Science.gov

Sample records for methylcellulose

  1. 21 CFR 172.874 - Hydroxypropyl methylcellulose.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Hydroxypropyl methylcellulose. 172.874 Section 172.874 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Multipurpose Additives § 172.874 Hydroxypropyl methylcellulose. The...

  2. 21 CFR 172.874 - Hydroxypropyl methylcellulose.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... CONSUMPTION Multipurpose Additives § 172.874 Hydroxypropyl methylcellulose. The food additive hydroxypropyl... provide for such use if: (a) The additive complies with the definition and specifications prescribed in..., protective colloid, stabilizer, suspending agent, or thickener, in accordance with good...

  3. 21 CFR 172.874 - Hydroxypropyl methylcellulose.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... CONSUMPTION Multipurpose Additives § 172.874 Hydroxypropyl methylcellulose. The food additive hydroxypropyl... provide for such use if: (a) The additive complies with the definition and specifications prescribed in..., protective colloid, stabilizer, suspending agent, or thickener, in accordance with good...

  4. 21 CFR 172.874 - Hydroxypropyl methylcellulose.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... CONSUMPTION Multipurpose Additives § 172.874 Hydroxypropyl methylcellulose. The food additive hydroxypropyl... provide for such use if: (a) The additive complies with the definition and specifications prescribed in..., protective colloid, stabilizer, suspending agent, or thickener, in accordance with good...

  5. 21 CFR 172.874 - Hydroxypropyl methylcellulose.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... CONSUMPTION Multipurpose Additives § 172.874 Hydroxypropyl methylcellulose. The food additive hydroxypropyl... provide for such use if: (a) The additive complies with the definition and specifications prescribed in..., protective colloid, stabilizer, suspending agent, or thickener, in accordance with good...

  6. LT-HSC Methylcellulose Assay

    PubMed Central

    Kerenyi, Marc A.

    2016-01-01

    Hematopoietic differentiation is a highly complex process originating from an extraordinary population of cells called long-term repopulating hematopoietic stem cells (LT-HSCs). The unique feature of all stem cells, including HSCs, is their exceptional ability to divide asymmetrically giving rise to two different kinds of offspring. One daughter cell becomes an LT-HSC itself (self-renews) to maintain the LT-HSC pool, whereas the second daughter cell pursues a differentiation fate to ultimately give rise to terminally differentiated mature blood cells (Orkin and Zon, 2008). Quantification of phenotypic LT-HSCs can be performed by multi-color flow cytometry and the gold standard for assessment of LT-HSC self-renewal and function is competitive bone marrow transplantation (Miller et al., 2008). Although these methods are irreplaceable to determine LT-HSC abundance and functionality, they have their disadvantages and limitations. For example, competitive bone marrow transplantation is typically monitored as a function of peripheral blood donor contribution over 12–16 weeks. While reduced peripheral blood donor contribution by itself signifies impairment in the stem/progenitor cells compartment, it cannot unambiguously discriminate between reduced LT-HSC self-renewal, impaired LT-HSC differentiation or compromised progenitor cell differentiation. Here we describe an LT-HSCs methylcellulose colony-forming assay, as a fast complementary in vitro method to directly assess LT-HSC differentiation capacity. As described in Kerenyi et al. (2013), this technique acts as a powerful tool to differentiate between LT-HSC or progenitor cell differentiation defects.

  7. Bacterial culture preservation in frozen and dry-film methylcellulose.

    PubMed

    Suslow, T V; Schroth, M N

    1981-11-01

    Forty-seven of 61 bacterial cultures, including strains of Pseudomonas, Xanthomonas, Erwinia, Agrobacterium, Corynebacterium, Serratia, Klebsiella, and Escherichia, remained viable after storage in frozen methylcellulose or in dried methylcellulose for up to 38 months. Pathogenicity remained intact for those strains tested. Bacteria were grown on a solid medium and then removed and placed in 1.0% methylcellulose (cellulose methyl ether) to make a final suspension of 10 colony-forming units (CFU) per ml. For storage in dried form, the bacteria-methylcellulose suspension was placed in a petri dish and dried in a forced-air incubator. After 24 h of storage at 25 degrees C, viable populations of 10 CFU/mg (equivalent to 10 CFU/ml) were recovered. Populations of 10 to 10 CFU/mg were recovered after storage of up to 38 months. Similar results were obtained in frozen methylcellulose. Survival was greatly enhanced when the growth medium for the bacteria was potato dextrose peptone rather than nutrient agar, yeast dextrose calcium carbonate peptone, or King's medium B. Addition of 0.1 M MgSO(4) to the methylcellulose suspension and to the resuspending liquid also increased survival and recovery from storage for some strains. Methylcellulose storage should be a simple, inexpensive, and reliable method of maintaining cultures for short or long periods of time. PMID:16345889

  8. Properties of Novel Hydroxypropyl Methylcellulose Films Containing Chitosan Nanoparticles

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this work, chitosan nanoparticles were prepared and incorporated in hydroxypropyl methylcellulose (HPMC) films under different conditions. Mechanical properties, water vapor and oxygen permeability, water solubility and scanning and transmission electron microscopy (SEM and TEM) results were ana...

  9. Mechanism of misoprostol stabilization in hydroxypropyl methylcellulose.

    PubMed

    Kararli, T T; Catalano, T; Needham, T E; Finnegan, P M

    1991-01-01

    The stability of misoprostol oil is significantly improved in a hydroxypropyl methylcellulose (HPMC) dispersion (1:100). In order to understand the enhanced stability of misoprostol oil in HPMC, the physical state of misoprostol oil in HPMC films was investigated using differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and transmission IR (TIR). Further, to determine the effect of polymer structure and the mobility of both water and misoprostol on misoprostol stability, the rate of misoprostol degradation was investigated in the misoprostol/HPMC dispersion (1:100) at 55 degrees C. The water sorption isotherm of the dispersion at 55 degrees C was determined, at seven different relative humidities, ranging from zero to 81%. The DSC and DMA measurements indicated that misoprostol oil, up to 29% in dry weight, is molecularly dispersed in the glassy HPMC. The TIR studies showed no evidence of complexation between misoprostol and HPMC. Stability studies of the misoprostol/HPMC (1:100) dispersion indicated that the first-order rate constants for misoprostol degradation increased in a concave-up fashion as the water content of the dispersion increased. Below two percent water content, the rate of misoprostol degradation was found to be minimal. Overall, it is suggested that misoprostol is stabilized in the dispersion by being molecularly dispersed in HPMC. Further, the glassy state of HPMC should reduce the mobility of misoprostol and water, leading to a minimal rate of degradation for misoprostol at low moisture levels. PMID:1746334

  10. Agarose and methylcellulose hydrogel blends for nerve regeneration applications

    NASA Astrophysics Data System (ADS)

    Martin, Benton C.; Minner, Eric J.; Wiseman, Sherri L.; Klank, Rebecca L.; Gilbert, Ryan J.

    2008-06-01

    Trauma sustained to the central nervous system is a debilitating problem for thousands of people worldwide. Neuronal regeneration within the central nervous system is hindered by several factors, making a multi-faceted approach necessary. Two factors contributing to injury are the irregular geometry of injured sites and the absence of tissue to hold potential nerve guides and drug therapies. Biocompatible hydrogels, injectable at room temperature, that rapidly solidify at physiological temperatures (37 °C) are beneficial materials that could hold nerve guidance channels in place and be loaded with therapeutic agents to aid wound healing. Our studies have shown that thermoreversible methylcellulose can be combined with agarose to create hydrogel blends that accommodate these properties. Three separate novel hydrogel blends were created by mixing methylcellulose with one of the three different agaroses. Gelation time tests show that the blends solidify at a faster rate than base methylcellulose at 37 °C. Rheological data showed that the elastic modulus of the hydrogel blends rapidly increases at 37 °C. Culturing experiments reveal that the morphology of dissociated dorsal root ganglion neurons was not altered when the hydrogels were placed onto the cells. The different blends were further assessed using dissolution tests, pore size evaluations using scanning electron microscopy and measuring the force required for injection. This research demonstrates that blends of agarose and methylcellulose solidify much more quickly than plain methylcellulose, while solidifying at physiological temperatures where agarose cannot. These hydrogel blends, which solidify at physiological temperatures naturally, do not require ultraviolet light or synthetic chemical cross linkers to facilitate solidification. Thus, these hydrogel blends have potential use in delivering therapeutics and holding scaffolding in place within the nervous system.

  11. Effects of coating rectangular microscopic electrophoresis chamber with methylcellulose

    NASA Technical Reports Server (NTRS)

    Plank, L. D.

    1985-01-01

    One of the biggest problems in obtaining high accuracy in microscopic electrophoresis is the parabolic flow of liquid in the chamber due to electroosmotic backflow during application of the electric field. In chambers with glass walls the source of polarization leading to electroosmosis is the negative charge of the silicare and other ions that form the wall structure. It was found by Hjerten, who used a rotating 3.0 mm capillary tube for free zone electrophoresis, that precisely neutralizing this charge was extremely difficult, but if a neutral polymer matrix (formaldehyde fixed methylcellulose) was formed over the glass (quartz) wall the double layer was displaced and the viscosity at the shear plane increased so that electroosmotic flow could be eliminated. Experiments were designed to determine the reliability with which methylcellulose coating of the Zeiss Cytopherometer chamber reduced electroosmotic backflow and the effect of coating on the accuracy of cell electrophoretic mobility (EPN) determinations. Fixed rat erythrocytes (RBC) were used as test particles.

  12. TiO2/methylcellulose nanocomposite films for photocatalytic applications

    NASA Astrophysics Data System (ADS)

    Rosu, M. C.; Suciu, R. C.; Dreve, S. V.; Silipas, T. D.; Bratu, I.; Indrea, E.

    2012-02-01

    TiO2/methylcellulose (MeC) nanocomposite films were obtained by wet-chemical techniques using MeC and/or additives (acetylacetone, polyethylene glycol and Triton X-100). Thin films were obtained by spin-coating the colloidal suspensions on conductive indium tin oxide (ITO) glass, followed by a heat-treatment. The effect of MeC and additives on TiO2 nanoparticles dispersion was investigated by FTIR microscopy and X-ray diffraction (for structural and morphological properties), UV-VIS absorption spectroscopy and spectrofluorimetry (for optoelectronic properties) and wet technique adhesion test (for mechanical integrity). The composite film with methylcellulose and additives has good integrity and better adhesion to ITO substrate, without losing its photocatalytic activity. The results of these experiments showed that such nanocomposite films are interesting candidate for applications in the field of photocatalytic degradation of organic pollutants.

  13. Size-exclusion chromatography of ultrahigh molecular weight methylcellulose ethers and hydroxypropyl methylcellulose ethers for reliable molecular weight distribution characterization.

    PubMed

    Li, Yongfu; Shen, Hongwei; Lyons, John W; Sammler, Robert L; Brackhagen, Meinolf; Meunier, David M

    2016-03-15

    Size-exclusion chromatography (SEC) coupled with multi-angle laser light scattering (MALLS) and differential refractive index (DRI) detectors was employed for determination of the molecular weight distributions (MWD) of methylcellulose ethers (MC) and hydroxypropyl methylcellulose ethers (HPMC) having weight-average molecular weights (Mw) ranging from 20 to more than 1,000kg/mol. In comparison to previous work involving right-angle light scattering (RALS) and a viscometer for MWD characterization of MC and HPMC, MALLS yields more reliable molecular weight for materials having weight-average molecular weights (Mw) exceeding about 300kg/mol. A non-ideal SEC separation was observed for cellulose ethers with Mw>800kg/mol, and was manifested by upward divergence of logM vs. elution volume (EV) at larger elution volume at typical SEC flow rate such as 1.0mL/min. As such, the number-average molecular weight (Mn) determined for the sample was erroneously large and polydispersity (Mw/Mn) was erroneously small. This non-ideality resulting in the late elution of high molecular weight chains could be due to the elongation of polymer chains when experimental conditions yield Deborah numbers (De) exceeding 0.5. Non-idealities were eliminated when sufficiently low flow rates were used. Thus, using carefully selected experimental conditions, SEC coupled with MALLS and DRI can provide reliable MWD characterization of MC and HPMC covering the entire ranges of compositions and molecular weights of commercial interest. PMID:26794765

  14. Properties of novel hydroxypropyl methylcellulose films containing chitosan nanoparticles.

    PubMed

    de Moura, M R; Avena-Bustillos, R J; McHugh, T H; Krochta, J M; Mattoso, L H C

    2008-09-01

    In this study, chitosan nanoparticles were prepared and incorporated in hydroxypropyl methylcellulose (HPMC) films under different conditions. Mechanical properties, water vapor and oxygen permeability, water solubility, and scanning and transmission electron microscopy (SEM and TEM) results were analyzed. Incorporation of chitosan nanoparticles in the films improved their mechanical properties significantly, while also improving film barrier properties significantly. The chitosan poly(methacrylic acid) (CS-PMAA) nanoparticles tend to occupy the empty spaces in the pores of the HPMC matrix, inducing the collapse of the pores and thereby improving film tensile and barrier properties. This study is the first to investigate the use of nanoparticles for the purpose of strengthening HPMC films. PMID:18803724

  15. Radiation effects on hydroxypropyl methylcellulose phthalate in aqueous system

    NASA Astrophysics Data System (ADS)

    Xu, Ling; Yue, Zhiying; Wang, Min; Zhai, Maolin; Yoshii, Fumio; Seko, Noriaki; Peng, Jing; Wei, Genshuan; Li, Jiuqiang

    2007-12-01

    A water-insoluble cellulose derivative, hydroxypropyl methylcellulose phthalate (HPMCP) hydrogels, was converted to Na type to form hydrogel in paste-like status by radiation crosslinking. Mechanism for radiation crosslinking of cellulose-derivatives in paste-like status was discussed. Crosslinkers, i.e. methyl N, N-bis-acrylamide (MBA) or ethyleneglycol dimethacrylate (EGDMA) has been used to decrease gelation dose (Dg) of synthesis HPMCP hydrogels and improve its mechanical properties. HPMCP-MBA hydrogels were found to be more rigid and HPMCP-EGDMA hydrogels were more flexible. Swelling degree of HPMCP hydrogel in many kinds of salt solutions followed Hofmeister series, which is ubiquitous in polyelectrolyte hydrogel. Specific reswelling was observed in concentrated KF solution, implying a very strong F - binding ability of benzyl group. The comprehensive results obtained in this study will be utilized on the design of HPMCP-based controlled release system.

  16. The characterization of hydroxypropyl methylcellulose through the analysis of its substituents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The methyl and hydroxypropyl substituents in hydroxypropyl methylcellulose (HPMC) affect the resulting gel properties. These substituents in five HPMC gels were characterized using Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, small-amplitude oscillatory shear measurements, a...

  17. Dietary hydroxypropyl methylcellulose increases excretion of saturated and trans fats by hamsters fed fast food diets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The hypocholesterolemic and hypoglycemic effects of hydroxypropyl methylcellulose (HPMC), a semisynthetic nonfermentable soluble dietary fiber, are well established. However, effects of HPMC on dietary saturated fatty acids and trans fatty acids are largely unknown. This study investigated the eff...

  18. Improved barrier and mechanical properties of novel hydroxypropyl methylcellulose edible films with chitosan/tripolyphosphate nanoparticles

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chitosan/tripolyphosphate nanoparticles were prepared and incorporated in hydroxypropyl methylcellulose (HPMC) films. FT-IR and transmission electron microscopy (TEM) analyses of the nanoparticles, mechanical properties, water vapor permeability, thermal stability, scanning electron microscopy (SEM...

  19. Characterization of paraffin oil emulsions stabilized by hydroxypropyl methylcellulose.

    PubMed

    Futamura, Taiki; Kawaguchi, Masami

    2012-02-01

    To study the relationship between emulsion stability and polymer emulsifier concentration, the preparation of paraffin oil emulsions by hydroxypropyl methylcellulose (HPMC) was carried out with HPMC concentrations below the overlapping concentration (C(*)) of HPMC. The stability of the emulsions incorporating HPMC was investigated by measuring the creaming velocity, volume fraction of emulsified paraffin oil, oil droplet size, and some rheological responses such as the stress-strain sweep curve and strain and frequency dependences of dynamic viscoelastic moduli. The paraffin oil was almost emulsified by HPMC above C(*)/20: the volume fraction of paraffin oil in the emulsion was higher than 0.72. Increasing in the HPMC concentration led to decreases in both the average oil droplet size and creaming velocity and an increase in the yield stress. All emulsions behaved as solid-like viscoelastic matter. Additionally, the measured dynamic storage moduli were compared with those calculated from a relationship based on functions of the volume fraction of oil in the emulsions and Laplace pressure; good agreement between the measured and calculated moduli was obtained. On the other hand, at HPMC concentrations below C(*)/50, the emulsified paraffin oil became unstable and the oil and the HPMC solution eventually separated. PMID:22138268

  20. Thermally responsive wettability of self-assembled methylcellulose nanolayers

    NASA Astrophysics Data System (ADS)

    Yokota, Shingo; Matsuyama, Kana; Kitaoka, Takuya; Wariishi, Hiroyuki

    2007-03-01

    Thermo-responsive cellulosic nanolayers were prepared from methylcellulose (MC), which is known to have a unique lower critical solution temperature. Thiosemicarbazide (TSC) was selectively introduced into the MC reducing end groups, and the corresponding MC-TSC derivative was spontaneously chemisorbed on an Au substrate at 4 °C to give MC self-assembled monolayers (SAMs). Linear MC chains were stably fixed onto the Au substrate, yielding an MC-SAM of thickness ca. 15 nm with a root mean square value less than 1 nm. The MC-SAM surface exhibited thermally responsive wetting characteristics; the water contact angle was found to rise and fall around 70 °C, possibly due to the solid-state phase transition of the MC nanolayers resulting from the inherent gelation of MC molecules in water. Such wetting behavior was shown to be reversible following repeated heating and cooling. The MC-SAM immersed in salt solution revealed lower phase transition temperatures, and an increase in sodium chloride concentration ranging from 0.0 to 1.0 M brought about a dramatic decrease in the apparent phase transition temperature from ca. 70 to 30 °C. For the purposely designed MC nanolayers, such controllable wetting properties are expected to prompt growing interest in the applications of cellulosic biopolymer interfaces.

  1. Structure and phase behavior of aqueous methylcellulose solutions

    NASA Astrophysics Data System (ADS)

    McAllister, John; Schmidt, Peter; Lodge, Timothy; Bates, Frank

    2015-03-01

    Cellulose ethers (CE) constitute a multi-billion dollar industry, and have found end uses in a broad array of applications from construction materials, food products, personal care products, and pharmaceuticals for more than 80 years. Methylcellulose (MC, with the trade name METHOCEL™) is a CE in which there is a partial substitution of -OH groups with -OCH3 groups. This results in a polymer that is water-soluble at low temperatures, and aqueous solutions of MC display gelation and phase separation at higher temperatures. The nature of MC gelation has been debated for many years, and this project has made significant advances in the understanding of the solution properties of CEs. We have characterized a fibrillar structure of MC gels by cryogenic transmission electron microscopy (cryo-TEM) and small angle neutron scattering (SANS). Using light scattering, turbidity measurements, and dynamic mechanical spectroscopy (DMS) we report that MC microphase separates by nucleation and growth of fibril aggregates, and is a different process from LCST phase separation.

  2. Development of photocrosslinked methylcellulose hydrogels for soft tissue reconstruction.

    PubMed

    Stalling, Simone S; Akintoye, Sunday O; Nicoll, Steven B

    2009-07-01

    A variety of materials have been used as fillers for soft tissue augmentation. In this study, methylcellulose (MC), a water-soluble derivative of the polysaccharide cellulose, was modified with functional methacrylate groups and photocrosslinked to produce hydrogels for potential application in plastic and reconstructive surgery. Purified macromer (5% theoretical modification, 2.3% actual) was resuspended in 0.05wt.% of the photoinitiator, 2-methyl-1-[4-(hydroxyethoxy)phenyl]-2-methyl-1-propanone, cast into custom molds, and exposed to long-wavelength UV light for 10min to form gels. Photocrosslinked MC hydrogels at varying weight/volume percentages displayed equilibrium weight swelling ratios (wet weight/dry weight) and elastic moduli of 30+/-3 to 17+/-2 and 8.48+/-0.25kPa to 23.21+/-1.55kPa, respectively, demonstrating the formation of stable gels with tunable properties. Human dermal fibroblasts grown in the presence of MC hydrogels in vitro exhibited no significant changes in cell viability after 5days of co-culture, indicating that the materials are non-cytotoxic. Higher weight percentage MC hydrogels (6%) implanted subcutaneously in CD-1 mice maintained their integrity and original dimensions after 80days in vivo, eliciting a mild inflammatory response with no observed inflammatory exudate, minimal vascular infiltration and thin translucent fibrous capsule formation of approximately 50microm in thickness. Taken together, the material and biological properties of photocrosslinked MC hydrogels suggest that they may be of use in soft tissue reconstruction. PMID:19303378

  3. Stability of methylcellulose-based films after being subjected to different conservation and processing temperatures.

    PubMed

    Tavera Quiroz, M J; Lecot, J; Bertola, N; Pinotti, A

    2013-07-01

    Methylcellulose films with and without sorbitol addition were developed. The major objective of this study was to attempt insights into the stability of the methylcellulose-based film properties after having been subjected to freezing, storage or a combination of both procedures. The importance of the sorbitol concentration and process temperature was also to be elucidated. As-prepared film solubility decreased at 100 °C, as a result of the methylcellulose thermogelation property when the samples were exposed to high temperatures. By analyzing the film pattern behavior and its properties 0.25% w/v sorbitol concentration turned out to be an inflexion point. The moisture content as well as the mechanical and thermal properties made this fact evident. Moreover the elastic modulus (Ec) and glass transition temperature (Tg) did not undergo significant changes for higher plasticizer concentrations. The methylcellulose film properties remained more stable in the presence of sorbitol, which would act as a protective agent due to its hydrogen bonding capacity. This stability is crucial for film and coating applications in the food industry. PMID:23623115

  4. Solution blow spun Poly(lactic acid)/Hydroxypropyl methylcellulose nanofibers with antimicrobial properties

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Poly(lactic acid) (PLA) nanofibers containing hydroxypropyl methylcellulose (HPMC) and tetracycline hydrochloride (THC) were solution blow spun from two different solvents, chloroform/acetone (CA, 80:20 v/v) and 2,2,2-triflouroethanol (TFE). The diameter distribution, chemical, thermal, thermal stab...

  5. Hybrid Crosslinked Methylcellulose Hydrogel: A Predictable and Tunable Platform for Local Drug Delivery.

    PubMed

    Pakulska, Malgosia M; Vulic, Katarina; Tam, Roger Y; Shoichet, Molly S

    2015-09-01

    Design of experiment is used to develop a hybrid methylcellulose hydrogel that combines physical and chemical crosslinks, resulting in an injectable, in situ stiffening, and long-lasting material with predictable swelling and rheological properties. Chemical crosslinking is complete prior to injection, allowing for ease of use and storage. Controlled release of two relevant protein therapeutics and biocompatibility of the hydrogel are demonstrated. PMID:26184559

  6. Nanoparticle suspensions enclosed in methylcellulose: a new approach for quantifying nanoparticles in transmission electron microscopy

    PubMed Central

    Hacker, Christian; Asadi, Jalal; Pliotas, Christos; Ferguson, Sophie; Sherry, Lee; Marius, Phedra; Tello, Javier; Jackson, David; Naismith, James; Lucocq, John Milton

    2016-01-01

    Nanoparticles are of increasing importance in biomedicine but quantification is problematic because current methods depend on indirect measurements at low resolution. Here we describe a new high-resolution method for measuring and quantifying nanoparticles in suspension. It involves premixing nanoparticles in a hydrophilic support medium (methylcellulose) before introducing heavy metal stains for visualization in small air-dried droplets by transmission electron microscopy (TEM). The use of methylcellulose avoids artifacts of conventional negative stain-TEM by (1) restricting interactions between the nanoparticles, (2) inhibiting binding to the specimen support films and (3) reducing compression after drying. Methylcellulose embedment provides effective electron imaging of liposomes, nanodiscs and viruses as well as comprehensive visualization of nanoparticle populations in droplets of known size. These qualities facilitate unbiased sampling, rapid size measurement and estimation of nanoparticle numbers by means of ratio counting using a colloidal gold calibrant. Specimen preparation and quantification take minutes and require a few microliters of sample using only basic laboratory equipment and a standard TEM. PMID:27141843

  7. Nanoparticle suspensions enclosed in methylcellulose: a new approach for quantifying nanoparticles in transmission electron microscopy.

    PubMed

    Hacker, Christian; Asadi, Jalal; Pliotas, Christos; Ferguson, Sophie; Sherry, Lee; Marius, Phedra; Tello, Javier; Jackson, David; Naismith, James; Lucocq, John Milton

    2016-01-01

    Nanoparticles are of increasing importance in biomedicine but quantification is problematic because current methods depend on indirect measurements at low resolution. Here we describe a new high-resolution method for measuring and quantifying nanoparticles in suspension. It involves premixing nanoparticles in a hydrophilic support medium (methylcellulose) before introducing heavy metal stains for visualization in small air-dried droplets by transmission electron microscopy (TEM). The use of methylcellulose avoids artifacts of conventional negative stain-TEM by (1) restricting interactions between the nanoparticles, (2) inhibiting binding to the specimen support films and (3) reducing compression after drying. Methylcellulose embedment provides effective electron imaging of liposomes, nanodiscs and viruses as well as comprehensive visualization of nanoparticle populations in droplets of known size. These qualities facilitate unbiased sampling, rapid size measurement and estimation of nanoparticle numbers by means of ratio counting using a colloidal gold calibrant. Specimen preparation and quantification take minutes and require a few microliters of sample using only basic laboratory equipment and a standard TEM. PMID:27141843

  8. Organic/inorganic hybrid synaptic transistors gated by proton conducting methylcellulose films

    NASA Astrophysics Data System (ADS)

    Wan, Chang Jin; Zhu, Li Qiang; Wan, Xiang; Shi, Yi; Wan, Qing

    2016-01-01

    The idea of building a brain-inspired cognitive system has been around for several decades. Recently, electric-double-layer transistors gated by ion conducting electrolytes were reported as the promising candidates for synaptic electronics and neuromorphic system. In this letter, indium-zinc-oxide transistors gated by proton conducting methylcellulose electrolyte films were experimentally demonstrated with synaptic plasticity including paired-pulse facilitation and spatiotemporal-correlated dynamic logic. More importantly, a model based on proton-related electric-double-layer modulation and stretched-exponential decay function was proposed, and the theoretical results are in good agreement with the experimentally measured synaptic behaviors.

  9. Preparation and characterization of SiO2/TiO2/methylcellulose hybrid thick films for optical waveguides

    NASA Astrophysics Data System (ADS)

    Yang, Jun; Zhang, Xinyu; Wang, Pei; Ming, Hai; Wu, Yunxia; Xie, Jianping; Zhang, Junying

    2005-07-01

    SiO2/TiO2/methylcellulose composite materials processed by the sol-gel technique were studied for optical waveguide applications. With the help of methylcellulose, an organic binder, SiO2/TiO2/methylcellulose hybrid thick films were prepared by a single spin-coating processes. After annealing at 70 Celsius degree for an hour, 2.5-?m crack-free and dense organic--inorganic hybrid optical films with a refractive index of 1.537 were achieved. Optical losses of plane waveguide made up of those films and ordinary slide glass substrate are around 0.3 dB/cm at 650 nm. Scanning electronmicroscopy (SEM) and UV-visible spectroscopy (UV-VIS), have been used to characterize the thick films.

  10. A Coarse Grained Model for Methylcellulose: Spontaneous Ring Formation at Elevated Temperature

    NASA Astrophysics Data System (ADS)

    Huang, Wenjun; Larson, Ronald

    Methylcellulose (MC) is widely used as food additives and pharma applications, where its thermo-reversible gelation behavior plays an important role. To date the gelation mechanism is not well understood, and therefore attracts great research interest. In this study, we adopted coarse-grained (CG) molecular dynamics simulations to model the MC chains, including the homopolymers and random copolymers that models commercial METHOCEL A, in an implicit water environment, where each MC monomer modeled with a single bead. The simulations are carried using a LAMMPS program. We parameterized our CG model using the radial distribution functions from atomistic simulations of short MC oligomers, extrapolating the results to long chains. We used dissociation free energy to validate our CG model against the atomistic model. The CG model captured the effects of monomer substitution type and temperature from the atomistic simulations. We applied this CG model to simulate single chains up to 1000 monomers long and obtained persistence lengths that are close to those determined from experiment. We observed the chain collapse transition for random copolymer at 600 monomers long at 50C. The chain collapsed into a stable ring structure with outer diameter around 14nm, which appears to be a precursor to the fibril structure observed in the methylcellulose gel observed by Lodge et al. in the recent studies. Our CG model can be extended to other MC derivatives for studying the interaction between these polymers and small molecules, such as hydrophobic drugs.

  11. Development of crosslinked methylcellulose hydrogels for soft tissue augmentation using an ammonium persulfate-ascorbic acid redox system.

    PubMed

    Gold, Gittel T; Varma, Devika M; Taub, Peter J; Nicoll, Steven B

    2015-12-10

    Hydrogels composed of methylcellulose are candidate materials for soft tissue reconstruction. Although photocrosslinked methylcellulose hydrogels have shown promise for such applications, gels crosslinked using reduction-oxidation (redox) initiators may be more clinically viable. In this study, methylcellulose modified with functional methacrylate groups was polymerized using an ammonium persulfate (APS)-ascorbic acid (AA) redox initiation system to produce injectable hydrogels with tunable properties. By varying macromer concentration from 2% to 4% (w/v), the equilibrium moduli of the hydrogels ranged from 1.47 ± 0.33 to 5.31 ± 0.71 kPa, on par with human adipose tissue. Gelation time was found to conform to the ISO standard for injectable materials. Cellulase treatment resulted in complete degradation of the hydrogels within 24h, providing a reversible corrective feature. Co-culture with human dermal fibroblasts confirmed the cytocompatibility of the gels based on DNA measurements and Live/Dead imaging. Taken together, this evidence indicates that APS-AA redox-polymerized methylcellulose hydrogels possess properties beneficial for use as soft tissue fillers. PMID:26428151

  12. Hypocholesterolemic effects of hydroxypropyl methylcellulose are mediated by altered gene expression in hepatic bile and cholesterol pathways of male hamsters

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hydroxypropyl methylcellulose (HPMC), a semi-synthetic non-fermentable soluble dietary fiber (SDF) modulates plasma lipoprotein profiles and hepatic lipid levels. HPMC is not absorbed by the body but its presence in the intestinal lumen increases fecal fat, sterol, and bile acid excretion and decrea...

  13. Histology of a novel injectable filler (polymethylmethacrylate and cross-linked dextran in hydroxypropyl methylcellulose) in a rat model.

    PubMed

    Lee, Young Bok; Park, Sae Mi; Song, Eun Jong; Park, Jun-Gyu; Cho, Kyoung-Oh; Kim, Jin Wou; Yu, Dong Soo

    2014-08-01

    A novel injectable filler of polymethylmethacrylate (PMMA) and cross-linked dextran in hydroxypropyl methylcellulose was introduced in the commercial filler market. For soft tissue augmentation, safety and biocompatibility should be evaluated and the stability at the implantation site should be assessed using histologic evaluation. In order to evaluate the biocompatibility of the novel soft tissue filler, PMMA and cross-linked dextran in hydroxypropyl methylcellulose was subdermally injected into the skin of Sprague-Dawley Rats. Histologic evaluation was performed at 13 weeks and 12 months after the injection. Inflammatory cell infiltration, neovascularization, and fibrosis were scored according to defined grading systems. The mean score of the histologic evaluation was 5.7 and 3.9 at 13 weeks and 12 months, respectively. At 12 months after injection, the PMMA and cross-linked dextran in hydroxypropyl methylcellulose appeared to be kept in place through fine fibrous capsules. The mixture of PMMA and cross-linked dextran in hydroxypropyl methylcellulose can be safely applied for soft tissue augmentation with longevity of greater than 12 months. PMID:24684519

  14. Removal of paraquat pesticide from aqueous solutions using a novel adsorbent material based on polyacrylamide and methylcellulose hydrogels

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This research studied the characteristics of poly(acrylamide) and methylcellulose (PAAm-MC) hydrogels as a novel adsorbent material for removal of pesticide paraquat, from aqueous solution, with potential applications in curbing environmental risk from such herbicides. PAAm-MC hydrogels with differe...

  15. Miniaturization of cellulose fibers and effect of addition on the mechanical and barrier properties of hydroxypropyl methylcellulose

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cellulose fibers were miniaturized by microfluidics technology and incorporated in hydroxypropyl methylcellulose (HPMC) films to study the effect of the addition of such fibers on the mechanical and barrier properties of HPMC films suitable for food packaging applications. The particle size of the f...

  16. Relationship between morphologies and mechanical properties of hydroxypropyl methylcellulose/hydroxypropyl starch blends.

    PubMed

    Wang, Yanfei; Zhang, Liang; Liu, Hongsheng; Yu, Long; Simon, George P; Zhang, Nuozi; Chen, Ling

    2016-11-20

    Edible films from the blending hydroxypropyl methylcellulose (HPMC) with hydroxypropyl starch (HPS) have been developed. This work focuses on the relationship between morphologies and mechanical properties of such systems. To aid understanding of blend morphology, a new technique used to identify the two phases through dying of the HPS by iodine has been developed, which provided a simple and convenient way to clearly distinguish between HPMC and HPS phases. It was found that the blend system is immiscible and there is phase transition point depending on blending ratio and solution concentration. The lower transparency point of the blend and phase transition reign of HPMC from continuous phase to separated phase correspond with the variation of tensile modulus. The modulus and elongation decreased with increased solution concentration, which is correlatable with the morphologies present, where it was found that the HPMC gradually changed from a continuous phase to a distinct phase. PMID:27561503

  17. Characterization of antioxidant methylcellulose film incorporated with α-tocopherol nanocapsules.

    PubMed

    Noronha, Carolina Montanheiro; de Carvalho, Sabrina Matos; Lino, Renata Calegari; Barreto, Pedro Luiz Manique

    2014-09-15

    Biodegradable and antioxidant films based on methylcellulose (MC) and α-tocopherol nanocapsule suspension (NCs) were developed. MC and NCs films were prepared by a casting method in three different proportions. The mechanical, wettability, colour, light transmission, antioxidant and release characteristics of the films were studied. The addition of NCs to MC films decreased the tensile strength (TS) and the elastic modulus (EM) (p<0.05) but increased the percentage elongation at break (%E) and thickness (p<0.05). NCs films showed a higher hydrophobicity when compared to that of film control. Lightness and yellowish color were intensified in the NCs films which, in their turn, demonstrated high antioxidant activity and excellent barrier properties against UV and visible light. A burst and prolonged release of α-tocopherol to food simulant was also reported. PMID:24767092

  18. The shear dependence of the methylcellulose gelation phenomena in aqueous solution and in ceramic paste.

    PubMed

    Knarr, Matthias; Bayer, Roland

    2014-10-13

    The gelation temperature of methylcellulose (MC) in aqueous solutions as well as in aqueous ceramic paste depends on the applied shear. Rheological investigations in oscillation vs. shear mode show lower gelation temperature at low shear rates as for the corresponding angular frequencies. Above a critical shear rate the gelation temperature is shifted to higher temperatures. The paste extrusion process uses MC as a plasticizer and runs under high shear conditions. When extruding close to the gelation temperature of the MC in the paste, crack formation and other defects can occur. The upwards shift of the gelation temperature with increasing applied shear gives a larger temperature window during the extrusion process. The understanding of the shear influence on the gelation temperature is important to design the optimal process conditions. PMID:25037332

  19. Interaction between hydroxypropyl methylcellulose and biphasic calcium phosphate after steam sterilisation: capillary gas chromatography studies.

    PubMed

    Bourges, X; Schmitt, M; Amouriq, Y; Daculsi, G; Legeay, G; Weiss, P

    2001-01-01

    The purpose of this study was to check the chemical stability of an injectable bone substitute (IBS) composed of a 50/50 w/w mixture of 2.92% hydroxypropyl methylcellulose (HPMC) solution in deionized water containing biphasic calcium phosphate (BCP) granules (60% hydroxyapatite/40% beta-tricalcium phosphate w/w). After separation of the organic and mineral phases, capillary gas chromatography (GC) was used to study the possible modification of HPMC due to the contact with BCP granules following steam sterilisation and 32 days storage at room temperature. HPMC was extracted from IBS in aqueous medium, and a dialytic method was then used to extract calcium phosphate salts from the HPMC. The percentage of HPMC extracted from BCP was 98.5%+/-0.5%, as measured by UV. GC showed no chemical modifications after steam sterilisation and storage. PMID:11556737

  20. Interaction between hydroxypropyl methylcellulose and biphasic calcium phosphate after steam sterilisation: capillary gas chromatography studies

    PubMed Central

    Bourges, Xavier; Schmitt, Michel; Amouriq, Yves; Daculsi, Guy; Legeay, Gilbert; Weiss, Pierre

    2001-01-01

    The purpose of this study was to check the chemical stability of an injectable bone substitute (IBS) composed of a 50/50 w/w mixture of a 2.92% hydroxypropyl methylcellulose (HPMC) solution in deionised water containing biphasic calcium phosphate (BCP) granules (60% hydroxyapatite/40% β-tricalcium phosphate w/w). After separation of the organic and mineral phases, capillary gas chromatography (GC) was used to study the possible modification of HPMC due to the contact with BCP granules following steam sterilisation and 32 days of storage at room temperature. HPMC was extracted from IBS in aqueous medium, and a dialytic method was then use to extract calcium phosphate salts from HPMC. The percentage of HPMC extracted from BCP was 98.5% ± 0.5% as measured by a UV method. GC showed no chemical modifications after steam sterilisation and storage. PMID:11556737

  1. Effects of Methylcellulose on Cellulolytic Bacteria Attachment and Rice Straw Degradation in the In vitro Rumen Fermentation

    PubMed Central

    Sung, Ha Guyn; Kim, Min Ji; Upadhaya, Santi Devi; Ha, Jong K.; Lee, Sung Sill

    2013-01-01

    An in vitro experiment was conducted to evaluate the effect of methylcellulose on the attachment of major cellulolytic bacteria on rice straw and its digestibility. Rice straw was incubated with ruminal mixture with or without 0.1% methylcellulose (MC). The attachment of F. succinogenes, R. flavefaciens and R. albus populations on rice straw was measured using real-time PCR with specific primer sets. Methylcellulose at the level of 0.1% decreased the attachment of all three major cellulolytic bacteria. In particular, MC treatment reduced (p<0.05) attachment of F. succinogenes on rice straw after 10 min of incubation while a significant reduction (p<0.05) in attachment was not observed until 4 h incubation in the case of R. flavefaciens and R. albus. This result indicated F. succinogenes responded to MC more sensitively and earlier than R. flavefaciens and R. albus. Dry matter digestibility of rice straw was subsequently inhibited by 0.1% MC, and there was a significant difference between control and MC treatment (p<0.05). Incubated cultures containing MC had higher pH and lower gas production than controls. Current data clearly indicated that the attachment of F. succinogenes, R. flavefaciens and R. albus on rice straw was inhibited by MC, which apparently reduced rice straw digestion. PMID:25049909

  2. 3D patterned stem cell differentiation using thermo-responsive methylcellulose hydrogel molds

    NASA Astrophysics Data System (ADS)

    Lee, Wonjae; Park, Jon

    2016-07-01

    Tissue-specific patterned stem cell differentiation serves as the basis for the development, remodeling, and regeneration of the multicellular structure of the native tissues. We herein proposed a cytocompatible 3D casting process to recapitulate this patterned stem cell differentiation for reconstructing multicellular tissues in vitro. We first reconstituted the 2D culture conditions for stem cell fate control within 3D hydrogel by incorporating the sets of the diffusible signal molecules delivered through drug-releasing microparticles. Then, utilizing thermo-responsivity of methylcellulose (MC), we developed a cytocompatible casting process to mold these hydrogels into specific 3D configurations, generating the targeted spatial gradients of diffusible signal molecules. The liquid phase of the MC solution was viscous enough to adopt the shapes of 3D impression patterns, while the gelated MC served as a reliable mold for patterning the hydrogel prepolymers. When these patterned hydrogels were integrated together, the stem cells in each hydrogel distinctly differentiated toward individually defined fates, resulting in the formation of the multicellular tissue structure bearing the very structural integrity and characteristics as seen in vascularized bones and osteochondral tissues.

