hydrogel-based drug delivery systems is a topic of large interest for research in pharmacology. The mathematical modeling of the behavior of these systems is a tool of emerging relevance, since the simulations can be of use in the design of novel systems, in particular for complex shaped tablets. In this work a model, previously developed, was applied to complex-shaped oral drug delivery systems based on hydrogels (Dome Matrix®). Furthermore, the model was successfully adopted in the description of drug release from partially accessible Dome Matrix® systems (systems with some surfaces coated). In these simulations, the erosion rate was used asa fitting parameter, and its dependence upon the surface area/volume ratio and upon the local fluid dynamics was discussed. The model parameters were determined by comparison with the drug release profile from a cylindrical tablet, then the model was successfully used for the prediction of the drug release from a Dome Matrix® system, for simple module configuration and for module assembled (void and piled) configurations. It was also demonstrated that, given the same initial S/V ratio, the drug release is independent upon the shape of the tablets but it is only influenced by the S/V evolution. The model reveals itself able to describe the observed phenomena, and thus it can be of use for the design of oral drug delivery systems, even if complex shaped. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Control of drug releasing from biodegradable polymer drug delivery system by gamma-ray irradiation

    International Nuclear Information System (INIS)

    Yoshioka, Sumie; Aso, Yukio; Kojima, Shigeo

    1999-01-01

    In order to introduce the drug to the target organ, we developed a gel to control the drug releasing velocity by response to change of temperature by means of γ-ray irradiation to gelatin-GMA modified dextran mixture aqueous solution. A certain level of molecular weight of drug is necessary. The response to the temperature (change of drug releasing velocity) was affected by the concentration of gelatin and the modification rate of GMA. The Higuchi equation was applied to the releasing of β-galactosidase from gelatin-dextran gel and the releasing velocity was calculated. The releasing velocity decreased with increasing GMA modification rate at 37degC and 15degC. The releasing velocity of β-galactosidase decreased with increasing the concentration of gelatin at 15degC, but the velocity increased with increasing the concentration at 37degC. These results indicated that the good drug releasing conditions are obtained by controlling the GMA modification rate and the concentration of gelatin. (S.Y.)

  14. Synthesis of attapulgite/N-isopropylacrylamide and its use in drug release

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiaomo [Jiangsu Key Laboratory for Chemistry of Low-Dimensional Materials, School of Chemistry and Chemical Engineering, Huaiyin Normal University, Huaian 223300 (China); Faculty of Chemistry, Northeast Normal University, Changchun 130024, Jilin (China); Zhong, Hui, E-mail: huizhong@hytc.edu.cn [Jiangsu Key Laboratory for Chemistry of Low-Dimensional Materials, School of Chemistry and Chemical Engineering, Huaiyin Normal University, Huaian 223300 (China); Faculty of Chemistry, Northeast Normal University, Changchun 130024, Jilin (China); Li, Xiaorong, E-mail: lxr206206@163.com [Jiangsu Key Laboratory for Chemistry of Low-Dimensional Materials, School of Chemistry and Chemical Engineering, Huaiyin Normal University, Huaian 223300 (China); Jia, Feifei [Jiangsu Key Laboratory for Chemistry of Low-Dimensional Materials, School of Chemistry and Chemical Engineering, Huaiyin Normal University, Huaian 223300 (China); Faculty of Chemistry, Northeast Normal University, Changchun 130024, Jilin (China); Cheng, Zhipeng; Zhang, Lili; Yin, Jingzhou; An, Litao [Jiangsu Key Laboratory for Chemistry of Low-Dimensional Materials, School of Chemistry and Chemical Engineering, Huaiyin Normal University, Huaian 223300 (China); Guo, Liping, E-mail: guolp078@nenu.edu.cn [Faculty of Chemistry, Northeast Normal University, Changchun 130024, Jilin (China)

    2014-12-01

    Environmentally sensitive hydrogels as one of the most potential drug delivery systems have gained considerable interest in recent years. In the present study, we synthesized a newly temperature-responsive composite hydrogel based on attapulgite (ATP) and poly (N-isopropylacrylamide) (PNIPAM) as the localized drug carriers for drug delivery. The as-prepared ATP/PNIPAM hydrogel has large aperture which significantly improved the quantity of adsorption of drugs, exhibiting the excellent properties of drug release. The scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and X-ray diffraction (XRD) were used to characterize the ATP/PNIPAM. The swelling/deswelling behaviors and the release of ciprofloxacin lactate were studied. When the temperature was below the low critical solution temperature (LCST), the swelling property of hydrogels was excellent and the swelling rate was large. And, the drug release rate increased with the increase of the content of attapulgite in the composite hydrogel when it was put in the buffer solution (pH 7.38) at 37.0 °C. Therefore, the composite hydrogels might be very useful for its application in biomedical fields. - Highlights: • Attapulgite/N-isopropylacrylamide hydrogels were synthesized and characterized. • The swelling property of hydrogels was excellent when temperature was below 34.0 °C. • The composite hydrogels were used for the release of ciprofloxacin lactate. • The drug release rate increased with the increase of the content of attapulgite.

  15. Inorganically modified diatomite as a potential prolonged-release drug carrier.

    Science.gov (United States)

    Janićijević, Jelena; Krajišnik, Danina; Calija, Bojan; Dobričić, Vladimir; Daković, Aleksandra; Krstić, Jugoslav; Marković, Marija; Milić, Jela

    2014-09-01

    Inorganic modification of diatomite was performed with the precipitation product of partially neutralized aluminum sulfate solution at three different mass ratios. The starting and the modified diatomites were characterized by SEM-EDS, FTIR, thermal analysis and zeta potential measurements and evaluated for drug loading capacity in adsorption batch experiments using diclofenac sodium (DS) as a model drug. In vitro drug release studies were performed in phosphate buffer pH6.8 from comprimates containing: the drug adsorbed onto the selected modified diatomite sample (DAMD), physical mixture of the drug with the selected modified diatomite sample (PMDMD) and physical mixture of the drug with the starting diatomite (PMDD). In vivo acute toxicity testing of the modified diatomite samples was performed on mice. High adsorbent loading of the selected modified diatomite sample (~250mg/g in 2h) enabled the preparation of comprimates containing adsorbed DS in the amount near to its therapeutic dose. Drug release studies demonstrated prolonged release of DS over a period of 8h from both DAMD comprimates (18% after 8h) and PMDMD comprimates (45% after 8h). The release kinetics for DAMD and PMDMD comprimates fitted well with Korsmeyer-Peppas and Bhaskar models, indicating that the release mechanism was a combination of non-Fickian diffusion and ion exchange process. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Contact lenses as drug controlled release systems: a narrative review

    Directory of Open Access Journals (Sweden)

    Helena Prior Filipe

    2016-06-01

    Full Text Available ABSTRACT Topically applied therapy is the most common way to treat ocular diseases, however given the anatomical and physiological constraints of the eye, frequent dosing is required with possible repercussions in terms of patient compliance. Beyond refractive error correction, contact lenses (CLs have, in the last few decades emerged as a potential ophthalmic drug controlled release system (DCRS. Extensive research is underway to understand how to best modify CLs to increase residence time and bioavailability of drugs within therapeutic levels on the ocular surface.These devices may simultaneously correct ametropia and have a role in managing ophthalmic disorders that can hinder CL wear such as dry eye, glaucoma, ocular allergy and cornea infection and injury. In this narrative review the authors explain how the ocular surface structures determine drug diffusion in the eye and summarize the strategies to enhance drug residence time and bioavailability. They synthesize findings and clinical applications of drug soaked CLs as DCRS combined with delivery diffusion barriers, incorporation of functional monomers, ion related controlled release, molecular imprinting, nanoparticles and layering. The authors draw conclusions about the impact of these novel ophthalmic agents delivery systems in improving drug transport in the target tissue and patient compliance, in reducing systemic absorption and undesired side effects, and discuss future perspectives.

  17. Phototoxicity free quantum dot-based niosome formulation for controlled drug release and its monitoring

    Science.gov (United States)

    Kumar, Sunil; Kang, T. W.; Bala, Suman; Kamboj, Sunil; Jeon, H. C.

    2018-04-01

    A novel niosomes-based system composed of Hypromellose (HPMC) functionalized fluorescent, biocompatible ZnS:Mn quantum dots (QDs), and anti-HIV drug Tenofovir disoproxil fumarate (TDF) was designed. An appropriate ratio of surfactant Sorbitan Monostearate (SPAN-60) and cholesterol was used to obtain an optimal entrapment efficiency. Initially, after observing the successful interaction of HPMC with SPAN-60, the noisome formulation including (QDs + drug) and HPMC-coated QDs was synthesized by a wet chemical route and characterized by X-ray diffraction (XRD), Transmission electron microscope (TEM) and Selected Electron Diffraction (SAED). Secondly, (QDs + drug) loaded niosome formulations were studied by varying the ratio of SPAN-60 and cholesterol. Multiple studies were done to characterize the shape, size, viscosity, colloidal stability, and entrapment efficiency of (QDs + drug) loaded niosomes. Lastly, pH-dependent (QDs + drug) release profiles were studied by a spectroscopic technique considering the pH of the human gastrointestinal region to obtain the formulation stability of (QDs + drug) release from the niosome vesicles. These studies also include pH-dependent photo-stability measurements based on laser-induced multiphoton excitation technique in the Infrared region. The multiphoton time-resolved studies were completed to avoid the UV induced phototoxicity in the drug delivery modules. Current studies on the formulation of niosomes-based (QDs + drug) system laid a foundation to make a complete phototoxicity free system for tracking controlled drug release and its imaging.

  18. Microfluidic synthesis of microfibers for magnetic-responsive controlled drug release and cell culture.

    Directory of Open Access Journals (Sweden)

    Yung-Sheng Lin

    Full Text Available This study demonstrated the fabrication of alginate microfibers using a modular microfluidic system for magnetic-responsive controlled drug release and cell culture. A novel two-dimensional fluid-focusing technique with multi-inlets and junctions was used to spatiotemporally control the continuous laminar flow of alginate solutions. The diameter of the manufactured microfibers, which ranged from 211 µm to 364 µm, could be well controlled by changing the flow rate of the continuous phase. While the model drug, diclofenac, was encapsulated into microfibers, the drug release profile exhibited the characteristic of a proper and steady release. Furthermore, the diclofenac release kinetics from the magnetic iron oxide-loaded microfibers could be controlled externally, allowing for a rapid drug release by applying a magnetic force. In addition, the successful culture of glioblastoma multiforme cells in the microfibers demonstrated a good structural integrity and environment to grow cells that could be applied in drug screening for targeting cancer cells. The proposed microfluidic system has the advantages of ease of fabrication, simplicity, and a fast and low-cost process that is capable of generating functional microfibers with the potential for biomedical applications, such as drug controlled release and cell culture.

  19. Effects of amphiphilic chitosan-g-poly(ε-caprolactone) polymer additives on paclitaxel release from drug eluting implants

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Weibin [Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092 (China); Gu, Chunhua [Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China); Jiang, Han [Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092 (China); Zhang, Mengru [Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China); Lang, Meidong, E-mail: mdlang@ecust.edu.cn [Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China)

    2014-12-01

    Bioresorbable polymer stents have been proposed as promising medical implants to avoid long-term safety concerns and other potential issues caused by traditional materials. As an important member, poly(ε-caprolactone) (PCL) was used as the implant matrix with different drug loadings. To better regulate drug release rate, the hydrophilicity of PCL was adjusted by addition of amphiphilic graft copolymers, chitosan-g-poly(ε-caprolactone) (CP). The in vitro release results indicated that the improvement of bulk hydrophilicity could accelerate drug release better than that of surface coating. The optimum additive amount was 25% with CP9. Further study showed that the effect of aspirin molecules displayed no obvious difference to that of CP macromolecules on drug release rate. Moreover, these release profiles were fitted with mathematical models. The similarities were evaluated with similarity factors. Scanning electron microscopy (SEM) images displayed surface/cross-section morphologies of pure PCL and modified implants before and after release. - Highlights: • The improvement of bulk hydrophilicity better accelerated drug release. • The higher weight ratio of CP implants had, the faster the drug released. • The shorter PCL chain in CP graft coploymers, the faster the drug released. • The optimum additive amount was 25% with CP9. • Drug release profile conformed to controllable Fick diffusional release mechanism.

  20. A quality-by-design study for an immediate-release tablet platform: examining the relative impact of active pharmaceutical ingredient properties, processing methods, and excipient variability on drug product quality attributes.

    Science.gov (United States)

    Kushner, Joseph; Langdon, Beth A; Hicks, Ian; Song, Daniel; Li, Fasheng; Kathiria, Lalji; Kane, Anil; Ranade, Gautam; Agarwal, Kam

    2014-02-01

    The impact of filler-lubricant particle size ratio variation (3.4-41.6) on the attributes of an immediate-release tablet was compared with the impacts of the manufacturing method used (direct compression or dry granulation) and drug loading (1%, 5%, and 25%), particle size (D[4,3]: 8-114 μm), and drug type (theophylline or ibuprofen). All batches were successfully manufactured, except for direct compression of 25% drug loading of 8 μm (D[4,3]) drug, which exhibited very poor flow properties. All manufactured tablets possessed adequate quality attributes: tablet weight uniformity 1 MPa, friability ≤ 0.2% weight loss, and disintegration time impact on blend and granulation particle size and granulation flow, whereas drug property variation dominated blend flow, ribbon solid fraction, and tablet quality attributes. Although statistically significant effects were observed, the results of this study suggest that the manufacturability and performance of this immediate-release tablet formulation is robust to a broad range of variation in drug properties, both within-grade and extra-grade excipient particle size variations, and the choice of manufacturing method. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  1. Mesoporous hydroxyapatite: Preparation, drug adsorption, and release properties

    Energy Technology Data Exchange (ETDEWEB)

    Gu, Lina; He, Xiaomei; Wu, Zhenyu, E-mail: zhenyuwuhn@sina.com

    2014-11-14

    Mesoporous hydroxyapatite (HA) was synthesized through gas–liquid chemical precipitation method at ambient temperature without any template. Structure, morphology and pore size distribution of HA were analyzed via X-ray powder diffraction, scanning electron microscopy, transmission electron microscopy, high-resolution electron microscopy and N{sub 2} adsorption/desorption. The chemotherapeutic agent doxorubicin (DOX) was used to investigate the drug adsorption and release behavior of HA. The kinetics of DOX adsorption on HA followed the pseudo-second-order rate expression. Adsorption isotherms at various temperatures were obtained, and the equilibrium data fitted the Langmuir model. The values of thermodynamic parameters (Gibbs free energy, entropy, and enthalpy changes) demonstrated that the adsorption process was spontaneous and endothermic. In vitro pH-responsive (pH = 7.4, 5.8) controlled release was investigated. DOX-loaded HA showed a slow, long-term, and steady release rate. The release rate at pH5.8 was larger than that at pH7.4. Consequently, the as-prepared mesoporous HA has potential applications in controlled drug delivery systems. - Highlights: • Mesoporous HA was synthesized by a simple precipitation method without any template. • The kinetics of adsorption followed the pseudo-second-order rate expression. • Thermodynamics investigation showed that adsorption was spontaneous and endothermic. • DOX-loaded HA showed a long-term, steady, and pH-controlled release rate.

  2. Molecularly precise dendrimer-drug conjugates with tunable drug release for cancer therapy.

    Science.gov (United States)

    Zhou, Zhuxian; Ma, Xinpeng; Murphy, Caitlin J; Jin, Erlei; Sun, Qihang; Shen, Youqing; Van Kirk, Edward A; Murdoch, William J

    2014-10-06

    The structural preciseness of dendrimers makes them perfect drug delivery carriers, particularly in the form of dendrimer-drug conjugates. Current dendrimer-drug conjugates are synthesized by anchoring drug and functional moieties onto the dendrimer peripheral surface. However, functional groups exhibiting the same reactivity make it impossible to precisely control the number and the position of the functional groups and drug molecules anchored to the dendrimer surface. This structural heterogeneity causes variable pharmacokinetics, preventing such conjugates to be translational. Furthermore, the highly hydrophobic drug molecules anchored on the dendrimer periphery can interact with blood components and alter the pharmacokinetic behavior. To address these problems, we herein report molecularly precise dendrimer-drug conjugates with drug moieties buried inside the dendrimers. Surprisingly, the drug release rates of these conjugates were tailorable by the dendrimer generation, surface chemistry, and acidity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Electrochemically controlled release of anticancer drug methotrexate using nanostructured polypyrrole modified with cetylpyridinium: Release kinetics investigation

    International Nuclear Information System (INIS)

    Alizadeh, Naader; Shamaeli, Ehsan

    2014-01-01

    A new simple strategy for direct electrochemical incorporation of chemotherapeutic methotrexate (MTX) into conductive polypyrrole (PPy) has been suggested for an electrochemically controlled loading and release system. Electropolymerization of MTX doped polypyrrole yielded poor quality with low efficiency of doping, but a well-doped, nanostructure and increased capacity of drug loading (24.5 mg g −1 ) has been obtained in the presence of cetylpyridinium (CP) as a modifier. When CP was preloaded onto PPy, the hydrophobic surface of the PPy serves as a backbone to which the hydrophobic chain of the CP can be attached. Electrostatic interaction between cationic CP with anionic MTX and aromatic interaction between pyridinium head of CP with pyrimidine and pyrazine rings of MTX increases drug doping. Then release kinetics were investigated at various applied potentials and temperatures. Kinetics analysis based on Avrami's equation showed that the drug release was controlled and accelerated by increasing temperature and negative potential and sustained by increasing positive potential. At open circuit condition, the release parameter (n) represented a diffusive mechanism and at applying electrochemical potentials, a first-order mode. Activation energy parameters (E a , ΔG ≠ , ΔH ≠ and ΔS ≠ ) and half-life time (t 1/2 ) of drug release are also analyzed as a function of applied potential. The nanostructured polymer films (PPy/CP/MTX) were characterized by several techniques: scanning electron microscopy, Furrier transforms Infrared, UV-vis spectroscopy. Overall, our results demonstrate that the PPy/CP/MTX films, combined with electrical stimulation, permit a programmable release of MTX by altering the interaction strength between the PPy/CP and MTX

  4. An investigation of effects of modification processes on physical properties and mechanism of drug release for sustaining drug release from modified rice

    Energy Technology Data Exchange (ETDEWEB)

    Ngo, Vuong Duy; Luu, Thinh Duc; Van Vo, Toi [Pharmaceutical Engineering Laboratory, Biomedical Engineering Department, International University, Vietnam National University, Ho Chi Minh City (Viet Nam); Tran, Van-Thanh [Faculty of Pharmacy, University of Medicine and Pharmacy, Ho Chi Minh City (Viet Nam); Duan, Wei [School of Medicine, Deakin University, Pigdons Road, Waurn Ponds, Victoria (Australia); Tran, Phuong Ha-Lien, E-mail: phuong.tran1@deakin.edu.au [School of Medicine, Deakin University, Pigdons Road, Waurn Ponds, Victoria (Australia); Tran, Thao Truong-Dinh, E-mail: ttdthao@hcmiu.edu.vn [Pharmaceutical Engineering Laboratory, Biomedical Engineering Department, International University, Vietnam National University, Ho Chi Minh City (Viet Nam)

    2016-10-01

    The aim of this study was to investigate the effect of modification processes on physical properties and explain the mechanism of sustained drug release from modified rice (MR). Various types of Vietnamese rice were introduced in the study as the matrices of sustained release dosage form. Rice was thermally modified in water for a determined temperature at different times with a simple process. Then tablets containing MR and isradipine, the model drug, were prepared to investigate the capability of sustained drug release. Scanning electron microscopy (SEM) was used to determine different morphologies between MR formulations. Flow property of MR was analyzed by Hausner ratio and Carr's indices. The dissolution rate and swelling/erosion behaviors of tablets were evaluated at pH 1.2 and pH 6.8 at 37 ± 0.5 °C. The matrix tablet containing MR showed a sustained release as compared to the control. The SEM analyses and swelling/erosion studies indicated that the morphology as well as swelling/erosion rate of MR were modulated by modification time, drying method and incubation. It was found that the modification process was crucial because it could highly affect the granule morphologies and hence, leading to the change of flowability and swelling/erosion capacity for sustained release of drug. - Highlights: • Modification process affected granule morphologies and flowability of modified rice. • Modification process affected swelling/erosion capacity for drug sustained release. • Freeze-drying could decrease the erosion as well as increase the swelling rate.

  5. An investigation of effects of modification processes on physical properties and mechanism of drug release for sustaining drug release from modified rice

    International Nuclear Information System (INIS)

    Ngo, Vuong Duy; Luu, Thinh Duc; Van Vo, Toi; Tran, Van-Thanh; Duan, Wei; Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh

    2016-01-01

    The aim of this study was to investigate the effect of modification processes on physical properties and explain the mechanism of sustained drug release from modified rice (MR). Various types of Vietnamese rice were introduced in the study as the matrices of sustained release dosage form. Rice was thermally modified in water for a determined temperature at different times with a simple process. Then tablets containing MR and isradipine, the model drug, were prepared to investigate the capability of sustained drug release. Scanning electron microscopy (SEM) was used to determine different morphologies between MR formulations. Flow property of MR was analyzed by Hausner ratio and Carr's indices. The dissolution rate and swelling/erosion behaviors of tablets were evaluated at pH 1.2 and pH 6.8 at 37 ± 0.5 °C. The matrix tablet containing MR showed a sustained release as compared to the control. The SEM analyses and swelling/erosion studies indicated that the morphology as well as swelling/erosion rate of MR were modulated by modification time, drying method and incubation. It was found that the modification process was crucial because it could highly affect the granule morphologies and hence, leading to the change of flowability and swelling/erosion capacity for sustained release of drug. - Highlights: • Modification process affected granule morphologies and flowability of modified rice. • Modification process affected swelling/erosion capacity for drug sustained release. • Freeze-drying could decrease the erosion as well as increase the swelling rate.

  6. Controlled release of simvastatin from biomimetic β-TCP drug delivery system.

    Directory of Open Access Journals (Sweden)

    Joshua Chou

    Full Text Available Simvastatin have been shown to induce bone formation and there is currently a urgent need to develop an appropriate delivery system to sustain the release of the drug to increase therapeutic efficacy whilst reducing side effects. In this study, a novel drug delivery system for simvastatin by means of hydrothermally converting marine exoskeletons to biocompatible beta-tricalcium phosphate was investigated. Furthermore, the release of simvastatin was controlled by the addition of an outer apatite coating layer. The samples were characterized by x-ray diffraction analysis, fourier transform infrared spectroscopy, scanning electron microscopy and mass spectroscopy confirming the conversion process. The in-vitro dissolution of key chemical compositional elements and the release of simvastatin were measured in simulated body fluid solution showing controlled release with reduction of approximately 25% compared with un-coated samples. This study shows the potential applications of marine structures as a drug delivery system for simvastatin.

  7. A concise review on smart polymers for controlled drug release.

    Science.gov (United States)

    Aghabegi Moghanjoughi, Arezou; Khoshnevis, Dorna; Zarrabi, Ali

    2016-06-01

    Design and synthesis of efficient drug delivery systems are of critical importance in health care management. Innovations in materials chemistry especially in polymer field allows introduction of advanced drug delivery systems since polymers could provide controlled release of drugs in predetermined doses over long periods, cyclic and tunable dosages. To this end, researchers have taken advantages of smart polymers since they can undergo large reversible, chemical, or physical fluctuations as responses to small changes in environmental conditions, for instance, in pH, temperature, light, and phase transition. The present review aims to highlight various kinds of smart polymers, which are used in controlled drug delivery systems as well as mechanisms of action and their applications.

  8. Tunable drug loading and release from polypeptide multilayer nanofilms

    Science.gov (United States)

    Jiang, Bingbing; Li, Bingyun

    2009-01-01

    Polypeptide multilayer nanofilms were prepared using electrostatic layer-by-layer self-assembly nanotechnology. Small charged drug molecules (eg, cefazolin, gentamicin, and methylene blue) were loaded in polypeptide multilayer nanofilms. Their loading and release were found to be pH-dependent and could also be controlled by changing the number of film layers and drug incubation time, and applying heat-treatment after film formation. Antibioticloaded polypeptide multilayer nanofilms showed controllable antibacterial properties against Staphylococcus aureus. The developed biodegradable polypeptide multilayer nanofilms are capable of loading both positively- and negatively-charged drug molecules and promise to serve as drug delivery systems on biomedical devices for preventing biomedical device-associated infection, which is a significant clinical complication for both civilian and military patients. PMID:19421369

  9. Assessing the influence of media composition and ionic strength on drug release from commercial immediate-release and enteric-coated aspirin tablets.

    Science.gov (United States)

    Karkossa, Frank; Klein, Sandra

    2017-10-01

    The objective of this test series was to elucidate the importance of selecting the right media composition for a biopredictive in-vitro dissolution screening of enteric-coated dosage forms. Drug release from immediate-release (IR) and enteric-coated (EC) aspirin formulations was assessed in phosphate-based and bicarbonate-based media with different pH, electrolyte composition and ionic strength. Drug release from aspirin IR tablets was unaffected by media composition. In contrast, drug release from EC aspirin formulations was affected by buffer species and ionic strength. In all media, drug release increased with increasing ionic strength, but in bicarbonate-based buffers was delayed when compared with that in phosphate-based buffers. Interestingly, the cation species in the dissolution medium had also a clear impact on drug release. Drug release profiles obtained in Blank CarbSIF, a new medium simulating pH and average ionic composition of small intestinal fluid, were different from those obtained in all other buffer compositions studied. Results from this study in which the impact of various media parameters on drug release of EC aspirin formulations was systematically screened clearly show that when developing predictive dissolution tests, it is important to simulate the ionic composition of intraluminal fluids as closely as possible. © 2017 Royal Pharmaceutical Society.

  10. Defined drug release from 3D-printed composite tablets consisting of drug-loaded polyvinylalcohol and a water-soluble or water-insoluble polymer filler.

    Science.gov (United States)

    Tagami, Tatsuaki; Nagata, Noriko; Hayashi, Naomi; Ogawa, Emi; Fukushige, Kaori; Sakai, Norihito; Ozeki, Tetsuya

    2018-05-30

    3D-printed tablets are a promising new approach for personalized medicine. In this study, we fabricated composite tablets consisting of two components, a drug and a filler, by using a fused deposition modeling-type 3D printer. Polyvinylalcohol (PVA) polymer containing calcein (a model drug) was used as the drug component and PVA or polylactic acid (PLA) polymer without drug was used as the water-soluble or water-insoluble filler, respectively. Various kinds of drug-PVA/PVA and drug-PVA/PLA composite tablets were designed, and the 3D-printed tablets exhibited good formability. The surface area of the exposed drug component is highly correlated with the initial drug release rate. Composite tablets with an exposed top and a bottom covered with a PLA layer were fabricated. These tablets showed zero-order drug release by maintaining the surface area of the exposed drug component during drug dissolution. In contrast, the drug release profile varied for tablets whose exposed surface area changed. Composite tablets with different drug release lag times were prepared by changing the thickness of the PVA filler coating the drug component. These results which used PVA and PLA filler will provide useful information for preparing the tablets with multi-components and tailor-made tablets with defined drug release profiles using 3D printers. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Drug release, preclinical and clinical pharmacokinetics relationships of alginate pellets prepared by melt technology.

    Science.gov (United States)

    Bose, Anirbandeep; Harjoh, Nurulaini; Pal, Tapan Kumar; Dan, Shubhasis; Wong, Tin Wui

    2016-01-01

    Alginate pellets prepared by the aqueous agglomeration technique experience fast drug dissolution due to the porous pre-formed calcium alginate microstructure. This study investigated in vitro drug release, preclinical and clinical pharmacokinetics relationships of intestinal-specific calcium acetate-alginate pellets against calcium-free and calcium carbonate-alginate pellets. Alginate pellets were prepared by solvent-free melt pelletization instead of aqueous agglomeration technique using chlorpheniramine maleate as model drug. A fast in situ calcium acetate dissolution in pellets resulted in rapid pellet breakup, soluble Ca(2+) crosslinking of alginate fragments and drug dissolution retardation at pH 1.2, which were not found in other pellet types. The preclinical drug absorption rate was lower with calcium acetate loaded than calcium-free alginate pellets. In human subjects, however, the extent and the rate of drug absorption were higher from calcium acetate-loaded pellets than calcium-free alginate pellets. The fine, dispersible and weakly gastric mucoadhesive calcium alginate pellets underwent fast human gastrointestinal transit. They released the drug at a greater rate than calcium-free pellets in the intestine, thereby promoting drug bioavailability. Calcium acetate was required as a disintegrant more than as a crosslinking agent clinically to promote pellet fragmentation, fast gastrointestinal transit and drug release in intestinal medium, and intestinal-specific drug bioavailability.

  12. Release of a Poorly Soluble Drug from Hydrophobically Modified Poly (Acrylic Acid in Simulated Intestinal Fluids.

    Directory of Open Access Journals (Sweden)

    Patrik Knöös

    Full Text Available A large part of new pharmaceutical substances are characterized by a poor solubility and high hydrophobicity, which might lead to a difference in drug adsorption between fasted and fed patients. We have previously evaluated the release of hydrophobic drugs from tablets based on Pemulen TR2 and showed that the release can be manipulated by adding surfactants. Here we further evaluate the possibility to use Pemulen TR2 in controlled release tablet formulations containing a poorly soluble substance, griseofulvin. The release is evaluated in simulated intestinal media that model the fasted state (FaSSIF medium or fed state (FeSSIF. The rheology of polymer gels is studied in separate experiments, in order to gain more information on possible interactions. The release of griseofulvin in tablets without surfactant varied greatly and the slowest release were observed in FeSSIF. Addition of SDS to the tablets eliminated the differences and all tablets showed a slow linear release, which is of obvious relevance for robust drug delivery. Comparing the data from the release studies and the rheology experiment showed that the effects on the release from the different media could to a large extent be rationalised as a consequence of the interactions between the polymer and the surfactants in the media. The study shows that Pemulen TR2 is a candidate for controlled release formulations in which addition of surfactant provides a way to eliminate food effects on the release profile. However, the formulation used needs to be designed to give a faster release rate than the tablets currently investigated.

  13. The effects of particle properties on nanoparticle drug retention and release in dynamic minoxidil foams.

    Science.gov (United States)

    Zhao, Yanjun; Brown, Marc B; Jones, Stuart A

    2010-01-04

    Nanocarriers may act as useful tools to deliver therapeutic agents to the skin. However, balancing the drug-particle interactions; to ensure adequate drug loading, with the drug-vehicle interactions; to allow efficient drug release, presents a significant challenge using traditional semi-solid vehicles. The aim of this study was to determine how the physicochemical properties of nanoparticles influenced minoxidil release pre and post dose application when formulated as a simple aqueous suspension compared to dynamic hydrofluoroalkane (HFA) foams. Minoxidil loaded lipid nanoparticles (LN, 1.4 mg/ml, 50 nm) and polymeric nanoparticles with a lipid core (PN, 0.6 mg/ml, 260 nm) were produced and suspended in water to produce the aqueous suspensions. These aqueous suspensions were emulsified with HFA using pluronic surfactant to generate the foams. Approximately 60% of the minoxidil loaded into the PN and 80% of the minoxidil loaded into the LN was released into the external aqueous phase 24h after production. Drug permeation was superior from the PN, i.e. it was the particle that retained the most drugs, irrespective of the formulation method. Premature drug release, i.e. during storage, resulted in the performance of the topical formulation being dictated by the thermodynamic activity of the solubilised drug not the particle properties.

  14. Characterization of drug-release kinetics in trabecular bone from titania nanotube implants

    Directory of Open Access Journals (Sweden)

    Aw MS

    2012-09-01

    Full Text Available Moom Sinn Aw,1 Kamarul A Khalid,2,3 Karan Gulati,1 Gerald J Atkins,2 Peter Pivonka,4 David M Findlay,2 Dusan Losic11School of Chemical Engineering, 2Discipline of Orthopaedics and Trauma, The University of Adelaide, Adelaide, SA, Australia; 3Department of Orthopaedics, Traumatology and Rehabilitation, Faculty of Medicine, International Islamic University Malaysia, Kuantan, Pahang, Malaysia; 4Engineering Computational Biology Group, School of Computer Science and Software Engineering, The University of Western Australia, Perth, WA, AustraliaPurpose: The aim of this study was to investigate the application of the three-dimensional bone bioreactor for studying drug-release kinetics and distribution of drugs in the ex vivo cancellous bone environment, and to demonstrate the application of nanoengineered titanium (Ti wires generated with titania nanotube (TNT arrays as drug-releasing implants for local drug deliveryMethods: Nanoengineered Ti wires covered with a layer of TNT arrays implanted in bone were used as a drug-releasing implant. Viable bovine trabecular bone was used as the ex vivo bone substrate embedded with the implants and placed in the bone reactor. A hydrophilic fluorescent dye (rhodamine B was used as the model drug, loaded inside the TNT–Ti implants, to monitor drug release and transport in trabecular bone. The distribution of released model drug in the bone was monitored throughout the bone structure, and concentration profiles at different vertical (0–5 mm and horizontal (0–10 mm distances from the implant surface were obtained at a range of release times from 1 hour to 5 days.Results: Scanning electron microscopy confirmed that well-ordered, vertically aligned nanotube arrays were formed on the surface of prepared TNT–Ti wires. Thermogravimetric analysis proved loading of the model drug and fluorescence spectroscopy was used to show drug-release characteristics in-vitro. The drug release from implants inserted into bone ex

  15. Effect of surfactant chain length on drug release kinetics from microemulsion-laden contact lenses.

    Science.gov (United States)

    Maulvi, Furqan A; Desai, Ankita R; Choksi, Harsh H; Patil, Rahul J; Ranch, Ketan M; Vyas, Bhavin A; Shah, Dinesh O

    2017-05-30

    The effect of surfactant chain lengths [sodium caprylate (C 8 ), Tween 20 (C 12 ), Tween 80 (C 18 )] and the molecular weight of block copolymers [Pluronic F68 and Pluronic F 127] were studied to determine the stability of the microemulsion and its effect on release kinetics from cyclosporine-loaded microemulsion-laden hydrogel contact lenses in this work. Globule size and dilution tests (transmittance) suggested that the stability of the microemulsion increases with increase in the carbon chain lengths of surfactants and the molecular weight of pluronics. The optical transmittance of direct drug-laden contact lenses [DL-100] was low due to the precipitation of hydrophobic drugs in the lenses, while in microemulsion-laden lenses, the transmittance was improved when stability of the microemulsion was achieved. The results of in vitro release kinetics revealed that drug release was sustained to a greater extent as the stability of microemulsion was improved as well. This was evident in batch PF127-T80, which showed sustained release for 15days in comparison to batch DL-100, which showed release up to 7days. An in vivo drug release study in rabbit tear fluid showed significant increase in mean residence time (MRT) and area under curve (AUC) with PF-127-T80 lenses (stable microemulsion) in comparison to PF-68-SC lenses (unstable microemulsion) and DL-100 lenses. This study revealed the correlation between the stability of microemulsion and the release kinetics of drugs from contact lenses. Thus, it was inferred that the stable microemulsion batches sustained the release of hydrophobic drugs, such as cyclosporine from contact lenses for an extended period of time without altering critical lens properties. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. How Monte Carlo heuristics aid to identify the physical processes of drug release kinetics.

    Science.gov (United States)

    Lecca, Paola

    2018-01-01

    We implement a Monte Carlo heuristic algorithm to model drug release from a solid dosage form. We show that with Monte Carlo simulations it is possible to identify and explain the causes of the unsatisfactory predictive power of current drug release models. It is well known that the power-law, the exponential models, as well as those derived from or inspired by them accurately reproduce only the first 60% of the release curve of a drug from a dosage form. In this study, by using Monte Carlo simulation approaches, we show that these models fit quite accurately almost the entire release profile when the release kinetics is not governed by the coexistence of different physico-chemical mechanisms. We show that the accuracy of the traditional models are comparable with those of Monte Carlo heuristics when these heuristics approximate and oversimply the phenomenology of drug release. This observation suggests to develop and use novel Monte Carlo simulation heuristics able to describe the complexity of the release kinetics, and consequently to generate data more similar to those observed in real experiments. Implementing Monte Carlo simulation heuristics of the drug release phenomenology may be much straightforward and efficient than hypothesizing and implementing from scratch complex mathematical models of the physical processes involved in drug release. Identifying and understanding through simulation heuristics what processes of this phenomenology reproduce the observed data and then formalize them in mathematics may allow avoiding time-consuming, trial-error based regression procedures. Three bullet points, highlighting the customization of the procedure. •An efficient heuristics based on Monte Carlo methods for simulating drug release from solid dosage form encodes is presented. It specifies the model of the physical process in a simple but accurate way in the formula of the Monte Carlo Micro Step (MCS) time interval.•Given the experimentally observed curve of

  17. Evaluation of hydrophobic materials as matrices for controlled-release drug delivery.

    Science.gov (United States)

    Quadir, Mohiuddin Abdul; Rahman, M Sharifur; Karim, M Ziaul; Akter, Sanjida; Awkat, M Talat Bin; Reza, Md Selim

    2003-07-01

    The present study was undertaken to evaluate the effect of different insoluble and erodable wax-lipid based materials and their content level on the release profile of drug from matrix systems. Matrix tablets of theophylline were prepared using carnauba wax, bees wax, stearic acid, cetyl alcohol, cetostearyl alcohol and glyceryl monostearate as rate-retarding agents by direct compression process. The release of theophylline from these hydrophobic matrices was studied over 8-hours in buffer media of pH 6.8. Statistically significant difference was found among the drug release profile from different matrices. The release kinetics was found to be governed by the type and content of hydrophobic materials in the matrix. At lower level of wax matrices (25%), a potential burst release was observed with all the materials being studied. Bees wax could not exert any sustaining action while an extensive burst release was found with carnauba wax at this hydrophobic load. Increasing the concentration of fat-wax materials significantly decreased the burst effect of drug from the matrix. At higher hydrophobic level (50% of the matrix), the rate and extent of drug release was significantly reduced due to increased tortuosity and reduced porosity of the matrix. Cetostearyl alcohol imparted the strongest retardation of drug release irrespective of fat-wax level. Numerical fits indicate that the Higuchi square root of time model was the most appropriate one for describing the release profile of theophylline from hydrophobic matrices. The release mechanism was also explored and explained with biexponential equation. Application of this model indicates that Fickian or case I kinetics is the predominant mechanism of drug release from these wax-lipid matrices. The mean dissolution time (MDT) was calculated for all the formulations and the highest MDT value was obtained with cetostearyl matrix. The greater sustaining activity of cetostearyl alcohol can be attributed to some level of

  18. Pore geometry of ceramic device: The key factor of drug release kinetics

    Directory of Open Access Journals (Sweden)

    Čolović B.

    2013-01-01

    Full Text Available Release kinetics of tigecycline, a potential antibiotic in treatment of osteomyelitis, from calcium hydroxyapatite (CHA, as one of the most important ceramic materials in bone tissue engineering, was investigated in this study. Tigecycline, in solid state, was mixed with CHA powder and the obtained mixture was compressed into tablets using two different pressures. These tablets were immersed in a phosphate-buffered saline solution and tigecycline release was measured by a UV-VIS spectrophotometer. The total release time was 5 or 28 days, depending on the pressure applied during compression. It was shown that there is a close relationship between pore sizes and drug release rate. The drug release kinetics was interpreted on the base of pore sizes and pore size distribution. [Projekat Ministarstva nauke Republike Srbije, br. 172026

  19. Modulation of drug release from nanocarriers loaded with a poorly water soluble drug (flurbiprofen) comprising natural waxes.

    Science.gov (United States)

    Baviskar, D T; Amritkar, A S; Chaudhari, H S; Jain, D K

    2012-08-01

    In this study, flurbiprofen (FLB) Solid Lipid Nanoparticles (SLN) composed from a mixture of beeswax and carnauba wax, Tween 80 and egg lecithin as emulsifiers have been prepared. FLB was incorporated as model lipophilic drug to assess the influence of matrix composition in the drug release profile. SLN were produced by microemulsion technique. In vitro studies were performed in Phosphate Buffered Saline (PBS). The FLB loaded SLN showed a mean particle size of 75 +/- 4 nm, a polydispersity index approximately 0.2 +/- 0.02 and an entrapment efficiency (EE) of more than 95%. Suspensions were stable, with zeta potential values in the range of -15 to -17 mV. DSC thermograms and UV analysis indicated the stability of nanoparticles with negligible drug leakage. Nanoparticles with higher beeswax content in their core exhibited faster drug release than those containing more carnauba wax.

  20. Poly(dimethylsiloxane) coatings for controlled drug release--polymer modifications.

    Science.gov (United States)

    Schulze Nahrup, J; Gao, Z M; Mark, J E; Sakr, A

    2004-02-11

    Modifications of endhydroxylated poly(dimethylsiloxane) (PDMS) formulations were studied for their ability to be applied onto tablet cores in a spray-coating process and to control drug release in zero-order fashion. Modifications of the crosslinker from the most commonly used tetraethylorthosilicate (TEOS) to the trifunctional 3-(2,3-epoxypropoxy)propyltrimethoxysilane (SIG) and a 1:1 mixture of the two were undertaken. Addition of methylpolysiloxane-copolymers were studied. Lactose, microcrystalline cellulose (MCC) and polyethylene glycol 8000 (PEG) were the channeling agents applied. The effects on dispersion properties were characterized by particle size distribution and viscosity. Mechanical properties of resulting free films were studied to determine applicability in a pan-coating process. Release of hydrochlorothiazide (marker drug) was studied from tablets coated in a lab-size conventional coating pan. All dispersions were found suitable for a spray-coating process. Preparation of free films showed that copolymer addition was not possible due to great decline in mechanical properties. Tablets coated with formulations containing PEG were most suitable to control drug release, at only 5% coating weight. Constant release rates could be achieved for formulations with up to 25% PEG; higher amounts resulted in a non-linear release pattern. Upon adding 50% PEG, a drug release of 63% over 24 h could be achieved.

  1. Effect of a new drug releasing system on microencapsulated islet transplantation

    Science.gov (United States)

    Lu, Binjie; Gao, Qingkun; Liu, Rui; Ren, Ming; Wu, Yan; Jiang, Zaixing; Zhou, Yi

    2015-01-01

    Objective: This study aimed to develop a novel release system for grafted islets. Materials and methods: A graphene oxide-FTY720 release system was constructed to test the drug loading and releasing capacity. The recipient rats were divided into four groups as following: Experiment group A (EG A) and B (EG B); Control group A (CG A) and B (CG B). In each group, (2000±100) IEQ microencapsulated islets were implanted into the abdominal cavity of the recipients with oral FTY720, local graphene oxide-FTY720 injection, without immunosuppressants, and with graphene oxide-saturated solution respectively. We detected the immunological data, the blood glucose level, and pericapsular overgrowth to show the transplantation effect. Results: 31% of adsorptive FTY720 was released within 6 h, and 82% of FTY720 was released within 48 h. From day 5 to 8, the amount of PBL in EG B was significantly less than those in EG A (PGraphene oxide-FTY720 complex showed a drug releasing effect. Local application of graphene-FTY720 releasing system could decrease the amount of peripheral blood lymphocytes (PBL) and the percentage of CD3 and CD8 T lymphocytes in blood for longer time than oral drug application. This releasing system could achieve a better blood glucose control. PMID:26722425

  2. Optimization of primaquine diphosphate tablet formulation for controlled drug release using the mixture experimental design.

    Science.gov (United States)

    Duque, Marcelo Dutra; Kreidel, Rogério Nepomuceno; Taqueda, Maria Elena Santos; Baby, André Rolim; Kaneko, Telma Mary; Velasco, Maria Valéria Robles; Consiglieri, Vladi Olga

    2013-01-01

    A tablet formulation based on hydrophilic matrix with a controlled drug release was developed, and the effect of polymer concentrations on the release of primaquine diphosphate was evaluated. To achieve this purpose, a 20-run, four-factor with multiple constraints on the proportions of the components was employed to obtain tablet compositions. Drug release was determined by an in vitro dissolution study in phosphate buffer solution at pH 6.8. The polynomial fitted functions described the behavior of the mixture on simplex coordinate systems to study the effects of each factor (polymer) on tablet characteristics. Based on the response surface methodology, a tablet composition was optimized with the purpose of obtaining a primaquine diphosphate release closer to a zero order kinetic. This formulation released 85.22% of the drug for 8 h and its kinetic was studied regarding to Korsmeyer-Peppas model, (Adj-R(2) = 0.99295) which has confirmed that both diffusion and erosion were related to the mechanism of the drug release. The data from the optimized formulation were very close to the predictions from statistical analysis, demonstrating that mixture experimental design could be used to optimize primaquine diphosphate dissolution from hidroxypropylmethyl cellulose and polyethylene glycol matrix tablets.

  3. Development of novel diclofenac potassium controlled release tablets by wet granulation technique and the effect of co-excipients on in vitro drug release rates.

    Science.gov (United States)

    Shah, Shefaatullah; Khan, Gul Majid; Jan, Syed Umer; Shah, Kifayatullah; Hussain, Abid; Khan, Haroon; Khan, Haroon; Khan, Haroon; Khan, Kamran Ahmad

    2012-01-01

    The aim of the present study was the formulation and evaluation of controlled release polymeric tablets of Diclofenac Potassium by wet granulation method for the release rate, release pattern and the mechanism involved in drug release. Formulations having three grades of polymer Ethocel (7P; 7FP, 10P, 10FP, 100P, 100FP) in several drugs to polymer ratios (10:3 and 10:1) were compressed into tablets using wet granulation method. Co-excipients were added to some selected formulations to investigate their enhancement effect on in vitro drug release patterns. In vitro drug release studies were performed using USP Method-1 (Rotating Basket method) and Phosphate buffer (pH 7.4) was used as a dissolution medium. The similarities and dissimilarities of release profiles of test formulations with reference standard were checked using f2 similarity factor and f1 dissimilarity factor. Mathematical/Kinetic models were employed to determine the release mechanism and drug release kinetics.

  4. Influence of Hydrothermal Treatment on Physicochemical Properties and Drug Release of Anti-Inflammatory Drugs of Intercalated Layered Double Hydroxide Nanoparticles

    Directory of Open Access Journals (Sweden)

    Zi Gu

    2014-05-01

    Full Text Available The synthesis method of layered double hydroxides (LDHs determines nanoparticles’ performance in biomedical applications. In this study, hydrothermal treatment as an important synthesis technique has been examined for its influence on the physicochemical properties and the drug release rate from drug-containing LDHs. We synthesised MgAl–LDHs intercalated with non-steroidal anti-inflammatory drugs (i.e., naproxen, diclofenac and ibuprofen using a co-precipitation method with or without hydrothermal treatment (150 °C, 4 h. After being hydrothermally treated, LDH–drug crystallites increased in particle size and crystallinity, but did not change in the interlayer anion orientation, gallery height and chemical composition. The drug release patterns of all studied LDH–drug hybrids were biphasic and sustained. LDHs loaded with diclofenac had a quicker drug release rate compared with those with naproxen and ibuprofen, and the drug release from the hydrothermally-treated LDH–drug was slower than the freshly precipitated LDH–drug. These results suggest that the drug release of LDH–drugs is influenced by the crystallite size of LDHs, which can be controlled by hydrothermal treatment, as well as by the drug molecular physicochemical properties.