  3. 3D patterned stem cell differentiation using thermo-responsive methylcellulose hydrogel molds.

    PubMed

    Lee, Wonjae; Park, Jon

    2016-01-01

    Tissue-specific patterned stem cell differentiation serves as the basis for the development, remodeling, and regeneration of the multicellular structure of the native tissues. We herein proposed a cytocompatible 3D casting process to recapitulate this patterned stem cell differentiation for reconstructing multicellular tissues in vitro. We first reconstituted the 2D culture conditions for stem cell fate control within 3D hydrogel by incorporating the sets of the diffusible signal molecules delivered through drug-releasing microparticles. Then, utilizing thermo-responsivity of methylcellulose (MC), we developed a cytocompatible casting process to mold these hydrogels into specific 3D configurations, generating the targeted spatial gradients of diffusible signal molecules. The liquid phase of the MC solution was viscous enough to adopt the shapes of 3D impression patterns, while the gelated MC served as a reliable mold for patterning the hydrogel prepolymers. When these patterned hydrogels were integrated together, the stem cells in each hydrogel distinctly differentiated toward individually defined fates, resulting in the formation of the multicellular tissue structure bearing the very structural integrity and characteristics as seen in vascularized bones and osteochondral tissues. PMID:27381562

  4. Fluorescence study on the aggregation of collagen molecules in acid solution influenced by hydroxypropyl methylcellulose.

    PubMed

    Ding, Cuicui; Zhang, Min; Li, Guoying

    2016-01-20

    The effect of hydroxypropyl methylcellulose (HPMC) on the aggregation of collagen molecules with collagen concentrations of 0.25, 0.5 and 1.0mg/mL was studied by fluorescence techniques. On one hand, both the synchronous fluorescence spectra and fluorescence emission spectra showed that there was no change in the fluorescence intensity of collagen intrinsic fluorescence when 30% HPMC was added, while it decreased obviously when HPMC content ≥ 50%. From the two-dimensional fluorescence correlation analysis, it was indicated that collagen molecules in 0.25 and 0.5mg/mL collagen solutions were more sensitive to HPMC than those in 1.0mg/mL collagen solution. On the other hand, the pyrene fluorescence and the fluorescence anisotropy measurements indicated that HPMC inhibited the collagen aggregation for 0.25 and 0.5mg/mL collagen, but promoted it for 1.0mg/mL collagen. The atomic force microscopy images further confirmed the effect of HPMC on collagen with different initial states. PMID:26572350

  5. Antimicrobial and Antioxidant Activity of Chitosan/Hydroxypropyl Methylcellulose Film-Forming Hydrosols Hydrolyzed by Cellulase.

    PubMed

    Zimoch-Korzycka, Anna; Bobak, Łukasz; Jarmoluk, Andrzej

    2016-01-01

    The aim of this study was to evaluate the impact of cellulase (C) on the biological activity of chitosan/hydroxypropyl methylcellulose (CH/HPMC) film-forming hydrosols. The hydrolytic activity of cellulase in two concentrations (0.05% and 0.1%) was verified by determination of the progress of polysaccharide hydrolysis, based on viscosity measurement and reducing sugar-ends assay. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging effect, the ferric reducing antioxidant power (FRAP), and microbial reduction of Pseudomonas fluorescens, Yersinia enterocolitica, Bacillus cereus, and Staphylococcus aureus were studied. During the first 3 h of reaction, relative reducing sugar concentration increased progressively, and viscosity decreased rapidly. With increasing amount of enzyme from 0.05% to 0.1%, the reducing sugar concentration increased, and the viscosity decreased significantly. The scavenging effect of film-forming solutions was improved from 7.6% at time 0 and without enzyme to 52.1% for 0.1% cellulase after 20 h of reaction. A significant effect of cellulase addition and reaction time on antioxidant power of the tested film-forming solutions was also reported. Film-forming hydrosols with cellulase exhibited a bacteriostatic effect on all tested bacteria, causing a total reduction. PMID:27608008

  6. Gelatin/hydroxypropyl methylcellulose matrices - Polymer interactions approach for oral disintegrating films.

    PubMed

    Tedesco, Marcela P; Monaco-Lourenço, Carla A; Carvalho, Rosemary A

    2016-12-01

    Oral disintegrating film represents an optimal alternative for delivery system of active compounds. The choice of film-forming polymer is the first step in the development of oral disintegrating films and the knowledge of molecular interactions in this matrix is fundamental to advance in this area. Therefore, this study aimed to characterize gelatin and hydroxypropyl methylcellulose (HPMC) films and their blends as matrices of oral disintegrating films. The films were produced by casting technique and were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, mechanical properties, contact angle, time disintegration and bioadhesive strength. Differential scanning calorimetry showed that enthalpy of fusion and melting temperatures of the blends films were lower than those of the gelatin film, which may be associated with the lack of intra-chain interactions also observed in the Fourier transform infrared spectra. In blends, a less compact cross-section structure was observed in scanning electron microscopy images compared with isolated polymer films. The addition of HPMC increased the elongation, hydrophilicity and in vitro bioadhesive force and decreased in vitro disintegration time, important properties in the development of oral disintegrating films. Although the mixture of the polymers showed no synergistic behavior, this study may contribute to the development of new applications for polymeric matrices in the pharmaceutical industry. PMID:27612760

  7. Influence of hydroxypropyl methylcellulose edible coating on fresh-keeping and storability of tomato.

    PubMed

    Zhuang, Rong-yu; Huang, Yao-wen

    2003-01-01

    The effect of application of cellulose-based edible coating, hydroxypropyl methylcellulose (HPMC) to mature-green tomatoes on the firmness and color was investigated. Tomatoes were stored at 20 degrees C for up to 18 days. Firmness decreased as storage time increased in all treatments. However, application of HPMC edible coating delayed softening of tomatoes during 18 days of storage at 20 degrees C. At days 7, 13 and 18, the firmness of tomatoes coated with HPMC was significantly (P < or = 0.05) greater than the firmness of uncoated tomatoes. The study also confirmed that HPMC coatings could significantly (P < or = 0.05) delay the changes in color of tomatoes stored at 20 degrees C. The ripening of tomatoes from the pink stage to the red stage was successfully retarded. HPMC coating could extend the shelf life of fresh tomatoes. The retardation of the rate of loss of firmness could reduce the economic loss that would result from spoilage by mechanical injury during transportation of tomatoes. PMID:12656352

  8. Characterization of trilayer antimicrobial diffusion films (ADFs) based on methylcellulose-polycaprolactone composites.

    PubMed

    Boumail, Afia; Salmieri, Stephane; Klimas, Emilie; Tawema, Pamphile O; Bouchard, Jean; Lacroix, Monique

    2013-01-30

    Novel trilayer antimicrobial diffusion films (ADFs) were developed for food applications. ADFs were composed of two external layers of polycaprolactone and one internal layer of nanocrystalline cellulose (NCC)-reinforced methylcellulose (MC) matrix. Two antimicrobial mixtures (formulations A and B) were incorporated in the MC layer and compared via the evaluation of film properties. Resulting ADFs were inserted as diffusion devices into vegetable packages, and samples were stored at 4 °C for 14 days. Microbiological diffusion assays in the presence of ADFs were performed on pathogenic bacteria. From this, the study focused on characterizing the structural, physicochemical properties and total phenols (TP) release from ADFs. This TP release was determined by Folin-Ciocalteu's method and by FTIR analysis. Results indicated a controlled release of antimicrobials into the headspace (16.5% for formulation A and 13.4% for formulation B). Good correlations (≥90%) between both methods allowed validating an innovative, accurate, rapid FTIR procedure to quantify the diffusion of TP. SEM micrographs showed fibrillar structure due to NCC and a more compact network due to antimicrobials. Encapsulated antimicrobial formulations induced color changes without affecting visual attributes of films. ADFs containing formulation B exhibited the highest tensile strength (17.3 MPa) over storage. PMID:23286547

  9. Synergistic effect of salt mixture on the gelation temperature and morphology of methylcellulose hydrogel.

    PubMed

    Bain, Mrinal Kanti; Bhowmick, Biplab; Maity, Dipanwita; Mondal, Dibyendu; Mollick, Md Masud Rahaman; Rana, Dipak; Chattopadhyay, Dipankar

    2012-12-01

    Gelation temperature of methylcellulose (MC) can be altered by adding different additives. Pure MC showed sol-gel transition at 60°C. Sodium citrate and sodium tartrate were used alone and in combination to see the effect of individual salt and combination of salts on the gelation temperature of MC. The gelation temperature of all the binary and ternary combinations of MC and salts were measured with different methods such as test tube tilting method (TTM), UV-vis spectroscopy, viscometry, and by rheometer and also the morphology of gels were characterized with the help of environmental scanning electron microscopy (ESEM). It was observed that when 0.1 M sodium citrate (NaC) and 0.1 M sodium tartrate (NaT) were used separately, the gelation temperature of MC was reduced up to 44°C and 47°C respectively but when mixture of NaC and NaT (0.1 (M) NaC and 0.1 (M) (NaT)) were used the gelation temperature was further reduced to 36°C. It was clear from ESEM images that when NaC and NaT were used separately the formation of network was not distinguishable. But, well-connected network structure was observed when a mixture 0.1 M NaC and 0.1 M NaT was used. PMID:22884434

  10. Development and evaluation of wound healing hydrogels based on a quinolone, hydroxypropyl methylcellulose and biodegradable microfibres.

    PubMed

    Agubata, Chukwuma O; Okereke, Chiadikaobi; Nzekwe, Ifeanyi T; Onoja, Remigius I; Obitte, Nicholas C

    2016-06-30

    Ofloxacin is a synthetic antibiotic of the fluoroquinolone class, with activity against gram-positive and gram-negative bacteria. Wound healing involves a complex interaction of cells and processes which can be improved using appropriate wound- dressing materials. The aim of the present study was to develop and evaluate wound healing hydrogels containing hydroxypropyl methylcellulose (HPMC), ofloxacin and biodegradable microfibres from surgical sutures. The hydrogels were formulated by air-drying mixtures of dilute dispersions of micronized sutures (polyglycolic acid, Vicryl® and catgut), ofloxacin and HPMC gel. The prepared hydrogels were evaluated for gel fraction, swelling capacity, breaking elongation, particle size and morphology, and chemical interactions. Furthermore, in vivo wound healing activities were studied in rats using excision wound model and histological examination. The percentage gel fraction was ≥50% in all the batches, the percentage swelling ratio was within the range of 531.8-1700% and the percentage breaking elongation was found to be in the range of 70-120%. The chemical interaction studies using Fourier Transform Infra Red (FTIR) spectroscopy showed that there was no interaction between the drug and excipients used. Ofloxacin-loaded hydrogels containing dilute microfibres of the sutures showed 95% wound size reduction after fourteen days. These formulations also caused high collagen deposition after twenty one days of wounding, with minimal scar formation. Ofloxacin hydrogels containing HPMC and micronized suture fibres can be applied for effective wound healing. PMID:27094907

  11. Synthesis of surfactant-free hydroxypropyl methylcellulose nanogels for controlled release of insulin.

    PubMed

    Zhao, Di; Shi, Xiaodi; Liu, Tianqun; Lu, Xihua; Qiu, Gao; Shea, Kenneth J

    2016-10-20

    A facile controlled-release nanogels delivery system has been developed by using hydroxypropyl methylcellulose (HPMC) hybrid nanogels as encapsulation shell materials, which were synthesized by surfactant-free polymerization in aqueous solution. The effects of reaction time and cross-linker concentration on the size of the nanogels have been studied. The results showed that in a certain range, the particle size decreased with increasing reaction time and increasing concentration of cross-linker. Meanwhile, at the feeding ratio 0.05/1 of HPMC/methacrylic acid (MAA), the LCST of prepared nanogels at pH=6 was close to the body temperature, which can be used as sustained insulin delivery system. Besides, the HPMC nanogels loaded with insulin had a high drug loading of 21.3% and a high entrapment efficiency of 95.7%. The release behavior of the insulin nanogels can be adjusted by pH and temperature which will have potential applications in controlled release delivery system. PMID:27474648

  12. Photochromic Properties of Tungsten Oxide/Methylcellulose Composite Film Containing Dispersing Agents.

    PubMed

    Yamazaki, Suzuko; Ishida, Hiroki; Shimizu, Dai; Adachi, Kenta

    2015-12-01

    Tungsten oxide-based photochromic films which changed reversibly in air between colorless- transparent in the dark and dark blue under UV irradiation were prepared by using methylcellulose as a film matrix and polyols such as ethylene glycol (EG), propylene glycol (PG), and glycerin (Gly) as dispersing agents. Influence of the dispersing agents and water in the films on the photochromic behavior was systematically studied. Under UV irradiation, absorption bands around 640 and 980 nm increased and the coloring rate was the following order: Gly > EG > PG. An increase in the amounts of dispersing agents or water accelerated the coloring rate. By increasing the water content of the film, a new absorption peak appeared at ca. 775 nm and the Raman spectra indicated a shift of W-O-W stretching vibration to lower wavenumber which was due to the formation of hydrogen bonding. All absorption spectra were fit by three Lorentz functions, whose bands were ascribed to various packing of WO6 octahedra. After the light was turned off, the formation of W(5+) was stopped and bleaching occurred by the reaction with O2 in air to recover its original transparent state. We anticipate that the biodegradable photochromic films developed in this study can be applied in recyclable display medium and especially in detachable films for glass windows whose light transmission properties are changed by sunlight, i.e., for usage as an alternative of smart windows without applying voltage. PMID:26552031

  13. 3D patterned stem cell differentiation using thermo-responsive methylcellulose hydrogel molds

    PubMed Central

    Lee, Wonjae; Park, Jon

    2016-01-01

    Tissue-specific patterned stem cell differentiation serves as the basis for the development, remodeling, and regeneration of the multicellular structure of the native tissues. We herein proposed a cytocompatible 3D casting process to recapitulate this patterned stem cell differentiation for reconstructing multicellular tissues in vitro. We first reconstituted the 2D culture conditions for stem cell fate control within 3D hydrogel by incorporating the sets of the diffusible signal molecules delivered through drug-releasing microparticles. Then, utilizing thermo-responsivity of methylcellulose (MC), we developed a cytocompatible casting process to mold these hydrogels into specific 3D configurations, generating the targeted spatial gradients of diffusible signal molecules. The liquid phase of the MC solution was viscous enough to adopt the shapes of 3D impression patterns, while the gelated MC served as a reliable mold for patterning the hydrogel prepolymers. When these patterned hydrogels were integrated together, the stem cells in each hydrogel distinctly differentiated toward individually defined fates, resulting in the formation of the multicellular tissue structure bearing the very structural integrity and characteristics as seen in vascularized bones and osteochondral tissues. PMID:27381562

  14. Processing and characterization of chitosan/PVA and methylcellulose porous scaffolds for tissue engineering.

    PubMed

    Kanimozhi, K; Khaleel Basha, S; Sugantha Kumari, V

    2016-04-01

    Biomimetic porous scaffold chitosan/poly(vinyl alcohol) CS/PVA containing various amounts of methylcellulose (MC) (25%, 50% and 75%) incorporated in CS/PVA blend was successfully produced by a freeze drying method in the present study. The composite porous scaffold membranes were characterized by infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), swelling degree, porosity, degradation of films in Hank's solution and the mechanical properties. Besides these characterizations, the antibacterial activity of the prepared scaffolds was tested, toward the bacterial species Staphylococcus aureus (S.aureus) and Escherichia coli (E.coli). FTIR, XRD and DSC demonstrated that there was strong intermolecular hydrogen bonding between the molecules of CS/PVA and MC. The crystalline microstructure of the scaffold membranes was not well developed. SEM images showed that the morphology and diameter of the scaffolds were mainly affected by the weight ratio of MC. By increasing the MC content in the hybrid scaffolds, their swelling capacity and porosity increased. The mechanical properties of these scaffolds in dry and swollen state were greatly improved with high swelling ratio. The elasticity of films was also significantly improved by the incorporation of MC, and the scaffolds could also bear a relative high tensile strength. These findings suggested that the developed scaffold possess the prerequisites and can be used as a scaffold for tissue engineering. PMID:26838875

  15. Studies on methylcellulose/pectin/montmorillonite nanocomposite films and their application possibilities.

    PubMed

    Saha, Nayan Ranjan; Sarkar, Gunjan; Roy, Indranil; Rana, Dipak; Bhattacharyya, Amartya; Adhikari, Arpita; Mukhopadhyay, Asis; Chattopadhyay, Dipankar

    2016-01-20

    Films based on methylcellulose (MC) and pectin (PEC) of different ratios were prepared. MC/PEC (90:10) (MP10) gave the best results in terms of mechanical properties. Sodium montmorillonite (MMT) (1, 3 and 5 wt%) was incorporated in the MP10 matrix. The resulting films were characterized by X-ray diffraction and transmission electron microscopy, and it was found that nanocomposites were intercalated in nature. Mechanical studies established that addition of 3 wt% MMT gave best results in terms of mechanical properties. However, thermo-gravimetric and dynamic mechanical analysis proved that decomposition and glass transition temperature increased with increasing MMT concentration from 1 to 5 wt%. It was also observed that moisture absorption and water vapor permeability studies gave best result in the case of 3 wt% MMT. Optical clarity of the nanocomposite films was not much affected with loading of MMT. In vitro drug release studies showed that MC/PEC/MMT based films can be used for controlled transdermal drug delivery applications. PMID:26572465

  16. Modeling Anisotropic Self-Assembly of Isotropic Objects: from Hairy Nanoparticles to Methylcellulose Fibrils

    NASA Astrophysics Data System (ADS)

    Ginzburg, Valeriy

    Spontaneous symmetry breaking and formation of anisotropic structures from apparently isotropic building blocks is an exciting and not fully understood topic. I will discuss two examples of such self-assembly. The first example is related to the assembly of ``hairy'' nanoparticles in homopolymer matrices. The particles can assemble into long strings (they can also form other morphologies, as well) even though the shape of each particle and the distribution of ligands on the particle surface is spherically symmetric. Using the approach developed by Thompson, Ginzburg, Matsen, and Balazs, we show that presence of other particles can re-distribute the ligands and effectively ``polarize'' the particle-particle interaction, giving rise to the formation of 1d particle strings. In the second example, we consider aqueous solutions of methylcellulose (MC) polymers. It has been shown recently that at high temperature, the polymers form high-aspect ratio ``fibrils'' with diameter ~15 nm and length in the hundreds on nanometers. Using coarse-grained Molecular Dynamics (CG-MD), we propose that the ``fibrils'' are result of one-dimensional self-assembly of single molecule ``rings''. Each MC polymer chain is forced into a ring because of the balance between internal chain rigidity (favoring more expanded configuration) and unfavorable polymer-water interactions (favoring more collapsed conformation). We also develop a theory predicting rheology and phase behavior of aqueous MC, and validate it against experimental data. Both examples show that anisotropic self-assembly can show up in unexpected places, and various theoretical tools are needed to successfully model it. Funded by The Dow Chemical Company through Grant 223278AF. Collaborators: R. L. Sammler (Dow), W. Huang and R. Larson (U. of Michigan).

  17. Affinity-based release of chondroitinase ABC from a modified methylcellulose hydrogel.

    PubMed

    Pakulska, Malgosia M; Vulic, Katarina; Shoichet, Molly S

    2013-10-10

    Chondroitinase ABC (ChABC) is a promising therapeutic for spinal cord injury as it can degrade the glial scar that is detrimental to regrowth and repair. However, the sustained delivery of bioactive ChABC is a challenge requiring highly invasive methods such as intra-spinal injections, insertion of intrathecal catheters, or implantation of delivery vehicles directly into the tissue. ChABC is thermally unstable, further complicating its delivery. Moreover, there are no commercial antibodies available for its detection. To achieve controlled release, we designed an affinity-based system that sustained the release of bioactive ChABC for at least 7days. ChABC was recombinantly expressed as a fusion protein with Src homology domain 3 (SH3) with an N-terminal histidine (HIS) tag and a C-terminal FLAG tag (ChABC-SH3). Protein purification was achieved using a nickel affinity column and, for the first time, direct quantification of ChABC down to 0.1nM was attained using an in-house HIS/FLAG double tag ELISA. The release of active ChABC-SH3 was sustained from a methylcellulose hydrogel covalently modified with an SH3 binding peptide. The rate of release was tunable by varying either the binding strength of the SH3-protein/SH3-peptide pair or the SH3-peptide to SH3-protein ratio. This innovative system has the potential to be used as a platform technology for the release and detection of other proteins that can be expressed using a similar construct. PMID:23831055

  18. Effects of Methylcellulose on Fibrolytic Bacterial Detachment and In vitro Degradation of Rice Straw

    PubMed Central

    Kim, Min Ji; Sung, Ha Guyn; Upadhaya, Santi Devi; Ha, Jong K.; Lee, Sung Sill

    2013-01-01

    Two in vitro experiments were conducted to evaluate the effect of methylcellulose (MC) on i) bacterial detachment from rice straw as well as ii) inhibition of bacterial attachment and fiber digestibility. To evaluate the effect of MC on fibrolytic bacterial detachment (Exp 1), in vitro bacterial cultures with 0.1% (w/v) MC solution were compared with cultures without MC after 8 h incubation. The effect of MC on inhibition of bacterial attachment was determined by comparing with real-time PCR the populations of F. succinogenes, R. flavefaciens and R. albus established on rice straw pre-treated with 0.1% MC with those on untreated straw after incubation for 0, 6 and 12 h (Exp 2). The major fibrolytic bacterial attachment on rice straw showed significantly lower populations with either the addition of MC to the culture or pre-treated rice straw compared to controls (p<0.05). Also, the digestibility of rice straw with MC was significantly lower compared with control (p<0.05). The F. succinogenes population did not show detachment from rice straw, but showed an inhibition of attachment and proliferation on rice straw in accordance with a decrease of fiber digestion. The detachments of Ruminococcus species co-existed preventing the proliferations with subsequent reduction of fiber degradation by MC during the incubation. Their detachments were induced from stable colonization as well as the initial adhesion on rice straw by MC in in vitro ruminal fermentation. Furthermore, the detachment of R. albus was more sensitive to MC than was R. flavefaciens. These results showed the certain evidence that attachment of major fibrolytic bacteria had an effect on fiber digestion in the rumen, and each of fibrolytic bacteria, F. succinogenes, R. flavefaciens and R. albus had a specific mechanism of attachment and detachment to fiber. PMID:25049729

  19. Effects of Methylcellulose on Fibrolytic Bacterial Detachment and In vitro Degradation of Rice Straw.

    PubMed

    Kim, Min Ji; Sung, Ha Guyn; Upadhaya, Santi Devi; Ha, Jong K; Lee, Sung Sill

    2013-10-01

    Two in vitro experiments were conducted to evaluate the effect of methylcellulose (MC) on i) bacterial detachment from rice straw as well as ii) inhibition of bacterial attachment and fiber digestibility. To evaluate the effect of MC on fibrolytic bacterial detachment (Exp 1), in vitro bacterial cultures with 0.1% (w/v) MC solution were compared with cultures without MC after 8 h incubation. The effect of MC on inhibition of bacterial attachment was determined by comparing with real-time PCR the populations of F. succinogenes, R. flavefaciens and R. albus established on rice straw pre-treated with 0.1% MC with those on untreated straw after incubation for 0, 6 and 12 h (Exp 2). The major fibrolytic bacterial attachment on rice straw showed significantly lower populations with either the addition of MC to the culture or pre-treated rice straw compared to controls (p<0.05). Also, the digestibility of rice straw with MC was significantly lower compared with control (p<0.05). The F. succinogenes population did not show detachment from rice straw, but showed an inhibition of attachment and proliferation on rice straw in accordance with a decrease of fiber digestion. The detachments of Ruminococcus species co-existed preventing the proliferations with subsequent reduction of fiber degradation by MC during the incubation. Their detachments were induced from stable colonization as well as the initial adhesion on rice straw by MC in in vitro ruminal fermentation. Furthermore, the detachment of R. albus was more sensitive to MC than was R. flavefaciens. These results showed the certain evidence that attachment of major fibrolytic bacteria had an effect on fiber digestion in the rumen, and each of fibrolytic bacteria, F. succinogenes, R. flavefaciens and R. albus had a specific mechanism of attachment and detachment to fiber. PMID:25049729

  20. Thermo-responsive methylcellulose hydrogels as temporary substrate for cell sheet biofabrication.

    PubMed

    Altomare, Lina; Cochis, Andrea; Carletta, Andrea; Rimondini, Lia; Farè, Silvia

    2016-05-01

    Methylcellulose (MC), a water-soluble polymer derived from cellulose, was investigated as a possible temporary substrate having thermo-responsive properties favorable for cell culturing. MC-based hydrogels were prepared by a dispersion technique, mixing MC powder (2, 4, 6, 8, 10, 12 % w/v) with selected salts (sodium sulphate, Na2SO4), sodium phosphate, calcium chloride, or phosphate buffered saline, to evaluate the influence of different compositions on the thermo-responsive behavior. The inversion test was used to determine the gelation temperatures of the different hydrogel compositions; thermo-mechanical properties and thermo-reversibility of the MC hydrogels were investigated by rheological analysis. Gelation temperatures and rheological behavior depended on the MC concentration and type and concentration of salt used in hydrogel preparation. In vitro cytotoxicity tests, performed using L929 mouse fibroblasts, showed no toxic release from all the tested hydrogels. Among the investigated compositions, the hydrogel composed of 8 % w/v MC with 0.05 M Na2SO4 had a thermo-reversibility temperature at 37 °C. For that reason, this formulation was thus considered to verify the possibility of inducing in vitro spontaneous detachment of cells previously seeded on the hydrogel surface. A continuous cell layer (cell sheet) was allowed to grow and then detached from the hydrogel surface without the use of enzymes, thanks to the thermo-responsive behavior of the MC hydrogel. Immunofluorescence observation confirmed that the detached cell sheet was composed of closely interacting cells. PMID:26984360

  1. Effect of methylcellulose on the formation and drug release behavior of silk fibroin hydrogel.

    PubMed

    Park, Cho Hee; Jeong, Lim; Cho, Donghwan; Kwon, Oh Hyeong; Park, Won Ho

    2013-10-15

    In this study, methylcellulose (MC) was used to control the gelation time of silk fibroin (SF) aqueous solution. The gelation time was measured using a Vibro Viscometer at 50 °C. Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and a texture meter were used to investigate the effect of MC on the hydrogelation of SF solution. SF/MC hydrogels could be formed by the addition of MC, although their gelation time was increased with MC content. To examine the conformational change of SF/MC hydrogels, time-resolved FT-IR spectra were obtained at constant temperature using a custom-made IR chamber. From FT-IR spectra focused on the amide I peak position, the transition of SF molecules in SF/MC solution from a random coil to a β-sheet structure was inhibited in the presence of MC molecules. In addition, the drug release of SF/MC hydrogels loaded with 5-aminosalicylic acid was studied in 2-dimensional (2-D) and 3-dimensional (3-D) conditions in vitro. The drug release behavior of SF or SF/MC hydrogels was measured using UV-Vis spectroscopy. The release rate of 5-aminosalicylic acid in SF/MC hydrogel was lower than that of SF hydrogel, which may be closely associated with the hydrophilic interaction between MC and 5-aminosalicylic acid. This approach to controlling the sol-gel transition and the drug release of SF hydrogels by the addition of MC will be useful in the design and tailoring of novel materials for biomedical applications. PMID:23987461

  2. Physicochemical and morphological properties of poly (acrylamide) and methylcellulose hydrogels: rffects of monomer, crosslinker and polysaccharide compositions, polymer engineering and science

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This paper describes the physicochemical (mechanical and swelling) and morphological characterization of poly (acrylamide) and methylcellulose (PAAm-MC) hydrogels synthesized with different formulations by the free radical polymerization method. The structure-property relationship of the PAAm-MC hyd...

  3. Physical and sensory properties of all-barley and all-oat breads with additional hydroxypropyl methylcellulose (HPMC) ß-glucan

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hydroxypropyl methylcellulose (HPMC) is a substituted cellulose that reduces serum cholesterol at modest intake levels. HPMC has also been used for decades in gluten-free breads at a level to optimize loaf volume. Because consumers resist the consumption of whole wheat breads, we evaluated the sen...

  4. Ibuprofen microencapsulation within acrylamide-grafted chitosan and methylcellulose interpenetrating polymer network microspheres: Synthesis, characterization, and release studies.

    PubMed

    Bulut, Emine

    2016-06-01

    This study deals with the development of interpenetrating polymer network (IPN) microspheres of acrylamide (AAm) grafted onto a chitosan (CS) backbone and methylcellulose (MC). Chitosan-graft-polyacrylamide (CS-g-PAAm) was synthesized by cerium (IV) ammonium nitrate-induced free radical graft polymerization. The grafting percentage was found to be 50.58%. The synthesized graft copolymer and MC were used to prepare microspheres by the water-in-oil (w/o) emulsion-crosslinking method, and crosslinked with glutaraldehyde (GA) as drug delivery matrices of ibuprofen (IBU). The release of IBU from microspheres decreased when the amount of CS-g-PAAm in the polymer matrix and amount of crosslinker added were increased, while it increased with the increase of the IBU/polymer ratio. PMID:25749277

  5. Durability and synergistic effects of KI on the acid corrosion inhibition of mild steel by hydroxypropyl methylcellulose.

    PubMed

    Arukalam, I O

    2014-11-01

    The performance of hydroxypropyl methylcellulose (HPMC) as safe corrosion inhibitor for mild steel in aerated 0.5M H2SO4 solution was appraised by weight loss, impedance and polarization measurements. Results indicate that HPMC functions as a good inhibitor in the studied environment and inhibition efficiency increased with increasing concentration of inhibitor and temperature. Time-dependent effect of the inhibition efficiency reveals that inhibition efficiency increased with time up to the fourth day after which it waned, but improved on addition of KI. The synergism parameter evaluated confirmed the synergistic effect of KI and HPMC. Impedance results clearly show that HPMC inhibited the corrosion reaction via adsorption onto the metal/solution interface following Freundlich adsorption isotherm. Polarization results indicate that HPMC acts as a mixed-type inhibitor with predominant cathodic effect. Theoretical study using density functional theory was employed to establish the correlation between the structure (molecular and electronic) and the inhibition efficiency. PMID:25129747

  6. Edible films from methylcellulose and nanoemulsions of clove bud (Syzygium aromaticum) and oregano (Origanum vulgare) essential oils as shelf life extenders for sliced bread.

    PubMed

    Otoni, Caio G; Pontes, Silvania F O; Medeiros, Eber A A; Soares, Nilda de F F

    2014-06-01

    Consumers are increasingly demanding foods with lower synthetic preservatives. Plant essential oils are natural compounds with remarkable antimicrobial properties and may be incorporated as emulsions into water-soluble polymers to form antimicrobial films. Coarse emulsions (diameters of 1.3-1.9 μm) and nanoemulsions (diameters of 180-250 nm) of clove bud (Syzygium aromaticum) and oregano (Origanum vulgare) essential oils were produced through low-speed mixing and ultrasonication, respectively. Methylcellulose was added for film-forming purposes. Both essential oils reduced the rigidity and increased the extensibility of the methylcellulose films, effects that were even more pronounced for nanodroplets. Both essential oils lessened the counts of yeasts and molds in sliced bread during 15 days, and droplet size reduction provided a further improvement in antimicrobial properties. Due to increased bioavailability, less preservative content might be used and still deliver the same antimicrobial efficiency if encapsulated in smaller particles. PMID:24815228

  7. Pharmacokinetic and milk penetration of a difloxacin long-acting poloxamer gel formulation with carboxy-methylcellulose in lactating goats.

    PubMed

    Escudero, Elisa; Marín, Pedro; Cárceles, Carlos M; Ramírez, María J; Fernández-Varón, Emilio

    2011-04-01

    The single-dose disposition kinetics of difloxacin were determined in clinically normal lactating goats (n=6) after subcutaneous administration of a long-acting poloxamer 407 gel formulation with carboxy-methylcellulose (P407-CMC). Difloxacin concentrations were determined by high performance liquid chromatography with fluorescence detection. The concentration-time data were analysed by non-compartmental kinetic methods. Plasma and milk elimination half-lives after P407-CMC dosing were 35.19 h and 33.93 h, respectively. With this formulation, difloxacin achieved maximum plasma concentrations of 2.67±0.34 mg/L at 2.92±1.20 h and maximum milk concentrations of 2.31±0.35 mg/L at 4.00±0.00 h. The area under the curve (AUC) ratio AUC(milk)/AUC(plasma) was 0.89 after P407-CMC administration. It was concluded that a 15 mg/kg dose of difloxacin within P407-CMC would be effective against mastitis pathogens with a minimum inhibitory concentration (MIC)≤0.12 mg/L. PMID:20359917

  8. Gelatin-hydroxypropyl methylcellulose water-in-water emulsions as a new bio-based packaging material.

    PubMed

    Esteghlal, Sara; Niakosari, Mehrdad; Hosseini, Seyed Mohammad Hashem; Mesbahi, Gholam Reza; Yousefi, Gholam Hossein

    2016-05-01

    Gelatin and hydroxypropyl methylcellulose (HPMC) are two incompatible and immiscible biopolymers which cannot form homogeneous composite films using usual methods. In this study, to prevent phase separation, gelatin-HPMC water-in-water (W/W) emulsion was utilized to from transparent composite films by entrapment the HPMC dispersed droplets in gelatin continuous network. The physicochemical and mechanical properties of emulsion-based films containing different amounts (5-30%) of dispersed phase were determined and compared with those of individual polymer-based films. Incorporating HPMC into W/W emulsion-based films had no significant effect on the tensile strength. The flexibility of composite films decreased at HPMC concentrations below 20%. The depletion layer at the droplets interface reduced the diffusion of water vapor molecules because of its hydrophobic nature, so the water vapor permeability remained constant. Increasing the HPMC content in the emulsion films increased the swelling and decreased the transparency. The entrapment of HPMC in continuous gelatin phase decreased its solubility. Therefore, W/W emulsions are capable of holding two incompatible polymers alongside each other within a homogeneous film network without weakening the physical properties. PMID:26808017

  9. Injectable cell constructs fabricated via culture on a thermoresponsive methylcellulose hydrogel system for the treatment of ischemic diseases.

    PubMed

    Huang, Chieh-Cheng; Liao, Zi-Xian; Chen, Ding-Yuan; Hsiao, Chun-Wen; Chang, Yen; Sung, Hsing-Wen

    2014-08-01

    Cell transplantation via direct intramuscular injection is a promising therapy for patients with ischemic diseases. However, following injections, retention of transplanted cells in engrafted areas remains problematic, and can be deleterious to cell-transplantation therapy. In this Progress Report, a thermoresponsive hydrogel system composed of aqueous methylcellulose (MC) blended with phosphate-buffered saline is constructed to grow cell sheet fragments and cell bodies for the treatment of ischemic diseases. The as-prepared MC hydrogel system undergoes a sol-gel reversible transition upon heating or cooling at ≈32 °C. Via this unique property, the grown cell sheet fragments (cell bodies) can be harvested without using proteolytic enzymes; consequently, their inherent extracellular matrices (ECMs) and integrative adhesive agents remain well preserved. In animal studies using rats and pigs with experimentally created myocardial infarction, the injected cell sheet fragments (cell bodies) become entrapped in the interstices of muscular tissues and adhere to engraftment sites, while a minimal number of cells exist in the group receiving dissociated cells. Moreover, transplantation of cell sheet fragments (cell bodies) significantly increases vascular density, thereby improving the function of an infarcted heart. These experimental results demonstrate that cell sheet fragments (cell bodies) function as a cell-delivery construct by providing a favorable ECM environment to retain transplanted cells locally and consequently, improving the efficacy of therapeutic cell transplantation. PMID:24470263

  10. In Situ Observations of Thermoreversible Gelation and Phase Separation of Agarose and Methylcellulose Solutions under High Pressure.

    PubMed

    Kometani, Noritsugu; Tanabe, Masahiro; Su, Lei; Yang, Kun; Nishinari, Katsuyoshi

    2015-06-01

    Thermoreversible sol-gel transitions of agarose and methylcellulose (MC) aqueous solutions on isobaric cooling or heating under high pressure up to 400 MPa have been investigated by in situ observations of optical transmittance and falling-ball experiments. For agarose, which undergoes the gelation on cooling, the application of pressure caused a gradual rise in the cloud-point temperature over the whole pressure range examined, which is almost consistent with the pressure dependence of gelling temperature estimated by falling-ball experiments, suggesting that agarose gel is stabilized by compression and that the gelation occurs nearly in parallel with phase separation under ambient and high-pressure conditions. For MC, which undergoes the gelation on heating, the cloud-point temperature showed a slight rise with an initial elevation of pressure up to ∼150 MPa, whereas it showed a marked depression above 200 MPa. In contrast, the gelling temperature of MC, which is nearly identical to the cloud-point temperature at ambient pressure, showed a monotonous rise with increasing pressure up to 350 MPa, which means that MC undergoes phase separation prior to gelation on heating under high pressure above 200 MPa. Similar results were obtained for the melting process of MC gel on cooling. The unique behavior of the sol-gel transition of MC under high pressure has been interpreted in terms of the destruction of hydrophobic hydration by compression. PMID:25984597

  11. The influence of substituted phenols on the sol:gel transition of hydroxypropyl methylcellulose (HPMC) aqueous solutions.

    PubMed

    Banks, Simon R; Pygall, Samuel R; Bajwa, Gurjit S; Doughty, Stephen W; Timmins, Peter; Melia, Colin D

    2014-01-30

    The influence of the physicochemical parameters of substituted aromatic molecules on the phase transition from sol to gel of hydroxypropyl methylcellulose (HPMC) has been investigated using a homologous series of substituted phenols. Using a turbimetric methodology, concentration dependent suppression of phase transition temperature of HPMC was observed for phenol and its derivatives, including methyl-, nitro- and chloro-substituted molecules. Although no strong direct relationship between single molecular physicochemical properties of the phenolic compounds (such as pKa, LogP and other molecular descriptors) and ΔCPT was found for the compounds tested, a successful prediction of behaviour could be obtained by using a combination of parameters. This suggested that the interaction mechanism between HPMC and the substituted aromatic moiety is a complex summation of the different molecular physicochemical properties. Identification of these potentially deleterious chemical moieties may be of value in a pharmaceutical context when considering preformulation of drug structures containing them. An incompatibility between drug and polymer may be indicative of deleterious effects resulting from formulation with hydrophilic matrix dosage forms containing cellulose ethers such as HPMC. PMID:24299892

  12. A novel white film for pharmaceutical coating formed by interaction of calcium lactate pentahydrate with hydroxypropyl methylcellulose.