  5. Evaluation of chitosan–anionic polymers based tablets for extended-release of highly water-soluble drugs

    Directory of Open Access Journals (Sweden)

    Yang Shao

    2015-02-01

    Full Text Available The objective of this study is to develop chitosan–anionic polymers based extended-release tablets and test the feasibility of using this system for the sustained release of highly water-soluble drugs with high drug loading. Here, the combination of sodium valproate (VPS and valproic acid (VPA were chosen as the model drugs. Anionic polymers studied include xanthan gum (XG, carrageenan (CG, sodium carboxymethyl cellulose (CMC-Na and sodium alginate (SA. The tablets were prepared by wet granulation method. In vitro drug release was carried out under simulated gastrointestinal condition. Drug release mechanism was studied. Compared with single polymers, chitosan–anionic polymers based system caused a further slowdown of drug release rate. Among them, CS–xanthan gum matrix system exhibited the best extended-release behavior and could extend drug release for up to 24 h. Differential scanning calorimetry (DSC and Fourier transform infrared spectroscopy (FTIR studies demonstrated that polyelectrolyte complexes (PECs were formed on the tablet surface, which played an important role on retarding erosion and swelling of the matrix in the later stage. In conclusion, this study demonstrated that it is possible to develop highly water-soluble drugs loaded extended-release tablets using chitosan–anionic polymers based system.

  6. Role of various natural, synthetic and semi-synthetic polymers on drug release kinetics of losartan potassium oral controlled release tablets.

    Science.gov (United States)

    Jayasree, J; Sivaneswari, S; Hemalatha, G; Preethi, N; Mounika, B; Murthy, S Vasudeva

    2014-10-01

    The objective of the present work was to formulate and to characterize controlled release matrix tablets of losartan potassium in order to improve bioavailability and to minimize the frequency of administration and increase the patient compliance. Losartan potassium controlled release matrix tablets were prepared by direct compression technique by the use of different natural, synthetic and semisynthetic polymers such as gum copal, gum acacia, hydroxypropyl methyl cellulose K100 (HPMC K100), eudragit RL 100 and carboxy methyl ethyl cellulose (CMEC) individually and also in combination. Studies were carried out to study the influence of type of polymer on drug release rate. All the formulations were subjected to physiochemical characterization such as weight variation, hardness, thickness, friability, drug content, and swelling index. In vitro dissolution studies were carried out simulated gastric fluid (pH 1.2) for first 2 h and followed by simulated intestinal fluid (pH 6.8) up to 24 h, and obtained dissolution data were fitted to in vitro release kinetic equations in order to know the order of kinetics and mechanism of drug release. Results of physiochemical characterization of losartan potassium matrix tablets were within acceptable limits. Formulation containing HPMC K100 and CMEC achieved the desired drug release profile up to 24 h followed zero order kinetics, release pattern dominated by Korsmeyer - Peppas model and mechanism of drug release by nonfickian diffusion. The good correlation obtained from Hixson-Crowell model indicates that changes in surface area of the tablet also influences the drug release. Based on the results, losartan potassium controlled release matrix tablets prepared by employing HPMC K100 and CMEC can attain the desired drug release up to 24 h, which results in maintaining steady state concentration and improving bioavailability.

  7. Polymeric nanoparticles - Influence of the glass transition temperature on drug release.

    Science.gov (United States)

    Lappe, Svenja; Mulac, Dennis; Langer, Klaus

    2017-01-30

    The physico-chemical characterisation of nanoparticles is often lacking the determination of the glass transition temperature, a well-known parameter for the pure polymer carrier. In the present study the influence of water on the glass transition temperature of poly (DL-lactic-co-glycolic acid) nanoparticles was assessed. In addition, flurbiprofen and mTHPP as model drugs were incorporated in poly (DL-lactic-co-glycolic acid), poly (DL-lactic acid), and poly (L-lactic acid) nanoparticles. For flurbiprofen-loaded nanoparticles a decrease in the glass transition temperature was observed while mTHPP exerted no influence on this parameter. Based on this observation, the release behaviour of the drug-loaded nanoparticles was investigated at different temperatures. For all preparations an initial burst release was measured that could be attributed to the drug adsorbed to the large nanoparticle surface. At temperatures above the glass transition temperature an instant drug release of the nanoparticles was observed, while at lower temperatures less drug was released. It could be shown that the glass transition temperature of drug loaded nanoparticles in suspension more than the corresponding temperature of the pure polymer is the pivotal parameter when characterising a nanostructured drug delivery system. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Carbohydrate polymer based pH-sensitive IPN microgels: Synthesis, characterization and drug release characteristics

    International Nuclear Information System (INIS)

    Eswaramma, S.; Reddy, N. Sivagangi; Rao, K.S.V. Krishna

    2017-01-01

    pH-sensitive interpenetrating polymer network (IPN) microgels of chitosan (CS) and guargum-g-poly((2-dimethylamino)ethylmethacrylate) (GG-g-PDMAEMA) were developed by emulsion crosslinking method using glutaraldehyde as a crosslinker. In this regard, primarily guargum (GG) is grafted with (2-dimethylamino)ethylmethacrylate (DMAEMA) followed by blended with CS to prepare various microgel formulations. These microgels were treated as responsive drug carriers for an anticancer agent, 5-fluorouracil (5-FU). The maximum % encapsulation efficiency was found to be 81. Fourier transform infrared analysis was used to investigate the formation of graft copolymer (GG-g-PDMAEMA), chemical structure of microgels as well as the chemical interactions of drug molecules with the polymer matrix. The surface morphological studies and average particle size were examined by scanning electron microscopy. The average size of microgels is 130 ± 20 μm. Thermal behavior and molecular distribution of 5-FU within the polymer matrix were confirmed from thermogravimetric analysis and X-ray diffraction experiments. The pH-sensitive swelling behavior of IPN microgels was investigated in different pH solutions. To study the release profile of 5-FU, in vitro release profiles were performed in both pH 1.2 and 7.4. The release kinetics showed pH- dependent drug release and IPN microgels exhibited an excellent controlled release pattern for 5-FU over a period of more than 24 h. The release mechanism was analyzed by evaluating the release data using different empirical equations. - Highlights: • poly((2-dimethylamino)ethylmethacrylate) was grafted on to guargum backbone. • pH-responsive IPN microgels were developed from chitosan and graft copolymer. • Microgels were treated as responsive drug carriers for an anticancer agent, 5-fluorouracil. • Swelling and drug release studies were greatly dependent on pH.

  9. Carbohydrate polymer based pH-sensitive IPN microgels: Synthesis, characterization and drug release characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Eswaramma, S. [Polymer Biomaterial Design and Synthesis Laboratory, Department of Chemistry, Yogi Vemana University, Kadapa, Andhra Pradesh, 516003 (India); Reddy, N. Sivagangi [Advanced Nanomaterials Lab, Department of Polymer Science and Engineering, Pusan National University, Busan, 46241 (Korea, Republic of); Rao, K.S.V. Krishna, E-mail: ksvkr@yogivemanauniversity.ac.in [Polymer Biomaterial Design and Synthesis Laboratory, Department of Chemistry, Yogi Vemana University, Kadapa, Andhra Pradesh, 516003 (India)

    2017-07-01

    pH-sensitive interpenetrating polymer network (IPN) microgels of chitosan (CS) and guargum-g-poly((2-dimethylamino)ethylmethacrylate) (GG-g-PDMAEMA) were developed by emulsion crosslinking method using glutaraldehyde as a crosslinker. In this regard, primarily guargum (GG) is grafted with (2-dimethylamino)ethylmethacrylate (DMAEMA) followed by blended with CS to prepare various microgel formulations. These microgels were treated as responsive drug carriers for an anticancer agent, 5-fluorouracil (5-FU). The maximum % encapsulation efficiency was found to be 81. Fourier transform infrared analysis was used to investigate the formation of graft copolymer (GG-g-PDMAEMA), chemical structure of microgels as well as the chemical interactions of drug molecules with the polymer matrix. The surface morphological studies and average particle size were examined by scanning electron microscopy. The average size of microgels is 130 ± 20 μm. Thermal behavior and molecular distribution of 5-FU within the polymer matrix were confirmed from thermogravimetric analysis and X-ray diffraction experiments. The pH-sensitive swelling behavior of IPN microgels was investigated in different pH solutions. To study the release profile of 5-FU, in vitro release profiles were performed in both pH 1.2 and 7.4. The release kinetics showed pH- dependent drug release and IPN microgels exhibited an excellent controlled release pattern for 5-FU over a period of more than 24 h. The release mechanism was analyzed by evaluating the release data using different empirical equations. - Highlights: • poly((2-dimethylamino)ethylmethacrylate) was grafted on to guargum backbone. • pH-responsive IPN microgels were developed from chitosan and graft copolymer. • Microgels were treated as responsive drug carriers for an anticancer agent, 5-fluorouracil. • Swelling and drug release studies were greatly dependent on pH.

  10. Comparative study of some mechanical and release properties of ...

    African Journals Online (AJOL)

    The mechanical and release properties of paracetamol tablets formulated with cashew gum (CAG), povidone (PVP) and gelatin (GEL) as binders were studied and compared. The parameters studied were tensile strength (TS), brittle fracture index (BFI), friability (F), disintegration time (DT) and percentage drug released ...

  11. Sustained Release and Cytotoxicity Evaluation of Carbon Nanotube-Mediated Drug Delivery System for Betulinic Acid

    Directory of Open Access Journals (Sweden)

    Julia M. Tan

    2014-01-01

    Full Text Available Carbon nanotubes (CNTs have been widely utilized as a novel drug carrier with promising future applications in biomedical therapies due to their distinct characteristics. In the present work, carboxylic acid-functionalized single-walled carbon nanotubes (f-SWCNTs were used as the starting material to react with anticancer drug, BA to produce f-SWCNTs-BA conjugate via π-π stacking interaction. The conjugate was extensively characterized for drug loading capacity, physicochemical properties, surface morphology, drug releasing characteristics, and cytotoxicity evaluation. The results indicated that the drug loading capacity was determined to be around 20 wt% and this value has been verified by thermogravimetric analysis. The binding of BA onto the surface of f-SWCNTs was confirmed by FTIR and Raman spectroscopies. Powder XRD analysis showed that the structure of the conjugate was unaffected by the loading of BA. The developed conjugate was found to release the drug in a controlled manner with a prolonged release property. According to the preliminary in vitro cytotoxicity studies, the conjugate was not toxic in a standard fibroblast cell line, and anticancer activity was significantly higher in A549 than HepG2 cell line. This study suggests that f-SWCNTs could be developed as an efficient drug carrier to conjugate drugs for pharmaceutical applications in cancer chemotherapies.

  12. Modification of concomitant drug release from oil vehicles using drug-prodrug combinations to achieve sustained balanced analgesia after joint installation

    DEFF Research Database (Denmark)

    Thing, Mette; Jensen, Sabrine Smedegaard; Larsen, Claus Selch

    2012-01-01

    Intra-articular injection of two drugs in a sustained drug delivery system combining the use of lipophilic solution with the prodrug approach may provide efficient and prolonged postoperative pain treatment after arthroscopic procedures. In the present study, the concomitant release of N...... using buffer. In both release models, the use of ropivacaine-prodrug combination provided concomitant release from the oil into synovial fluid with ropivacaine being released faster than naproxen. The use of lipophilic prodrugs that are converted fast to the parent drug in synovial fluid seems...

  13. TiO2 nanocomposite for the controlled release of drugs against pathogens causing wound infections

    Science.gov (United States)

    Devanand Venkatasubbu, G.; Nagamuthu, S.; Anusuya, T.; Kumar, J.; Chelliah, Ramachandran; Rani Ramakrishnan, Sudha; Antony, Usha; Khan, Imran; Oh, Deog-Hwan

    2018-02-01

    Chitosan titanium dioxide nanocomposite has been used for wound healing. Titanium dioxide (TiO2) nanoparticles are synthesised and made in to nanocomposite along with chitosan. Curcumin nanoparticles are synthesised. Three different drugs with antimicrobial activity are incorporated into the chitosan/TiO2nanocomposite. Ciprofloxacin, amoxicillin and curcumin nanoparticles are incorporated within the chitosan/TiO2 nanoparticles. The nanoparticles and nanocomposite are characterized with XRD, FTIR, TEM and SEM. Drug loading was found to be around 45% for all the three drug molecules. The drug release profile shows a controlled release of drug molecules from the nanocomposite. Antibacterial studies shows a good inhibition of bacterial species by the nanocomposites.

  14. In Vitro Sustained Release Study of Gallic Acid Coated with Magnetite-PEG and Magnetite-PVA for Drug Delivery System

    Science.gov (United States)

    Kura, Aminu Umar; Hussein-Al-Ali, Samer Hasan; Bin Hussein, Mohd Zobir; Fakurazi, Sharida; Shaari, Abdul Halim; Ahmad, Zalinah

    2014-01-01

    The efficacy of two nanocarriers polyethylene glycol and polyvinyl alcohol magnetic nanoparticles coated with gallic acid (GA) was accomplished via X-ray diffraction, infrared spectroscopy, magnetic measurements, thermal analysis, and TEM. X-ray diffraction and TEM results showed that Fe3O4 nanoparticles were pure iron oxide having spherical shape with the average diameter of 9 nm, compared with 31 nm and 35 nm after coating with polyethylene glycol-GA (FPEGG) and polyvinyl alcohol-GA (FPVAG), respectively. Thermogravimetric analyses proved that after coating the thermal stability was markedly enhanced. Magnetic measurements and Fourier transform infrared (FTIR) revealed that superparamagnetic iron oxide nanoparticles could be successfully coated with two polymers (PEG and PVA) and gallic acid as an active drug. Release behavior of gallic acid from two nanocomposites showed that FPEGG and FPVAG nanocomposites were found to be sustained and governed by pseudo-second-order kinetics. Anticancer activity of the two nanocomposites shows that the FPEGG demonstrated higher anticancer effect on the breast cancer cell lines in almost all concentrations tested compared to FPVAG. PMID:24737969

  15. In Vitro Sustained Release Study of Gallic Acid Coated with Magnetite-PEG and Magnetite-PVA for Drug Delivery System

    Directory of Open Access Journals (Sweden)

    Dena Dorniani

    2014-01-01

    Full Text Available The efficacy of two nanocarriers polyethylene glycol and polyvinyl alcohol magnetic nanoparticles coated with gallic acid (GA was accomplished via X-ray diffraction, infrared spectroscopy, magnetic measurements, thermal analysis, and TEM. X-ray diffraction and TEM results showed that Fe3O4 nanoparticles were pure iron oxide having spherical shape with the average diameter of 9 nm, compared with 31 nm and 35 nm after coating with polyethylene glycol-GA (FPEGG and polyvinyl alcohol-GA (FPVAG, respectively. Thermogravimetric analyses proved that after coating the thermal stability was markedly enhanced. Magnetic measurements and Fourier transform infrared (FTIR revealed that superparamagnetic iron oxide nanoparticles could be successfully coated with two polymers (PEG and PVA and gallic acid as an active drug. Release behavior of gallic acid from two nanocomposites showed that FPEGG and FPVAG nanocomposites were found to be sustained and governed by pseudo-second-order kinetics. Anticancer activity of the two nanocomposites shows that the FPEGG demonstrated higher anticancer effect on the breast cancer cell lines in almost all concentrations tested compared to FPVAG.

  16. Physicochemical properties and drug release behavior of biguanidino and O-carboxymethyl chitosan microcapsules.

    Science.gov (United States)

    Huo, Weiqiang; Zhang, Weixin; Wang, Wei; Zhou, Xiaohua

    2014-09-01

    Two types of microcapsules (MCs) were prepared by the emulsion cross-linking method, where biguanidino chitosan (BGCS)and O-carboxymethyl chitosan (O-CMCS) served as the wall materials, and the antibacterial agent 2,4-diamino-6-(2-pyridyl)-1,3,5-triazine (PyTNH) served as a model water-soluble drug. The physicochemical performance of the MCs and their drug release behavior were investigated by Fourier transform infrared spectroscopy, thermogravimetric analysis/derivative thermogravimetric analysis, scanning electron microscopy, and swelling and in vitro drug release studies of the two MCs with unmodified chitosan-MCs (CS-MCs) used as the control. The results indicated that the degree of cross-linking, encapsulation efficiency, and thermal stability of the shell wall of the BGCS-microcapsules (BGCS-MCs) were much higher than those of the control and the O-CMCS-microcapsules (CMCS-MCs), owing to the reduction of steric hindrance and development of the conjugation effect in the cross-linking process. Studies on the swelling and in vitro drug-release behavior revealed a sustained release effect of the BGCS-MCs. Moreover, the CMCS-MCs were found to exhibit a pH-dependent drug release behavior, which can be attributed to the successive formation of H-bonds and repulsive forces with the change in the pH of the medium. Based on these results, the swelling-release models and the drug release kinetics of BGCS-MCs and CMCS-MCs are proposed. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Natural Non-Mulberry Silk Nanoparticles for Potential-Controlled Drug Release

    Science.gov (United States)

    Wang, Juan; Yin, Zhuping; Xue, Xiang; Kundu, Subhas C.; Mo, Xiumei; Lu, Shenzhou

    2016-01-01

    Natural silk protein nanoparticles are a promising biomaterial for drug delivery due to their pleiotropic properties, including biocompatibility, high bioavailability, and biodegradability. Chinese oak tasar Antheraea pernyi silk fibroin (ApF) nanoparticles are easily obtained using cations as reagents under mild conditions. The mild conditions are potentially advantageous for the encapsulation of sensitive drugs and therapeutic molecules. In the present study, silk fibroin protein nanoparticles are loaded with differently-charged small-molecule drugs, such as doxorubicin hydrochloride, ibuprofen, and ibuprofen-Na, by simple absorption based on electrostatic interactions. The structure, morphology and biocompatibility of the silk nanoparticles in vitro are investigated. In vitro release of the drugs from the nanoparticles depends on charge-charge interactions between the drugs and the nanoparticles. The release behavior of the compounds from the nanoparticles demonstrates that positively-charged molecules are released in a more prolonged or sustained manner. Cell viability studies with L929 demonstrated that the ApF nanoparticles significantly promoted cell growth. The results suggest that Chinese oak tasar Antheraea pernyi silk fibroin nanoparticles can be used as an alternative matrix for drug carrying and controlled release in diverse biomedical applications. PMID:27916946

  18. Phytantriol based liquid crystal provide sustained release of anticancer drug as a novel embolic agent.

    Science.gov (United States)

    Qin, Lingzhen; Mei, Liling; Shan, Ziyun; Huang, Ying; Pan, Xin; Li, Ge; Gu, Yukun; Wu, Chuanbin

    2016-01-01

    Phytantriol has received increasing amount of attention in drug delivery system, however, the ability of the phytantriol based liquid crystal as a novel embolic agent to provide a sustained release delivery system is yet to be comprehensively demonstrated. The purpose of this study was to prepare a phytantriol-based cubic phase precursor solution loaded with anticancer drug hydroxycamptothecine (HCPT) and evaluate its embolization properties, in vitro drug release and cytotoxicity. Phase behavior of the phytantriol-solvent-water system was investigated by visual inspection and polarized light microscopy, and no phase transition was observed in the presence of HCPT within the studied dose range. Water uptake by the phytantriol matrices was determined gravimetrically, suggesting that the swelling complied with the second order kinetics. In vitro evaluation of embolic efficacy indicated that the isotropic solution displayed a satisfactory embolization effect. In vitro drug release results showed a sustained-release up to 30 days and the release behavior was affected by the initial composition and drug loading. Moreover, the in vitro cytotoxicity and anticancer activity were evaluated by MTT assay. No appreciable mortality was observed for NIH 3T3 cells after 48 h exposure to blank formulations, and the anticancer activity of HCPT-loaded formulations to HepG2 and SMMC7721 cells was strongly dependent on the drug loading and treatment time. Taken together, these results indicate that phytantriol-based cubic phase embolic gelling solution is a promising potential carrier for HCPT delivery to achieve a sustained drug release by vascular embolization, and this technology may be potential for clinical applications.

  19. Effect of temperature and ph on the drug release rate from a polymer conjugate system

    International Nuclear Information System (INIS)

    Kenawy, E.; Abdel-Hay, F.I.; El-Newehy, M.H.; Ottenbrite, R.M.

    2005-01-01

    Hydroximide and A-methylhydroxamic acid of poly(ethylene-altmaleic anhydride) (average MW 100-500 k) were used as a carrier for a new drug delivery system. The synthesis of the hydroximide and N methylhydroxamic acid of poly(ethylene-alt-maleic anhydride) were carried out by chemical modification of poly(ethylene-alt-maleic anhydride) with hydroxylamine and N-methyl hydroxylamine, respectively, in N,N- dimethylformamide at room temperature to yield water soluble copolymer. Ketoprofen was reacted with hydroximide and N-methylhydroxamic acid derivatives of poly(ethylene-alt-maleic anhydride) using dicyclohexylcarbodiimide as condensation agent at -5 degree C to yield water insoluble ketoprofen conjugates. All products were characterized by elemental analysis, FTIR and 1HNMR spectra. The in-vitro ketoprofen release was carried out by UV spectrophotometer at max =260 nm. The results demonstrated the effectiveness of hydroximide and N-methylhydroxamic acid of polyethylene-alt-maleic anhydride) as a drug delivery system. The release rates were studied at various ph and temperatures. The copolymer-drug adducts released the drug very slowly at the low ph found in the stomach thus protecting the drug from the action of high concentrations of digestive acids. These results showed the usefulness of hydroxamic acid polymer-drug conjugates as a new drug delivery system for drugs to be targeted to sites in the GI system

  20. Drug release control in delivery system for biodegradable polymer drugs by γ-radiation

    International Nuclear Information System (INIS)

    Yoshioka, Sumie; Azo, Yukio; Kojima, Shigeo

    1997-01-01

    Characterizations of the drug release from microsphere and hydrogel preparation made from biodegradable polymers were investigated aiming at development of a drug delivery system which allows an optimum drug delivery and the identification of the factors which control its delivery. Poly-lactic acid microspheres containing 10% of progesterone were produced from poly DL-lactic acid and exposed to γ-ray at 5-1000 kGy. And its glass transition temperature (Tg) was determined by differential scanning calorimetry. The temperature was gradually lowered with an increase in the dose of radiation. Tg of the microsphere exposed at 1000 kGy was lower by 10degC compared with the untreated one, showing that Tg control is possible without changing the size distribution of microsphere. Then, the amount of progesterone released from microsphere was determined. The release rate of the drug linearly increased with a square root of radiation time. These results indicate that the control of drug release rate is possible through controling the microsphere's Tg by γ-ray radiation. (M.N.)

  1. Immobilization and controlled release of drug using plasma polymerized thin film

    Energy Technology Data Exchange (ETDEWEB)

    Myung, Sung-Woon [Department of Dental Materials, School of Dentistry, MRC Center, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju (Korea, Republic of); Jung, Sang-Chul [Department of Environmental Engineering, Sunchon National University, Sunchon 540-742 (Korea, Republic of); Kim, Byung-Hoon, E-mail: kim5055@chosun.ac.kr [Department of Dental Materials, School of Dentistry, MRC Center, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju (Korea, Republic of)

    2015-06-01

    In this study, plasma polymerization of acrylic acid was employed to immobilize drug and control its release. Doxorubicin (DOX) was immobilized covalently on the glass surface deposited with plasma polymerized acrylic acid (PPAAc) thin film containing the carboxylic group. At first, the PPAAc thin film was coated on a glass surface at a pressure of 1.33 Pa and radio frequency (RF) discharge power of 20 W for 10 min. DOX was immobilized on the PPAAc deposition in a two environment of phosphate buffer saline (PBS) and dimethyl sulfoxide (DMSO) solutions. The DOX immobilized surface was characterized by scanning electron microscope, atomic force microscope and attenuated total reflection Fourier transform infrared spectroscopy. The DOX molecules were more immobilized in PBS than DMSO solution. The different immobilization and release profiles of DOX result from the solubility of hydrophobic DOX in aqueous and organic solutions. Second, in order to control the release of the drug, PPAAc thin film was covered over DOX dispersed layer. Different thicknesses and cross-linked PPAAc thin films by adjusting deposition time and RF discharge power were covered on the DOX layer dispersed. PPAAc thin film coated DOX layer reduced the release rate of DOX. The thickness control of plasma deposition allows controlling the release rate of drug. - Highlights: • Doxorubicin was immobilized on the surface of plasma polymerized acrylic acid thin film. • Release profile of doxorubicin was affected by aqueous and organic solutions. • Plasma polymerized acrylic acid thin film can be used to achieve controlled release.

  2. Immobilization and controlled release of drug using plasma polymerized thin film

    International Nuclear Information System (INIS)

    Myung, Sung-Woon; Jung, Sang-Chul; Kim, Byung-Hoon

    2015-01-01

    In this study, plasma polymerization of acrylic acid was employed to immobilize drug and control its release. Doxorubicin (DOX) was immobilized covalently on the glass surface deposited with plasma polymerized acrylic acid (PPAAc) thin film containing the carboxylic group. At first, the PPAAc thin film was coated on a glass surface at a pressure of 1.33 Pa and radio frequency (RF) discharge power of 20 W for 10 min. DOX was immobilized on the PPAAc deposition in a two environment of phosphate buffer saline (PBS) and dimethyl sulfoxide (DMSO) solutions. The DOX immobilized surface was characterized by scanning electron microscope, atomic force microscope and attenuated total reflection Fourier transform infrared spectroscopy. The DOX molecules were more immobilized in PBS than DMSO solution. The different immobilization and release profiles of DOX result from the solubility of hydrophobic DOX in aqueous and organic solutions. Second, in order to control the release of the drug, PPAAc thin film was covered over DOX dispersed layer. Different thicknesses and cross-linked PPAAc thin films by adjusting deposition time and RF discharge power were covered on the DOX layer dispersed. PPAAc thin film coated DOX layer reduced the release rate of DOX. The thickness control of plasma deposition allows controlling the release rate of drug. - Highlights: • Doxorubicin was immobilized on the surface of plasma polymerized acrylic acid thin film. • Release profile of doxorubicin was affected by aqueous and organic solutions. • Plasma polymerized acrylic acid thin film can be used to achieve controlled release

  3. Layered double hydroxides as supports for intercalation and sustained release of antihypertensive drugs

    International Nuclear Information System (INIS)

    Xia Shengjie; Ni Zheming; Xu Qian; Hu Baoxiang; Hu Jun

    2008-01-01

    Zn/Al layered double hydroxides (LDHs) were intercalated with the anionic antihypertensive drugs Enalpril, Lisinopril, Captopril and Ramipril by using coprecipitation or ion-exchange technique. TG-MS analyses suggested that the thermal stability of Ena - , Lis - (arranged with monolayer, resulted from X-ray diffraction (XRD) and Fourier transform infrared spectra (FT-IR) analysis was enhanced much more than Cap - and Ram - (arranged with bilayer). The release studies show that the release rate of all samples markedly decreased in both pH 4.25 and 7.45. However, the release time of Ena - , Lis - were much longer compared with Cap - , Ram - in both pH 4.25 and 7.45, it is possible that the intercalated guests, arranged with monolayer in the interlayer, show lesser repulsive force and strong affinity with the LDH layers. And the release data followed both the Higuchi-square-root law and the first-order equation well. Based on the analysis of batch release, intercalated structural models as well as the TG-DTA results, we conclude that for drug-LDH, stronger the affinity between intercalated anions and the layers is, better the thermal property and the stability to the acid attack of drug-LDH, and the intercalated anions are easier apt to monolayer arrangement within the interlayer, were presented. - Graphical abstract: A series of antihypertensive drugs including Enalpril, Lisinopril, Captopril and Ramipril were intercalated into Zn/Al-NO 3 -LDHs successfully by coprecipitation or ion-exchange technique. We focus on the structure, thermal property and low/controlled release property of as-synthesized drug-LDH composite intended for the possibility of applying these LDH-antihypertensive nanohybrids in drug delivery and controlled release systems

  4. HPMA Copolymer-Drug Conjugates with Controlled Tumor-Specific Drug Release.

    Science.gov (United States)

    Chytil, Petr; Koziolová, Eva; Etrych, Tomáš; Ulbrich, Karel

    2018-01-01

    Over the past few decades, numerous polymer drug carrier systems are designed and synthesized, and their properties are evaluated. Many of these systems are based on water-soluble polymer carriers of low-molecular-weight drugs and compounds, e.g., cytostatic agents, anti-inflammatory drugs, or multidrug resistance inhibitors, all covalently bound to a carrier by a biodegradable spacer that enables controlled release of the active molecule to achieve the desired pharmacological effect. Among others, the synthetic polymer carriers based on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers are some of the most promising carriers for this purpose. This review focuses on advances in the development of HPMA copolymer carriers and their conjugates with anticancer drugs, with triggered drug activation in tumor tissue and especially in tumor cells. Specifically, this review highlights the improvements in polymer drug carrier design with respect to the structure of a spacer to influence controlled drug release and activation, and its impact on the drug pharmacokinetics, enhanced tumor uptake, cellular trafficking, and in vivo antitumor activity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Multi-purposable filaments of HPMC for 3D printing of medications with tailored drug release and timed-absorption.

    Science.gov (United States)

    Kadry, Hossam; Al-Hilal, Taslim A; Keshavarz, Ali; Alam, Farzana; Xu, Changxue; Joy, Abraham; Ahsan, Fakhrul

    2018-04-20

    Three-dimensional printing (3DP), though developed for nonmedical applications and once regarded as futuristic only, has recently been deployed for the fabrication of pharmaceutical products. However, the existing feeding materials (inks and filaments) that are used for printing drug products have various shortcomings, including the lack of biocompatibility, inadequate extrudability and printability, poor drug loading, and instability. Here, we have sought to develop a filament using a single pharmaceutical polymer, with no additives, which can be multi-purposed and manipulated by computational design for the preparation of tablets with desired release and absorption patterns. As such, we have used hydroxypropyl-methylcellulose (HPMC) and diltiazem, a model drug, to prepare both drug-free and drug-impregnated filaments, and investigated their thermal and crystalline properties, studied the cytotoxicity of the filaments, designed and printed tablets with various infill densities and patterns. By alternating the drug-free and drug-impregnated filaments, we fabricated various types of tablets, studied the drug release profiles, and assessed oral absorption in rats. Both diltiazem and HPMC were stable at extrusion and printing temperatures, and the drug loading was 10% (w/w). The infill density, as well as infill patterns, influenced the drug release profile, and thus, when the infill density was increased to 100%, the percentage of drug released dramatically declined. Tablets with alternating drug-free and drug-loaded layers showed delayed and intermittent drug release, depending on when the drug-loaded layers encountered the dissolution media. Importantly, the oral absorption patterns accurately reproduced the drug release profiles and showed immediate, extended, delayed and episodic absorption of the drug from the rat gastrointestinal tract (GIT). Overall, we have demonstrated here that filaments for 3D printers can be prepared from a pharmaceutical polymer with no

  6. Assessment of drug salt release from solutions, suspensions and in situ suspensions using a rotating dialysis cell

    DEFF Research Database (Denmark)

    Parshad, Henrik; Frydenvang, Karla; Liljefors, Tommy

    2003-01-01

    buffer is used as release media. Generally, the initial release of the drug salt from in situ suspensions occurred faster as compared to conventional suspensions, probably due to incomplete precipitation of the drug salt, and hence formation of supersaturated solutions where the rate of release......A rotating dialysis cell consisting of a small (10 ml) and a large compartment (1000 ml) was used to study the release of drug salt (bupivacaine 9-anthracene carboxylate) from (i). solutions, (ii). suspensions and (iii). in situ formed suspensions. Initial release experiments from suspensions...... indicated that the release of drug salt in deionized water was predominantly limited by the diffusion across the membrane whereas it is essentially dissolution rate controlled in 0.05 M phosphate buffer (pH 7.40). Thus, the in vitro model appears to have a potential in formulation screening when phosphate...

  7. The effects of cyclodextrins on drug release from fatty suppository bases : III. Application of cyclodextrin derivatives

    NARCIS (Netherlands)

    Frijlink, H.W.; Paiotti, S.; Eissens, Anko; Lerk, C.F.

    1992-01-01

    The complexation of both n-butyl-4-aminobenzoate and diazepam with dimethyl-beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin, respectively, was studied. Solid complexes were prepared by freeze-drying. The complexes were incorporated in fatty suppositories and drug release was studied, both in

  8. Development of sustained and dual drug release co-extrusion formulations for individual dosing.

    Science.gov (United States)

    Laukamp, Eva Julia; Vynckier, An-Katrien; Voorspoels, Jody; Thommes, Markus; Breitkreutz, Joerg

    2015-01-01

    In personalized medicine and patient-centered medical treatment individual dosing of medicines is crucial. The Solid Dosage Pen (SDP) allows for an individual dosing of solid drug carriers by cutting them into tablet-like slices. The aim of the present study was the development of sustained release and dual release formulations with carbamazepine (CBZ) via hot-melt co-extrusion for the use in the SDP. The selection of appropriate coat- and core-formulations was performed by adapting the mechanical properties (like tensile strength and E-modulus) for example. By using different excipients (polyethyleneglycols, poloxamers, white wax, stearic acid, and carnauba wax) and drug loadings (30-50%) tailored dissolution kinetics was achieved showing cube root or zero order release mechanisms. Besides a biphasic drug release, the dose-dependent dissolution characteristics of sustained release formulations were minimized by a co-extruded wax-coated formulation. The dissolution profiles of the co-extrudates were confirmed during short term stability study (six months at 21.0 ± 0.2 °C, 45%r.h.). Due to a good layer adhesion of core and coat and adequate mechanical properties (maximum cutting force of 35.8 ± 2.0 N and 26.4 ± 2.8 N and E-modulus of 118.1 ± 8.4 and 33.9 ± 4.5 MPa for the dual drug release and the wax-coated co-extrudates, respectively) cutting off doses via the SDP was precise. While differences of the process parameters (like the barrel temperature) between the core- and the coat-layer resulted in unsatisfying content uniformities for the wax-coated co-extrudates, the content uniformity of the dual drug release co-extrudates was found to be in compliance with pharmacopoeial specification. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Improvement of Tenofovir vaginal release from hydrophilic matrices through drug granulation with hydrophobic polymers.

    Science.gov (United States)

    Notario-Pérez, Fernando; Martín-Illana, Araceli; Cazorla-Luna, Raúl; Ruiz-Caro, Roberto; Peña, Juan; Veiga, María-Dolores

    2018-05-30

    Sustained-release vaginal microbicides hold out great hope for the prevention of sexual transmission of HIV from men to women. Tenofovir (TFV) -an antiretroviral drug- sustained-release vaginal compacts combining two release control systems (by drug-loading granules with hydrophobic polymers and incorporating them in a hydrophilic matrix) are proposed in this work as a possible microbicide. The polymers used for the drug granules are Eudragit® RS (ERS), an acrylic derivative, and Zein, a maize protein. The hydrophilic matrix is composed of a mixture of hydroxypropylmethyl cellulose (HPMC) and chitosan (CH). The thermal, microscopic, spectrophotometric and X-ray diffraction analysis showed that the drug was not altered during the granulation process. Studies of TFV release, swelling and ex vivo mucoadhesion were subsequently performed on simulated vaginal fluid. The formulation whereby TFV is granulated using twice its weight in ERS, and then including these granules in a matrix in which the CH predominates over HPMC, allows the sustained release of TFV for 144 h, mucoadhesion to the vaginal mucosa for 150 h and a moderate swelling, making it the most suitable formulation of all those studied. These compacts would therefore offer women protection against the sexual acquisition of HIV. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Sol-gel Derived Warfarin - Silica Composites for Controlled Drug Release.

    Science.gov (United States)

    Dolinina, Ekaterina S; Parfenyuk, Elena V

    2017-01-01

    Warfarin, commonly used anticoagulant in clinic, has serious shortcomings due to its unsatisfactory pharmacodynamics. One of the efficient ways for the improvement of pharmacological and consumer properties of drugs is the development of optimal drug delivery systems. The aim of this work is to synthesize novel warfarin - silica composites and to study in vitro the drug release kinetics to obtain the composites with controlled release. The composites of warfarin with unmodified (UMS) and mercaptopropyl modified silica (MPMS) were synthesized by sol-gel method. The composite formation was confirmed by FTIR spectra. The concentrations of warfarin released to media with pH 1.6, 6.8 and 7.4 were measured using UV spectroscopy. The drug release profiles from the solid composites were described by a series of kinetic models which includes zero order kinetics, first order kinetics, the modified Korsmeyer-Peppas model and Hixson-Crowell model. The synthesized sol-gel composites have different kinetic behavior in the studied media. In contrast to the warfarin composite with unmodified silica, the drug release from the composite with mercaptopropyl modified silica follows zero order kinetics for 24 h irrespective to the release medium pH due to mixed mechanism (duffusion + degradation and/or disintegration of silica matrix). The obtained results showed that warfarin - silica sol-gel composites have a potential application for the development of novel oral formulation of the drug with controlled delivery. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Drug kinetics release from Eudragit – Tenofovir@SiOC tablets

    Energy Technology Data Exchange (ETDEWEB)

    Tamayo, A., E-mail: aitanath@icv.csic.es [Ceramics and Glass Institute, CSIC, Madrid (Spain); Mazo, M.A. [Ceramics and Glass Institute, CSIC, Madrid (Spain); Veiga, M.D.; Ruiz-Caro, R.; Notario-Pérez, F. [Dpt. Pharmaceutical Technology, Faculty of Pharmacy, Complutense University of Madrid, Madrid (Spain); Rubio, J. [Ceramics and Glass Institute, CSIC, Madrid (Spain)

    2017-06-01

    A novel drug release system has been obtained in form of tablets from Eudragit® RS and tenofovir loaded on porous silicon oxycarbide glasses (SiOC). Active carbon (AC) and mesoporous silica (MCM-41) have also been used for comparative purposes. The porous silicon oxycarbide presents a bimodal mesopore size distribution that is maintained after functionalization with amino groups. We have studied the adsorption kinetics and adsorption equilibrium when the materials are loaded with tenofovir and, in all cases, pseudo-second order kinetics and Langmuir isotherm have been revealed as the most representative models describing the kinetic and thermodynamic parameters. Besides, the tenofovir adsorption on these materials turns out to be a favorable process. In vitro release of tenofovir has been studied in simulated vaginal medium by applying different release models. Continuous tenofovir release for > 20 days has been obtained for the SiOC material functionalized with amine groups. We concluded that the drug release occurs in two steps that involve a drug diffusion step through the material pores and diffusion through the swollen polymer. The interactions between the tenofovir drug and de amine groups of the functionalized silicon oxycarbide also play an important role in the release process. - Highlights: • Kinetic and thermodinamic parameters of the adsorption of tenofovir on porous substrates have been obtained. • Sustained release of TFV for > 20 days in SVF when it is supported on SiOC and manufactured as Eudragit®RS-containing tablets. • Release described by a two-step process involving diffusion through SiOC matrix and subsequent diffusion through the polymer.

  12. Effect of bioceramic functional groups on drug binding and release kinetics

    Science.gov (United States)

    Trujillo, Christopher

    Bioceramics have been studied extensively as drug delivery systems (DDS). Those studies have aimed to tailor the drug binding and release kinetics to successfully treat infections and other diseases. This research suggests that the drug binding and release kinetics are predominantly driven by the functional groups available on the surface of a bioceramic. The goal of the present study is to explain the role of silicate and phosphate functional groups in drug binding to and release kinetics from bioceramics. alpha-cristobalite (Cris; SiO2) particles (90-150 microm) were prepared and doped with 0 microg (P-0), 39.1 microg (P-39.1), 78.2 microg (P-78.2), 165.5 microg (P-165.5) or 331 microg (P-331) of P 2O5 per gram Cris, using 85% orthophosphoric (H3PO 4) acid and thermal treatment. The material structure was analyzed using X-ray diffraction (XRD) with Rietveld Refinement and Fourier Transform Infrared (FTIR) spectroscopy with Gaussian fitting. XRD demonstrated an increase from sample P-0 (170.5373 A3) to P-331 (170.6466 A 3) in the unit cell volume as the P2O5 concentration increased in the material confirming phosphate silicate substitution in Cris. Moreover, FTIR showed the characteristic bands of phosphate functional groups of nu4 PO4/O-P-O bending, P-O-P stretching, P-O-P bending, P=O stretching, and P-O-H bending in doped Cris indicating phosphate incorporation in the silicate structure. Furthermore, FTIR showed that the nu4 PO4/O-P-O bending band around 557.6 cm-1 and P=O stretching band around 1343.9 cm-1 increased in area for samples P-39.1 to P-331 from 3.5 to 10.5 and from 10.1 to 22.4, respectively due to phosphate doping. In conjunction with the increase of the nu4 PO4/O-P-O bending band and P=O stretching band, a decrease in area of the O-Si-O bending bands around 488.1 and 629.8 cm-1 was noticed for samples P-39.1 to P-331 from 5 to 2 and from 11.8 to 5.4, respectively. Furthermore, Cris samples (200 mg, n=5 for each sample) were immersed separately in

  13. Drug-releasing nano-engineered titanium implants: therapeutic efficacy in 3D cell culture model, controlled release and stability

    Energy Technology Data Exchange (ETDEWEB)

    Gulati, Karan [School of Chemical Engineering, The University of Adelaide, SA 5005 (Australia); Kogawa, Masakazu; Prideaux, Matthew; Findlay, David M. [Discipline of Orthopaedics and Trauma, The University of Adelaide, SA 5005 (Australia); Atkins, Gerald J., E-mail: gerald.atkins@adelaide.edu.au [Discipline of Orthopaedics and Trauma, The University of Adelaide, SA 5005 (Australia); Losic, Dusan, E-mail: dusan.losic@adelaide.edu.au [School of Chemical Engineering, The University of Adelaide, SA 5005 (Australia)

    2016-12-01

    There is an ongoing demand for new approaches for treating localized bone pathologies. Here we propose a new strategy for treatment of such conditions, via local delivery of hormones/drugs to the trauma site using drug releasing nano-engineered implants. The proposed implants were prepared in the form of small Ti wires/needles with a nano-engineered oxide layer composed of array of titania nanotubes (TNTs). TNTs implants were inserted into a 3D collagen gel matrix containing human osteoblast-like, and the results confirmed cell migration onto the implants and their attachment and spread. To investigate therapeutic efficacy, TNTs/Ti wires loaded with parathyroid hormone (PTH), an approved anabolic therapeutic for the treatment of severe bone fractures, were inserted into 3D gels containing osteoblast-like cells. Gene expression studies revealed a suppression of SOST (sclerostin) and an increase in RANKL (receptor activator of nuclear factor kappa-B ligand) mRNA expression, confirming the release of PTH from TNTs at concentrations sufficient to alter cell function. The performance of the TNTs wire implants using an example of a drug needed at relatively higher concentrations, the anti-inflammatory drug indomethacin, is also demonstrated. Finally, the mechanical stability of the prepared implants was tested by their insertion into bovine trabecular bone cores ex vivo followed by retrieval, which confirmed the robustness of the TNT structures. This study provides proof of principle for the suitability of the TNT/Ti wire implants for localized bone therapy, which can be customized to cater for specific therapeutic requirements. - Highlights: • Ti wire with titania nanotubes (TNTs) are proposed as ‘in-bone’ therapeutic implants. • 3D cell culture model is used to confirm therapeutic efficacy of drug releasing implants. Osteoblasts migrated and firmly attached to the TNTs and the micro-scale cracks. • Tailorable drug loading from few nanograms to several hundred

  14. Sodium alginate-polyvinyl alcohol-bovin serum albumin coated Fe3O4 nanoparticles as anticancer drug delivery vehicle: Doxorubicin loading and in vitro release study and cytotoxicity to HepG2 and L02 cells.

    Science.gov (United States)

    Prabha, G; Raj, V

    2017-10-01

    The challenging part of this work was to research the potential aspects of sodium alginate (SA)-polyvinyl alcohol (PVA)-bovin serum albumin (BSA) coated Fe 3 O 4 nanoparticles (Fe 3 O 4 -SA-PVA-BSA) as a drug delivery system for doxorubicin (DOX). The anticancer drug doxorubicin was selected as a model drug which is powerful for numerous cancer treatments. Superparamagnetic Fe 3 O 4 nanoparticles were prepared by co-precipitation method. The mixture solution of Fe 3 O 4 -sodium alginate (SA) - doxorubicin (DOX) was crosslinked with Ca 2+ to form (Fe 3 O 4 -SA-DOX) nanoparticles and addition of PVA and BSA with (Fe 3 O 4 -SA-DOX) nanoparticles was prepared by coating procedure. Doxorubicin drug loaded NPs were prepared by a simple crosslinking method by calcium chloride solution. The prepared polymer coated magnetic nanoparticles (Fe 3 O 4 -SA-PVA-BSA) were characterized by using SEM, AFM, FT-IR, XRD and VSM. The mean sizes of the obtained drug loaded nanoparticles (Fe 3 O 4 -SA-DOX, Fe 3 O 4 -SA-DOX-PVA and Fe 3 O 4 -SA-DOX-PVA-BSA) were between 240±8.3 and 460±8.7nm and zeta potential of the particles also was evaluated using Malvern Zetasizer which ranged between -48.1±2.3 and -22.4±4.1mV. The encapsulation efficiency, was between 36.2±0.01 and 96.45±2.12. Moreover drug loading and drug release properties of the polymer coated magnetic nanoparticles loaded with doxorubicin (Fe 3 O 4 -SA-DOX-PVA-BSA) were also studied. In addition, the cytotoxicity of the created nanoparticles was performed by using MTT assay analysis which showed that DOX loaded nanoparticles (Fe 3 O 4 -SA-DOX-PVA-BSA) were toxic to HepG2 cell lines and non-toxic to L02 cell lines. The in-vitro drug release was studied by using UV-Visible spectrophotometer at acidic environment (pH5.0) and basic environment (pH7.4) as well as at different temperatures (37°C and 42°C). It was found that DOX drug is released much faster in acidic environment (pH5.0) than in the basic environment (pH7

  15. Nanocapsule@xerogel microparticles containing sodium diclofenac: a new strategy to control the release of drugs.

    Science.gov (United States)

    da Fonseca, Letícia Sias; Silveira, Rodrigo Paulo; Deboni, Alberto Marçal; Benvenutti, Edilson Valmir; Costa, Tânia M H; Guterres, Sílvia S; Pohlmann, Adriana R

    2008-06-24

    The aim of this work was to evaluate the potentiality to control the drug release of a new architecture of microparticles organized at the nanoscopic scale by assembling polymeric nanocapsules at the surface of drug-loaded xerogels. Xerogel was prepared by sol-gel method using sodium diclofenac, as hydrophilic drug model, and coated by spray-drying. After coating, the surface areas decreased from 82 to 28 m(2)/g, the encapsulation efficiency was 71% and SEM analysis showed irregular microparticles coated by the nanocapsules. Formulation showed satisfactory gastro-resistance presenting drug release lower than 3% (60 min) in acid medium. In water, the pure drug dissolved 92% after 5 min, uncoated drug-loaded xerogel released 60% and nanocapsule coated drug-loaded xerogel 36%. After 60 min, uncoated drug-loaded xerogel released 82% and nanocapsule coated drug-loaded xerogel 62%. In conclusion, the new system was able to control the release of the hydrophilic drug model.

  16. Optimization of matrix tablets controlled drug release using Elman dynamic neural networks and decision trees.

    Science.gov (United States)

    Petrović, Jelena; Ibrić, Svetlana; Betz, Gabriele; Đurić, Zorica

    2012-05-30

    The main objective of the study was to develop artificial intelligence methods for optimization of drug release from matrix tablets regardless of the matrix type. Static and dynamic artificial neural networks of the same topology were developed to model dissolution profiles of different matrix tablets types (hydrophilic/lipid) using formulation composition, compression force used for tableting and tablets porosity and tensile strength as input data. Potential application of decision trees in discovering knowledge from experimental data was also investigated. Polyethylene oxide polymer and glyceryl palmitostearate were used as matrix forming materials for hydrophilic and lipid matrix tablets, respectively whereas selected model drugs were diclofenac sodium and caffeine. Matrix tablets were prepared by direct compression method and tested for in vitro dissolution profiles. Optimization of static and dynamic neural networks used for modeling of drug release was performed using Monte Carlo simulations or genetic algorithms optimizer. Decision trees were constructed following discretization of data. Calculated difference (f(1)) and similarity (f(2)) factors for predicted and experimentally obtained dissolution profiles of test matrix tablets formulations indicate that Elman dynamic neural networks as well as decision trees are capable of accurate predictions of both hydrophilic and lipid matrix tablets dissolution profiles. Elman neural networks were compared to most frequently used static network, Multi-layered perceptron, and superiority of Elman networks have been demonstrated. Developed methods allow simple, yet very precise way of drug release predictions for both hydrophilic and lipid matrix tablets having controlled drug release. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Doxorubicin loaded nanodiamond-silk spheres for fluorescence tracking and controlled drug release

    Science.gov (United States)

    Khalid, Asma; Mitropoulos, Alexander N.; Marelli, Benedetto; Tomljenovic-Hanic, Snjezana; Omenetto, Fiorenzo G.

    2015-01-01

    Nanoparticle (NP) based technologies have proved to be considerably beneficial for advances in biomedicine especially in the areas of disease detection, drug delivery and bioimaging. Over the last few decades, NPs have garnered interest for their exemplary impacts on the detection, treatment, and prevention of cancer. The full potential of these technologies are yet to be employed for clinical use. The ongoing research and development in this field demands single multifunctional composite materials that can be employed simultaneously for drug delivery and biomedical imaging. In this manuscript, a unique combination of silk fibroin (SF) and nanodiamonds (NDs) in the form of nanospheres are fabricated and investigated. The spheres were loaded with the anthracyline Doxorubicin (DoX) and the drug release kinetics for these ND-SF-DoX (NDSX) spheres were studied. NDs provided the fluorescence modality for imaging while the degradable SF spheres stabilized and released the drug in a controlled manner. The emission and structural properties of the spheres were characterized during drug release. The degradability of SF and the subsequent release of DoX from the spheres were monitored through fluorescence of NDs inside the spheres. This research demonstrates the enormous potential of the ND-SF nanocomposite platforms for diagnostic and therapeutic purposes, which are both important for pharmaceutical research and clinical settings. PMID:26819823

  18. IONP-doped nanoparticles for highly effective NIR-controlled drug release and combination tumor therapy

    Directory of Open Access Journals (Sweden)

    Fu X

    2017-05-01

    Full Text Available Xudong Fu,1 Xinjun Wang,1 Shaolong Zhou,1 Yanyan Zhang2 1The Fifth Affiliated Hospital of Zhengzhou University, 2School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China Abstract: Despite advances in controlled drug delivery, drug delivery systems (DDSs with controlled activated drug release and high spatial and temporal resolution are still required. Theranostic nanomedicine is capable of diagnosis, therapy, and monitoring the delivery and distribution of drug molecules and has received growing interest. In this study, a near-infrared light-controlled “off–on” DDS with magnetic resonance imaging and magnetic targeting properties was developed using a hybrid nanoplatform (carbon nanotubes [CNTs]-iron oxide nanoparticle. Doxorubicin (DOX and distearoyl-sn-glycero-3-phosphoethanolamine-PEG were adsorbed onto CNTs-iron oxide nanoparticle, and then to avoid the unexpected drug release during circulation, 1-myristyl alcohol was used to encapsulate the CNTs–drug complex. Herein, multifunctional DOX-loaded nanoparticles (NPs with “off–on” state were developed. DOX-NPs showed an obvious “off–on” effect (temperature increase, drug release controlled by near-infrared light in vitro and in vivo. In the in vivo and in vitro studies, DOX-NPs exhibited excellent magnetic resonance imaging ability, magnetic targeting property, high biosafety, and high antitumor combined therapeutic efficacy (hyperthermia combined with chemotherapy. These results highlight the great potential of DOX-NPs in the treatment of cancer. Keywords: controlled drug release, magnetic targeting, MRI, combination therapy

  19. Influence of Surface Chemistry on the Release of an Antibacterial Drug from Nanostructured Porous Silicon.

    Science.gov (United States)

    Wang, Mengjia; Hartman, Philip S; Loni, Armando; Canham, Leigh T; Bodiford, Nelli; Coffer, Jeffery L

    2015-06-09

    Nanostructured mesoporous silicon possesses important properties advantageous to drug loading and delivery. For controlled release of the antibacterial drug triclosan, and its associated activity versus Staphylococcus aureus, previous studies investigated the influence of porosity of the silicon matrix. In this work, we focus on the complementary issue of the influence of surface chemistry on such properties, with particular regard to drug loading and release kinetics that can be ideally adjusted by surface modification. Comparison between drug release from as-anodized, hydride-terminated hydrophobic porous silicon and the oxidized hydrophilic counterpart is complicated due to the rapid bioresorption of the former; hence, a hydrophobic interface with long-term biostability is desired, such as can be provided by a relatively long chain octyl moiety. To minimize possible thermal degradation of the surfaces or drug activity during loading of molten drug species, a solution loading method has been investigated. Such studies demonstrate that the ability of porous silicon to act as an effective carrier for sustained delivery of antibacterial agents can be sensitively altered by surface functionalization.

  20. Bilayer tablets of Paliperidone for Extended release osmotic drug delivery

    Science.gov (United States)

    Chowdary, K. Sunil; Napoleon, A. A.

    2017-11-01

    The purpose of this study is to develop and optimize the formulation of paliperidone bilayer tablet core and coating which should meet in vitro performance of trilayered Innovator sample Invega. Optimization of core formulations prepared by different ratio of polyox grades and optimization of coating of (i) sub-coating build-up with hydroxy ethyl cellulose (HEC) and (ii).enteric coating build-up with cellulose acetate (CA). Some important influence factors such as different core tablet compositions and different coating solution ingredients involved in the formulation procedure were investigated. The optimization of formulation and process was conducted by comparing different in vitro release behaviours of Paliperidone. In vitro dissolution studies of Innovator sample (Invega) with formulations of different release rate which ever close release pattern during the whole 24 h test is finalized.

  1. Evaluation of gum mastic (Pistacia lentiscus as a microencapsulating and matrix forming material for sustained drug release

    Directory of Open Access Journals (Sweden)

    Dinesh M. Morkhade

    2017-09-01

    Full Text Available In this study, a natural gum mastic was evaluated as a microencapsulating and matrix-forming material for sustained drug release. Mastic was characterized for its physicochemical properties. Microparticles were prepared by oil-in-oil solvent evaporation method. Matrix tablets were prepared by wet and melt granulation techniques. Diclofenac sodium (DFS and diltiazem hydrochloride (DLTZ were used as model drugs. Mastic produced discrete and spherical microspheres with DLTZ and microcapsules with DFS. Particle size and drug loading of microparticles was in the range of 22–62 µm and 50–87%, respectively. Increase in mastic: drug ratio increased microparticle size, improved drug loading and decreased the drug release rate. Microparticles with gum: drug ratio of 2:1 could sustain DLTZ release up to 12 h and released 57% DFS in 12 h. Mastic produced tablets with acceptable pharmacotechnical properties. A 30% w/w of mastic in tablet could sustain DLTZ release for 5 h from wet granulation, and DFS release for 8 h and 11 h from wet and melt granulation, respectively. Results revealed that a natural gum mastic can be used successfully to formulate matrix tablets and microparticles for sustained drug release.

  2. pH-controlled drug loading and release from biodegradable microcapsules.

    Science.gov (United States)

    Zhao, Qinghe; Li, Bingyun

    2008-12-01

    Microcapsules made of biopolymers are of both scientific and technological interest and have many potential applications in medicine, including their use as controlled drug delivery devices. The present study makes use of the electrostatic interaction between polycations and polyanions to form a multilayered microcapsule shell and also to control the loading and release of charged drug molecules inside the microcapsule. Micron-sized calcium carbonate (CaCO3) particles were synthesized and integrated with chondroitin sulfate (CS) through a reaction between sodium carbonate and calcium nitrate tetrahydrate solutions suspended with CS macromolecules. Oppositely charged biopolymers were alternately deposited onto the synthesized particles using electrostatic layer-by-layer self-assembly, and glutaraldehyde was introduced to cross-link the multilayered shell structure. Microcapsules integrated with CS inside the multilayered shells were obtained after decomposition of the CaCO3 templates. The integration of a matrix (i.e., CS) permitted the subsequent selective control of drug loading and release. The CS-integrated microcapsules were loaded with a model drug, bovine serum albumin labeled with fluorescein isothiocyanate (FITC-BSA), and it was shown that pH was an effective means of controlling the loading and release of FITC-BSA. Such CS-integrated microcapsules may be used for controlled localized drug delivery as biodegradable devices, which have advantages in reducing systemic side effects and increasing drug efficacy.

  3. Effect of Na2SO3 concentration to drug loading and drug release of ascorbic acid in chitosan edible film as drug delivery system membrane

    Directory of Open Access Journals (Sweden)

    Kistriyani Lilis

    2018-01-01

    Full Text Available Chitosan is a type of carbohydrate compounds produced from waste marine products, in particular the class of shrimp, crabs and clams. Chitosan is often process into edible films and utilized for food packaging also has potential as a membrane for drug delivery system. Drug loading and drug release can be controlled by improve the characteristics of the membrane by adding crosslinker. The purpose of this research is to study the effect of addition of crosslinker to the rate of loading and release of ascorbic acid in the chitosan edible film. Na2SO3 was used as crosslinker. Two grams of chitosan was dissolved into 100 ml of distilled water. Acetic acid and plasticizer were added in the solution then heated at 50°C. Na2SO3 solution with mass various of Na2SO3 dissolved, 01026 0.3; and 0.5 grams were added about 30 mL to make edible film. The analysis include of drug loading, drug release and tensile strength. The result showed that the loading of edible film with crosslinker 0.15 g; 0.3 g; and 0.5 g respectively were 60.98 ppm; 52.53 ppm; and 40.88 ppm, meanwhile for the release with crosslinker 0.15 g; 0.3 g; and 0.5 g respectively were 3.78 ppm; 5.72 ppm; and 5.97 ppm.

  4. Swelling, erosion and drug release characteristics of salbutamol sulfate from hydroxypropyl methylcellulose-based matrix tablets.

    Science.gov (United States)

    Chaibva, Faith A; Khamanga, Sandile M M; Walker, Roderick B

    2010-12-01

    Hydrophilic matrix formulations are important and simple technologies that are used to manufacture sustained release dosage forms. Hydroxypropyl methylcellulose-based matrix tablets, with and without additives, were manufactured to investigate the rate of hydration, rate of erosion, and rate and mechanism of drug release. Scanning electron microscopy was used to assess changes in the microstructure of the tablets during drug release testing and whether these changes could be related to the rate of drug release from the formulations. The results revealed that the rate of hydration and erosion was dependent on the polymer combination(s) used, which in turn affected the rate and mechanism of drug release from these formulations. It was also apparent that changes in the microstructure of matrix tablets could be related to the different rates of drug release that were observed from the test formulations. The use of scanning electron microscopy provides useful information to further understand drug release mechanisms from matrix tablets.

  5. Relapse to opioid use in opioid-dependent individuals released from compulsory drug detention centres compared with those from voluntary methadone treatment centres in Malaysia: a two-arm, prospective observational study.

    Science.gov (United States)

    Wegman, Martin P; Altice, Frederick L; Kaur, Sangeeth; Rajandaran, Vanesa; Osornprasop, Sutayut; Wilson, David; Wilson, David P; Kamarulzaman, Adeeba

    2017-02-01

    Detention of people who use drugs into compulsory drug detention centres (CDDCs) is common throughout East and Southeast Asia. Evidence-based pharmacological therapies for treating substance use disorders, such as opioid agonist treatments with methadone, are generally unavailable in these settings. We used a unique opportunity where CDDCs coexisted with voluntary drug treatment centres (VTCs) providing methadone in Malaysia to compare the timing and occurrence of opioid relapse (measured using urine drug testing) in individuals transitioning from CDDCs versus methadone maintenance in VTCs. We did a parallel, two-arm, prospective observational study of opioid-dependent individuals aged 18 years and older who were treated in Malaysia in the Klang Valley in two settings: CDDCs and VTCs. We used sequential sampling to recruit individuals. Assessed individuals in CDDCs were required to participate in services such as counselling sessions and manual labour. Assessed individuals in VTCs could voluntarily access many of the components available in CDDCs, in addition to methadone therapy. We undertook urinary drug tests and behavioural interviews to assess individuals at baseline and at 1, 3, 6, 9, and 12 months post-release. The primary outcome was time to opioid relapse post-release in the community confirmed by urinary drug testing in individuals who had undergone baseline interviewing and at least one urine drug test (our analytic sample). Relapse rates between the groups were compared using time-to-event methods. This study is registered at ClinicalTrials.gov (NCT02698098). Between July 17, 2012, and August 21, 2014, we screened 168 CDDC attendees and 113 VTC inpatients; of these, 89 from CDDCs and 95 from VTCs were included in our analytic sample. The baseline characteristics of the two groups were similar. In unadjusted analyses, CDDC participants had significantly more rapid relapse to opioid use post-release compared with VTC participants (median time to relapse

  6. Hydroxyapatite-alginate nanocomposite as drug delivery matrix for sustained release of ciprofloxacin.

    Science.gov (United States)

    Venkatasubbu, G Devanand; Ramasamy, S; Ramakrishnan, V; Kumar, J

    2011-12-01

    Hydroxyapatite is a bioceramic which has a wide range of medical application for bone diseases. To enhance its usage, we have prepared ciprofloxacin loaded nano hydroxyapatite (HA) composite with a natural polymer, alginate, using wet chemical method at low temperature. The prepared composites were analyzed by various physicochemical methods. The results show that the nano HA crystallites are well intact with the alginate macromolecules. For the composite system FT-IR and micro Raman results are reported in this paper. Studies on the drug loading and drug release have been done. The drug is pre-adsorbed onto the ceramic particle before the formation of composite. The thermal behavior of composite has been studied using thermo gravimetric analysis (TGA). This work, reports that the nanocomposite prepared under optimum condition could prolong the release of ciprofloxacin compared with the ciprofloxacin loaded hydroxyapatite.

  7. Simulated food effects on drug release from ethylcellulose: PVA-PEG graft copolymer-coated pellets.

    Science.gov (United States)

    Muschert, Susanne; Siepmann, Florence; Leclercq, Bruno; Carlin, Brian; Siepmann, Juergen

    2010-02-01

    Food effects might substantially alter drug release from oral controlled release dosage forms in vivo. The robustness of a novel type of controlled release film coating was investigated using various types of release media and two types of release apparatii. Importantly, none of the investigated conditions had a noteworthy impact on the release of freely water-soluble diltiazem HCl or slightly water-soluble theophylline from pellets coated with ethylcellulose containing small amounts of PVA-PEG graft copolymer. In particular, the presence of significant amounts of fats, carbohydrates, surfactants, bile salts, and calcium ions in the release medium did not alter drug release. Furthermore, changes in the pH and differences in the mechanical stress the dosage forms were exposed to did not affect drug release from the pellets. The investigated film coatings allowing for oral controlled drug delivery are highly robust in vitro and likely to be poorly sensitive to classical food effects in vivo.

  8. HPMA copolymer-drug conjugates with controlled tumor-specific drug release

    Czech Academy of Sciences Publication Activity Database

    Chytil, Petr; Koziolová, Eva; Etrych, Tomáš; Ulbrich, Karel

    2018-01-01

    Roč. 18, č. 1 (2018), s. 1-15, č. článku 1700209. ISSN 1616-5187 R&D Projects: GA ČR(CZ) GA15-02986S; GA ČR(CZ) GA17-13283S; GA ČR(CZ) GA17-08084S; GA MŠk(CZ) LO1507 Institutional support: RVO:61389013 Keywords : biodegradable spacer * controlled drug release * drug delivery systems Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 3.238, year: 2016

  9. Effect of amine functionalization of spherical MCM-41 and SBA-15 on controlled drug release

    International Nuclear Information System (INIS)

    Szegedi, A.; Popova, M.; Goshev, I.; Mihaly, J.

    2011-01-01

    MCM-41 and SBA-15 silica materials with spherical morphology and different particle sizes were synthesized and modified by post-synthesis method with 3-aminopropyltriethoxysilane (APTES). A comparative study of the adsorption and release of a model drug, ibuprofen, were carried out. The modified and drug loaded mesoporous materials were characterized by XRD, TEM, N 2 physisorption, thermal analysis, elemental analysis and FT-IR spectroscopy. Surface modification with amino groups resulted in high degree of ibuprofen loading and slow rate of release for MCM-41, whereas it was the opposite for SBA-15. The adsorbed drug content and the delivery rate can be predetermined by the choice of mesoporous material with the appropriate structural characteristics and surface functionality. -- Graphical Abstract: Ibuprofen delivery from the parent and amino-modified spherical MCM-41 materials with 100 nm (small) and 500 nm (large) particle sizes. Display Omitted Highlights: → Spherical type MCM-41 and SBA-15 with different particle sizes were modified by APTES. → Adsorption and release rate of ibuprofen were compared. → High degree of ibuprofen loading, slow release rate for MCM-41, the opposite for SBA-15. → MCM-41 with 100 nm particles was more stable and showed slower release rate

  10. Functionalized PLA polymers to control loading and/or release properties of drug-loaded nanoparticles.

    Science.gov (United States)

    Thauvin, Cédric; Schwarz, Bettina; Delie, Florence; Allémann, Eric

    2017-11-15

    Advantages associated with the use of polylactic acid (PLA) nano- or microparticles as drug delivery systems have been widely proven in the field of pharmaceutical sciences. These biodegradable and biocompatible carriers have demonstrated different loading and release properties depending on interactions with the cargo, preparation methods, particles size or molecular weight of PLA. In this study, we sought to show the possibility of influencing these properties by modifying the structure of the constituting polymer. Seven non-functionalized or functionalized PLA polymers were specifically designed and synthesized by microwave-assisted ring-opening polymerization of d,l-lactide. They presented short hydrophobic and/or hydrophilic groups thanks to the use of C20 aliphatic chain, mPEG1000, sorbitan esters (Spans ® ) or polysorbates (Tweens ® ), their PEGylated analogues, as initiators. Then, seven types of drug-loaded nanoparticles (NP) were prepared from these polymers and compared in terms of physico-chemical characteristics, drug loading and release profiles. Although the loading properties were not improved with any of the functionalized PLA NP, different release profiles were observed in an aqueous medium at 37 °C and over a period of five days. The presence of PEG moieties in the core of PLA-polysorbates NP induced a faster release while the addition of a single aliphatic chain induced a slower release due to better interactions with the active molecule. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. [Preparation of hydrophilic matrix sustained release tablets of total lactones from Andrographis paniculata and study on its in vitro release mechanism].

    Science.gov (United States)

    Xu, Fang-Fang; Shi, Wei; Zhang, Hui; Guo, Qing-Ming; Wang Zhen-Zhong; Bi, Yu-An; Wang, Zhi-Min; Xiao, Wei

    2015-01-01

    In this study, hydrophilic matrix sustained release tablets of total lactones from Andrographis paniculata were prepared and the in vitro release behavior were also evaluated. The optimal prescription was achieved by studying the main factor of the type and amount of hydroxypropyl methylcellulose (HPMC) using single factor test and evaluating through cumulative release of three lactones. No burst drug release from the obtained matrix tablets was observed. Drug release sustained to 14 h. The release mechanism of three lactones from A. paniculata was accessed by zero-order, first-order, Higuchi and Peppas equation. The release behavior of total lactones from A. paniculata was better agreed with Higuchi model and the drug release from the tablets was controlled by degradation of the matrix. The preparation of hydrophilic matrix sustained release tablets of total lactones from A. paniculata with good performance of drug release was simple.

  12. Molecular weight-dependent degradation and drug release of surface-eroding poly(ethylene carbonate).

    Science.gov (United States)

    Bohr, Adam; Wang, Yingya; Harmankaya, Necati; Water, Jorrit J; Baldursdottír, Stefania; Almdal, Kristoffer; Beck-Broichsitter, Moritz

    2017-06-01

    Poly(ethylene carbonate) (PEC) is a unique biomaterial showing significant potential for controlled drug delivery applications. The current study investigated the impact of the molecular weight on the biological performance of drug-loaded PEC films. Following the preparation and thorough physicochemical characterization of diverse PEC (molecular weights: 85, 110, 133, 174 and 196kDa), the degradation and drug release behavior of rifampicin- and bovine serum albumin-loaded PEC films was investigated in vitro (in the presence and absence of cholesterol esterase), in cell culture (RAW264.7 macrophages) and in vivo (subcutaneous implantation in rats). All investigated samples degraded by means of surface erosion (mass loss, but constant molecular weight), which was accompanied by a predictable, erosion-controlled drug release pattern. Accordingly, the obtained in vitro degradation half-lives correlated well with the observed in vitro half-times of drug delivery (R 2 =0.96). Here, the PEC of the highest molecular weight resulted in the fastest degradation/drug release. When incubated with macrophages or implanted in animals, the degradation rate of PEC films superimposed the results of in vitro incubations with cholesterol esterase. Interestingly, SEM analysis indicated a distinct surface erosion process for enzyme-, macrophage- and in vivo-treated polymer films in a molecular weight-dependent manner. Overall, the molecular weight of surface-eroding PEC was identified as an essential parameter to control the spatial and temporal on-demand degradation and drug release from the employed delivery system. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Controlled release of non-steroidal antiinflammatory and anticancer drugs from hybrid materials

    Energy Technology Data Exchange (ETDEWEB)

    Caravieri, Beatriz Bernardes; Molina, Eduardo Ferreira, E-mail: bia_ms_@hotmail.com [Universidade de Franca, SP (Brazil)

    2016-07-01

    Full text: Chronic inflammation is a well known risk factor for the development of human cancer, and at least one third of all human cancers have been associated with inflammation. This can lead to cellular proliferation, a process which per se increases the risk of abnormal cell formation and ultimately the development of cancer. For treating clinical conditions such as inflammation and cancer, the most common methods (e.g., oral administration, injection) can cause unwanted side effects due to drug delivery to non-target sites and the introduction of high doses of the drug to reach the desired location. An alternative to these problems is the preparation of materials that can release drugs with different activities. Thinking about it, the aim of this study was to use a class of hybrid materials based on siloxane-polyether known as ureasil for controlled release of non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (IBU) and naproxen (NAP), and anticancer, such as 5-fluorouracil (5- FU). These drugs have been incorporated in the matrix in different proportions and thereafter, were characterized by different techniques such as XRD, FTIR, DSC and SAXS. In addition, it has been evaluated the release kinetics of these species with different chemical structures. The results have shown that the drug molecules were homogeneously distributed in the xerogel hybrids, which contributed to the drug’s release profile fine-tuning. The chemical environment of the polyether chains was amended by incorporating the drugs. The analysis from XRD, FTIR, SAXS and DSC confirm the good solubility of the substances within hybrid matrix. This hybrid material based on polymers and inorganic compounds may have potential applications in human health. (author)

  14. Controlled release of non-steroidal antiinflammatory and anticancer drugs from hybrid materials

    International Nuclear Information System (INIS)

    Caravieri, Beatriz Bernardes; Molina, Eduardo Ferreira

    2016-01-01

    Full text: Chronic inflammation is a well known risk factor for the development of human cancer, and at least one third of all human cancers have been associated with inflammation. This can lead to cellular proliferation, a process which per se increases the risk of abnormal cell formation and ultimately the development of cancer. For treating clinical conditions such as inflammation and cancer, the most common methods (e.g., oral administration, injection) can cause unwanted side effects due to drug delivery to non-target sites and the introduction of high doses of the drug to reach the desired location. An alternative to these problems is the preparation of materials that can release drugs with different activities. Thinking about it, the aim of this study was to use a class of hybrid materials based on siloxane-polyether known as ureasil for controlled release of non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (IBU) and naproxen (NAP), and anticancer, such as 5-fluorouracil (5- FU). These drugs have been incorporated in the matrix in different proportions and thereafter, were characterized by different techniques such as XRD, FTIR, DSC and SAXS. In addition, it has been evaluated the release kinetics of these species with different chemical structures. The results have shown that the drug molecules were homogeneously distributed in the xerogel hybrids, which contributed to the drug’s release profile fine-tuning. The chemical environment of the polyether chains was amended by incorporating the drugs. The analysis from XRD, FTIR, SAXS and DSC confirm the good solubility of the substances within hybrid matrix. This hybrid material based on polymers and inorganic compounds may have potential applications in human health. (author)

  15. Understanding drug-related mortality in released prisoners: a review of national coronial records

    Directory of Open Access Journals (Sweden)

    Andrews Jessica Y

    2012-04-01

    Full Text Available Abstract Background The prisoner population is characterised by a high burden of disease and social disadvantage, and ex-prisoners are at increased risk of death following release. Much of the excess mortality can be attributed to an increased risk of unnatural death, particularly from drug overdose; however, relatively few studies have investigated the circumstances surrounding drug-related deaths among released prisoners. This study aimed to explore and compare the circumstances of death for those who died from accidental drug-related causes to those who died from all other reportable causes. Methods A nationwide search of the Australian National Coroners Information System (NCIS was conducted to identify reportable deaths among ex-prisoners from 2000 to 2007. Using a structured coding form, NCIS records for these cases were interrogated to explore causes and circumstances of death. Results Coronial records for 388 deceased ex-prisoners were identified. Almost half of these deaths were a result of accidental drug-related causes (45%. The majority of accidental drug-related deaths occurred in a home environment, and poly-substance use at or around the time of death was common, recorded in 72% of drug-related deaths. Ex-prisoners who died of accidental drug-related causes were on average younger and less likely to be Indigenous, born in Australia, married, or living alone at or around the time of death, compared with those who died from all other reportable causes. Evidence of mental illness or self-harm was less common among accidental drug-related deaths, whereas evidence of previous drug overdose, injecting drug use, history of heroin use and history of drug withdrawal in the previous six months were more common. Conclusions Drug-related deaths are common among ex-prisoners and often occur in a home (vs. public setting. They are often associated with use of multiple substances at or around the time of death, risky drug-use patterns, and even

  16. The Impact of Bubbles on Measurement of Drug Release from Echogenic Liposomes

    OpenAIRE

    Kopechek, Jonathan A.; Haworth, Kevin J.; Radhakrishnan, Kirthi; Huang, Shaoling; Klegerman, Melvin E.; McPherson, David D.; Holland, Christy K.

    2012-01-01

    Echogenic liposomes (ELIP) encapsulate gas bubbles and drugs within lipid vesicles, but the mechanisms of ultrasound-mediated drug release from ELIP are not well understood. The effect of cavitation activity on drug release from ELIP was investigated in flowing solutions using two fluorescent molecules: a lipophilic drug (rosiglitazone) and a hydrophilic drug substitute (calcein). ELIP samples were exposed to pulsed Doppler ultrasound from a clinical diagnostic ultrasound scanner at pressures...

  17. Drug-sensing hydrogels for the inducible release of biopharmaceuticals

    Science.gov (United States)

    Ehrbar, Martin; Schoenmakers, Ronald; Christen, Erik H.; Fussenegger, Martin; Weber, Wilfried

    2008-10-01

    Drug-dependent dissociation or association of cellular receptors represents a potent pharmacologic mode of action for regulating cell fate and function. Transferring the knowledge of pharmacologically triggered protein-protein interactions to materials science will enable novel design concepts for stimuli-sensing smart hydrogels. Here, we show the design and validation of an antibiotic-sensing hydrogel for the trigger-inducible release of human vascular endothelial growth factor. Genetically engineered bacterial gyrase subunit B (GyrB) (ref. 4) coupled to polyacrylamide was dimerized by the addition of the aminocoumarin antibiotic coumermycin, resulting in hydrogel formation. Addition of increasing concentrations of clinically validated novobiocin (Albamycin) dissociated the GyrB subunits, thereby resulting in dissociation of the hydrogel and dose- and time-dependent liberation of the entrapped protein pharmaceutical VEGF121 for triggering proliferation of human umbilical vein endothelial cells. Pharmacologically controlled hydrogels have the potential to fulfil the promises of stimuli-sensing materials as smart devices for spatiotemporally controlled delivery of drugs within the patient.

  18. INVESTIGATION OF DRUG RELEASE FROM BIODEGRADABLE PLG MICROSPHERES: EXPERIMENT AND THEORY

    Energy Technology Data Exchange (ETDEWEB)

    ANDREWS, MALCOLM J. [Los Alamos National Laboratory; BERCHANE, NADER S. [Los Alamos National Laboratory; CARSON, KENNETH H. [Los Alamos National Laboratory; RICE-FICHT, ALLISON C. [Los Alamos National Laboratory

    2007-01-30

    Piroxicam containing PLG microspheres having different size distributions were fabricated, and in vitro release kinetics were determined for each preparation. Based on the experimental results, a suitable mathematical theory has been developed that incorporates the effect of microsphere size distribution and polymer degradation on drug release. We show from in vitro release experiments that microsphere size has a significant effect on drug release rate. The initial release rate decreased with an increase in microsphere size. In addition, the release profile changed from first order to concave-upward (sigmoidal) as the system size was increased. The mathematical model gave a good fit to the experimental release data.

  19. Multifunctional Polymer Nanoparticles for Dual Drug Release and Cancer Cell Targeting

    Directory of Open Access Journals (Sweden)

    Yu-Han Wen

    2017-06-01

    Full Text Available Multifunctional polymer nanoparticles have been developed for cancer treatment because they could be easily designed to target cancer cells and to enhance therapeutic efficacy according to cancer hallmarks. In this study, we synthesized a pH-sensitive polymer, poly(methacrylic acid-co-histidine/doxorubicin/biotin (HBD in which doxorubicin (DOX was conjugated by a hydrazone bond to encapsulate an immunotherapy drug, imiquimod (IMQ, to form dual cancer-targeting and dual drug-loaded nanoparticles. At low pH, polymeric nanoparticles could disrupt and simultaneously release DOX and IMQ. Our experimental results show that the nanoparticles exhibited pH-dependent drug release behavior and had an ability to target cancer cells via biotin and protonated histidine.

  20. Improved antimicrobial property and controlled drug release kinetics of silver sulfadiazine loaded ordered mesoporous silica

    Directory of Open Access Journals (Sweden)

    Suman Jangra

    2016-09-01

    Full Text Available The present study deals with the loading of silver sulfadiazine into ordered mesoporous silica material by post-impregnation method and its effect on the in vitro release kinetics and antimicrobial property of the drug. The formulated SBA-15 silica material with rope-like morphology and SBA-15-silver sulfadiazine (SBA-AgSD were characterized by UV–visible spectrophotometer, small and wide-angle powder X-ray diffraction (PXRD, field emission scanning electron microscope (FESEM and high resolution transmission electron microscope (HRTEM. Thermo-gravimetric analysis of SBA-AgSD revealed a high loading amount of 52.87%. Nitrogen adsorption–desorption analysis confirmed the drug entrapment into host material by revealing a reduced surface area (214 m2/g and pore diameter (6.7 nm of the SBA-AgSD. The controlled release of silver sulfadiazine drug from the mesoporous silica to simulated gastric, intestinal and body fluids was evaluated. The Korsmeyer–Peppas model fits the drug release data with the non-Fickian diffusion model and zero order kinetics of SBA-AgSD. The antibacterial performance of the SBA-AgSD was evaluated with respect to Staphylococcus aureus, Bacillus subtilis and Pseudomonas aeruginosa. The controlled drug delivery of the SBA-AgSD revealed improved antibacterial activity, thus endorsing its applicability in effective wound dressing.

  1. 3D printed, controlled release, tritherapeutic tablet matrix for advanced anti-HIV-1 drug delivery.

    Science.gov (United States)

    Siyawamwaya, Margaret; du Toit, Lisa C; Kumar, Pradeep; Choonara, Yahya E; Kondiah, Pierre P P D; Pillay, Viness

    2018-04-12

    A 3D-Bioplotter® was employed to 3D print (3DP) a humic acid-polyquaternium 10 (HA-PQ10) controlled release fixed dose combination (FDC) tablet comprising of the anti-HIV-1 drugs, efavirenz (EFV), tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC). Chemical interactions, surface morphology and mechanical strength of the FDC were ascertained. In vitro drug release studies were conducted in biorelevant media followed by in vivo study in the large white pigs, in comparison with a market formulation, Atripla®. In vitro-in vivo correlation of results was undertaken. EFV, TDF and FTC were successfully entrapped in the 24-layered rectangular prism-shaped 3DP FDC with a loading of ∼12.5 mg/6.3 mg/4 mg of EFV/TDF/FTC respectively per printed layer. Hydrogen bonding between the EFV/TDF/FTC and HA-PQ10 was detected which was indicative of possible drug solubility enhancement. The overall surface of the tablet exhibited a fibrilla structure and the 90° inner pattern was determined to be optimal for 3DP of the FDC. In vitro and in vivo drug release profiles from the 3DP FDC demonstrated that intestinal-targeted and controlled drug release was achieved. A 3DP FDC was successfully manufactured with the aid of a 3D-Bioplotter in a single step process. The versatile HA-PQ10 entrapped all drugs and achieved an enhanced relative bioavailability of EFV, TDF, and FTC compared to the market formulation for potentially enhanced HIV treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Drug release characteristics of quercetin-loaded TiO2 nanotubes coated with chitosan.

    Science.gov (United States)

    Mohan, L; Anandan, C; Rajendran, N

    2016-12-01

    TiO 2 nanotubes formed by anodic oxidation of Ti-6Al-7Nb were loaded with quercetin (TNTQ) and chitosan was coated on the top of the quercetin (TNTQC) to various thicknesses. Field emission scanning electron microscopy (FESEM), 3D and 2D analyses were used to characterize the samples. The drug release studies of TNTQ and TNTQC were studied in Hanks' solution for 192h. The studies showed that the native oxide on the sample is substituted by self assembled nanotube arrays by anodisation. FESEM images of chitosan-loaded TNT samples showed that filling of chitosan takes place in inter-tubular space and pores. Drug release studies revealed that the release of drug into the local environment during that duration was constant. The local concentration of the drug can be controlled and tuned by controlling the thickness of the chitosan (0.6, 1 and 3μm) to fit into an optimal therapeutic window in order to treat postoperative infections, inflammation and for quick healing with better osseointegration of the titanium implants. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Drug Release Kinetics and Front Movement in Matrix Tablets Containing Diltiazem or Metoprolol/λ-Carrageenan Complexes

    Directory of Open Access Journals (Sweden)

    Ruggero Bettini

    2014-01-01

    Full Text Available In this work we investigated the moving boundaries and the associated drug release kinetics in matrix tablets prepared with two complexes between λ-carrageenan and two soluble model drugs, namely, diltiazem HCl and metoprolol tartrate aiming at clarifying the role played by drug/polymer interaction on the water uptake, swelling, drug dissolution, and drug release performance of the matrix. The two studied complexes released the drug with different mechanism indicating two different drug/polymer interaction strengths. The comparison between the drug release behaviour of the complexes and the relevant physical mixtures indicates that diltiazem gave rise to a less soluble and more stable complex with carrageenan than metoprolol. The less stable metoprolol complex afforded an erodible matrix, whereas the stronger interaction between diltiazem and carrageenan resulted in a poorly soluble, slowly dissolving matrix. It was concluded that the different stability of the studied complexes affords two distinct drug delivery systems: in the case of MTP, the dissociation of the complex, as a consequence of the interaction with water, affords a classical soluble matrix type delivery system; in the case of DTZ, the dissolving/diffusing species is the complex itself because of the very strong interaction between the drug and the polymer.

  4. Montmorillonite/Poly (L-Lactide microcomposite spheres as reservoirs of antidepressant drugs and their controlled release property

    Directory of Open Access Journals (Sweden)

    Shalini Rajkumar

    2015-10-01

    Full Text Available This work evaluates intercalation of Nortriptyline (NT and Venlafaxine (VFX in an interlayer gallery of Na+-MMT (Montmorillonite, which was further compounded with Poly (L-Lactide (PLLA to form microcomposite spheres (MPs for oral controlled drug delivery. The XRD patterns, thermal and spectroscopic analyses indicated intercalation of drugs into the MMT interlayer that was stabilized by electrostatic interaction. No significant changes in structural and functional properties of drugs were found in the MMT layers. In vitro drug release studies showed controlled release pattern.

  5. Ampicillin-Ester Bonded Branched Polymers: Characterization, Cyto-, Genotoxicity and Controlled Drug-Release Behaviour

    Directory of Open Access Journals (Sweden)

    Ewa Oledzka

    2014-06-01

    Full Text Available The development and characterization of novel macromolecular conjugates of ampicillin using branched biodegradable polymers has been described in this study. The conjugates have been prepared coupling the β-lactam antibiotic with branched polymer matrices based on the natural oligopeptide core. The cyto- and genotoxicity of the synthesized polymers were evaluated with a bacterial luminescence test, two protozoan assays and Salmonella typhimurium TA1535. The presence of a newly formed covalent bond between the drug and the polymer matrices was confirmed by 1H-NMR and FTIR studies. A drug content (15.6 and 10.2 mole % in the macromolecular conjugates has been determined. The obtained macromolecular products have been subjected to further in vitro release studies. The total percentage of ampicillin released after 21 days of incubation was nearly 60% and 14% and this resulted from the different physicochemical properties of the polymeric matrices. This is the first report on the application of branched biodegradable polymeric matrices for the covalent conjugation of ampicillin. The obtained results showed that the synthesized macromolecular drug-conjugates might slowly release the active drug molecule and improve the pharmacokinetics of ampicillin.

  6. A study of correlations between the release of drugs from petrolatum-based gels containing nonionic surfactants and some physical and physico-chemical characteristics of the gel systems.

    Science.gov (United States)

    Colo, G D; Nannipieri, E; Serafini, M F; Vitale, D

    1986-06-01

    Synopsis The in vitro release of benzocaine and 2-ethyIhexyl p-di-methylaminobenzoate (EH-PABA) from petrolatum-based gels either containing two nonionic surfactants, or not, was compared with some physical and/or physico-chemical characteristics of the drugs, the gels and the drug-gel systems. The surfactants had no effect on the release of EH-PABA, the less polar drug, whereas they decreased the release of benzocaine. Moreover, the release data show a complex dependence of diffusive properties of ben-zocaine on drug and surfactant concentration. Benzocaine appears to form mixed micelles with each of the two surfactants and/or undergoes self-aggregation phenomena within surfactant micelles. The results indicate that drug diffusion is influenced by gel porosity, drug molecular size and polarity and molecular interactions. Etude des corrélations entre la disponibilité des medicaments dans les gels a base de vaseline contenant des surfactifs non ioniques et quelques propriétés physiques et physicochimiques des gels.

  7. In-vitro Release Study of Carvedilol Phosphate Matrix Tablets ...

    African Journals Online (AJOL)

    decreased while Starch 1500 and lactose monohydrate increased drug release. Drug release mechanism ... case of antihypertensive agents to maintain constant blood levels ... systems because of their low toxicity, pH- independent swelling ...

  8. Drug-loaded electrospun mats of poly(vinyl alcohol) fibres and their release characteristics of four model drugs

    Science.gov (United States)

    Taepaiboon, Pattama; Rungsardthong, Uracha; Supaphol, Pitt

    2006-05-01

    Mats of PVA nanofibres were successfully prepared by the electrospinning process and were developed as carriers of drugs for a transdermal drug delivery system. Four types of non-steroidal anti-inflammatory drug with varying water solubility property, i.e. sodium salicylate (freely soluble in water), diclofenac sodium (sparingly soluble in water), naproxen (NAP), and indomethacin (IND) (both insoluble in water), were selected as model drugs. The morphological appearance of the drug-loaded electrospun PVA mats depended on the nature of the model drugs. The 1H-nuclear magnetic resonance results confirmed that the electrospinning process did not affect the chemical integrity of the drugs. Thermal properties of the drug-loaded electrospun PVA mats were analysed by differential scanning calorimetry and thermogravimetric analysis. The molecular weight of the model drugs played a major role on both the rate and the total amount of drugs released from the as-prepared drug-loaded electrospun PVA mats, with the rate and the total amount of the drugs released decreasing with increasing molecular weight of the drugs. Lastly, the drug-loaded electrospun PVA mats exhibited much better release characteristics of the model drugs than drug-loaded as-cast films.

  9. Thermal treating of acrylic matrices as a tool for controlling drug release.

    Science.gov (United States)

    Hasanzadeh, Davood; Ghaffari, Solmaz; Monajjemzadeh, Farnaz; Al-Hallak, M H D-Kamal; Soltani, Ghazal; Azarmi, Shirzad

    2009-12-01

    The purpose of the present study was to investigate the effect of thermal-treating on the release of ibuprofen from the granules prepared using aqueous dispersions of Eudragit. To accomplish this goal, different formulations were prepared using wet granulation method containing two different types of Eudragit aqueous dispersions, RS30D, RL30D and Avicel as filler. Tablets were prepared using direct compression method. The prepared tablets were thermally treated at 50 and 70 degrees C for 24 h. The drug release from tablets was assessed before and after thermal-treating. The results of release study showed that, thermally-treating the tablets at the temperatures higher than glass transition temperature (Tg) of the polymer can decrease the drug release from matrices. For mechanistic evaluation of the effect of thermal-treating, powder X-ray diffraction (XPD), scanning electron microscopy (SEM), differential scanning calorimeter (DSC), Fourier transform infrared (FT-IR) and helium pycnometer have been employed. The SEM graphs showed that the tablets have smoother surface with less porosity after thermal-treating. FT-IR spectra showed no change in the spectrum of thermally-treated tablet compared to control. In DSC graphs, no crystalline change was seen in the heat-treated samples of ibuprofen tablets, but decreased and widened peak size were related to the probable formation of solid solution of ibuprofen in Eudragit matrix. The results of helium pycnometer showed a significant decrease in the total porosity of some heat-treated samples. This study revealed the importance of thermal treating on the drug release from sustained release tablets containing Eudragit polymer.

  10. Bioactive Glass Nanoparticles as a New Delivery System for Sustained 5-Fluorouracil Release: Characterization and Evaluation of Drug Release Mechanism

    Directory of Open Access Journals (Sweden)

    Abeer M. El-Kady

    2015-01-01

    Full Text Available Bioactive glass nanoparticles were synthesized and tested for the first time as a new delivery system for sustained 5-fluorouracil (5-FU release. They were characterized by TEM, DTA, TGA, and FT-IR. The porosity % and specific surface area of glass nanoparticles were 85.59% and 378.36 m2/g, respectively. The in vitro bioactivity evaluation confirmed that bioactive glass disks prepared from these nanoparticles could induce hydroxyapatite layer over their surfaces in simulated body fluid. The in vitro drug release experiment indicated that glass nanoparticles could serve as long-term local delivery vehicles for sustained 5-FU release. The release profile of 5-FU showed an initial fast release stage followed by a second stage of slower release. The initial burst release of 5-FU in the first day was about 23% (28.92 mg·L−1 of the total amount of loaded 5-FU, while the final cumulative percentage of the 5-FU released after 32 days was about 45.6% (57.31 mg·L−1 of the total amount of loaded 5-FU. The application of different mathematical models indicated that 5-FU was released by diffusion controlled mechanism and suggested that its release rate was dependent on glass particles dissolution, changes of surface area as well as diameter of glass particles, and concentration of loaded drug.

  11. Cyclodextrin-containing hydrogels as an intraocular lens for sustained drug release.

    Directory of Open Access Journals (Sweden)

    Xiao Li

    Full Text Available To improve the efficacy of anti-inflammatory factors in patients who undergo cataract surgery, poly(2-hydroxyethyl methacrylate-co-methyl methacrylate (p(HEMA-co-MMA hydrogels containing β-cyclodextrin (β-CD (pHEMA/MMA/β-CD were designed and prepared as intraocular lens (IOLs biomaterials that could be loaded with and achieve the sustained release of dexamethasone. A series of pHEMA/MMA/β-CD copolymers containing different ratios of β-CD (range, 2.77 to 10.24 wt.% were obtained using thermal polymerization. The polymers had high transmittance at visible wavelengths and good biocompatibility with mouse connective tissue fibroblasts. Drug loading and release studies demonstrated that introducing β-CD into hydrogels increased loading efficiency and achieved the sustained release of the drug. Administering β-CD via hydrogels increased the equilibrium swelling ratio, elastic modulus and tensile strength. In addition, β-CD increased the hydrophilicity of the hydrogels, resulting in a lower water contact angle and higher cellular adhesion to the hydrogels. In summary, pHEMA/MMA/β-CD hydrogels show great potential as IOL biomaterials that are capable of maintaining the sustained release of anti-inflammatory drugs after cataract surgery.

  12. Chitosan/alginate based multilayers to control drug release from ophthalmic lens.

    Science.gov (United States)

    Silva, Diana; Pinto, Luís F V; Bozukova, Dimitriya; Santos, Luís F; Serro, Ana Paula; Saramago, Benilde

    2016-11-01

    In this study we investigated the possibility of using layer-by-layer deposition, based in natural polymers (chitosan and alginate), to control the release of different ophthalmic drugs from three types of lens materials: a silicone-based hydrogel recently proposed by our group as drug releasing soft contact lens (SCL) material and two commercially available materials: CI26Y for intraocular lens (IOLs) and Definitive 50 for SCLs. The optimised coating, consisting in one double layer of (alginate - CaCl2)/(chitosan+glyoxal) topped with a final alginate-CaCl2 layer to avoid chitosan degradation by tear fluid proteins, proved to have excellent features to control the release of the anti-inflammatory, diclofenac, while keeping or improving the physical properties of the lenses. The coating leads to a controlled release of diclofenac from SCL and IOL materials for, at least, one week. Due to its high hydrophilicity (water contact angle≈0) and biocompatibility, it should avoid the use of further surface treatments to enhance the useŕs comfort. However, the barrier effect of this coating is specific for diclofenac, giving evidence to the need of optimizing the chemical composition of the layers in view of the desired drug. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Drug delivery systems with modified release for systemic and biophase bioavailability.

    Science.gov (United States)

    Leucuta, Sorin E

    2012-11-01

    This review describes the most important new generations of pharmaceutical systems: medicines with extended release, controlled release pharmaceutical systems, pharmaceutical systems for the targeted delivery of drug substances. The latest advances and approaches for delivering small molecular weight drugs and other biologically active agents such as proteins and nucleic acids require novel delivery technologies, the success of a drug being many times dependent on the delivery method. All these dosage forms are qualitatively superior to medicines with immediate release, in that they ensure optimal drug concentrations depending on specific demands of different disease particularities of the body. Drug delivery of these pharmaceutical formulations has the benefit of improving product efficacy and safety, as well as patient convenience and compliance. This paper describes the biopharmaceutical, pharmacokinetic, pharmacologic and technological principles in the design of drug delivery systems with modified release as well as the formulation criteria of prolonged and controlled release drug delivery systems. The paper presents pharmaceutical prolonged and controlled release dosage forms intended for different routes of administration: oral, ocular, transdermal, parenteral, pulmonary, mucoadhesive, but also orally fast dissolving tablets, gastroretentive drug delivery systems, colon-specific drug delivery systems, pulsatile drug delivery systems and carrier or ligand mediated transport for site specific or receptor drug targeting. Specific technologies are given on the dosage forms with modified release as well as examples of marketed products, and current research in these areas.

  14. Nonlinearities in Drug Release Process from Polymeric Microparticles: Long-Time-Scale Behaviour

    Directory of Open Access Journals (Sweden)

    Elena Simona Bacaita

    2012-01-01

    Full Text Available A theoretical model of the drug release process from polymeric microparticles (a particular type of polymer matrix, through dispersive fractal approximation of motion, is built. As a result, the drug release process takes place through cnoidal oscillations modes of a normalized concentration field. This indicates that, in the case of long-time-scale evolutions, the drug particles assemble in a lattice of nonlinear oscillators occur macroscopically, through variations of drug concentration. The model is validated by experimental results.