    PubMed

    Sakata, Yukoh; Shiraishi, Sumihiro; Otsuka, Makoto

    2006-07-24

    We have found that a white film forms on tablets when a coating solution consisting of hydroxypropyl methylcellulose (HPMC), polyethylene glycol (PEG 6000) and calcium lactate pentahydrate (CLP) is used. The white film has also been found in casting film consisting of HPMC and CLP, and the surface state of coated tablets has been shown to be strongly affected by addition of PEG 6000. The aim of the present study was to investigate the mechanism of formation of this white film in order to derive an appropriate film prescription. Interaction among the base ingredients of the film was investigated using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform-infrared (FT-IR) spectroscopy. The casting film formed with HPMC and a large excess of PEG 6000 was found to be crystalline in form. In contrast, the amorphous film consisting of HPMC, PEG 6000 and excess CLP exhibited the crystallinity film by an excess addition of CLP. Although the crystalline film had many cracks, the amorphous film appeared to be excellent as a tablet coating. The most probable interaction sites between HPMC and CLP were demonstrated by FT-IR analysis of casting films consisting of HPMC, CLP and PVP. PMID:16621357

  13. Optimization and Evaluation of a Chitosan/Hydroxypropyl Methylcellulose Hydrogel Containing Toluidine Blue O for Antimicrobial Photodynamic Inactivation

    PubMed Central

    Chen, Chueh-Pin; Hsieh, Chien-Ming; Tsai, Tsuimin; Yang, Jen-Chang; Chen, Chin-Tin

    2015-01-01

    Photodynamic inactivation (PDI) combined with chitosan has been shown as a promising antimicrobial approach. The purpose of this study was to develop a chitosan hydrogel containing hydroxypropyl methylcellulose (HPMC), chitosan and toluidine blue O (TBO) to improve the bactericidal efficacy for topical application in clinics. The PDI efficacy of hydrogel was examined in vitro against the biofilms of Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa). Confocal scanning laser microscopy (CSLM) was performed to investigate the penetration level of TBO into viable S. aureus biofilms. Incorporation of HMPC could increase the physicochemical properties of chitosan hydrogel including the hardness, viscosity as well as bioadhesion; however, higher HMPC concentration also resulted in reduced antimicrobial effect. CSLM analysis further demonstrated that higher HPMC concentration constrained TBO diffusion into the biofilm. The incubation of biofilm and hydrogel was further performed at an angle of 90 degrees. After light irradiation, compared to the mixture of TBO and chitosan, the hydrogel treated sample showed increased PDI efficacy indicated that incorporation of HPMC did improve antimicrobial effect. Finally, the bactericidal efficacy could be significantly augmented by prolonged retention of hydrogel in the biofilm as well as in the animal model of rat skin burn wounds after light irradiation. PMID:26340623

  14. Injectable thermo-responsive hydrogel composed of xanthan gum and methylcellulose double networks with shear-thinning property.

    PubMed

    Liu, Zhijia; Yao, Ping

    2015-11-01

    Injectable hydrogel precursor solution was prepared by physical blend of xanthan gum (XG) and methylcellulose (MC) in aqueous solution. Due to the formation of XG network composed of XG double helical strand structure, XG/MC blend was a high viscous solution with good shear-thinning property at room temperature. When the temperature was changed from 23 to 37 °C, thermo-responsive MC network formed, which caused XG/MC blend solution to gelate. The gelation time and storage modulus of the blend can be tuned by XG and/or MC concentrations. Both in vitro and in vivo investigations revealed that the blend solution immediately recovered its high viscosity and rapidly formed hydrogel at body temperature after injection using a syringe. In vivo biocompatibility and biodegradability of the hydrogel were validated by implantation of the hydrogel in rats. In vitro investigation demonstrated that XG/MC blend is a promising injectable hydrogel material for long-term drug delivery. PMID:26256374

  15. Extended release of high molecular weight hydroxypropyl methylcellulose from molecularly imprinted, extended wear silicone hydrogel contact lenses.

    PubMed

    White, Charles J; McBride, Matthew K; Pate, Kayla M; Tieppo, Arianna; Byrne, Mark E

    2011-08-01

    Symptoms of contact lenses induced dry eye (CLIDE) are typically treated through application of macromolecular re-wetting agents via eye drops. Therapeutic soft contact lenses can be formulated to alleviate CLIDE symptoms by slowly releasing comfort agent from the lens. In this paper, we present an extended wear silicone hydrogel contact lens with extended, controllable release of 120 kDa hydroxypropyl methylcellulose (HPMC) using a molecular imprinting strategy. A commercial silicone hydrogel lens was tailored to release approximately 1000 μg of HPMC over a period of up to 60 days in a constant manner at a rate of 16 μg/day under physiological flowrates, releasing over the entire range of continuous wear. Release rates could be significantly varied by the imprinting effect and functional monomer to template ratio (M/T) with M/T values 0, 0.2, 2.8, 3.4 corresponding to HPMC release durations of 10, 13, 23, and 53 days, respectively. Lenses had high optical quality and adequate mechanical properties for contact lens use. This work highlights the potential of imprinting in the design and engineering of silicone hydrogel lenses to release macromolecules for the duration of wear, which may lead to decreased CLIDE symptoms and more comfortable contact lenses. PMID:21601274

  16. Preparation and performance of hydroxypropyl methylcellulose esters of substituted succinates for in vitro supersaturation of a crystalline hydrophobic drug.

    PubMed

    Yin, Ligeng; Hillmyer, Marc A

    2014-01-01

    We prepared hydroxypropyl methylcellulose (HPMC) esters of substituted succinates and examined their performance for improving the aqueous solubility of crystalline hydrophobic drugs in spray-dried dispersions (SDDs). From one HPMC, we synthesized five HPMC esters using various monosubstituted succinic anhydrides. These HPMC esters along with a commercial HPMC acetate succinate (HPMCAS) were spray-dried from solutions with phenytoin. The SDDs with different matrices at 10 wt % loading had very similar bulk properties with a minimal amount of detectable crystalline phenytoin as revealed by scanning electron microscopy (SEM), powder X-ray diffraction (powder XRD), and differential scanning calorimetry (DSC). In solution, while the SDD with HPMCAS was very effective at achieving high levels of phenytoin supersaturation initially, it was not competent at maintaining such supersaturation due to the rapid crystallization of the dissolved phenytoin. Alternatively, SDDs with several synthesized HPMC esters of substituted succinates not only achieved rather high initial supersaturation but also maintained high concentrations for extended time (i.e., 1.5 h and longer). Such maintenance was largely ascribed to the inhibition of phenytoin nucleation. Structure-property relationships were established, and the most successful systems contained a high degree of substitution and a combination of a thioether with neighboring weak electron-withdrawing groups in the substituted succinic anhydrides. The effective maintenance of supersaturated solutions was only found in SDDs with rather low drug loadings, which indicates the significance of sufficiently high concentrations of polymer additives in the dissolution media. PMID:24320108

  17. Effects of ultrasound treatment on lipid self-association and properties of methylcellulose/stearic acid blending films.

    PubMed

    Zhong, Tian; Huang, Ran; Sui, Siyao; Lian, Zixuan; Sun, Xiuxiu; Wan, Ajun; Li, Huili

    2015-10-20

    The effects of ultrasound treatment (UT) on the properties of methylcellulose (MC)/stearic acid (SA) blending films were studied. Film-forming emulsions were prepared with different UT conditions and characterized with respect to viscosity. The lipid aggregation and distribution in the blending dispersions were studied by the micrographs of Transmission Electron Microscopy (TEM). The micrographs of both surface and cross-section of the films were observed by scanning electron microscope (SEM) and the tensile strength (TS), elongation at break (E), water vapor permeability (WVP) and contact angles of the resulting films were determined as well. The intensification of the UT condition led to a decrease of viscosity of the MC-SA blending emulsions, a more homogeneous lipid distribution and a denser internal microstructure of the resulting films. UT exposure affected the mechanical, moisture barrier and surface hydrophobic properties. The optimal values of both TS and E was obtained from the sample treated for 10min and 180W power, while the sample treated for 10min and 270W presented the lowest value of WVP. However, an excessive exposure of UT led to a decrease of the mechanical and moisture barrier performance. By observing and analyzing the SEM graphs and the contact angles of the film surfaces, it was found that UT within the appropriate bounds had a notably positive effect on improving the surface hydrophobic property of the MC-SA blending films. PMID:26256202

  18. Rheological response of methylcellulose toward alkanediyl-α,ω-bis(dimethylcetylammonium bromide) surfactants with varying spacer length.

    PubMed

    Shah, Rais Ahmad; Chat, Oyais Ahmad; Maswal, Masrat; Rather, Ghulam Mohammad; Dar, Aijaz Ahmad

    2016-06-25

    The modulation of properties of methylcellulose (MC) by cationic gemini surfactants with varying spacer lengths was studied employing tensiometry, rheometry and turbidimetry. Surface tension measurements anticipate that the gemini surfactant with longer spacer chain length saturates MC at lower concentrations owing to its greater hydrophobicity compared to shorter spacer analogues. Rheometric and turbidimetric measurements suggest that at very low concentrations of gemini surfactants, ion-dipole type of interactions between MC and gemini surfactants promote the extension of polymer chains which is manifested by an initial increase in the low shear viscosity and gelation temperature of MC-gemini surfactant systems, and lowering of turbidity. Such interactions were found to be stronger in case of 16-4-16 than 16-5-16, and almost absent in case of 16-6-16 surfactant system. However at concentrations above CAC, hydrophobic forces operative between MC and gemini surfactants were found to be more for 16-6-16 than that of 16-5-16 and 16-4-16. The final levelling of MC viscosity in presence of all the three gemini surfactants and the variation of gelation temperature suggests the solubilization of network junctions in the surfactant micelles. Moreover, the presence of gemini surfactant strongly affects the interaction of MC with a model hydrophobic drug rifampicin.The results highlight the importance of gemini surfactants and their spacer length in controlling the structural dynamics of MC and its effective use in pharmaceutical and food industry. PMID:27083805

  19. Equilibrium state at supersaturated drug concentration achieved by hydroxypropyl methylcellulose acetate succinate: molecular characterization using (1)H NMR technique.

    PubMed

    Ueda, Keisuke; Higashi, Kenjirou; Yamamoto, Keiji; Moribe, Kunikazu

    2015-04-01

    The maintenance mechanism of the supersaturated state of poorly water-soluble drugs, glibenclamide (GLB) and chlorthalidone (CLT), in hydroxypropyl methylcellulose acetate succinate (HPMC-AS) solution was investigated at a molecular level. HPMC-AS suppressed drug crystallization from supersaturated drug solution and maintained high supersaturated level of drugs with small amount of HPMC-AS for 24 h. However, the dissolution of crystalline GLB into HPMC-AS solution failed to produce supersaturated concentrations, although supersaturated concentrations were achieved by adding amorphous GLB to HPMC-AS solution. HPMC-AS did not improve drug dissolution and/or solubility but efficiently inhibited drug crystallization from supersaturated drug solutions. Such an inhibiting effect led to the long-term maintenance of the amorphous state of GLB in HPMC-AS solution. NMR measurements showed that HPMC-AS suppressed the molecular mobility of CLT depending on their supersaturation level. Highly supersaturated CLT in HPMC-AS solution formed a gel-like structure with HPMC-AS in which the molecular mobility of the CLT was strongly suppressed. The gel-like structure of HPMC-AS could inhibit the reorganization from drug prenuclear aggregates to the crystal nuclei and delay the formation of drug crystals. The prolongation subsequently led to the redissolution of the aggregated drugs in aqueous solution and formed the equilibrium state at the supersaturated drug concentration in HPMC-AS solution. The equilibrium state formation of supersaturated drugs by HPMC-AS should be an essential mechanism underlying the marked drug concentration improvement. PMID:25723893

  20. Modification and characterization of biodegradable methylcellulose films with trimethylolpropane trimethacrylate (TMPTMA) by γ radiation: effect of nanocrystalline cellulose.

    PubMed

    Sharmin, Nusrat; Khan, Ruhul A; Salmieri, Stephane; Dussault, Dominic; Bouchard, Jean; Lacroix, Monique

    2012-01-18

    Methylcellulose (MC)-based films were prepared by solution casting from its 1% aqueous suspension containing 0.25% glycerol. Trimethylolpropane trimethacrylate (TMPTMA) monomer (0.1-2% by wt) along with the glycerol was added to the MC suspension. The films were cast and irradiated from a radiation dose varied from 0.1 to 10 kGy. Then the mechanical properties such as tensile strength (TS), tensile modulus (TM), and elongation at break (Eb) and barrier properties of the films were evaluated. The highest TS (47.88 PMa) and TM (1791.50 MPa) of the films were found by using 0.1% monomer at 5 kGy dose. The lowest water vapor permeability (WVP) of the films was found to be 5.57 g·mm/m(2)·day·kPa (at 0.1% monomer and 5 kGy dose), which is 12.14% lower than control MC-based films. Molecular interactions due to incorporation of TMPTMA were supported by FTIR spectroscopy. A band at 1720 cm(-1) was observed due to the addition of TMPTMA in MC-based films, which indicated the typical (C═O) carbonyl stretching. For the further improvement of the mechanical and barrier properties of the film, 0.025-1% nanocrystalline cellulose (NCC) was added to the MC-based suspension containing 1% TMPTMA. Addition of NCC led to a significant improvement in the mechanical and barrier properties. The novelty of this investigation was to graft insoluble monomer using γ radiation with MC-based films and use of biodegradable NCC as the reinforcing agent. PMID:22217269

  1. Preparation, characterization and in vitro drug release of poly-epsilon-caprolactone and hydroxypropyl methylcellulose phthalate ketoprofen loaded microspheres.

    PubMed

    Guzman, M; Molpeceres, J; Garcia, F; Aberturas, M R

    1996-01-01

    Ketoprofen was encapsulated within poly-epsilon-caprolactone (PCL) and hydroxypropyl methylcellulose phthalate 50 (HPMCP50) microspheres (MS). Scanning electron microscopy (SEM) studies showed spherical particles without surface crystal formation and differential scanning calorimetry (DSC) supported these results. MS of PCL or HPMCP50 had a mean particle size of 10.7 +/- 2.2 and 10.9 +/- 2.0 mu m respectively, whereas a mixture of these polymers increased the MS particle size to 30 mu m. Greater incorporation efficiencies were found for HPMCP50 MS (98.1 +/- 0.7). MS of PCL and HPMCP50 mixtures showed a decreased drug entrapment as the amount of PCL was increased (96.0 +/- 0.2 for 25% PCL, 95.6 +/- 1.8 for 50% PCL, 80.2 +/- 0.7 for 75% PCL and 78.9 +/- 9.0 for 100% PCL). Size exclusion chromatography (SEC) studies revealed a weak interaction between ketoprofen and PCL and some polymer degradation was found during HPMCP50 MS storage, probably by breaking of the phthalic anhydride bond to be anyhydroglucose backbone. Four types of cryoprotectors (glucose, trehalose, mannitol and sorbitol, at 5 and 10% W/V) and two freezing conditions (-196 and -20 degrees C) were evaluated in freeze-drying studies. For HPMCP50, the sizes of MS after reconstitution of liophylizates were nearly the same as the initial ones. For PCL MS only, those formulations with sorbitol or glucose at 10% and frozen at -196 degrees C showed acceptable results. In contrast to the rapid release rate of ketoprofen from PCL MS as a result of carrier porosity (80% released within 15 min), the release from HPMCP50 MS could be controlled by means of pH (40% released in the first 15 min in simulated gastric fluid and nearly 100% ketoprofen delivered in the same time in simulated intestinal fluid). PMID:8903783

  2. Factorial designed 5-fluorouracil-loaded microsponges and calcium pectinate beads plugged in hydroxypropyl methylcellulose capsules for colorectal cancer

    PubMed Central

    Gupta, Ankita; Tiwari, Gaurav; Tiwari, Ruchi; Srivastava, Rishabh

    2015-01-01

    Introduction: The work was aimed to develop an enteric-coated hydroxypropyl methylcellulose (HPMC) capsules (ECHC) plugged with 5-fluorouracil (5-FU)-loaded microsponges in combination with calcium pectinate beads. Materials and Methods: The modified quasi-emulsion solvent diffusion method was used to prepare microsponges. A 32 factorial design was employed to study the formulation and the effects of independent variables (volume of organic solvent and Eudragit-RS100 content) on dependent variables (particle size, %entrapment efficiency, and %cumulative drug release). The optimized microsponge (F4) was characterized by scanning electron microscopy, powder X-ray diffraction, and thermogravimetric analysis. F4 was plugged along with the calcium pectinate beads in HPMC capsules coated with enteric polymer Eudragit-L100 (Ed-L100) and/or Eudragit-S100 (Ed-S100) in different proportions. An in vitro release study of ECHC was performed in simulated gastric fluid for 2 h, followed by simulated intestinal fluid for next 6 h and then in simulated colonic fluid (in the presence and absence of pectinase enzyme for further 16 h). The optimized formulation was subjected to in vivo roentgenographic and pharmacokinetic studies in New Zealand white rabbits to analyze the in vivo behavior of the developed colon-targeted capsules. Results: Drug release was retarded on coating with Ed-S100 in comparison to a blend of Ed-S100:Ed-L100 coating. The percentage of 5-FU released at the end of 24 h from ECHC3 was 97.83 ± 0.12% in the presence of pectinase whereas in the control study, it was 40.08 ± 0.02%. Conclusion: Thus, enteric-coated HPMC capsules plugged with 5-FU-loaded microsponges and calcium pectinate beads proved to be a promising dosage form for colon targeting. PMID:26682194

  3. Preparation of magnetite-chitosan/methylcellulose nanospheres by entrapment and adsorption techniques for targeting the anti-cancer drug 5-fluorouracil.

    PubMed

    Şanlı, Oya; Kahraman, Aslı; Kondolot Solak, Ebru; Olukman, Merve

    2016-05-01

    In this work, we have formulated novel nanospheres that could be used in the controlled release of the anticancer drug, 5-fluorouracil (5-FU). The nanospheres are composed of magnetite, containing chitosan (CS) and methylcellulose (MC). The drug entrapment was achieved through the encapsulation and adsorption processes. The effects of the preparation conditions, such as magnetite content, CS/MC ratio, crosslinking concentration, exposure time to glutaraldehyde (GA), and the drug/polymer ratio were investigated for both processes. The 5-FU release was found to follow the Fickian mechanism, and the Langmuir isotherm for the nanospheres was achieved through encapsulation and adsorption processes, respectively. PMID:25677468

  4. Physical and sensory properties of all-barley and all-oat breads with additional hydroxypropyl methylcellulose (HPMC) β-glucan.

    PubMed

    Kim, Yookyung; Yokoyama, Wallace H

    2011-01-26

    Hydroxypropyl methylcellulose (HPMC) is a substituted cellulose that reduces serum cholesterol at modest intake levels. HPMC has also been used for decades in gluten-free breads at a level to optimize loaf volume. Because consumers resist the consumption of whole wheat breads, the sensory and physical properties of all oat and barley breads incorporating HPMC were evaluated. Oat and barley also contain β-glucan, a glucose polymer similar to HPMC that also lowers cholesterol. The textural and sensory properties of the breads were determined by instrumental and chemical methods and sensory panels. HPMC increased the loaf volume of the breads by up to 2 times and decreased hardness immediately after baking and after up to 3 days of storage. Barley bread with HPMC was rated the highest in overall acceptability by sensory panelists compared to oat and wheat breads with or without HPMC. PMID:21189014

  5. Correlation between the permeability of metoprolol tartrate through plasticized isolated ethylcellulose/hydroxypropyl methylcellulose films and drug release from reservoir pellets.

    PubMed

    Ye, Zhi-wei; Rombout, Patrick; Remon, Jean Paul; Vervaet, Chris; Van den Mooter, Guy

    2007-09-01

    The present study investigates if drug diffusion through plasticized isolated ethylcellulose (EC)/hydroxypropyl methylcellulose (HPMC) films prepared by solvent casting can be used as a tool to develop spray-coated dosage forms. In particular, the importance of the level and type of plasticizers was investigated. The permeability of the model drug metoprolol tartrate through plasticized isolated films could be adjusted by selecting the type and amount of plasticizer in the films due to the different hydrophilicity of the plasticizers. The release of metoprolol tartrate from coated pellets is consistent with the drug diffusion through the films made up of the same polymer blends. This indicated that it is useful to test isolated films for early predictions and for formulation optimization. PMID:17383166

  6. Improvement of the mechanical and barrier properties of methylcellulose-based films by treatment with HEMA and silane monomers under gamma radiation

    NASA Astrophysics Data System (ADS)

    Khan, Ruhul A.; Dussault, Dominic; Salmieri, Stephane; Safrany, Agnes; Lacroix, Monique

    2012-08-01

    Methylcellulose (MC)-based films were prepared by casting from its 1% aqueous solution containing 0.5% vegetable oil, 0.25% glycerol and 0.025% Tween®-80. Puncture strength (PS), puncture deformation (PD) and water vapor permeability (WVP) of the films were found to be 147 N/mm, 3.46 mm, and 6.34 g mm/m2 day kPa, respectively. The monomer, 2-hydroxyethyl methacrylate (HEMA) (0.1-1%, w/w) was incorporated into the MC-based solution and films were prepared by casting. Films were then exposed to gamma radiation (5-25 kGy) and it revealed that 1% HEMA containing films showed the highest PS values (282 N/mm at 10 kGy). Silane monomer (3-aminopropyl tri-ethoxy silane) (0.1-1%, w/w) was also added into the MC-based films and were found to improve the strength of the films significantly. In comparison between HEMA and silane treatment onto MC-based films, it was observed that silane performed better strength and barrier properties. Surface morphology of the monomer treated films was examined by scanning electron microscopy and suggested better appearance than MC-based film.

  7. Effect of plasticizer type and amount on hydroxypropyl methylcellulose-beeswax edible film properties and postharvest quality of coated plums (cv. Angeleno).

    PubMed

    Navarro-Tarazaga, Maria Ll; Sothornvit, Rungsinee; Pérez-Gago, María B

    2008-10-22

    The effect of the composition of hydroxypropyl methylcellulose (HPMC)-beeswax (BW) edible coatings on stand-alone film properties and on postharvest quality of coated 'Angeleno' plums was studied. Glycerol (G) and mannitol (M) were tested as plasticizers at two different plasticizer/HPMC ratios (100:1 and 300:1 molar basis). BW content was 20 or 40% (dry basis). An increase in G content increased film flexibility and vapor permeability (WVP), whereas an increase in M content enhanced film brittleness without affecting WVP. An increase in BW content reduced film flexibility and reduced WVP of only G-plasticized films. Coatings reduced plum softening and bleeding, but were not effective in reducing plum weight loss. At low plasticizer content, coatings reduced texture loss effectively. Low BW also lowered plum bleeding. Plasticizer type affected only ethanol and acetaldehyde contents without affecting the remaining quality parameters. Therefore, HPMC-BW coatings have the potential to extend the shelf life of plums. However, this effect depends on coating composition. Differences between coating and film performance indicate that data from stand-alone films may be used as a preliminary screening, but coating performance should be analyzed on coated fruit. PMID:18823125

  8. Inhibition of Penicillium digitatum and Penicillium italicum by hydroxypropyl methylcellulose-lipid edible composite films containing food additives with antifungal properties.

    PubMed

    Valencia-Chamorro, Silvia A; Palou, Lluís; del Río, Miguel A; Pérez-Gago, María B

    2008-12-10

    New hydroxypropyl methylcellulose (HPMC)-lipid edible composite films containing low-toxicity chemicals with antifungal properties were developed. Tested chemicals were mainly salts of organic acids, salts of parabens, and mineral salts, classified as food additives or generally recognized as safe (GRAS) compounds. Selected films containing food preservatives were used for in vitro evaluation (disk diameter test) of their antifungal activity against Penicillium digitatum (PD) and Penicillium italicum (PI), the most important postharvest pathogens of fresh citrus fruit. Mechanical properties and oxygen (OP) and water vapor permeabilities (WVP) of selected films were also determined. Film disks containing parabens and their mixtures inhibited PD and PI to a higher extent than the other chemicals tested. Among all organic acid salts tested, potassium sorbate (PS) and sodium benzoate (SB) were the most effective salts in controlling both PD and PI. The use of mixtures of parabens or organic acid salts did not provide an additive or synergistic effect for mold inhibition when compared to the use of single chemicals. Barrier and mechanical properties of films were affected by the addition of food preservatives. Results showed that HPMC-lipid films containing an appropriate food additive should promise as potential commercial antifungal edible coatings for fresh citrus fruit. PMID:19012404

  9. SYNTHESIS AND IN VITRO CHARACTERIZATION OF HYDROXYPROPYL METHYLCELLULOSE-GRAFT-POLY (ACRYLIC ACID/2-ACRYLAMIDO-2-METHYL-1-PROPANESULFONIC ACID) POLYMERIC NETWORK FOR CONTROLLED RELEASE OF CAPTOPRIL.

    PubMed

    Furqan Muhammad, Iqbal; Mahmood, Ahmad; Aysha, Rashid

    2016-01-01

    A super-absorbent hydrogel was developed by crosslinking of 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) and acrylic acid with hydroxypropyl methylcellulose (HPMC) for controlled release drug delivery of captopril, a well known antihypertensive drug. Acrylic acid and AMPS were polymerized and crosslinked with HPMC by free radical polymerization, a widely used chemical crosslinking method. N,N'-methylenebisacrylamide (MBA) and potassium persulfate (KPS) were added as cross-linker and initiator, respectively. The hydrogel formulation was loaded with captopril (as model drug). The concentration of captopril was monitored at 205 nm using UV spectrophotometer. Equilibrium swelling ratio was determined at pH 2, 4.5 and 7.4 to evaluate the pH responsiveness of the formed hydrogel. The super-absorbent hydrogels were evaluated by FTIR, SEM, XRD, and thermal analysis (DSC and TGA). The formation of new copolymeric network was determined by FTIR, XRD, TGA and DSC analysis. The hydrogel formulations with acrylic acid and AMPS ratio of 4: 1 and lower amounts of crosslinker had shown maximum swelling. Moreover, higher release rate of captopril was observed at pH 7.4 than at pH 2, because of more swelling capacity of copolymer with increasing pH of the aqueous medium. The present research work confirms the development of a stable hydrogel comprising of HPMC with acrylic acid and AMPS. The prepared hydrogels exhibited pH sensitive behav-ior. This superabsorbent composite prepared could be a successful drug carrier for treating hypertension. PMID:27008813

  10. Evaluating food additives as antifungal agents against Monilinia fructicola in vitro and in hydroxypropyl methylcellulose-lipid composite edible coatings for plums.

    PubMed

    Karaca, Hakan; Pérez-Gago, María B; Taberner, Verònica; Palou, Lluís

    2014-06-01

    Common food preservative agents were evaluated in in vitro tests for their antifungal activity against Monilinia fructicola, the most economically important pathogen causing postharvest disease of stone fruits. Radial mycelial growth was measured in Petri dishes of PDA amended with three different concentrations of the agents (0.01-0.2%, v/v) after 7 days of incubation at 25 °C. Thirteen out of fifteen agents tested completely inhibited the radial growth of the fungus at various concentrations. Among them, ammonium carbonate, ammonium bicarbonate and sodium bicarbonate were the most effective while sodium acetate and sodium formate were the least effective. The effective agents and concentrations were tested as ingredients of hydroxypropyl methylcellulose (HPMC)-lipid edible coatings against brown rot disease on plums previously inoculated with M. fructicola (curative activity). 'Friar' and 'Larry Ann' plums were inoculated with the pathogen, coated with stable edible coatings about 24h later, and incubated at 20 °C and 90% RH. Disease incidence (%) and severity (lesion diameter) were determined after 4, 6, and 8 days of incubation and the 'area under the disease progress stairs' (AUDPS) was calculated. Coatings containing bicarbonates and parabens significantly reduced brown rot incidence in plums, but potassium sorbate, used at 1.0% in the coating formulation, was the most effective agent with a reduction rate of 28.6%. All the tested coatings reduced disease severity to some extent, but coatings containing 0.1% sodium methylparaben or sodium ethylparaben or 0.2% ammonium carbonate or ammonium bicarbonate were superior to the rest, with reduction rates of 45-50%. Overall, the results showed that most of the agents tested in this study had significant antimicrobial activity against M. fructicola and the application of selected antifungal edible coatings is a promising alternative for the control of postharvest brown rot in plums. PMID:24742996

  11. Preparation and characterization of gatifloxacin-loaded sodium alginate hydrogel membranes supplemented with hydroxypropyl methylcellulose and hydroxypropyl cellulose polymers for wound dressing

    PubMed Central

    Prabu, Durai; Majdalawieh, Amin F.; Abu-Yousef, Imad A.; Inbasekaran, Kadambari; Balasubramaniam, Tharani; Nallaperumal, Narayanan; Gunasekar, Conjeevaram J.

    2016-01-01

    Introduction: The aim of this study is to evaluate gatifloxacin-loaded sodium alginate hydrogel membranes, supplemented with glycerol (a plasticizer), glutaraldehyde (a cross-linking agent), and hydroxypropyl methylcellulose (HPMC) or hydroxypropyl cellulose (HPC) polymers, as potential wound dressing materials based on their physicochemical properties and the sustain-release phenomenon. Materials and Methods: The physicochemical properties of the prepared hydrogel membranes were evaluated by several methods including Fourier transform infrared and differential scanning calorimetry. Different techniques were used to assess the swelling behavior, tensile strength and elongation, % moisture absorption, % moisture loss, water vapor transmission rate (WVTR), and microbial penetration for the hydrogel membranes. In vitro gatifloxacin release from the hydrogel membranes was examined using the United States Pharmacopeia XXIII dissolution apparatus. Four kinetics models (zero-order, first-order, Higuchi equation, and Korsmeyer-Peppas equation) were applied to study drug release kinetics. Results: The addition of glycerol, glutaraldehyde, HPMC, and HPC polymers resulted in a considerable increase in the tensile strength and flexibility/elasticity of the hydrogel membranes. WVTR results suggest that hydrated hydrogel membranes can facilitate water vapor transfer. None of the hydrogel membranes supported microbial growth. HPMC-treated and HPC-treated hydrogel membranes allow slow, but sustained, release of gatifloxacin for 48 h. Drug release kinetics revealed that both diffusion and dissolution play an important role in gatifloxacin release. Conclusions: Given their physicochemical properties and gatifloxacin release pattern, HPMC-treated and HPC-treated hydrogel membranes exhibit effective and sustained drug release. Furthermore, HPMC-treated and HPC-treated hydrogel membranes possess physiochemical properties that make them effective and safe wound dressing materials. PMID

  12. Influence of Hydroxypropyl Methylcellulose on Metronidazole Crystallinity in Spray-Congealed Polyethylene Glycol Microparticles and Its Impact with Various Additives on Metronidazole Release.

    PubMed

    Oh, Ching Mien; Heng, Paul Wan Sia; Chan, Lai Wah

    2015-12-01

    The purpose of this study was to investigate the effect of a hydrophilic polymer, hydroxypropyl methylcellulose (HPMC), on the crystallinity and drug release of metronidazole (MNZ) in spray-congealed polyethylene glycol (PEG) microparticles and to further modify the drug release using other additives in the formulation. HPMC has been used in many pharmaceutical formulations and processes but to date, it has not been employed as an additive in spray congealing. Crystallinity of a drug is especially important to the development of pharmaceutical products as active pharmaceutical ingredients (APIs) are mostly crystalline in nature. A combination of X-ray diffractometry, differential scanning calorimetry, Raman spectroscopy and Fourier transform-infrared spectroscopy (FT-IR) spectroscopy was employed to investigate the degree of crystallinity and possible solid-state structure of MNZ in the microparticles. The microparticles with HPMC were generally spherical. Spray congealing decreased MNZ crystallinity, and the presence of HPMC reduced the drug crystallinity further. The reduction in MNZ crystallinity was dependent on the concentration of HPMC. Smaller HPMC particles also resulted in a greater percentage reduction in MNZ crystallinity. Appreciable modification to MNZ release could be obtained with HPMC. However, this was largely attributed to the role of HPMC in forming a diffusion barrier. Further modification of drug release from spray-congealed PEG-HPMC microparticles was achieved with the addition of 5% w/w dicalcium phosphate but not with magnesium stearate, methyl cellulose, polyvinylpyrrolidone, silicon dioxide and sodium oleate/citric acid. Dicalcium phosphate facilitated formation of the diffusion barrier. PMID:25933626

  13. Effect of antifungal hydroxypropyl methylcellulose-lipid edible composite coatings on Penicillium decay development and postharvest quality of cold-stored "Ortanique" mandarins.

    PubMed

    Valencia-Chamorro, Silvia A; Pérez-Gago, María B; Del Río, Miguel A; Palou, Lluís

    2010-10-01

    Edible composite coatings based on hydroxypropyl methylcellulose (HPMC), hydrophobic components (beeswax and shellac), and food preservatives with antifungal properties were evaluated on "Ortanique" mandarins during long-term cold storage. Selected food preservatives included potassium sorbate (PS), sodium benzoate (SB), sodium propionate (SP), and their mixtures. Intact mandarins or mandarins artificially inoculated with the pathogens Penicillium digitatum and Penicillium italicum, the causal agents of citrus postharvest green (GM) and blue (BM) molds, respectively, were coated and stored up to 8 wk at 5 °C + 1 wk of shelf-life at 20 °C. HPMC-lipid coatings containing food preservatives controlled better GM than BM on Ortanique mandarins. SB- and SB + SP-based coatings reduced the incidence of GM by about 35% after 4 wk at 5 °C. Among all coatings, only the SB-based coating reduced the incidence of GM (about 16%) after 6 wk at 5 °C. All coatings significantly reduced disease severity of both GM and BM after 6 wk at 5 °C. Analytical and sensory fruit quality was evaluated on intact mandarins. All coatings, especially the SB + SP-based coatings, were effective to control weight loss and maintain the firmness of coated mandarins. Internal gas concentration, juice ethanol and acetaldehyde content, sensory flavor, off-flavor, and fruit appearance were not adversely affected by the application of the antifungal coatings. Further studies should focus on the modification of some physical characteristics of the coatings to improve the gloss and visual aspect of treated mandarins. PMID:21535515

  14. Spatio-temporal morphology changes in and quenching effects on the 2D spreading dynamics of cell colonies in both plain and methylcellulose-containing culture media.

    PubMed

    Muzzio, N E; Pasquale, M A; Huergo, M A C; Bolzán, A E; González, P H; Arvia, A J

    2016-06-01

    To deal with complex systems, microscopic and global approaches become of particular interest. Our previous results from the dynamics of large cell colonies indicated that their 2D front roughness dynamics is compatible with the standard Kardar-Parisi-Zhang (KPZ) or the quenched KPZ equations either in plain or methylcellulose (MC)-containing gel culture media, respectively. In both cases, the influence of a non-uniform distribution of the colony constituents was significant. These results encouraged us to investigate the overall dynamics of those systems considering the morphology and size, the duplication rate, and the motility of single cells. For this purpose, colonies with different cell populations (N) exhibiting quasi-circular and quasi-linear growth fronts in plain and MC-containing culture media are investigated. For small N, the average radial front velocity and its change with time depend on MC concentration. MC in the medium interferes with cell mitosis, contributes to the local enlargement of cells, and increases the distribution of spatio-temporal cell density heterogeneities. Colony spreading in MC-containing media proceeds under two main quenching effects, I and II; the former mainly depending on the culture medium composition and structure and the latter caused by the distribution of enlarged local cell domains. For large N, colony spreading occurs at constant velocity. The characteristics of cell motility, assessed by measuring their trajectories and the corresponding velocity field, reflect the effect of enlarged, slow-moving cells and the structure of the medium. Local average cell size distribution and individual cell motility data from plain and MC-containing media are qualitatively consistent with the predictions of both the extended cellular Potts models and the observed transition of the front roughness dynamics from a standard KPZ to a quenched KPZ. In this case, quenching effects I and II cooperate and give rise to the quenched

  15. Management of irritable bowel syndrome in primary care: the results of an exploratory randomised controlled trial of mebeverine, methylcellulose, placebo and a self-management website

    PubMed Central

    2013-01-01

    Background Many patients with IBS suffer on-going symptoms. The evidence base is poor for IBS drugs but they are widely prescribed and advised in Guidelines. Cognitive Behavioural Therapy (CBT) can be helpful, but availability is poor in the NHS. We developed a web-based CBT self-management programme (Regul8) in partnership with patients and trialled it and common IBS medications in an exploratory factorial RCT to test trial procedures and provide information for a larger trial. Methods Patients, 16 to 60 years, with IBS symptoms fulfilling Rome III criteria were recruited via GP practices and randomised to over-encapsulated mebeverine, methylcellulose or placebo for 6 weeks and to 1 of 3 website conditions: Regul8 with a nurse telephone session and email support, Regul8 with minimal email support, or no website. Results 135 patients recruited from 26 GP practices. Mean IBS SSS score 241.9 (sd 87.7), IBS-QOL 64 (sd 20) at baseline. 91% follow-up at 12 weeks. Mean IBS SSS decreased by 35 points from baseline to 12 weeks. There was no significant difference in IBS SSS or IBS-QOL score between medication or website groups at 12 weeks, or in medication groups at 6 weeks, or IBS-QOL in website groups at 6 weeks. However, IBS SSS at 6 weeks was lower in the No website group than the website groups (IBS SSS no website =162.8 (95% CI 137.4-188.3), website 197.0 (172.4 - 221.7), Website + telephone support 208.0 (183.1-233.0) p = 0.037). Enablement and Subjects Global Assessment of relief (SGA) were significantly improved in the Regul8 groups compared to the non-website group at 12 weeks (Enablement = 0 in 56.8% of No website group, 18.4% website, 10.5% Website + support, p = 0.001) (SGA; 32.4% responders in No website group, 45.7% website group, 63.2% website + support group, p = 0.035). Conclusions This exploratory study demonstrates feasibility and high follow-up rates and provides information for a larger trial. Primary outcomes (IBS SS and IBS

  16. Sensitive determination of aspirin and its metabolites in plasma by LC-UV using on-line solid-phase extraction with methylcellulose-immobilized anion-exchange restricted access media.

    PubMed

    Yamamoto, Eiichi; Takakuwa, Susumu; Kato, Takashi; Asakawa, Naoki

    2007-02-01

    We describe a sensitive determination of aspirin (ASA) and its three metabolites (salicylic acid [SA], 2,3-dihydroxybenzoic acid [2,3-DHBA], and 2,5-dihydroxybenzoic acid [gentisic acid (GA)]) in rat plasma. Analysis was carried out by on-line solid-phase extraction (SPE) using a methylcellulose-immobilized-strong anion-exchanger (MC-SAX), followed by liquid chromatography (LC) coupled with UV detection. The lower limits of quantitation for ASA and SA were 60 ng/mL in 100 microL of plasma, respectively. This method was validated with respect to intra- and inter-day precision, accuracy, and linearity up to concentrations of 20,000 ng/mL for ASA, SA, 2,3-DHBA and gentisic acid, respectively. The method was successfully applied to an analysis of the pharmacokinetics of ASA and SA in rats. PMID:16959551

  17. Matrix tablets: the effect of hydroxypropyl methylcellulose/anhydrous dibasic calcium phosphate ratio on the release rate of a water-soluble drug through the gastrointestinal tract I. In vitro tests.

    PubMed

    Mamani, Pseidy L; Ruiz-Caro, Roberto; Veiga, María D

    2012-12-01

    Different hydroxypropyl methylcellulose (HPMC)/anhydrous dibasic calcium phosphate (ADCP) matrix tablets have been developed aiming to evaluate the influence of both components ratio in the control release of a water-soluble drug (theophylline). In order to characterise the matrix tablets, swelling, buoyancy and dissolution studies have been carried out in different aqueous media (demineralised water, progressive pH medium, simulated gastric fluid, simulated intestinal fluid and simulated colonic fluid). The HPMC/ADCP ratio has turned out to be the determinant in the matrix behaviour: the HPMC characteristic swelling behaviour was modulated, in some cases, by the ADCP characteristic acidic dissolution. When the HPMC/ADCP ratio was ≥0.69, buoyancy, continuous swelling and low theophylline dissolution rate from the matrices (H1, H2 and H3) were observed in all dissolution media. Consequently, these formulations could be adequate as gastro-retentive drug delivery systems. Additionally, HPMC/ADCP ratio ≤0.11 (H5 and H6) induces a pH-dependent drug release which could be applied to design control drug release enteric formulations (with a suitable enteric coating). Finally, a HPMC/ADCP ratio between 0.11 and 0.69 (H4) yield a gastrointestinal controlled drug release, due to its time-dependent buoyancy (7 h) and a total drug delivery in 17 h in simulated colonic fluid. PMID:22907778

  18. Composite edible films based on hydroxypropyl methylcellulose reinforced with microcrystalline cellulose nanoparticles.