  15. In situ synthesis of magnetic CaraPVA IPN nanocomposite hydrogels and controlled drug release

    International Nuclear Information System (INIS)

    Mahdavinia, Gholam Reza; Etemadi, Hossein

    2014-01-01

    In this work, the magnetic nanocomposite hydrogels that focused on targeted drug delivery were synthesized by incorporation of polyvinyl alcohol (PVA), kappa-carrageenan (Cara), and magnetite Fe 3 O 4 nanoparticles. The magnetic nanoparticles were obtained in situ in the presence of a mixture of polyvinyl alcohol/kappa-carrageenan (CaraPVA). The produced magnetite-polymers were cross-linked with freezing–thawing technique and subsequent with K + solution. The synthesized hydrogels were thoroughly characterized by transmittance electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), thermal gravimetric analysis (TGA), Fourier transform infrared spectroscopy (FT-IR), and vibrating sample magnetometer (VSM) techniques. The dynamic swelling kinetic models of hydrogels were analyzed according to the first- and second-order kinetic models and were found that the experimental kinetics data followed the second-order model well. Drug loading and release efficiency were evaluated by diclofenac sodium (DS) as the model drug. The in vitro drug release studies from hydrogels exhibited significant behaviors on the subject of physiological simulated pHs and external magnetic fields. Investigation on the antibacterial activity revealed the ability of drug-loaded hydrogels to inactivate the Gram-positive Staphylococcus aureus (S. aureus) bacteria. The mucoadhesive properties of the hydrogels were studied and the hydrogels containing kappa-carrageenan showed good mucoadhesiveness in both simulated gastric and intestinal conditions. - Highlights: • In situ synthesis of magnetic kappa-carrageenan/PVA nanocomposite hydrogel. • Low salt sensitivity of magnetic nanocomposite hydrogels was observed. • The release of diclofenac sodium from hydrogels was pH-dependent. • The release of diclofenac sodium from magnetic hydrogels was affected by external magnetic field. • The hydrogels containing carrageenan component showed high mucoadhesiveness

  16. In situ synthesis of magnetic CaraPVA IPN nanocomposite hydrogels and controlled drug release

    Energy Technology Data Exchange (ETDEWEB)

    Mahdavinia, Gholam Reza, E-mail: grmnia@maragheh.ac.ir; Etemadi, Hossein

    2014-12-01

    In this work, the magnetic nanocomposite hydrogels that focused on targeted drug delivery were synthesized by incorporation of polyvinyl alcohol (PVA), kappa-carrageenan (Cara), and magnetite Fe{sub 3}O{sub 4} nanoparticles. The magnetic nanoparticles were obtained in situ in the presence of a mixture of polyvinyl alcohol/kappa-carrageenan (CaraPVA). The produced magnetite-polymers were cross-linked with freezing–thawing technique and subsequent with K{sup +} solution. The synthesized hydrogels were thoroughly characterized by transmittance electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), thermal gravimetric analysis (TGA), Fourier transform infrared spectroscopy (FT-IR), and vibrating sample magnetometer (VSM) techniques. The dynamic swelling kinetic models of hydrogels were analyzed according to the first- and second-order kinetic models and were found that the experimental kinetics data followed the second-order model well. Drug loading and release efficiency were evaluated by diclofenac sodium (DS) as the model drug. The in vitro drug release studies from hydrogels exhibited significant behaviors on the subject of physiological simulated pHs and external magnetic fields. Investigation on the antibacterial activity revealed the ability of drug-loaded hydrogels to inactivate the Gram-positive Staphylococcus aureus (S. aureus) bacteria. The mucoadhesive properties of the hydrogels were studied and the hydrogels containing kappa-carrageenan showed good mucoadhesiveness in both simulated gastric and intestinal conditions. - Highlights: • In situ synthesis of magnetic kappa-carrageenan/PVA nanocomposite hydrogel. • Low salt sensitivity of magnetic nanocomposite hydrogels was observed. • The release of diclofenac sodium from hydrogels was pH-dependent. • The release of diclofenac sodium from magnetic hydrogels was affected by external magnetic field. • The hydrogels containing carrageenan component showed high

  17. Understanding release kinetics of biopolymer drug delivery microcapsules for biomedical applications

    International Nuclear Information System (INIS)

    Desai, Salil; Perkins, Jessica; Harrison, Benjamin S.; Sankar, Jag

    2010-01-01

    Drug delivery and dosage concentrations are considered as major focal points in conventional as well as battlefield emergency medicine. The concept of localizing drug delivery via microcapsules is an evolving field to confine the adverse side effects of high concentration drug doses. This paper focuses on understanding release kinetics through biopolymer microcapsules for time-dependent drug release. Calcium alginate microcapsules were manufactured using a direct-write inkjet technique. Rhodamine 6G was used as the release agent to observe the release kinetics from calcium alginate beads in distilled water. A design of experiments was constructed to compare the effect of the microcapsule diameter and different concentrations of calcium chloride (M) and sodium alginate (%, w/v) solutions on the release kinetics profiles of the microcapsules. This research gives insight to identify favorable sizes of microcapsules and concentrations of sodium alginate and calcium chloride solutions for controlled release behavior of drug delivery microcapsules.

  18. Setting accelerated dissolution test for PLGA microspheres containing peptide, investigation of critical parameters affecting drug release rate and mechanism.

    Science.gov (United States)

    Tomic, I; Vidis-Millward, A; Mueller-Zsigmondy, M; Cardot, J-M

    2016-05-30

    The objective of this study was development of accelerated in vitro release method for peptide loaded PLGA microspheres using flow-through apparatus and assessment of the effect of dissolution parameters (pH, temperature, medium composition) on drug release rate and mechanism. Accelerated release conditions were set as pH 2 and 45°C, in phosphate buffer saline (PBS) 0.02M. When the pH was changed from 2 to 4, diffusion controlled phases (burst and lag) were not affected, while release rate during erosion phase decreased two-fold due to slower ester bonds hydrolyses. Decreasing temperature from 45°C to 40°C, release rate showed three-fold deceleration without significant change in release mechanism. Effect of medium composition on drug release was tested in PBS 0.01M (200 mOsm/kg) and PBS 0.01M with glucose (380 mOsm/kg). Buffer concentration significantly affected drug release rate and mechanism due to the change in osmotic pressure, while ionic strength did not have any effect on peptide release. Furthermore, dialysis sac and sample-and-separate techniques were used, in order to evaluate significance of dissolution technique choice on the release process. After fitting obtained data to different mathematical models, flow-through method was confirmed as the most appropriate for accelerated in vitro dissolution testing for a given formulation. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. A reappraisal of drug release laws using Monte Carlo simulations: the prevalence of the Weibull function.

    Science.gov (United States)

    Kosmidis, Kosmas; Argyrakis, Panos; Macheras, Panos

    2003-07-01

    To verify the Higuchi law and study the drug release from cylindrical and spherical matrices by means of Monte Carlo computer simulation. A one-dimensional matrix, based on the theoretical assumptions of the derivation of the Higuchi law, was simulated and its time evolution was monitored. Cylindrical and spherical three-dimensional lattices were simulated with sites at the boundary of the lattice having been denoted as leak sites. Particles were allowed to move inside it using the random walk model. Excluded volume interactions between the particles was assumed. We have monitored the system time evolution for different lattice sizes and different initial particle concentrations. The Higuchi law was verified using the Monte Carlo technique in a one-dimensional lattice. It was found that Fickian drug release from cylindrical matrices can be approximated nicely with the Weibull function. A simple linear relation between the Weibull function parameters and the specific surface of the system was found. Drug release from a matrix, as a result of a diffusion process assuming excluded volume interactions between the drug molecules, can be described using a Weibull function. This model, although approximate and semiempirical, has the benefit of providing a simple physical connection between the model parameters and the system geometry, which was something missing from other semiempirical models.

  20. Electrospinning of doxorubicin loaded silica/poly(ɛ-caprolactone) hybrid fiber mats for sustained drug release

    Science.gov (United States)

    El Gohary, Mohammed I.; El Hady, Bothaina M. Abd; Saeed, Aziza A. Al; Tolba, Emad; El Rashedi, Ahlam M. I.; Saleh, Safaa

    2018-06-01

    Loading of anticancer drugs into electrospun fiber matrices is a portentous approach for clinical treatment of diseased tissues or organs. In this study, doxorubicin hydrochloride (DOX) is added to silica nanoparticles () during the formation of via the sol-gel approach. The obtained nanoparticles are then added to poly(-caprolactone) (PCL) and poly(ethylene oxide) (PEO) blend before electrospinning process via different methods. The effects of DOX addition as a free form or as nanoparticles on physical and chemical properties of obtained PCL-PEO fibers, as well as release profiles are evaluated to give a continual DOX release for several days. The morphology observed with scanning electron microscope (FESEM) revealed significant changes in the average diameter of obtained fibers ranging from 2164 nm to 659 nm and distribution of drug-loaded nanoparticles in the final mats according to the mode of additions. With the same manner, the releasing performances of obtained mats are quite different. Therefore, fabrication of drug loaded mats would offer a powerful approach to minimize serious side effects for clinical patients and allows us to control the drug concentration in the bloodstream.

  1. Chitosan-Gated Magnetic-Responsive Nanocarrier for Dual-Modal Optical Imaging, Switchable Drug Release, and Synergistic Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hui [Department of Materials Science and Engineering, University of Washington, Seattle WA 98195 USA; Mu, Qingxin [Department of Materials Science and Engineering, University of Washington, Seattle WA 98195 USA; Revia, Richard [Department of Materials Science and Engineering, University of Washington, Seattle WA 98195 USA; Wang, Kui [Department of Materials Science and Engineering, University of Washington, Seattle WA 98195 USA; Zhou, Xuezhe [Department of Materials Science and Engineering, University of Washington, Seattle WA 98195 USA; Pauzauskie, Peter J. [Department of Materials Science and Engineering, University of Washington, Seattle WA 98195 USA; Fundamental and Computational Sciences Directorate, Pacific Northwest National Laboratory, Richland WA 99354 USA; Zhou, Shuiqin [Department of Chemistry, The College of Staten Island, City University of New York, Staten Island NY 10314 USA; Zhang, Miqin [Department of Materials Science and Engineering, University of Washington, Seattle WA 98195 USA

    2017-01-25

    In this study, we present a multifunctional yet structurally simple nanocarrier that has a high drug loading capacity, releases drug in response to onset of an AC magnetic field, and can serve as a long-term imaging contrast agent and effectively kills cancer cells by synergistic action. This nanocarrier (HMMC-NC) has a spherical shell structure with a center cavity of 80 nm in diameter. The shell is comprised of two layers: an inner layer of magnetite that exhibits superparamagnetism and an outer layer of mesoporous carbon embedded with carbon dots that exhibit photoluminescence property. Thus in addition to being a drug carrier, HMMC-NC is also a contrast agent for bioimaging. The switchable drug release is enabled by the chitosan molecules attached on the nanocarrier as the switching material which turns on or off the drug release in response to the application or withdrawal of an AC magnetic field.

  2. Sodium lauryl sulfate impedes drug release from zinc-crosslinked alginate beads: switching from enteric coating release into biphasic profiles.

    Science.gov (United States)

    Taha, Mutasem O; Nasser, Wissam; Ardakani, Adel; Alkhatib, Hatim S

    2008-02-28

    The aim of this research is to investigate the effects of sodium lauryl sulfate (SLS) on ionotropically cross-linked alginate beads. Different levels of SLS were mixed with sodium alginate and chlorpheniramine maleate (as loaded model drug). The resulting viscous solutions were dropped onto aqueous solutions of zinc or calcium ions for ionotropic curing. The generated beads were assessed by their drug releasing profiles, infrared and differential scanning colorimetery (DSC) traits. SLS was found to exert profound concentration-dependent impacts on the characteristics of zinc-crosslinked alginate beads such that moderate modifications in the levels of SLS switched drug release from enteric coating-like behavior to a biphasic release modifiable to sustained-release by the addition of minute amounts of xanthan gum. Calcium cross-linking failed to reproduce the same behavior, probably due to the mainly ionic nature of calcium-carboxylate bonds compared to the coordinate character of their zinc-carboxylate counterparts. Apparently, moderate levels of SLS repel water penetration into the beads, and therefore minimize chlorpheniramine release. However, higher SLS levels seem to discourage polymeric cross-linking and therefore allow biphasic drug release.

  3. Competitive release of drug resistance following drug treatment of mixed Plasmodium chabaudi infections.

    Science.gov (United States)

    de Roode, Jacobus C; Culleton, Richard; Bell, Andrew S; Read, Andrew F

    2004-09-14

    Malaria infections are often genetically diverse, potentially leading to competition between co-infecting strains. Such competition is of key importance in the spread of drug resistance. The effects of drug treatment on within-host competition were studied using the rodent malaria Plasmodium chabaudi. Mice were infected simultaneously with a drug-resistant and a drug-sensitive clone and were then either drug-treated or left untreated. Transmission was assessed by feeding mice to Anopheles stephensi mosquitoes. In the absence of drugs, the sensitive clone competitively suppressed the resistant clone; this resulted in lower asexual parasite densities and also reduced transmission to the mosquito vector. Drug treatment, however, allowed the resistant clone to fill the ecological space emptied by the removal of the sensitive clone, allowing it to transmit as well as it would have done in the absence of competition. These results show that under drug pressure, resistant strains can have two advantages: (1) they survive better than sensitive strains and (2) they can exploit the opportunities presented by the removal of their competitors. When mixed infections are common, such effects could increase the spread of drug resistance.

  4. Improved Tumor-Specific Drug Accumulation by Polymer Therapeutics with pH-Sensitive Drug Release Overcomes Chemotherapy Resistance.

    Science.gov (United States)

    Heinrich, Anne-Kathrin; Lucas, Henrike; Schindler, Lucie; Chytil, Petr; Etrych, Tomáš; Mäder, Karsten; Mueller, Thomas

    2016-05-01

    The success of chemotherapy is limited by poor selectivity of active drugs combined with occurrence of tumor resistance. New star-like structured N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based drug delivery systems containing doxorubicin attached via a pH-sensitive hydrazone bond were designed and investigated for their ability to overcome chemotherapy resistance. These conjugates combine two strategies to achieve a high drug concentration selectively at the tumor site: (I) high accumulation by passive tumor targeting based on enhanced permeability and retention effect and (II) pH-sensitive site-specific drug release due to an acidic tumor microenvironment. Mice bearing doxorubicin-resistant xenograft tumors were treated with doxorubicin, PBS, poly HPMA (pHPMA) precursor or pHPMA-doxorubicin conjugate at different equivalent doses of 5 mg/kg bodyweight doxorubicin up to a 7-fold total dose using different treatment schedules. Intratumoral drug accumulation was analyzed by fluorescence imaging utilizing intrinsic fluorescence of doxorubicin. Free doxorubicin induced significant toxicity but hardly any tumor-inhibiting effects. Administering at least a 3-fold dose of pHPMA-doxorubicin conjugate was necessary to induce a transient response, whereas doses of about 5- to 6-fold induced strong regressions. Tumors completely disappeared in some cases. The onset of response was differential delayed depending on the tumor model, which could be ascribed to distinct characteristics of the microenvironment. Further fluorescence imaging-based analyses regarding underlying mechanisms of the delayed response revealed a related switch to a more supporting intratumoral microenvironment for effective drug release. In conclusion, the current study demonstrates that the concept of tumor site-restricted high-dose chemotherapy is able to overcome therapy resistance. Mol Cancer Ther; 15(5); 998-1007. ©2016 AACR. ©2016 American Association for Cancer Research.

  5. Formulation and optimization of pH sensitive drug releasing O/W emulsions using Albizia lebbeck L. seed polysaccharide.

    Science.gov (United States)

    Varma, Chekuri Ashok Kumar; Jayaram Kumar, K

    2018-04-30

    Smart polymers, one of the class of polymers with extensive growth in the last few decades due to their wide applications in drug targeting and controlled delivery systems. With this in mind, the aim of the present study is to design and formulate smart releasing o/w emulsion by using Albizia lebbeck L. seed polysaccharide (ALPS). For this purpose, the physicochemical and drug release characteristics like emulsion capacity (EC), emulsion stability (ES), viscosity, microscopy, zeta potential, polydispersity index (PDI) and in-vitro drug release were performed. The EC and ES values were found to increase with an increased concentration of ALPS. The emulsion formulations were statistically designed by using 3 2 full factorial design. All the emulsions showed a shear-thinning behavior. The zeta potential and polydispersity index were found to be in the range of -35.83 mV to -19.00 mV and 0.232-1.000 respectively. Further, the percent cumulative drug release of the emulsions at 8 h was found to be in the range of 30.19-82.65%. The drug release profile exhibited zero order release kinetics. In conclusion, the ALPS can be used as a natural emulsifier and smart polymer for the preparation of pH sensitive emulsions in drug delivery systems. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Correlation between the viscoelastic properties of the gel layer of swollen HPMC matrix tablets and their in vitro drug release.

    Science.gov (United States)

    Hamed, Rania; Al Baraghthi, Tamadur; Sunoqrot, Suhair

    2016-11-21

    Drug release from hydroxypropyl methylcellulose (HPMC) hydrophilic matrix tablets is controlled by drug diffusion through the gel layer of the matrix-forming polymer upon hydration, matrix erosion or combination of diffusion and erosion mechanisms. In this study, the relationship between viscoelastic properties of the gel layer of swollen intact matrix tablets and drug release was investigated. Two sets of quetiapine fumarate (QF) matrix tablets were prepared using the high viscosity grade HPMC K4M at low (70 mg/tablet) and high (170 mg/tablet) polymer concentrations. Viscoelastic studies using a controlled stress rheometer were performed on swollen matrices following hydration in the dissolution medium for predetermined time intervals. The gel layer of swollen tablets exhibited predominantly elastic behavior. Results from the in vitro release study showed that drug release was strongly influenced by the viscoelastic properties of the gel layer of K4M tablets, which was further corroborated by results from water uptake studies conducted on intact tablets. The results provide evidence that the viscoelastic properties of the gel layer can be exploited to guide the selection of an appropriate matrix-forming polymer, to better understand the rate of drug release from matrix tablets in vitro and to develop hydrophilic controlled-release formulations.

  7. Photocuring of stimulus responsive membranes for controlled-release of drugs having different molecular weights

    International Nuclear Information System (INIS)

    Ng, Loo-Teck; Nakayama, Hiroshi; Kaetsu, Isao; Uchida, Kumao

    2005-01-01

    Intelligent drug delivery membranes were prepared by photocuring poly(acrylic acid) coatings onto poly(2-hydroxyethyl methacrylate) membranes each with model drugs of different molecular weights being incorporated. pH-responsive release behaviours of the model drugs which included sodium salicylate, nicotinamide, nicotinic acid, methylene blue, brilliant green and crystal violet were investigated. Only the membrane with methylene blue incorporated showed a clear pH-responsive release and other drug-incorporated membranes showed no intelligent behaviour. These phenomena were explained in terms of the difference in diffusivity of drugs through polymer matrices of the membranes attributable to the difference in the molecular weights of drugs

  8. Photocuring of stimulus responsive membranes for controlled-release of drugs having different molecular weights

    Energy Technology Data Exchange (ETDEWEB)

    Ng, Loo-Teck [School of Science, Food and Horticulture, University of Western Sydney, Locked bag 1797, Penrith South DC, NSW 1797 (Australia)]. E-mail: l.ng@uws.edu.au; Nakayama, Hiroshi [Department of Nuclear Engineering, Faculty of Science and technology, Kinki University, Kowakae, 3-4-1, Higashi-Osaka 577-8502 (Japan); Kaetsu, Isao [Department of Nuclear Engineering, Faculty of Science and technology, Kinki University, Kowakae, 3-4-1, Higashi-Osaka 577-8502 (Japan)]. E-mail: kaetsu@ned.kindai.ac.jp; Uchida, Kumao [Department of Nuclear Engineering, Faculty of Science and technology, Kinki University, Kowakae, 3-4-1, Higashi-Osaka 577-8502 (Japan)

    2005-06-01

    Intelligent drug delivery membranes were prepared by photocuring poly(acrylic acid) coatings onto poly(2-hydroxyethyl methacrylate) membranes each with model drugs of different molecular weights being incorporated. pH-responsive release behaviours of the model drugs which included sodium salicylate, nicotinamide, nicotinic acid, methylene blue, brilliant green and crystal violet were investigated. Only the membrane with methylene blue incorporated showed a clear pH-responsive release and other drug-incorporated membranes showed no intelligent behaviour. These phenomena were explained in terms of the difference in diffusivity of drugs through polymer matrices of the membranes attributable to the difference in the molecular weights of drugs.

  9. Near-infrared induced release for localized on-demand drug delivery

    NARCIS (Netherlands)

    Vertommen, M.A.M.E.

    2009-01-01

    By non-invasive external triggering of drug release from an implant, pulsewise administration can be realized according to the patient’s needs and at specific locations in the human body. In comparison to more traditional delivery forms (e.g. oral or by injection), externally triggered drug release

  10. Effect of micropatterning induced surface hydrophobicity on drug release from electrospun cellulose acetate nanofibers

    Science.gov (United States)

    Adepu, Shivakalyani; Gaydhane, Mrunalini K.; Kakunuri, Manohar; Sharma, Chandra S.; Khandelwal, Mudrika; Eichhorn, Stephen J.

    2017-12-01

    Sustained release and prevention of burst release for low half-life drugs like Diclofenac sodium is crucial to prevent drug related toxicity. Electrospun nanofibers have emerged recently as potential carrier materials for controlled and sustained drug release. Here, we present a facile method to prevent burst release by tuning the surface wettability through template assisted micropatterning of drug loaded electrospun cellulose acetate (CA) nanofibers. A known amount of drug (Diclofenac sodium) was first mixed with CA and then electrospun in the form of a nanofabric. This as-spun network was hydrophilic in nature. However, when electrospinning was carried out through non-conducting templates, viz nylon meshes with 50 and 100 μm size openings, two kinds of hydrophobic micro-patterned CA nanofabrics were produced. In vitro transdermal testing of our nanofibrous mats was carried out; these tests were able to show that it would be possible to create a patch for transdermal drug release. Further, our results show that with optimized micro-patterned dimensions, a zero order sustained drug release of up to 12 h may be achieved for the transdermal system when compared to non-patterned samples. This patterning caused a change in the surface wettability, to a hydrophobic surface, resulting in a controlled diffusion of the hydrophilic drug. Patterning assisted in controlling the initial burst release, which is a significant finding especially for low half-life drugs.

  11. Relationship among reaction rate, release rate and efficiency of nanomachine-based targeted drug delivery.

    Science.gov (United States)

    Zhao, Qingying; Li, Min; Luo, Jun

    2017-12-04

    In nanomachine applications towards targeted drug delivery, drug molecules released by nanomachines propagate and chemically react with tumor cells in aqueous environment. If the nanomachines release drug molecules faster than the tumor cells react, it will result in loss and waste of drug molecules. It is a potential issue associated with the relationship among reaction rate, release rate and efficiency. This paper aims to investigate the relationship among reaction rate, release rate and efficiency based on two drug reception models. We expect to pave a way for designing a control method of drug release. We adopted two analytical methods that one is drug reception process based on collision with tumors and another is based on Michaelis Menten enzymatic kinetics. To evaluate the analytical formulations, we used the well-known simulation framework N3Sim to establish simulations. The analytical results of the relationship among reaction rate, release rate and efficiency is obtained, which match well with the numerical simulation results in a 3-D environment. Based upon two drug reception models, the results of this paper would be beneficial for designing a control method of nanomahine-based drug release.

  12. An investigation into the mechanisms of drug release from taste-masking fatty acid microspheres.

    Science.gov (United States)

    Qi, Sheng; Deutsch, David; Craig, Duncan Q M

    2008-09-01

    Fatty acid microspheres based on stearic and palmitic acids are known to form effective taste masking systems, although the mechanisms by which the drug is preferentially released in the lower gastrointestinal tract are not known. The objective of the present study was to identify the mechanisms involved, with a particular view to clarify the role of acid soap formation in the dissolution process. Microspheres were prepared by a spray chilling process. Using benzoic acid as a model drug and an alkaline dissolution medium, a faster drug release was observed in the mixed fatty acid formulation (50:50 stearic:palmitic acid (w/w)) compared to the single fatty acid component systems. Thermal and powder X-ray diffraction studies indicated a greater degree of acid soap formation for the mixed formulation in alkaline media compared to the single fatty acid systems. Particle size and porosity studies indicated a modest reduction in size for the mixed systems and an increase in porosity on immersion in the dissolution medium. It is proposed that the mixed fatty acid system form a mixed crystal system which in turn facilitates interaction with the dissolution medium, thereby leading to a greater propensity for acid soap formation which in turn forms a permeable liquid crystalline phase through which the drug may diffuse. The role of dissolution of palmitic acid into the dissolution medium is also discussed as a secondary mechanism.

  13. The production of volvox spheres and their potential application in multi-drugs encapsulation and release

    Energy Technology Data Exchange (ETDEWEB)

    Teong, Benjamin; Chang, Shwu Jen [Department of Biomedical Engineering, I-Shou University, College of Medicine, No. 8, Yida Rd., Jiaosu Village, Yanchao District, Kaohsiung City 82445, Taiwan (China); Chuang, Chin Wen [Department of Electrical Engineering, I-Shou University, No. 1, Sec. 1, Syuecheng Rd., Dashu District, Kaohsiung City 84001, Taiwan (China); Kuo, Shyh Ming, E-mail: smkuo@isu.edu.tw [Department of Biomedical Engineering, I-Shou University, College of Medicine, No. 8, Yida Rd., Jiaosu Village, Yanchao District, Kaohsiung City 82445, Taiwan (China); Manousakas, Ioannis, E-mail: i.manousakas@ieee.org [Department of Biomedical Engineering, I-Shou University, College of Medicine, No. 8, Yida Rd., Jiaosu Village, Yanchao District, Kaohsiung City 82445, Taiwan (China)

    2013-12-01

    Volvox sphere is a bio-mimicking concept of an innovative biomaterial structure of a sphere that contains smaller microspheres which then encapsulate chemicals, drugs and/or cells. The volvox spheres were produced via a high-voltage electrostatic field system, using alginate as the primary material. Encapsulated materials tested in this study include staining dyes, nuclear fast red and trypan blue, and model drugs, bovine serum albumin (BSA) and cytochrome c (CytC). The external morphology of the volvox spheres was observed via electron microscopy whereas the internal structure of the volvox spheres was observed via an optical microscope with the aid of the staining dyes, since alginate is colorless and transparent. The diameter of the microspheres was about 200 to 300 μm, whereas the diameter of the volvox spheres was about 1500 μm. Volvox spheres were durable, retaining about 95% of their mass after 4 weeks. Factors affecting entrapment efficiency, such as temperature and concentration of the bivalent cross-linker, were compared followed by a 7-day in vitro release study. The encapsulation efficiency of CytC within the microspheres was higher at cold (∼ 4 °C) and warm (∼ 50 °C) temperatures whereas temperature has no obvious effect on the BSA encapsulation. High crosslinking concentration (25% w/v) of calcium chloride has resulted higher entrapment efficiency for BSA but not for CytC. Furthermore, volvox spheres showed a different release pattern of BSA and CytC when compared to microspheres encapsulating BSA and CytC. Despite the fact that the mechanisms behind remain unclear and further investigation is required, this study demonstrates the potential of the volvox spheres for drug delivery. - Highlights: • Volvox spheres contain smaller microspheres which can encapsulate drugs and/or cells. • Alginate is the primary material for the inner and outer spheres. • Encapsulation is affected by the crosslinking, temperature and the selection of drugs.

  14. The production of volvox spheres and their potential application in multi-drugs encapsulation and release

    International Nuclear Information System (INIS)

    Teong, Benjamin; Chang, Shwu Jen; Chuang, Chin Wen; Kuo, Shyh Ming; Manousakas, Ioannis

    2013-01-01

    Volvox sphere is a bio-mimicking concept of an innovative biomaterial structure of a sphere that contains smaller microspheres which then encapsulate chemicals, drugs and/or cells. The volvox spheres were produced via a high-voltage electrostatic field system, using alginate as the primary material. Encapsulated materials tested in this study include staining dyes, nuclear fast red and trypan blue, and model drugs, bovine serum albumin (BSA) and cytochrome c (CytC). The external morphology of the volvox spheres was observed via electron microscopy whereas the internal structure of the volvox spheres was observed via an optical microscope with the aid of the staining dyes, since alginate is colorless and transparent. The diameter of the microspheres was about 200 to 300 μm, whereas the diameter of the volvox spheres was about 1500 μm. Volvox spheres were durable, retaining about 95% of their mass after 4 weeks. Factors affecting entrapment efficiency, such as temperature and concentration of the bivalent cross-linker, were compared followed by a 7-day in vitro release study. The encapsulation efficiency of CytC within the microspheres was higher at cold (∼ 4 °C) and warm (∼ 50 °C) temperatures whereas temperature has no obvious effect on the BSA encapsulation. High crosslinking concentration (25% w/v) of calcium chloride has resulted higher entrapment efficiency for BSA but not for CytC. Furthermore, volvox spheres showed a different release pattern of BSA and CytC when compared to microspheres encapsulating BSA and CytC. Despite the fact that the mechanisms behind remain unclear and further investigation is required, this study demonstrates the potential of the volvox spheres for drug delivery. - Highlights: • Volvox spheres contain smaller microspheres which can encapsulate drugs and/or cells. • Alginate is the primary material for the inner and outer spheres. • Encapsulation is affected by the crosslinking, temperature and the selection of drugs.

  15. In Situ Formation of Steroidal Supramolecular Gels Designed for Drug Release

    Directory of Open Access Journals (Sweden)

    Hana Bunzen

    2013-03-01

    Full Text Available In this work, a steroidal gelator containing an imine bond was synthesized, and its gelation behavior as well as a sensitivity of its gels towards acids was investigated. It was shown that the gels were acid-responsive, and that the gelator molecules could be prepared either by a conventional synthesis or directly in situ during the gel forming process. The gels prepared by both methods were studied and it was found that they had very similar macro- and microscopic properties. Furthermore, the possibility to use the gels as carriers for aromatic drugs such as 5-chloro-8-hydroxyquinoline, pyrazinecarboxamide, and antipyrine was investigated and the prepared two-component gels were studied with regard to their potential applications in drug delivery, particularly in a pH-controlled drug release.

  16. Drug release from non-aqueous suspensions. II. The release of methylxanthines from paraffin suspensions

    NARCIS (Netherlands)

    Blaey, C.J. de; Fokkens, J.G.

    1984-01-01

    The release of 3 methylxanthines, i.e. caffeine, theobromine and theophylline, from suspensions in liquid paraffin to an aqueous phase was determined in an in vitro apparatus. The release rates were determined as a function of the pH of the aqueous phase. It was proved that the release process was

  17. Probing intra-cellular drug release event using activatable (OFF/ON) CdS:Mn/ZnS quantum dots (Qdots): spectroscopic studies to investigate interaction of Qdots with quencher

    Science.gov (United States)

    Tharkur, Jeremy; Teblum, Andrew; Basumallick, Srijita; Shah, Rikhav; Cantarero, Karishma; Maity, Niharika; Rifai, Sara; Doshi, Mona; Gesquiere, Andre J.; Santra, Swadeshmukul

    2013-02-01

    In recent years, activatable Quantum Dots (AQdots) are gaining popularity in a number of chemical and biological sensing applications. A basic design of AQdot probes involves a suitable quencher which is capable of altering optical properties of the Qdots. In our previous studies we have shown that CdS:Mn/ZnS fluorescence can be effectively quenched using small molecule quenchers (such as dopamine, chemotherapeutic drug) as well as iron oxide nanoparticle via electron/energy transfer process. We have also shown that the quenched Qdot fluorescence can be restored when the Qdots are separated from the quencher. Using Qdot based activatable probes, we detected intracellular drug release event. Qdot fluorescence was restored upon interaction with the intracellular glutathione (GSH). In this paper, we report a GSH induced quenching of water-soluble N-Acetyl Cysteine (NAC) surface-conjugated Cds:Mn/ZnS Qdots. Quenching of NAC-Qdots was due to aggregation of Qdots in solution. This aggregation induced fluorescence quenching phenomenon resembles with the self-quenching phenomenon of traditional organic fluorescence dyes at high concentrations. UV-VIS and fluorescence emission spectroscopy data support the interaction and binding of GSH with the NAC-Qdots. Increase in particle size due to GSH induced aggregation of NAC-Qdots was confirmed by the Dynamic Light Scattering (DLS) data.

  18. Polyvinyl alcohol composite nanofibres containing conjugated levofloxacin-chitosan for controlled drug release

    International Nuclear Information System (INIS)

    Jalvandi, Javid; White, Max; Gao, Yuan; Truong, Yen Bach; Padhye, Rajiv; Kyratzis, Ilias Louis

    2017-01-01

    A range of biodegradable drug-nanofibres composite mats have been reported as drug delivery systems. However, their main disadvantage is the rapid release of the drug immediately after application. This paper reports an improved system based on the incorporation of drug conjugated-chitosan into polyvinyl alcohol (PVA) nanofibers. The results showed that controlled release of levofloxacin (LVF) could be achieved by covalently binding LVF to low molecular weight chitosan (CS) via a cleavable amide bond and then blending the conjugated CS with polyvinyl alcohol (PVA) nanofibres prior to electrospinning. PVA/LVF and PVA-CS/LVF nanofibres were fabricated as controls. The conjugated CS-LVF was characterized by FTIR, DSC, TGA and 1 H NMR. Scanning electron microscopy (SEM) showed that the blended CS-PVA nanofibres had a reduced fibre diameter compared to the controls. Drug release profiles showed that burst release was decreased from 90% in the control PVA/LVF electrospun mats to 27% in the PVA/conjugated CS-LVF mats after 8 h in phosphate buffer at 37 °C. This slower release is due to the cleavable bond between LVF and CS that slowly hydrolysed over time at neutral pH. The results indicate that conjugation of the drug to the polymer backbone is an effective way of minimizing burst release behaviour and achieving sustained release of the drug, LVF. - Highlights: • A novel drug delivery system for controlled release of drug was designed. • Composite PVA/conjugated CS-LVF nanofibres was fabricated by electrospinning. • Conjugated chitosan and composite nanofibres were characterized by various techniques. • Release profiles of drug were significantly improved in composite nanofibres containing drug conjugated chitosan.

  19. Polyvinyl alcohol composite nanofibres containing conjugated levofloxacin-chitosan for controlled drug release

    Energy Technology Data Exchange (ETDEWEB)

    Jalvandi, Javid, E-mail: Javid.jlv@gmail.com [CSIRO, Manufacturing Flagship, Bayview Ave, Clayton, Victoria 3168 (Australia); School of Fashion and Textiles, College of Design and Social Context, RMIT University, 25 Dawson Street, Brunswick, Victoria 3056 (Australia); White, Max, E-mail: tamrak@bigpond.com [School of Fashion and Textiles, College of Design and Social Context, RMIT University, 25 Dawson Street, Brunswick, Victoria 3056 (Australia); Gao, Yuan, E-mail: Yuan.Gao@csiro.au [CSIRO, Manufacturing Flagship, Bayview Ave, Clayton, Victoria 3168 (Australia); Truong, Yen Bach, E-mail: Yen.truong@csiro.au [CSIRO, Manufacturing Flagship, Bayview Ave, Clayton, Victoria 3168 (Australia); Padhye, Rajiv, E-mail: rajiv.padhye@rmit.edu.au [School of Fashion and Textiles, College of Design and Social Context, RMIT University, 25 Dawson Street, Brunswick, Victoria 3056 (Australia); Kyratzis, Ilias Louis, E-mail: Louis.kyratzis@csiro.au [CSIRO, Manufacturing Flagship, Bayview Ave, Clayton, Victoria 3168 (Australia)

    2017-04-01

    A range of biodegradable drug-nanofibres composite mats have been reported as drug delivery systems. However, their main disadvantage is the rapid release of the drug immediately after application. This paper reports an improved system based on the incorporation of drug conjugated-chitosan into polyvinyl alcohol (PVA) nanofibers. The results showed that controlled release of levofloxacin (LVF) could be achieved by covalently binding LVF to low molecular weight chitosan (CS) via a cleavable amide bond and then blending the conjugated CS with polyvinyl alcohol (PVA) nanofibres prior to electrospinning. PVA/LVF and PVA-CS/LVF nanofibres were fabricated as controls. The conjugated CS-LVF was characterized by FTIR, DSC, TGA and {sup 1}H NMR. Scanning electron microscopy (SEM) showed that the blended CS-PVA nanofibres had a reduced fibre diameter compared to the controls. Drug release profiles showed that burst release was decreased from 90% in the control PVA/LVF electrospun mats to 27% in the PVA/conjugated CS-LVF mats after 8 h in phosphate buffer at 37 °C. This slower release is due to the cleavable bond between LVF and CS that slowly hydrolysed over time at neutral pH. The results indicate that conjugation of the drug to the polymer backbone is an effective way of minimizing burst release behaviour and achieving sustained release of the drug, LVF. - Highlights: • A novel drug delivery system for controlled release of drug was designed. • Composite PVA/conjugated CS-LVF nanofibres was fabricated by electrospinning. • Conjugated chitosan and composite nanofibres were characterized by various techniques. • Release profiles of drug were significantly improved in composite nanofibres containing drug conjugated chitosan.

  20. Preparation of ionic-crosslinked chitosan-based gel beads and effect of reaction conditions on drug release behaviors.

    Science.gov (United States)

    Chen, Shilan; Liu, Mingzhu; Jin, Shuping; Wang, Bin

    2008-02-12

    Drug-loaded chitosan (CS) beads were prepared under simple and mild condition using trisodium citrate as ionic crosslinker. The beads were further coated with poly(methacrylic acid) (PMAA) by dipping the beads in PMAA aqueous solution. The surface and cross-section morphology of these beads were observed by scanning electron microscopy and the observation showed that the coating beads had core-shell structure. In vitro release of model drug from these beads obtained under different reaction conditions was investigated in buffer medium (pH 1.8). The results showed that the rapid drug release was restrained by PMAA coating and the optimum conditions for preparing CS-based drug-loaded beads were decided through the effect of reaction conditions on the drug release behaviors. In addition, the drug release mechanism of CS-based drug-loaded beads was analyzed by Peppa's potential equation. According to this study, the ionic-crosslinked CS beads coated by PMAA could serve as suitable candidate for drug site-specific carrier in stomach.

  1. Oral controlled release drug delivery system and Characterization of oral tablets; A review

    OpenAIRE

    Muhammad Zaman; Junaid Qureshi; Hira Ejaz; Rai Muhammad Sarfraz; Hafeez ullah Khan; Fazal Rehman Sajid; Muhammad Shafiq ur Rehman

    2016-01-01

    Oral route of drug administration is considered as the safest and easiest route of drug administration. Control release drug delivery system is the emerging trend in the pharmaceuticals and the oral route is most suitable for such kind of drug delivery system. Oral route is more convenient for It all age group including both pediatric and geriatrics. There are various systems which are adopted to deliver drug in a controlled manner to different target sites through oral route. It includes dif...

  2. Composite poly(vinyl alcohol/poly(vinyl acetate electrospun nanofibrous mats as a novel wound dressing matrix for controlled release of drugs

    Directory of Open Access Journals (Sweden)

    Jannesari M

    2011-05-01

    Full Text Available Marziyeh Jannesari1, Jaleh Varshosaz2, Mohammad Morshed1, Maedeh Zamani11Department of Textile Engineering, Isfahan University of Technology, Isfahan, Iran; 2Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, IranAbstract: The aim of this study was to develop novel biomedicated nanofiber electrospun mats for controlled drug release, especially drug release directly to an injury site to accelerate wound healing. Nanofibers of poly(vinyl alcohol (PVA, poly(vinyl acetate (PVAc, and a 50:50 composite blend, loaded with ciprofloxacin HCl (CipHCl, were successfully prepared by an electrospinning technique for the first time. The morphology and average diameter of the electrospun nanofibers were investigated by scanning electron microscopy. X-ray diffraction studies indicated an amorphous distribution of the drug inside the nanofiber blend. Introducing the drug into polymeric solutions significantly decreased solution viscosities as well as nanofiber diameter. In vitro drug release evaluations showed that both the kind of polymer and the amount of drug loaded greatly affected the degree of swelling, weight loss, and initial burst and rate of drug release. Blending PVA and PVAc exhibited a useful and convenient method for electrospinning in order to control the rate and period of drug release in wound healing applications. Also, the thickness of the blend nanofiber mats strongly influenced the initial release and rate of drug release.Keywords: biodegradable polymers, drug delivery, controlled release, electrospun nanofibers, wound dressing

  3. The Effect of Acid pH Modifiers on the Release Characteristics of Weakly Basic Drug from Hydrophlilic–Lipophilic Matrices

    OpenAIRE

    Dvořáčková, Kateřina; Doležel, Petr; Mašková, Eliška; Muselík, Jan; Kejdušová, Martina; Vetchý, David

    2013-01-01

    The solubility of weakly basic drugs within passage though GI tract leads to pH-dependent or even incomplete release of these drugs from extended release formulations and consequently to lower drug absorption and bioavailability. The aim of the study was to prepare and evaluate hydrophilic–lipophilic (hypromellose–montanglycol wax) matrix tablets ensuring the pH-independent delivery of the weakly basic drug verapamil-hydrochloride by an incorporation of three organic acidifiers (citric, fumar...

  4. Robotic UV-Vis apparatus for long-term characterization of drug release from nanochannels

    International Nuclear Information System (INIS)

    Geninatti, T; Grattoni, A; Small, E

    2014-01-01

    Reliable monitoring of the kinetics of molecular release from drug delivery devices is crucial for their therapeutic success. Commercially available UV-Vis spectrophotometers provide reliable quantification of analyte concentrations directly correlated to the absorbance of fluids. However, they are not suitable for long-term measurements requiring high frequency of sampling from a large number of replicates and continuous fluid mixing, all of which are necessary for evaluation of drug delivery devices. To address this need, we developed a novel robotic apparatus serially connected to a commercial UV-Vis spectrophotometer. The robotic apparatus enables us to automatically and reliably acquire long-term data for up to 48 samples with high frequency of measurements and independent magnetic stirring. We equipped the robotic apparatus with independent connectors that allowed us to apply an electric potential to each sample for electrokinetic studies. The apparatus repeatability and accuracy was demonstrated in comparison to a commercial UV-Vis spectrophotometer. The system was successfully employed to characterize the diffusion kinetics of acetone and doxorubicin through nanochannel membranes (nDS) designed for long-term drug delivery. Dendritic fullerene 1 was used to show that the robotic apparatus routes the electric potential to nanochannel membranes enabling us to investigate the actively controlled release of molecules. Our results demonstrate that the robotic apparatus could widely broaden the range of applications of UV-Vis spectrophotometry, especially in the case of large sample processing and for long-term diffusive and electrokinetic studies in drug delivery. (technical design note)

  5. Biodegradable Drug-Loaded Hydroxyapatite Nanotherapeutic Agent for Targeted Drug Release in Tumors.

    Science.gov (United States)

    Sun, Wen; Fan, Jiangli; Wang, Suzhen; Kang, Yao; Du, Jianjun; Peng, Xiaojun

    2018-03-07

    Tumor-targeted drug delivery systems have been increasingly used to improve the therapeutic efficiency of anticancer drugs and reduce their toxic side effects in vivo. Focused on this point, doxorubicin (DOX)-loaded hydroxyapatite (HAP) nanorods consisting of folic acid (FA) modification (DOX@HAP-FA) were developed for efficient antitumor treatment. The DOX-loaded nanorods were synthesized through in situ coprecipitation and hydrothermal method with a DOX template, demonstrating a new procedure for drug loading in HAP materials. DOX could be efficiently released from DOX@HAP-FA within 24 h in weakly acidic buffer solution (pH = 6.0) because of the degradation of HAP nanorods. With endocytosis under the mediation of folate receptors, the nanorods exhibited enhanced cellular uptake and further degraded, and consequently, the proliferation of targeted cells was inhibited. More importantly, in a tumor-bearing mouse model, DOX@HAP-FA treatment demonstrated excellent tumor growth inhibition. In addition, no apparent side effects were observed during the treatment. These results suggested that DOX@HAP-FA may be a promising nanotherapeutic agent for effective cancer treatment in vivo.

  6. The effect of solvents and hydrophilic additive on stable coating and controllable sirolimus release system for drug-eluting stent.

    Science.gov (United States)

    Kim, Seong Min; Park, Sung-Bin; Bedair, Tarek M; Kim, Man-Ho; Park, Bang Ju; Joung, Yoon Ki; Han, Dong Keun

    2017-09-01

    Various drug-eluting stents (DESs) have been developed to prevent restenosis after stent implantation. However, DES still needs to improve the drug-in-polymer coating stability and control of drug release for effective clinical treatment. In this study, the cobalt-chromium (CoCr) alloy surface was coated with biodegradable poly(D,L-lactide) (PDLLA) and sirolimus (SRL) mixed with hydrophilic Pluronic F127 additive by using ultrasonic spray coating system in order to achieve a stable coating surface and control SRL release. The degradation of PDLLA/SRL coating was studied under physiological solution. It was found that adding F127 reduced the degradation of PDLLA and improved the coating stability during 60days. The effects of organic solvent such as chloroform and tetrahydrofuran (THF) on the coating uniformity were also examined. It was revealed that THF produced a very smooth and uniform coating compared to chloroform. The patterns of in vitro drug release according to the type of organic solvent and hydrophilic additive proposed the possibility of controllable drug release design in DES. It was found that using F127 the drug release was sustained regardless of the organic solvent used. In addition, THF was able to get faster and controlled release profile when compared to chloroform. The structure of SRL molecules in different organic solvents was investigated using ultra-small angle neutron scattering. Furthermore, the structure of SRL is concentration-dependent in chloroform with tight nature under high concentration, but concentration-independent in THF. These results strongly demonstrated that coating stability and drug release patterns can be changed by physicochemical properties of various parameters such as organic solvents, additive, and coating strategy. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. The effects of cyclodextrins on drug release from fatty suppository bases : II. In vivo observations

    NARCIS (Netherlands)

    Frijlink, H.W.; Eissens, Anko; Schoonen, Adelbert; Lerk, C.F.

    The effects of cyclodextrin complexation on the absorption of drugs from fatty suppositories was evaluated in human volunteers. Three model drugs: diazepam, ibuprofen and prednisolone were used. When diazepam was complexed with γ-cyclcodextrin the drug release from the fatty suppositories was

  8. Effect of ca2+ to salicylic acid release in pectin based controlled drug delivery system

    Science.gov (United States)

    Kistriyani, L.; Wirawan, S. K.; Sediawan, W. B.

    2016-01-01

    Wastes from orange peel are potentially be utilized to produce pectin, which are currently an import commodity. Pectin can be used in making edible film. Edible films are potentially used as a drug delivery system membrane after a tooth extraction. Drug which is used in the drug delivery system is salicylic acid. It is an antiseptic. In order to control the drug release rate, crosslinking process is added in the manufacturing of membrane with CaCl2.2H2O as crosslinker. Pectin was diluted in water and mixed with a plasticizer and CaCl2.2H2O solution at 66°C to make edible film. Then the mixture was dried in an oven at 50 °C. After edible film was formed, it was coated using plasticizer and CaCl2.2H2O solution with various concentration 0, 0.015, 0.03 and 0.05g/mL. This study showed that the more concentration of crosslinker added, the slower release of salicylic acid would be. This was indicated by the value of diffusivites were getting smaller respectively. The addition of crosslinker also caused smaller gels swelling value,which made the membrane is mechanically stronger

  9. Physical capture and release of drug molecules, water and cations by a smectite clay

    DEFF Research Database (Denmark)

    Carvalho dos Santos, Éverton

    -fluorohectorite (LiFh, Li1.2(Mg4.8Li1.2)Si8O20F4), a synthetic clay mineral from the smectite family, have been experimentally analyzed. By means of X-rays powder diffraction (XRD), using both an in-house instrument and synchrotron radiation, UV-Vis spectroscopy, Thermogravimetric Analysis coupled to an Infrared......-analysis and inelastic neutron scattering data we established that the drug presence into the interlayer space of Fh is weakening the water-clay interactions. Furthermore, CIPRO’s release from Fh in synthetic gastric acid juice (SGA) as a function of time and temperature was also carefully followed. Our studies showed...... and toxicological tests, we demonstrated that the effectiveness and toxicity of pure CIPRO is unaffected in the clay-drug complex. To conclude, the high drug adsorption capacity as well as the slow and gradual release from CIPRO when intercalated in Fh adds this synthetic smectite to the list of promising drug...

  10. One-dimensional drug release from finite Menger sponges: In silico simulation

    International Nuclear Information System (INIS)

    Villalobos, Rafael; Dominguez, Armando; Ganem, Adriana; Vidales, Ana Maria; Cordero, Salomon

    2009-01-01

    The purpose of this work was to evaluate the consequences of the spatial distribution of components in pharmaceutical matrices type Menger sponge on the drug release kinetic from this kind of platforms by means of Monte Carlo computer simulation. First, six kinds of Menger sponges (porous fractal structures) with the same fractal dimension, d f =2.727, but with different random walk dimension, d w element of [2.149,3.183], were constructed as models of drug release device. Later, Monte Carlo simulation was used to describe drug release from these structures as a diffusion-controlled process. The obtained results show that drug release from Menger sponges is characterized by an anomalous behavior: there are important effects of the microstructure anisotropy, and porous structures with the same fractal dimension but with different topology produce different release profiles. Moreover, the drug release kinetic from heteromorphic structures depends on the axis used to transport the material to the external medium. Finally, it was shown that the number of releasing sites on the matrix surface has a significant impact on drug release behavior and it can be described quantitatively by the Weibull function.

  11. One-dimensional drug release from finite Menger sponges: In silico simulation

    Energy Technology Data Exchange (ETDEWEB)

    Villalobos, Rafael [Division de Estudios de Posgrado (Tecnologia Farmaceutica), Facultad de Estudios Superiores Cuautitlan, Universidad Nacional Autonoma de Mexico, Av. Primero de Mayo S/N, Cuautitlan Izcalli 54740, Estado de Mexico (Mexico)], E-mail: yeccanv@yahoo.com; Dominguez, Armando [UAM-Iztapalapa, Depto. de Quimica, Av. San Rafael Atlixco 186, Col. Vicentina, 09340 Mexico City (Mexico); Ganem, Adriana [Division de Estudios de Posgrado (Tecnologia Farmaceutica), Facultad de Estudios Superiores Cuautitlan, Universidad Nacional Autonoma de Mexico, Av. Primero de Mayo S/N, Cuautitlan Izcalli 54740, Estado de Mexico (Mexico); Vidales, Ana Maria [Laboratorio de Ciencia de Superficies y Medios Porosos, Departamento de Fisica, CONICET, Universidad Nacional de San Luis, 5700 San Luis (Argentina); Cordero, Salomon [UAM-Iztapalapa, Depto. de Quimica, Av. San Rafael Atlixco 186, Col. Vicentina, 09340 Mexico City (Mexico)

    2009-12-15

    The purpose of this work was to evaluate the consequences of the spatial distribution of components in pharmaceutical matrices type Menger sponge on the drug release kinetic from this kind of platforms by means of Monte Carlo computer simulation. First, six kinds of Menger sponges (porous fractal structures) with the same fractal dimension, d{sub f}=2.727, but with different random walk dimension, d{sub w} element of [2.149,3.183], were constructed as models of drug release device. Later, Monte Carlo simulation was used to describe drug release from these structures as a diffusion-controlled process. The obtained results show that drug release from Menger sponges is characterized by an anomalous behavior: there are important effects of the microstructure anisotropy, and porous structures with the same fractal dimension but with different topology produce different release profiles. Moreover, the drug release kinetic from heteromorphic structures depends on the axis used to transport the material to the external medium. Finally, it was shown that the number of releasing sites on the matrix surface has a significant impact on drug release behavior and it can be described quantitatively by the Weibull function.

  12. The control of beads diameter of bead-on-string electrospun nanofibers and the corresponding release behaviors of embedded drugs

    Energy Technology Data Exchange (ETDEWEB)

    Li, Tingxiao [Key Laboratory of Textile Science and Technology (Donghua University), Ministry of Education of China, Shanghai 201620 (China); College of Textiles, Donghua University, Shanghai 201620 (China); Ding, Xin, E-mail: xding@dhu.edu.cn [Key Laboratory of Textile Science and Technology (Donghua University), Ministry of Education of China, Shanghai 201620 (China); College of Textiles, Donghua University, Shanghai 201620 (China); Tian, Lingling, E-mail: lingling_tian@nus.edu.sg [Center of Nanofibers & Nanotechnology, Department of Mechanical Engineering, National University of Singapore, 117576 (Singapore); Hu, Jiyong; Yang, Xudong [Key Laboratory of Textile Science and Technology (Donghua University), Ministry of Education of China, Shanghai 201620 (China); College of Textiles, Donghua University, Shanghai 201620 (China); Ramakrishna, Seeram [Center of Nanofibers & Nanotechnology, Department of Mechanical Engineering, National University of Singapore, 117576 (Singapore); Guangdong-Hongkong-Macau Institute of CNS Regeneration (GHMICR), Jinan University, Guangzhou 510632 (China)

    2017-05-01

    Bead-on-string nanofibers, with appropriate control of the beads diameter, are potential fibrous structures for efficient encapsulation of particle drugs in micron scales and could achieve controlled drug release for tissue engineering applications. In this study, the beads diameter of electrospun bead-on-string nanofibers was controlled by adjusting the concentration of spinning polymer, poly (lactic-co-glycolic acid) (PLGA), and the solvent ratio of chloroform to acetone. The images of the scanning electron microscopy (SEM) suggested that bead-on-string nanofibers could be successfully obtained only with a certain range of PLGA solution concentration. Moreover, with the decrease in the solvent ratio of chloroform to acetone, the range was left-shifted towards a smaller concentration. In addition, increase in the PLGA solution concentration within the range the beads diameter became greater and the shape of the beads changed from oval to slender when increasing the PLGA concentration within the range. The bead-on-string nanofibers with different beads diameter were further used to load micro-particle drugs of tetracycline hydrochloride, as a model drug, to examine the release behavior of nanofibers scaffold. The release profiles of drug loaded bead-on-string nanofibers demonstrated the possibility to alleviate the burst drug release by means of beads diameter control. - Highlights: • Bead diameter of bead-on-string electrospun nanofibers was controlled by varying solvent ratio and polymer concentration. • The effect of the addition of particle drugs on BD of bead-on-string electrospun nanofibers was studied. • The corresponding release behaviors of nanofibers with different BD loading micro-particle drugs were investigated. • Bead-on-string nanofibers with bigger BD could alleviate the initial burst release.

  13. The control of beads diameter of bead-on-string electrospun nanofibers and the corresponding release behaviors of embedded drugs

    International Nuclear Information System (INIS)

    Li, Tingxiao; Ding, Xin; Tian, Lingling; Hu, Jiyong; Yang, Xudong; Ramakrishna, Seeram

    2017-01-01

    Bead-on-string nanofibers, with appropriate control of the beads diameter, are potential fibrous structures for efficient encapsulation of particle drugs in micron scales and could achieve controlled drug release for tissue engineering applications. In this study, the beads diameter of electrospun bead-on-string nanofibers was controlled by adjusting the concentration of spinning polymer, poly (lactic-co-glycolic acid) (PLGA), and the solvent ratio of chloroform to acetone. The images of the scanning electron microscopy (SEM) suggested that bead-on-string nanofibers could be successfully obtained only with a certain range of PLGA solution concentration. Moreover, with the decrease in the solvent ratio of chloroform to acetone, the range was left-shifted towards a smaller concentration. In addition, increase in the PLGA solution concentration within the range the beads diameter became greater and the shape of the beads changed from oval to slender when increasing the PLGA concentration within the range. The bead-on-string nanofibers with different beads diameter were further used to load micro-particle drugs of tetracycline hydrochloride, as a model drug, to examine the release behavior of nanofibers scaffold. The release profiles of drug loaded bead-on-string nanofibers demonstrated the possibility to alleviate the burst drug release by means of beads diameter control. - Highlights: • Bead diameter of bead-on-string electrospun nanofibers was controlled by varying solvent ratio and polymer concentration. • The effect of the addition of particle drugs on BD of bead-on-string electrospun nanofibers was studied. • The corresponding release behaviors of nanofibers with different BD loading micro-particle drugs were investigated. • Bead-on-string nanofibers with bigger BD could alleviate the initial burst release.

  14. Mechanistic modelling of drug release from polymer-coated and swelling and dissolving polymer matrix systems.

    Science.gov (United States)

    Kaunisto, Erik; Marucci, Mariagrazia; Borgquist, Per; Axelsson, Anders

    2011-10-10

    The time required for the design of a new delivery device can be sensibly reduced if the release mechanism is understood and an appropriate mathematical model is used to characterize the system. Once all the model parameters are obtained, in silico experiments can be performed, to provide estimates of the release from devices with different geometries and compositions. In this review coated and matrix systems are considered. For coated formulations, models describing the diffusional drug release, the osmotic pumping drug release, and the lag phase of pellets undergoing cracking in the coating due to the build-up of a hydrostatic pressure are reviewed. For matrix systems, models describing pure polymer dissolution, diffusion in the polymer and drug release from swelling and eroding polymer matrix formulations are reviewed. Importantly, the experiments used to characterize the processes occurring during the release and to validate the models are presented and discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Hindered disulfide bonds to regulate release rate of model drug from mesoporous silica.

    Science.gov (United States)

    Nadrah, Peter; Maver, Uroš; Jemec, Anita; Tišler, Tatjana; Bele, Marjan; Dražić, Goran; Benčina, Mojca; Pintar, Albin; Planinšek, Odon; Gaberšček, Miran

    2013-05-01

    With the advancement of drug delivery systems based on mesoporous silica nanoparticles (MSNs), a simple and efficient method regulating the drug release kinetics is needed. We developed redox-responsive release systems with three levels of hindrance around the disulfide bond. A model drug (rhodamine B dye) was loaded into MSNs' mesoporous voids. The pore opening was capped with β-cyclodextrin in order to prevent leakage of drug. Indeed, in absence of a reducing agent the systems exhibited little leakage, while the addition of dithiothreitol cleaved the disulfide bonds and enabled the release of cargo. The release rate and the amount of released dye were tuned by the level of hindrance around disulfide bonds, with the increased hindrance causing a decrease in the release rate as well as in the amount of released drug. Thus, we demonstrated the ability of the present mesoporous systems to intrinsically control the release rate and the amount of the released cargo by only minor structural variations. Furthermore, an in vivo experiment on zebrafish confirmed that the present model delivery system is nonteratogenic.

  16. pH- and temperature-sensitive polymeric microspheres for drug delivery: the dissolution of copolymers modulates drug release.

    Science.gov (United States)

    Fundueanu, Gheorghe; Constantin, Marieta; Stanciu, Cristina; Theodoridis, Georgios; Ascenzi, Paolo

    2009-12-01

    Most pH-/temperature-responsive polymers for controlled release of drugs are used as cross-linked hydrogels. However, the solubility properties of the linear polymers below and above the lower critical solution temperature (LCST) are not exploited. Here, the preparation and characterization of poly (N-isopropylacrylamide-co-methacrylic acid-co-methyl methacrylate) (poly (NIPAAm-co-MA-co-MM)) and poly (N-isopropylacrylamide-co-acrylamide) (poly (NIPAAm-co-AAm)), known as "smart" polymers (SP), is reported. Both poly (NIPAAm-co-MA-co-MM) and poly (NIPAAm-co-AAm) display pH- and temperature-responsive properties. Poly (NIPAAm-co-MA-co-MM) was designed to be insoluble in the gastric fluid (pH = 1.2), but soluble in the intestinal fluid (pH = 6.8 and 7.4), at the body temperature (37 degrees C). Poly (NIPAAm-co-AAm) was designed to have a lower critical solution temperature (LCST) corresponding to 37 degrees C at pH = 7.4, therefore it is not soluble above the LCST. The solubility characteristics of these copolymers were exploited to modulate the rate of release of drugs by changing pH and/or temperature. These copolymers were solubilized with hydrophobic cellulose acetate butyrate (CAB) and vitamin B(12) (taken as a water soluble drug model system) in an acetone/methanol mixture and dispersed in mineral oil. By a progressive evaporation of the solvent, the liquid droplets were transformed into loaded CAB/SP microspheres. Differential scanning calorimetric studies and scanning electron microscopy analysis demonstrated that the polymeric components of the microspheres precipitated separately during solvent evaporation forming small microdomains. Moreover, vitamin B(12) was found to be molecularly dispersed in both microdomains with no specific affinity for any polymeric component of microspheres. The release of vitamin B(12) was investigated as a function of temperature, pH, and the CAB/SP ratio.

  17. The influence of spray-drying parameters on phase behavior, drug distribution, and in vitro release of injectable microspheres for sustained release.

    Science.gov (United States)

    Meeus, Joke; Lenaerts, Maité; Scurr, David J; Amssoms, Katie; Davies, Martyn C; Roberts, Clive J; Van Den Mooter, Guy

    2015-04-01

    For ternary solid dispersions, it is indispensable to characterize their structure, phase behavior, and the spatial distribution of the dispersed drug as this might influence the release profile and/or stability of these formulations. This study shows how formulation (feed concentration) and process (feed rate, inlet air temperature, and atomizing air pressure) parameters can influence the characteristics of ternary spray-dried solid dispersions. The microspheres considered here consist of a poly(lactic-co-glycolic acid) (PLGA) surface layer and an underlying polyvinylpyrrolidone (PVP) phase. A poorly soluble active pharmaceutical ingredient (API) was molecularly dispersed in this matrix. Differences were observed in component miscibility, phase heterogeneity, particle size, morphology, as well as API surface coverage for selected spray-drying parameters. Observed differences are likely because of changes in the droplet generation, evaporation, and thus particle formation processes. However, varying particle characteristics did not influence the drug release of the formulations studied, indicating the robustness of this approach to produce particles of consistent drug release characteristics. This is likely because of the fact that the release is dominated by diffusion from the PVP layer through pores in the PLGA surface layer and that observed differences in the latter have no influence on the release. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  18. Stable and biocompatible genipin-inducing interlayer-crosslinked micelles for sustained drug release

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Yu; Zhang, Xiaojin, E-mail: zhangxj@cug.edu.cn [China University of Geosciences, Faculty of Materials Science and Chemistry (China)

    2017-05-15

    To develop the sustained drug release system, here we describe genipin-inducing interlayer-crosslinked micelles crosslinked via Schiff bases between the amines of amphiphilic linear-hyperbranched polymer poly(ethylene glycol)-branched polyethylenimine-poly(ε-caprolactone) (PEG-PEI-PCL) and genipin. The generation of Schiff bases was confirmed by the color changes and UV-Vis absorption spectra of polymeric micelles after adding genipin. The particle size, morphology, stability, in vitro cytotoxicity, drug loading capacity, and in vitro drug release behavior of crosslinked micelles as well as non-crosslinked micelles were characterized. The results indicated that genipin-inducing interlayer-crosslinked micelles had better stability and biocompatibility than non-crosslinked micelles and glutaraldehyde-inducing interlayer-crosslinked micelles. In addition, genipin-inducing interlayer-crosslinked micelles were able to improve drug loading capacity, reduce the initial burst release, and achieve sustained drug release.

  19. Disintegration mediated controlled release supersaturating solid dispersion formulation of an insoluble drug: design, development, optimization, and in vitro evaluation.

    Science.gov (United States)

    Verma, Sanjay; Rudraraju, Varma S

    2015-02-01

    The objective of this study was to develop a solid dispersion based controlled release system for drug substances that are poorly soluble in water. A wax-based disintegration mediated controlled release system was designed based on the fact that an amorphous drug can crystallize out from hydrophilic matrices. For this study, cilostazol (CIL) was selected as the model drug, as it exhibits poor aqueous solubility. An amorphous solid dispersion was prepared to assist the drug to attain a supersaturated state. Povidone was used as carrier for solid dispersion (spray drying technique), hydrogenated vegetable oil (HVO) as wax matrix former, and sodium carboxymethyl cellulose (NaCMC) as a disintegrant. The extreme vertices mixture design (EVMD) was applied to optimize the designed and developed composition. The optimized formulation provided a dissolution pattern which was equivalent to the predicted curve, ascertaining that the optimal formulation could be accomplished with EVMD. The release profile of CIL was described by the Higuchi's model better than zero-order, first-order, and Hixson-Crowell's model, which indicated that the supersaturation state of CIL dominated to allow drug release by diffusion rather than disintegration regulated release as is generally observed by Hixson-Crowell's model. The optimized composition was evaluated for disintegration, dissolution, XRD, and stability studies. It was found that the amorphous state as well as the dissolution profile of CIL was maintained under the accelerated conditions of 40°C/75% RH for 6 months.

  20. A novel fluoride anion modified gelatin nanogel system for ultrasound-triggered drug release.

    Science.gov (United States)

    Wu, Daocheng; Wan, Mingxi

    2008-01-01

    Controlled drug release, especially tumor-targeted drug release, remains a great challenge. Here, we prepare a novel fluoride anion-modified gelatin nanogel system and investigate its characteristics of ultrasound-triggered drug release. Adriamycin gelatin nanogel modified with fluoride anion (ADM-GNMF) was prepared by a modified co-precipitation method with fluoride anion and sodium sulfate. The loading and encapsulation efficiency of the anti-neoplastic agent adriamycin (ADM) were measured by high performance liquid chromatography (HPLC). The size and shape of ADM-GNMF were determined by electron microscopy and photo-correlation spectroscopy. The size distribution and drug release efficiency of ADM-GNMF, before and after sonication, were measured by two designed measuring devices that consisted of either a submicron particle size analyzer and an ultrasound generator as well as an ultrasound generator, automatic sampler, and HPLC. The ADM-GNMF was stable in solution with an average diameter of 46+/-12 nm; the encapsulation and loading efficiency of adriamycin were 87.2% and 6.38%, respectively. The ultrasound-triggered drug release and size change were most efficient at a frequency of 20 kHz, power density of 0.4w/cm2, and a 1~2 min duration. Under this ultrasound-triggered condition, 51.5% of drug in ADM-GNMF was released within 1~2 min, while the size of ADM-GNMF changed from 46 +/- 12 nm to 1212 +/- 35 nm within 1~2 min of sonication and restored to its previous size in 2~3 min after the ultrasound stopped. In contrast, 8.2% of drug in ADM-GNMF was released within 2~3 min without sonication, and only negligible size changes were found. The ADM-GNMF system efficiently released the encompassed drug in response to ultrasound, offering a novel and promising controlled drug release system for targeted therapy for cancer or other diseases.

  1. Development and in vitro evaluation of sustained release multiparticulate tablet of freely water soluble drug

    Directory of Open Access Journals (Sweden)

    Ashlesha Pravin Pandit

    2010-09-01

    Full Text Available Blends of aqueous dispersion of a hydrophobic and hydrophilic polymer, namely Surelease®: hydroxypropyl methylcellulose (Surelease®: HPMC E15 were used as coating materials to control the drug release from coated pellets of the highly water soluble drug metoprolol succinate. Varying the polymer blends, ranges of drug release patterns were obtained at pH 6.8. The present study dealt with diffusion of drug through plasticized Surelease®/ hydroxypropyl methylcellulose (HPMC E15 films prepared by coating of drug and polymers onto non-pareil seeds using the solution layering technique. The release of metoprolol succinate from coated pellets was decreased with increased coating load of polymer. The optimized formulation was obtained by 3² full factorial design. The release profile revealed that the optimized formulation follows zero order release kinetics. The stability data showed no interaction for storage at 25ºC and 60% relative humidity.Misturas das dispersões aquosas de polímero hidrofóbico e de polímero hidrofílico, a saber, Surelease®: hidroxipropil metilcelulose (Surelease®: HPMC E15, foram utilizadas como material de revestimento para controlar a liberação de fármacos de péletes revestidos de fármaco altamente solúvel, o succinato de metoprolol. Variando as misturas de polímeros, obtiveram-se faixas de padrão de liberação do fármaco em pH 6,8. O presente estudo tratou da difusão do fármaco através de filmes de Surelease®/hidroxipropil metilcelulose(HPMC E15, preparados pelo revestimento do fármaco e dos polímeros em sementes nonpareil, utilizando técnica de solução em camada. A liberação de succinato de metoprolol dos péletes revestidos diminuiu com o aumento da carga de polímero de revestimento. A formulação otimizada foi obtida por planejamento fatorial 3². O perfil de liberação revelou que a formulação otimizada segue a cinética de liberação de ordem zero. Os dados de estabilidade mostraram n

  2. Dual drug delivery using “smart” liposomes for triggered release of anticancer agents

    International Nuclear Information System (INIS)

    Jain, Ankit; Gulbake, Arvind; Jain, Ashish; Shilpi, Satish; Hurkat, Pooja; Jain, Sanjay K.

    2013-01-01

    Ovarian cancer is one of the most fatal gynecologic cancers. In this debut study, dual approach using synergistically active combination of paclitaxel–topotecan (Pac–Top; 20:1, w/w) is investigated with utilization of characteristic features of tumor micro-environment and additionally overexpressed folate receptors (FR-α) to achieve targeting to tumor site. Various liposomes namely liposomes, PEGylated liposomes, and FR-targeted PEGylated liposomes with lipid compositions viz. DPPC:DMPG (85.5:9.5), DPPC:DMPG:mPEG 2000 –DSPE (85.5:9.5:5), and DPPC:DMPG:mPEG 2000 –DSPE:DSPE–PEG–folate (85.5:9.5:4.5:0.5), respectively, were developed using thin film casting method. These were nanometric in size around 200 nm. In vitro drug release study showed initial burst release followed by sustained release for more than 72 h at physiological milieu (37 ± 0.5 °C, pH 7.4) while burst release (i.e., more than 90 %) within 5 min at simulated tumor milieu (41 ± 1 °C, pH 4). SRB cytotoxicity assay in OVCAR-3 cell line revealed Pac–Top free (20:1, w/w) to be more toxic (GI 50 = 6.5 μg/ml) than positive control (Adriamycin, GI 50 = 9.1 μg/ml) and FR-targeted PEGylated liposomes GI 50 (14.7 μg/ml). Moreover, florescence microscopy showed the highest cell uptake of FR-targeted PEGylated liposomes so called “smart liposomes” which has not only mediated effective targeting to FR-α but also triggered release of drugs upon hyperthermia

  3. Dual drug delivery using 'smart' liposomes for triggered release of anticancer agents

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Ankit; Gulbake, Arvind; Jain, Ashish; Shilpi, Satish; Hurkat, Pooja; Jain, Sanjay K., E-mail: drskjainin@yahoo.com [Dr. Hari Singh Gour Vishwavidyalaya, Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences (India)

    2013-07-15

    Ovarian cancer is one of the most fatal gynecologic cancers. In this debut study, dual approach using synergistically active combination of paclitaxel-topotecan (Pac-Top; 20:1, w/w) is investigated with utilization of characteristic features of tumor micro-environment and additionally overexpressed folate receptors (FR-{alpha}) to achieve targeting to tumor site. Various liposomes namely liposomes, PEGylated liposomes, and FR-targeted PEGylated liposomes with lipid compositions viz. DPPC:DMPG (85.5:9.5), DPPC:DMPG:mPEG{sub 2000}-DSPE (85.5:9.5:5), and DPPC:DMPG:mPEG{sub 2000}-DSPE:DSPE-PEG-folate (85.5:9.5:4.5:0.5), respectively, were developed using thin film casting method. These were nanometric in size around 200 nm. In vitro drug release study showed initial burst release followed by sustained release for more than 72 h at physiological milieu (37 {+-} 0.5 Degree-Sign C, pH 7.4) while burst release (i.e., more than 90 %) within 5 min at simulated tumor milieu (41 {+-} 1 Degree-Sign C, pH 4). SRB cytotoxicity assay in OVCAR-3 cell line revealed Pac-Top free (20:1, w/w) to be more toxic (GI{sub 50} = 6.5 {mu}g/ml) than positive control (Adriamycin, GI{sub 50} = 9.1 {mu}g/ml) and FR-targeted PEGylated liposomes GI{sub 50} (14.7 {mu}g/ml). Moreover, florescence microscopy showed the highest cell uptake of FR-targeted PEGylated liposomes so called 'smart liposomes' which has not only mediated effective targeting to FR-{alpha} but also triggered release of drugs upon hyperthermia.

  4. Dual drug delivery using "smart" liposomes for triggered release of anticancer agents

    Science.gov (United States)

    Jain, Ankit; Gulbake, Arvind; Jain, Ashish; Shilpi, Satish; Hurkat, Pooja; Jain, Sanjay K.

    2013-07-01

    Ovarian cancer is one of the most fatal gynecologic cancers. In this debut study, dual approach using synergistically active combination of paclitaxel-topotecan (Pac-Top; 20:1, w/w) is investigated with utilization of characteristic features of tumor micro-environment and additionally overexpressed folate receptors (FR-α) to achieve targeting to tumor site. Various liposomes namely liposomes, PEGylated liposomes, and FR-targeted PEGylated liposomes with lipid compositions viz. DPPC:DMPG (85.5:9.5), DPPC:DMPG:mPEG2000-DSPE (85.5:9.5:5), and DPPC:DMPG:mPEG2000-DSPE:DSPE-PEG-folate (85.5:9.5:4.5:0.5), respectively, were developed using thin film casting method. These were nanometric in size around 200 nm. In vitro drug release study showed initial burst release followed by sustained release for more than 72 h at physiological milieu (37 ± 0.5 °C, pH 7.4) while burst release (i.e., more than 90 %) within 5 min at simulated tumor milieu (41 ± 1 °C, pH 4). SRB cytotoxicity assay in OVCAR-3 cell line revealed Pac-Top free (20:1, w/w) to be more toxic (GI50 = 6.5 μg/ml) than positive control (Adriamycin, GI50 = 9.1 μg/ml) and FR-targeted PEGylated liposomes GI50 (14.7 μg/ml). Moreover, florescence microscopy showed the highest cell uptake of FR-targeted PEGylated liposomes so called "smart liposomes" which has not only mediated effective targeting to FR-α but also triggered release of drugs upon hyperthermia.

  5. POLYCAPROLACTONE-POLY (ETHYLENE GLYCOL) BLOCK COPOLYMER Ⅲ DRUG RELEASE BEHAVIOR

    Institute of Scientific and Technical Information of China (English)

    BEI Jianzhong; WANG Zhifeng; WANG Shenguo

    1995-01-01

    The drug release behavior of degradable polymer - polycaprolactone-poly (ethylene glycol)block copolymer(PCE) in vitro was investigated by using 5-Fluoro-uracil (5-Fu) as a model drug under a condition of pH 7.4 at 37℃. It is found that the release rate of 5-Fu from PCE increased with increasing polyether content of the copolymer. The results show that the increasing polyether content of the copolymer caused increasing hydrophilicity and decreasing crystallinity of the PCE copolymer. Thus, the drug release behavior and the degradable property of the PCE can be controlled by adjusting the composition of the copolymer.

  6. 5-Fluorouracil Encapsulated Chitosan Nanoparticles for pH-Stimulated Drug Delivery: Evaluation of Controlled Release Kinetics

    Directory of Open Access Journals (Sweden)

    R. Seda Tığlı Aydın

    2012-01-01

    Full Text Available Nanoparticles consisting of human therapeutic drugs are suggested as a promising strategy for targeted and localized drug delivery to tumor cells. In this study, 5-fluorouracil (5-FU encapsulated chitosan nanoparticles were prepared in order to investigate potentials of localized drug delivery for tumor environment due to pH sensitivity of chitosan nanoparticles. Optimization of chitosan and 5-FU encapsulated nanoparticles production revealed 148.8±1.1 nm and 243.1±17.9 nm particle size diameters with narrow size distributions, which are confirmed by scanning electron microscope (SEM images. The challenge was to investigate drug delivery of 5-FU encapsulated chitosan nanoparticles due to varied pH changes. To achieve this objective, pH sensitivity of prepared chitosan nanoparticle was evaluated and results showed a significant swelling response for pH 5 with particle diameter of ∼450 nm. In vitro release studies indicated a controlled and sustained release of 5-FU from chitosan nanoparticles with the release amounts of 29.1–60.8% due to varied pH environments after 408 h of the incubation period. pH sensitivity is confirmed by mathematical modeling of release kinetics since chitosan nanoparticles showed stimuli-induced release. Results suggested that 5-FU encapsulated chitosan nanoparticles can be launched as pH-responsive smart drug delivery agents for possible applications of cancer treatments.

  7. Reliability of a Novel Model for Drug Release from 2D HPMC-Matrices

    Directory of Open Access Journals (Sweden)

    Rumiana Blagoeva

    2010-04-01

    Full Text Available A novel model of drug release from 2D-HPMC matrices is considered. Detailed mathematical description of matrix swelling and the effect of the initial drug loading are introduced. A numerical approach to solution of the posed nonlinear 2D problem is used on the basis of finite element domain approximation and time difference method. The reliability of the model is investigated in two steps: numerical evaluation of the water uptake parameters; evaluation of drug release parameters under available experimental data. The proposed numerical procedure for fitting the model is validated performing different numerical examples of drug release in two cases (with and without taking into account initial drug loading. The goodness of fit evaluated by the coefficient of determination is presented to be very good with few exceptions. The obtained results show better model fitting when accounting the effect of initial drug loading (especially for larger values.

  8. A Smart pH-responsive Nano-Carrier as a Drug Delivery System: A hybrid system comprised of mesoporous nanosilica MCM-41 (as a nano-container) & a pH-sensitive polymer (as smart reversible gatekeepers): Preparation, characterization and in vitro release studies of an anti-cancer drug.

    Science.gov (United States)

    Abbaszad Rafi, Abdolrahim; Mahkam, Mehrdad; Davaran, Soodabeh; Hamishehkar, Hamed

    2016-10-10

    A smart pH-responsive drug nano-carrier for controlled release of anti-cancer therapeutics was developed through a facile route. The nano-carrier consisted of two main parts: first, the nano-container part (that mesoporous silica nanoparticles (MCM-41) were selected for this aim); and second, pH-sensitive gatekeepers (that a pH-sensitive polymer, Poly4-vinylpyridine, played this role). In the first step, MCM-41 was synthesized via template assisted sol-gel process. In the second step, polymerizable functional groups were attached onto pore entrances rather than inside walls. In the third step, polymeric gatekeepers were introduced onto pore entrances via precipitation polymerization of functionalized MCM-41 with monomers. Different methods and analysis, such as Fourier Transform Infrared Spectroscopy (FT-IR), X-ray Powder Diffraction (XRD), Thermo-Gravimetric Analysis (TGA), Energy-Dispersive X-ray Spectroscopy (EDX), Zeta Potentials, Dynamic Light Scattering (DLS), Field Emission Scanning Electron Microscope (FE-SEM) and Transmission Electron Microscopy (TEM) were employed to approve the successful attachment of gatekeepers. Furthermore, the release studies of methotroxate (MTX), an anti-cancer drug, were performed in different media (pH4, 5.8 and 7.4) at 37±1°C. The release profiles and curves show that the release rates are completely pH-dependent and it proceeds with a decrease in pH. It is concluded that in the higher pH the gatekeepers are in their close state, but they switch to the open state as a consequence of repulsive forces between positively charged polymer chains appear in acidic media. The results suggest that this smart nano-carrier can be considered as an appropriate candidate to deliver therapeutics to cancerous tissues. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Floating matrix tablets based on low density foam powder: effects of formulation and processing parameters on drug release.

    Science.gov (United States)

    Streubel, A; Siepmann, J; Bodmeier, R

    2003-01-01

    The aim of this study was to develop and physicochemically characterize single unit, floating controlled drug delivery systems consisting of (i). polypropylene foam powder, (ii). matrix-forming polymer(s), (iii). drug, and (iv). filler (optional). The highly porous foam powder provided low density and, thus, excellent in vitro floating behavior of the tablets. All foam powder-containing tablets remained floating for at least 8 h in 0.1 N HCl at 37 degrees C. Different types of matrix-forming polymers were studied: hydroxypropyl methylcellulose (HPMC), polyacrylates, sodium alginate, corn starch, carrageenan, gum guar and gum arabic. The tablets eroded upon contact with the release medium, and the relative importance of drug diffusion, polymer swelling and tablet erosion for the resulting release patterns varied significantly with the type of matrix former. The release rate could effectively be modified by varying the "matrix-forming polymer/foam powder" ratio, the initial drug loading, the tablet geometry (radius and height), the type of matrix-forming polymer, the use of polymer blends and the addition of water-soluble or water-insoluble fillers (such as lactose or microcrystalline cellulose). The floating behavior of the low density drug delivery systems could successfully be combined with accurate control of the drug release patterns.

  10. Externally controlled on-demand release of anti-HIV drug using magneto-electric nanoparticles as carriers.

    Science.gov (United States)

    Nair, Madhavan; Guduru, Rakesh; Liang, Ping; Hong, Jeongmin; Sagar, Vidya; Khizroev, Sakhrat

    2013-01-01

    Although highly active anti-retroviral therapy has resulted in remarkable decline in the morbidity and mortality in AIDS patients, inadequately low delivery of anti-retroviral drugs across the blood-brain barrier results in virus persistence. The capability of high-efficacy-targeted drug delivery and on-demand release remains a formidable task. Here we report an in vitro study to demonstrate the on-demand release of azidothymidine 5'-triphosphate, an anti-human immunodeficiency virus drug, from 30 nm CoFe2O4@BaTiO3 magneto-electric nanoparticles by applying a low alternating current magnetic field. Magneto-electric nanoparticles as field-controlled drug carriers offer a unique capability of field-triggered release after crossing the blood-brain barrier. Owing to the intrinsic magnetoelectricity, these nanoparticles can couple external magnetic fields with the electric forces in drug-carrier bonds to enable remotely controlled delivery without exploiting heat. Functional and structural integrity of the drug after the release was confirmed in in vitro experiments with human immunodeficiency virus-infected cells and through atomic force microscopy, spectrophotometry, Fourier transform infrared and mass spectrometry studies.

  11. Comparative evaluation of polymersome versus micelle structures as vehicles for the controlled release of drugs

    Energy Technology Data Exchange (ETDEWEB)

    Alibolandi, Mona [Mashhad University of Medical Sciences, Biotechnology Research Center, School of Pharmacy (Iran, Islamic Republic of); Ramezani, Mohammad; Abnous, Khalil [Mashhad University of Medical Sciences, Pharmaceutical Research Center, School of Pharmacy (Iran, Islamic Republic of); Sadeghi, Fatemeh, E-mail: sadeghif@mums.ac.ir [Mashhad University of Medical Sciences, Targeted Drug Delivery Research Center, School of Pharmacy (Iran, Islamic Republic of); Hadizadeh, Farzin, E-mail: hadizadehf@mums.ac.ir [Mashhad University of Medical Sciences, Biotechnology Research Center, School of Pharmacy (Iran, Islamic Republic of)

    2015-02-15

    Di-block copolymers composed of two biocompatible polymers, poly(ethylene glycol) and poly(d,l-lactide), were synthesized by ring-opening polymerization for the preparation of doxorubicin-loaded self-assembled nanostructures, including polymeric vesicles (polymersomes) and micelles. The capability and stability of the nanostructures prepared for the controlled release of DOX are discussed in this paper. The in vitro drug release at 37 °C was evaluated up to 6 days at pH 7.4 and 5.5 and in the presence of 50 % FBS. The cellular uptake and cytotoxicity effect of both formulations were also evaluated in the MCF-7 cell line. The SEM and AFM images confirmed the hollow spherical structure of the polymersomes and the solid round structures of the micelles. The TEM results also revealed the uniformity in size and shape of the drug-loaded micelle and polymersome nanostructures. The DOX-loaded micelles and polymersomes presented efficient anticancer performance, as verified by flow cytometry and MTT assay tests. The most important finding of this study is that the prepared nanopolymersomes presented significant increases in the doxorubicin encapsulation efficiency and the stability of the formulation in comparison with the micelle formulation. In vitro studies revealed that polymersomes may be stable in the blood circulation and meet the requirements for an effective drug delivery system.

  12. Light-Regulated Release of Entrapped Drugs from Photoresponsive Gold Nanoparticles

    Directory of Open Access Journals (Sweden)

    Kaniknun Sreejivungsa

    2016-01-01

    Full Text Available Release of a payload in a spatiotemporal fashion has a substantial impact on increasing therapeutic efficacy. In this work, a novel monolayer of gold nanoparticles (AuNPs featuring light-responsive ligands was investigated as a potential drug carrier whose drug release can be triggered by UV light. Hydrophobic molecules were noncovalently entrapped in the compartments of its monolayers. Once irradiated with UV light, the dinitrobenzyl linker was cleaved, leading to release of the entrapped agent. AuNPs were characterized using UV spectrophotometry, TEM, and a zetasizer. A naturally occurring compound extracted from Goniothalamus elegans Ast was chosen as a hydrophobic model drug. Entrapment and release of dye were monitored using fluorimetry. The percent encapsulation of dye was of 13.53%. Entrapped dye can be released upon UV irradiation and can be regulated by changing irradiation time. Up to 83.95±2.2% entrapped dye can be released after irradiation for 20 minutes. In the absence of UV light, dye release was only 19.75%. For comparison purposes, AuNPs having no dinitrobenzyl groups showed a minimal release of 12.23% and 11.69% with and without UV light, respectively. This demonstrated an alternative strategy to encapsulate drugs using a noncovalent approach followed by their controlled release upon UV irradiation.

  13. Drug Loading and Release Behavior Depending on the Induced Porosity of Chitosan/Cellulose Multilayer Nanofilms.

    Science.gov (United States)

    Park, Sohyeon; Choi, Daheui; Jeong, Hyejoong; Heo, Jiwoong; Hong, Jinkee

    2017-10-02

    The ability to control drug loading and release is the most important feature in the development of medical devices. In this research, we prepared a functional nanocoating technology to incorporate a drug-release layer onto a desired substrate. The multilayer films were prepared using chitosan (CHI) and carboxymethyl cellulose (CMC) polysaccharides by the layer-by-layer (LbL) method. By using chemical cross-linking to change the inner structure of the assembled multilayer, we could control the extent of drug loading and release. The cross-linked multilayer film had a porous structure and enhanced water wettability. Interestingly, more of the small-molecule drug was loaded into and released from the non-cross-linked multilayer film, whereas more of the macromolecular drug was loaded into and released from the cross-linked multilayer film. These results indicate that drug loading and release can be easily controlled according to the molecular weight of the desired drug by changing the structure of the film.

  14. A Mechanistic Model for Drug Release in PLGA Biodegradable Stent Coatings Coupled with Polymer Degradation and Erosion

    Science.gov (United States)

    Zhu, Xiaoxiang; Braatz, Richard D.

    2015-01-01

    Biodegradable poly(D,L-lactic-co-glycolic acid) (PLGA) coating for applications in drug-eluting stents has been receiving increasing interest as a result of its unique properties compared with biodurable polymers in delivering drug for reducing stents-related side effects. In this work, a mathematical model for describing the PLGA degradation and erosion and coupled drug release from PLGA stent coating is developed and validated. An analytical expression is derived for PLGA mass loss that predicts multiple experimental studies in the literature. An analytical model for the change of the number-average degree of polymerization (or molecular weight) is also derived. The drug transport model incorporates simultaneous drug diffusion through both the polymer solid and the liquid-filled pores in the coating, where an effective drug diffusivity model is derived taking into account factors including polymer molecular weight change, stent coating porosity change, and drug partitioning between solid and aqueous phases. The model is used to describe in vitro sirolimus release from PLGA stent coating, and demonstrates the significance of simultaneous sirolimus release via diffusion through both polymer solid and pore space. The proposed model is compared to existing drug transport models, and the impact of model parameters, limitations and possible extensions of the model are also discussed. PMID:25345656

  15. Advances in research of targeting delivery and controlled release of drug-loaded nanoparticles

    International Nuclear Information System (INIS)

    Tan Zhonghua

    2003-01-01

    Biochemistry drug, at present, is still the main tool that human struggle to defeat the diseases. So, developing safe and efficacious technique of drug targeting delivery and controlled release is key to enhance curative effect, decrease drug dosage, and lessen its side effect. Drug-loaded nanoparticles, which is formed by conjugate between nanotechnology and modern pharmaceutics, is a new fashioned pharmic delivery carrier. Because of advantages in pharmic targeting transport and controlled or slow release and improving bioavailability, it has been one of developing trend of modern pharmaceutical dosage forms

  16. Nanovesicles released by Dictyostelium cells: a potential carrier for drug delivery.

    Science.gov (United States)

    Lavialle, Françoise; Deshayes, Sophie; Gonnet, Florence; Larquet, Eric; Kruglik, Sergei G; Boisset, Nicolas; Daniel, Régis; Alfsen, Annette; Tatischeff, Irène

    2009-10-01

    Nanovesicles released by Dictyostelium discoideum cells grown in the presence of the DNA-specific dye Hoechst 33342 have been previously shown to mediate the transfer of the dye into the nuclei of Hoechst-resistant cells. The present investigation extends this work by conducting experiments in the presence of hypericin, a fluorescent therapeutic photosensitizer assayed for antitumoral photodynamic therapy. Nanovesicles released by Dictyostelium cells exhibit an averaged diameter between 50 and 150 nm, as measured by transmission cryoelectron microscopy. A proteomic analysis reveals a predominance of actin and actin-related proteins. The detection of a lysosomal membrane protein (LIMP II) indicates that these vesicles are likely generated in the late endosomal compartment. The use of the hypericin-containing nanovesicles as nanodevices for in vitro drug delivery was investigated by fluorescence microscopy. The observed signal was almost exclusively located in the perinuclear area of two human cell lines, skin fibroblasts (HS68) and cervix carcinoma (HeLa) cells. Studies by confocal microscopy with specific markers of cell organelles, provided evidence that hypericin was accumulated in the Golgi apparatus. All these data shed a new light on in vitro drug delivery by using cell-released vesicles as carriers.

  17. Acoustically Triggered Disassembly of Multilayered Polyelectrolyte Thin Films through Gigahertz Resonators for Controlled Drug Release Applications

    Directory of Open Access Journals (Sweden)

    Zhixin Zhang

    2016-11-01

    Full Text Available Controlled drug release has a high priority for the development of modern medicine and biochemistry. To develop a versatile method for controlled release, a miniaturized acoustic gigahertz (GHz resonator is designed and fabricated which can transfer electric supply to mechanical vibrations. By contacting with liquid, the GHz resonator directly excites streaming flows and induces physical shear stress to tear the multilayered polyelectrolyte (PET thin films. Due to the ultra-high working frequency, the shear stress is greatly intensified, which results in a controlled disassembling of the PET thin films. This technique is demonstrated as an effective method to trigger and control the drug release. Both theory analysis and controlled release experiments prove the thin film destruction and the drug release.

  18. Effect of Coating Solvent Ratio on the Drug Release Lag Time of ...

    African Journals Online (AJOL)

    Erah

    Research Article ... Lag Time of Coated Theophylline Osmotic Tablets ... Key words: Coating solvent, Drug release, Lag time, Osmotic tablet, HPMC, .... following composition (w/w): theophylline ... tablets was measured by UV absorption.

  19. Ultrasound, liposomes, and drug delivery: principles for using ultrasound to control the release of drugs from liposomes.

    Science.gov (United States)

    Schroeder, Avi; Kost, Joseph; Barenholz, Yechezkel

    2009-11-01

    Ultrasound is used in many medical applications, such as imaging, blood flow analysis, dentistry, liposuction, tumor and fibroid ablation, and kidney stone disruption. In the past, low frequency ultrasound (LFUS) was the main method to downsize multilamellar (micron range) vesicles into small (nano scale) unilamellar vesicles. Recently, the ability of ultrasound to induce localized and controlled drug release from liposomes, utilizing thermal and/or mechanical effects, has been shown. This review, deals with the interaction of ultrasound with liposomes, focusing mainly on the mechanical mechanism of drug release from liposomes using LFUS. The effects of liposome lipid composition and physicochemical properties, on one hand, and of LFUS parameters, on the other, on liposomal drug release, are addressed. Acoustic cavitation, in which gas bubbles oscillate and collapse in the medium, thereby introducing intense mechanical strains, increases release substantially. We suggest that the mechanism of release may involve formation and collapse of small gas nuclei in the hydrophobic region of the lipid bilayer during exposure to LFUS, thereby inducing the formation of transient pores through which drugs are released. Introducing PEG-lipopolymers to the liposome bilayer enhances responsivity to LFUS, most likely due to absorption of ultrasonic energy by the highly hydrated PEG headgroups. The presence of amphiphiles, such as phospholipids with unsaturated acyl chains, which destabilize the lipid bilayer, also increases liposome susceptibility to LFUS. Application of these principles to design highly LFUS-responsive liposomes is discussed.

  20. Functionality Effect of Pressure Sensitive Adhesives on In Vitro Drug Release Behavior of Fentanyl Drug in an Adhesive Patch

    Directory of Open Access Journals (Sweden)

    S.M. Taghizadeh

    2009-12-01

    Full Text Available Some formulations of drug in adhesive transdermal drug delivery systems (TDDSs( with different functional and non-functional acrylic pressure sensitive adhesives PSAs( were prepared. For this purpose fentanyl was used as a drug component. The effects of PSAs type on skin permeation and in vitro drug release from devices were evaluated using hydrodynamically well-characterized Chien permeation system fitted with excised rat abdominal skin. The adhesion properties of devices (peel strength and tack values( were obtained. It was found that TDDS with –COOH functional PSA had the lowest steady state flux. Drug release was followed by Higuchi's kinetic model. Adhesion properties of the samples were improved by addition of functional PSA in the formulations.

  1. A programmed release multi-drug implant fabricated by three-dimensional printing technology for bone tuberculosis therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wu Weigang; Zheng Qixin; Guo Xiaodong; Sun Jianhua; Liu Yudong, E-mail: Zheng-qx@163.co [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China)

    2009-12-15

    In the world, bone tuberculosis is still very difficult to treat and presents a challenge to clinicians. In this study, we utilized 3D printing technology to fabricate a programmed release multi-drug implant for bone tuberculosis therapy. The construction of the drug implant was a multi-layered concentric cylinder divided into four layers from the center to the periphery. Isoniazid and rifampicin were distributed individually into the different layers in a specific sequence of isoniazid-rifampicin-isoniazid-rifampicin. The drug release assays in vitro and in vivo showed that isoniazid and rifampicin were released orderly from the outside to the center to form the multi-drug therapeutic alliance, and the peak concentrations of drugs were detected in sequence at 8 to 12 day intervals. In addition, no negative effect on the proliferation of rabbit bone marrow mesenchymal stem cells was detected during the cytocompatibility assay. Due to its ideal pharmacologic action and cytocompatibility, the programmed release multi-drug implant with a complex construction fabricated by 3D printing technology could be of interest in prevention and treatment of bone tuberculosis.