    PubMed

    Bilbao-Sáinz, Cristina; Avena-Bustillos, Roberto J; Wood, Delilah F; Williams, Tina G; McHugh, Tara H

    2010-03-24

    It has been stated that hydroxypropyl methyl cellulose (HPMC) based films have promising applications in the food industry because of their environmental appeal, low cost, flexibility and transparency. Nevertheless, their mechanical and moisture barrier properties should be improved. The aim of this work was to enhance these properties by reinforcing the films with microcrystalline cellulose (MCC) at the nano scale level. Three sizes of MCC nanoparticles were incorporated into HPMC edible films at different concentrations. Identical MCC nanoparticles were lipid coated (LC) prior to casting into HPMC/LC-MCC composite films. The films were examined for mechanical and moisture barrier properties verifying how the addition of cellulose nanoparticles affected the water affinities (water adsorption/desorption isotherms) and the diffusion coefficients. The expected reinforcing effect of the MCC was observed: HPMC/MCC and HPMC/LC-MCC films showed up to 53% and 48% increase, respectively, in tensile strength values in comparison with unfilled HPMC films. Furthermore, addition of unmodified MCC nanoparticles reduced the moisture permeability up to 40% and use of LC-MCC reduced this value up to 50%. Water vapor permeability was mainly influenced by the differences in water solubility of different composite films since, in spite of the increase in water diffusivity values with the incorporation of MCC to HPMC films, better moisture barrier properties were achieved for HPMC/MCC and HPMC/LC-MCC composite films than for HPMC films. PMID:20187652

  19. Properties of starch-hydroxypropyl methylcellulose based films obtained by compression molding.

    PubMed

    Ortega-Toro, Rodrigo; Jiménez, Alberto; Talens, Pau; Chiralt, Amparo

    2014-08-30

    Corn starch-glycerol (1:0.3) films, containing or not citric acid (1g/100g starch) and HPMC (10 and 20g/100g starch), are obtained by compression molding. The microstructure of the films, the thermal behavior, the X-ray diffraction spectra and the physical properties (mechanical, barrier and optical) were analyzed after 1 and 5 storage weeks at 25°C and 53% relative humidity. The bonded citric acid and film solubility were also determined. Starch-HPMC blend films showed a dispersed phase of HPMC in a continuous, starch-rich phase with lower glass transition than HPMC-free films. The addition of citric acid also provoked a decrease in glass transition in line with the partial hydrolysis of starch chains. Both components implied a decrease in the water vapour permeability while the oxygen permeability slightly increased. Although citric acid only provoked a small hardening effect in the films, it greatly decreased their extensibility (weak cross-linking effect), which seems to increase during film storage. Starch crystallization during storage was inhibited by both citric acid and HPMC. PMID:24815412

  20. Physical properties of emulsion-based hydroxypropyl methylcellulose films: effect of their microstructure.

    PubMed

    Zúñiga, R N; Skurtys, O; Osorio, F; Aguilera, J M; Pedreschi, F

    2012-10-01

    The initial characteristics of emulsions and the rearrangement of the oil droplets in the film matrix during film drying, which defines its microstructure, has an important role in the physical properties of the emulsion-based films. The objective of this work was to study the effect of the microstructure (two droplet size distributions) and stability (with or without surfactant) of HPMC oil-in-water emulsions over physical properties of HPMC emulsion-based edible films. HPMC was used to prepare sunflower oil-in-water emulsions containing 0.3 or 1.0% (w/w) of oil with or without SDS, as surfactant, using an ultrasonic homogenizer. Microstructure, rheological properties and stability of emulsions (creaming) were measured. In addition, microstructure, coalescence of oil droplets, surface free energy, optical and mechanical properties and water vapor transfer of HPMC films were evaluated. Image analysis did not show differences among droplet size distributions of emulsions prepared at different oil contents; however, by using SDS the droplet size distributions were shifted to lower values. Volume mean diameters were 3.79 and 3.77 μm for emulsions containing 0.3 and 1.0% without surfactant, respectively, and 2.72 and 2.71 μm for emulsions with SDS. Emulsions formulated with 1.0% of oil presented higher stability, with almost no change during 5 and 3 days of storage, for emulsions with and without SDS, respectively. Internal and surface microstructure of emulsion-based films was influenced by the degree of coalescence and creaming of the oil droplets. No effect of microstructure over the surface free energy of films was found. The incorporation of oil impaired the optical properties of films due to light scattering of light. Addition of oil and SDS decreased the stress at break of the emulsion-based films. The replace of HPMC by oil and SDS produce a lower "amount" of network structure in the films, leading to a weakening of their structure. The oil content and SDS addition had an effect over the microstructure and physical properties of HPMC-based emulsions which lead to different microstructures during film formation. The way that oil droplets were structured into the film had an enormous influence over the physical properties of HPMC films. PMID:22840052

  1. Evaluation of the film-coating properties of a hydroxyethyl cellulose/hydroxypropyl methylcellulose polymer system.

    PubMed

    Li, Shun Por; Martellucci, Stephen A; Bruce, Richard D; Kinyon, Adam C; Hay, Michael B; Higgins, John D

    2002-04-01

    The effect of different grades of hydroxyethyl cellulose (HEC) and hydroxypropyl methllcellulose (HPMC) on the film-formation and taste-masking ability for ibuprofen granules was evaluated. Three batches of coated ibuprofen granules were prepared using a roto-granulator, each with a different coating composition. Two grades of HEC [MW300,000 (H) and MW90,000 (L)] were combined with three different grades of HPMC [MW 11,000 (L), MW 25,000 (M) and MW 35,000 (H)] to prepare the coating solutions. Mechanical strength and physical properties of the polymer films were evaluated. Films made from HPMC (L)/HEC (H), HPMC (M)/HEC (H), and HPMC (H)/HEC (H) were stronger and more flexible than the HPMC (L) HEC (L) films. The assay, dissolution, particle size distribution, and environmental scanning electron microscopy (ESEM) data of the three batches of the coated ibuprofen granules were similar. PMID:12056532

  2. Preparation and characterization of collagen/hydroxypropyl methylcellulose (HPMC) blend film.

    PubMed

    Ding, Cuicui; Zhang, Min; Li, Guoying

    2015-03-30

    This study aimed to prepare and characterize the collagen/HPMC blend film (1/1). Thermogravimetric analysis and differential scanning calorimetry were used to investigate the thermal properties of the film. Both thermal decomposition temperature and denaturation temperature of the blend film were higher than those of the collagen film due to the intermolecular hydrogen bonding interaction between collagen and HPMC, which was demonstrated by Fourier transform infrared spectroscopy. Additionally, the morphologies, mechanical properties and hydrophilicity of films were examined. The blend film exhibited a more homogeneous and compact structure compared with that of the collagen film, as observed from scanning electron microscopy and atomic force microscopy. The tensile strength, ultimate elongation and hydrophilicity of the blend film were superior to those of the pure collagen film. Furthermore, the introduction of polyethylene glycol 1500 had almost no influence on the thermal properties of the blend film but obviously improved its stretch-ability and smoothness. PMID:25563960

  3. STUDYING THE IMPACT OF FORMULATION AND PROCESSING PARAMETERS ON THE RELEASE CHARACTERISTICS FROM HYDROXYPROPYL METHYLCELLULOSE MATRIX TABLETS OF DICLOFENAC.

    PubMed

    Elzayat, Ehab M; Abdel-Rahman, Ali A; Ahmed, Sayed M; Alanazi, Fars K; Habib, Walid A; Sakr, Adel

    2016-01-01

    Hydrophilic matrices, especially HPMC based, are widely used to provide sustained delivery where drug release occurs mainly by diffusion. A 3(2) full factorial design was used to develop and evaluate HPMC matrix tablet for sustained delivery of diclofenac. The influences of polymer concentration/viscosity, diluent type/ratio, drug load/solubility, compression force and pH change on drug release were investigated. Ten tablet formulations were prepared using wet granulation. HPMC K15M (10-30% w/w) was used as the polymer forming matrix. The release kinetics, compatibility studies, lot reproducibility and effect on storage were discussed. Increasing polymer concentration and compression force showed antagonistic effect on release rate. Mannitol tends to increase release rate more than lactose. Reversing diluent ratio between lactose and MCC did not affect drug release. Changing pH resulted in burst release whereas drug solubility is pH independent. F1 showed similar release to Voltaren SR and followed Higuchi model. Drug and polymer were compatible to each other. The formulation is stable at long and intermediate conditions with a significant increase in release rate at accelerated conditions due to water uptake and polymer swelling. The developed formulation was successful for a sustained delivery of diclofenac. PMID:27180437

  4. Physical properties of emulsion-based hydroxypropyl methylcellulose/whey protein isolate (HPMC/WPI) edible films.

    PubMed

    Rubilar, Javiera F; Zúñiga, Rommy N; Osorio, Fernando; Pedreschi, Franco

    2015-06-01

    The objective of this research was to study the effect of the film microstructure of oil-in-water emulsions stabilized by hydroxypropyl methyl cellulose/whey protein isolate (HPMC/WPI) with or without sodium dodecyl sulfate (SDS) over physical properties of HPMC/WPI emulsion-based films. The films were prepared with different HPMC/WPI-oil-SDS combinations (%w/w for 100g of dispersion): HPMC; WPI; HPMC/1WPI-0.5-SDS; HPMC/1WPI-1; HPMC/2WPI-0.5; HPMC/2WPI-1-SDS. Physical properties of films were evaluated. The results showed no statistical differences (p>0.05) between the thicknesses of EFs (0.156 ± 0.004 mm). The effect of oil content and incorporation of SDS showed the inverse trend for WI and ΔE, the increasing order of change, for WI and ΔE, among the formulation evaluated was: HPMC/1WPI-1>HPMC/2WPI-0.5>HPMC/2WPI-1.0-SDS≈HPMC/1WPI-0.5-SDS≈WPI>HPMC for WI and HPMC/1WPI-0.5-SDS>HPMC/2WPI-1.0-SDS>HPMC/2WPI-0.5>HPMC/1WPI-1 for ΔE, respectively. The addition of oil and SDS decreased the TS and EB, because oil addition into EF induces the development of structural discontinuities, producing an EF with less chain mobility, and consequently, with less flexibility and resistance to fracture. PMID:25843831

  5. Biopolymeric antimicrobial films: study of the influence of hydroxypropyl methylcellulose, tapioca starch and glycerol contents on physical properties.

    PubMed

    Espinel Villacrés, Ricardo A; Flores, Silvia K; Gerschenson, Lía N

    2014-03-01

    Mixture design methodology was applied to study the effect of different levels of tapioca starch (TS), hydroxypropyl methylcelullose (HPMC), and glycerol (Gly) on the physical properties of biopolymeric films supporting potassium sorbate (KS; 0.3% w/w) with the goal of contributing to the development of materials for preventing food surface contamination. Mechanical properties, water vapour permeability (WVP), solubility in water (S) and colour attributes were evaluated on the films. HPMC addition produced an increase of elastic modulus (Ec), stress at break (σb) and S. It also decreased the yellow index (YI) values and the strain at break (εb). The study was deepened using the formulation containing 2.67 g/100g of TS, 0.67 g/100g of HPMC, 1.67 g/100g Gly and 0.3g/100g KS, observing that it behaved as an effective antimicrobial barrier against Zygosaccharomyces bailii external contamination. Microstructural analysis allowed us to conclude that HPMC incorporation to a TS network decreased roughness of the films and it also increased permeability to oxygen (PO2). PMID:24433893

  6. Hydroxypropyl methylcellulose mediated precipitation inhibition of sirolimus: from a screening campaign to a proof-of-concept human study.

    PubMed

    Petruševska, Marija; Homar, Miha; Petek, Boštjan; Resman, Aleksander; Kocjan, Darko; Urleb, Uroš; Peternel, Luka

    2013-06-01

    The aim of this study was to develop a sirolimus (BCS class II drug substance) solid oral dosage form containing a precipitation inhibitor, which would result in an improved sirolimus absorption in humans compared to the formulation containing nanosized sirolimus without a precipitation inhibitor, i.e., Rapamune. The selection of the precipitation inhibitor was based on the results of a screening campaign that identified two "hit" excipients: HPMC 603 (i.e., Pharmacoat 603) and Poloxamer 407. However, in a confirmatory precipitation inhibitor study using biorelevant media (Fa/FeSSIF) HPMC 603 more effectively inhibited sirolimus precipitation than Poloxamer 407. In the PAMPA assay, HPMC 603, but not Poloxamer 407, significantly increased the flux of the sirolimus across the membrane lipid layer. Additionally, a differential scanning calorimetry (DSC) and an infrared (IR) spectroscopy study revealed that interactions between the sirolimus and HPMC 603 were developed that could lead to the observed precipitation inhibition effect. Based on the above data, two formulations with HPMC 603-coated sirolimus particles were developed, namely, formulation A (d (0.5) = 0.21 μm) and formulation B (d (0.5) = 1.7 μm). A human pharmacokinetic study outlined that significantly higher AUC and Cmax were obtained for formulations A and B in comparison to Rapamune. This result could be attributed to the HPMC 603 (Pharmacoat 603) mediated sirolimus precipitation inhibition resulting in improved sirolimus absorption from the gastrointestinal tract in humans. PMID:23586335

  7. Controlled release of dual drug-loaded hydroxypropyl methylcellulose matrix tablet using drug-containing polymeric coatings.

    PubMed

    Lee, B J; Ryu, S G; Cui, J H

    1999-10-15

    A dual drug-loaded hydroxypropylmethylcellulose (HPMC) matrix tablet simultaneously containing drug in inner tablet core and outer coated layer was formulated using drug-containing aqueous-based polymeric Eudragit RS30D dispersions. Effects of coating levels, drug loadings in outer layers, amount and type of five plasticizers and talc concentration on the release characteristics were evaluated on the characteristics in simulated gastric fluid for 2 h followed by a study in intestinal fluids. Melatonin (MT) was selected as a model drug. The surface morphology of dual drug-loaded HPMC tablets using scanning electron microscope (SEM) was smooth, showing the distinct coated layer with about 75-microm coating thickness at the 15% coating level. Unlike the uncoated and conventionally coated HPMC tablet, the dual drug-loaded HPMC matrix tablet gave a biphasic linear release, showing a zero-order for 4 h (first) followed by another zero-order release when fitted using linear regression (r(2) = 0.99). As the coating levels (15, 25%) increased, the release rate was further decreased. The biphasic release profiles of dual drug-loaded HPMC matrix tablet was unchanged except when 25% coating level containing 0.5% drug concentration was applied. As the drug concentration in polymeric coating dispersion increased (0.25-1.0%), the amount of drug released increased. The time for the first linear release was also advanced. However, the biphasic release pattern was not changed. The biphasic release profiles of dual drug-loaded HPMC matrix tablet were highly modified, depending on the amount and type of five plasticizers. Talc (10-30%) in coating dispersion as an anti-sticking material did not affect the release profiles. The current dual drug-loaded HPMC matrix tablet, showing biphasic release profiles may provide an alternative to deliver drugs with circadian rhythmic behaviors in the body but needs to be further validated in future in human studies. The dual drug-loaded coating method is also interesting for the modified release of poorly water-soluble drugs because solubilizers and other additives can be added in drug-containing polymeric coating dispersions. PMID:10528084

  8. 21 CFR 201.319 - Water-soluble gums, hydrophilic gums, and hydrophilic mucilloids (including, but not limited to...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... gum, kelp, methylcellulose, plantago seed (psyllium), polycarbophil tragacanth, and xanthan gum) as... gum, kelp, methylcellulose, plantago seed (psyllium), polycarbophil tragacanth, and xanthan gum) as..., methylcellulose, plantago seed (psyllium), polycarbophil, tragacanth, and xanthan gum. Esophageal obstruction...

  9. 21 CFR 201.319 - Water-soluble gums, hydrophilic gums, and hydrophilic mucilloids (including, but not limited to...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... gum, kelp, methylcellulose, plantago seed (psyllium), polycarbophil tragacanth, and xanthan gum) as... gum, kelp, methylcellulose, plantago seed (psyllium), polycarbophil tragacanth, and xanthan gum) as..., methylcellulose, plantago seed (psyllium), polycarbophil, tragacanth, and xanthan gum. Esophageal obstruction...

  10. The suitability of tris(hydroxylmethyl) aminomethane (THAM) as a buffering system for hydroxypropyl methylcellulose (HPMC) hydrophilic matrices containing a weak acid drug.

    PubMed

    Pygall, Samuel R; Kujawinski, Sarah; Timmins, Peter; Melia, Colin D

    2010-03-15

    There are few studies of alkalising pH-modifiers in HPMC hydrophilic matrices. These agents may be incorporated to provide microenvironmental buffering and facilitate pH-independent release of weak acid drugs. This study compared tris(hydroxylmethyl) aminomethane (THAM, TRIS, tromethamine, trometamol) with sodium citrate as internal buffering agents for HPMC (4000 cps) 2208 and 2910 matrices containing felbinac, a weak acid drug which exhibits pH-dependent solubility. Drug release at pH 1.2 and 7.5 was accelerated by both buffers, but THAM-buffered matrices provided extended, diffusion-based release kinetics, without loss of matrix integrity at high buffer concentrations. Release kinetics appeared to be independent of media pH. THAM did not depress the sol-gel transition temperature or suppress HPMC particle swelling, and had minimal effects on gel layer formation. Sodium citrate promoted greater thickness of the early gel layer than THAM. Measurements of internal gel layer pH showed that both buffers produced a rapid alkalisation of the gel layer which was progressively lost. As result of its higher pK(a) and molar ratio on a percent weight basis, THAM provided a higher internal pH and a greater longevity of pH modification. It is concluded that THAM offers a useful buffering option for weak acid drugs in HPMC-based systems. PMID:20005935

  11. Formulation and in vitro evaluation of floating tablets of hydroxypropyl methylcellulose and polyethylene oxide using ranitidine hydrochloride as a model drug

    PubMed Central

    Gharti, KP; Thapa, P; Budhathoki, U; Bhargava, A

    2012-01-01

    The present study was carried out with an objective of preparation and in vitro evaluation of floating tablets of hydroxypropyl methyl cellulose (HPMC) and polyethylene oxide (PEO) using ranitidine hydrochloride as a model drug. The floating tablets were based on effervescent approach using sodium bicarbonate a gas generating agent. The tablets were prepared by dry granulation method. The effect of polymers concentration and viscosity grades of HPMC on drug release profile was evaluated. The effect of sodium bicarbonate and stearic acid on drug release profile and floating properties were also investigated. The result of in vitro dissolution study showed that the drug release profile could be sustained by increasing the concentration of HPMC K15MCR and Polyox WSR303. The formulation containing HPMC K15MCR and Polyox WSR303 at the concentration of 13.88% showed 91.2% drug release at the end of 24 hours. Changing the viscosity grade of HPMC from K15MCR to K100MCR had no significant effect on drug release profile. Sodium bicarbonate and stearic acid in combination showed no significant effect on drug release profile. The formulations containing sodium bicarbonate 20 mg per tablet showed desired buoyancy (floating lag time of about 2 minutes and total floating time of >24 hours). The present study shows that polymers like HPMC K15MCR and Polyox WSR303 in combination with sodium bicarbonate as a gas generating agent can be used to develop sustained release floating tablets of ranitidine hydrochloride. PMID:23493037

  12. Formulation and in vitro evaluation of floating tablets of hydroxypropyl methylcellulose and polyethylene oxide using ranitidine hydrochloride as a model drug.

    PubMed

    Gharti, Kp; Thapa, P; Budhathoki, U; Bhargava, A

    2012-10-01

    The present study was carried out with an objective of preparation and in vitro evaluation of floating tablets of hydroxypropyl methyl cellulose (HPMC) and polyethylene oxide (PEO) using ranitidine hydrochloride as a model drug. The floating tablets were based on effervescent approach using sodium bicarbonate a gas generating agent. The tablets were prepared by dry granulation method. The effect of polymers concentration and viscosity grades of HPMC on drug release profile was evaluated. The effect of sodium bicarbonate and stearic acid on drug release profile and floating properties were also investigated. The result of in vitro dissolution study showed that the drug release profile could be sustained by increasing the concentration of HPMC K15MCR and Polyox WSR303. The formulation containing HPMC K15MCR and Polyox WSR303 at the concentration of 13.88% showed 91.2% drug release at the end of 24 hours. Changing the viscosity grade of HPMC from K15MCR to K100MCR had no significant effect on drug release profile. Sodium bicarbonate and stearic acid in combination showed no significant effect on drug release profile. The formulations containing sodium bicarbonate 20 mg per tablet showed desired buoyancy (floating lag time of about 2 minutes and total floating time of >24 hours). The present study shows that polymers like HPMC K15MCR and Polyox WSR303 in combination with sodium bicarbonate as a gas generating agent can be used to develop sustained release floating tablets of ranitidine hydrochloride. PMID:23493037

  13. Effect of thermal gelation on dissolution from coated tablets.

    PubMed

    Schwartz, J B; Alvino, T P

    1976-04-01

    Tablets with a methylcellulose coating were found to exhibit lower dissolution profiles than those coated with a hydroxypropyl methylcellulose coating at 37 degrees, and the cause was investigated. The differences are attributed to thermal gelation of the methylcellulose at temperatures near 37 degrees, which creates a barrier to the dissolution process and essentially changes the dissolution mechanism. This mechanism is substantiated by the fact that at temperatures below the gel point and at increased agitation, the effect disappears. The retarded dissolution effect is not peculiar to the drug involved. PMID:1271258

  14. Analysis of the permeation and mechanical characteristics of some aqueous-based film coating systems.

    PubMed

    Okhamafe, A O; York, P

    1983-07-01

    The moisture permeability and mechanical properties of some aqueous-based free films have been evaluated using sorption-desorption and stress-strain techniques, respectively. These properties for blends of two film-formers--hydroxypropyl methylcellulose and polyvinyl alcohol--have been compared with those of hydroxypropyl methylcellulose films plasticized with polyethylene glycols. The polyethylene glycols generally increased the moisture permeability of hydroxypropyl methylcellulose films while polyvinyl alcohol decreased it. Both polyvinyl alcohol and the polyethylene glycols lowered tensile strength at break and Young's modulus but the effects of the polyethylene glycols were more pronounced. These results are discussed in terms of structural interactions between film components. All film systems evaluated, except that containing hydroxypropyl methylcellulose alone, exhibited a degree of anisotropy, a phenomenon with potentially adverse consequences in tablet film coating. PMID:6136580

  15. Improved assay for quantitating adherence of ruminal bacteria to cellulose.

    PubMed Central

    Rasmussen, M A; White, B A; Hespell, R B

    1989-01-01

    A quantitative technique suitable for the determination of adherence of ruminal bacteria to cellulose was developed. This technique employs adherence of cells to cellulose disks and alleviates the problem of nonspecific cell entrapment within cellulose particles. By using this technique, it was demonstrated that the adherence of Ruminococcus flavefaciens FD1 to cellulose was inhibited by formaldehyde, methylcellulose, and carboxymethyl cellulose. Adherence was unaffected by acid hydrolysates of methylcellulose, glucose, and cellobiose. PMID:2782879

  16. Effect of various polymers concentrations on physicochemical properties of floating microspheres.

    PubMed

    Jagtap, Y M; Bhujbal, R K; Ranade, A N; Ranpise, N S

    2012-11-01

    Floating microspheres have emerged as a potential candidate for gastroretentive drug delivery system. For developing a desired intragastric floatation system employing these microspheres, it is necessary to select an appropriate balance between buoyancy and drug releasing rate. These properties mainly depend on the polymers used in the formulation of the microspheres. Hence it is necessory to study the effect of these polymer concentrations on the various physicochemical properties of the microspheres. Floating microspheres were prepared by emulsion solvent evaporation technique utilising different polymers such as ethyl cellulose, Eudragit(®) RS and Eudragit(®) RL by dissolving them in a mixture of dichloromethane and methanol. Release modifiers studied were hydroxypropyl methylcellulose K4M, hydroxypropyl methylcellulose E50 LV and Eudragit(®) EPO. Prepared microspheres were analysed for particle size, surface morphology, entrapment efficiency, buoyancy, differential scanning calorimetry and in-vitro drug release. Ethyl cellulose and Eudragit(®) EPO resulted microspheres with high percentage yield, excellent spherical shape but had very less buoyancies with a high cumulative drug release. Ethyl cellulose microspheres prepared using hydroxypropyl methylcellulose K4M showed more sustained drug release and high buoyancies than that of the microspheres formulated with the hydroxypropyl methylcellulose E50 LV. Amongst these hydroxypropyl methylcellulose E50 LV showed good balance between buoyancy and the drug release. PMID:23798776

  17. Development and In vitro Evaluation of Mucoadhesive Buccal Films of Nebivolol

    PubMed Central

    Mane, P. P.; Bushetti, S. S.; Keshavshetti, G. G.

    2014-01-01

    Nebivolol, a cardioselective β-blocker undergoes extensive metabolism in the liver after its oral administration resulting in low bioavailability. Oral administration of nebivolol also causes gastrointestinal disturbances characterised by stomach ache. To overcome these short comings, mucoadhesive buccal films of nebivolol were prepared using different concentrations of hydroxypropyl methylcellulose and hydroxyl ethylcellulose in the ratios of 2:1, 4:1 and 6:1 and hydroxypropyl methylcellulose and methylcellulose in the ratio of 2:2, 4:3 and 6:4 by solvent casting technique. All the prepared films were found to be smooth, elegant and uniform in thickness and weight. Among the three polymer combinations used, 6:4 (BFN6) showed increased in vitro residence time, which appeared to be mainly due to mucoadhesive nature of hydroxylpropyl methylcellulose and methylcellulose. Evaluation of the films showed uniform dispersion of the drug throughout the formulation (96.21±0.71 to 97.02±0.12%). In vitro drug release studies showed better results at the end of 8 h. The release profile of all the formulations was subjected to kinetic analyses, which suggested that the drug was released by diffusion mechanism following super case-II transport. PMID:24843191

  18. A new use of K-Y jelly as a gonioscopy fluid.

    PubMed

    Mehta, H K

    1984-10-01

    Methylcellulose drops varying in strength between 0.3% and 2.0% and isotonic saline are the fluids currently used for gonioscopy and posterior segment examination of the eye with diagnostic contact lenses. The author reports the use of K-Y jelly for such examinations in over 80 patients after having it used on his own eyes without any immediate or delayed ill effects. No observable difference was found between saline drops, methylcellulose drops of 0.3% and 2.0%, and K-Y jelly as regards the visibility of the anterior and posterior segments of the eyes. The more viscous fluids of 2% methylcellulose and K-Y jelly were more convenient to use, as they rarely allowed interposition of air bubbles between the cornea and the contact lens. K-Y jelly was well tolerated by all subjects. PMID:6477858

  19. Conductivity study and fourier transform infrared (FTIR) characterization of methyl cellulose solid polymer electrolyte with sodium iodide conducting ion

    SciTech Connect

    Abiddin, Jamal Farghali Bin Zainal; Ahmad, Azizah Hanom

    2015-08-28

    Sodium ion (Na{sup +}) based solid polymer electrolyte (SPE) has been prepared using solution cast technique with distilled water as solvent and Methylcellulose (MC) as a polymer host. Methylcellulose polymer was chosen as the polymer host due to the abundance of lone pair electrons in the carbonyl and C-O-C constituents, which in turn provide multiple hopping sites for the Na{sup +} conducting ions. Variable compositions of sodium iodide (NaI) salt were prepared to investigate the optimum MC-NaI weight ratio. Results from Electrical Impedance Spectroscopy (EIS) technique show that pure methylcellulose has a low conductivity of 3.61 × 10{sup −11} S/cm.The conductivity increases as NaI content increases up to optimum NaIcomposition of 40 wt%, which yields an average conductivity of 2.70 × 10{sup −5} S/cm.

  20. 21 CFR 524.960 - Flumethasone, neomycin sulfate, and polymyxin B sulfate ophthalmic solutions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    .... Dogs: 1 to 2 drops per eye, every 6 hours. (ii) Preparation without hydroxyproply methylcellulose. Dogs and cats: 2 to 3 drops per eye, every 4 hours. (2) Indications for use. Treatment of the inflammation, edema, and secondary bacterial infections associated with topical ophthalmological conditions of the...

  1. 21 CFR 524.960 - Flumethasone, neomycin sulfate, and polymyxin B sulfate ophthalmic solutions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    .... Dogs: 1 to 2 drops per eye, every 6 hours. (ii) Preparation without hydroxyproply methylcellulose. Dogs and cats: 2 to 3 drops per eye, every 4 hours. (2) Indications for use. Treatment of the inflammation, edema, and secondary bacterial infections associated with topical ophthalmological conditions of the...

  2. 21 CFR 524.960 - Flumethasone, neomycin sulfate, and polymyxin B sulfate ophthalmic solutions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    .... Dogs: 1 to 2 drops per eye, every 6 hours. (ii) Preparation without hydroxyproply methylcellulose. Dogs and cats: 2 to 3 drops per eye, every 4 hours. (2) Indications for use. Treatment of the inflammation, edema, and secondary bacterial infections associated with topical ophthalmological conditions of the...

  3. Gluten-free sorghum bread improved by sourdough fermentation: Biochemical, rheological and microstructural background

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was conducted to improve quality and theoretical understanding of gluten-free sorghum bread. Addition of 2% hydroxypropyl methylcellulose improved bread based on 105% water, 70% sorghum flour, and 30% potato starch. Nevertheless, a flat top and tendency towards a hole in the crumb remaine...

  4. TEXTILE WARP SIZE RECLAMATION USING THERMAL PRECIPITATION

    EPA Science Inventory

    The report describes a novel method for reclaiming size based on precipitation of the size material by heating the desize washwater. The method uses hydroxypropyl cellulose (HPC) or hydroxypropyl methylcellulose (HPMC) which are soluble in cool water but insoluble in warm water. ...

  5. Potential of Prolamins from Maize and Sorghum to Form Gluten-like Structures in Wheat-free Bread

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prolamins from maize (zeins) are known to form viscoelastic, extensible, cohesive dough when mixed together with starch and water above their glass transition temperature (Tg, approximately 28 °C). By adding hydroxypropyl methylcellulose (HPMC, a surface-active hydrocolloid) to this formulation, lea...

  6. Effect of different dispersants in compressive strength of carbon fiber cementitious composites

    NASA Astrophysics Data System (ADS)

    Lestari, Yulinda; Bahri, Saiful; Sugiarti, Eni; Ramadhan, Gilang; Akbar, Ari Yustisia; Martides, Erie; Khaerudini, Deni S.

    2013-09-01

    Carbon Fiber Cementitious Composites (CFCC) is one of the most important materials in smart concrete applications. CFCC should be able to have the piezoresistivity properties where its resistivity changes when there is applied a stress/strain. It must also have the compressive strength qualification. One of the important additives in carbon fiber cementitious composites is dispersant. Dispersion of carbon fiber is one of the key problems in fabricating piezoresistive carbon fiber cementitious composites. In this research, the uses of dispersants are methylcellulose, mixture of defoamer and methylcellulose and superplasticizer based polycarboxylate. The preparation of composite samples is similar as in the mortar technique according to the ASTM C 109/109M standard. The additives material are PAN type carbon fibers, methylcellulose, defoamer and superplasticizer (as water reducer and dispersant). The experimental testing conducts the compressive strength and resistivity at various curing time, i.e. 3, 7 and 28 days. The results obtained that the highest compressive strength value in is for the mortar using superplasticizer based polycarboxylate dispersant. This also shown that the distribution of carbon fiber with superplasticizer is more effective, since not reacting with the cementitious material which was different from the methylcellulose that creates the cement hydration reaction. The research also found that the CFCC require the proper water cement ratio otherwise the compressive strength becomes lower.

  7. Factors affecting quality of batter-based gluten-free bread

    Technology Transfer Automated Retrieval System (TEKTRAN)

    While wheat bread has been extensively studied, the quality basis for gluten-free bread remains controversial. Common gluten-free breads are prepared from soft batters, and in such systems, intact and damaged starch, pentosans, added hydrocolloids like xanthan gum and hydroxypropyl methylcellulose (...

  8. Removal of surface lipids improves the functionality of commercial zein in viscoelastic zein-starch dough for gluten-free breadmaking

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maize prolamin (zein), together with starch, hydroxypropyl methylcellulose, sugar, salt, yeast and water can form wheat-like cohesive, extensible, viscoelastic dough when mixed above room temperature (e.g. 40 °C). This dough is capable of holding gas. However, it is excessively extensible, and when ...

  9. Formulation and Evaluation of Cefixime Trihydrate Matrix Tablets Using HPMC, Sodium CMC, Ethyl Cellulose.

    PubMed

    Sirisolla, Janakidevi; Ramanamurthy, K V

    2015-01-01

    The objective of the present work is to design sustained release matrix tablets of cefixime trihydrate by incorporating drug in a matrix made up of release retardant polymers, which prolong drug release leading to minimization of the peak and valley effect in the plasma and provide patient convenience. The effect of combination of polymers on parameters like release pattern, release mechanism of the drug were studied. Total nine formulations each containing 200 mg of drug were prepared by direct compression method. The formulations F-1, F-2, F-3 were prepared with a 1:1 drug to polymer ratio using hydroxypropyl methylcellulose, carboxymethyl cellulose sodium and ethyl cellulose. F-4 was prepared with a 1:1 ratio of hydroxypropyl methylcellulose, carboxymethyl cellulose sodium, F-5 as prepared with a 1:1 ratio of hydroxypropyl methylcellulose and ethyl cellulose, F-6 was prepared with a 1:1 ratio of carboxymethyl cellulose sodium and ethyl cellulose, F-7, F-8, F-9 were prepared by using polymers hydroxypropyl methylcellulose, carboxymethyl cellulose sodium and ethyl cellulose in the ratios of 0.5:0.5:1, 0.5:1:0.5, and 1:0.5:0.5. Designed matrix tablets were evaluated for various pre-compression and post-compression parameters. Formulation F-5 showed 102.15 % release at the end of 12 h and it is selected as the best formulation. All Formulations followed zero order with non-Fickian diffusion method. PMID:26180278

  10. Formulation and Evaluation of Cefixime Trihydrate Matrix Tablets Using HPMC, Sodium CMC, Ethyl Cellulose

    PubMed Central

    Sirisolla, Janakidevi; Ramanamurthy, K. V.

    2015-01-01

    The objective of the present work is to design sustained release matrix tablets of cefixime trihydrate by incorporating drug in a matrix made up of release retardant polymers, which prolong drug release leading to minimization of the peak and valley effect in the plasma and provide patient convenience. The effect of combination of polymers on parameters like release pattern, release mechanism of the drug were studied. Total nine formulations each containing 200 mg of drug were prepared by direct compression method. The formulations F-1, F-2, F-3 were prepared with a 1:1 drug to polymer ratio using hydroxypropyl methylcellulose, carboxymethyl cellulose sodium and ethyl cellulose. F-4 was prepared with a 1:1 ratio of hydroxypropyl methylcellulose, carboxymethyl cellulose sodium, F-5 as prepared with a 1:1 ratio of hydroxypropyl methylcellulose and ethyl cellulose, F-6 was prepared with a 1:1 ratio of carboxymethyl cellulose sodium and ethyl cellulose, F-7, F-8, F-9 were prepared by using polymers hydroxypropyl methylcellulose, carboxymethyl cellulose sodium and ethyl cellulose in the ratios of 0.5:0.5:1, 0.5:1:0.5, and 1:0.5:0.5. Designed matrix tablets were evaluated for various pre-compression and post-compression parameters. Formulation F-5 showed 102.15 % release at the end of 12 h and it is selected as the best formulation. All Formulations followed zero order with non-Fickian diffusion method. PMID:26180278

  11. Encapsulation and modified-release of thymol from oral microparticles as adjuvant or substitute to current medications.

    PubMed

    Rassu, G; Nieddu, M; Bosi, P; Trevisi, P; Colombo, M; Priori, D; Manconi, P; Giunchedi, P; Gavini, E; Boatto, G

    2014-10-15

    The aim of this study was to encapsulate, thymol, in natural polymers in order to obtain (i) taste masking effect and, then, enhancing its palatability and (ii) two formulations for systemic and local delivery of herbal drug as adjuvants or substitutes to current medications to prevent and treat several human and animal diseases. Microspheres based on methylcellulose or hydroxypropyl methylcellulose phthalate (HPMCP) were prepared by spray drying technique. Microparticles were in vitro characterized in terms of yield of production, drug content and encapsulation efficiency, particle size, morphology and drug release. Both formulations were in vivo orally administered and pharmacokinetic analysis was carried out. The polymers used affect the release and, then, the pharmacokinetic profile of thymol. Encapsulation into methylcellulose microspheres leads to short half/life but bioavailability remarkably increases compared to the free thymol. In contrast, enteric formulation based on HPMCP shows very limited systemic absorption. These formulations could be proposed as alternative or adjuvants for controlling pathogen infections in human or animal. In particular, methylcellulose microspheres can be used for thymol systemic administration at low doses and HPMCP particles for local treatment of intestinal infections. PMID:25442269

  12. 21 CFR 524.960 - Flumethasone, neomycin sulfate, and polymyxin B sulfate ophthalmic solutions.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    .... Dogs: 1 to 2 drops per eye, every 6 hours. (ii) Preparation without hydroxyproply methylcellulose. Dogs and cats: 2 to 3 drops per eye, every 4 hours. (2) Indications for use. Treatment of the inflammation, edema, and secondary bacterial infections associated with topical ophthalmological conditions of the...

  13. The influence of binder film thickness on the mechanical properties of binder films in tension.

    PubMed

    Ononokpono, O E; Spring, M S

    1988-02-01

    The physicomechanical properties of films of different thicknesses, made from methylcellulose and gelatinized maize starch, have been studied in tension. There was a linear relation between film thickness and tensile strength, toughness, elastic resilence and elongation at fracture. Young's modulus increased with decreasing film thickness particularly with films with a thickness of less than 15 micron. PMID:2897444

  14. HPMC supplementation reduces fatty liver, intestinal permeability, and insulin resistance with altered hepatic gene expression in diet-induced obese mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of hydroxypropyl methylcellulose (HPMC), a highly viscous nonfermentable soluble dietary fiber, were evaluated on global hepatic gene profiles, steatosis and insulin resistance in high-fat (HF) diet-induced obese (DIO) mice. DIO C57BL/6J mice were fed a HF diet supplemented with either ...

  15. Adiponectin in Hamster: Characterization and Functions in Soluble Dietary Fiber Mediated Lipid Homeostatis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aim: The hypocholesterolemic and hypoglycemic effects of various natural and semisynthetic dietary fibers have been studied in the past for their potential use in the prevention and improvement of metabolic syndrome. Among these dietary fibers, hydroxypropyl methylcellulose (HPMC) has been shown to...

  16. 21 CFR 182.1745 - Sodium carboxymethylcellu-lose.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Sodium carboxymethylcellu-lose. 182.1745 Section... GRAS Food Substances § 182.1745 Sodium carboxymethylcellu-lose. (a) Product. Sodium carboxy-methylcellulose is the sodium salt of carboxymethylcellulose not less than 99.5 percent on a dry-weight...

  17. 21 CFR 182.1745 - Sodium carboxymethylcellu-lose.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Sodium carboxymethylcellu-lose. 182.1745 Section... (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Multiple Purpose GRAS Food Substances § 182.1745 Sodium carboxymethylcellu-lose. (a) Product. Sodium carboxy-methylcellulose is the sodium salt of carboxymethylcellulose...

  18. 21 CFR 182.1745 - Sodium carboxymethylcellu-lose.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Sodium carboxymethylcellu-lose. 182.1745 Section... GRAS Food Substances § 182.1745 Sodium carboxymethylcellu-lose. (a) Product. Sodium carboxy-methylcellulose is the sodium salt of carboxymethylcellulose not less than 99.5 percent on a dry-weight...

  19. 21 CFR 182.1745 - Sodium carboxymethylcellu-lose.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Sodium carboxymethylcellu-lose. 182.1745 Section... GRAS Food Substances § 182.1745 Sodium carboxymethylcellu-lose. (a) Product. Sodium carboxy-methylcellulose is the sodium salt of carboxymethylcellulose not less than 99.5 percent on a dry-weight...

  20. Fibril Formation and Phase Separation in Aqueous Cellulose Ethers

    NASA Astrophysics Data System (ADS)

    Maxwell, Amanda; Schmidt, Peter; McAllister, John; Lott, Joseph; Bates, Frank; Lodge, Timothy

    Aqueous solutions of many cellulose ethers are known to undergo thermoreversible gelation and phase separation upon heating to form turbid hydrogels, but the mechanism and resulting structures have not been well understood. Turbidity, light scattering and small-angle neutron scattering (SANS) are used to show that hydroxypropyl methylcellulose (HPMC) chains are dissolved in water below 50 °C and undergo phase separation at higher temperatures. At 70 °C, at sufficiently high concentrations in water, HPMC orders into fibrillar structures with a well-defined radius of 18 +/- 2 nm, as characterized by cryogenic transmission electron microscopy and SANS. The HPMC fibril structure is independent of concentration and heating rate. However, HPMC fibrils do not form a percolating network as readily as is seen in methylcellulose, resulting in a lower hot-gel modulus, as demonstrated by rheology.