  2. A programmed release multi-drug implant fabricated by three-dimensional printing technology for bone tuberculosis therapy

    International Nuclear Information System (INIS)

    Wu Weigang; Zheng Qixin; Guo Xiaodong; Sun Jianhua; Liu Yudong

    2009-01-01

    In the world, bone tuberculosis is still very difficult to treat and presents a challenge to clinicians. In this study, we utilized 3D printing technology to fabricate a programmed release multi-drug implant for bone tuberculosis therapy. The construction of the drug implant was a multi-layered concentric cylinder divided into four layers from the center to the periphery. Isoniazid and rifampicin were distributed individually into the different layers in a specific sequence of isoniazid-rifampicin-isoniazid-rifampicin. The drug release assays in vitro and in vivo showed that isoniazid and rifampicin were released orderly from the outside to the center to form the multi-drug therapeutic alliance, and the peak concentrations of drugs were detected in sequence at 8 to 12 day intervals. In addition, no negative effect on the proliferation of rabbit bone marrow mesenchymal stem cells was detected during the cytocompatibility assay. Due to its ideal pharmacologic action and cytocompatibility, the programmed release multi-drug implant with a complex construction fabricated by 3D printing technology could be of interest in prevention and treatment of bone tuberculosis.

  3. Coaxial Electrospray of Curcumin-Loaded Microparticles for Sustained Drug Release.

    Directory of Open Access Journals (Sweden)

    Shuai Yuan

    Full Text Available Curcumin exhibits superior anti-inflammatory, antiseptic and analgesic activities without significant side effects. However, clinical dissemination of this natural medicine is limited by its low solubility and poor bio-availability. To overcome this limitation, we propose to encapsulate curcumin in poly(lactic-co-glycolic acid (PLGA microparticles (MPs by an improved coaxial electrospray (CES process. This process is able to generate a stable cone-jet mode in a wide range of operation parameters in order to produce curcumin-loaded PLGA MPs with a clear core-shell structure and a designated size of several micrometers. In order to optimize the process outcome, the effects of primary operation parameters such as the applied electric voltages and the liquid flow rates are studied systemically. In vitro drug release experiments are also carried out for the CES-produced MPs in comparison with those by a single axial electrospray process. Our experimental results show that the CES process can be effectively controlled to encapsulate drugs of low aqueous solubility for high encapsulation efficiency and optimal drug release profiles.

  4. Laser-activated nano-biomaterials for tissue repair and controlled drug release

    International Nuclear Information System (INIS)

    Matteini, P; Ratto, F; Rossi, F; Pini, R

    2014-01-01

    We present recent achievements of minimally invasive welding of biological tissue and controlled drug release based on laser-activated nano-biomaterials. In particular, we consider new advancements in the biomedical application of near-IR absorbing gold nano-chromophores as an original solution for the photothermal repair of surgical incisions and as nanotriggers of controlled drug release from hybrid biopolymer scaffolds. (laser biophotonics)

  5. The biowaiver extension for BCS class III drugs: the effect of dissolution rate on the bioequivalence of BCS class III immediate-release drugs predicted by computer simulation.

    Science.gov (United States)

    Tsume, Yasuhiro; Amidon, Gordon L

    2010-08-02

    The Biopharmaceutical Classification System (BCS) guidance issued by the FDA allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release (IR) solid oral dosage forms only for BCS class I drugs. However, a number of drugs within BCS class III have been proposed to be eligible for biowaivers. The World Health Organization (WHO) has shortened the requisite dissolution time of BCS class III drugs on their Essential Medicine List (EML) from 30 to 15 min for extended biowaivers; however, the impact of the shorter dissolution time on AUC(0-inf) and C(max) is unknown. The objectives of this investigation were to assess the ability of gastrointestinal simulation software to predict the oral absorption of the BCS class I drugs propranolol and metoprolol and the BCS class III drugs cimetidine, atenolol, and amoxicillin, and to perform in silico bioequivalence studies to assess the feasibility of extending biowaivers to BCS class III drugs. The drug absorption from the gastrointestinal tract was predicted using physicochemical and pharmacokinetic properties of test drugs provided by GastroPlus (version 6.0). Virtual trials with a 200 mL dose volume at different drug release rates (T(85%) = 15 to 180 min) were performed to predict the oral absorption (C(max) and AUC(0-inf)) of the above drugs. Both BCS class I drugs satisfied bioequivalence with regard to the release rates up to 120 min. The results with BCS class III drugs demonstrated bioequivalence using the prolonged release rate, T(85%) = 45 or 60 min, indicating that the dissolution standard for bioequivalence is dependent on the intestinal membrane permeability and permeability profile throughout the gastrointestinal tract. The results of GastroPlus simulations indicate that the dissolution rate of BCS class III drugs could be prolonged to the point where dissolution, rather than permeability, would control the overall absorption. For BCS class III drugs with intestinal absorption patterns

  6. Influence of different test parameters on in vitro drug release from topical diclofenac formulations in a vertical diffusion cell setup.

    Science.gov (United States)

    Klein, S

    2013-07-01

    In the past decades, the vertical diffusion cell has emerged as a useful device for testing drug release of topical dosage forms. However, to date neither a general USP method nor formulation-related monographs have been published in international pharmacopoeia. The purpose of the present work was to examine the influence of different test parameters in a vertical diffusion cell setup on in vitro drug release from semi-solid preparations for cutaneous application. Diclofenac was selected as the model compound. Release experiments were performed in a 7 ml Microett vertical diffusion cell system. Various test parameters, including the media composition and pH, degassing, membrane material and pore size, stirring speed and stirrer type, were varied. Results obtained with different test parameter settings clearly indicate that both drug properties and instrumental details can have a huge impact on the outcome of in vitro diffusion/drug release studies with the vertical diffusion cell. Thus, the selection of adequate test parameters is crucial for the success of the release experiments and, as shown in the present study, optimal test parameters/conditions need to be established and validated on a case by case study.

  7. Oral matrix tablet formulations for concomitant controlled release of anti-tubercular drugs: design and in vitro evaluations.

    Science.gov (United States)

    Hiremath, Praveen S; Saha, Ranendra N

    2008-10-01

    The aim of the present investigation was to develop controlled release (C.R.) matrix tablet formulations of rifampicin and isoniazid combination, to study the design parameters and to evaluate in vitro release characteristics. In the present study, a series of formulations were developed with different release rates and duration using hydrophilic polymers hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC). The duration of rifampicin and isoniazid release could be tailored by varying the polymer type, polymer ratio and processing techniques. Further, Eudragit L100-55 was incorporated in the matrix tablets to compensate for the pH-dependent release of rifampicin. Rifampicin was found to follow linear release profile with time from HPMC formulations. In case of formulations with HPC, there was an initial higher release in simulated gastric fluid (SGF) followed by zero order release profiles in simulated intestinal fluid (SIFsp) for rifampicin. The release of isoniazid was found to be predominantly by diffusion mechanism in case of HPMC formulations, and with HPC formulations release was due to combination of diffusion and erosion. The initial release was sufficiently higher for rifampicin from HPC thus ruling out the need to incorporate a separate loading dose. The initial release was sufficiently higher for isoniazid in all formulations. Thus, with the use of suitable polymer or polymer combinations and with the proper optimization of the processing techniques it was possible to design the C.R. formulations of rifampicin and isoniazid combination that could provide the sufficient initial release and release extension up to 24h for both the drugs despite of the wide variations in their physicochemical properties.

  8. Incorporation and release of drug into/from superparamagnetic iron oxide nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Maver, Uros; Bele, Marjan [National Institute of Chemistry Slovenia, Hajdrihova 19, 1000 Ljubljana (Slovenia); Makovec, Darko; Campelj, Stanislav [Jozef Stefan Institute, Jamova 39, 1000 Ljubljana (Slovenia); Jamnik, Janko [National Institute of Chemistry Slovenia, Hajdrihova 19, 1000 Ljubljana (Slovenia); Gaberscek, Miran [National Institute of Chemistry Slovenia, Hajdrihova 19, 1000 Ljubljana (Slovenia)], E-mail: miran.gaberscek@ki.si

    2009-10-15

    The aim of this study was to attach a model drug (naproxen) onto superparamagnetic iron oxide nanoparticles (SPION). First, SPION were coated with thin layer of silica that contained micropores. We demonstrated that such surface functionalization could be optimized by the use of citric acid which prevented SPION agglomeration during the procedure. HRTEM investigation showed a uniform 1-2-nm-thick silica coating around SPION. This coating did not affect significantly the magnetic properties of the SPION. Into the coated SPION we successfully incorporated about 30 wt% of naproxen. The latter was readily released after immersion into a testing solution. The composites could be interesting for potential use in diagnostics.

  9. Incorporation and release of drug into/from superparamagnetic iron oxide nanoparticles

    International Nuclear Information System (INIS)

    Maver, Uros; Bele, Marjan; Makovec, Darko; Campelj, Stanislav; Jamnik, Janko; Gaberscek, Miran

    2009-01-01

    The aim of this study was to attach a model drug (naproxen) onto superparamagnetic iron oxide nanoparticles (SPION). First, SPION were coated with thin layer of silica that contained micropores. We demonstrated that such surface functionalization could be optimized by the use of citric acid which prevented SPION agglomeration during the procedure. HRTEM investigation showed a uniform 1-2-nm-thick silica coating around SPION. This coating did not affect significantly the magnetic properties of the SPION. Into the coated SPION we successfully incorporated about 30 wt% of naproxen. The latter was readily released after immersion into a testing solution. The composites could be interesting for potential use in diagnostics.

  10. Drug release control and system understanding of sucrose esters matrix tablets by artificial neural networks.

    Science.gov (United States)

    Chansanroj, Krisanin; Petrović, Jelena; Ibrić, Svetlana; Betz, Gabriele

    2011-10-09

    Artificial neural networks (ANNs) were applied for system understanding and prediction of drug release properties from direct compacted matrix tablets using sucrose esters (SEs) as matrix-forming agents for controlled release of a highly water soluble drug, metoprolol tartrate. Complexity of the system was presented through the effects of SE concentration and tablet porosity at various hydrophilic-lipophilic balance (HLB) values of SEs ranging from 0 to 16. Both effects contributed to release behaviors especially in the system containing hydrophilic SEs where swelling phenomena occurred. A self-organizing map neural network (SOM) was applied for visualizing interrelation among the variables and multilayer perceptron neural networks (MLPs) were employed to generalize the system and predict the drug release properties based on HLB value and concentration of SEs and tablet properties, i.e., tablet porosity, volume and tensile strength. Accurate prediction was obtained after systematically optimizing network performance based on learning algorithm of MLP. Drug release was mainly attributed to the effects of SEs, tablet volume and tensile strength in multi-dimensional interrelation whereas tablet porosity gave a small impact. Ability of system generalization and accurate prediction of the drug release properties proves the validity of SOM and MLPs for the formulation modeling of direct compacted matrix tablets containing controlled release agents of different material properties. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Employment of the porous particles for preparation of the capsules containing aspirin and drug release property

    International Nuclear Information System (INIS)

    Hosoi, Fumio; Makuuchi, Keizo; Saito, Kenji; Koishi, Masumi.

    1985-01-01

    Polymer-coated porous particles containing aspirin as a drug were prepared and the rate of release of aspirin was studied. The impregnation of aspirin was carried out by post-graft polymerization, where methyl methacrylate or methacrylic acid was treated with porous particles, pre-irradiated with γ-ray from 60 Co, in the presence of aspirin. Release of aspirin from modified particles was tested with 50 % methanol solution and/or pH 5.2 buffer solution of acetic acid. The amount of aspirin released from capsules increased with time and reached a constant values after 140 h. The amount of aspirin absorbed in porous particles was increased with graft polymerization. In addition, absorption of aspirin in porous particles was significantly enhanced by treating the particle surface with TiO 2 before irradiation. The amount of aspirin released was linearly to the square root of time. It was concluded that the diffusion of aspirin through the polymer matrix was the rate limiting step. (author)

  12. Synthesis, characterization, release kinetics and toxicity profile of drug-loaded starch nanoparticles.

    Science.gov (United States)

    El-Naggar, Mehrez E; El-Rafie, M H; El-sheikh, M A; El-Feky, Gina S; Hebeish, A

    2015-11-01

    The current research work focuses on the medical application of the cost-effective cross-linked starch nanoparticles, for the transdermal delivery using Diclofenac sodium (DS) as a model drug. The prepared DS-cross-linked starch nanoparticles were synthesized using nanoprecipitation technique at different concentrations of sodium tripolyphosphate (STPP) in the presence of Tween 80 as a surfactant. The resultant cross-linked starch nanoparticles loaded with DS were characterized using world-class facilities such as TEM, DLS, FT-IR, XRD, and DSc. The efficiency of DS loading was also evaluated via entrapment efficiency as well as in vitro release and histopathological study on rat skin. The optimum nanoparticles formulation selected by the JMP(®) software was the formula that composed of 5% maize starch, 57.7mg DS and 0.5% STPP and 0.4% Tween 80, with particle diameter of about 21.04nm, polydispersity index of 0.2 and zeta potential of -35.3mV. It is also worth noting that this selected formula shows an average entrapment efficiency of 95.01 and sustained DS release up to 6h. The histophathological studies using the best formula on rat skin advocate the use of designed transdermal DS loaded cross-linked starch nanoparticles as it is safe and non-irritant to rat skin. The overall results indicate that, the starch nanoparticles could be considered as a good carrier for DS drug regarding the enhancement in its controlled release and successful permeation, thus, offering a promising nanoparticulate system for the transdermal delivery non-steroidal anti-inflammatory drug (NSAID). Copyright © 2015 Elsevier B.V. All rights reserved.

  13. 3D printing of tablets containing multiple drugs with defined release profiles.

    Science.gov (United States)

    Khaled, Shaban A; Burley, Jonathan C; Alexander, Morgan R; Yang, Jing; Roberts, Clive J

    2015-10-30

    We have employed three-dimensional (3D) extrusion-based printing as a medicine manufacturing technique for the production of multi-active tablets with well-defined and separate controlled release profiles for three different drugs. This 'polypill' made by a 3D additive manufacture technique demonstrates that complex medication regimes can be combined in a single tablet and that it is viable to formulate and 'dial up' this single tablet for the particular needs of an individual. The tablets used to illustrate this concept incorporate an osmotic pump with the drug captopril and sustained release compartments with the drugs nifedipine and glipizide. This combination of medicines could potentially be used to treat diabetics suffering from hypertension. The room temperature extrusion process used to print the formulations used excipients commonly employed in the pharmaceutical industry. Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) and X-ray powder diffraction (XRPD) were used to assess drug-excipient interaction. The printed formulations were evaluated for drug release using USP dissolution testing. We found that the captopril portion showed the intended zero order drug release of an osmotic pump and noted that the nifedipine and glipizide portions showed either first order release or Korsmeyer-Peppas release kinetics dependent upon the active/excipient ratio used. Copyright © 2015. Published by Elsevier B.V.

  14. A novel and alternative approach to controlled release drug delivery system based on solid dispersion technique

    Directory of Open Access Journals (Sweden)

    Tapan Kumar Giri

    2012-12-01

    Full Text Available The solid dispersion method was originally used to improve the dissolution properties and the bioavailability of poorly water soluble drugs by dispersing them into water soluble carriers. In addition to the above, dissolution retardation through solid dispersion technique using water insoluble and water swellable polymer for the development of controlled release dosage forms has become a field of interest in recent years. Development of controlled release solid dispersion has a great advantage for bypassing the risk of a burst release of drug; since the structure of the solid dispersion is monolithic where drug molecules homogeneously disperse. Despite the remarkable potential and extensive research being conducted on controlled release solid dispersion system, commercialization and large scale production are limited. The author expects that recent technological advances may overcome the existing limitations and facilitate the commercial utilization of the techniques for manufacture of controlled release solid dispersions. This article begins with an overview of the different carriers being used for the preparation of controlled release solid dispersion and also different techniques being used for the purpose. Kinetics of drug release from these controlled release solid dispersions and the relevant mathematical modeling have also been reviewed in this manuscript.

  15. Development of a cell-based bioassay for phospholipase A2-triggered liposomal drug release

    DEFF Research Database (Denmark)

    Arouri, Ahmad; Trojnar, Jakub; Schmidt, Steffen

    2015-01-01

    models, the pattern of sPLA2-assisted drug release is unknown due to the lack of a suitable bio-relevant model. We report here on the development of a novel bioluminescence living-cell-based luciferase assay for the monitoring of sPLA2-triggered release of luciferin from liposomes. To this end, we...

  16. 77 FR 4227 - Implantation or Injectable Dosage Form New Animal Drugs; Gonadotropin Releasing Factor Analog...

    Science.gov (United States)

    2012-01-27

    ... Factor Analog-Diphtheria Toxoid Conjugate AGENCY: Food and Drug Administration, HHS. ACTION: Final rule... extends the slaughter interval for intact male swine injected with gonadotropin releasing factor analog...-322 for IMPROVEST (gonadotropin releasing factor analog-diphtheria toxoid conjugate) Sterile Solution...

  17. 76 FR 27888 - Implantation or Injectable Dosage Form New Animal Drugs; Gonadotropin Releasing Factor-Diphtheria...

    Science.gov (United States)

    2011-05-13

    ... Factor-Diphtheria Toxoid Conjugate AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. [[Page... veterinary prescription use of gonadotropin releasing factor-diphtheria toxoid conjugate by subcutaneous... provides for the veterinary prescription use of IMPROVEST (gonadotropin releasing factor-diphtheria toxoid...

  18. UV imaging for in vitro dissolution and release studies: Initial experiences

    DEFF Research Database (Denmark)

    Østergaard, Jesper; Lenke, James; Jensen, Sabrine Smedegaard

    2014-01-01

    UV imaging has recently been introduced as a method in drug dissolution and release testing. Spatially and temporally resolved mapping of drug oncentrations in a 7 × 9 mm imaging area provides new opportunities for visualization and study of drug dissolution and release. This review describes...... in hydrogels with relevance for characterization of parenteral depots. UV imaging may be of particular use when the amounts of material are sparse and detailed insights into dissolution and release processes are required, that is in solid form screening, preformulation, and early drug development....

  19. Near-infrared remotely triggered drug-release strategies for cancer treatment

    Science.gov (United States)

    Goodman, Amanda M.; Neumann, Oara; Nørregaard, Kamilla; Henderson, Luke; Choi, Mi-Ran; Clare, Susan E.; Halas, Naomi J.

    2017-11-01

    Remotely controlled, localized drug delivery is highly desirable for potentially minimizing the systemic toxicity induced by the administration of typically hydrophobic chemotherapy drugs by conventional means. Nanoparticle-based drug delivery systems provide a highly promising approach for localized drug delivery, and are an emerging field of interest in cancer treatment. Here, we demonstrate near-IR light-triggered release of two drug molecules from both DNA-based and protein-based hosts that have been conjugated to near-infrared-absorbing Au nanoshells (SiO2 core, Au shell), each forming a light-responsive drug delivery complex. We show that, depending upon the drug molecule, the type of host molecule, and the laser illumination method (continuous wave or pulsed laser), in vitro light-triggered release can be achieved with both types of nanoparticle-based complexes. Two breast cancer drugs, docetaxel and HER2-targeted lapatinib, were delivered to MDA-MB-231 and SKBR3 (overexpressing HER2) breast cancer cells and compared with release in noncancerous RAW 264.7 macrophage cells. Continuous wave laser-induced release of docetaxel from a nanoshell-based DNA host complex showed increased cell death, which also coincided with nonspecific cell death from photothermal heating. Using a femtosecond pulsed laser, lapatinib release from a nanoshell-based human serum albumin protein host complex resulted in increased cancerous cell death while noncancerous control cells were unaffected. Both methods provide spatially and temporally localized drug-release strategies that can facilitate high local concentrations of chemotherapy drugs deliverable at a specific treatment site over a specific time window, with the potential for greatly minimized side effects.

  20. Photoimages and the release characteristics of lipophilic matrix tablets containing highly water-soluble potassium citrate with high drug loadings.

    Science.gov (United States)

    Cao, Qing-Ri; Kim, Tae-Wan; Lee, Beom-Jin

    2007-07-18

    Two types of the carnauba wax-based lipophilic matrix tablet using spray-dried granules (SDT) or directly compressible powdered mixtures (DCT) were prepared for sustained release. The model drug was a highly water-soluble potassium citrate and loaded about 74% of the total tablet weight. The SDT slowly eroded and disintegrated during the release study without showing sustained release when the hydrophilic excipients were added. In contrast, the DCT was more efficient for sustained release. The release rate decreased with increasing carnauba wax concentration. In particular, the sustained release rate was markedly pronounced when the lipophilic stearyl alcohol and stearic acid were combined with the carnauba wax. The surface of the intact DCT appeared to be smooth and rusty. The DCT rose to the surface from the bottom of the vessel during the release test, and numerous pores and cracks with no signs of disintegration were also observed after the release test. The release profile was dependent on the formulation composition and preparation method of the matrix tablet. Diffusion-controlled leaching through the channels of the pores and cracks of the lipophilic matrix tablet (DCT) is a key to the sustained release.

  1. Normalization of doxorubicin release from graphene oxide: New approach for optimization of effective parameters on drug loading.

    Science.gov (United States)

    Hashemi, Mohadeseh; Yadegari, Amir; Yazdanpanah, Ghasem; Omidi, Meisam; Jabbehdari, Sayena; Haghiralsadat, Fatemeh; Yazdian, Fatemeh; Tayebi, Lobat

    2017-05-01

    Graphene oxide (GO) has been recently introduced as a suitable anticancer drug carrier, which could be loaded with doxorubicin (DOX) as a general chemotherapy agent. Herein, the attempts were made to optimize the effective parameters on both loading and release of DOX on GO. GO and GO-DOX were characterized using transition electron microscopy , zeta potential, Raman spectroscopy, UV-visible spectroscopy, and Fourier transform infrared spectroscopy. In addition, loading and releasing behaviors of DOX on GO were studied in terms of different temperature and pH values. The primary optimized values of pH and temperature for best-loaded amount of DOX were 8.9 and 309 K, respectively. Moreover, we found that the smallest amount of released DOX, in pH of cancer microenvironment (5.4), occurs when DOX had been previously loaded in pH 7.8 and 310 K. Although the highest amount of loaded DOX was in basic pH, the results of efficient release of DOX from the GO-DOX complex and also cellular toxicity assay revealed that the best pH for loading of DOX on GO was 7.8. Therefore, in addition to optimization of parameters for efficient loading of DOX on GO, this study suggested that normalization of a released drug compared with the amount of a loaded drug could be a new approach for optimization of drug loading on nanocarriers. © 2016 International Union of Biochemistry and Molecular Biology, Inc.

  2. Rhamnogalacturonan-I based microcapsules for targeted drug release

    DEFF Research Database (Denmark)

    Svagan, Anna J.; Kusic, Anja; De Gobba, Cristian

    2016-01-01

    Drug targeting to the colon via the oral administration route for local treatment of e.g. inflammatory bowel disease and colonic cancer has several advantages such as needle-free administration and low infection risk. A new source for delivery is plant-polysaccharide based delivery platforms...... such as Rhamnogalacturonan-I (RG-I). In the gastro-intestinal tract the RG-I is only degraded by the action of the colonic microflora. For assessment of potential drug delivery properties, RG-I based microcapsules (~1 μm in diameter) were prepared by an interfacial poly-addition reaction. The cross-linked capsules were...

  3. Tailored release drug delivery system for rifampicin and isoniazid for enhanced bioavailability of rifampicin.

    Science.gov (United States)

    Avachat, Amelia M; Bhise, Satish B

    2011-04-01

    The front line antitubercular drugs rifampicin (RMP) and isoniazid (INH), when co-administered, face the problem of reduced bioavailability of RMP. Stabilization of RMP in the presence of INH under acidic environment may improve the bioavailability of RMP. In vitro degradation studies showed around 15-25% degradation of RMP under the aforesaid conditions if the ratio of RMP: INH is above 1:0.5.This degradation is reduced to less than 10% when the ratio of RMP: INH is below 1:0.25. Based on these findings, an innovative drug delivery system was designed with the immediate release of RMP and tailored prolonged release of INH. The bilayer tablets prepared with this concept were subjected to relative bioavailability studies in healthy human volunteers in an open label, balanced, randomized, single-dose, cross-over study under fasted state. A validated LC-MS/MS bioanalytical method was employed for estimation of RMP and INH in plasma. Bioavailability studies revealed that C(max) and AUC for RMP increased by 18 and 20%, respectively, confirming the above innovative concept. Even in the case of INH, AUC increased significantly by around 30% and thus time above minimum inhibitory concentration (MIC) would also increase, which may result in further improved clinical outcome.

  4. Preparation and controlled release of mesoporous MCM-41/propranolol hydrochloride composite drug.

    Science.gov (United States)

    Zhai, Qing-Zhou

    2013-01-01

    This article used MCM-41 as a carrier for the assembly of propranolol hydrochloride by the impregnation method. By means of chemical analysis, powder X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) spectroscopy and low-temperature N(2) adsorption-desorption at 77 K, the characterization was made for the prepared materials. The propranolol hydrochloride guest assembly capacity was 316.20 ± 0.31 mg/g (drug/MCM-41). Powder XRD test results indicated that during the process of incorporation, the frameworks of the MCM-41 were not destroyed and the crystalline degrees of the host-guest nanocomposite materials prepared still remained highly ordered. Characterization by SEM and TEM showed that the composite material presented spherical particle and the average particle size of composite material was 186 nm. FT-IR spectra showed that the MCM-41 framework existed well in the (MCM-41)-propranolol hydrochloride composite. Low-temperature nitrogen adsorption-desorption results at 77 K showed that the guest partially occupied the channels of the molecular sieves. Results of the release of the prepared composite drug in simulated body fluid indicated that the drug can release up to 32 h and its maximum released amount was 99.20 ± 0.11%. In the simulated gastric juice release pattern of drug, the maximum time for the drug release was discovered to be 6 h and the maximum cumulative released amount of propranolol hydrochloride was 45.13 ± 0.23%. The drug sustained-release time was 10 h in simulated intestinal fluid and the maximum cumulative released amount was 62.05 ± 0.13%. The prepared MCM-41 is a well-controlled drug delivery carrier.

  5. A Comparative Study on Micellar and Solubilizing Behavior of Three EO-PO Based Star Block Copolymers Varying in Hydrophobicity and Their Application for the In Vitro Release of Anticancer Drugs

    Directory of Open Access Journals (Sweden)

    Bijal Vyas

    2018-01-01

    Full Text Available The temperature and pH dependent self-assembly of three star shaped ethylene oxide-propylene oxide (EO-PO block copolymers (Tetronics® 304, 904 and 908 with widely different hydrophobicity was examined in aqueous solutions. Physico-chemical methods viz. viscosity, cloud point, solubilization along with thermal, scattering and spectral techniques shows strongly temperature and salt dependent solution behavior. T304 possessing low molecular weight did not form micelles; moderately hydrophilic T904 remained as micelles at ambient temperature and showed micellar growth while very hydrophilic T908 formed micelles at elevated temperatures. The surface activity/micellization/solubilization power was favored in the presence of salt. The copolymers turn more hydrophilic in acidic pH due to protonation of central ethylene diamine moiety that hinders micelle formation. The solubilization of a model insoluble azo dye 1-(o-Tolylazo-2-naphthol (Orange OT and hydrophobic drugs (quercetin and curcumin for copolymer solutions in aqueous and salt solutions are also reported. Among the three copolymers, T904 showed maximum solubility of dye and drugs, hence the in vitro release of drugs from T904 micelles was estimated and the effect on cytotoxicity of loading the drugs in T904 micelles was compared with the cytotoxicity of free drugs on the CHO-K1 cells. The results from the present work provide a better insight in selection of Tetronics® for their application in different therapeutic applications.

  6. Magnetic Active Agent Release System (MAARS): evaluation of a new way for a reproducible, externally controlled drug release into the small intestine.

    Science.gov (United States)

    Dietzel, Christian T; Richert, Hendryk; Abert, Sandra; Merkel, Ute; Hippius, Marion; Stallmach, Andreas

    2012-08-10

    Human absorption studies are used to test new drug candidates for their bioavailability in different regions of the gastrointestinal tract. In order to replace invasive techniques (e.g. oral or rectal intubation) a variety of externally controlled capsule-based drug release systems has been developed. Most of these use ionizing radiation, internal batteries, heating elements or even chemicals for the localization and disintegration process of the capsule. This embodies potential harms for volunteers and patients. We report about a novel technique called "Magnetic Active Agent Release System" (MAARS), which uses purely magnetic effects for this purpose. In our trial thirteen healthy volunteers underwent a complete monitoring and release procedure of 250 mg acetylsalicylic acid (ASA) targeting the flexura duodenojejunalis and the mid-part of the jejunum. During all experiments MAARS initiated a sufficient drug release and was well tolerated. Beside this we also could show that the absorption of ASA is about two times faster in the more proximal region of the flexura duodenojejunalis with a tmax of 47±13 min compared to the more distal jejunum with tmax values of 100±10 min (p=0.031). Copyright © 2012 Elsevier B.V. All rights reserved.

  7. The effects of cyclodextrins on drug release from fatty suppository bases : I. In vitro observations

    NARCIS (Netherlands)

    Frijlink, H.W.; Eissens, Anko; Schoonen, Adelbert; Lerk, C.F.

    The effect of cyclodextrins on suppository drug release was investigated. Complexes of several lipophilic drugs with β- and/or γ-cyclodextrin were prepared using the coprecipitation method. The formation of true complexes was confirmed by DSC and an 'ether-wash' method. Witepsol H15 suppositories

  8. Design Project on Controlled-Release Drug Delivery Devices: Implementation, Management, and Learning Experiences

    Science.gov (United States)

    Xu, Qingxing; Liang, Youyun; Tong, Yen Wah; Wang, Chi-Hwa

    2010-01-01

    A design project that focuses on the subject of controlled-release drug delivery devices is presented for use in an undergraduate course on mass transfer. The purpose of the project is to introduce students to the various technologies used in the fabrication of drug delivery systems and provide a practical design exercise for understanding the…

  9. Enzyme-triggered nanomedicine: Drug release strategies in cancer therapy (Invited Review)

    DEFF Research Database (Denmark)

    Andresen, Thomas Lars; Thompson, David H.; Kaasgaard, Thomas

    2010-01-01

    -based strategies are particularly interesting as they require no prior knowledge of the tumour localization. The basis of this review is an evaluation of the current status of drug delivery strategies focused on triggered drug release by disease-associated enzymes. We limit ourselves to reviewing the liposome...

  10. Aggregation of gold nanoparticles followed by methotrexate release enables Raman imaging of drug delivery into cancer cells

    International Nuclear Information System (INIS)

    Durgadas, C. V.; Sharma, C. P.; Paul, W.; Rekha, M. R.; Sreenivasan, K.

    2012-01-01

    This study refers an aqueous synthesis of methotrexate (MTX)-conjugated gold nanoparticles (GNPs), their interaction with HepG2 cells, and the use of Raman imaging to observe cellular internalization and drug delivery. GNPs of average size 3.5–5 nm were stabilized using the amine terminated bifunctional biocompatible copolymer and amended by conjugating MTX, an anticancer drug. The nanoparticles were released MTX at a faster rate in acidic pH and subsequently found to form aggregates. The Raman signals of cellular components were found to be enhanced by the aggregated particles enabling the mapping to visualize site-specific drug delivery. The methodology seems to have potential in optimizing the characteristics of nanodrug carriers for emptying the cargo precisely at specified sites.Graphical AbstractDrug release induced particle aggregation enhances Raman signals to aid in imaging.

  11. Time-oriented experimental design method to optimize hydrophilic matrix formulations with gelation kinetics and drug release profiles.

    Science.gov (United States)

    Shin, Sangmun; Choi, Du Hyung; Truong, Nguyen Khoa Viet; Kim, Nam Ah; Chu, Kyung Rok; Jeong, Seong Hoon

    2011-04-04

    A new experimental design methodology was developed by integrating the response surface methodology and the time series modeling. The major purposes were to identify significant factors in determining swelling and release rate from matrix tablets and their relative factor levels for optimizing the experimental responses. Properties of tablet swelling and drug release were assessed with ten factors and two default factors, a hydrophilic model drug (terazosin) and magnesium stearate, and compared with target values. The selected input control factors were arranged in a mixture simplex lattice design with 21 experimental runs. The obtained optimal settings for gelation were PEO, LH-11, Syloid, and Pharmacoat with weight ratios of 215.33 (88.50%), 5.68 (2.33%), 19.27 (7.92%), and 3.04 (1.25%), respectively. The optimal settings for drug release were PEO and citric acid with weight ratios of 191.99 (78.91%) and 51.32 (21.09%), respectively. Based on the results of matrix swelling and drug release, the optimal solutions, target values, and validation experiment results over time were similar and showed consistent patterns with very small biases. The experimental design methodology could be a very promising experimental design method to obtain maximum information with limited time and resources. It could also be very useful in formulation studies by providing a systematic and reliable screening method to characterize significant factors in the sustained release matrix tablet. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Partially polymerized liposomes: stable against leakage yet capable of instantaneous release for remote controlled drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Qin Guoting; Li Zheng; Xia Rongmin; Li Feng; O' Neill, Brian E; Li, King C [Department of Radiology, The Methodist Hospital Research Institute, Houston, TX 77030 (United States); Goodwin, Jessica T; Khant, Htet A; Chiu, Wah, E-mail: zli@tmhs.org, E-mail: kli@tmhs.org [National Center for Macromolecular Imaging, Baylor College of Medicine, Houston, TX 77030 (United States)

    2011-04-15

    A critical issue for current liposomal carriers in clinical applications is their leakage of the encapsulated drugs that are cytotoxic to non-target tissues. We have developed partially polymerized liposomes composed of polydiacetylene lipids and saturated lipids. Cross-linking of the diacetylene lipids prevents the drug leakage even at 40 deg. C for days. These inactivated drug carriers are non-cytotoxic. Significantly, more than 70% of the encapsulated drug can be instantaneously released by a laser that matches the plasmon resonance of the tethered gold nanoparticles on the liposomes, and the therapeutic effect was observed in cancer cells. The remote activation feature of this novel drug delivery system allows for precise temporal and spatial control of drug release.

  13. Controlled release studies of calcium alginate hydrogels

    International Nuclear Information System (INIS)

    Rendevski, S.; Andonovski, A.; Mahmudi, N.

    2012-01-01

    Controlled release of substances in many cases may be achieved from calcium alginate hydrogels. In this research, the time dependence of the mass of released model substance bovine serum albumin (BSA) from calcium alginate spherical hydrogels of three different types (G/M ratio) have been investigated. The hydrogels were prepared with the drop-wise method of sodium alginate aqueous solutions with concentration of 0.02 g/cm 3 with 0.01 g/cm 3 BSA and a gelling water bath of chitosan in 0.2 M CH 3 COOH/0.4 M CH 3 COONa with added 0.2 M CaCl 2 .The hydrogel structures were characterized by dynamic light scattering and scanning electron microscopy. The controlled release studies were conducted by UV-Vis spectrophotometry of the released medium with p H=7 at 37 °C. The results showed that the model of osmotic pumping is the dominant mechanism of the release. Also, large dependences of the release profile on the homogeneity of the hydrogels were found. (Author)

  14. Sustained drug release and electrochemical performance of ethyl cellulose-magnesium hydrogen phosphate composite

    Energy Technology Data Exchange (ETDEWEB)

    Mohammad, Faruq, E-mail: fmohammad@ksu.edu.sa [Surfactant Research chair, Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451 (Saudi Arabia); Arfin, Tanvir, E-mail: t_arfin@neeri.res.in [Environmental Materials Division, CSIR-National Environmental Engineering Research Institute (CSIR-NEERI), Nehru Marg, Nagpur 440020 (India); Al-Lohedan, Hamad A. [Surfactant Research chair, Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451 (Saudi Arabia)

    2017-02-01

    In this, a sol-gel method was applied to prepare ethyl cellulose-magnesium hydrogen phosphate (EC-MgHPO{sub 4}) composite that can have potential applications in the sensory, pharmaceutical, and biomedical sectors. The formed composite was thoroughly characterized by making use of the instrumental analysis such as UV–Vis, FT-IR, HRTEM, EDAX, SEM and XRD. For the composite, the other parameters determined includes the water uptake, porosity, thickness, bulk and tapped densities, angle of repose, Carr's index and Hausner ratio. From the results, the material found to exhibit good flowing properties with a Carr's index of 11.11%, Hausner ratio of 1.125, and angle of response of 33°. The EDAX spectrum and HRTEM analysis confirmed for the composite formation and the particles size is investigated to be around 52 nm. The surface porosity due to the EC matrices was confirmed by the SEM analysis, which further used for the loading of drug, Proguanil. In addition, the material's conductivity was studied by taking uni-univalent electrolyte solution (KCl and NaCl) indicated that the conductivity follows the order of KCl > NaCl, while the activation energy obtained from Arrhenius method resembled that the conductivity is strongly influenced by the electrolyte type used. We found from the analysis that, with a decrease in the size of hydrated radii of ions, the conductivity of EC-MgHPO{sub 4} material also observed to be decreased in the order K{sup +} > Na{sup +} and the material proved to be mechanically stable and can be operated over a range of pHs, temperatures, and electrolyte solutions. Further, the drug loading and efficiency studies indicated that the material can trap up to 80% of Proguanil (antimalarial drug) applied for its loading. The Proguanil drug release profiles confirmed for the controlled and sustained release from the EC-MgHPO{sub 4} matrix, as the material can release up to 87% of its total loaded drug over a 90 min period. Finally, the

  15. Sustained drug release and electrochemical performance of ethyl cellulose-magnesium hydrogen phosphate composite

    International Nuclear Information System (INIS)

    Mohammad, Faruq; Arfin, Tanvir; Al-Lohedan, Hamad A.

    2017-01-01

    In this, a sol-gel method was applied to prepare ethyl cellulose-magnesium hydrogen phosphate (EC-MgHPO 4 ) composite that can have potential applications in the sensory, pharmaceutical, and biomedical sectors. The formed composite was thoroughly characterized by making use of the instrumental analysis such as UV–Vis, FT-IR, HRTEM, EDAX, SEM and XRD. For the composite, the other parameters determined includes the water uptake, porosity, thickness, bulk and tapped densities, angle of repose, Carr's index and Hausner ratio. From the results, the material found to exhibit good flowing properties with a Carr's index of 11.11%, Hausner ratio of 1.125, and angle of response of 33°. The EDAX spectrum and HRTEM analysis confirmed for the composite formation and the particles size is investigated to be around 52 nm. The surface porosity due to the EC matrices was confirmed by the SEM analysis, which further used for the loading of drug, Proguanil. In addition, the material's conductivity was studied by taking uni-univalent electrolyte solution (KCl and NaCl) indicated that the conductivity follows the order of KCl > NaCl, while the activation energy obtained from Arrhenius method resembled that the conductivity is strongly influenced by the electrolyte type used. We found from the analysis that, with a decrease in the size of hydrated radii of ions, the conductivity of EC-MgHPO 4 material also observed to be decreased in the order K + > Na + and the material proved to be mechanically stable and can be operated over a range of pHs, temperatures, and electrolyte solutions. Further, the drug loading and efficiency studies indicated that the material can trap up to 80% of Proguanil (antimalarial drug) applied for its loading. The Proguanil drug release profiles confirmed for the controlled and sustained release from the EC-MgHPO 4 matrix, as the material can release up to 87% of its total loaded drug over a 90 min period. Finally, the cell viability and

  16. A prominent anchoring effect on the kinetic control of drug release from mesoporous silica nanoparticles (MSNs).

    Science.gov (United States)

    Tran, Vy Anh; Lee, Sang-Wha

    2018-01-15

    This work demonstrated kinetically controlled release of model drugs (ibuprofen, FITC) from well-tailored mesoporous silica nanoparticles (MSNs) depending on the surface charges and molecular sizes of the drugs. The molecular interactions between entrapped drugs and the pore walls of MSNs controlled the release of the drugs through the pore channels of MSNs. Also, polydopamine (PDA) layer-coated MSNs (MSNs@PDA) was quite effective to retard the release of large FITC, in contrast to a slight retardation effect on relatively small Ibuprofen. Of all things, FITC (Fluorescein isothiocyanate)-labeled APTMS (3-aminopropyltrimethoxysilane) (APTMS-FITC conjugates) grafted onto the MSNs generate a pinch-effect on the pore channel (so-called a prominent anchoring effect), which was highly effective in trapping (or blocking) drug molecules at the pore mouth of the MSNs. The anchored APTMS-FITC conjugates provided not only tortuous pathways to the diffusing molecules, but also sustained release of the ibuprofen over a long period of time (∼7days). The fast release kinetics was predicted by an exponential equation based on Fick's law, while the slow release kinetics was predicted by Higuchi model. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Drug Release Profile from Calcium-Induced Alginate-Phosphate Composite Gel Beads

    Directory of Open Access Journals (Sweden)

    Yoshifumi Murata

    2009-01-01

    Full Text Available Calcium-induced alginate-phosphate composite gel beads were prepared, and model drug release profiles were investigated in vitro. The formation of calcium phosphate in the alginate gel matrix was observed and did not affect the rheological properties of the hydrogel beads. X-ray diffraction patterns showed that the calcium phosphate does not exist in crystalline form in the matrix. The initial release amount and release rate of a water-soluble drug, diclofenac, from the alginate gel beads could be controlled by modifying the composition of the matrix with calcium phosphate. In contrast, the release profile was not affected by the modification for hydrocortisone, a drug only slightly soluble in water.

  18. [In vitro drug release behavior of carrier made of porous glass ceramics].

    Science.gov (United States)

    Wang, De-ping; Huang, Wen-hai; Zhou, Nai

    2002-09-01

    To conduct the in vitro test on drug release of rifampin encapsulated in a carrier made of porous phosphate glass ceramics and to analyze main factors which affect the drug release rate. A certain quantitative of rifampin was sealed in a hollow cylindrical capsule which consisted of chopped calcium phosphate crystal fiber obtained from glass crystallization. The rifampin concentration was measured in the simulated physiological solution in which the capsule soaked. Rifampin could be released in a constant rate from the porous glass ceramic carrier in a long time. The release rate was dependent on the size of crystal fiber and the wall thickness of the capsule. This kind of calcium phosphate glass ceramics can be a candidate of the carrier materials used as long term drug therapy after osteotomy surgery.

  19. Effect of co-administration of probiotics with polysaccharide based colon targeted delivery systems to optimize site specific drug release.

    Science.gov (United States)

    Prudhviraj, G; Vaidya, Yogyata; Singh, Sachin Kumar; Yadav, Ankit Kumar; Kaur, Puneet; Gulati, Monica; Gowthamarajan, K

    2015-11-01

    Significant clinical success of colon targeted dosage forms has been limited by their inappropriate release profile at the target site. Their failure to release the drug completely in the colon may be attributed to changes in the colonic milieu because of pathological state, drug effect and psychological stress accompanying the diseased state or, a combination of these. Alteration in normal colonic pH and bacterial picture leads to incomplete release of drug from the designed delivery system. We report the effectiveness of a targeted delivery system wherein the constant replenishment of the colonic microbiota is achieved by concomitant administration of probiotics along with the polysaccharide based drug delivery system. Guar gum coated spheroids of sulfasalazine were prepared. In the dissolution studies, these spheroids showed markedly higher release in the simulated colonic fluid. In vivo experiments conducted in rats clearly demonstrated the therapeutic advantage of co-administration of probiotics with guar gum coated spheroids. Our results suggest that concomitant use of probiotics along with the polysaccharide based delivery systems can be a simple strategy to achieve satisfactory colon targeting of drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. A novel dissolution media for testing drug release from a nanostructured polysaccharide-based colon specific drug delivery system: an approach to alternative colon media.

    Science.gov (United States)

    Kotla, Niranjan G; Singh, Sima; Maddiboyina, Balaji; Sunnapu, Omprakash; Webster, Thomas J

    2016-01-01

    The aim of this study was to develop a novel microbially triggered and animal-sparing dissolution method for testing of nanorough polysaccharide-based micron granules for colonic drug delivery. In this method, probiotic cultures of bacteria present in the colonic region were prepared and added to the dissolution media and compared with the performance of conventional dissolution methodologies (such as media with rat cecal and human fecal media). In this study, the predominant species (such as Bacteroides, Bifidobacterium, Lactobacillus species, Eubacterium and Streptococcus) were cultured in 12% w/v skimmed milk powder and 5% w/v grade "A" honey. Approximately 10(10)-10(11) colony forming units m/L of probiotic culture was added to the dissolution media to test the drug release of polysaccharide-based formulations. A USP dissolution apparatus I/II using a gradient pH dissolution method was used to evaluate drug release from formulations meant for colonic drug delivery. Drug release of guar gum/Eudragit FS30D coated 5-fluorouracil granules was assessed under gastric and small intestine conditions within a simulated colonic environment involving fermentation testing with the probiotic culture. The results with the probiotic system were comparable to those obtained from the rat cecal and human fecal-based fermentation model, thereby suggesting that a probiotic dissolution method can be successfully applied for drug release testing of any polysaccharide-based oral formulation meant for colonic delivery. As such, this study significantly adds to the nanostructured biomaterials' community by elucidating an easier assay for colonic drug delivery.

  1. Multi-Drug-Loaded Microcapsules with Controlled Release for Management of Parkinson's Disease.

    Science.gov (United States)

    Baek, Jong-Suep; Choo, Chee Chong; Qian, Cheng; Tan, Nguan Soon; Shen, Zexiang; Loo, Say Chye Joachim

    2016-07-01

    Parkinson's disease (PD) is a progressive disease of the nervous system, and is currently managed through commercial tablets that do not sufficiently enable controlled, sustained release capabilities. It is hypothesized that a drug delivery system that provides controlled and sustained release of PD drugs would afford better management of PD. Hollow microcapsules composed of poly-l-lactide (PLLA) and poly (caprolactone) (PCL) are prepared through a modified double-emulsion technique. They are loaded with three PD drugs, i.e., levodopa (LD), carbidopa (CD), and entacapone (ENT), at a ratio of 4:1:8, similar to commercial PD tablets. LD and CD are localized in both the hollow cavity and PLLA/PCL shell, while ENT is localized in the PLLA/PCL shell. Release kinetics of hydrophobic ENT is observed to be relatively slow as compared to the other hydrophilic drugs. It is further hypothesized that encapsulating ENT into PCL as a surface coating onto these microcapsules can aid in accelerating its release. Now, these spray-coated hollow microcapsules exhibit similar release kinetics, according to Higuchi's rate, for all three drugs. The results suggest that multiple drug encapsulation of LD, CD, and ENT in gastric floating microcapsules could be further developed for in vivo evaluation for the management of PD. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Fabrication, characterization, in vitro drug release and glucose uptake activity of 14-deoxy, 11, 12-didehydroandrographolide loaded polycaprolactone nanoparticles

    Directory of Open Access Journals (Sweden)

    Nagalakshmi Kamaraj

    2017-07-01

    Full Text Available Biodegradable polymer based novel drug delivery systems brought a considerable attention in enhancing the therapeutic efficacy and bioavailability of various drugs. 14-deoxy 11, 12-didehydro andrographolide (poorly water soluble compound loaded polycaprolactone (nano-DDA was synthesized using the solvent evaporation technique. Nano-DDA was characterized by scanning electron microscopy (SEM and dynamic light scattering (DLS studies. Fourier Transform InfraRed Spectroscopy (FTIR was used to investigate the structural interaction between the drug and the polymer. Functional characterization of the formulation was determined using drug content, cellular uptake and in vitro drug release. 2-deoxy-D-[1-3H] glucose uptake assay was carried out to assess the antidiabetic potential of nano-DDA in L6 myotubes. The nano-DDA displayed spherical shape with a smooth surface (252.898 nm diameter, zeta potential, encapsulation and loading efficiencies of −38.9 mV, 91.98 ± 0.13% and 15.09 ± 0.18% respectively. No structural alteration between the drug and the polymer was evidenced (FTIR analysis. Confocal microscopy studies with rhodamine 123 loaded polycaprolactone nanoparticles (Rh123-PCL NPs revealed the internalization of Rh123-PCL NPs in a time dependent manner in L6 myoblasts. A dose dependent increase in glucose uptake was observed for nano-DDA with a maximal uptake of 108.54 ± 1.42% at 100 nM on L6 myotubes, thereby proving its anti-diabetic efficacy. A biphasic pattern of in vitro drug release demonstrated an initial burst release at 24 h followed by a sustained release for up to 11 days. To conclude, our results revealed that nano-DDA formulation can be a potent candidate for antidiabetic drug delivery.