  1. Development of cellulose derivatives as novel enteric coating agents soluble at pH 3.5-4.5 and higher.

    PubMed

    Kokubo, H; Obara, S; Minemura, K; Tanaka, T

    1997-08-01

    Hydroxypropyl methylcellulose (HPMC) was selected as a base polymer to develop novel enteric coating agents for acid protection which can dissolve at pH around 4, and was modified with trimellitic acid or maleic acid at various degrees of substitution. These carboxylic acids have higher dissociation constants and higher solubility in water than the carboxylic acids of existing enteric coating polymers. The synthesized polymers were micronized and dispersed in aqueous medium to determine their pKa values by potentiometric titration. The pH of dissolution and the water vapor permeability of the cast films prepared from organic solutions were also evaluated. Hydroxypropyl methylcellulose trimellitate (HPMCT) showed good acid resistance, and the pH at which it dissolves can be controlled in the range of pH 3.5 to 4.5 by varying the content of trimellityl groups and the methoxyl substitution of the base polymer. PMID:9301034

  2. Characterization of new eye drops with choline salicylate and assessment of their irritancy by in vitro short time exposure tests.

    PubMed

    Wroblewska, Katarzyna; Kucinska, Małgorzata; Murias, Marek; Lulek, Janina

    2015-09-01

    The aim of our study was to examine the irritation potential of new eye drops containing 2% choline salicylate (CS) as an active pharmaceutical ingredient (API) and various polymers increasing eye drop viscosity (hydroxyethylcellulose, hydroxypropyl methylcellulose, methylcellulose, polyvinyl alcohol, polyvinylpyrrolidone). The standard method for assessing the potential of irritating substances has been the Draize rabbit eye test. However the European Centre for Validation of Alternative Methods and the Coordinating Committee for Validation of Alternative Methods recommend, short time exposure (STE) in vitro tests as an alternative method for assessing eye irritation. The eye irritation potential was determined using cytotoxicity test methods for rabbit corneal cell line (SIRC) after 5 min exposure. The viability of cells was determined using two cytotoxicity assays: MTT and Neutral Red Uptake. According to the irritation rankings for the short time exposure test, all tested eye drops are classified as non-irritating (cell viability >70%). PMID:27134543

  3. Stress crack resistance of some pigmented and unpigmented tablet film coating systems.

    PubMed

    Okhamafe, A O; York, P

    1985-07-01

    Stress crack resistance parameters--tensile strength: Young's modulus ratio, relative surface energy, and toughness index--have been examined for unpigmented free films of hydroxypropyl methylcellulose containing polyvinyl alcohol, and polyethylene glycols 400 and 1000, as well as similar film systems pigmented with either talc or titanium dioxide. Incorporation of either polyvinyl alcohol or polyethylene glycols 400 and 1000 in hydroxypropyl methylcellulose film coatings eliminated the incidence of edge splitting in the coated tablets. Increase in pigment concentration generally led to a decrease in the crack resistance of pigmented films. There was a relation between the stress crack resistance of pigmented free films and the incidence of edge splitting of corresponding film coatings applied to aspirin tablets--generally, the higher the crack resistance the lower the incidence of edge splitting. A similar relationship applied to the unpigmented films only when the tensile strength: Young's modulus ratio was considered. PMID:2863345

  4. Development of polysaccharides-based edible coatings for citrus fruits: a layer-by-layer approach.

    PubMed

    Arnon, Hadar; Granit, Rina; Porat, Ron; Poverenov, Elena

    2015-01-01

    Biodegradable coatings for citrus fruits that would replace the currently used polyethylene-based waxes, are of great interest. Methylcellulose (MC), hydroxypropyl methylcellulose (HPMC), carboxymethyl cellulose (CMC) and chitosan (CH) coatings were examined on the most sensitive citrus fruit model: mandarins. Among the examined polysaccharides, CMC provided mandarins with the best firmness, lowest weight loss and satisfying gloss, while not affecting natural flavour and the respiration process. To enhance coating performance, glycerol, oleic acid and stearic acid were added; however, mandarin quality generally deteriorated with these additives. Then, a layer-by-layer (LBL) approach was applied. LbL coatings, based on a combination of two polysaccharides, CMC as an internal layer and chitosan as an external layer, gave the best performance. Different concentrations of chitosan were examined. The LbL coatings notably improved all quantified parameters of fruit quality, proving that polysaccharide-based edible coating may offer an alternative to synthetic waxes. PMID:25053081

  5. Characterization of new eye drops with choline salicylate and assessment of their irritancy by in vitro short time exposure tests

    PubMed Central

    Wroblewska, Katarzyna; Kucinska, Małgorzata; Murias, Marek; Lulek, Janina

    2014-01-01

    The aim of our study was to examine the irritation potential of new eye drops containing 2% choline salicylate (CS) as an active pharmaceutical ingredient (API) and various polymers increasing eye drop viscosity (hydroxyethylcellulose, hydroxypropyl methylcellulose, methylcellulose, polyvinyl alcohol, polyvinylpyrrolidone). The standard method for assessing the potential of irritating substances has been the Draize rabbit eye test. However the European Centre for Validation of Alternative Methods and the Coordinating Committee for Validation of Alternative Methods recommend, short time exposure (STE) in vitro tests as an alternative method for assessing eye irritation. The eye irritation potential was determined using cytotoxicity test methods for rabbit corneal cell line (SIRC) after 5 min exposure. The viability of cells was determined using two cytotoxicity assays: MTT and Neutral Red Uptake. According to the irritation rankings for the short time exposure test, all tested eye drops are classified as non-irritating (cell viability >70%). PMID:27134543

  6. Effect of alginate/carboxyl methyl cellulose composite coating incorporated with clove essential oil on the quality of silver carp fillet and Escherichia coli O157:H7 inhibition during refrigerated storage.

    PubMed

    Jalali, Nastaran; Ariiai, Peiman; Fattahi, Esmaeil

    2016-01-01

    The effects of alginate/carboxyl methylcellulose composite coating incorporated with clove essential oil on quality of silver carp fillet chilled storage (4 + 1 °C) were examined over a period of 16 days. The control samples (c), alginate/carboxyl methylcellulose coating (C-A), alginate/carboxyl methylcellulose composite coating incorporated with clove essential oil (with different concentration 1 and 1.5 %) (C-A + CEO1 % and C-A + CEO 15 % respectively) were analyzed by bacteriological (total viable counts (TVC) and total psychrotrophic counts (TPC)), biochemical (Peroxide value (PV), free fatty acid (FFA), total volatile base nitrogen (TVB-N), and pH) and sensory characteristics. Also, the efficacy of these treatments was investigated in control of the population of Eschershia coli O157:H7 inoculated in silver carp fillet. According to the obtained results, C-A + CEO 1.5 % showed lowest (p < 0.05) and acceptable biochemical, bacteriological and sensory characteristics attributes up to 16 days storage at 4 °C compared to the others. Also, this treated sample was acceptable even at the end of the 16-day storage and it could reduce the population of E. coli O157:H7 below the acceptable level (<2) from day 4 until the end of the storage period. The results indicate Alginate/carboxyl methylcellulose composite coating with clove essential oil might be recommended as a preservative in the meat products. PMID:26787996

  7. Electrochemical cell

    DOEpatents

    Redey, Laszlo I.; Vissers, Donald R.; Prakash, Jai

    1994-01-01

    An electrochemical cell having an alkali metal negative electrode such as sodium and a positive electrode including Ni or transition metals, separated by a .beta." alumina electrolyte and NaAlCl.sub.4 or other compatible material. Various concentrations of a bromine, iodine and/or sulfur containing additive and pore formers are disclosed, which enhance cell capacity and power. The pore formers may be the ammonium salts of carbonic acid or a weak organic acid or oxamide or methylcellulose.

  8. Structural, surface wettability and antibacterial properties of HPMC-ZnO nanocomposite

    SciTech Connect

    Rao, B. Lakshmeesha; Asha, S.; Madhukumar, R.; Latha, S.; Gowda, Mahadeva; Shetty, G. Rajesha; Sangappa; Chandra, K. Sharath; Naik, Prashantha

    2014-04-24

    The developed hydroxypropyl methylcellulose (HPMC)/Zinc oxide (ZnO) nanocomposite films were examined for structural property and surface wettability using X-ray diffraction and contact angle measurement. Antibacterial activity of these films was evaluated as a function of ZnO concentration. The microstructuralline parameters ( and (g in %)) decreased with increasing concentration of ZnO nanoparticles and there was increase in hydrophilicity. Addition of ZnO nanoparticles in films resulted in antimicrobial activity against tested microorganisms.

  9. The Aminosteroid Derivative RM-133 Shows In Vitro and In Vivo Antitumor Activity in Human Ovarian and Pancreatic Cancers

    PubMed Central

    Kenmogne, Lucie Carolle; Ayan, Diana; Roy, Jenny; Maltais, René; Poirier, Donald

    2015-01-01

    Ovarian and pancreatic cancers are two of the most aggressive and lethal cancers, whose management faces only limited therapeutic options. Typically, these tumors spread insidiously accompanied first with atypical symptoms, and usually shift to a drug resistance phenotype with the current pharmaceutical armamentarium. Thus, the development of new drugs acting via a different mechanism of action represents a clear priority. Herein, we are reporting for the first time that the aminosteroid derivative RM-133, developed in our laboratory, displays promising activity on two models of aggressive cancers, namely ovarian (OVCAR-3) and pancreatic (PANC-1) cancers. The IC50 value of RM-133 was 0.8 μM and 0.3 μM for OVCAR-3 and PANC-1 cell lines in culture, respectively. Based on pharmacokinetic studies on RM-133 using 11 different vehicles, we selected two main vehicles: aqueous 0.4% methylcellulose:ethanol (92:8) and sunflower oil:ethanol (92:8) for in vivo studies. Using subcutaneous injection of RM-133 with the methylcellulose-based vehicle, growth of PANC-1 tumors xenografted to nude mice was inhibited by 63%. Quite interestingly, RM-133 injected subcutaneously with the methylcellulose-based or sunflower-based vehicles reduced OVCAR-3 xenograft growth by 122% and 100%, respectively. After the end of RM-133 treatment using the methylcellulose-based vehicle, OVCAR-3 tumor growth inhibition was maintained for ≥ 1 week. RM-133 was also well tolerated in the whole animal, no apparent sign of toxicity having been detected in the xenograft studies. PMID:26660672

  10. Effect of Different Polymer Concentration on Drug Release Rate and Physicochemical Properties of Mucoadhesive Gastroretentive Tablets

    PubMed Central

    Agarwal, Shweta; Murthy, R. S. R.

    2015-01-01

    Mucoadhesive tablets have emerged as potential candidates for gastroretentive drug delivery providing controlled release along with prolonged gastric residence time. Gastroretentive mucoadhesive tablets could result in increased bioavailability due to prolonged gastric residence time. A hydrophilic matrix system was developed as mucoadhesion is achievable on appropriate wetting and swelling of the polymers used. The polymers were so chosen so as to provide a balance between swelling, mucoadhesion and drug release. The polymers chosen were hydroxypropyl methylcellulose K4M, chitosan, and Carbopol 934. The concentrations of these polymers used has a great impact on the physicochemical properties of the resulting formulation. The tablets were formulated using wet granulation method and tranexamic acid was used as the model drug. The prepared tablets were characterized for size, shape, appearance, hardness, friability, weight variation, swelling, mucoadhesion and in vitro drug release. Several batches of tablets were prepared by varying the ratio of hydroxypropyl methylcellulose K4M and Chitosan. The batches having a greater ratio of chitosan showed higher rate of swelling, greater erosion, less mucoadhesion and faster release rate of the drug whereas the batches having greater ratio of hydroxypropyl methylcellulose K4M showed lesser rate of swelling, less erosion, better mucoadhesion and a smaller drug release rate. The level of carbopol was kept constant in all the batches. PMID:26997698

  11. Effect of Different Polymer Concentration on Drug Release Rate and Physicochemical Properties of Mucoadhesive Gastroretentive Tablets.

    PubMed

    Agarwal, Shweta; Murthy, R S R

    2015-01-01

    Mucoadhesive tablets have emerged as potential candidates for gastroretentive drug delivery providing controlled release along with prolonged gastric residence time. Gastroretentive mucoadhesive tablets could result in increased bioavailability due to prolonged gastric residence time. A hydrophilic matrix system was developed as mucoadhesion is achievable on appropriate wetting and swelling of the polymers used. The polymers were so chosen so as to provide a balance between swelling, mucoadhesion and drug release. The polymers chosen were hydroxypropyl methylcellulose K4M, chitosan, and Carbopol 934. The concentrations of these polymers used has a great impact on the physicochemical properties of the resulting formulation. The tablets were formulated using wet granulation method and tranexamic acid was used as the model drug. The prepared tablets were characterized for size, shape, appearance, hardness, friability, weight variation, swelling, mucoadhesion and in vitro drug release. Several batches of tablets were prepared by varying the ratio of hydroxypropyl methylcellulose K4M and Chitosan. The batches having a greater ratio of chitosan showed higher rate of swelling, greater erosion, less mucoadhesion and faster release rate of the drug whereas the batches having greater ratio of hydroxypropyl methylcellulose K4M showed lesser rate of swelling, less erosion, better mucoadhesion and a smaller drug release rate. The level of carbopol was kept constant in all the batches. PMID:26997698

  12. Bimodal Gastroretentive Drug Delivery Systems of Lamotrigine: Formulation and Evaluation

    PubMed Central

    Poonuru, R. R.; Gonugunta, C. S. R

    2014-01-01

    Gastroretentive bimodal drug delivery systems of lamotrigine were developed using immediate release and extended release segments incorporated in a hydroxypropyl methylcellulose capsule and in vitro and in vivo evaluations were conducted. In vivo radiographic studies were carried out for the optimized formulation in healthy human volunteers with replacement of drug polymer complex by barium sulphate and the floating time was noted. Here the immediate release segment worked as loading dose and extended release segment as maintenance dose. The results of release studies of formulations with hydrophillic matrix to formulations with dual matrix hydroxypropyl methylcellulose acetate succinate shown that as the percentage of polymer increased, the release decreased. Selected formulation F2 having F-Melt has successfully released the drug within one hour and hydrophillic matrix composing polyethylene oxide with 5% hydroxypropyl methylcellulose acetate succinate showed a lag time of one hour and then extended its release up to 12th hour with 99.59% drug release following zero order kinetics with R2 value of 0.989. The Korsmeyer-Peppas equation showed the R2 value to be 0.941 and n value was 1.606 following non-Fickian diffusion pattern with supercase II relaxation mechanism. Here from extended release tablet the drug released slowly from the matrix while floating. PMID:25593380

  13. Cyclodextrin-based telmisartan ophthalmic suspension: Formulation development for water-insoluble drugs.

    PubMed

    Muankaew, Chutimon; Jansook, Phatsawee; Sigurđsson, Hákon Hrafn; Loftsson, Thorsteinn

    2016-06-30

    In this study, cyclodextrin-based aqueous eye drop suspension of the water insoluble drug telmisartan was developed. Formation of a drug/γ-cyclodextrin complex was enabled by preventing formation of a poorly water-soluble zwitterion using a volatile base that was removed upon drying of the complex powder. Hydroxypropyl methylcellulose was shown to have the overall best effect, stabilizing the complexes without hampering the drug release from the formulation. Two strategies for preparing cyclodextrin-based aqueous eye drop suspensions of telmisartan were investigated, one where hydroxypropyl methylcellulose was added to the medium during preparation of the drug/γ-cyclodextrin complex powder (ternary complex) and the other where hydroxypropyl methylcellulose was added to the complex powder after preparation of the complex (binary complex). The complexation was characterized by DSC, FT-IR and (1)H NMR and the eye drop suspensions formed were examined regarding their stability and in vitro mucoadhesion property. The ternary complex exhibited inferior mucoadhesive property compared to the binary complex. However, the ternary complex was more stable as no notable change in particle size and particle size distribution was observed during storage at 4°C over 6 months (p<0.05) with the mean particle size determined between 2.0 and 2.5μm. PMID:27139144

  14. Effect of additives on physicochemical properties in amorphous starch matrices.

    PubMed

    Liang, Jun; Wang, Simon; Ludescher, Richard D

    2015-03-15

    The effect of the addition of non-reducing sugars or methylcellulose on the matrix physical properties and rate of non-enzymatic browning (NBR) between exogenous glucose+lysine in a starch-based glassy matrix were studied, using the methods of luminescence and FTIR. Amorphous starch-based matrices were formulated by rapidly dehydrating potato starch gel mixed with additives at weight ratios of 7:93 (additive:starch). Data on the phosphorescence emission energy and lifetime from erythrosin B dispersed in the matrices indicated that sugars decreased starch matrix mobility in a Tg-dependent manner, except for trehalose that interacted with starch in a unique mode, while methylcellulose, the additive with the highest Tg, increased the molecular mobility. Using FTIR, we found that methylcellulose decreased the strength of hydrogen bond network and sugars enhanced the hydrogen bond strength in the order: trehalose>maltitol>sucrose. Comparing those changes with the rate of NBR between exogenous glucose+lysine, we suggest that NBR rates are primarily influenced by matrix mobility, which is modulated by the hydrogen bond network, and interactions among components. PMID:25308673

  15. [Experimental data on the penetration of gentamicin into the media of the eye].

    PubMed

    Shchekotova, I G

    1976-12-01

    Penetration of Soviet gentamicin into the humor of the anterior chamber and vitreous body of the eye with aseptic inflammation was studied after the antibiotic administration by various routed, i.e. instillations of 8 per cent antibiotic solution and 8 per cent antibiotic solution methylcellulose into the conjunctival sac, injections of 20 mg of gentamicin subconjunctivally and retrobulbarly, injections of gentamicin intramuscularly in doses of 0.6 mg/kg. The studies showed that gentamicin penetrated into the humor of the anterior chamber and vitreous body of the eye after all the administration routes mentioned above in concentrations sufficient for the antibiotic antimicrobial effect and persisted in the eye media for prolong periods of time (24--48 hours). The highest concentrations of the antibiotic in the tumor of the anterior chamber were achieved after its administration subconjunctivally or after instillation of its 8 per cent on methylcellulose, while in the vitreous body its highest concentrations were achieved after injections subconjunctively, retrobulbarly or intramuscularly. Instillations of gentamicin solution on methylcellulose provided higher and more persistant concentrations of the antibiotic in the humor as compared to instillations of its aqueous solutions. Retrobulbar injections of gentamicin had no advantages as compared to subconjunctival administration with respect to providing higher concentrations of the antibiotic in the eye media. PMID:1020943

  16. Mechanically Enhanced Liquid Interfaces at Human Body Temperature Using Thermosensitive Methylated Nanocrystalline Cellulose.

    PubMed

    Scheuble, N; Geue, T; Kuster, S; Adamcik, J; Mezzenga, R; Windhab, E J; Fischer, P

    2016-02-01

    The mechanical performance of materials at oil/water interfaces after consumption is a key factor affecting hydrophobic drug release. In this study, we methylated the surface of nanocrystalline cellulose (NCC) by mercerization and dimethyl sulfate exposure to produce thermosensitive biopolymers. These methylated NCC (metNCC) were used to investigate interfacial thermogelation at air/water and medium-chain triglyceride (MCT)/water interfaces at body temperature. In contrast to bulk fluid dynamics, elastic layers were formed at room temperature, and elasticity increased significantly at body temperature, which was measured by interfacial shear and dilatational rheology in situ. This unique phenomenon depends on solvent quality, temperature, and polymer concentration at interfaces. Thus, by adjusting the degree of hydrophobicity of metNCC, the interfacial elasticity and thermogelation of the interfaces could be varied. In general, these new materials (metNCC) formed more brittle interfacial layers compared to commercial methylcellulose (MC A15). Thermogelation of methylcellulose promotes attractive intermolecular forces, which were reflected in a change in self-assembly of metNCC at the interface. As a consequence, layer thickness and density increased as a function of temperature. These effects were measured by atomic force microscopy (AFM) images of the displaced interface and confirmed by neutron reflection. The substantial structural and mechanical change of methylcellulose interfaces at body temperature represents a controllable encapsulation parameter allowing optimization of lipid-based drug formulations. PMID:26779953

  17. Adhesion of rice flour-based batter to chicken drumsticks evaluated by laser scanning confocal microscopy and texture analysis.

    PubMed

    Mukprasirt, A; Herald, T J; Boyle, D L; Rausch, K D

    2000-09-01

    The convenience and appeal of battered or breaded products have resulted in a sales increase of 100% since 1980. Because of the rapid growth of the Asian-American population and increasing consumption of rice and rice products, rice flour is a logical alternative for wheat flour in traditional batter formulation. The effects of ingredients used in rice flour-based batters on adhesion characteristic for deep-fat fried chicken drumsticks were studied by laser scanning confocal microscopy (LSCM) and texture analysis. Raw chicken drumsticks were predusted with egg albumin powder before dipping into batters prepared from combinations of rice flour, yellow corn flour, oxidized cornstarch, methylcellulose, or xanthan gum. The drumsticks were fried at 175+/-5 C until the internal temperature reached at least 71 C. For LSCM, samples were fixed overnight and were sectioned by vibratome (200 microm) before viewing. Batter adhesion was determined using an attachment specifically designed for chicken drumsticks. Microstructural analysis showed that batter formulated with a 50:50 mixture of rice and corn flours adhered better to drumsticks than batter with other rice flour ratios. Xanthan gum (0.2%) or methylcellulose (0.3%) alone had poor adhesion to chicken skin. However, when combined with other ingredients, xanthan gum increased the amount of batter pick-up before frying by increasing viscosity. Egg albumin significantly facilitated batter adhesion. The results from texture analysis supported the microstructural studies. As rice flour ratio increased from 50 to 70%, the binding force decreased. Rice flour showed potential as an alternative to wheat flour for batter formulas when the appropriate levels of oxidized starch, xanthan gum, and methylcellulose were included in the formulation. PMID:11020085

  18. The formation and characterization of hydrocortisone-loaded poly((+/-)-lactide) microspheres.

    PubMed

    Cavalier, M; Benoit, J P; Thies, C

    1986-04-01

    The solvent evaporation process has been used to form hydrocortisone-loaded microspheres from poly((+/-)-lactide) (PLA) and a lactide-glycolide copolymer (65/35). Methylene chloride was the casting solvent. Partially hydrolysed (88%) poly(vinyl alcohol) and methylcellulose were used as aqueous phase emulsifiers. Methylcellulose was preferred, because it gave stable emulsions as the amount of hydrocortisone being encapsulated increased whereas poly(vinyl alcohol) did not. With methylcellulose as the emulsifier, a broad size range of spherical microspheres containing up to 50% (w/w) hydrocortisone could be prepared. Thermal and X-ray analyses established that poly((+/-)-lactide) microspheres containing hydrocortisone retained thermal events characteristic of both materials. This is evidence that such microspheres contain, to some extent, crystalline hydrocortisone domains dispersed in a PLA matrix. But most of the encapsulated drug was molecularly dispersed in the PLA glass. The stability of hydrocortisone in microspheres was evaluated in different storage conditions: no degradation of drug was found. The release of hydrocortisone from 250-350 microns diameter microspheres into agitated 37 degrees C water (nitrogen atmosphere) was determined by HPLC analysis. The microspheres evaluated had initial hydrocortisone payloads of 12 to 47% (w/w). The rate of drug release increased as the initial drug payload carried by the microspheres increased. The release data are not adequately described by zero order, first order, or square-root-of-time release kinetics. Drug release from microspheres that contain 12% (w/w) hydrocortisone approached a plateau value well below the amount of drug actually carried by the microspheres. This is particularly true for hydrocortisone encapsulated in lactide-glycolide polymer. PMID:2872287

  19. Polymer incompatibility as a potential tool for polyphenol recovery from olive mill wastewater.

    PubMed

    Hajji, Fuad; Kunz, Benno; Weissbrodt, Jenny

    2014-08-01

    Experiments were designed and preformed in consideration of polymer type (proteins, i.e. caseinate and ovalbumin, and polysaccharides, i.e. alginate and methylcellulose), charge character and polysaccharide concentrations, intended to understand how the polymer properties determine both phase separation and polyphenol partitioning from olive mill wastewater (OMW). The highest yield of polyphenols (YBP=92.9%) was achieved in an aqueous two-phase system (ATPS) using an ovalbumin-methylcellulose system (OMCS) in comparison to ATPS with caseinate-alginate system (CAS; YBP=85.8%) or caseinate methylcellulose system (CMCS; YBP=74%). The performance of CMCS for the ATPS partitioning of polyphenols in OMW was found to depend on the addition of salt (sodium chloride). The use of centrifugation as assistive technology appears to be necessary for the polyphenol partitioning in ATPS using OMCS. In contrast to these polymer systems, CAS caused a rapid ATPS without resorting to centrifugation and salt, mainly because of strong electrostatic repulsion between alginate and caseinate. In this regard, CAS in phase-separated OMW obtained a partition coefficient of protein (KP1) of 0.04, a tie-line length (TLL) of 10.47% (w/w) and a phase volume ratio (VR) of 0.7. Thus, ATPS based on CAS represent an efficient and environmentally friendly concept in recovery of polyphenols from OMW. The spray drying of the caseinate-polyphenol-rich phase from CAS could become a dry intermediate product with potential use in the food and non-food industry. PMID:24629933

  20. Prevention of Peritoneal Adhesions Using Polymeric Rheological Blends

    PubMed Central

    Hoare, Todd; Yeo, Yoon; Bellas, Evangelia; Bruggeman, Joost P.

    2014-01-01

    The effectiveness of rheological blends of high molecular weight hyaluronic acid (HA) and low molecular weight hydroxypropyl methylcellulose (HPMC) in the prevention of peritoneal adhesions post-surgery is demonstrated. The physical mixture of the two carbohydrates increased the dwell time in the peritoneum while significantly improving the injectability of the polymer compared to hyaluronic acid alone. HA-HPMC treatment decreased the total adhesion area by ~70% relative to a saline control or no treatment in a repeated cecal injury model in the rabbit. No significant cytotoxicity and minimal inflammation was associated with the blend, and no chemical or physical processing was required prior to their use beyond simple mixing. PMID:24365709

  1. Certain problems of space biotechnology

    NASA Technical Reports Server (NTRS)

    Gilyarov, V. N.

    1980-01-01

    Experiments in the field of biotechnology conducted by the USA Apollo and Skylab space probes are described, as well as the joint Soviet-American Apollo-Soyuz Test Project (ASTP). Experiments in electrophoretic separation in space of biological compounds in a liquid medium are detailed. Space processing of vaccines and separation of human and animal cells are described. Methyl-cellulose, a coating for use in electrophoresis was developed. Erythropoietin, which stimulates the formation of red blood corpuscles in bone marrow, was obtained in pure form.

  2. Control of electroosmosis in coated quartz capillaries

    NASA Technical Reports Server (NTRS)

    Herren, Blair J.; Van Alstine, James; Snyder, Robert S.; Shafer, Steven G.; Harris, J. Milton

    1987-01-01

    The effectiveness of various coatings for controlling the electroosmotic fluid flow that hinders electrophoretic processes is studied using analytical particle microelectrophoresis. The mobilities of 2-micron diameter glass and polystyrene latex spheres (exhibiting both negative and zero effective surface charge) were measured in 2-mm diameter quartz capillaries filled with NaCl solutions within the 3.5-7.8 pH range. It is found that capillary inner surface coatings using 5000 molecular weight (or higher) poly(ethylene glycol): significantly reduced electroosmosis within the selected pH range, were stable for long time periods, and appeared to be more effective than dextran, methylcellulose, or silane coatings.

  3. Effect of iontophoresis and permeation enhancers on the permeation of an acyclovir gel.

    PubMed

    Vaghani, Subhash S; Gurjar, Mitesh; Singh, Sachin; Sureja, Sunil; Koradia, Shailesh; Jivani, N P; Patel, M M

    2010-10-01

    The purpose of the present study was to explore the combined effect of chemical enhancers and iontophoresis on the in vitro permeation of acyclovir gel across porcine skin. Acyclovir gel was formulated using carbopol 940 and hydroxypropyl methylcellulose K4M (HPMC K4M). Effect of drug concentration on the delivery of acyclovir was examined. Increasing drug concentration of acyclovir enhanced its flux across the skin. Incorporation of permeation enhancers (menthol, n-methyl-2-pyrrolidone and polyethylene glycol 400) into the gel resulted in enhanced acyclovir permeation when combined with iontophoresis. Menthol showed the highest drug permeation and when combined with iontophoresis it significantly increased the acyclovir skin permeation. PMID:20695844

  4. Evaluation of thermal gelation behavior of different cellulose ether polymers by rheology

    NASA Astrophysics Data System (ADS)

    Balaghi, S.; Edelby, Y.; Senge, B.

    2014-05-01

    Hydroxypropylmethylcellulose (HPMC) and Methylcellulose (MC) are cellulose ethers which can be dispersed in water and used as thickeners, emulsifiers, binders, film formers, and water-retention agents due to their hydrophilic and hydrophobic characteristics. In this study, various types of HPMCs, in comparison with two types of MCs were examined. The formed gels of the different cellulose ethers showed specific and various structural formation and network properties. The degree of methylation (Meth.) and hydroxypropylation (HyPr.) affected drastically the heat-induced gelation of the examined cellulose ethers.

  5. Electrochemical cell

    DOEpatents

    Redey, L.I.; Vissers, D.R.; Prakash, J.

    1994-08-23

    An electrochemical cell is described having an alkali metal negative electrode such as sodium and a positive electrode including Ni or transition metals, separated by a [beta] alumina electrolyte and NaAlCl[sub 4] or other compatible material. Various concentrations of a bromine, iodine and/or sulfur containing additive and pore formers are disclosed, which enhance cell capacity and power. The pore formers may be the ammonium salts of carbonic acid or a weak organic acid or oxamide or methylcellulose. 6 figs.

  6. PROCESS OF MAKING SHAPED FUEL FOR NUCLEAR REACTORS

    DOEpatents

    O'Leary, W.J.; Fisher, E.A.

    1964-02-11

    A process for making uranium dioxide fuel of great strength, density, and thermal conductivity by mixing it with 0.1 to 1% of a densifier oxide (tin, aluminum, zirconium, ferric, zinc, chromium, molybdenum, titanium, or niobium oxide) and with a plasticizer (0.5 to 3% of bentonite and 0.05 to 2% of methylcellulose, propylene glycol alginate, or ammonium alginate), compacting the mixture obtained, and sintering the bodies in an atmosphere of carbon monoxide or carbon dioxide, with or without hydrogen, or of a nitrogen-hydrogen mixture is described. (AEC)

  7. [Comparison of the selected methods of cord processing for transplantation purposes].

    PubMed

    Ołdak, T; Machaj, E K; Gajkowska, A; Kruszewski, M; Kłos, M; Szczecina, R; Czajkowski, K; Kuczyńska-Sicińska, J; Pojda, Z

    2000-09-01

    Human umbilical cord blood (UCB) has been successfully used as a source of allogeneic hematopoietic cells for transplantation. Banking of the UCB requires its volume reduction to decrease storage space, costs and volume of infused DMSO. In order to select an optimal method for volume reduction we compared several methods of cord blood processing, namely buffy coat centrifugation, red cell lysis, hydroxyethyl starch (HES)-, methylcellulose- and gelatin-sedimentations. The viability of cells and the recoveries of total white blood cells, mononuclear cells and CD34+ cells was evaluated. We also compared the efficacy of red cells depletion from the original UCB sample. Buffy coat centrifugation, red cell lysis, HES, gelatin or methylcellulose resulted in high mononuclear cell recoveries, whereas high hematopoietic cell recovery was observed only after HES sedimentation and buffy coat processing. The HES sedimentation procedure compared to buffy coat processing is more time and labor consuming and resulted in higher red blood cell and platelets depletion. Both methods can be recommended as a method at choice for the umbilical cord blood processing before banking. PMID:11083012

  8. Statistical Modelling for Controlled Drug Delivery Systems and its Applications in HPMC based Hydrogels

    NASA Astrophysics Data System (ADS)

    Ghosal, Kajal; Chandra, Aniruddha

    2010-10-01

    Different concentrations of hydrophobically modified hydroxypropyl methylcellulose (HPMC, 60 M Grade) and conventional hydrophilic hydroxypropyl methylcellulose (50 cPs) were used to prepare four topical hydrogel formulations using a model non steroidal anti-inflammatory drug (NSAID) diclofenac potassium (DP). For all the formulations, suitability of different common empirical (zero-order, first-order, and Higuchi), semi-empirical (Ritger-Peppas and Peppas-Sahlin), and some new statistical (logistic, log-logistic, Weibull, Gumbel, and generalized extreme value distribution) models to describe the drug release profile were tested through non-linear least-square curve fitting. A general purpose mathematical analysis tool MATLAB is used for the purpose. Further, instead of the widely used transformed linear fit method, direct fitting was used in the paper to avoid any sort of truncation and transformation errors. The results revealed that the log-logistic distribution, among all the models that were investigated, was the best fit for hydrophobic formulations. For hydrophilic cases, the semi-empirical models and Weibull distribution worked best, although log-logistic also showed a close fit.

  9. ISL1 cardiovascular progenitor cells for cardiac repair after myocardial infarction

    PubMed Central

    Bartulos, Oscar; Zhuang, Zhen Wu; Huang, Yan; Mikush, Nicole; Suh, Carol; Bregasi, Alda; Wang, Lin; Chang, William; Krause, Diane S.; Young, Lawrence H.; Pober, Jordan S.; Qyang, Yibing

    2016-01-01

    Cardiovascular progenitor cells (CPCs) expressing the ISL1-LIM–homeodomain transcription factor contribute developmentally to cardiomyocytes in all 4 chambers of the heart. Here, we show that ISL1-CPCs can be applied to myocardial regeneration following injury. We used a rapid 3D methylcellulose approach to form murine and human ISL1-CPC spheroids that engrafted after myocardial infarction in murine hearts, where they differentiated into cardiomyocytes and endothelial cells, integrating into the myocardium and forming new blood vessels. ISL1-CPC spheroid–treated mice exhibited reduced infarct area and increased blood vessel formation compared with control animals. Moreover, left ventricular (LV) contractile function was significantly better in mice transplanted with ISL1-CPCs 4 weeks after injury than that in control animals. These results provide proof-of-concept of a cardiac repair strategy employing ISL1-CPCs that, based on our previous lineage-tracing studies, are committed to forming heart tissue, in combination with a robust methylcellulose spheroid–based delivery approach. PMID:27525311

  10. Development of bioactive coatings based on γ-irradiated proteins to preserve strawberries

    NASA Astrophysics Data System (ADS)

    Vu, K. D.; Hollingsworth, R. G.; Salmieri, S.; Takala, P. N.; Lacroix, M.

    2012-08-01

    Gamma irradiation was applied for creating cross-linked proteins to enhance the physicochemical properties of edible films made of calcium caseinate, whey protein isolate and glycerol. The characteristics of γ irradiated cross-linked proteins were analyzed by Fourier Transform Infrared spectroscopy. A second derivative spectra exhibited changes in band intensities that were correlated to an increase of β-sheet structure and a decrease of α-helix and unordered fractions of γ irradiated-cross-linked proteins as compared to the control without irradiation. Furthermore, on addition of methylcellulose to the irradiated protein matrix it was found that it has potential in enhancing the puncture strength and has no detrimental effect on water vapor permeability of protein based films. Finally, these film formulations were used as bioactive edible coatings containing natural antimicrobial agents (limonene and peppermint) to preserve the shelf life of fresh strawberries during storage. The bioactive coatings containing peppermint was found to be more efficient as preserving coatings than the formulations containing limonene. Irradiated proteins/methylcellulose/peppermint formulation had only 40% of decay at day 8 while it was 65% for the control.

  11. Development and evaluation of ethyl cellulose-based transdermal films of furosemide for improved in vitro skin permeation.

    PubMed

    Patel, Dhaval P; Setty, Chitral Mallikarjuna; Mistry, Gaurav N; Patel, Santnu L; Patel, Tarun J; Mistry, Pritesh C; Rana, Amar K; Patel, Pritesh K; Mishra, Rishabh S

    2009-01-01

    Transdermal films of the furosemide were developed employing ethyl cellulose and hydroxypropyl methylcellulose as film formers. The effect of binary mixture of polymers and penetration enhancers on physicochemical parameters including thickness, moisture content, moisture uptake, drug content, drug-polymer interaction, and in vitro permeation was evaluated. In vitro permeation study was conducted using human cadaver skin as penetration barrier in modified Keshary-Chein diffusion cell. In vitro skin permeation study showed that binary mixture, ethyl cellulose (EC)/hydroxypropyl methylcellulose (HPMC), at 8.5:1.5 ratio provided highest flux and also penetration enhancers further enhanced the permeation of drug, while propylene glycol showing higher enhancing effect compared to dimethyl sulfoxide and isopropyl myristate. Different kinetic models, used to interpret the release kinetics and mechanism, indicated that release from all formulations followed apparent zero-order kinetics and non-Fickian diffusion transport except formulation without HPMC which followed Fickian diffusion transport. Stability studies conducted as per International Conference on Harmonization guidelines did not show any degradation of drug. Based on the above observations, it can be reasonably concluded that blend of EC-HPMC polymers and propylene glycol are better suited for the development of transdermal delivery system of furosemide. PMID:19381831

  12. Polymers for use in controlled release systems: the effect of surfactants on their swelling properties.

    PubMed

    Vlachou, M; Hani, N; Efentakis, M; Tarantili, P A; Andreopoulos, A G

    2000-07-01

    The effect of an ampholytic surfactant on the swelling properties of polymeric materials was studied, using various swelling liquids. Tablets were prepared consisting of hydroxypropyl methylcellulose, poly(oxyethylene) and sodium alginate. Tego betain was the non-ionic surfactant used as an additive in a series of samples made of the above polymers. Those tablets were immersed in distilled water, phosphate buffer and 0.1 N HCl, and their weight uptake was recorded as a function of time, in order to assess the swelling process. Measurements of the contact angle of the above systems were also carried out for estimating their wetting properties. The results of this study showed a selectivity among polymers, surfactant and surrounding liquid. Clearly, an enhancement of the swelling capacity of hydroxypropyl methylcellulose tablets due to the surfactant was recorded. An unclear effect was observed in the case of poly(oxyethylene), whereas for sodium alginate, the dominant factor is its water solubility that controls swelling behaviour. PMID:10972160

  13. Development and physical characterization of polymer-fish oil bigel (hydrogel/oleogel) system as a transdermal drug delivery vehicle.

    PubMed

    Rehman, Khurram; Mohd Amin, Mohd Cairul Iqbal; Zulfakar, Mohd Hanif

    2014-01-01

    Polymer-Fish oil bigel (hydrogel/oleogel colloidal mixture) was developed by using fish oil and natural (sodium alginate) and synthetic (hydroxypropyl methylcellulose) polymer for pharmaceutical purposes. The bigels were closely monitored and thermal, rheological and mechanical properties were compared with the conventional hydrogels for their potential use as an effective transdermal drug delivery vehicle. Stability of the fish oil fatty acids (especially eicosapentanoic acid, EPA and docosahexanoic acid, DHA) was determined by gas chromatography and the drug content (imiquimod) was assessed with liquid chromatography. Furthermore, in vitro permeation study was conducted to determine the capability of the fish oil-bigels as transdermal drug delivery vehicle. The bigels showed pseudoplastic rheological features, with excellent mechanical properties (adhesiveness, peak stress and hardness), which indicated their excellent spreadability for application on the skin. Bigels prepared with mixture of sodium alginate and fish oil (SB1 and SB2), and the bigels prepared with the mixture of hydroxypropyl methylcellulose and fish oil (HB1-HB3) showed high cumulative permeation and drug flux compared to hydrogels. Addition of fish oil proved to be beneficial in increasing the drug permeation and the results were statistically significant (p < 0.05, one-way Anova, SPSS 20.0). Thus, it can be concluded that bigel formulations could be used as an effective topical and transdermal drug delivery vehicle for pharmaceutical purposes. PMID:25252741

  14. Formulation and optimization of mucoadhesive bilayer buccal tablets of atenolol using simplex design method

    PubMed Central

    Shirsand, SB; Suresh, Sarasija; Keshavshetti, GG; Swamy, PV; Reddy, P Vijay Prakash

    2012-01-01

    Introduction: In the present study, mucoadhesive buccal bilayer tablets of atenolol were fabricated with the objective of avoiding first pass metabolism and to improve its bioavailability with reduction in dosing frequency. Hence, the aim of this work was to design oral controlled release mucoadhesive tablets of atenolol and to optimize the drug release profile and bioadhesion. Materials and Methods: Bilayer buccal tablets of atenolol were prepared by direct compression method using simplex method of optimization to investigate the combined effect of hydroxypropyl methylcellulose 15 cps (X1), Carbopol (X2) and mannitol (X3); the in vitro drug release (Y1) and mucoadhesive strength (Y2) were taken as responses. The designed tablets were evaluated for various physical and biological parameters like drug content uniformity, in vitro drug release, short-term stability, and drug- excipient interactions (FTIR). Results: The formulation C containing hydroxypropyl methylcellulose 15 cps (10% w/w of matrix layer), Carbopol 934p (10% w/w of matrix layer) and mannitol (channeling agent, 40% w/w of matrix layer) was found to be promising. This formulation exhibited an in vitro drug release of 89.43% in 9 h along with satisfactory bioadhesion strength (7.20 g). Short-term stability studies on the promising formulation indicated that there are no significant changes in drug content and in vitro dissolution characteristics (P<0.05). IR spectroscopic studies indicated that there are no drug-excipient interactions. PMID:23071958

  15. Effect of AGM and fetal liver-derived stromal cell lines on globin expression in adult baboon (P. anubis) bone marrow-derived erythroid progenitors.

    PubMed

    Lavelle, Donald; Vaitkus, Kestutis; Ruiz, Maria Armila; Ibanez, Vinzon; Kouznetsova, Tatiana; Saunthararajah, Yogen; Mahmud, Nadim; DeSimone, Joseph

    2012-01-01

    This study was performed to investigate the hypothesis that the erythroid micro-environment plays a role in regulation of globin gene expression during adult erythroid differentiation. Adult baboon bone marrow and human cord blood CD34+ progenitors were grown in methylcellulose, liquid media, and in co-culture with stromal cell lines derived from different developmental stages in identical media supporting erythroid differentiation to examine the effect of the micro-environment on globin gene expression. Adult progenitors express high levels of γ-globin in liquid and methylcellulose media but low, physiological levels in stromal cell co-cultures. In contrast, γ-globin expression remained high in cord blood progenitors in stromal cell line co-cultures. Differences in γ-globin gene expression between adult progenitors in stromal cell line co-cultures and liquid media required cell-cell contact and were associated with differences in rate of differentiation and γ-globin promoter DNA methylation. We conclude that γ-globin expression in adult-derived erythroid cells can be influenced by the micro-environment, suggesting new potential targets for HbF induction. PMID:22693559

  16. Effect of AGM and Fetal Liver-Derived Stromal Cell Lines on Globin Expression in Adult Baboon (P. anubis) Bone Marrow-Derived Erythroid Progenitors

    PubMed Central

    Lavelle, Donald; Vaitkus, Kestutis; Ruiz, Maria Armila; Ibanez, Vinzon; Kouznetsova, Tatiana; Saunthararajah, Yogen; Mahmud, Nadim; DeSimone, Joseph

    2012-01-01

    This study was performed to investigate the hypothesis that the erythroid micro-environment plays a role in regulation of globin gene expression during adult erythroid differentiation. Adult baboon bone marrow and human cord blood CD34+ progenitors were grown in methylcellulose, liquid media, and in co-culture with stromal cell lines derived from different developmental stages in identical media supporting erythroid differentiation to examine the effect of the micro-environment on globin gene expression. Adult progenitors express high levels of γ-globin in liquid and methylcellulose media but low, physiological levels in stromal cell co-cultures. In contrast, γ-globin expression remained high in cord blood progenitors in stromal cell line co-cultures. Differences in γ-globin gene expression between adult progenitors in stromal cell line co-cultures and liquid media required cell-cell contact and were associated with differences in rate of differentiation and γ-globin promoter DNA methylation. We conclude that γ-globin expression in adult-derived erythroid cells can be influenced by the micro-environment, suggesting new potential targets for HbF induction. PMID:22693559

  17. Mechanical properties of some pigmented and unpigmented aqueous-based film coating formulations applied to aspirin tablets.

    PubMed

    Okhamafe, A O; York, P

    1986-06-01

    The Brinell hardness and Young's modulus of pigmented and unpigmented films of hydroxypropyl methylcellulose alone, and in combination with either polyethylene glycol 400 (plasticizer) or polyvinyl alcohol, which were applied to aspirin tablets, have been measured. Generally hardness and modulus data showed similar trends. The hardness and modulus of hydroxypropyl methylcellulose fell in the presence of polyethylene glycol 400 as a result of its plasticizing action. On the other hand, the hardness and modulus of the film former rose slightly when polyvinyl alcohol was initially incorporated, probably due to the crystalline phase of the additive, and then decreased when the level of the additive was further raised. Hardness and modulus were higher in films pigmented with talc than in those containing titanium dioxide because of the plate-like shape of talc and its greater interaction with the polymer systems. Some correlation was found between the Young's moduli of the applied films and those of the corresponding free films, with the moduli of the latter two 2-5 times greater. Ageing at 37 degrees C and 75% r.h. was found to cause a decrease in the mechanical properties of the unplasticized film coating systems probably as a result of decreased molecular order and enhanced polymer chain mobility. PMID:2873217

  18. Cytotoxicity of Different Excipients on RPMI 2650 Human Nasal Epithelial Cells.

    PubMed

    Horváth, Tamás; Bartos, Csilla; Bocsik, Alexandra; Kiss, Lóránd; Veszelka, Szilvia; Deli, Mária A; Újhelyi, Gabriella; Szabó-Révész, Piroska; Ambrus, Rita

    2016-01-01

    The nasal route receives a great deal of attention as a non-invasive method for the systemic administration of drugs. For nasal delivery, specific formulations containing excipients are used. Because of the sensitive respiratory mucosa, not only the active ingredients, but also additives need to be tested in appropriate models for toxicity. The aim of the study was to measure the cytotoxicity of six pharmaceutical excipients, which could help to reach larger residence time, better permeability, and increased solubility dissolution rate. The following excipients were investigated on RPMI 2650 human nasal septum tumor epithelial cells: β-d-mannitol, sodium hyaluronate, α and β-cyclodextrin, polyvinyl alcohol and methylcellulose. 3-(4,5-dimethyltiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye conversion assay and real-time impedance analysis were used to investigate cytotoxicity. No excipient showed toxicity at 0.3% (w/v) concentration or below while 1% concentration a significantly reduced metabolic activity was measured by MTT assay for methylcellulose and cyclodextrins. Using impedance measurements, only β-cyclodextrin (1%) was toxic to cells. Mannitol at 1% concentration had a barrier opening effect on epithelial cells, but caused no cellular damage. Based on the results, all additives at 0.3%, sodium hyaluronate and polyvinyl alcohol at 1% concentrations can be safely used for nasal formulations. PMID:27213303

  19. Influence of hydrophilic polymers on the complexation of carbamazepine with hydroxypropyl-β-cyclodextrin.

    PubMed

    Medarević, Djordje; Kachrimanis, Kyriakos; Djurić, Zorica; Ibrić, Svetlana

    2015-10-12

    In this study binary carbamazepine-hydroxypropyl-β-cyclodextrin, as well as ternary carbamazepine-hydroxypropyl-β-cyclodextrin-hydrophilic polymer systems were used to improve dissolution rate of carbamazepine. It has been shown that addition of hydrophilic polymers (Soluplus® and two types of hydroxypropyl methylcellulose-Metolose® 90SH-100 and Metolose® 65SH-1500) significantly increased solubilization capacity of hydroxypropyl-β-cyclodextrin for carbamazepine. Evaluation of carbamazepine-hydroxypropyl-β-cyclodextrin-hydrophilic polymer interactions using molecular modeling techniques showed interactions between carbamazepine, which dissociates from inclusion complexes and hydroxypropyl methylcellulose that can prevent crystallization of dissolved carbamazepine. These results can contribute to better understanding of drug-cyclodextrin-hydrophilic polymer interactions which are still not well understood. After evaluation of carbamazepine solubilization with hydroxypropyl-β-cyclodextrin and hydrophilic polymers, both binary carbamazepine-hydroxypropyl-β-cyclodextrin and ternary carbamazepine-hydroxypropyl-β-cyclodextrin-hydrophilic polymer systems were prepared by spray drying. The results of solid state characterization methods showed amorphous nature of carbamazepine in all spray dried systems, which together with the results of molecular modeling techniques indicates inclusion complex formation. Carbamazepine dissolution rate was significantly improved from spray dried formulations compared to pure drug. Binary carbamazepine-hydroxypropyl-β-cyclodextrin and ternary carbamazepine-hydroxypropyl-β-cyclodextrin-Soluplus® systems exhibited the fastest carbamazepine release, wherein the entire amount of carbamazepine was released during first 5 min. PMID:26255049

  20. Combining ibuprofen sodium with cellulosic polymers: a deep dive into mechanisms of prolonged supersaturation.

    PubMed

    Terebetski, Jenna L; Michniak-Kohn, Bozena

    2014-11-20

    The combination of a highly soluble salt form of a drug with a polymeric precipitation inhibitor has the potential to prolong drug supersaturation even following salt disproportionation. In this study, dissolution profiles of ibuprofen sodium in the presence of various cellulosic polymers, including hydroxypropyl methylcellulose (HPMC), methylcellulose (MC), and hydroxypropyl cellulose (HPC), were examined in order to assess degree and duration of supersaturation. In addition, the roles that the polymers played in altering drug solubility, media viscosity, physical form, and particle morphology were also assessed. A deep dive into the mechanisms of supersaturation revealed that intermolecular hydrogen bonding between ibuprofen and HPMC was driving supersaturation through nucleation inhibition and crystal growth modification. Polymer viscosity was proposed as the primary factor prolonging supersaturation of ibuprofen in the presence of MC, while mechanisms other than hydrogen bonding were likely to be attributed to supersaturation with the most hydrophobic polymer evaluated, HPC. Overall, the study suggested that induction of intermolecular interactions between ibuprofen and HPMC were more effective at inhibiting nucleation and maintaining prolonged supersaturation than physical modulation of solution properties, such as viscosity. PMID:25219860

  1. Pairwise polymer blends for oral drug delivery.

    PubMed

    Marks, Joyann A; Wegiel, Lindsay A; Taylor, Lynne S; Edgar, Kevin J

    2014-09-01

    Blends of polymers with complementary properties hold promise for addressing the diverse, demanding polymer performance requirements in amorphous solid dispersions (ASDs), but we lack comprehensive property understanding for blends of important ASD polymers. Herein, we prepare pairwise blends of commercially available polymers polyvinylpyrrolidone (PVP), the cationic acrylate copolymer Eudragit 100 (E100), hydroxypropyl methylcellulose acetate succinate (HPMCAS), carboxymethyl cellulose acetate butyrate (CMCAB), hydroxypropyl methylcellulose (HPMC), and the new derivative cellulose acetate adipate propionate (CAAdP). This study identifies miscible binary blends that may find use, for example, in ASDs for solubility and bioavailability enhancement of poorly water-soluble drugs. Differential scanning calorimetry, FTIR spectroscopy, and film clarity were used to determine blend miscibility. Several polymer combinations including HPMCAS/PVP, HPMC/CMCAB, and PVP/HPMC appear to be miscible in all proportions. In contrast, blends of E100/PVP and E100/HPMC showed a miscibility gap. Combinations of water-soluble and hydrophobic polymers like these may permit effective balancing of ASD performance criteria such as release rate and polymer-drug interaction to prevent nucleation and crystal growth of poorly soluble drugs. Miscible polymer combinations described herein will enable further study of their drug delivery capabilities, and provide a potentially valuable set of ASD formulation tools. PMID:24823790

  2. Zolpidem Mucoadhesive Formulations for Intranasal Delivery: Characterization, In Vitro Permeability, Pharmacokinetics, and Nasal Ciliotoxicity in Rats.

    PubMed

    Wang, Yanfeng; Li, Mi; Qian, Shuai; Zhang, Qizhi; Zhou, Limin; Zuo, Zhong; Lee, Benjamin; Toh, Melvin; Ho, Tony

    2016-09-01

    Zolpidem is a non-benzodiazepine hypnotic for the treatment of insomnia characterized by difficulties with sleep initiation. Our study aimed at developing a zolpidem mucoadhesive formulation with minimal local toxicity, prolonged nasal residence time, and enhanced absorption after intranasal delivery. In vitro permeability studies using artificial membrane and Calu-3 cell culture model indicated efficient permeability of zolpidem. Aqueous solubility of zolpidem was found to be significantly improved by hydroxypropyl-β-cyclodextrin. Various mucoadhesive formulations were then prepared comprising zolpidem, hydroxypropyl-β-cyclodextrin, and mucoadhesive polymers such as hydroxypropyl methylcellulose, sodium carboxymethylcellulose, and sodium alginate. Pharmacokinetic studies in rats demonstrated that intranasally administered zolpidem could achieve significantly faster absorption rate and higher plasma concentration than that from oral route. In comparison with solution formulation (ZLP-S03), the optimized mucoadhesive formulation (ZLP-B01) containing 0.25% hydroxypropyl methylcellulose was found to improve Cmax from 352.6 ± 86.0 to 555.7 ± 175.8 ng/mL, and AUC0-inf from 32,890 ± 7547 to 65,447 ± 36,996 ng·min/mL with mild nasal ciliotoxicity in rats. PMID:27189774

  3. Multiple bidirectional alterations of phenotype and changes in proliferative potential during the in vitro and in vivo passage of clonal mast cell populations derived from mouse peritoneal mast cells

    SciTech Connect

    Kanakura, Y.; Thompson, H.; Nakano, T.; Yamamura, T.; Asai, H.; Kitamura, Y.; Metcalfe, D.D.; Galli, S.J.

    1988-09-01

    Mouse peritoneal mast cells (PMC) express a connective tissue-type mast cell (CTMC) phenotype, including reactivity with the heparin-binding fluorescent dye berberine sulfate and incorporation of (35S) sulfate predominantly into heparin proteoglycans. When PMC purified to greater than 99% purity were cultured in methylcellulose with IL-3 and IL-4, approximately 25% of the PMC formed colonies, all of which contained both berberine sulfate-positive and berberine sulfate-negative mast cells. When these mast cells were transferred to suspension culture, they generated populations that were 100% berberine sulfate-negative, a characteristic similar to that of mucosal mast cells (MMC), and that synthesized predominantly chondroitin sulfate (35S) proteoglycans. When ''MMC-like'' cultured mast cells derived from WBB6F1-+/+ PMC were injected into the peritoneal cavities of mast cell-deficient WBB6F1-W/Wv mice, the adoptively transferred mast cell population became 100% berberine sulfate-positive. In methylcellulose culture, these ''second generation PMC'' formed clonal colonies containing both berberine sulfate-positive and berberine sulfate-negative cells, but exhibited significantly less proliferative ability than did normal +/+ PMC. Thus, clonal mast cell populations initially derived from single PMC exhibited multiple and bidirectional alterations between CTMC-like and MMC-like phenotypes. However, this process was associated with a progressive diminution of the mast cells' proliferative ability.

  4. Feasibility Investigation of Cellulose Polymers for Mucoadhesive Nasal Drug Delivery Applications.

    PubMed

    Hansen, Kellisa; Kim, Gwangseong; Desai, Kashappa-Goud H; Patel, Hiren; Olsen, Karl F; Curtis-Fisk, Jaime; Tocce, Elizabeth; Jordan, Susan; Schwendeman, Steven P

    2015-08-01

    The feasibility of various cellulose polymer derivatives, including methylcellulose (MC), hydroxypropyl methylcellulose (HPMC), sodium-carboxymethylcellulose (sodium-CMC), and cationic-hydroxyethylcellulose (cationic-HEC), for use as an excipient to enhance drug delivery in nasal spray formulations was investigated. Three main parameters for evaluating the polymers in nasal drug delivery applications include rheology, ciliary beat frequency (CBF), and permeation across nasal tissue. Reversible thermally induced viscosity enhancement was observed at near nasal physiological temperature when cellulose derivatives were combined with an additional excipient, poly(vinyl caprolactam)-poly(vinyl acetate)-poly(ethylene glycol) graft copolymer (PVCL-PVA-PEG). Cationic-HEC was shown to enhance acyclovir permeation across the nasal mucosa. None of the tested cellulosic polymers caused any adverse effects on porcine nasal tissues and cells, as assessed by alterations in CBF. Upon an increase in polymer concentration, a reduction in CBF was observed when ciliated cells were immersed in the polymer solution, and this decrease returned to baseline when the polymer was removed. While each cellulose derivative exhibited unique advantages for nasal drug delivery applications, none stood out on their own to improve more than one of the performance characteristics examined. Hence, these data may be useful for the development of new cellulose derivatives in nasal drug formulations. PMID:26097994

  5. In Vitro Colony Assays for Characterizing Tri-potent Progenitor Cells Isolated from the Adult Murine Pancreas.

    PubMed

    Tremblay, Jacob R; LeBon, Jeanne M; Luo, Angela; Quijano, Janine C; Wedeken, Lena; Jou, Kevin; Riggs, Arthur D; Tirrell, David A; Ku, H Teresa

    2016-01-01

    Stem and progenitor cells from the adult pancreas could be a potential source of therapeutic beta-like cells for treating patients with type 1 diabetes. However, it is still unknown whether stem and progenitor cells exist in the adult pancreas. Research strategies using cre-lox lineage-tracing in adult mice have yielded results that either support or refute the idea that beta cells can be generated from the ducts, the presumed location where adult pancreatic progenitors may reside. These in vivo cre-lox lineage-tracing methods, however, cannot answer the questions of self-renewal and multi-lineage differentiation-two criteria necessary to define a stem cell. To begin addressing this technical gap, we devised 3-dimensional colony assays for pancreatic progenitors. Soon after our initial publication, other laboratories independently developed a similar, but not identical, method called the organoid assay. Compared to the organoid assay, our method employs methylcellulose, which forms viscous solutions that allow the inclusion of extracellular matrix proteins at low concentrations. The methylcellulose-containing assays permit easier detection and analyses of progenitor cells at the single-cell level, which are critical when progenitors constitute a small sub-population, as is the case for many adult organ stem cells. Together, results from several laboratories demonstrate in vitro self-renewal and multi-lineage differentiation of pancreatic progenitor-like cells from mice. The current protocols describe two methylcellulose-based colony assays to characterize mouse pancreatic progenitors; one contains a commercial preparation of murine extracellular matrix proteins and the other an artificial extracellular matrix protein known as a laminin hydrogel. The techniques shown here are 1) dissociation of the pancreas and sorting of CD133(+)Sox9/EGFP(+) ductal cells from adult mice, 2) single cell manipulation of the sorted cells, 3) single colony analyses using microfluidic q

  6. Effect of gamma irradiation on HPMC/ZnO nanocomposite films

    SciTech Connect

    Rao, B. Lakshmeesha; Asha, S.; Madhukumar, R.; Latha, S.; Gowda, Mahadeva; Shivananda, C. S.; Harish, K. V.; Sangappa; Shetty, G. Rajesha

    2015-06-24

    The present work looks into the structural and mechanical properties modification in ZnO nanoparticle incorporated Hydroxypropyl methylcellulose (HPMC) polymer films, induced by gamma irradiation. The irradiation process was performed in gamma chamber at room temperature by use of Cobalt-60 source (Average energy of 1.25MeV) at different doses: 0, 50, 100, 150 and 200 kGy respectively. The changes in structural parameters and mechanical properties in pure and gamma irradiated HPMC/ZnO nanocomposite films have been studied using X-ray scattering (XRD) data and universal testing machine (UTM). It is found that gamma irradiation decreases the structural parameters and improves the mechanical properties of nanocomposite films.

  7. Formulation Development and Evaluation of Fast Dissolving Film of Telmisartan

    PubMed Central

    Londhe, Vaishali Y.; Umalkar, Kashmira B.

    2012-01-01

    Hypertension is a major cause of concern not just in the elderly but also in the youngsters. An effort was made to formulate a fast dissolving film containing telmisartan which is used in the treatment of hypertension with a view to improve the onset of action, therapeutic efficacy, patient compliance and convenience. The major challenge in formulation of oral films of telmisatran is that it shows very less solubility in the pH range of 3–9. Various film forming agents and polyhydric alcohols were evaluated for optimizing composition of fast dissolving films. Fast dissolving films using hydroxypropyl methylcellulose, polyvinyl alcohol, glycerol, sorbitol, menthol and an alkalizer were formulated using solvent casting method. Optimized formulations were evaluated for their weight, thickness, folding endurance, appearance, tensile strength, disintegration time and dissolution profile. PMID:23325992

  8. Roller compactor: The effect of mechanical properties of primary particles.

    PubMed

    Al-Asady, Riyadh B; Osborne, James D; Hounslow, Michael J; Salman, Agba D

    2015-12-30

    In this study, the nano-indentation hardness of a single primary particle was measured for six different materials; microcrystalline cellulose, hydroxypropyl methylcellulose, maltodextrin, lactose, sodium carbonate and calcium carbonate. This was linked to the properties of the ribbons produced by roller compactor at different hydraulic pressures in the range of 30-230 bar. The main investigated ribbon properties were strength, porosity and width. For the range of materials that were tested, it was found that the lower the nano-indentation hardness of the powder particles, the higher the strength, width and lower the ribbon porosity. This is because the applied pressure by the rollers was enough to plastically deform the particles and create bonds between them. A method was suggested to predict the workability of the powder in roller compactor by using the data of nano-indentation for three materials. PMID:26024822

  9. Developing dissolution testing methodologies for extended-release oral dosage forms with supersaturating properties. Case example: Solid dispersion matrix of indomethacin.

    PubMed

    Tajiri, Tomokazu; Morita, Shigeaki; Sakamoto, Ryosaku; Mimura, Hisahi; Ozaki, Yukihiro; Reppas, Christos; Kitamura, Satoshi

    2015-07-25

    The objective of this study was to develop an in vitro dissolution test method with discrimination ability for an extended-release solid dispersion matrix of a lipophilic drug using the United States Pharmacopeia (USP) Apparatus 4, flow-through cell apparatus. In the open-loop configuration, the sink condition was maintained by manipulating the flow rate of the dissolution medium. To evaluate the testing conditions, the drug release mechanism from an extended-release solid dispersion matrix containing hydrophobic and hydrophilic polymers was investigated. As the hydroxypropyl methylcellulose (HPMC) maintained concentrations of indomethacin higher than the solubility in a dissolution medium, the release of HPMC into the dissolution medium was also quantified using size-exclusion chromatography. We concluded that the USP Apparatus 4 is suitable for application to an in vitro dissolution method for orally administered extended-release solid dispersion matrix formulations containing poorly water-soluble drugs. PMID:26022889

  10. Preparation and characterization of methacrylate hydrogels for zeta potential control

    NASA Technical Reports Server (NTRS)

    Gregonis, D. E.; Ma, S. M.; Vanwagenen, R.; Andrade, J. D.

    1976-01-01

    A technique based on the measurement of streaming potentials has been developed to evaluate the effects of hydrophilic coatings on electroosmotic flow. The apparatus and procedure are described as well as some results concerning the electrokinetic potential of glass capillaries as a function of ionic strength, pH, and temperature. The effect that turbulence and entrance flow conditions have on accurate streaming potential measurements is discussed. Various silane adhesion promoters exhibited only a slight decrease in streaming potential. A coating utilizing a glycidoxy silane base upon which methylcellulose is applied affords a six-fold decrease over uncoated tubes. Hydrophilic methacrylate gels show similar streaming potential behavior, independent of the water content of the gel. By introduction of positive or negative groups into the hydrophilic methacrylate gels, a range of streaming potential values are obtained having absolute positive or negative signs.

  11. Formulation development and evaluation of fast dissolving film of telmisartan.

    PubMed

    Londhe, Vaishali Y; Umalkar, Kashmira B

    2012-03-01

    Hypertension is a major cause of concern not just in the elderly but also in the youngsters. An effort was made to formulate a fast dissolving film containing telmisartan which is used in the treatment of hypertension with a view to improve the onset of action, therapeutic efficacy, patient compliance and convenience. The major challenge in formulation of oral films of telmisatran is that it shows very less solubility in the pH range of 3-9. Various film forming agents and polyhydric alcohols were evaluated for optimizing composition of fast dissolving films. Fast dissolving films using hydroxypropyl methylcellulose, polyvinyl alcohol, glycerol, sorbitol, menthol and an alkalizer were formulated using solvent casting method. Optimized formulations were evaluated for their weight, thickness, folding endurance, appearance, tensile strength, disintegration time and dissolution profile. PMID:23325992

  12. Development of novel guava puree films containing chitosan nanoparticles.

    PubMed

    Lorevice, Marcos V; de Moura, Márcia R; Aouada, Fauze A; Mattoso, Luiz H C

    2012-03-01

    One of the overall goals of industries is to use packages that do not cause environmental problems at disposal time, but that have the same properties as the conventional ones. The goal of this study is to synthesize edible films based on hydroxypropyl methylcellulose (HPMC) with guava puree and chitosan (CS) nanoparticles. This was divided into two stages, the first is the synthesis of chitosan nanoparticles and the second is the production of the films. For the nanoparticles, average size and zeta potential measurements were performed. The characterizations of mechanical and thermal properties, solubility and water vapor permeability tests were conducted in the films. It was observed that when the nanoparticles were added to HPMC and guava puree films, they improved their mechanical and thermal properties, as well as decreased the films solubility and permeability. The potential application of the films prepared would be in edible films with flavor and odor to extend the shelf life of products. PMID:22755113

  13. Moisture permeability mechanisms of some aqueous-based tablet film coatings containing soluble additives.

    PubMed

    Okhamafe, A O; Iwebor, H U

    1987-09-01

    Moisture permeation parameters--diffusion, solubility and permeation coefficients--for hydroxypropyl methylcellulose (HPMC) and partially hydrolyzed polyvinyl alcohol (PVA) films containing either of two water-soluble additives (citric acid and urea) have been evaluated from transmission and time lag data. Contrary to expectations, the moisture diffusivities of the films were markedly lowered by the presence of these additives. However, the solubility coefficients increased while the permeability coefficients were largely unchanged up to 10 wt% of the additives. A complex phenomenon involving an extensive interlacing network of mainly hydrogen bond interactions between additive and films former was believed to influence the permeation properties of the films. The estimated limits of compatibility of the additives with the film-former were in the range of 5-10 wt%. PMID:3432347

  14. Compressive strength, chloride permeability, and freeze-thaw resistance of MWNT concretes under different chemical treatments.

    PubMed

    Wang, Xingang; Rhee, Inkyu; Wang, Yao; Xi, Yunping

    2014-01-01

    This study investigated compressive strength, chloride penetration, and freeze-thaw resistance of multiwalled carbon nanotube (MWNT) concrete. More than 100 cylindrical specimens were used to assess test variables during sensitivity observations, including water-cement ratios (0.75, 0.5, and 0.4) and exposure to chemical agents (including gum arabic, propanol, ethanol, sodium polyacrylate, methylcellulose, sodium dodecyl sulfate, and silane). To determine the adequate sonication time for MWNT dispersal in water, the compressive strengths of MWNT concrete cylinders were measured after sonication times ranging from 2 to 24 minutes. The results demonstrated that the addition of MWNT can increase the compressive strength of concrete by up to 108%. However, without chemical treatment, MWNT concretes tend to have poor freeze-thaw resistance. Among the different chemical treatments, MWNT concrete treated with sodium polyacrylate has the best compressive strength, chloride resistance, and freeze-thaw durability. PMID:25140336

  15. In vitro evaluation of porous carrier-based floating granular delivery system of orlistat.

    PubMed

    Jain, Sunil K; Agrawal, G P; Jain, N K

    2008-01-01

    The purpose of the study is to prepare and evaluate an intragastric floating granular delivery system of orlistat using (i) calcium silicate as porous carrier; and (ii) hydroxypropyl methylcellulose K4M, ethyl cellulose, and Carbopol 940 as matrix-forming polymers. The effect of various formulation and process variables on the micro-meritic properties, in vitro floating behavior, percent drug content, and in vitro drug release was studied. The release mechanism of orlistat from these granules was evaluated on the basis of various theoretical equations. The optimized formulation demonstrated favorable in vitro floating and release characteristics. The release pattern of optimized, secondary-coated granules of orlistat in simulated gastrointestinal fluids corresponded best to the Peppas-Korsmeyer model and Higuchi matrix model. The results clearly indicated the controlled and sustained release of orlistat from its gastro-retentive floating granular delivery system. PMID:19174957

  16. Preparation and evaluation of gastroretentive floating tablets of acyclovir.

    PubMed

    Garg, Rajeev; Gupta, G D

    2009-10-01

    The present study performed by preparation and evaluation of floating tablets of Acyclovir as model drug for prolongation of gastric residence time. Floating effervescent tablets were formulated by various materials like hydroxypropyl methylcellulose K 4M, K 15M, psyllium husk, swelling agent as crospovidone and microcrystalline cellulose and gas generating agent like sodium bicarbonate and citric acid and evaluated for floating properties, swelling characteristics and in vitro drug release studies. Floating noneffervescent tablets were prepared by polypropylene foam powder and different matrix forming polymers like HPMC K 4M, Carbopol 934P, xanthan gum and sodium alginate. In vitro drug release studies were performed and drug release kinetics evaluated using the linear regression method was found to follow both the Higuchi and the Korsmeyer and Peppas equation. The drug release mechanism was found fickian type in most of the formulations. PMID:19751200

  17. Development and Evaluation of Sustained Release Tablet of Betahistine Hydrochloride Using Ion Exchange Resin Tulsion T344

    PubMed Central

    Wagh, Vijay D.; Pawar, Nilesh

    2012-01-01

    An attempt was made to sustain the release of Betahistine hydrochloride by complexation technique using strong cation-exchange resin, Tulsion T344. The drug loading onto ion-exchange resin was optimized for mixing time, activation, effect of pH, swelling time, ratio of drug : resin, and temperature. The resinate was evaluated for micromeritic properties and characterized using XRPD and IR. For resinate sustained release tablets were formulated using hydoxypropyl methylcellulose K100M. The tablets were evaluated for hardness, thickness, friability, drug content, weight variation, and in vitro drug release. Tablets thus formulated (Batch T-3) provided sustained release of drug over a period of 12 h. The release of Betahistine HCl from resinate controls the diffusion of drug molecules through the polymeric material into aqueous medium. Results showed that Betahistine HCl was formulated into a sustained dosage form as an alternative to the conventional tablet. PMID:22779010

  18. Flexible and printable paper-based strain sensors for wearable and large-area green electronics.

    PubMed

    Liao, Xinqin; Zhang, Zheng; Liao, Qingliang; Liang, Qijie; Ou, Yang; Xu, Minxuan; Li, Minghua; Zhang, Guangjie; Zhang, Yue

    2016-07-14

    Paper-based (PB) green electronics is an emerging and potentially game-changing technology due to ease of recycling/disposal, the economics of manufacture and the applicability to flexible electronics. Herein, new-type printable PB strain sensors (PPBSSs) from graphite glue (graphite powder and methylcellulose) have been fabricated. The graphite glue is exposed to thermal annealing to produce surface micro/nano cracks, which are very sensitive to compressive or tensile strain. The devices exhibit a gauge factor of 804.9, response time of 19.6 ms and strain resolution of 0.038%, all performance indicators attaining and even surpassing most of the recently reported strain sensors. Due to the distinctive sensing properties, flexibility and robustness, the PPBSSs are suitable for monitoring of diverse conditions such as structural strain, vibrational motion, human muscular movements and visual control. PMID:27314505

  19. Effect of gamma irradiation on HPMC/ZnO nanocomposite films

    NASA Astrophysics Data System (ADS)

    Rao, B. Lakshmeesha; Asha, S.; Madhukumar, R.; Latha, S.; Gowda, Mahadeva; Shetty, G. Rajesha; Shivananda, C. S.; Harish, K. V.; Sangappa

    2015-06-01

    The present work looks into the structural and mechanical properties modification in ZnO nanoparticle incorporated Hydroxypropyl methylcellulose (HPMC) polymer films, induced by gamma irradiation. The irradiation process was performed in gamma chamber at room temperature by use of Cobalt-60 source (Average energy of 1.25MeV) at different doses: 0, 50, 100, 150 and 200 kGy respectively. The changes in structural parameters and mechanical properties in pure and gamma irradiated HPMC/ZnO nanocomposite films have been studied using X-ray scattering (XRD) data and universal testing machine (UTM). It is found that gamma irradiation decreases the structural parameters and improves the mechanical properties of nanocomposite films.

  20. Detection of pharmaceutical crystals in polymer particles by transmission electron microscopy

    NASA Astrophysics Data System (ADS)

    Ricarte, Ralm; Hillmyer, Marc; Lodge, Timothy

    2015-03-01

    The use of solid dispersions, blends of an active pharmaceutical ingredient (API) and a polymer excipient, may significantly enhance the dissolution performance of a poorly water soluble drug. However, the polymer's role in inhibiting API crystallization within the solid dispersion is not well understood. One of the main challenges in elucidating this mechanism is the difficulty of detecting small amounts of API crystals (less than 5 volume percent) within the polymer matrix. In this work, we explore the use of transmission electron microscopy (TEM) to characterize the crystallinity of griseofulvin (GF) in hydroxypropyl methylcellulose acetate succinate (HPMCAS) solid dispersions. Using both real-space images and electron diffraction patterns from TEM, GF crystals in the HPMCAS matrix were unambiguously identified with nanometer resolution and with a crystal detection sensitivity superior to both wide-angle X-ray scattering and differential scanning calorimetry. TEM shows great potential for characterizing even trace API crystallinity in solid polymeric dispersions.

  1. Microencapsulation of Lactobacillus acidophilus NCIMB 701748 in matrices containing soluble fibre by spray drying: Technological characterization, storage stability and survival after in vitro digestion☆

    PubMed Central

    Yonekura, Lina; Sun, Han; Soukoulis, Christos; Fisk, Ian

    2014-01-01

    We evaluated sodium alginate, chitosan and hydroxypropyl methylcellulose (HPMC) as co-encapsulants for spray dried Lactobacillus acidophilus NCIMB 701748 by assessing their impact on cell viability and physicochemical properties of the dried powders, viability over 35 days of storage at 25 °C and survival after simulated digestion. Fibres were added to a control carrier medium containing whey protein concentrate, d-glucose and maltodextrin. Sodium alginate and HPMC did not affect cell viability but chitosan reduced viable counts in spray dried powders, as compared to the control. Although chitosan caused large losses of viability during spray-drying, these losses were counteracted by the excellent storage stability compared to control, sodium alginate and HPMC, and the overall effect became positive after the 35-day storage. Chitosan also improved survival rates in simulated GI conditions, however no single fibre could improve L. acidophilus NCIMB 701748 viability in all steps from production through storage and digestion. PMID:24748900

  2. Antioxidant films based on cross-linked methyl cellulose and native Chilean berry for food packaging applications.

    PubMed

    López de Dicastillo, Carol; Rodríguez, Francisco; Guarda, Abel; Galotto, Maria José

    2016-01-20

    Development of antioxidant and antimicrobial active food packaging materials based on biodegradable polymer and natural plant extracts has numerous advantages as reduction of synthetic additives into the food, reduction of plastic waste, and food protection against microorganisms and oxidation reactions. In this way, active films based on methylcellulose (MC) and maqui (Aristotelia chilensis) berry fruit extract, as a source of antioxidants agents, were studied. On the other hand, due to the high water affinity of MC, this polymer was firstly cross-linked with glutaraldehyde (GA) at different concentrations. The results showed that the addition of GA decreased water solubility, swelling, water vapor permeability of MC films, and the release of antioxidant substances from the active materials increased with the concentration of GA. Natural extract and active cross-linked films were characterized in order to obtain the optimal formulation with the highest antioxidant activity and the best physical properties for latter active food packaging application. PMID:26572446

  3. Development and evaluation of sustained release tablet of betahistine hydrochloride using ion exchange resin tulsion t344.

    PubMed

    Wagh, Vijay D; Pawar, Nilesh

    2012-01-01

    An attempt was made to sustain the release of Betahistine hydrochloride by complexation technique using strong cation-exchange resin, Tulsion T344. The drug loading onto ion-exchange resin was optimized for mixing time, activation, effect of pH, swelling time, ratio of drug : resin, and temperature. The resinate was evaluated for micromeritic properties and characterized using XRPD and IR. For resinate sustained release tablets were formulated using hydoxypropyl methylcellulose K100M. The tablets were evaluated for hardness, thickness, friability, drug content, weight variation, and in vitro drug release. Tablets thus formulated (Batch T-3) provided sustained release of drug over a period of 12 h. The release of Betahistine HCl from resinate controls the diffusion of drug molecules through the polymeric material into aqueous medium. Results showed that Betahistine HCl was formulated into a sustained dosage form as an alternative to the conventional tablet. PMID:22779010

  4. Core-in-cup tablet design of metoprolol succinate and its evaluation for controlled release.

    PubMed

    Nagaraju, Ravouru; Meera, Durgumahanthi Sai; Kaza, Rajesh; Arvind, Vakati Venkata; Venkateswarlu, Vobalaboina

    2009-12-01

    The core-in-cup matrix tablets of Metoprolol succinate were prepared by wet granulation technique. Of all the investigated formulations, the optimized formulation of MS-09 followed zero-order kinetics of drug release. Trail on MS-09 was formulated using 7.5% hydrogenated castor-oil (HCO) and 4% of hydroxyl propyl methylcellulose (HPMC K15M) with an objective to achieve a linear release profile for 24 h. There is no initial burst release, with 16.17% of drug released during the first hour and release was extended up to 24 hrs. Study of drug release kinetics was performed by application of dissolution data to various kinetic equations like zero-order; first order, Higuchi and Korsmeyer-Peppas, from R(2) value (0.9975) it was concluded that the drug release followed zero order kinetics with both erosion and diffusion as the release mechanisms. PMID:20025598

  5. Electrophoresis experiment for space

    NASA Technical Reports Server (NTRS)

    Vanderhoff, J. W.; Micale, F. J.

    1976-01-01

    The Apollo 16 electrophoresis experiment was analyzed, demonstrating that the separation of the two different-size monodisperse latexes did indeed take place, but that the separation was obscured by the pronounced electroosmotic flow of the liquid medium. The results of this experiment, however, were dramatic since it is impossible to carry out a similar separation on earth. It can be stated unequivocally from this experiment that any electrophoretic separation will be enhanced under microgravity conditions. The only question is the degree of this enhancement, which can be expected to vary from one experimental technique to another. The low-electroosmotic-mobility coating (Z6040-MC) developed under this program was found to be suitable for a free-fluid electrophoretic separation such as the experiment designed for the ASTP flight. The problem with this coating, however, is that its permanency is limited because of the slow desorption of the methylcellulose from the coated surface.