  3. Advances in Hybrid Polymer-Based Materials for Sustained Drug Release

    Directory of Open Access Journals (Sweden)

    Lígia N. M. Ribeiro

    2017-01-01

    Full Text Available The use of biomaterials composed of organic pristine components has been successfully described in several purposes, such as tissue engineering and drug delivery. Drug delivery systems (DDS have shown several advantages over traditional drug therapy, such as greater therapeutic efficacy, prolonged delivery profile, and reduced drug toxicity, as evidenced by in vitro and in vivo studies as well as clinical trials. Despite that, there is no perfect delivery carrier, and issues such as undesirable viscosity and physicochemical stability or inability to efficiently encapsulate hydrophilic/hydrophobic molecules still persist, limiting DDS applications. To overcome that, biohybrid systems, originating from the synergistic assembly of polymers and other organic materials such as proteins and lipids, have recently been described, yielding molecularly planned biohybrid systems that are able to optimize structures to easily interact with the targets. This work revised the biohybrid DDS clarifying their advantages, limitations, and future perspectives in an attempt to contribute to further research of innovative and safe biohybrid polymer-based system as biomaterials for the sustained release of active molecules.

  4. Preparation of 5-fluorouracil loaded chitosan microparticle and its drug release properties

    Directory of Open Access Journals (Sweden)

    Li Mingming

    2017-01-01

    Full Text Available Chitosan is one kind of good biocompatible polymer and is suitble for drug carriers. Preparation of 5-fluorouracil (5-Fu loaded chitosan (CS particles and in vitro release experiment were performed using ionic crosslinking method with sodium tripolyphosphate (TPP as crosslinker. The optimal preparing parameters were verified by 5-Fu release experiments. The drug loading, and release behavior of drug loaded microparticles in vitro were investigated. The optimal preparation conditions were: the temperature 25°C, the ratio of CS to TPP 5:1, the CS concentration 1.5g/L, stirring speed 650rpm. Under these conditions, the drug loading of particles was up to 45%.

  5. The effect of powder blend and tablet structure on drug release mechanisms of hydrophobic starch acetate matrix tablets

    NARCIS (Netherlands)

    Van Veen, B.; Pajander, J.; Zuurman, K.; Lappalainen, R.; Poso, A.; Frijlink, H.W.; Ketolainen, J.

    2005-01-01

    This study investigates the release mechanism of a hydrophilic drug (caffeine) from hydrophobic matrix tablets composed of starch acetate. Different particle size fractions of starch acetate were mixed with caffeine (22% V/V) to obtain various mixture organisations in the powder, as 14 well as in

  6. Corrosion and drug release properties of EN-plating/PLGA composite coating on MAO film

    International Nuclear Information System (INIS)

    Lu Ping; Liu Yin; Guo Meiqing; Fang Haidong; Xu Xinhua

    2011-01-01

    The electroless nickel plating/poly(DL-lactide-co-glycolide) composite coating (EN-plating/PLGA composite coating) was fabricated on the surface of the micro-arc oxidation (MAO) film of the magnesium alloy AZ81 to double control the corrosion and drug release in the hanks' solution. The EN-plating was fabricated on the MAO coating to improve the corrosion resistance by overlaying most pores and micro-cracks on the surface of the MAO film. Meanwhile, a double layered organic poly(DL-lactide-co-glycolide)/paclitaxel (PLGA/PTX) drug releasing coating with a top layered PLGA drug controlled releasing coating on EN plating was prepared to control the drug release rate by adjusting the different lactide: glycolide (LA:GA) ratio of PLGA. Scanning electron microscopy (SEM) and the X-ray powder diffraction (XRD) were used to analyze the morphology and the composition of the EN-plating. The corrosion behavior of the magnesium alloy substrate and the status of the drug in the PLGA matrix were respectively evaluated by Potentiodynamic polarization and Differential scanning calorimetry (DSC). The drug release was determined by ultraviolet-visible (UV-visible) spectrophotometer. EN-plating coating which was composed of compact cauliflower nodules was uniform in size and defect free with no pores or cracks. EN-plating could seal the microcracks and microholes on the outer layer of the MAO coating effectively. The corrosion resistance was improved by preventing the corrosive ions from diffusing to the magnesium alloy substrate. The drug release rate of PTX exhibited a nearly linear sustained-release profile with no significant burst releases. - Research highlights: → An organic and in organic EN-plating/PLGA composite coating was first fabricated on the surface of the MAO film. → This composite coating the magnesium alloy AZ81could double control the corrosion and drug release in the hanks' solution. → The drug release rate could be controlled by LG:GA ratio and the PTX

  7. Corrosion and drug release properties of EN-plating/PLGA composite coating on MAO film

    Energy Technology Data Exchange (ETDEWEB)

    Lu Ping [School of Materials Science and Engineering, and Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin 300072 (China); Liu Yin [Department of Cardiology, Tianjin Chest Hospital, Tianjin 300051 (China); Guo Meiqing; Fang Haidong [School of Materials Science and Engineering, and Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin 300072 (China); Xu Xinhua, E-mail: xhxu_tju@eyou.com [School of Materials Science and Engineering, and Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin 300072 (China)

    2011-10-10

    The electroless nickel plating/poly(DL-lactide-co-glycolide) composite coating (EN-plating/PLGA composite coating) was fabricated on the surface of the micro-arc oxidation (MAO) film of the magnesium alloy AZ81 to double control the corrosion and drug release in the hanks' solution. The EN-plating was fabricated on the MAO coating to improve the corrosion resistance by overlaying most pores and micro-cracks on the surface of the MAO film. Meanwhile, a double layered organic poly(DL-lactide-co-glycolide)/paclitaxel (PLGA/PTX) drug releasing coating with a top layered PLGA drug controlled releasing coating on EN plating was prepared to control the drug release rate by adjusting the different lactide: glycolide (LA:GA) ratio of PLGA. Scanning electron microscopy (SEM) and the X-ray powder diffraction (XRD) were used to analyze the morphology and the composition of the EN-plating. The corrosion behavior of the magnesium alloy substrate and the status of the drug in the PLGA matrix were respectively evaluated by Potentiodynamic polarization and Differential scanning calorimetry (DSC). The drug release was determined by ultraviolet-visible (UV-visible) spectrophotometer. EN-plating coating which was composed of compact cauliflower nodules was uniform in size and defect free with no pores or cracks. EN-plating could seal the microcracks and microholes on the outer layer of the MAO coating effectively. The corrosion resistance was improved by preventing the corrosive ions from diffusing to the magnesium alloy substrate. The drug release rate of PTX exhibited a nearly linear sustained-release profile with no significant burst releases. - Research highlights: {yields} An organic and in organic EN-plating/PLGA composite coating was first fabricated on the surface of the MAO film. {yields} This composite coating the magnesium alloy AZ81could double control the corrosion and drug release in the hanks' solution. {yields} The drug release rate could be controlled by LG

  8. Swelling kinetics of spray-dried chitosan acetate assessed by magnetic resonance imaging and their relation to drug release kinetics of chitosan matrix tablets.

    Science.gov (United States)

    Huanbutta, Kampanart; Sriamornsak, Pornsak; Limmatvapirat, Sontaya; Luangtana-anan, Manee; Yoshihashi, Yasuo; Yonemochi, Etsuo; Terada, Katsuhide; Nunthanid, Jurairat

    2011-02-01

    Magnetic resonance imaging (MRI) was used to assess in situ swelling behaviors of spray-dried chitosan acetate (CSA) in 0.1N HCl, pH 6.8 and pH 5.0 Tris-HCl buffers. The in vitro drug releases from CSA matrix tablets containing the model drugs, diclofenac sodium and theophylline were investigated in all media using USP-4 apparatus. The effect of chitosan molecular weight, especially in pH 6.8 Tris-HCl, was also studied. In 0.1N HCl, the drug release from the matrix tablets was the lowest in relation to the highest swelling of CSA. The swelling kinetics in Tris-HCl buffers are Fickian diffusion according to their best fit to Higuchi's model as well as the drug release kinetics in all the media. The high swelling rate (k(s)(')) was found to delay the drug release rate (k'). The linear relationship between the swelling and fractions of drug release in Tris-HCl buffers was observed, indicating an important role of the swelling on controlling the drug release mechanism. Additionally, CSA of 200 and 800 kDa chitosan did not swell in pH 6.8 Tris-HCl but disintegrated into fractions, and the drug release from the matrix tablets was the highest. Copyright © 2010 Elsevier B.V. All rights reserved.

  9. In Situ Probing Intracellular Drug Release from Redox-Responsive Micelles by United FRET and AIE.

    Science.gov (United States)

    Wang, Xuelin; Li, Juanjuan; Yan, Qi; Chen, Yanrui; Fan, Aiping; Wang, Zheng; Zhao, Yanjun

    2018-03-01

    Redox-responsive micelles are versatile nanoplatforms for on-demand drug delivery, but the in situ evaluation of drug release is challenging. Fluorescence resonance energy transfer (FRET) technique shows potential for addressing this, while the aggregation-caused quenching effect limits the assay sensitivity. The aim of the current work is to combine aggregation-induced emission (AIE) probe with FRET to realize drug release assessment from micelles. Tetraphenylethene (TPE) is selected as AIE dye and curcumin (Cur) is chosen as the model drug as well as FRET receptor. The drug is covalently linked to a block copolymer via the disulfide bond linker and TPE is also chemically linked to the polymer via an amide bond; the obtained amphiphilic polymer conjugate self-assembles into micelles with a hydrodynamic size of ≈125 nm. Upon the supplement of glutathione or tris(2-carboxyethyl)phosphine) trigger (10 × 10 -3 m), the drug release induces the fluorescence increase of both TPE and Cur. Accompanied with the FRET decay, absorption enhancement and particle size increase are observed. The same phenomenon is observed in MCF-7 cells. The FRET-AIE approach can be a useful addition to the spectrum of available methods for monitoring drug release from stimuli-responsive nanomedicine. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Tailoring the properties of mPEG-PLLA nanoparticles for better encapsulation and tuned release of the hydrophilic anticancer drug.

    Science.gov (United States)

    Surwase, Sachin S; Munot, Neha M; Idage, Bhaskar B; Idage, Susheela B

    2017-06-01

    Gemcitabine is used as a first-line drug for treating many solid tumours. However, it suffers from a major drawback of strong side effects and short plasma half-life because of degradation by enzyme when administered intravenously. Polyesters and copolyesters are the most widely used and preferred class of biodegradable polymer. In the present work, efforts have been made to prepare poly(ethylene glycol) monomethoxy ether-poly(L-lactide) (mPEG-PLLA), a biodegradable amphiphilic copolymer with a view to improve the entrapment and tuned release of hydrophilic drug gemcitabine. The different mPEG-PLLA copolymers were synthesized with the varying ratios of mPEG and characterized by different techniques namely FTIR and 1 H NMR spectroscopy, solution viscosity, differential scanning calorimetry (DSC) and gel permeation chromatography (GPC). Gemcitabine-loaded nanoparticles were prepared using mPEG-PLLA copolymers by two methods i.e. nanoprecipitation and double emulsion solvent evaporation. The nanoprecipitation method showed very less entrapment and polymer solubility in the acetone-water mixture leading to uncontrolled polymer precipitation. The difficulties encountered in the nanoprecipitation method were overcome with the help of the double emulsion (w/o/w) solvent evaporation technique. It has been observed from the results that biodegradable copolymer nanoparticles protect the drug from degradation and also help in controlling the release of encapsulated drug. The properties of nanoparticles can be tailored by varying the composition of mPEG in order to get improved entrapment efficiency and desired drug release. The nanoparticles were assessed for their in vitro cytotoxicity (MTT and FACS) and cellular uptake (fluorescence microscopy) study which showed very promising results. Nanoparticles were also studied for their in vivo release after intravenous administration to Wistar albino rats, which successfully showed controlled drug release for more than 14 days.

  11. Biocompatible magnetic and molecular dual-targeting polyelectrolyte hybrid hollow microspheres for controlled drug release.

    Science.gov (United States)

    Du, Pengcheng; Zeng, Jin; Mu, Bin; Liu, Peng

    2013-05-06

    Well-defined biocompatible magnetic and molecular dual-targeting polyelectrolyte hybrid hollow microspheres have been accomplished via the layer-by-layer (LbL) self-assembly technique. The hybrid shell was fabricated by the electrostatic interaction between the polyelectrolyte cation, chitosan (CS), and the hybrid anion, citrate modified ferroferric oxide nanoparticles (Fe3O4-CA), onto the uniform polystyrene sulfonate microsphere templates. Then the magnetic hybrid core/shell composite particles were modified with a linear, functional poly(ethylene glycol) (PEG) monoterminated with a biotargeting molecule (folic acid (FA)). Afterward the dual targeting hybrid hollow microspheres were obtained after etching the templates by dialysis. The dual targeting hybrid hollow microspheres exhibit exciting pH response and stability in high salt-concentration media. Their pH-dependent controlled release of the drug molecule (anticancer drug, doxorubicin (DOX)) was also investigated in different human body fluids. As expected, the cell viability of the HepG2 cells which decreased more rapidly was treated by the FA modified hybrid hollow microspheres rather than the unmodified one in the in vitro study. The dual-targeting hybrid hollow microspheres demonstrate selective killing of the tumor cells. The precise magnetic and molecular targeting properties and pH-dependent controlled release offers promise for cancer treatment.

  12. The synthesis and application involving regulation of the insoluble drug release from mesoporous silica nanotubes

    International Nuclear Information System (INIS)

    Li, Jia; Wang, Yan; Zheng, Xin; Zhang, Ying; Sun, Changshan; Gao, Yikun; Jiang, Tongying; Wang, Siling

    2015-01-01

    Highlights: • Mesoporous silica nanotubes (SNT) were synthesized by using CNT as hard template, and the formation of the SNT shows that CTAB played a significant effect on the coating process. • The tube mesoporous silica materials which were seldom reported were applied in the drug delivery system to improve the loading amount and the drug dissolution. • The release rate could be controlled by the gelatin layer on the silica surface and the mechanism was illustrated. - Abstract: Mesoporous silica nanotubes (SNT) were synthesized using hard template carbon nanotubes (CNT) with the aid of cetyltrimethyl ammonium bromide (CTAB) in a method, which was simple and inexpensive. Scanning electron microscopy, transmission electron microscopy and specific surface area analysis were employed to characterize the morphology and structure of SNT, and the formation mechanism of SNT was also examined by Fourier transform infrared spectroscopy. There are few published reports of the mesoporous SNT with large specific surface area applied in the drug delivery systems to improve the amount of drug loading. In addition, the structure of SNT allows investigators to control the drug particle size in the pore channels and significantly increase the drug dissolution rate. The insoluble drug, cilostazol, was chosen as a model drug to be loaded into SNT and we developed a simple and efficient method for regulating the drug release by using a gelatin coating with different thicknesses around the SNT. The release rate was adjusted by the amount of gelatin surrounding the SNT, with an increased barrier leading to a reduction in the release rate. A model developed on the basis of the Weibull modulus was established to fit the release results

  13. Sustained release of intravitreal flurbiprofen from a novel drug-in-liposome-in-hydrogel formulation.

    Science.gov (United States)

    Pachis, K; Blazaki, S; Tzatzarakis, M; Klepetsanis, P; Naoumidi, E; Tsilimbaris, M; Antimisiaris, S G

    2017-11-15

    A novel Flurbiprofen (FLB)-in-liposome-in-hydrogel formulation was developed, as a method to sustain the release and increase the ocular bioavailability of FLB following intravitreal injection. For this, FLB loading into liposomes was optimized and liposomes were entrapped in thermosensitive hydrogels consisted of Pluronic F-127 (P). FLB solution, liposomes, and FLB dissolved in hydrogel were also used as control formulations. Actively loaded liposomes were found to be optimal for high FLB loading and small size, while in vitro studies revealed that P concentration of 18% (w/v) was best to retain the integrity of the hydrogel-dispersed liposome, compared to a 20% concentration. The in vitro release of FLB was significantly sustained when FLB-liposomes were dispersed in the hydrogel compared to hydrogel dissolved FLB, as well as the other control formulations. In vivo studies were carried out in pigmented rabbits which were injected through a 27G needle with 1mg/mL FLB in the different formulation-types. Ophthalmic examinations after intravitreal injection of all FLB formulations, revealed no evidence of inflammation, hemorrhage, uveitis or endophthalmitis. Pharmacokinetic analysis results confirm that the hybrid drug delivery system increases the bioavailability (by 1.9 times compared to solution), and extends the presence of the drug in the vitreous cavity, while liposome and hydrogel formulations demonstrate intermediate performance. Furthermore the hybrid system increases MRT of FLB in aqueous humor and retina/choroid tissues, compared to all the control formulations. Currently the potential therapeutic advances of FLB sustained release formulations for IVT administration are being evaluated. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Piroxicam loaded alginate beads obtained by prilling/microwave tandem technique: morphology and drug release.

    Science.gov (United States)

    Aquino, Rita P; Auriemma, Giulia; d'Amore, Matteo; D'Ursi, Anna Maria; Mencherini, Teresa; Del Gaudio, Pasquale

    2012-07-01

    This paper presents a tandem technique, based on the combination of prilling and microwave (MW) assisted treatments, to produce biodegradable alginate carriers of piroxicam with different drug controlled release behaviours. Results showed that alginate/piroxicam beads demonstrated high encapsulation efficiency and very narrow dimensional distribution. Beads dried by MW retained shape and size distribution of the hydrated particles while drying rate was strongly increased compared to convective drying processes. Moreover, different MW irradiation regimes promoted interactions between the drug and alginate matrix, affected drug polymorphism as well as inner and surface matrix structure leading to different piroxicam release profiles. High level MW irradiation led to beads with highly porous and swellable matrix able to release piroxicam in few minutes in the intestine while convective drying produced gastro-resistant beads that exhibit sustained piroxicam release (total release in 5.5h) in intestinal environment. On these results the tandem technique prilling/MW irradiation appears to be promising to obtain alginate carrier with tailored NSAIDs release depending on drug characteristics and MW irradiation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Magnetic nanoparticles for a new drug delivery system to control quercetin releasing for cancer chemotherapy

    International Nuclear Information System (INIS)

    Barreto, A. C. H.; Santiago, V. R.; Mazzetto, S. E.; Denardin, J. C.; Lavín, R.; Mele, Giuseppe; Ribeiro, M. E. N. P.; Vieira, Icaro G. P.; Gonçalves, Tamara; Ricardo, N. M. P. S.

    2011-01-01

    Quercetin belongs to the chemical class of flavonoids and can be found in many common foods, such as apples, nuts, berries, etc. It has been demonstrated that quercetin has a wide array of biological effects that are considered beneficial to health treatment, mainly as anticancer. However, therapeutic applications of quercetin have been restricted to oral administration due to its sparing solubility in water and instability in physiological medium. A drug delivery methodology was proposed in this work to study a new quercetin release system in the form of magnetite–quercetin–copolymer (MQC). These materials were characterized through XRD, TEM, IR, and Thermal analysis. In addition, the magnetization curves and quercetin releasing experiments were performed. It was observed a nanoparticle average diameter of 11.5 and 32.5 nm at Fe 3 O 4 and MQC, respectively. The presence of magnetic nanoparticles in this system offers the promise of targeting specific organs within the body. These results indicate the great potential for future applications of the MQC to be used as a new quercetin release system.

  16. Coaxial PCL/PVA electrospun nanofibers: osseointegration enhancer and controlled drug release device

    International Nuclear Information System (INIS)

    Song, Wei; Shi, Tong; Ren, Weiping; Yu, Xiaowei; Markel, David C

    2013-01-01

    The failure of prosthesis after total joint replacement is mainly due to dysfunctional osseointegration and implant infection. There is a critical need for orthopedic implants that promote rapid osseointegration and prevent bacterial colonization, particularly when placed in bone compromised by disease or physiology of the patients. The aim of this study was to fabricate a novel coaxial electrospun polycaprolactone (PCL)/polyvinyl alcohol (PVA) core-sheath nanofiber (NF) blended with both hydroxyapatite nanorods (HA) and type I collagen (Col) (PCL Col /PVA HA ). Doxycycline (Doxy) and dexamethasone (Dex) were successfully incorporated into the PCL Col /PVA HA NFs for controlled release. The morphology, surface hydrophilicity and mechanical properties of the PCL/PVA NF mats were analyzed by scanning electron microscopy, water contact angle and atomic force microscopy. The PCL Col /PVA HA NFs are biocompatible and enhance the adhesion and proliferation of murine pre-osteoblastic MC3T3 cells. The release of Doxy and Dex from coaxial PCL Col /PVA HA NFs showed more controlled release compared with the blended NFs. Using an ex vivo porcine bone implantation model we found that the PCL Col /PVA HA NFs bind firmly on the titanium rod surface and the NFs coating remained intact on the surface of titanium rods after pullout. No disruption or delamination was observed after the pullout test. These findings indicate that PCL Col /PVA HA NFs encapsulating drugs have great potential in enhancing implant osseointegration and preventing implant infection. (paper)

  17. Coaxial PCL/PVA electrospun nanofibers: osseointegration enhancer and controlled drug release device.

    Science.gov (United States)

    Song, Wei; Yu, Xiaowei; Markel, David C; Shi, Tong; Ren, Weiping

    2013-09-01

    The failure of prosthesis after total joint replacement is mainly due to dysfunctional osseointegration and implant infection. There is a critical need for orthopedic implants that promote rapid osseointegration and prevent bacterial colonization, particularly when placed in bone compromised by disease or physiology of the patients. The aim of this study was to fabricate a novel coaxial electrospun polycaprolactone (PCL)/polyvinyl alcohol (PVA) core-sheath nanofiber (NF) blended with both hydroxyapatite nanorods (HA) and type I collagen (Col) (PCL(Col)/PVA(HA)). Doxycycline (Doxy) and dexamethasone (Dex) were successfully incorporated into the PCL(Col)/PVA(HA) NFs for controlled release. The morphology, surface hydrophilicity and mechanical properties of the PCL/PVA NF mats were analyzed by scanning electron microscopy, water contact angle and atomic force microscopy. The PCL(Col)/PVA(HA) NFs are biocompatible and enhance the adhesion and proliferation of murine pre-osteoblastic MC3T3 cells. The release of Doxy and Dex from coaxial PCL(Col)/PVA(HA) NFs showed more controlled release compared with the blended NFs. Using an ex vivo porcine bone implantation model we found that the PCL(Col)/PVA(HA) NFs bind firmly on the titanium rod surface and the NFs coating remained intact on the surface of titanium rods after pullout. No disruption or delamination was observed after the pullout test. These findings indicate that PCL(Col)/PVA(HA) NFs encapsulating drugs have great potential in enhancing implant osseointegration and preventing implant infection.

  18. Mini-tablets versus pellets as promising multiparticulate modified release delivery systems for highly soluble drugs.

    Science.gov (United States)

    Gaber, Dina M; Nafee, Noha; Abdallah, Osama Y

    2015-07-05

    Whether mini-tablets (tablets, diameters ≤6mm) belong to single- or multiple-unit dosage forms is still questionable. Accordingly, Pharmacopoeial evaluation procedures for mini-tablets are lacking. In this study, the aforementioned points were discussed. Moreover, their potential for oral controlled delivery was assessed. The antidepressant venlafaxine hydrochloride (Vx), a highly soluble drug undergoing first pass effect, low bioavailability and short half-life was selected as a challenging payload. In an attempt to weigh up mini-tablets versus pellets as multiparticulate carriers, Vx-loaded mini-tablets were compared to formulated pellets of the same composition and the innovator Effexor(®)XR pellets. Formulations were prepared using various polymer hydrogels in the core and ethyl cellulose film coating with increasing thickness. Mini-tablets (diameter 2mm) showed extended Vx release (<60%, 8h). Indeed, release profiles comparable to Effexor(®)XR pellets were obtained. Remarkably higher coating thickness was required for pellets to provide equivalent retardation. Ethyl cellulose in the core ensured faster release due to polymer migration to the surface and pore formation in the coat. mini-tablets showed higher stability to pellets upon storage. Industrially speaking, mini-tablets proved to be superior to pellets in terms of manufacturing, product quality and economical aspects. Results point out the urgent need for standardized evaluation procedures for mini-tablets. Copyright © 2015. Published by Elsevier B.V.

  19. Magnetoliposomes for controlled drug release in the presence of low-frequency magnetic field

    KAUST Repository

    Nappini, Silvia

    2010-01-01

    In this work we have studied the effect of a low-frequency alternating magnetic field (LF-AMF) on the permeability of magnetoliposomes, i.e. liposomes including magnetic nanoparticles within their water pool. Large unilamellar liposomes loaded with magnetic cobalt ferrite nanoparticles (CoFe 2O4) have been prepared and characterized. Structural characterization of the liposomal dispersion has been performed by dynamic light scattering (DLS). The enhancement of liposome permeability upon exposure to LF-AMF has been measured as the self-quenching decrease of a fluorescent hydrophilic molecule (carboxyfluorescein, CF) entrapped in the liposome pool. Liposome leakage has been monitored as a function of field frequency, time of exposure and concentration, charge and size of the embedded nanoparticles. The results show that CF release from magnetoliposomes is strongly promoted by LF-AMF, reasonably as a consequence of nanoparticle motions in the liposome pool at the applied frequency. CF release as a function of time in magnetoliposomes unexposed to magnetic field follows Fickian diffusion, while samples exposed to LF-AMF show zero-order kinetics, consistently with an anomalous transport, due to an alteration of the bilayer permeability. These preliminary results open up new perspectives in the use of these systems as carriers in targeted and controlled release of drugs. © The Royal Society of Chemistry 2010.

  20. Regenerated cellulose micro-nano fiber matrices for transdermal drug release

    International Nuclear Information System (INIS)

    Liu, Yue; Nguyen, Andrew; Allen, Alicia; Zoldan, Janet; Huang, Yuxiang; Chen, Jonathan Y.

    2017-01-01

    In this work, biobased fibrous membranes with micro- and nano-fibers are fabricated for use as drug delivery carries because of their biocompatibility, eco-friendly approach, and potential for scale-up. The cellulose micro-/nano-fiber (CMF) matrices were prepared by electrospinning of pulp in an ionic liquid, 1-butyl-3-methylimidazolium chloride. A model drug, ibuprofen (IBU), was loaded on the CMF matrices by a simple immersing method. The amount of IBU loading was about 6% based on the weight of cellulose membrane. The IBU-loaded CMF matrices were characterized by Fourier-transform infrared spectroscopy, thermal gravimetric analysis, and scanning electron microscopy. The test of ibuprofen release was carried out in an acetate buffer solution of pH 5.5 and examined by UV–Vis spectroscopy. Release profiles from the CMF matrices indicated that the drug release rate could be determined by a Fickian diffusion mechanism. - Highlights: • Cellulose micro-nano fiber matrix was prepared by dry-wet electrospinning. • Ibuprofen was loaded on the matrix by a simple immersing method. • The drug loaded matrix showed a biphasic release profile. • The drug release was determined by a Fickian diffusion mechanism.

  1. Regenerated cellulose micro-nano fiber matrices for transdermal drug release

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yue [School of Human Ecology, The University of Texas at Austin, Austin, TX (United States); Department of Chemistry, School of Science, Tianjin University, Tianjin (China); Nguyen, Andrew; Allen, Alicia; Zoldan, Janet [Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX (United States); Huang, Yuxiang [School of Human Ecology, The University of Texas at Austin, Austin, TX (United States); Chen, Jonathan Y., E-mail: jychen2@austin.utexas.edu [School of Human Ecology, The University of Texas at Austin, Austin, TX (United States)

    2017-05-01

    In this work, biobased fibrous membranes with micro- and nano-fibers are fabricated for use as drug delivery carries because of their biocompatibility, eco-friendly approach, and potential for scale-up. The cellulose micro-/nano-fiber (CMF) matrices were prepared by electrospinning of pulp in an ionic liquid, 1-butyl-3-methylimidazolium chloride. A model drug, ibuprofen (IBU), was loaded on the CMF matrices by a simple immersing method. The amount of IBU loading was about 6% based on the weight of cellulose membrane. The IBU-loaded CMF matrices were characterized by Fourier-transform infrared spectroscopy, thermal gravimetric analysis, and scanning electron microscopy. The test of ibuprofen release was carried out in an acetate buffer solution of pH 5.5 and examined by UV–Vis spectroscopy. Release profiles from the CMF matrices indicated that the drug release rate could be determined by a Fickian diffusion mechanism. - Highlights: • Cellulose micro-nano fiber matrix was prepared by dry-wet electrospinning. • Ibuprofen was loaded on the matrix by a simple immersing method. • The drug loaded matrix showed a biphasic release profile. • The drug release was determined by a Fickian diffusion mechanism.

  2. Community reentry challenges after release from prison among people who inject drugs in St. Petersburg, Russia.

    Science.gov (United States)

    Cepeda, Javier A; Vetrova, Marina V; Lyubimova, Alexandra I; Levina, Olga S; Heimer, Robert; Niccolai, Linda M

    2015-01-01

    Little is known about the context of the post-release risk environment among formerly incarcerated people who inject drugs (PWID) in Russia. The purpose of this paper is to explore these challenges as they relate to reentry, relapse to injection opioid use, and overdose. The authors conducted 25 in-depth semi-structured interviews among PWID living in St Petersburg, Russia who had been incarcerated within the past two years. Participants were recruited from street outreach (n=20) and a drug treatment center (n=5). Emergent themes related to the post-release environment included financial instability, negative interactions with police, return to a drug using community, and reuniting with drug using peers. Many respondents relapsed to opioid use immediately after release. Those whose relapse occurred weeks or months after their release expressed more motivation to resist. Alcohol or stimulant use often preceded the opioid relapse episode. Among those who overdosed, alcohol use was often reported prior to overdosing on opioids. Future post-release interventions in Russia should effectively link PWID to social, medical, and harm reduction services. Particular attention should be focussed on helping former inmates find employment and overdose prevention training prior to leaving prison that should also cover the heightened risk of concomitant alcohol use. In addition to describing a syndemic involving the intersection of incarceration, injection drug use, poverty, and alcohol abuse, the findings can inform future interventions to address these interrelated public health challenges within the Russian setting.

  3. Modulation of the formation and release of bovine SRS-A in vitro by several anti-anaphylactic drugs.

    Science.gov (United States)

    Burka, J F; Eyre, P

    1975-01-01

    Slow-reacting substance of anaphylaxis (SRS-A) is released immunologically from bovine lung in vitro. Various drugs known to protect calves and other animals during anaphylaxis were tested to investigate their modulation of the formation and release of SRS-A. The anti-inflammatory drugs, meclofenamate and aspirin, potentiated SRS-A release. Chlorphenesin and diethylcarbamazine citrate at high concentrations both inhibited SRS-A release. Two new anti-anaphylactic drugs, PR-D-92-EA and M&B 22,948, were particularly effective in inhibiting SRS-A release at low concentrations. The possible modes of actions of these drugs are discussed.

  4. Tracking of Drug Release and Material Fate for Naturally Derived Omega-3 Fatty Acid Biomaterials.

    Science.gov (United States)

    Faucher, Keith M; Artzi, Natalie; Beck, Moshe; Beckerman, Rita; Moodie, Geoff; Albergo, Theresa; Conroy, Suzanne; Dale, Alicia; Corbeil, Scott; Martakos, Paul; Edelman, Elazer R

    2016-03-01

    In vitro and in vivo studies were conducted on omega-3 fatty acid-derived biomaterials to determine their utility as an implantable material for adhesion prevention following soft tissue hernia repair and as a means to allow for the local delivery of antimicrobial or antibiofilm agents. Naturally derived biomaterials offer several advantages over synthetic materials in the field of medical device development. These advantages include enhanced biocompatibility, elimination of risks posed by the presence of toxic catalysts and chemical crosslinking agents, and derivation from renewable resources. Omega-3 fatty acids are readily available from fish and plant sources and can be used to create implantable biomaterials either as a stand-alone device or as a device coating that can be utilized in local drug delivery applications. In-depth characterization of material erosion degradation over time using non-destructive imaging and chemical characterization techniques provided mechanistic insight into material structure: function relationship. This in turn guided rational tailoring of the material based on varying fatty acid composition to control material residence time and hence drug release. These studies demonstrate the utility of omega-3 fatty acid derived biomaterials as an absorbable material for soft tissue hernia repair and drug delivery applications.

  5. Stepwise-activable multifunctional peptide-guided prodrug micelles for cancerous cells intracellular drug release

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jing, E-mail: zhangjing@zjut.edu.cn; Li, Mengfei [Zhejiang University of Technology, College of Materials Science and Engineering (China); Yuan, Zhefan [Zhejiang University, Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Department of Chemical and Biological Engineering (China); Wu, Dan; Chen, Jia-da; Feng, Jie, E-mail: fengjie@zjut.edu.cn [Zhejiang University of Technology, College of Materials Science and Engineering (China)

    2016-10-15

    A novel type of stepwise-activable multifunctional peptide-guided prodrug micelles (MPPM) was fabricated for cancerous cells intracellular drug release. Deca-lysine sequence (K{sub 10}), a type of cell-penetrating peptide, was synthesized and terminated with azido-glycine. Then a new kind of molecule, alkyne modified doxorubicin (DOX) connecting through disulfide bond (DOX-SS-alkyne), was synthesized. After coupling via Cu-catalyzed azide–alkyne cycloaddition (CuAAC) click chemistry reaction, reduction-sensitive peptide-guided prodrug was obtained. Due to the amphiphilic property of the prodrug, it can assemble to form micelles. To prevent the nanocarriers from unspecific cellular uptake, the prodrug micelles were subsequently modified with 2,3-dimethyl maleic anhydride to obtain MPPM with a negatively charged outer shell. In vitro studies showed that MPPM could be shielded from cells under psychological environment. However, when arriving at mild acidic tumor site, the cell-penetrating capacity of MPPM would be activated by charge reversal of the micelles via hydrolysis of acid-labile β-carboxylic amides and regeneration of K{sub 10}, which enabled efficient internalization of MPPM by tumor cells as well as following glutathione- and protease-induced drug release inside the cancerous cells. Furthermore, since the guide peptide sequences can be accurately designed and synthesized, it can be easily changed for various functions, such as targeting peptide, apoptotic peptide, even aptamers, only need to be terminated with azido-glycine. This method can be used as a template for reduction-sensitive peptide-guided prodrug for cancer therapy.Graphical abstractA novel type of stepwise-activable multifunctional peptide-guided prodrug micelles (MPPM) was fabricated for selective drug delivery in cancerous cells. MPPM could be shielded from cells under psychological environment. However, when arriving at mild acidic tumor site, the cell-penetrating capacity of MPPM would

  6. Repetitive on-demand drug release from polymeric matrices containing a macroscopic spherical iron core.

    Science.gov (United States)

    Rovers, Stefan A; Kemmere, Maartje F; Keurentjes, Jos T F; Hoogenboom, Richard

    2017-09-15

    A system for multiple on-demand drug release has been prepared that can be activated with an alternating magnetic field as external trigger. The core/shell samples have been developed based on a macroscopic spherical iron core coated with a thermoresponsive polymer, poly(styrene-stat-butyl methacrylate), containing ibuprofen as a model drug. During exposure of the samples to the magnetic field (ON state), the release rate of ibuprofen is significantly increased, up to 35 times the release rate without the magnetic field (OFF state). Using one sample or two samples in line with the magnetic field does not influence the ON/OFF ratio of the system, showing the possibility of using multiple samples to increase and tune the drug dose. Increasing the concentration of ibuprofen in the polymer layer is shown to increase the release rate in both the ON and OFF states. Increasing the size of the iron core and, consequently, decreasing the polymer thickness, was found to only increase the release rate during exposure resulting in higher ON/OFF ratios. The developed on demand drug delivery systems represents a promising development towards on demand drug delivery implants. During my chemical engineering studies, it was only during my master thesis work that I decided to continue with PhD research as I really enjoyed doing original research. When coming to the end of my PhD research under supervision of Prof. Ulrich S. Schubert, I developed the ambition to pursue an academic career. Fortunately, I got the opportunity to stay with Prof. Schubert as project leader for the Dutch Polymer Institute (DPI). Within this position, I supervised ten researchers and was able to start developing my independent research lines. Despite that I now advise students to not stay in the same laboratory, this first position allowed me to gain some initial independence and to publish a large number of papers that has been a great benefit in my further career. After two and a half years I needed a new

  7. Drug release from enzyme-mediated in situ-forming hydrogel based on gum tragacanth-tyramine conjugate.

    Science.gov (United States)

    Dehghan-Niri, Maryam; Tavakol, Moslem; Vasheghani-Farahani, Ebrahim; Ganji, Fariba

    2015-05-01

    In the present study, injectable hydrogels based on gum tragacanth-tyramine conjugate were prepared by enzymatic oxidation of tyramine radicals in the presence of hydrogen peroxide. Then, in vitro release of bovine serum albumin and insulin as model protein drugs from this polymeric network was investigated. Also, to improve the properties of this hydrogel, a blended hydrogel composed of tyramine-conjugated gelatin and tyramine-conjugated tragacanth was prepared. Experimental results showed that the gelation time ranged from 3 to 28 s depending on the polymer and enzyme concentrations. Results of morphological investigation of hydrogels indicated that the average pore size of hydrogels varied from 120 to 160 µm. Swelling degree of hydrogels and the rate of drug release decreased by increasing of hydrogen peroxide and polymer concentrations. The release profile of drug from hydrogels followed Higuchi and Fickian diffusion mechanism. Finally, it was shown that the swelling characteristics and drug release behavior of this polymeric network could be improved by blending it with tyramine-conjugated gelatin. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  8. Fully glutathione degradable waterborne polyurethane nanocarriers: Preparation, redox-sensitivity, and triggered intracellular drug release

    Energy Technology Data Exchange (ETDEWEB)

    Omrani, Ismail; Babanejad, Niloofar; Shendi, Hasan Kashef; Nabid, Mohammad Reza, E-mail: m-nabid@sbu.ac.ir

    2017-01-01

    Polyurethanes are important class of biomaterials that are extensively used in medical devices. In spite of their easy synthesis, polyurethanes that are fully degradable in response to the intracellular reducing environment are less explored for controlled drug delivery. Herein, a novel glutathione degradable waterborne polyurethane (WPU) nanocarrier for redox triggered intracellular delivery of a model lipophilic anticancer drug, doxorubicin (DOX) is reported. The WPU was prepared from polyaddition reaction of isophorone diisocyanate (IPDI) and a novel linear polyester polyol involving disulfide linkage, disulfide labeled chain extender, dimethylolpropionic acid (DMPA) using dibutyltin dilaurate (DBTDL) as a catalyst. The resulting polyurethane self-assembles into nanocarrier in water. The dynamic light scattering (DLS) measurements and scanning electron microscope (SEM) revealed fast swelling and disruption of nanocarriers under an intracellular reduction-mimicking environment. The in vitro release studies showed that DOX was released in a controlled and redox-dependent manner. MTT assays showed that DOX-loaded WPU had a high in vitro antitumor activity in both HDF noncancer cells and MCF- 7 cancer cells. In addition, it is found that the blank WPU nanocarriers are nontoxic to HDF and MCF-7 cells even at a high concentration of 2 mg/mL. Hence, nanocarriers based on disulfide labeled WPU have appeared as a new class of biocompatible and redox-degradable nanovehicle for efficient intracellular drug delivery. - Highlights: • A novel fully glutathione degradable waterborne polyurethane was developed. • The waterborne nanocarrier with disulfide bonds in both hard and soft segment were developed for redox-triggered intracellular delivery of DOX. • The polyester diol bearing disulfide bonds in the backbone was prepared by a polycondensation polymerization reaction.

  9. A magnetic nanoparticle stabilized gas containing emulsion for multimodal imaging and triggered drug release.

    Science.gov (United States)

    Guo, Wei; Li, Diancheng; Zhu, Jia-an; Wei, Xiaohui; Men, Weiwei; Yin, Dazhi; Fan, Mingxia; Xu, Yuhong

    2014-06-01

    To develop a multimodal imaging guided and triggered drug delivery system based on a novel emulsion formulation composed of iron oxide nanoparticles, nanoscopic bubbles, and oil containing drugs. Iron oxide paramagnetic nanoparticles were synthesized and modified with surface conjugation of polyethylenimide (PEI) or Bovine Serum Albumin (BSA). Both particles were used to disperse and stabilize oil in water emulsions containing coumarin-6 as the model drug. Sulfur hexafluoride was introduced into the oil phase to form nanoscopic bubbles inside the emulsions. The resulted gas containing emulsions were evaluated for their magnetic resonance (MR) and ultrasound (US) imaging properties. The drug release profile triggered by ultrasound was also examined. We have successfully prepared the highly integrated multi-component emulsion system using the surface modified iron oxide nanoparticles to stabilize the interfaces. The resulted structure had distinctive MR and US imaging properties. Upon application of ultrasound waves, the gas containing emulsion would burst and encapsulated drug could be released. The integrated emulsion formulation was multifunctional with paramagnetic, sono-responsive and drug-carrying characteristics, which may have potential applications for disease diagnosis and imaging guided drug release.

  10. Direct encapsulation of water-soluble drug into silica microcapsules for sustained release applications

    International Nuclear Information System (INIS)

    Wang Jiexin; Wang Zhihui; Chen Jianfeng; Yun, Jimmy

    2008-01-01

    Direct encapsulation of water-soluble drug into silica microcapsules was facilely achieved by a sol-gel process of tetraethoxysilane (TEOS) in W/O emulsion with hydrochloric acid (HCl) aqueous solution containing Tween 80 and drug as well as cyclohexane solution containing Span 80. Two water-soluble drugs of gentamicin sulphate (GS) and salbutamol sulphate (SS) were chosen as model drugs. The characterization of drug encapsulated silica microcapsules by scanning electronic microscopy (SEM), FTIR, thermogravimetry (TG) and N 2 adsorption-desorption analyses indicated that drug was successfully entrapped into silica microcapsules. The as-prepared silica microcapsules were uniform spherical particles with hollow structure, good dispersion and a size of 5-10 μm, and had a specific surface area of about 306 m 2 /g. UV-vis and thermogravimetry (TG) analyses were performed to determine the amount of drug encapsulated in the microcapsules. The BJH pore size distribution (PSD) of silica microcapsules before and after removing drug was examined. In vitro release behavior of drug in simulated body fluid (SBF) revealed that such system exhibited excellent sustained release properties

  11. Modeling drug release from functionalized magnetic nanoparticles actuated by non-heating low frequency magnetic field

    Energy Technology Data Exchange (ETDEWEB)

    Golovin, Y., E-mail: nano@tsutmb.ru [M.V. Lomonosov Moscow State University, School of Chemistry (Russian Federation); Golovin, D. [G.R. Derzhavin Tambov State University (Russian Federation); Klyachko, N.; Majouga, A.; Kabanov, A. [M.V. Lomonosov Moscow State University, School of Chemistry (Russian Federation)

    2017-02-15

    Various plausible acceleration mechanisms of drug release from nanocarriers composed of a single-domain magnetic nanoparticle core with attached long macromolecule chains activated by low frequency non-heating alternating magnetic field (AMF) are discussed. The most important system characteristics affecting the AMF exposure impact are determined. Impact of several reasonable mechanisms is estimated analytically or obtained using numerical modeling. Some conditions providing manifold release acceleration as a result from exposure in AMF are found.

  12. Modeling drug release from functionalized magnetic nanoparticles actuated by non-heating low frequency magnetic field

    International Nuclear Information System (INIS)

    Golovin, Y.; Golovin, D.; Klyachko, N.; Majouga, A.; Kabanov, A.

    2017-01-01

    Various plausible acceleration mechanisms of drug release from nanocarriers composed of a single-domain magnetic nanoparticle core with attached long macromolecule chains activated by low frequency non-heating alternating magnetic field (AMF) are discussed. The most important system characteristics affecting the AMF exposure impact are determined. Impact of several reasonable mechanisms is estimated analytically or obtained using numerical modeling. Some conditions providing manifold release acceleration as a result from exposure in AMF are found.

  13. Evaluations of dielectric property and drug release profile of 5-FU patches based on plasma charged electrets

    Science.gov (United States)

    Wang, YUAN; Hejuan, LIANG; Ping, HUANG; Xiaoqiang, AN; Jian, JIANG; Lili, CUI

    2018-05-01

    In the present study, the electret 5-fluorouracil patch was developed, the effective surface potential, piezoelectric coefficient d 33, open-circuit thermally stimulated discharge (TSD) current spectra and shear adhesion of the patch were measured. The drug release profile of the patch was determined by using high performance liquid chromatography method. A stable potential difference which was positively dependent on the surface potential of the electret was generated on two sides of the patch. The measurements of d 33 coefficient, TSD current spectra and adhesion performance showed that the electrostatic field of the electret could cause polarization and cohesive strength decreasing of the matrix molecules, change the distribution and interaction of the drug molecules in patch, therefore to increase the release of drug from the transdermal patch.

  14. Oral controlled release drug delivery system and Characterization of oral tablets; A review

    Directory of Open Access Journals (Sweden)

    Muhammad Zaman

    2016-01-01

    Full Text Available Oral route of drug administration is considered as the safest and easiest route of drug administration. Control release drug delivery system is the emerging trend in the pharmaceuticals and the oral route is most suitable for such kind of drug delivery system. Oral route is more convenient for It all age group including both pediatric and geriatrics. There are various systems which are adopted to deliver drug in a controlled manner to different target sites through oral route. It includes diffusion controlled drug delivery systems; dissolution controlled drug delivery systems, osmotically controlled drug delivery systems, ion-exchange controlled drug delivery systems, hydrodynamically balanced systems, multi-Particulate drug delivery systems and microencapsulated drug delivery system. The systems are formulated using different natural, semi-synthetic and synthetic polymers. The purpose of the review is to provide information about the orally controlled drug delivery system, polymers which are used to formulate these systems and characterizations of one of the most convenient dosage form which is the tablets. 

  15. The ability of retention, drug release and rheological properties of nanogel bioadhesives based on cellulose derivatives.

    Science.gov (United States)

    Keshavarz, M; Kaffashi, B

    2014-12-01

    The rheological and drug release behavior of biopolymer nanocomposite gels based on the cellulose derivatives, formulated as the bioadhesive drug delivery platforms, were investigated. The bioadhesive gel is composed of the microcrystalline cellulose, sodium carboxymethyl cellulose and phosphate buffered saline (pH = 7.4 at 20 °C) as the dissolution and release medium. The reinforcing nanofillers such as MMT-clay, fumed porous silica and porous starch were used as additives in the nanogel bioadhesive. The constant steady state viscosities of this nanogels upon incorporation of various nanofillers into the systems is the sign of structural stability. Hence, this system is suitable for use in the controlled drug delivery systems in contact with the biological tissues. Based on the rheological measurements, the shear flow properties (i.e. zero shear viscosity and yield stress) were influenced by the concentration of polymers and nanoparticles. The results indicate that the nonlinear rheological data are fitted properly by the Giesekus model. Furthermore, the results showed that the nonlinear viscoelastic parameters (λ and α) are highly affected by the biogel and nanoparticles concentrations. Finally, the drug release was measured, and the results indicated that the biopolymer-clay nanocomposites have appropriate release pattern as the release is better controlled compared to the other nanogel formulations.