  6. Microwave assisted synthesis of acrylamide grafted locust bean gum and its application in drug delivery.

    PubMed

    Kaity, Santanu; Isaac, Jinu; Kumar, P Mahesh; Bose, Anirbandeep; Wong, Tin Wui; Ghosh, Animesh

    2013-10-15

    Acrylamide grafted copolymer of locust bean gum was prepared by microwave irradiation using ceric ammonium nitrate as redox initiator. The grafting process was optimized in terms of irradiation time, amount of initiator and acrylamide by using constant amount of native locust bean gum. The grafted gum was characterized by Fourier transform infrared spectroscopy (FT-IR), (13)C nuclear magnetic resonance (NMR), scanning electron microscopy (SEM), X-ray diffraction study (XRD), differential scanning calorimetry (DSC), elemental analysis, contact angle, viscosity, molecular weight, swelling and biodegradability studies. The grafted gum was found to be biodegradable and non-toxic. It was further used to prepare controlled-release matrix tablet of buflomedil hydrochloride. The in vitro release profile of the tablet showed the rate controlling property of acrylamide grafted locust bean gum was similar to that of hydroxypropyl methylcellulose (HPMC-K15M). PMID:23987450

  7. Using white sorghum flour for gluten-free breadmaking.

    PubMed

    Velázquez, Noemí; Sánchez, Hugo; Osella, Carlos; Santiago, Liliana G

    2012-06-01

    Cornstarch/sorghum flour (X₁) ratio, water added (X₂) and amount of hydroxypropyl methylcellulose (HPMC) used (X₃) were varied for making gluten-free bread so as to optimize batter softness (Y₁), specific volume (Y₂) and crumb grain (Y₃). A second-order model was employed to generate a response surface. It was found that the softness of the batter depends significantly on three factors in a linear way. The specific volume (Y₂), in particular, was increased significantly with the increment of X₁ and X₃. The crumb grain (Y₃) depended significantly on three factors, its scores increased with X₁ and decreased with the water added (X₂). Finally, 0.55 cornstarch/sorghum flour ratio, 90% of water added and 3% of HPMC were chosen as the best conditions, considering acceptable levels of specific volume and of crumb grain, and also taking into account the possibility of using the highest proportion of sorghum flour. PMID:22111686

  8. Baking loss of bread with special emphasis on increasing water holding capacity.

    PubMed

    Kotoki, D; Deka, S C

    2010-01-01

    Potato flour (PF), hydroxypropyl methylcellulose (HPMC) and honey were used as baking agents and their effects on baking loss and sensory quality were studied. PF at 1, 2 and 4% levels decreased baking loss followed by HPMC and honey. Water absorption was substantially high with the HPMC (70.8-80.8%) and PF (61.7-71.7%) compared to honey and normal standard bread. PF incorporation increased shelf-life (6-7 days) as compared to HPMC and honey. HPMC incorporated bread had higher moisture content (36.8-38.0%) followed by PF (34.5-35.8%) and honey (34.7%). The ash content was in the order of PF (1%) > honey (4%) > PF (2%) > normal bread > HPMC (0.5 g) > PF (4%) > HPMC (1 g) > HPMC (1.5 g). PF incorporated bread had sensorily highest acceptance followed by HPMC and honey. PMID:23572615

  9. Shear and extensional properties of kefiran.

    PubMed

    Piermaría, Judith; Bengoechea, Carlos; Abraham, Analía Graciela; Guerrero, Antonio

    2016-11-01

    Kefiran is a neutral polysaccharide constituted by glucose and galactose produced by Lactobacillus kefiranofaciens. It is included into kefir grains and has several health promoting properties. In the present work, shear and extensional properties of different kefiran aqueous dispersions (0.5, 1 and 2% wt.) were assessed and compared to other neutral gums commonly used in food, cosmetic and pharmaceutics industries (methylcellulose, locust bean gum and guar gum). Kefiran showed shear flow characteristics similar to that displayed by other representative neutral gums, although it always yielded lower viscosities at a given concentration. For each gum system it was possible to find a correlation between dynamic and steady shear properties by a master curve including both the apparent and complex viscosities. When studying extensional properties of selected gums at 2% wt. by means of a capillary break-up rheometer, kefiran solutions did not show important extensional properties, displaying a behaviour close the Newtonian. PMID:27516254

  10. Compressive Strength, Chloride Permeability, and Freeze-Thaw Resistance of MWNT Concretes under Different Chemical Treatments

    PubMed Central

    Wang, Xingang; Wang, Yao; Xi, Yunping

    2014-01-01

    This study investigated compressive strength, chloride penetration, and freeze-thaw resistance of multiwalled carbon nanotube (MWNT) concrete. More than 100 cylindrical specimens were used to assess test variables during sensitivity observations, including water-cement ratios (0.75, 0.5, and 0.4) and exposure to chemical agents (including gum arabic, propanol, ethanol, sodium polyacrylate, methylcellulose, sodium dodecyl sulfate, and silane). To determine the adequate sonication time for MWNT dispersal in water, the compressive strengths of MWNT concrete cylinders were measured after sonication times ranging from 2 to 24 minutes. The results demonstrated that the addition of MWNT can increase the compressive strength of concrete by up to 108%. However, without chemical treatment, MWNT concretes tend to have poor freeze-thaw resistance. Among the different chemical treatments, MWNT concrete treated with sodium polyacrylate has the best compressive strength, chloride resistance, and freeze-thaw durability. PMID:25140336

  11. Online preconcentration by transient isotachophoresis in linear polymer on a poly(methyl methacrylate) microchip for separation of human serum albumin immunoassay mixtures.

    PubMed

    Mohamadi, Mohamad Reza; Kaji, Noritada; Tokeshi, Manabu; Baba, Yoshinobu

    2007-05-15

    Online preconcentration of human serum albumin (HSA) and its immunocomplex with a monoclonal antibody by on-chip transient isotachophoresis is reported. An 800-fold signal enhancement was achieved following the preconcentration on standard cross-channel microchips made of poly (methyl methacrylate). Sample injection, preconcentration, and separation were done continuously and controlled solely by a sequential voltage switching program. The preconcentration was followed by on-chip nondenaturing gel electrophoresis in methylcellulose solution. The method was applied to microchip electrophoresis immunoassay of HSA. Baseline separation of HSA and its immunocomplex was achieved in 25 s in the first 1 cm of the microchannel. In a direct immunoassay, the minimum detectable concentration of fluorescent labeled HSA by laser-induced fluorescence detection was 7.5 pM. PMID:17437335

  12. A novel once daily microparticulate dosage form comprising lansoprazole to prevent nocturnal acid breakthrough in the case of gastro-esophageal reflux disease: preparation, pharmacokinetic and pharmacodynamic evaluation.

    PubMed

    Alai, Milind; Lin, Wen Jen

    2013-01-01

    The objective of this study was to formulate and evaluate the lansoprazole (LPZ)-loaded microparticles to prevent nocturnal acid breakthrough in the case of gastro-esophageal reflux disease (GERD). The microparticulate delivery system was prepared by solvent evaporation method using Eudragit RS100 as a matrix polymer followed by enteric coated with Eudragit S100 and hydroxypropyl methylcellulose phthalate HP55 using spray drying method. The enteric coated microparticles were stable in gastric pH condition. In vivo pharmacokinetic and pharmacodynamic studies in male Wistar rats demonstrated that enteric coated microparticles sustained release of LPZ and promoted ulcer healing activity. In other words, the microparticulate dosage form provided effective drug concentration for a longer period as compared to conventional extended release dosage form, and showed sufficient anti-acid secretion activity to treat acid related disorders including the enrichment of nocturnal acid breakthrough event based on a once daily administration. PMID:23294453

  13. Albizia procera gum as an excipient for oral controlled release matrix tablet.

    PubMed

    Pachuau, Lalduhsanga; Mazumder, Bhaskar

    2012-09-01

    The purpose of this research was to develop and evaluate controlled release matrix tablets of paracetamol based on natural gum exudates of Albizia procera. Procera gum was characterized of its properties like compressibility index, angle of repose, viscosity and moisture content. The interaction between the gum and paracetamol was also studied through differential scanning calorimetry (DSC) and FTIR spectroscopy. Matrix tablets were then prepared by wet granulation method with different concentrations of procera gum and hydroxypropyl methylcellulose (HPMC) and evaluated for their physical properties like weight variation, hardness, friability and content uniformity. Dissolution study was conducted to characterize release mechanism from the matrix system and data were fitted to various kinetic models. The mechanism of drug release from both types of matrix tablets was found to be anomalous type. Results from various evaluations suggested that A. procera gum could be used as drug release retardant in controlled release matrix systems. PMID:24751043

  14. Evaluation of Phosphorylated Psyllium Seed Polysaccharide as a Release Retardant.

    PubMed

    Rao, Monica R P; Warrier, Deepa U; Rao, Shivani H

    2015-01-01

    The aim of the present study was to modify psyllium seed polysaccharide and evaluate the modified polysaccharide as release retardant in tablets employing ciprofloxacin hydrochloride as model drug. Studies on polysaccharide from psyllium husk has been reported but no work has been reported on characterization and modification of the polysaccharide present in the psyllium (Plantago ovata) seed and the use of the modified polysaccharide as a release retardant in tablets. In this study, the seed gum was modified using sodium trimetaphosphate as crosslinking agent. Sustained release matrix tablets of ciprofloxacin hydrochloride were prepared by wet granulation using various drug-polymer ratios. The polymers investigated were psyllium polysaccharide, phosphorylated psyllium polysaccharide and widely used release retardant hydroxypropyl methylcellulose K100M. The tablets were evaluated for hardness, friability, drug content, swelling profile and in vitro dissolution studies. The matrix tablets containing 1:3 proportion of drug-phosphorylated psyllium polysaccharide was found to have higher hardness as compared to tablets containing 1:1 and 1:2 proportions. The results of swelling behavior in water showed that the tablets containing 1:3 drug:phosphorylated psyllium polysaccharide ratio had swelling comparable to that of tablets containing 1:3 drug:hydroxypropyl methylcellulose ratio. The in vitro dissolution studies shows that the dissolution rate was retarded from 98.41 to 37.6% in 6 h with increase in concentration of phosphorylated psyllium polysaccharide from 100 to 300 mg. Formulations containing psyllium polysaccharide showed complete drug release in 8 h whereas those formulated with phosphorylated psyllium polysaccharide exhibited extended drug release over the 12 h period. Drug release kinetic studies revealed that drug release followed Korsmeyer-Peppas model. PMID:26798177

  15. Effects of PMMA and Cross-Linked Dextran Filler for Soft Tissue Augmentation in Rats

    PubMed Central

    Huh, Jung-Bo; Kim, Joo-Hyun; Kim, Soyun; Lee, So-Hyoun; Shim, Kyung Mi; Kim, Se Eun; Kang, Seong Soo; Jeong, Chang-Mo

    2015-01-01

    This study was conducted for evaluation of the ability to maintain efficacy and biocompatibility of cross-linked dextran in hydroxypropyl methylcellulose (DiHM) and cross-linked dextran mixed with PMMA in hydroxypropyl methylcellulose (PDiHM), compared with hyaluronic acid (HA) filler. Saline and HA solution was administered in the negative and positive control groups, and DiHM and PDiHM were administered in the test groups (n = 10 in each group). The site of cranial subcutaneous injection was the mid-point of the interpupillary line, and the site of intraoral submucosal injection was the ridge crest 2 mm below the cervical line of the mandibular left incisor. Before and immediately after filler injection, intraoral photos and lateral cephalometric radiographs were taken for analysis and comparison of the effect of the filler on the injection sites. The filler injected areas were converted into sequential size changes (%) of the baseline. Histomorphologic examination was performed after 12 weeks. The smallest value in the filler injected area was observed during the experimental period in the normal saline group (p < 0.001), which was almost absorbed at 4 weeks (7.19% ± 12.72%). The HA group exhibited a steady decrease in sequential size and showed a lower value than the DiHM and PDiHM groups (saline < HA < DHiM, PDHiM, p < 0.001). DiHM and PDiHM tended to increase for the first 4 weeks and later decreased until 12 weeks. In this study on DiHM and PDiHM, there was no histological abnormality in cranial skin and oral mucosa. DiHM and PDiHM filler materials with injection system provide an excellent alternative surgical method for use in oral and craniofacial fields. PMID:26633376

  16. Preformulation and characterization of a lidocaine hydrochloride and dexamethasone sodium phosphate thermo-reversible and bioadhesive long-acting gel for intraperitoneal administration.

    PubMed

    Arbelaez-Camargo, Diana; Suñé-Negre, Josep Maria; Roig-Carreras, Manel; García-Montoya, Encarna; Pérez-Lozano, Pilar; Miñarro-Carmona, Montserrat; Ticó-Grau, Josep Ramon

    2016-02-10

    The search for new formulations of anaesthetic agents that allow a localized administration and provide a prolonged effect is of great interest in the multimodal management of postoperative pain. The pre-formulation and characterization of a lidocaine and dexamethasone thermosensitive and bioadhesive long-acting gel for intraperitoneal administration was done as a tool in the management of pain in abdominal surgeries. The pre-formulation process was conducted by a systematic variation of the concentration of the different polymers, until setting it, in a suitable concentration that allowed an adequate gelation temperature. The poloxamer 407 (P407) was used as the main polymer; hydroxypropyl methylcellulose (HPMC) as the bioadhesive agent and polyvinyl pyrrolidone (PVP) to adjust the gelation temperature and physicochemical properties. The formulations were characterized by gelation temperature, pH, viscosity at 25°C and 37°C, gelation time, density and osmolality. Gelation temperature was decreased when increasing the concentration of hydroxypropyl methylcellulose and poloxamer 407, this effect was also observed when adding lidocaine hydrochloride and dexamethasone sodium phosphate to the formulations. The gelation temperature did not have statistically significant relation with the PVP concentration (P-value of 0.6797), even though, there is a tendency in the gelation temperature by varying it. Between the developed formulations, the 12.5/3.3/0.4% (P407/HPMC/PVP) formulation presents an appropriate gelation temperature, a suitable viscosity for administration by syringe, an adequate and stable pH and osmolality to prevent tissue damage and a correct gelation time that allowed the formation of a prolonged release implant. PMID:26685726

  17. Evaluation of Phosphorylated Psyllium Seed Polysaccharide as a Release Retardant

    PubMed Central

    Rao, Monica R. P.; Warrier, Deepa U.; Rao, Shivani H.

    2015-01-01

    The aim of the present study was to modify psyllium seed polysaccharide and evaluate the modified polysaccharide as release retardant in tablets employing ciprofloxacin hydrochloride as model drug. Studies on polysaccharide from psyllium husk has been reported but no work has been reported on characterization and modification of the polysaccharide present in the psyllium (Plantago ovata) seed and the use of the modified polysaccharide as a release retardant in tablets. In this study, the seed gum was modified using sodium trimetaphosphate as crosslinking agent. Sustained release matrix tablets of ciprofloxacin hydrochloride were prepared by wet granulation using various drug-polymer ratios. The polymers investigated were psyllium polysaccharide, phosphorylated psyllium polysaccharide and widely used release retardant hydroxypropyl methylcellulose K100M. The tablets were evaluated for hardness, friability, drug content, swelling profile and in vitro dissolution studies. The matrix tablets containing 1:3 proportion of drug-phosphorylated psyllium polysaccharide was found to have higher hardness as compared to tablets containing 1:1 and 1:2 proportions. The results of swelling behavior in water showed that the tablets containing 1:3 drug:phosphorylated psyllium polysaccharide ratio had swelling comparable to that of tablets containing 1:3 drug:hydroxypropyl methylcellulose ratio. The in vitro dissolution studies shows that the dissolution rate was retarded from 98.41 to 37.6% in 6 h with increase in concentration of phosphorylated psyllium polysaccharide from 100 to 300 mg. Formulations containing psyllium polysaccharide showed complete drug release in 8 h whereas those formulated with phosphorylated psyllium polysaccharide exhibited extended drug release over the 12 h period. Drug release kinetic studies revealed that drug release followed Korsmeyer-Peppas model. PMID:26798177

  18. Long-term Stability of Zonisamide, Amitriptyline, and Glycopyrrolate in Extemporaneously Prepared Liquid-dosage Forms at Two Temperatures.

    PubMed

    Nahata, Milap C

    2016-01-01

    The lack of commercially available liquid dosage forms for pediatric patients prompted this study. The objectives of our study were to determine the stability of zonisamide, amitriptyline, and glycopyrrolate in extemporaneously prepared oral suspensions in plastic prescription bottles. One group of suspensions was prepared in OraPlus:OraSweet (1:1) for each drug and stored either under refrigeration (4°C) or at room temperature (25°C). A second group of suspensions were compounded in 1% methylcellulose:simple syrup at a 1:10 proportion for zonisamide, amitriptyline, and glycopyrrolate; these suspensions were stored at either under refrigeration (4°C) or at room temperature (25°C). The drug concentrations were measured by the stability-indicating high-performance liquid chromatographic methods. The mean concentration of zonisamide (10 mg/mL) remained above 95% of the original concentration for 91 days in each group of suspensions at both 4°C and 25°C. The mean concentration of amitriptyline (20 mg/mL) was above 95% for 91 days in the suspensions containing OraPlus/ OraSweet at both 4°C and 25°C. However, in the suspensions containing methylcellulose:simple syrup, the mean concentration of amitriptyline was about 95% for 42 days at 4°C and 28 days at 25°C. The mean concentration of glycopyrrolate (0.2 mg/mL) was above 95% in each group of suspensions during the 14-day study period. These data indicate that zonisamide, amitriptyline, and glycopyrrolate can be prepared extemporaneously as suspensions and stored in plastic prescription bottles for varying periods at 4°C and 25°C for use in pediatric patients. PMID:27323428

  19. Rifaximin diminishes neutropenia following potentially lethal whole-body radiation.

    PubMed

    Jahraus, Christopher D; Schemera, Bettina; Rynders, Patricia; Ramos, Melissa; Powell, Charles; Faircloth, John; Brawner, William R

    2010-07-01

    Terrorist attacks involving radiological or nuclear weapons are a substantial geopolitical concern, given that large populations could be exposed to potentially lethal doses of radiation. Because of this, evaluating potential countermeasures against radiation-induced mortality is critical. Gut microflora are the most common source of systemic infection following exposure to lethal doses of whole-body radiation, suggesting that prophylactic antibiotic therapy may reduce mortality after radiation exposure. The chemical stability, easy administration and favorable tolerability profile of the non-systemic antibiotic, rifaximin, make it an ideal potential candidate for use as a countermeasure. This study evaluated the use of rifaximin as a countermeasure against low-to-intermediate-dose whole-body radiation in rodents. Female Wistar rats (8 weeks old) were irradiated with 550 cGy to the whole body and were evaluated for 30 d. Animals received methylcellulose, neomycin (179 mg/kg/d) or variably dosed rifaximin (150-2000 mg/kg/d) one hour after irradiation and daily throughout the study period. Clinical assessments (e.g. body weight) were made daily. On postirradiation day 30, blood samples were collected and a complete blood cell count was performed. Animals receiving high doses of rifaximin (i.e. 1000 or 2000 mg/kg/d) had a greater increase in weight from the day of irradiation to postirradiation day 30 compared with animals that received placebo or neomycin. For animals with an increase in average body weight from irradiation day within 80-110% of the group average, methylcellulose rendered an absolute neutrophil count (ANC) of 211, neomycin rendered an ANC of 334, rifaximin 300 mg/kg/d rendered an ANC of 582 and rifaximin 1000 mg/kg/d rendered an ANC of 854 (P = 0.05 for group comparison). Exposure to rifaximin after near-lethal whole-body radiation resulted in diminished levels of neutropenia. PMID:20558844

  20. Modulation of distal colonic epithelial barrier function by dietary fibre in normal rats

    PubMed Central

    Mariadason, J; Catto-Smith, A; Gibson, P

    1999-01-01

    BACKGROUND—Dietary fibre influences the turnover and differentiation of the colonic epithelium, but its effects on barrier function are unknown. 
AIMS—To determine whether altering the type and amount of fibre in the diet affects paracellular permeability of intestinal epithelium, and to identify the mechanisms of action. 
METHODS—Rats were fed isoenergetic low fibre diets with or without supplements of wheat bran (10%) or methylcellulose (10%), for four weeks. Paracellular permeability was determined by measurement of conductance and 51Cr-EDTA flux across tissue mounted in Ussing chambers. Faecal short chain fatty acid (SCFA) concentrations were assessed by gas chromatography, epithelial kinetics stathmokinetically, and mucosal brush border hydrolase activities spectrophotometrically. 
RESULTS—Body weight was similar across the dietary groups. Conductance and 51Cr-EDTA flux were approximately 25% higher in animals fed no fibre, compared with those fed wheat bran or methylcellulose in the distal colon, but not in the caecum or jejunum. Histologically, there was no evidence of epithelial injury or erosion associated with any diet. The fibres exerted different spectra of effects on luminal SCFA concentrations and pH, and on mucosal indexes, but both bulked the faeces, were trophic to the epithelium, and stimulated expression of a marker of epithelial differentiation. 
CONCLUSIONS—Both a fermentable and a non-fermentable fibre reduce paracellular permeability specifically in the distal colon, possibly by promoting epithelial cell differentiation. The mechanisms by which the two fibres exert their effects are likely to be different. 

 Keywords: colon; differentiation; epithelium; fibre; paracellular permeability; proliferation PMID:10026327

  1. Flexible and printable paper-based strain sensors for wearable and large-area green electronics

    NASA Astrophysics Data System (ADS)

    Liao, Xinqin; Zhang, Zheng; Liao, Qingliang; Liang, Qijie; Ou, Yang; Xu, Minxuan; Li, Minghua; Zhang, Guangjie; Zhang, Yue

    2016-06-01

    Paper-based (PB) green electronics is an emerging and potentially game-changing technology due to ease of recycling/disposal, the economics of manufacture and the applicability to flexible electronics. Herein, new-type printable PB strain sensors (PPBSSs) from graphite glue (graphite powder and methylcellulose) have been fabricated. The graphite glue is exposed to thermal annealing to produce surface micro/nano cracks, which are very sensitive to compressive or tensile strain. The devices exhibit a gauge factor of 804.9, response time of 19.6 ms and strain resolution of 0.038%, all performance indicators attaining and even surpassing most of the recently reported strain sensors. Due to the distinctive sensing properties, flexibility and robustness, the PPBSSs are suitable for monitoring of diverse conditions such as structural strain, vibrational motion, human muscular movements and visual control.Paper-based (PB) green electronics is an emerging and potentially game-changing technology due to ease of recycling/disposal, the economics of manufacture and the applicability to flexible electronics. Herein, new-type printable PB strain sensors (PPBSSs) from graphite glue (graphite powder and methylcellulose) have been fabricated. The graphite glue is exposed to thermal annealing to produce surface micro/nano cracks, which are very sensitive to compressive or tensile strain. The devices exhibit a gauge factor of 804.9, response time of 19.6 ms and strain resolution of 0.038%, all performance indicators attaining and even surpassing most of the recently reported strain sensors. Due to the distinctive sensing properties, flexibility and robustness, the PPBSSs are suitable for monitoring of diverse conditions such as structural strain, vibrational motion, human muscular movements and visual control. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr02172g

  2. Detailed stability investigation of amorphous solid dispersions prepared by single-needle and high speed electrospinning.

    PubMed

    Démuth, B; Farkas, A; Pataki, H; Balogh, A; Szabó, B; Borbás, E; Sóti, P L; Vigh, T; Kiserdei, É; Farkas, B; Mensch, J; Verreck, G; Van Assche, I; Marosi, G; Nagy, Z K

    2016-02-10

    In this research the long-term stability (one year) of amorphous solid dispersions (ASDs) prepared by high speed electrospinning was investigated at 25 °C/60% relative humidity (RH) (closed conditions) and 40 °C/75% RH (open conditions). Single needle electrospinning and film casting were applied as reference technologies. Itraconazole (ITR) was used as the model API in 40% concentration and the ASDs consisted of either one of the following polymers as a comparison: polyvinylpyrrolidone-vinyl acetate 6:4 copolymer (no hydrogen bonds between API and polymer) and hydroxypropyl methylcellulose (possible hydrogen bonds between oxo or tertiary nitrogen function of API and hydroxyl moiety of polymer). DSC, XRPD and dissolution characteristics of samples at 0, 3 and 12 months were investigated. In addition, Raman maps of certain electrospun ASDs were assessed to investigate crystallinity. A new chemometric method, based on Multivariate Curve Resolution-Alternating Least Squares algorithm, was developed to calculate the spectrum of amorphous ITR in the matrices and to determine the crystalline/amorphous ratio of aged samples. As it was expected ITR in single needle electrospun SDs was totally amorphous at the beginning, in addition hydroxypropyl methylcellulose could keep ITR in this form at 40 °C/75% RH up to one year due to the hydrogen bonds and high glass transition temperature of the SD. In polyvinylpyrrolidone-vinyl acetate matrix ITR remained amorphous at 25 °C/60% RH throughout one year. Materials prepared by scaled-up, high throughput version of electrospinning, which is compatible with pharmaceutical industry, also gained the same quality. Therefore these ASDs are industrially applicable and with an appropriate downstream process it would be possible to bring them to the market. PMID:26705153

  3. Formulation, Pharmacokinetic, and Efficacy Studies of Mannosylated Self-Emulsifying Solid Dispersions of Noscapine

    PubMed Central

    Andey, Terrick; Patel, Apurva; Marepally, Srujan; Chougule, Mahavir; Spencer, Shawn D.; Rishi, Arun K.; Singh, Mandip

    2016-01-01

    Purpose To formulate hydroxypropyl methylcellulose-stabilized self-emulsifying solid dispersible carriers of noscapine to enhance oral bioavailability. Methods Formulation of noscapine (Nos) self-emulsifying solid dispersible microparticles (SESDs) was afforded by emulsification using an optimized formula of Labrafil M1944, Tween-80, and Labrasol followed by spray-drying with hydroxypropyl methylcellulose (HPMC), with and without mannosamine (Mann-Nos_SESDs and Nos_SESDs respectively); self-microemulsifying liquid dispersions (SMEDDs) with and without mannosamine (Mann-Nos_SMEDDs and Nos_SMEDDs respectively) were also prepared. SMEDDs and SESDs were characterized for size, polydispersity, surface charge, entrapment efficiency, in vitro permeability, in vitro release kinetics, and oral pharmacokinetics in Sprague-Dawley rats (10 mg/kg p.o). The antitumor efficacy of Mann-Nos_SESDs on the basis of chemosensitization to cisplatin (2.0 mg/kg, IV) was investigated in a chemorefractory lung tumor Nu/Nu mouse model up to a maximal oral dose of 300 mg/kg. Results The oil/surfactant/co-surfactant mixture of Labrafil M1944, Tween-80, and Labrasol optimized at weight ratios of 62.8:9.30:27.90% produced stable self-microemulsifying dispersions (SMEDDs) at a SMEDD to water ratio of 1–3:7–9 parts by weight. SMEDDs had hydrodynamic diameters between 231 and 246 nm; surface charges ranged from -16.50 to -18.7 mV; and entrapment efficiencies were between 32 and 35%. SESDs ranged in size between 5.84 and 6.60 μm with surface charges from -10.62 to -12.40 mV and entrapment efficiencies of 30.96±4.66 and 32.05±3.72% (Nos_SESDs and Mann-Nos_SESDs respectively). Mann-Nos_SESDs exhibited saturating uptake across Caco-2 monolayers (Papp = 4.94±0.18 × 10−6 cm/s), with controlled release of 50% of Nos in 6 hr at pH 6.8 following Higuchi kinetics. Mann-Nos_ SESDs was 40% more bioavailable compared to Nos_SESDs; and was effective in sensitizing H1650 SP cells to Cisplatin in vitro

  4. A simple method for isolating chicken egg yolk immunoglobulin using effective delipidation solution and ammonium sulfate.

    PubMed

    Tong, Chenyao; Geng, Fang; He, Zhenjiao; Cai, Zhaoxia; Ma, Meihu

    2015-01-01

    Chicken egg yolk immunoglobulin (IgY) is a superior alternative to mammalian immunoglobulin. However, the practical application of IgY in research, diagnostics, and functional food is limited due to complex or time-consuming purification procedures. The objective of this study was to develop a simple, safe, large-scale separation method for IgY from egg yolk. Egg yolk was diluted with 6-fold delipidation solutions made of different types (pectin, λ-carrageenan, carboxymethylcellulose, methylcellulose, and dextran sulfate) and concentrations (0.01, 0.05, 0.1, 0.15, and 0.2%) of polysaccharides, respectively. The yolk solution was adjusted to pH 5.0, and then kept overnight at 4°C before being centrifuged at 4°C. The resulting supernatant was added to 35% (w/v) (NH4)2SO4 and then centrifuged. The precipitant, which contained IgY, was dissolved in distilled water and then dialyzed. SDS-PAGE and Western blotting were utilized to conduct qualitative analysis of IgY; high-performance liquid chromatography (HPLC) was used for quantitative analysis. The immunoreactivity of IgY was measured by ELISA. The results showed that yield, purity, and immunoreactivity varied with types and concentrations of polysaccharides. The optimal isolation of IgY for pectin, λ-carrageenan, dextran sulfate, and carboxymethylcellulose was at the concentration of 0.1%; for methylcellulose, optimal isolation was at 0.15%. The best results were obtained in the presence of 0.1% pectin. In this condition, yield and purity can reach 8.36 mg/mL egg yolk and 83.3%, respectively, and the negative effect of IgY on immunoreactivity can be minimized. The procedure of isolation was simplified to 2 steps with a higher yield of IgY, avoiding energy- and time-consuming methods. Therefore, the isolation condition under study has a great potential for food industry production of IgY on a large scale. PMID:25542196

  5. The effects of multiple dosing with zileuton on antigen-induced responses in sheep.

    PubMed

    Scuri, M; Allegra, L; Abraham, W M

    1998-01-01

    In a previous study, a single dose of zileuton (10 mg/kg, po) given 2 h before antigen challenge, had a minimal effect on the antigen-induced early airway response (EAR), although it was effective in blocking the late airway response (LAR). Because our previous data indicated that 5-lipoxygenase (5-LO) products contribute to the severity of the antigen-induced EAR in these animals, we hypothesized that the lack of effect of zileuton on the EAR may have had to do with inadequate tissue levels. Therefore, in this study, we determined if multiple dosing with zileuton, which theoretically could improve tissue levels, would provide protection against the antigen-induced EAR as well as the LAR. Each sheep was used in each of the three trials (> or = 15 days apart), the order of which was randomized. For trial 1, the sheep were treated with zileuton (10 mg/kg in 0.1% methylcellulose, p.o.) once a day for 4 days; for trials 2, the sheep were treated with zileuton (10 mg/kg, p.o.) for 2 days; and, for trial 3, the animals were treated with vehicle (0.1% methylcellulose) for 4 days as in trial 1. In all trials, antigen challenge followed 1 h after the last treatment. In the placebo trial, antigen challenge resulted in characteristic EAR (407 +/- 102%, increase over baseline) and LAR (335 +/- 75%, increase over baseline). The antigen-induced effects were completely blocked by the 4-day treatment (EAR = 24 +/- 3%; LAR = 17 +/- 3%, P < 0.05 vs. placebo). In the 2-day trial, the immediate increase in R1, after antigen challenge was only partially blocked (EAR = 163 +/- 16%, P < 0.10 vs. placebo and P < 0.05 vs. 4-day trial), but the late response was completely blocked (24 +/- 3%). The protection against the EAR obtained with the 4-day treatment was significantly better (P < 0.05) than that obtained with the 2-day treatment. The results of this study show that multiple dosing with the 5-LO inhibitor, zileuton, provides protection against the antigen-induced EAR as well as LAR

  6. Genome-Wide DNA Methylation as an Epigenetic Consequence of Epstein-Barr Virus Infection of Immortalized Keratinocytes

    PubMed Central

    Birdwell, Christine E.; Queen, Krista J.; Kilgore, Phillip C. S. R.; Rollyson, Phoebe; Trutschl, Marjan; Cvek, Urska

    2014-01-01

    ABSTRACT The oral cavity is a persistent reservoir for Epstein-Barr virus (EBV) with lifelong infection of resident epithelial and B cells. Infection of these cell types results in distinct EBV gene expression patterns regulated by epigenetic modifications involving DNA methylation and chromatin structure. Regulation of EBV gene expression relies on viral manipulation of the host epigenetic machinery that may result in long-lasting host epigenetic reprogramming. To identify epigenetic events following EBV infection, a transient infection model was established to map epigenetic changes in telomerase-immortalized oral keratinocytes. EBV-infected oral keratinocytes exhibited a predominantly latent viral gene expression program with some lytic or abortive replication. Calcium and methylcellulose-induced differentiation was delayed in EBV-positive clones and in clones that lost EBV compared to uninfected controls, indicating a functional consequence of EBV epigenetic modifications. Analysis of global cellular DNA methylation identified over 13,000 differentially methylated CpG residues in cells exposed to EBV compared to uninfected controls, with CpG island hypermethylation observed at several cellular genes. Although the vast majority of the DNA methylation changes were silent, 65 cellular genes that acquired CpG methylation showed altered transcript levels. Genes with increased transcript levels frequently acquired DNA methylation within the gene body while those with decreased transcript levels acquired DNA methylation near the transcription start site. Treatment with the DNA methyltransferase inhibitor, decitabine, restored expression of some hypermethylated genes in EBV-infected and EBV-negative transiently infected clones. Overall, these observations suggested that EBV infection of keratinocytes leaves a lasting epigenetic imprint that can enhance the tumorigenic phenotype of infected cells. IMPORTANCE Here, we show that EBV infection of oral keratinocytes led to

  7. Influence of aqueous coatings on the stability of enteric coated pellets and tablets.

    PubMed

    Thoma, K; Bechtold, K

    1999-01-01

    Pancreatin pellets, placebo pellets and tablets containing vitamin B2 were coated with various aqueous and organic enteric polymers, HPMCAS, HP, Eudragit L 100-55, Eudragit L 30 D-55, CAP, CAT, CMEC and PVAP, comparatively investigated and tested for storage stability. With the exception of Eudragit L 100-55 and Eudragit L 30 D-55, higher amounts of coating material were needed to achieve gastro-resistance with aqueous coating than with organic coating. Film formation from aqueous dispersions of micronized HP 55 was affected by the degree of micronization and was improved by reducing the particle size of the polymer. Undercoating was another suitable measure to decrease the amount of coating material required. The choice of plasticizer was of special importance in the aqueous dispersions, and type and quantity must be appropriate for the polymer applied. Non-polymeric plasticizers such as triethyl citrate (TEC) evaporated along with water during the spraying or drying process and high temperatures promoted such losses. The moisture-sensitive pancreatic enzymes were damaged both by humidity and heat during aqueous coating. The extent of damage was dependent on the coating equipment used. Upon storage, coatings obtained from aqueous dispersions showed changes in enteric performance or release characteristics as a consequence of three chemical/physical mechanisms: hydrolysis of ester linkages in the polymer or plasticizer, evaporation of the plasticizer, delayed film formation. The active ingredient pancreatin induced hydrolysis of the ester based film-former hydroxypropyl methylcellulose acetate succinate (HPMCAS). However, even without the influence of enzymes, the phthalic ester groups of aqueous hydroxypropyl methylcellulose phthalate (HP) were partly cleaved after 11 months storage. In HPMCAS-coated pancreatin pellets, the plasticizer glyceryl triacetate was almost completely hydrolyzed by the enzymes, whilst triethyl citrate was lost by evaporation through

  8. A liquid chromatography method for quantifying caffeine dissolution from pharmaceutical formulations into colloidal, fat-rich media.

    PubMed

    Williams, Hywel D; Barrett, David A; Ward, Robert; Hardy, Ian J; Melia, Colin D

    2010-07-01

    A simple and rapid high-performance liquid-chromatography method is presented that permits quantification of caffeine in colloidal fat emulsions proposed as new 'biorelevant' dissolution media (Intralipid and various milks). Using a mobile phase of 0.1 M sodium acetate (pH 4.0) and acetonitrile (89.5:10.5, v/v) at 1 ml min(-1), the drug and internal standard (7-beta-hydroxyethyltheophylline) were eluted within 8 min. Caffeine extraction was undertaken by protein precipitation in ice-cold 12% (w/v) trichloroacetic acid and centrifugation at 10,000 rpm for 15 min. This simple extraction method generated caffeine recovery values (corrected for % fat content) of 75.4+/-1.4-100.6+/-5.5%. The limit of detection was within the range 0.25-0.4 microg ml(-1) and linearity was demonstrated in each medium up to 125 microg ml(-1). Precision was <11.5% RSD and intra- and inter-day accuracy was 93.4-109.3%. The validated method was applied to in vitro USP dissolution tests in milk which compared the kinetics of caffeine release from (i) extended release matrices containing hydroxypropyl methylcellulose (HPMC) and (ii) an immediate release commercial analgesic tablet. Good reproducibility was obtained in both extended and immediate release dissolution tests. The method provides high-throughput quantification of this common drug in fat emulsions used as biorelevant dissolution media. PMID:20483672

  9. Improved anti-melanoma effect of a transdermal mitoxantrone ethosome gel.

    PubMed

    Yu, Xiang; Du, Lina; Li, Yu; Fu, Guiying; Jin, Yiguang

    2015-07-01

    Melanomas are malignant tumors characterized by early metastasis, rapid development, poor prognosis and high mortality. A highly effective and convenient method is necessary for long-term treatment of melanomas. Mitoxantrone (MTO) was topically applied for melanoma therapy using an MTO ethosome gel. Firstly, an ethosome was prepared from MTO, phospholipids, ethanol and water followed by addition of hydroxypropyl methylcellulose to obtain an ethosome gel. The ethosome was characterized. The cytotoxicity on B16 melanoma cells was evaluated on an electrical cell-substrate impedance sensing system with a novel modified chip. In vivo anti-melanoma effect of the ethosome gel was explored. Immunohistochemical and flow cytometric investigations were done. The MTO ethosomes had the size of 78nm and the zeta potential of -55mV. The ethosomes were flexible vesicles and showed much higher in vitro permeability across the rat skin than MTO aqueous solutions. The ethosomes had significant cytotoxicity and higher in vivo anti-melanoma effect than MTO solutions. The calreticulin membrane translocation of B16 cells was improved by the MTO ethosomes and the cell uptake of MTO was confirmed. The MTO ethosome gel is a promising transdermal delivery system for melanoma therapy with the advantages of non-invasion and no significant side effects. PMID:26211575

  10. Design and evaluation of gastroretentive levofloxacin floating mini-tablets-in-capsule system for eradication of Helicobacter pylori.

    PubMed

    El-Zahaby, Sally A; Kassem, Abeer A; El-Kamel, Amal H

    2014-12-01

    Gastroretentive levofloxacin (LVF) floating mini-tablets for the eradication of Helicobacter pylori (H. pylori) were prepared using the matrix forming polymer hydroxypropyl methylcellulose (HPMC K100M), alone or with Carbopol 940P in different ratios by wet granulation technique. Buoyancy of mini-tablets was achieved by an addition of an effervescent mixture consisting of sodium bicarbonate and anhydrous citric acid to some formulations. The prepared mini-tablets were evaluated for weight variation, thickness, friability, hardness, drug content, in vitro buoyancy, water uptake and in vitro release. The optimized formula was subjected to further studies: FT-IR, DSC analysis and in vivo examination in healthy volunteers. The prepared mini-tablets exhibited satisfactory physicochemical characteristics. Incorporation of gas-generating agent improved the floating parameters. HPMC K100M mini-tablet formulation (F1) offered the best controlled drug release (>8 h) along with floating lag time <1 s and total floating time >24 h. The obtained DSC thermograms and FT-IR charts indicated that there is no positive evidence for the interaction between LVF and ingredients of the optimized formula. The in vivo test confirmed the success of the optimized formula F1 in being retained in the stomach of the volunteers for more than 4 h. LVF floating mini-tablets based on HPMC K100M is a promising formulation for eradication of H. pylori. PMID:25561871

  11. Roller compaction of hydrophilic extended release tablets-combined effects of processing variables and drug/matrix former particle size.

    PubMed

    Heiman, Johanna; Tajarobi, Farhad; Gururajan, Bindhumadhavan; Juppo, Anne; Abrahmsén-Alami, Susanna

    2015-04-01

    The present study shows that roller compaction (RC) can successfully be used as a granulation method to prepare hydroxypropyl methylcellulose (HPMC)-based extended release matrix tablets containing a high drug load, both for materials deforming mainly by fragmentation (paracetamol) as for those having mainly plastic deformation (ibuprofen). The combined effect of RC process variables and composition on the manufacturability of HPMC tablets was investigated. Standard wet granulation grade HPMC was compared with a larger particle size direct compressible HPMC grade. Higher roll pressure was found to result in larger paracetamol granules and narrower granule particle size distributions, especially for formulations containing smaller size HPMC. However, for ibuprofen, no clear effect of roll pressure was observed. High roll pressure also resulted in denser ribbon and less bypass fines during RC. Loss of compactibility was observed for granules compared to powder blends, which was found to be related to differences in granule porosity and morphology. Using the large-sized HPMC grade did in some cases result in lower tensile strength tablets but had the advantage to improve the powder flow into the roller compactor. This work also indicates that when the HPMC level lies near the percolation threshold, significant changes can occur in the drug release rate due to changes in other factors (raw material characteristics and processing). PMID:25273028

  12. Laminated sponges as challenging solid hydrophilic matrices for the buccal delivery of carvedilol microemulsion systems: Development and proof of concept via mucoadhesion and pharmacokinetic assessments in healthy human volunteers.