  16. Formulation of porous poly(lactic-co-glycolic acid) microparticles by electrospray deposition method for controlled drug release

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Shilei; Wang, Yazhou; Wang, Bochu, E-mail: wangbc2000@126.com; Deng, Jia; Zhu, Liancai; Cao, Yang

    2014-06-01

    In the present study, the electrospray deposition was successfully applied to prepare the porous poly(lactic-co-glycolic acid) (PLGA) microparticles by one-step processing. Metronidazole was selected as the model drug. The porous PLGA microparticles had high drug loading and low density, and the porous structure can be observed by scanning electron microscope (SEM) and transmission electron microscopy (TEM). The production time has been shortened considerably compared with that of the traditional multi-emulsion method. In addition, no chemical reaction occurred between the drug and polymer in the preparation of porous microparticles, and the crystal structure of drug did not change after entrapment into the porous microparticles. The porous microparticles showed a sustained release in the simulated gastric fluid, and the release followed non-Fickian or case II transport. Furthermore, porous microparticles showed a slight cytotoxicity in vitro. The results indicated that electrospray deposition is a good technique for preparation of porous microparticles, and the low-density porous PLGA microparticles has a potential for the development of gastroretentive systems or for pulmonary drug delivery. - Highlights: • The porous PLGA microparticles were successfully prepared by the electrospray deposition method at one step. • The porous microparticles had high loading capacity and low density. • The microparticle showed a sustained release in the simulated gastric liquid. • The microparticles showed a slight cytotoxicity in vitro.

  17. Formulation of porous poly(lactic-co-glycolic acid) microparticles by electrospray deposition method for controlled drug release

    International Nuclear Information System (INIS)

    Hao, Shilei; Wang, Yazhou; Wang, Bochu; Deng, Jia; Zhu, Liancai; Cao, Yang

    2014-01-01

    In the present study, the electrospray deposition was successfully applied to prepare the porous poly(lactic-co-glycolic acid) (PLGA) microparticles by one-step processing. Metronidazole was selected as the model drug. The porous PLGA microparticles had high drug loading and low density, and the porous structure can be observed by scanning electron microscope (SEM) and transmission electron microscopy (TEM). The production time has been shortened considerably compared with that of the traditional multi-emulsion method. In addition, no chemical reaction occurred between the drug and polymer in the preparation of porous microparticles, and the crystal structure of drug did not change after entrapment into the porous microparticles. The porous microparticles showed a sustained release in the simulated gastric fluid, and the release followed non-Fickian or case II transport. Furthermore, porous microparticles showed a slight cytotoxicity in vitro. The results indicated that electrospray deposition is a good technique for preparation of porous microparticles, and the low-density porous PLGA microparticles has a potential for the development of gastroretentive systems or for pulmonary drug delivery. - Highlights: • The porous PLGA microparticles were successfully prepared by the electrospray deposition method at one step. • The porous microparticles had high loading capacity and low density. • The microparticle showed a sustained release in the simulated gastric liquid. • The microparticles showed a slight cytotoxicity in vitro

  18. The Drug Release Profile from Calcium-induced Alginate Gel Beads Coated with an Alginate Hydrolysate

    Directory of Open Access Journals (Sweden)

    Susumu Kawashima

    2007-11-01

    Full Text Available Calcium-induced alginate gel bead (Alg-Ca coated with an alginate hydrolysate(Alg, e.g. the guluronic acid block (GB was prepared and the model drug, hydrocortisonerelease profiles were investigated under simulated gastrointestinal conditions. Theirmolecular weights were one sixth or one tenth that of Alg and the diffraction patterns of thehydrolysates resembled that of Alg. The drug release rate from Alg-Ca coated with GBapparently lowered than that of Alg-Ca (coating-free in the gastric juice (pH1.2. And thecoating did not resist the disintegration of Alg-Ca in the intestinal juice (pH 6.8 and thegel erosion accelerated the drug release. On the other hand, for the coated Alg-Cacontaining chitosan, the drug release showed zero-order kinetics without rapid erosion ofAlg-Ca. The drug release rate from Alg-Ca was able to be controlled by the coating andmodifying the composition of the gel matrix.

  19. Obtaining of Sol-Gel Ketorolac-Silica Nanoparticles: Characterization and Drug Release Kinetics

    International Nuclear Information System (INIS)

    Goerne, T.M.L.; Garcia, M.G.L.; Grada, G.R.; Perez, I.O.; Goerne, T.M.L.; Garcia, M.G.L.; Grada, G.R.; Perez, I.O.; Lemus, M.A.A.; Goerne, T.M.L.; Loez, E.G.

    2013-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are among most commonly prescribed medications worldwide. NSAIDs play an important role due to their pronounced analgesic potency, anti-inflammatory effects, and lesser side effects compared to opioids. However, adverse effects including gastrointestinal and cardiovascular effects seriously complicate their prolonged use. In the present work we prepare SiO 2 -based nanoparticles with ketorolac, for controlled release proposes. The nano materials were prepared by the sol-gel technology at acidic conditions and two different water/alcoxide ratios were used. FTIR spectroscopy was performed in order to characterize the solids and drug-SiO 2 interactions. Thermal analysis and nitrogen adsorption isotherms showed thermal stability of the drug and confirmed the presence of particles with high surface area. Transmission electron micrographs of the samples showed the nano size particles (20 nm) forming aggregates. Drug release profiles were collected by means of UV-Vis spectroscopy and kinetic analysis was developed. Release data were fitted and 1:8 sample showed a sustained release over ten hours; 90% of the drug was delivered at the end of the time.

  20. Construction of a novel pH-sensitive drug release system from mesoporous silica tablets coated with Eudragit

    Science.gov (United States)

    Xu, Yingpu; Qu, Fengyu; Wang, Yu; Lin, Huiming; Wu, Xiang; Jin, Yingxue

    2011-03-01

    A novel pH-sensitive drug release system has been established by coating Eudragit (Eud) on drug-loaded mesoporous silica (MS) tablets. The release rate of ibuprofen (IBU) from the MS was retarded by coating with Eudragit S-100, and the higher retardation was due to the increase of coating concentration and the coating layers. The target position of the release depended on the pH of the release medium, which was confirmed by the drug release from IBU/MS/Eud increasing rapidly with the change of medium pH from 1.2 to 7.4. This drug delivery system could prohibit irritant drug from leaking in the stomach and make it only release in the intestine. The loaded and unloaded drug samples were characterized by powder X-ray diffraction (XRD), Fourier transform infrared spectrometer (FTIR), N 2 adsorption/desorption, scanning electron microscopy (SEM), and transmission electron microscopy (TEM).

  1. Effect of drug content and agglomerate size on tabletability and drug release characteristics of bromhexine hydrochloridetalc agglomerates prepared by crystallo-co-agglomeration.

    Science.gov (United States)

    Jadhav, Namdeo; Pawar, Atmaram; Paradkar, Anant

    2010-03-01

    The objective of the investigation was to study the effect of bromhexine hydrochloride (BXH) content and agglomerate size on mechanical, compressional and drug release properties of agglomerates prepared by crystallo-co-agglomeration (CCA). Studies on optimized batches of agglomerates (BXT1 and BXT2) prepared by CCA have showed adequate sphericity and strength required for efficient tabletting. Trend of strength reduction with a decrease in the size of agglomerates was noted for both batches, irrespective of drug loading. However, an increase in mean yield pressure (14.189 to 19.481) with an increase in size was observed for BXT2 having BXH-talc (1:15.7). Surprisingly, improvement in tensile strength was demonstrated by compacts prepared from BXT2, due to high BXH load, whereas BXT1, having a low amount of BXH (BXH-talc, 1:24), showed low tensile strength. Consequently, increased tensile strength was reflected in extended drug release from BXT2 compacts (Higuchi model, R(2) = 0.9506 to 0.9981). Thus, it can be concluded that interparticulate bridges formed by BXH and agglomerate size affect their mechanical, compressional and drug release properties.

  2. 3D extrusion printing of high drug loading immediate release paracetamol tablets.

    Science.gov (United States)

    Khaled, Shaban A; Alexander, Morgan R; Wildman, Ricky D; Wallace, Martin J; Sharpe, Sonja; Yoo, Jae; Roberts, Clive J

    2018-03-01

    The manufacture of immediate release high drug loading paracetamol oral tablets was achieved using an extrusion based 3D printer from a premixed water based paste formulation. The 3D printed tablets demonstrate that a very high drug (paracetamol) loading formulation (80% w/w) can be printed as an acceptable tablet using a method suitable for personalisation and distributed manufacture. Paracetamol is an example of a drug whose physical form can present challenges to traditional powder compression tableting. Printing avoids these issues and facilitates the relatively high drug loading. The 3D printed tablets were evaluated for physical and mechanical properties including weight variation, friability, breaking force, disintegration time, and dimensions and were within acceptable range as defined by the international standards stated in the United States Pharmacopoeia (USP). X-ray Powder Diffraction (XRPD) was used to identify the physical form of the active. Additionally, XRPD, Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR) and differential scanning calorimetry (DSC) were used to assess possible drug-excipient interactions. The 3D printed tablets were evaluated for drug release using a USP dissolution testing type I apparatus. The tablets showed a profile characteristic of the immediate release profile as intended based upon the active/excipient ratio used with disintegration in less than 60 s and release of most of the drug within 5 min. The results demonstrate the capability of 3D extrusion based printing to produce acceptable high-drug loading tablets from approved materials that comply with current USP standards. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. A poly({epsilon}-caprolactone) device for sustained release of an anti-glaucoma drug

    Energy Technology Data Exchange (ETDEWEB)

    Natu, Madalina V; De Sousa, HermInio C; Gil, M H [Department of Chemical Engineering, University of Coimbra, Polo II, Pinhal de Marrocos, 3030-290, Coimbra (Portugal); Gaspar, Manuel N; Fontes Ribeiro, Carlos A [Institute of Pharmacology and Experimental Therapeutics, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-354, Coimbra (Portugal); Correia, IlIdio J; Silva, Daniela, E-mail: hgil@eq.uc.pt [Centro de Investigacao em Ciencias da Saude, Faculdade de Ciencias da Saude, Universidade da Beira Interior, Covilha (Portugal)

    2011-04-15

    Implantable dorzolamide-loaded discs were prepared by blending poly({epsilon}-caprolactone), PCL, with poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide), Lu. By blending, crystallinity, water uptake and mass loss were modified relative to the pure polymers. Burst was diminished by coating the discs with a PCL shell. All samples presented burst release except PCL-coated samples that showed controlled release during 18 days. For PCL-coated samples, barrier control of diffusion coupled with partition control from the core slowed down the release, while for 50/50 Lu/PCL-coated samples, the enhancement in the porosity of the core diminished partition control of drug release. Nonlinear regression analysis suggested that a degradation model fully describes the release curve considering a triphasic release mechanism: the instantaneous diffusion (burst), diffusion and polymer degradation stages. The MTT test indicated that the materials are not cytotoxic for corneal endothelial cells. A good in vitro-in vivo correlation was obtained, with similar amounts of drug released in vitro and in vivo. The discs decreased intraocular pressure (IOP) in normotensive rabbit eyes by 13.0% during 10 days for PCL-coated and by 13.0% during 4 days for 50/50 Lu/PCL-coated samples. The percentages of IOP decrease are similar to those obtained by dorzolamide eyedrop instillation (11.0%).

  4. On spray drying of oxidized corn starch cross-linked gelatin microcapsules for drug release

    International Nuclear Information System (INIS)

    Dang, Xugang; Yang, Mao; Shan, Zhihua; Mansouri, Shahnaz; May, Bee K; Chen, Xiaodong; Chen, Hui; Woo, Meng Wai

    2017-01-01

    Spray-dried gelatin/oxidized corn starch (G/OCS) microcapsules were produced for drug release application. The prepared microcapsules were characterized through a scanning electron microscope (SEM) picture and thermogravimetric analysis (TGA). The swelling characteristics of the G/OCS microcapsules and release properties of vitamin C were then investigated. The results from structural analysis indicated that the presence of miscibility and compatibility between oxidized corn starch and gelatin, and exhibits high thermal stability up to 326 °C. The swelling of G/OCS microcapsules increased with increasing pH and reduced with decreasing ionic strength, attributed to the cross-linking between gelatin and oxidized corn starch, ionization of functional groups. Vitamin C release characteristic revealed controlled release behavior in the first 3 h of contact with an aqueous medium. This release behavior was independent of the swelling behavior indicating the potential of the encapsulating matrix to produce controlled release across a spectrum of pH environment. - Highlights: • It's first time to prepare microencapsulation with gelatin and oxidized corn starch. • The microencapsulation material can be biodegradable completely. • The production technology of microcapsule is convenient. • This work explores the potential to use oxidized starch cross-linked gelatin. • The microencapsulation material can be used for drug release.

  5. On spray drying of oxidized corn starch cross-linked gelatin microcapsules for drug release

    Energy Technology Data Exchange (ETDEWEB)

    Dang, Xugang; Yang, Mao; Shan, Zhihua [National Engineering Laboratory for Clean Technology Leather Manufacture, Sichuan University, Chengdu, Sichuan 610065 (China); Mansouri, Shahnaz [Department of Chemical Engineering, Monash University, VIC 3800 (Australia); May, Bee K [School of Applied Science, RMIT University, 124 La Trobe St, Melbourne, VIC 3001 (Australia); Chen, Xiaodong [Department of Chemical Engineering, Monash University, VIC 3800 (Australia); School of Chemical and Environmental Engineering, College of Chemistry, Chemical Engineering and Material Science, Soochow University (China); Chen, Hui, E-mail: leather2088@sina.com [National Engineering Laboratory for Clean Technology Leather Manufacture, Sichuan University, Chengdu, Sichuan 610065 (China); Department of Chemical Engineering, Monash University, VIC 3800 (Australia); Woo, Meng Wai, E-mail: meng.woo@monash.edu [Department of Chemical Engineering, Monash University, VIC 3800 (Australia)

    2017-05-01

    Spray-dried gelatin/oxidized corn starch (G/OCS) microcapsules were produced for drug release application. The prepared microcapsules were characterized through a scanning electron microscope (SEM) picture and thermogravimetric analysis (TGA). The swelling characteristics of the G/OCS microcapsules and release properties of vitamin C were then investigated. The results from structural analysis indicated that the presence of miscibility and compatibility between oxidized corn starch and gelatin, and exhibits high thermal stability up to 326 °C. The swelling of G/OCS microcapsules increased with increasing pH and reduced with decreasing ionic strength, attributed to the cross-linking between gelatin and oxidized corn starch, ionization of functional groups. Vitamin C release characteristic revealed controlled release behavior in the first 3 h of contact with an aqueous medium. This release behavior was independent of the swelling behavior indicating the potential of the encapsulating matrix to produce controlled release across a spectrum of pH environment. - Highlights: • It's first time to prepare microencapsulation with gelatin and oxidized corn starch. • The microencapsulation material can be biodegradable completely. • The production technology of microcapsule is convenient. • This work explores the potential to use oxidized starch cross-linked gelatin. • The microencapsulation material can be used for drug release.

  6. An understanding of modified release matrix tablets behavior during drug dissolution as the key for prediction of pharmaceutical product performance - case study of multimodal characterization of quetiapine fumarate tablets.

    Science.gov (United States)

    Kulinowski, Piotr; Woyna-Orlewicz, Krzysztof; Rappen, Gerd-Martin; Haznar-Garbacz, Dorota; Węglarz, Władysław P; Dorożyński, Przemysław P

    2015-04-30

    Motivation for the study was the lack of dedicated and effective research and development (R&D) in vitro methods for oral, generic, modified release formulations. The purpose of the research was to assess multimodal in vitro methodology for further bioequivalence study risk minimization. Principal results of the study are as follows: (i) Pharmaceutically equivalent quetiapine fumarate extended release dosage form of Seroquel XR was developed using a quality by design/design of experiment (QbD/DoE) paradigm. (ii) The developed formulation was then compared with originator using X-ray microtomography, magnetic resonance imaging and texture analysis. Despite similarity in terms of compendial dissolution test, developed and original dosage forms differed in micro/meso structure and consequently in mechanical properties. (iii) These differences were found to be the key factors of failure of biorelevant dissolution test using the stress dissolution apparatus. Major conclusions are as follows: (i) Imaging methods allow to assess internal features of the hydrating extended release matrix and together with the stress dissolution test allow to rationalize the design of generic formulations at the in vitro level. (ii) Technological impact on formulation properties e.g., on pore formation in hydrating matrices cannot be overlooked when designing modified release dosage forms. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Regulating Drug Release Behavior and Kinetics from Matrix Tablets Based on Fine Particle-Sized Ethyl Cellulose Ether Derivatives: An In Vitro and In Vivo Evaluation

    Directory of Open Access Journals (Sweden)

    Kifayat Ullah Shah

    2012-01-01

    Full Text Available The design and fabrication of sustained/controlled release dosage forms, employing new excipients capable of extending/controlling the release of drugs from the dosage forms over prolonged periods, has worked well in achieving optimally enhanced therapeutic levels of the drugs. In this sense, the objective of this study was to investigate the suitability of selected cellulose ether derivatives for use in direct compression (DC and as efficient drug release controlling agents. Controlled release matrix tablets of ciprofloxacin were prepared at different drug-to-polymer (D : P ratios by direct compression using a fine particle sized ethylcellulose ether derivative (ETHOCEL Standard Premium 7FP as rate controlling polymer. The tablets obtained were evaluated for various physico-chemical characteristics and in-vitro drug release studies were conducted in phosphate buffer (pH 7.4 using PharmaTest dissolution apparatus at constant temperature of 37∘C±0.1. Similarity factor 2 was employed to the release profiles of test formulations and were compared with marketed ciprofloxacin conventional tablets. Drug release mechanism and the kinetics involved were investigated by fitting the release profile data to various kinetic models. It was found that with increasing the proportion of ethylcellulose ether derivative in the matrix, the drug release was significantly extended up to 24 hours. The tablets exhibited zero order or nearly zero order drug transport mechanism. In vivo drug release performance of the developed controlled release tablets and reference conventional tablets containing ciprofloxacin were determined in rabbit serum according to randomized two-way crossover study design using High Performance Liquid Chromatography. Several bioavailability parameters of both the test tablets and conventional tablets including max, max and AUC0- were compared which showed an optimized max and max (<0.05. A good correlation was obtained between in vitro

  8. A novel dissolution media for testing drug release from a nanostructured polysaccharide-based colon specific drug delivery system: an approach to alternative colon media

    Directory of Open Access Journals (Sweden)

    Kotla NG

    2016-03-01

    Full Text Available Niranjan G Kotla,1,2 Sima Singh,1,3 Balaji Maddiboyina,4 Omprakash Sunnapu,2 Thomas J Webster5,6 1School of Pharmaceutical Sciences, Lovely Professional University, Punjab, India; 2Technologies for the Advancement of Science, Institute for Stem Cell Biology and Regenerative Medicine, Bangalore, Karnataka, India; 3Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India; 4Department of Pharmaceutics, Vishwabharathi College of Pharmaceutical Sciences, Guntur, Andhra Pradesh, India; 5Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 6Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia Abstract: The aim of this study was to develop a novel microbially triggered and animal-sparing dissolution method for testing of nanorough polysaccharide-based micron granules for colonic drug delivery. In this method, probiotic cultures of bacteria present in the colonic region were prepared and added to the dissolution media and compared with the performance of conventional dissolution methodologies (such as media with rat cecal and human fecal media. In this study, the predominant species (such as Bacteroides, Bifidobacterium, Lactobacillus species, Eubacterium and Streptococcus were cultured in 12% w/v skimmed milk powder and 5% w/v grade “A” honey. Approximately 1010–1011 colony forming units m/L of probiotic culture was added to the dissolution media to test the drug release of polysaccharide-based formulations. A USP dissolution apparatus I/II using a gradient pH dissolution method was used to evaluate drug release from formulations meant for colonic drug delivery. Drug release of guar gum/Eudragit FS30D coated 5-fluorouracil granules was assessed under gastric and small intestine conditions within a simulated colonic environment involving fermentation testing with the probiotic culture. The results with the probiotic system were

  9. Relationship between diffusivity of water molecules inside hydrating tablets and their drug release behavior elucidated by magnetic resonance imaging.

    Science.gov (United States)

    Kikuchi, Shingo; Onuki, Yoshinori; Kuribayashi, Hideto; Takayama, Kozo

    2012-01-01

    We reported previously that sustained release matrix tablets showed zero-order drug release without being affected by pH change. To understand drug release mechanisms more fully, we monitored the swelling and erosion of hydrating tablets using magnetic resonance imaging (MRI). Three different types of tablets comprised of polyion complex-forming materials and a hydroxypropyl methylcellulose (HPMC) were used. Proton density- and diffusion-weighted images of the hydrating tablets were acquired at intervals. Furthermore, apparent self-diffusion coefficient maps were generated from diffusion-weighted imaging to evaluate the state of hydrating tablets. Our findings indicated that water penetration into polyion complex tablets was faster than that into HPMC matrix tablets. In polyion complex tablets, water molecules were dispersed homogeneously and their diffusivity was relatively high, whereas in HPMC matrix tablets, water molecule movement was tightly restricted within the gel. An optimal tablet formulation determined in a previous study had water molecule penetration and diffusivity properties that appeared intermediate to those of polyion complex and HPMC matrix tablets; water molecules were capable of penetrating throughout the tablets and relatively high diffusivity was similar to that in the polyion complex tablet, whereas like the HPMC matrix tablet, it was well swollen. This study succeeded in characterizing the tablet hydration process. MRI provides profound insight into the state of water molecules in hydrating tablets; thus, it is a useful tool for understanding drug release mechanisms at a molecular level.

  10. The Relationship Between the Evolution of an Internal Structure and Drug Dissolution from Controlled-Release Matrix Tablets.

    Science.gov (United States)

    Kulinowski, Piotr; Hudy, Wiktor; Mendyk, Aleksander; Juszczyk, Ewelina; Węglarz, Władysław P; Jachowicz, Renata; Dorożyński, Przemysław

    2016-06-01

    In the last decade, imaging has been introduced as a supplementary method to the dissolution tests, but a direct relationship of dissolution and imaging data has been almost completely overlooked. The purpose of this study was to assess the feasibility of relating magnetic resonance imaging (MRI) and dissolution data to elucidate dissolution profile features (i.e., kinetics, kinetics changes, and variability). Commercial, hydroxypropylmethyl cellulose-based quetiapine fumarate controlled-release matrix tablets were studied using the following two methods: (i) MRI inside the USP4 apparatus with subsequent machine learning-based image segmentation and (ii) dissolution testing with piecewise dissolution modeling. Obtained data were analyzed together using statistical data processing methods, including multiple linear regression. As a result, in this case, zeroth order release was found to be a consequence of internal structure evolution (interplay between region's areas-e.g., linear relationship between interface and core), which eventually resulted in core disappearance. Dry core disappearance had an impact on (i) changes in dissolution kinetics (from zeroth order to nonlinear) and (ii) an increase in variability of drug dissolution results. It can be concluded that it is feasible to parameterize changes in micro/meso morphology of hydrated, controlled release, swellable matrices using MRI to establish a causal relationship between the changes in morphology and drug dissolution. Presented results open new perspectives in practical application of combined MRI/dissolution to controlled-release drug products.

  11. Poly(acrylic acid)-block-poly(vinyl alcohol) anchored maghemite nanoparticles designed for multi-stimuli triggered drug release

    Science.gov (United States)

    Liu, Ji; Detrembleur, Christophe; Debuigne, Antoine; de Pauw-Gillet, Marie-Claire; Mornet, Stéphane; Vander Elst, Luce; Laurent, Sophie; Labrugère, Christine; Duguet, Etienne; Jérôme, Christine

    2013-11-01

    Original core/corona nanoparticles composed of a maghemite core and a stimuli-responsive polymer coating made of poly(acrylic acid)-block-poly(vinyl alcohol) macromolecules were fabricated for drug delivery system (DDS) application. This kind of DDS aims to combine the advantage of stimuli-responsive polymer coating, in order to regulate the drug release behaviours under different conditions and furthermore, improve the biocompatibility and in vivo circulation half-time of the maghemite nanoparticles. Drug loading capacity was evaluated with methylene blue (MB), a cationic model drug. The triggered release of MB was studied under various stimuli such as pH, ionic strength and temperature. Local heating generated under alternating magnetic field (AMF) application was studied, and remotely AMF-triggered release was also confirmed, while a mild heating-up of the release medium was observed. Furthermore, their potential application as magnetic resonance imaging (MRI) contrast agents was explored via relaxivity measurements and acquisition of T2-weighted images. Preliminary studies on the cytotoxicity against mouse fibroblast-like L929 cell line and also their cellular uptake within human melanoma MEL-5 cell line were carried out. In conclusion, this kind of stimuli-responsive nanoparticles appears to be promising carriers for delivering drugs to some tumour sites or into cellular compartments with an acidic environment.Original core/corona nanoparticles composed of a maghemite core and a stimuli-responsive polymer coating made of poly(acrylic acid)-block-poly(vinyl alcohol) macromolecules were fabricated for drug delivery system (DDS) application. This kind of DDS aims to combine the advantage of stimuli-responsive polymer coating, in order to regulate the drug release behaviours under different conditions and furthermore, improve the biocompatibility and in vivo circulation half-time of the maghemite nanoparticles. Drug loading capacity was evaluated with methylene

  12. Tannate complexes of antihistaminic drug: sustained release and taste masking approaches.

    Science.gov (United States)

    Rahman, Ziyaur; Zidan, Ahmed S; Berendt, Robert T; Khan, Mansoor A

    2012-01-17

    The aim of this investigation was to evaluate the complexation potential of brompheniramine maleate (BPM) and tannic acid (TA) for sustained release and taste masking effects. The complexes (1:1-1:7 TA to BPM ratio) were prepared by the solvent evaporation method using methanol, phosphate buffer pH 6.8 or 0.1N HCl as common solvents. The complexes were characterized microscopically by scanning electron microscopy (SEM), chemically by Fourier transform infrared (FTIR) and solid-state NMR (SSNMR), thermally by differential scanning calorimetry (DSC), for crystallinity by powder X-ray powder diffraction (PXRD), for organoleptic evaluation by electronic tongue (e-tongue), and for solubility in 0.1N HCl and phosphate buffer pH 6.8. The dissolution studies were carried out using the USP II method at 50 rpm in 500 ml of dissolution media (0.1N HCl or phosphate buffer pH 6.8). SEM images revealed that the morphology of complexes were completely different from the individual components, and all complexes had the same morphological characteristics, irrespective of the solvent used for their preparation, pH or ratio of BPM and TA. The FTIR spectra showed the presence of chemical interactions between the TA and BPM. DSC, PXRD and SSNMR indicated that the drug lost its crystalline nature by formation of the complex. Complexation has significantly reduced the solubility of BPM and sustained the drug release up to 24h in phosphate buffer pH 6.8 media. The bitter taste of the BPM was completely masked which was indicated by Euclidean distance values which was far from the drug but near to its placebo in the complexes in all ratios studied. The taste masked complexes can be potentially developed as suitable dosage forms for pediatric use. In summary, complexation of BPM and TA effectively sustained the dissolution and masked the bitter taste of drug for the development of suitable dosage forms for pediatric use. Published by Elsevier B.V.

  13. On the exfoliating polymeric cellular dosage forms for immediate drug release.

    Science.gov (United States)

    Blaesi, Aron H; Saka, Nannaji

    2016-06-01

    The most prevalent pharmaceutical dosage forms at present-the oral immediate-release tablets and capsules-are granular solids. Though effective in releasing drug rapidly, development and manufacture of such dosage forms are fraught with difficulties inherent to particulate processing. Predictable dosage form manufacture could be achieved by liquid-based processing, but cast solid dosage forms are not suitable for immediate drug release due to their resistance to fluid percolation. To overcome this limitation, we have recently introduced cellular dosage forms that can be readily prepared from polymeric melts. It has been shown that open-cell structures comprising polyethylene glycol 8000 (PEG 8k) excipient and a drug exfoliate upon immersion in a dissolution medium. The drug is then released rapidly due to the large specific surface area of the exfoliations. In this work, we vary the molecular weight of the PEG excipient and investigate its effect on the drug release kinetics of structures with predominantly open-cell topology. We demonstrate that the exfoliation rate decreases substantially if the excipient molecular weight is increased from 12 to 100kg/mol, which causes the drug dissolution time to increase by more than a factor of ten. A model is then developed to elucidate the exfoliation behavior of cellular structures. Diverse transport processes are considered: percolation due to capillarity, diffusion of dissolution medium through the cell walls, and viscous flow of the saturated excipient. It is found that the lower exfoliation rate and the longer dissolution time of the dosage forms with higher excipient molecular weight are primarily due to the greater viscosity of the cell walls after fluid penetration. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Colon-specific pulsatile drug release provided by electrospun shellac nanocoating on hydrophilic amorphous composites.

    Science.gov (United States)

    Yang, Yao-Yao; Liu, Zhe-Peng; Yu, Deng-Guang; Wang, Ke; Liu, Ping; Chen, Xiaohong

    2018-01-01

    Colon-specific pulsatile drug release, as a combined drug controlled-release model, is a useful drug delivery manner for a series of diseases. New nanomedicines and related preparation methods are highly desired. With diclofenac sodium (DS) as a model drug, a new type of structural nanocomposite (SC), in which composite polyvinylpyrrolidone (PVP)-DS core was coated by shellac, was fabricated via modified coaxial electrospinning. For comparison, traditional PVP-DS monolithic hydrophilic nanocomposites (HCs) were generated using a traditional blending process. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), attenuated total reflectance-Fourier transform infrared (ATR-FTIR), water contact angle (WCA), and in vitro dissolution and ex vivo permeation tests were conducted to characterize the composites. SEM images demonstrated that both composites were linear nanofibers with smooth surface morphology and cross sections. TEM disclosed that the SCs had a thin shellac sheath layer of approximately 12 nm. XRD and ATR-FTIR results demonstrated that the crystalline DS was converted into amorphous composites with PVP because of favorable secondary interactions. WCA and in vitro dissolution tests demonstrated that the sheath shellac layers in SC could resist acid conditions and provide typical colon-specific pulsatile release, rather than a pulsatile release of HC under acid conditions. Ex vivo permeation results demonstrated that the SCs were able to furnish a tenfold drug permeation rate than the DS particles on the colon membrane. A new SC with a shellac coating on hydrophilic amorphous nanocomposites could furnish a colon-specific pulsatile drug release profile. The modified coaxial process can be exploited as a useful tool to create nanocoatings.

  15. Effect of Additives on the Physicochemical and Drug Release ...

    African Journals Online (AJOL)

    Erah

    This might be attributed to their large size (10 x original PGH ... XRPD and DSC studies indicate polymorphic transition of PGH in all agglomerates from ... The resultant solution was poured into 500 ml of distilled .... voltage and current used were 30kV and 30 ..... Sweetman S. Martindale: The extra pharmacopoeia. 17th ed.

  16. Morphologic characterization and properties of a nanocomposite matrix of polyvinylpyrrolidone and sodium bentonite for hydrophilic drug controlled release

    International Nuclear Information System (INIS)

    Almeida, Dario B.R. de; Tavares, Maria I.B.; Iulianelli, Gisele C.V.

    2015-01-01

    For several years, research in drug formulation field have been focused in seeking systems that enable a more efficient release of drug and greater time of acting. Aiming to bring numerous benefits to the patient and advantages for the pharmaceutical industry. Leading to greater acceptance and use by society. In this study polymer nanocomposites based on PVP and bentonite clay will be obtained with the drug Metformin, a known hydrophilic hypoglycemiating drug, in order to improve its properties and pharmacokinetics. This mixture will be obtained through spray drying, especially suited for administration of tablets. The characteristics of these materials are being studied by scanning electron microscopy (SEM), nuclear magnetic resonance (NMR), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA). (author)

  17. Preparation and characterization of chitosan/genipin/poly(N-vinyl-2-pyrrolidone) films for controlled release drugs

    Energy Technology Data Exchange (ETDEWEB)

    Aldana, Ana Agustina, E-mail: aaldana@fcq.unc.edu.ar [Departamento de Quimica Organica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba (UNC), Edificio de Ciencias II, Medina Allende y Haya de la Torre, Ciudad Universitaria, Cordoba 5000 (Argentina); Gonzalez, Agustin, E-mail: agustingonzalez@fcq.unc.edu.ar [Departamento de Quimica Organica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba (UNC), Edificio de Ciencias II, Medina Allende y Haya de la Torre, Ciudad Universitaria, Cordoba 5000 (Argentina); Strumia, Miriam C., E-mail: mcs@fcq.unc.edu.ar [Departamento de Quimica Organica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba (UNC), Edificio de Ciencias II, Medina Allende y Haya de la Torre, Ciudad Universitaria, Cordoba 5000 (Argentina); Martinelli, Marisa, E-mail: mmartinelli@fcq.unc.edu.ar [Departamento de Quimica Organica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba (UNC), Edificio de Ciencias II, Medina Allende y Haya de la Torre, Ciudad Universitaria, Cordoba 5000 (Argentina)

    2012-05-15

    Highlights: Black-Right-Pointing-Pointer Cross-linked chitosan films using genipin and/or PVP. Black-Right-Pointing-Pointer Propranolol hydrochloride was used like a model drug to release studies. Black-Right-Pointing-Pointer Incorporating PVP improves mechanical and diffusion properties. Black-Right-Pointing-Pointer Ch-Gen 0.10% and Ch-Gen 0.10%-PVP have optimal behavior. - Abstract: The study of the physicochemical and functional properties of chitosan films cross-linked with genipin and poly(N-vinyl-2-pyrrolidone) (PVP) was performed in this work. Cross-linked films were prepared by casting method from acetic acid solutions. The structure and physical properties of the films were analyzed by infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy ({sup 13}C NMR), differential scanning calorimetry (DSC) and mechanical testings. Propranolol hydrochloride was used like a model drug to determine the behavior of drug release from films. The drug release capacity was measured and compared with the degree of cross-linking, mechanical properties and swelling index. There was an appropriate balance of hydrophilicity, mechanical properties and diffusion by the incorporation of PVP into the networks cross-linked with genipin. The combination of both cross-linkers allows obtaining a soft and tough material potentially applicable as a controlled release. This research represents the first report where both cross-linkers, chemical and ionic agents, are used for obtaining films. These studies suggest that the chitosan films prepared here are promising drug delivery systems for buccal application, with thermal stability and acceptable mechanical properties. Buccal films may be preferred in terms of flexibility and comfort.

  18. Preparation and characterization of chitosan/genipin/poly(N-vinyl-2-pyrrolidone) films for controlled release drugs

    International Nuclear Information System (INIS)

    Aldana, Ana Agustina; González, Agustín; Strumia, Miriam C.; Martinelli, Marisa

    2012-01-01

    Highlights: ► Cross-linked chitosan films using genipin and/or PVP. ► Propranolol hydrochloride was used like a model drug to release studies. ► Incorporating PVP improves mechanical and diffusion properties. ► Ch–Gen 0.10% and Ch–Gen 0.10%–PVP have optimal behavior. - Abstract: The study of the physicochemical and functional properties of chitosan films cross-linked with genipin and poly(N-vinyl-2-pyrrolidone) (PVP) was performed in this work. Cross-linked films were prepared by casting method from acetic acid solutions. The structure and physical properties of the films were analyzed by infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy ( 13 C NMR), differential scanning calorimetry (DSC) and mechanical testings. Propranolol hydrochloride was used like a model drug to determine the behavior of drug release from films. The drug release capacity was measured and compared with the degree of cross-linking, mechanical properties and swelling index. There was an appropriate balance of hydrophilicity, mechanical properties and diffusion by the incorporation of PVP into the networks cross-linked with genipin. The combination of both cross-linkers allows obtaining a soft and tough material potentially applicable as a controlled release. This research represents the first report where both cross-linkers, chemical and ionic agents, are used for obtaining films. These studies suggest that the chitosan films prepared here are promising drug delivery systems for buccal application, with thermal stability and acceptable mechanical properties. Buccal films may be preferred in terms of flexibility and comfort.

  19. Thermo-responsive polymer-functionalized mesoporous carbon for controlled drug release

    Energy Technology Data Exchange (ETDEWEB)

    Zhu Shenmin, E-mail: smzhu@sjtu.edu.cn [State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240 (China); Chen Chenxin [State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240 (China); Chen Zhixin [Faculty of Engineering, University of Wollongong, Wollongong, NSW 2522 (Australia); Liu Xinye; Li Yao; Shi Yang; Zhang Di [State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240 (China)

    2011-03-15

    Research highlights: {yields} A responsive drug delivery system based on poly(N-isopropyl acrylamide) (PNIPAM) functionalized ordered mesoporous carbon (CMK-3) is developed. {yields} A combination of surface modification of CMK-3 and in situ internal polymerization of PNIPAM was used. {yields} The system exhibited a pronounced transition at around 20-25 deg. C. - Abstract: A novel responsive drug delivery system based on poly(N-isopropyl acrylamide) (PNIPAM) functionalized ordered mesoporous carbon (CMK-3) is developed. The polymer-functionalized CMK-3 was obtained by a combination of simple surface modification of CMK-3 and in situ internal polymerization of PNIPAM. The formation of the PNIPAM inside the CMK-3 was confirmed by thermal gravimetric analysis, Fourier transform-infrared spectroscopy, scanning and transmission electron microscopy and N{sub 2} adsorption/desorption measurements. Controlled drug release tests through the porous network of the PNIPAM functionalized CMK-3 were carried out by measuring the uptake and release of ibuprofen in vitro. The release profiles exhibited a pronounced transition at around 20-25 deg. C. This thermo-sensitive release property of this delivery system was further confirmed by temperature-variable hydrogen nuclear magnetic resonance analysis. The internal PNIPAM layers acted as a storage gate as well as a release switch in response to the stimuli of environment.

  20. Can Pulsed Electromagnetic Fields Trigger On-Demand Drug Release from High-Tm Magnetoliposomes?

    Directory of Open Access Journals (Sweden)

    Martina Nardoni

    2018-03-01

    Full Text Available Recently, magnetic nanoparticles (MNPs have been used to trigger drug release from magnetoliposomes through a magneto-nanomechanical approach, where the mechanical actuation of the MNPs is used to enhance the membrane permeability. This result can be effectively achieved with low intensity non-thermal alternating magnetic field (AMF, which, however, found rare clinic application. Therefore, a different modality of generating non-thermal magnetic fields has now been investigated. Specifically, the ability of the intermittent signals generated by non-thermal pulsed electromagnetic fields (PEMFS were used to verify if, once applied to high-transition temperature magnetoliposomes (high-Tm MLs, they could be able to efficiently trigger the release of a hydrophilic model drug. To this end, hydrophilic MNPs were combined with hydrogenated soybean phosphatidylcholine and cholesterol to design high-Tm MLs. The release of a dye was evaluated under the effect of PEMFs for different times. The MNPs motions produced by PEMF could effectively increase the bilayer permeability, without affecting the liposomes integrity and resulted in nearly 20% of release after 3 h exposure. Therefore, the current contribution provides an exciting proof-of-concept for the ability of PEMFS to trigger drug release, considering that PEMFS find already application in therapy due to their anti-inflammatory effects.

  1. Can Pulsed Electromagnetic Fields Trigger On-Demand Drug Release from High-Tm Magnetoliposomes?

    Science.gov (United States)

    Nardoni, Martina; Della Valle, Elena; Liberti, Micaela; Relucenti, Michela; Casadei, Maria Antonietta; Paolicelli, Patrizia; Apollonio, Francesca; Petralito, Stefania

    2018-03-27

    Recently, magnetic nanoparticles (MNPs) have been used to trigger drug release from magnetoliposomes through a magneto-nanomechanical approach, where the mechanical actuation of the MNPs is used to enhance the membrane permeability. This result can be effectively achieved with low intensity non-thermal alternating magnetic field (AMF), which, however, found rare clinic application. Therefore, a different modality of generating non-thermal magnetic fields has now been investigated. Specifically, the ability of the intermittent signals generated by non-thermal pulsed electromagnetic fields (PEMFS) were used to verify if, once applied to high-transition temperature magnetoliposomes (high-Tm MLs), they could be able to efficiently trigger the release of a hydrophilic model drug. To this end, hydrophilic MNPs were combined with hydrogenated soybean phosphatidylcholine and cholesterol to design high-Tm MLs. The release of a dye was evaluated under the effect of PEMFs for different times. The MNPs motions produced by PEMF could effectively increase the bilayer permeability, without affecting the liposomes integrity and resulted in nearly 20% of release after 3 h exposure. Therefore, the current contribution provides an exciting proof-of-concept for the ability of PEMFS to trigger drug release, considering that PEMFS find already application in therapy due to their anti-inflammatory effects.

  2. Preparation and evaluation of a timolol maleate drug-resin ophthalmic suspension as a sustained-release formulation in vitro and in vivo.

    Science.gov (United States)

    Qin, Fuhong; Zeng, Li; Zhu, Yongtao; Cao, Jingjing; Wang, Xiaohui; Liu, Wei

    2016-01-01

    The aim of this work was to assess the performance of resin as an ocular delivery system. Timolol maleate (TM) was chosen as the model drug and an ion exchange resin (IER) as the carrier. The drug-resin complex was prepared using an oscillation method and then characterized regarding particle size, zeta potential, morphology, and drug content. After in vitro drug release study and corneal permeation study were performed, in vivo studies were performed in New Zealand albino rabbits using a suspension with particles sized 4.8 ± 1.2 μm and drug loading at 43.00 ± 0.09%. The results indicate that drug released from the drug-resin ophthalmic suspension permeated the cornea and displayed a sustained-release behavior. Drug levels in the ocular tissues after administration of the drug-resin ophthalmic suspension were significantly higher than after treatment with an eye drop formulation but were lower in body tissues and in the plasma. In conclusion, resins have great potential as effective ocular drug delivery carriers to increase ocular bioavailability of timolol while simultaneously reducing systemic drug absorption.

  3. Controlled drug release from a novel injectable biodegradable microsphere/scaffold composite based on poly(propylene fumarate).

    Science.gov (United States)

    Kempen, Diederik H R; Lu, Lichun; Kim, Choll; Zhu, Xun; Dhert, Wouter J A; Currier, Bradford L; Yaszemski, Michael J

    2006-04-01

    The ideal biomaterial for the repair of bone defects is expected to have good mechanical properties, be fabricated easily into a desired shape, support cell attachment, allow controlled release of bioactive factors to induce bone formation, and biodegrade into nontoxic products to permit natural bone formation and remodeling. The synthetic polymer poly(propylene fumarate) (PPF) holds great promise as such a biomaterial. In previous work we developed poly(DL-lactic-co-glycolic acid) (PLGA) and PPF microspheres for the controlled delivery of bioactive molecules. This study presents an approach to incorporate these microspheres into an injectable, porous PPF scaffold. Model drug Texas red dextran (TRD) was encapsulated into biodegradable PLGA and PPF microspheres at 2 microg/mg microsphere. Five porous composite formulations were fabricated via a gas foaming technique by combining the injectable PPF paste with the PLGA or PPF microspheres at 100 or 250 mg microsphere per composite formulation, or a control aqueous TRD solution (200 microg per composite). All scaffolds had an interconnected pore network with an average porosity of 64.8 +/- 3.6%. The presence of microspheres in the composite scaffolds was confirmed by scanning electron microscopy and confocal microscopy. The composite scaffolds exhibited a sustained release of the model drug for at least 28 days and had minimal burst release during the initial phase of release, as compared to drug release from microspheres alone. The compressive moduli of the scaffolds were between 2.4 and 26.2 MPa after fabrication, and between 14.9 and 62.8 MPa after 28 days in PBS. The scaffolds containing PPF microspheres exhibited a significantly higher initial compressive modulus than those containing PLGA microspheres. Increasing the amount of microspheres in the composites was found to significantly decrease the initial compressive modulus. The novel injectable PPF-based microsphere/scaffold composites developed in this study

  4. Hypersonic Poration of Membranes : From Triggered Release and Encapsulation to Drug Delivery

    NARCIS (Netherlands)

    Lu, Yao

    2018-01-01

    In this thesis, hypersonic poration is introduced as a new physical method to precisely control membrane permeability for the applications of controlled release and encapsulation, and enhanced drug delivery. Bulk acoustic wave (BAW) resonators of gigahertz (GHz) frequency have been fabricated using

  5. In vivo drug release behavior and osseointegration of a doxorubicin-loaded tissue-engineered scaffold

    DEFF Research Database (Denmark)

    Sun, Ming; Chen, Muwan; Wang, Miao

    2016-01-01

    Bone tissue-engineered scaffolds with therapeutic effects must meet the basic requirements as to support bone healing at the defect side and to release an effect drug within the therapeutic window. Here, a rapid prototyped PCL scaffold embedded with chitosan/nanoclay/β-tricalcium phosphate...

  6. Synthesis, characterization and drug release properties of 3D chitosan/clinoptilolite biocomposite cryogels.

    Science.gov (United States)

    Dinu, Maria Valentina; Cocarta, Ana Irina; Dragan, Ecaterina Stela

    2016-11-20

    Three-dimensional (3D) biocomposites based on chitosan (CS) and clinoptilolite (CPL) were prepared by cryogelation and their potential application as drug carriers was investigated. Variation of CPL content from 0 to 33wt.% allowed the formation of biocomposites with heterogeneous morphologies consisting of randomly distributed pores. The further increase of CPL content led to ordered porous architectures where parallel pore channels were observed. The CPL content had a strong influence on water uptake, as well as on the cumulative release of diclofenac sodium (DS) and indomethacin (IDM). It was demonstrated that the drug delivery preferentially takes place in phosphate buffer saline (pH 7.4) in comparison to simulated gastric fluid (pH 1.2), where only a reduced drug release was observed. The drug release mechanism dominating these systems is described as a pseudo-Fickian diffusion, but it changes to non-Fickian release when 33wt.% of CPL was entrapped into the CS matrix or when IDM was loaded into biocomposites. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Medicinal chemistry and anti-inflammatory activity of nitric oxide-releasing NSAI drugs.

    Science.gov (United States)

    Koç And, Esra; Küçükgüzel, S Güniz

    2009-05-01

    Nitric Oxide, which acts as a non-specific cytotoxic mediator and a biological messenger on immunological competence, has been gaining significantly increasing importance. As an alternative to conventional NSAIDs having significant side effects, pharmacologically improved and therapeutically enhanced NO releasing non-steroidal anti-inflammatory drugs with less side effects are being planned to produce.

  8. Improved design and characterization of PLGA/PLA-coated Chitosan based micro-implants for controlled release of hydrophilic drugs.

    Science.gov (United States)

    Manna, Soumyarwit; Donnell, Anna M; Kaval, Necati; Al-Rjoub, Marwan F; Augsburger, James J; Banerjee, Rupak K

    2018-05-29

    Repetitive intravitreal injections of Methotrexate (MTX), a hydrophilic chemotherapeutic drug, are currently used to treat selected vitreoretinal (VR) diseases, such as intraocular lymphoma. To avoid complications associated with the rapid release of MTX from the injections, a Polylactic acid (PLA) and Chitosan (CS)-based MTX micro-implant prototype was fabricated in an earlier study, which showed a sustained therapeutic release rate of 0.2-2.0 µg/day of MTX for a period ∼1 month in vitro and in vivo. I