    PubMed

    Abd-Elbary, Ahmed; Makky, Amna M A; Tadros, Mina Ibrahim; Alaa-Eldin, Ahmed Adel

    2016-01-20

    Carvedilol (CVD) suffers from low absolute bioavailability (25%) due to its limited aqueous solubility and hepatic first-pass metabolism. Hydroxypropyl methylcellulose (HPMC) laminated buccal sponges loaded with CVD microemulsions (CVD-ME) were exploited to surmount such limitations. Six pseudoternary-phase diagrams were constructed using Capmul® MCM C8/Capmul® PG8, Tween® 80, propylene glycol and water. Six CVD-ME systems (0.625% w/v) were incorporated into HPMC core sponges backed with Ethocel® layers. The sponges were preliminary evaluated via FT-IR, DSC and XRD. The surface pH, morphology and in vitro drug release studies were evaluated. In vivo mucoadhesion and absorption studies of the best achieved laminated sponges (F4) were assessed in healthy volunteers. CVD-ME systems displayed nano-spherical clear droplets. The sponges showed interconnecting porous matrices through which CVD was dispersed in amorphous state. No intermolecular interaction was detected between CVD and HPMC. The surface pH values were almost neutral. The sponges loaded with CVD-ME systems showed more sustained-release profiles than those loaded with CVD-powder. Compared to Dilatrend® tablets, the significantly (P<0.05) higher bioavailability (1.5 folds), delayed Tmax and prolonged MRT(0-∞) unraveled the dual-potential of F4 sponges for water-insoluble drugs, like CVD, in improving drug oral bioavailability and in controlling drug release kinetics via buccal mucosa. PMID:26546947

  13. A Cationic Peptide, TAT-Cd0, Inhibits Herpes Simplex Virus Type 1 Ocular Infection In Vivo

    PubMed Central

    Jose, Gilbert G.; Larsen, Inna V.; Gauger, Joshua; Carballo, Erica; Stern, Rebecca; Brummel, Rachel; Brandt, Curtis R.

    2013-01-01

    Purpose. To test the in vivo activity of a peptide derived from the protein transducing domain of the human immunodeficiency virus (HIV) Tat protein, TAT-Cd0, in a murine herpes simplex type 1 (HSV-1) keratitis model. Methods. The efficacy of TAT-Cd0 was assessed in a postinfection treatment model with different concentrations (1 mg/mL, 0.1 mg/mL, 0.01 mg/mL) of the peptide in one of four delivery vehicles: artificial tears, PBS, methylcellulose, and aquaphor cream. Treatment began within 4 or 24 hours postinfection. Viral titers in the tear film were determined by plaque assay. Results. TAT-Cd0 reduced the severity of keratitis in all of the delivery vehicles tested when treatment started, 4 hours postinfection. Peptide in the tears or PBS delivery vehicle had the most significant reduction in disease severity and delayed the onset of vascularization and stromal keratitis. The percentage of mice presenting with disease was also significantly reduced and viral titers were reduced by 1 log at 24 hours postinfection in mice treated with 1 mg/mL TAT-Cd0, suggesting that inhibiting replication early is sufficient to achieve clinical effects. Lower concentrations were not effective and delaying treatment by 24 hours was also not effective. Conclusions. This study shows that TAT-Cd0 is an effective antiviral against HSV-1 strain KOS when applied shortly postinfection and that aqueous-based formulations are more suitable. PMID:23341013

  14. Newly Developed Topical Cefotaxime Sodium Hydrogels: Antibacterial Activity and In Vivo Evaluation.

    PubMed

    Zakaria, Azza S; Afifi, Samar A; Elkhodairy, Kadria A

    2016-01-01

    In an attempt to reach better treatment of skin infections, gel formulations containing Cefotaxime (CTX) were prepared. The gel was formulated using Carbopol 934 (C934), Hydroxypropyl Methylcellulose 4000 (HPMC 4000), Carboxymethylcellulose Sodium (Na CMC), Pectin (PEC), Xanthan Gum (XG), or Guar Gum (GG). Thirteen different formulas were prepared and characterized physically in terms of color, syneresis, spreadability, pH, drug content, and rheological properties. Drug-excipients compatibility studies were confirmed by FTIR and then in vitro drug release study was conducted. In vitro and in vivo antibacterial activities of CTX were studied against wound pathogens such as, Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and Pseudomonas aeruginosa (P. aeruginosa), using either pure drug or Fucidin® cream as control. F13 provides better spreadability compared to F1 (XG) or F11 (HPMC). Moreover, the release of the drug from hydrogel F13 containing C934 was slower and sustained for 8 h. Stability study revealed that, upon storage, there were no significant changes in pH, drug content, and viscosity of the gels. Also, F13 showed the larger inhibition zone and highest antibacterial activity among other formulations. Histological analysis demonstrated that after single treatment with F13 gel formulation, a noticeable reduction in microbial bioburden occurred in case of both Gram positive and Gram negative bacterial isolates. PMID:27314033

  15. A comparative study of vitamin E TPGS/HPMC supersaturated system and other solubilizer/polymer combinations to enhance the permeability of a poorly soluble drug through the skin.

    PubMed

    Ghosh, Indrajit; Michniak-Kohn, Bozena

    2012-11-01

    In transdermal drug delivery systems (TDDS), it is a challenge to achieve stable and prolonged high permeation rates across skin, because the concentration of the drug dissolved in the matrix has to be high in order to maintain zero order release kinetics of the drug. In case of poorly soluble drugs, due to thermodynamic challenges, there is a high tendency for the drug to nucleate immediately after formulating or even during storage. The present study focuses on the efficiency of vitamin E TPGS/HPMC supersaturated solution and other solubilizer/polymer systems to improve the solubility of the drug and inhibit crystal growth in the transdermal formulation. Effect of several solubilizers, for example, Pluronic F-127, vitamin E TPGS and co-solvent, for example, propylene glycol (PG) were studied on the supersaturated systems of ibuprofen as model drug. Various stabilizers such as hydroxylpropyl methylcellulose (HPMC 3 cps) and polyvinylpyrrolidone (PVP K-30) were examined to evaluate their crystal inhibitory effects. Different analytical tools were used in this study to detect the growth of crystals in the systems. Vitamin E TPGS and HPMC 3 cps formulation produced the highest permeation rate of the drug as compared to other systems. In addition, the onset of crystallization time was shown to be longer with this formulation as compared to other solubilizer/polymer combinations. PMID:22296239

  16. Poloxamer-based curcumin solid dispersions for ex tempore preparation of supersaturated solutions intended for antimicrobial photodynamic therapy.

    PubMed

    Vukićević, Milica; Hegge, Anne Bee; Vulić, Predrag; Tønnesen, Hanne Hjorth

    2014-06-19

    Abstract Phototoxic effect of curcumin supersaturated solutions toward pathogenic bacteria has already been demonstrated. However, to be useful in the clinical practice, a supersaturated solution needs to be physically and chemically stabile over the relevant time period. Poloxamer-based solid dispersions (SD) intended for ex tempore preparation of a supersaturated solution were designed to simultaneously facilitate dissolution and inhibit precipitation of curcumin in vitro. Due to the transformation of the crystalline compound to an amorphous form, as shown by X-ray powder diffraction, the desired concentration of curcumin could easily be achieved upon hydration of SDs. The efficiency of selected poloxamers (Pluronic® F-127, F-68 and P-123) as the precipitation inhibitors (PIs) and influence of an additional PI (polyethylene glycol 400, hydroxypropyl methylcellulose, and hyaluronic acid) on the physical stability of the solutions were examined by UV-Vis spectrophotometry. HPLC-PDA was employed to evaluate hydrolytic and photolytic stability of curcumin in the SD solutions. At sub-micellar concentrations, Pluronics® F-127 and P-123, but not F-68, delayed curcumin precipitation in aqueous media and protected the compound from hydrolytic degradation up to 24 h. Complete inactivation of Enterococcus faecalis was achieved after exposure to solutions of selected SDs at curcumin concentration ≥1 µM and the light dose of 9.4 J/cm(2). PMID:24946137

  17. Comparative studies for ciprofloxacin hydrochloride pre-formed gels and thermally triggered (in situ) gels: in vitro and in vivo appraisal using a bacterial keratitis model in rabbits.

    PubMed

    Abdelkader, Hamdy; Mansour, Heba F

    2015-06-01

    This article reports on comparative in vitro characterization and in vivo evaluation of pre-formed cellulose-based gels, methylcellulose (MC) and carboxymethylcellulose sodium (CMC) and in situ gel-forming Pluronic F127 (PL) for ocular delivery of ciprofloxacin hydrochloride (Cipro) by using a bacterial keratitis model and histological corneal examination. Drug-polymer interactions were studied employing thermal analysis. Further, different concentrations (1-3% w/w or 10-30% w/w) of gels depending on the nature of the polymer used were prepared, characterized for clarity, pH, rheology and in vitro release. Selected gel formulations were evaluated for ocular delivery to Staphylococcus aureus-infected rabbit corneas; and ocular toxicity through histological examination of the cornea. The results demonstrated no Cipro-polymers physicochemical interactions and pseudoplastic flow for all gels used at 35 °C. Both polymer concentrations and drug solubility in the gels are dominantly the rate-determining factors for in vitro drug release. The corneal healing rate for all gel-based formulations was significantly faster (p < 0.05) than that for Cipro solution-treated rabbits. PL-based gel induced significant swelling/edema of the corneal stroma, compared with MC- and CMC-based gels. In conclusion, cellulose-based polymers have superior ocular tolerability/dramatically less irritant; and superior efficacy with more convenient administration compared with PL and Cipro solution, respectively. PMID:24392945

  18. Itraconazole solid dispersion prepared by a supercritical fluid technique: preparation, in vitro characterization, and bioavailability in beagle dogs.

    PubMed

    Yin, Xuezhi; Daintree, Linda Sharon; Ding, Sheng; Ledger, Daniel Mark; Wang, Bing; Zhao, Wenwen; Qi, Jianping; Wu, Wei; Han, Jiansheng

    2015-01-01

    This research aimed to develop a supercritical fluid (SCF) technique for preparing a particulate form of itraconazole (ITZ) with good dissolution and bioavailability characteristics. The ITZ particulate solid dispersion was formulated with hydroxypropyl methylcellulose, Pluronic F-127, and L-ascorbic acid. Aggregated particles showed porous structure when examined by scanning electron microscopy. Powder X-ray diffraction and Fourier transform infrared spectra indicated an interaction between ITZ and excipients and showed that ITZ existed in an amorphous state in the composite solid dispersion particles. The solid dispersion obtained by the SCF process improved the dissolution of ITZ in media of pH 1.0, pH 4.5, and pH 6.8, compared with a commercial product (Sporanox(®)), which could be ascribed to the porous aggregated particle shape and amorphous solid state of ITZ. While the solid dispersion did not show a statistical improvement (P=0.50) in terms of oral bioavailability of ITZ compared with Sporanox(®), the C max (the maximum plasma concentration of ITZ in a pharmacokinetic curve) of ITZ was raised significantly (P=0.03) after oral administration. Thus, the SCF process has been shown to be an efficient, single step process to form ITZ-containing solid dispersion particles with good dissolution and oral bioavailability characteristics. PMID:26060397

  19. Effects of Commonly Used Excipients on the Expression of CYP3A4 in Colon and Liver Cells

    PubMed Central

    Tompkins, Leslie; Lynch, Caitlin; Haidar, Sam; Polli, James; Wang, Hongbing

    2013-01-01

    Purpose The objective of this investigation was to assess whether common pharmaceutical excipients regulate the expression of drug-metabolizing enzymes in human colon and liver cells. Methods Nineteen commonly used excipients were evaluated using a panel of experiments including cell-based human PXR activation assays, real-time RT-PCR assays for CYP3A4 mRNA expression, and immunoblot analysis of CYP3A4 protein expression in immortalized human liver cells (HepG2 and Fa2N4), human primary hepatocytes, and the intestinal LS174T cell models. Results No excipient activated human PXR or practically induced CYP3A4. However, three excipients (polysorbate 80, pregelatinized starch, and hydroxypropyl methylcellulose) tended to decrease mRNA and protein expression across experimental models. Conclusion This study represents the first investigation of the potential role of excipients in the expression of drug-metabolizing enzymes. Findings imply that some excipients may hold potential for excipient-drug interactions by repression of CYP3A4 expression. PMID:20503067

  20. Injectable hydrogel promotes early survival of induced pluripotent stem cell-derived oligodendrocytes and attenuates longterm teratoma formation in a spinal cord injury model.

    PubMed

    Führmann, T; Tam, R Y; Ballarin, B; Coles, B; Elliott Donaghue, I; van der Kooy, D; Nagy, A; Tator, C H; Morshead, C M; Shoichet, M S

    2016-03-01

    Transplantation of pluripotent stem cells and their differentiated progeny has the potential to preserve or regenerate functional pathways and improve function after central nervous system injury. However, their utility has been hampered by poor survival and the potential to form tumors. Peptide-modified biomaterials influence cell adhesion, survival and differentiation in vitro, but their effectiveness in vivo remains uncertain. We synthesized a peptide-modified, minimally invasive, injectable hydrogel comprised of hyaluronan and methylcellulose to enhance the survival and differentiation of human induced pluripotent stem cell-derived oligodendrocyte progenitor cells. Cells were transplanted subacutely after a moderate clip compression rat spinal cord injury. The hydrogel, modified with the RGD peptide and platelet-derived growth factor (PDGF-A), promoted early survival and integration of grafted cells. However, prolific teratoma formation was evident when cells were transplanted in media at longer survival times, indicating that either this cell line or the way in which it was cultured is unsuitable for human use. Interestingly, teratoma formation was attenuated when cells were transplanted in the hydrogel, where most cells differentiated to a glial phenotype. Thus, this hydrogel promoted cell survival and integration, and attenuated teratoma formation by promoting cell differentiation. PMID:26773663

  1. In vitro and in vivo evaluation of amorphous solid dispersions generated by different bench-scale processes, using griseofulvin as a model compound.

    PubMed

    Chiang, Po-Chang; Cui, Yong; Ran, Yingqing; Lubach, Joe; Chou, Kang-Jye; Bao, Linda; Jia, Wei; La, Hank; Hau, Jonathan; Sambrone, Amy; Qin, Ann; Deng, Yuzhong; Wong, Harvey

    2013-04-01

    Drug polymer-based amorphous solid dispersions (ASD) are widely used in the pharmaceutical industry to improve bioavailability for poorly water-soluble compounds. Spray-drying is the most common process involved in the manufacturing of ASD material. However, spray-drying involves a high investment of material quantity and time. Lower investment manufacturing processes such as fast evaporation and freeze-drying (lyophilization) have been developed to manufacture ASD at the bench level. The general belief is that the overall performance of ASD material is thermodynamically driven and should be independent of the manufacturing process. However, no formal comparison has been made to assess the in vivo performance of material generated by different processes. This study compares the in vitro and in vivo properties of ASD material generated by fast evaporation, lyophilization, and spray-drying methods using griseofulvin as a model compound and hydroxypropyl methylcellulose acetate succinate as the polymer matrix. Our data suggest that despite minor differences in the formulation release properties and stability of the ASD materials, the overall exposure is comparable between the three manufacturing processes under the conditions examined. These results suggest that fast evaporation and lyophilization may be suitable to generate ASD material for oral evaluation. However, caution should be exercised since the general applicability of the present findings will need to be further evaluated. PMID:23456436

  2. Desktop 3D printing of controlled release pharmaceutical bilayer tablets.

    PubMed

    Khaled, Shaban A; Burley, Jonathan C; Alexander, Morgan R; Roberts, Clive J

    2014-01-30

    Three dimensional (3D) printing was used as a novel medicine formulation technique for production of viable tablets capable of satisfying regulatory tests and matching the release of standard commercial tablets. Hydroxypropyl methylcellulose (HPMC 2208) (Methocel™ K100M Premium) and poly(acrylic acid) (PAA) (Carbopol(®) 974P NF) were used as a hydrophilic matrix for a sustained release (SR) layer. Hypromellose(®) (HPMC 2910) was used as a binder while microcrystalline cellulose (MCC) (Pharmacel(®) 102) and sodium starch glycolate (SSG) (Primojel(®)) were used as disintegrants for an immediate release (IR) layer. Commercial guaifenesin bi-layer tablets (GBT) were used as a model drug (Mucinex(®)) for this study. There was a favourable comparison of release of the active guaifenesin from the printed hydrophilic matrix compared with the commercially available GBT. The printed formulations were also evaluated for physical and mechanical properties such as weight variation, friability, hardness and thickness as a comparison to the commercial tablet and were within acceptable range as defined by the international standards stated in the United States Pharmacopoeia (USP). All formulations (standard tablets and 3D printed tablets) showed Korsmeyer-Peppas n values between 0.27 and 0.44 which indicates Fickian diffusion drug release through a hydrated HPMC gel layer. PMID:24280018

  3. Dissolution enhancement of chlorzoxazone using cogrinding technique

    PubMed Central

    Raval, Mihir K.; Patel, Jaydeep M.; Parikh, Rajesh K.; Sheth, Navin R.

    2015-01-01

    Purpose: The aim of the present work was to improve rate of dissolution and processing parameters of BCS class II drug, chlorzoxazone using cogrinding technique in the presence of different excipients as a carrier. Materials and Methods: The drug was coground with various carriers like polyethylene glycol (PEG 4000), hydroxypropyl methylcellulose (HPMC) E50LV, polyvinylpyrrolidone (PVP)K30, Kaolin and Neusilin US2 using ball mill, where only PEG 4000 improved dissolution rate of drug by bringing amorphization in 1:3 ratio. The coground mixture after 3 and 6 h was evaluated for various analytical, physicochemical and mechanical parameters. Results: The analysis showed conversion of Chlorzoxazone from its crystalline to amorphization form upon grinding with PEG 4000. Coground mixture as well as its directly compressed tablet showed 2.5-fold increment in the dissolution rate compared with pure drug. Directly compressible tablets prepared from pure drug required a large quantity of microcrystalline cellulose (MCC) during compression. The coground mixture and formulation was found stable in nature even after storage (40°C/75% relative humidity). Conclusions: Cogrinding can be successfully utilized to improve the rate of dissolution of poorly water soluble drugs and hence bioavailability. PMID:26682195

  4. A novel vaginal drug delivery system: anti-HIV bioadhesive film containing abacavir.

    PubMed

    Ghosal, Kajal; Ranjan, Alok; Bhowmik, Benoy Brata

    2014-07-01

    Women are very much susceptible for acquired immunodeficiency syndrome (AIDS) and other sexually transmitted diseases (STDs), mainly due to unprotected heterosexual vaginal intercourse and for some other social and economical disadvantages. Our aim was to formulate and optimize vaginal film of abacavir, a potent nucleoside reverse transcriptase inhibitor, for the treatment of AIDS and HIV. Abacavir films were prepared by solvent evaporation method using sodium alginate (Na-alginate) as the main polymer, Hydroxypropyl Methylcellulose E 15 (HPMC E 15) as the copolymer and glycerol as a humectant. Abacavir sulphate (ABC) was used here as a drug. Films were optimized for various physicochemical parameters such as tensile strength, % elongation at break, swelling capacity, drug content (mg/cm(2)), thickness, folding endurance, bioadhesion, pH, moisture content and SEM. Drug polymer interaction was studied by FTIR Spectra. The drug release study was accomplished in dissolution apparatus. In vivo study was also carried out. This newly formed film was one kind of sustain release type and can be considered as a novel drug carrier system for the treatment of AIDS and other STDs. It was suitable for local as well as systemic effect. The films showed good physicochemical property with good aesthetic appeal. PMID:24699799

  5. Flotability and flotation separation of polymer materials modulated by wetting agents.

    PubMed

    Wang, Hui; Wang, Chong-qing; Fu, Jian-gang; Gu, Guo-hua

    2014-02-01

    The surface free energy, surface tension and contact angles were performed to investigate the properties of wetting agents. Adsorption of wetting agents changes wetting behavior of polymer resins. Flotability of polymer materials modulated by wetting agents was studied, and wetting agents change significantly flotability of polymer materials. The flotability decreases with increasing the concentration of wetting agents, and the wetting ability is lignin sulfonate (LS)>tannic acid (TA)>methylcellulose (MC)>triton X-100 (TX-100) (from strong to weak). There is significant difference in the flotability between polymer resins and plastics due to the presence of additives in the plastics. Flotation separation of two-component and multicomponent plastics was conducted based on the flotability modulated by wetting agents. The two-component mixtures can be efficiently separated using proper wetting agent through simple flotation flowsheet. The multicomponent plastic mixtures can be separated efficiently through multi-stage flotation using TA and LS as wetting agents, and the purity of separated component was above 94%, and the recovery was more than 93%. PMID:24355830

  6. Cinemicrographic analysis of the movement of flagellated bacteria. II. The ratio of the propulsive velocity to the frequency of the wave propagation along flagellar tail.

    PubMed

    Shimada, K; Ikkai, T; Yoshida, T; Asakura, S

    1976-03-01

    We took cinemicrographs of the movement of the flagellar tail of the peritrichously flagellated bacterium, Salmonella, swimming in a medium containing methylcellulose under a dark-ground microscope. By analysing the film, the velocity of translation u, the frequency of the propagation of helical waves along the tail fF and the frequency of the induced rotation of bacterial body fB of individual organism were measured and the experimental values of the ratios u/fF, u/fB and fF/fB were obtained. On the other hand, the theoretical values of these ratios were calculated by inserting the geometrical parameters describing the shapes and the sizes of the body and the tail of individual organism into the equations previously derived for the hydrodynamic model of the propulsion of flagellated bacteria (Holwill and Burge, 1963; Chwang and Wu, 1971). For four bacterial specimens presently analysed, the experimental values of u/fF ranged from 0.5 to 0.9, whereas the theoretical values were about 0.3. As reported by the preceding paper, such a tendency for the experimental values to exceed the theoretical ones by two or three times was also seen in u/fB and, consequently, the experimental and the theoretical values of fF/fB showed good agreement. From the results of these quantitative analyses of the movements of flagellated bacteria, it was concluded that the validity of the hydrodynamic model was further supported experimentally. PMID:932565

  7. Muse Cells, a New Type of Pluripotent Stem Cell Derived from Human Fibroblasts.

    PubMed

    Liu, Qi; Zhang, Ru-zhi; Li, Di; Cheng, Sai; Yang, Yu-hua; Tian, Ting; Pan, Xiao-ru

    2016-04-01

    A new type of mesenchymal stem cells (MSCs) that expresses stage-specific embryonic antigen 3 (SSEA-3) and the mesenchymal cell marker CD105 are known as multilineage-differentiating stress-enduring (Muse) cells. Studies have shown that stem cells in suspension cultures are more likely to generate embryoid body-like stem cell spheres and maintain an undifferentiated phenotype and pluripotency. We separated Muse cells derived from human dermal fibroblasts by long-term trypsin incubation (LTT) through suspension cultures in methylcellulose. The Muse cells obtained expressed several pluripotency markers, including Nanog, Oct4, Sox2, and SSEA-3, and could differentiate in vitro into cells of the three germ layers, such as hepatocytes (endodermal), neural cells (ectodermal) and adipocytes, and osteocytes (mesodermal cells). These cells showed a low level of DNA methylation and a high nucleo-cytoplasmic ratio. Our study provides an innovative and exciting platform for exploring the potential cell-based therapy of various human diseases using Muse cells as well as their great possibility for regenerative medicine. PMID:27055628

  8. Studies on biological macromolecules lipid-Gelucire based gastroretentive multiparticulate.

    PubMed

    Upadhyay, Prashant; Pandit, Jayanta Kumar; Wahi, Arun Kumar

    2014-06-01

    Studies on biological macromolecules lipid-Gelucire based sustained release gastroretentive multiparticulates of metformin hydrochloride (MH) were developed by dispersing MH in melted Gelucire 39/01 and 43/01 using the melt granulation technique while fast release solid dispersions gastroretentive multiparticulates of glibenclamide (GLB), poorly soluble drug were developed using Gelucire 50/13 and PEG 200, 400, 4000, 6000 as carrier at different ratios. Percent drug entrapment of MH was 99.6±0.35% and in vitro floating ability was 11.3±0.47h. Model dependent analysis shows that zero order kinetics was followed while drug release mechanism was anomalous diffusion controlled. Combination of ethylcellulose, methylcellulose and microcrystalline cellulose with Gelucire were explored for release of drug, floatability and consistency for optimized formulation. While GLB multiparticulates showed entrapment efficiency of 99.8±0.11%, in vitro buoyancy for 11±0.2h and improved solubility and dissolution rate. Zero order kinetics was promising for all formulations. Model independent analysis f2 value for GIV was 40 while for M II was 54. Characterization was done by SEM, FTIR and PXRD. RP-HPLC method was adopted for simultaneous pharmacokinetic analysis of the drugs in rat plasma. In IVIVC studies confirm increased bioavailability of drugs in combination form and followed level A correlation using the diabetic type II Wistar rat. PMID:24699418

  9. Studies on canine bone marrow long-term culture: effect of stem cell factor.

    PubMed

    Neuner, E; Schumm, M; Schneider, E M; Guenther, W; Kremmer, E; Vogl, C; Büttner, M; Thierfelder, S; Kolb, H J

    1998-02-16

    Long-term culture of canine marrow cells allows in vitro studies of the hematopoietic system of the dog and characterization of early progenitor cells. Colonies of fresh marrow cells grew equally good in both agar or methylcellulose supplemented with fetal calf serum, while colonies of long-term cultures required agar-based medium containing human serum. Optimum colony growth was obtained when stem cell factor (SCF) and granulocyte-macrophage-colony-stimulating factor (GM-CSF) were used as growth stimuli of colony forming units (CFU). Similar results were achieved with several cell culture media. Addition of hydrocortisone to long-term cultures improved clonogenic growth of cultured cells. Addition of 2-mercaptoethanol had no effect. Strong differences were observed in long-term culture with different horse serum lots and the addition of fetal calf serum to long-term culture suppressed CFU growth of cultured cells. Recharging of cultures with fresh marrow cells on day 7 of culture improved CFU growth only in the following week but had little effect on the outcome. Adding SCF to long-term cultures led to differentiation of more primitive cells and destruction of the stromal layer. Investigation of purified and cultured cell populations was possible when preestablished long-term cultures as stromal layers were used. Loss of long-term culture-initiating ability could be demonstrated in this system with lineage negative marrow cells expanded ex vivo with SCF and GM-CSF. PMID:9613468

  10. Design and evaluation of gastroretentive levofloxacin floating mini-tablets-in-capsule system for eradication of Helicobacter pylori

    PubMed Central

    El-Zahaby, Sally A.; Kassem, Abeer A.; El-Kamel, Amal H.

    2014-01-01

    Gastroretentive levofloxacin (LVF) floating mini-tablets for the eradication of Helicobacter pylori (H. pylori) were prepared using the matrix forming polymer hydroxypropyl methylcellulose (HPMC K100M), alone or with Carbopol 940P in different ratios by wet granulation technique. Buoyancy of mini-tablets was achieved by an addition of an effervescent mixture consisting of sodium bicarbonate and anhydrous citric acid to some formulations. The prepared mini-tablets were evaluated for weight variation, thickness, friability, hardness, drug content, in vitro buoyancy, water uptake and in vitro release. The optimized formula was subjected to further studies: FT-IR, DSC analysis and in vivo examination in healthy volunteers. The prepared mini-tablets exhibited satisfactory physicochemical characteristics. Incorporation of gas-generating agent improved the floating parameters. HPMC K100M mini-tablet formulation (F1) offered the best controlled drug release (>8 h) along with floating lag time <1 s and total floating time >24 h. The obtained DSC thermograms and FT-IR charts indicated that there is no positive evidence for the interaction between LVF and ingredients of the optimized formula. The in vivo test confirmed the success of the optimized formula F1 in being retained in the stomach of the volunteers for more than 4 h. LVF floating mini-tablets based on HPMC K100M is a promising formulation for eradication of H. pylori. PMID:25561871

  11. Low dose of methyltestosterone in ovariectomised rats improves baroreflex sensitivity without geno- and cytotoxicity.

    PubMed

    Terra, Denise G; de Lima, Ewelyne M; do Nascimento, Andrews M; Brasil, Girlandia A; Filete, Placielle F; Kalil, Ieda C; Lenz, Dominik; Endringer, Denise C; Bissoli, Nazaré S; de Andrade, Tadeu U

    2016-08-01

    This study evaluated the effects of the isolated use of a low dose of methyltestosterone (MT) on cardiovascular reflexes and hormonal levels and its geno- and cytotoxic safety in ovariectomized rats. Female Wistar rats were divided into four groups (n = 6), respectively: SHAM (received vehicle methylcellulose 0.5%), SHAM + MT (received MT 0.05 mg/kg), OVX (received vehicle), and OVX + MT (received MT). Twenty-one days after ovariectomy, treatment was given orally daily for 28 days. The Bezold-Jarisch reflex (BJR) was analyzed by measuring the bradycardic and hypotensive responses elicited by phenylbiguanide (PBG) administration. The baroreflex sensitivity (BRS) was evaluated by phenylephrine and sodium nitroprussite. Myocyte hypertrophy was determined by morphometric analysis of H&E stained slides. Biochemical data were analyzed, as well as micronucleus assay. MT improved BRS and increased testosterone values, but did not change estradiol in the OVX group. MT did not promote changes in mean arterial pressure, heart rate, BJR, serum concentrations of troponin I, weight and histopathology of the heart. MT was able to restore the BRS in OVX rats. The geno- and cytotoxic safety of the MT was demonstrated by the absence of an increase in the micronucleus (PCEMN) or change in the ratio between normochromatic erythrocytes and polychromatic erythrocytes (NCE/PCE). PMID:27148800

  12. [Polycythemia vera terminating in chronic neutrophilic leukemia: studies on in vitro growth of hematopoietic progenitor cells].

    PubMed

    Fujisawa, S; Matuzaki, M; Harano, H; Matomura, S; Okubo, T; Maruta, A; Kodama, F; Ikuta, K; Sasaki, H

    1992-12-01

    A 57-year-old man, diagnosed as Polycythemia vera (PV), had been treated with administrations of Busulfan since 1984. Three years later, the number of neutrophils in peripheral blood increased to 50,000/microliters with progression of splenomegaly, and the case was diagnosed as Chronic neutrophilic leukemia (CNL) based on the criteria by Miura et al, in November, 1989. In spite of 6MP and Busulfan therapy, marked neutrophilia and splenomegaly progressed, and the patient died due to liver dysfunction in June of 1991. To clarify the pathophysiology of PV and CNL, we studied the in vitro growth kinetics of hematopoietic progenitor cells in bone marrow of this unique case and made a comparison with those of 4 cases of PV and 4 normal volunteers employing methylcellulose culture. As in other cases of PV, erythroid colonies were formed in culture of bone marrow from this patient without addition of erythropoietin. Furthermore, spontaneous colonies derived from CFU-GM and CFU-Mix increased remarkably in this case only. The results suggest that the hematopoietic abnormalities in this case involve the multipotent stem cells as well as erythroid and granuloid-macrophage progenitors. PMID:1479700

  13. Rapid authentication of ginseng species using microchip electrophoresis with laser-induced fluorescence detection.

    PubMed

    Qin, Jianhua; Leung, Frederick C; Fung, Yingsing; Zhu, Derong; Lin, Bingcheng

    2005-02-01

    Ginseng is one of the most expensive Chinese herbal medicines and the effectiveness of ginseng depends strongly on its botanical sources and the use of different parts of the plants. In this study, a microchip electrophoresis method coupled with the polymerase chain reaction (PCR)-short tandem repeats (STR) technique was developed for rapid authentication of ginseng species. A low viscosity hydroxypropyl methylcellulose (HPMC) solution was used as the sieving matrix for separation of the amplified STR fragments. The allele sizing of the amplified PCR products could be detected within 240 s or less. Good reproducibility and accuracy of the fragment size were obtained with the relative standard deviation for the allele sizes less than 1.0% (n=11). At two microsatellite loci (CT 12, CA 33), American ginseng had a different allele pattern on the electropherograms compared with that of the Oriental ginseng. Moreover, cultivated and wild American ginseng can be distinguished on the basis of allele sizing. This work establishes the feasibility of fast genetic authentication of ginseng species by use of microchip electrophoresis. PMID:15750870

  14. Natural Micronized Progesterone Sustained Release (SR) and Luteal Phase: Role Redefined!!

    PubMed

    Malik, Sonia; Krishnaprasad, Korukonda

    2016-02-01

    Role of progesterone in reproductive medicine is evolving with its suggested clinical role for the hormonal and nonhormonal actions in reproductive medicine. The main function of progesterone is to induce 'secretory' changes in endometrium that is further complimented by its immunomodulatory and anti-inflammatory actions. It positively modulates PIBF, NK cells and HOXA 10 genes for better implantation. MHRA recommends Serum Progesterone levels ≥14ng/ml in the mid-luteal phase for supporting pregnancy adequately. Oral Natural Micronized Progesterone SR formulation represents a therapeutic advance in this direction offering 'therapeutic compliance' with oral formulation while avoiding the local side effects related to long-term patient compliance in reproductive disorders. The formulation offers round the clock efficiency and efficacy with single dose administration thereby improving patient convenience and compliance. This formulation has been marketed globally since 1986 utilizing the well validated drug delivery system involving Methylcellulose base. The clinical utility of this formulation is further suggested especially in various conditions related with luteal phase insufficiency and Bad obstetric history (BOH) or luteal phase support in ART. The level of evidence has been quite robust with several clinical studies including Prescription Event Monitoring and Investigator initiated studies supporting the clinical role of oral NMP SR formulation especially in 'Real world' clinic settings for Luteal phase insufficiency that may be physiological or iatrogenic. PMID:27042538

  15. Welding of silver nanowire networks via flash white light and UV-C irradiation for highly conductive and reliable transparent electrodes.

    PubMed

    Chung, Wan-Ho; Kim, Sang-Ho; Kim, Hak-Sung

    2016-01-01

    In this work, silver nanowire inks with hydroxypropyl methylcellulose (HPMC) binders were coated on polyethylene terephthalate (PET) substrates and welded via flash white light and ultraviolet C (UV-C) irradiation to produce highly conductive transparent electrodes. The coated silver nanowire films were firmly welded and embedded into PET substrate successfully at room temperature and under ambient conditions using an in-house flash white light welding system and UV-C irradiation. The effects of light irradiation conditions (light energy, irradiation time, pulse duration, and pulse number) on the silver nanowire networks were studied and optimized. Bending fatigue tests were also conducted to characterize the reliability of the welded transparent conductive silver nanowire films. The surfaces of the welded silver nanowire films were analyzed via scanning electron microscopy (SEM), while the transmittance of the structures was measured using a spectrophotometer. From the results, a highly conductive and transparent silver nanowire film with excellent reliability could be achieved at room temperature under ambient conditions via the combined flash white light and UV-C irradiation welding process. PMID:27553755

  16. Design and Evaluation of Ocular Controlled Delivery System for Diclofenac Sodium.

    PubMed

    Jafariazar, Zahra; Jamalinia, Nasim; Ghorbani-Bidkorbeh, Fatemeh; Mortazavi, Seyed Alireza

    2015-01-01

    Diclofenac sodium as ophthalmic dosage form is used for the treatment of the pain, swelling and redness of patients' eyes recovering from cataract surgery; however, it faces the bioavailability limitation of eye drops due to effective protective mechanisms and corneal barrier functions in the eyes. Therefore, this investigation was aimed to develop ocular film formulations to achieve controlled drug release. Drug films were prepared using polymers, namely hydroxypropyl methylcellulose (HPMC) and polyvinyl pyrrolidone (PVP), Eudragit RL PO, and Eudragit RS PO by solvent casting method considering parameters such as drug: polymer ratio, different polymer combinations as well as plasticizer effect. Ocular films were evaluated for various physicochemical parameters such as physical characters, film thickness, uniformity of weight, drug content, swelling index, mucoadhesion time and in-vitro release study. Ocular films complied with all physicochemical parameters underwent in-vitro release study. Finally, the film formulation with HPMC: Eudragit RS PO 1:1 ratio, Drug: Polymer ratio 1:45 and glycerin as plasticizer showed controlled and prolonged release following the zero order and non-Fickian transport. PMID:26185502

  17. Formulation, optimization and in vitro-in vivo evaluation of febuxostat nanosuspension.

    PubMed

    Ahuja, Bhupesh K; Jena, Sunil K; Paidi, Sharan K; Bagri, Surbhi; Suresh, Sarasija

    2015-01-30

    The purpose of the present study was to develop febuxostat nanosuspension and investigate its effect on febuxostat solubility, dissolution rate and oral bioavailability. The wet media milling technique was adopted with a combination of hydroxypropyl methylcellulose (HPMC E3) and d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) as surface stabilizers for the generation of nanocrystals. Rotatable central composite design (CCD) was selected for nanosuspension optimization. The critical parameters were bead volume, milling time, polymer and surfactant concentrations; whereas particle size, polydispersity index (PDI) and zeta potential were taken as responses. The presence of crystallinity was confirmed by differential scanning calorimetry and powder X-ray diffraction. Scanning electron microscopy and transmission electron microscopy revealed small and uniform plate like morphology. A significant increase was observed in saturation solubility and dissolution rate of the optimized nanosuspension in all the pH conditions tested. Oral bioavailability of FXT and optimized FNC was evaluated in SD rats. The nanosuspension exhibited enhanced Cmax (26.48±2.71 vs. 19.85±2.96μg/mL) and AUC0-∞ (222.29±9.81 vs. 100.32±9.36μgh/mL) with a 221.6% increase in relative bioavailability. Thus, FNC is a viable approach to enhance the bioavailability of FXT, a BCS Class II drug. PMID:25490182

  18. Formulation and in vitro evaluation of salbutamol sulphate in situ gelling nasal inserts.

    PubMed

    Farid, Ragwa M; Etman, Mohamed A; Nada, Aly H; Ebian, Abd El Azeem R

    2013-06-01

    The aim of this study was to formulate salbutamol sulfate (SS), a model drug, as mucoadhesive in situ gelling inserts having a high potential as nasal drug delivery system bypassing the first-pass metabolism. In situ gelling inserts, each containing 1.4% SS and 2% gel-forming polymer, hydroxypropyl methylcellulose (HPMC), carboxymethylcellulose sodium (CMC Na), sodium alginate (AL), and chitosan (CH) were prepared. The inserts were investigated for their different physicochemical properties. The weight of inserts was 16-27 mg, drug content was 3.9-4.2 mg, thickness ranged between 15 and 28 μm and surface pH was 5-7. Cumulative drug released from the inserts exhibited extended release for more than 10 h following the decreasing order: CH>AL>CMC Na>HPMC. The drug release from CMC Na and AL inserts followed zero-order kinetics while HPMC and CH inserts exhibited non-Fickian diffusion mechanism. The inserts exhibited different water uptake (7-23%) with the smallest values for CH. Differential scanning calorimetry study pointed out possible interaction of SS and oppositely charged anionic polymers (CMC Na and AL). The mucoadhesive in situ gelling inserts exhibited satisfactory mucoadhesive and extended drug release characteristics. The inserts could be used for nasal delivery of SS over about 12 h; bypassing the hepatic first-pass metabolism without potential irritation. PMID:23516112

  19. Scintigraphic evaluation of colon targeting pectin-HPMC tablets in healthy volunteers.

    PubMed

    Hodges, L A; Connolly, S M; Band, J; O'Mahony, B; Ugurlu, T; Turkoglu, M; Wilson, C G; Stevens, H N E

    2009-03-31

    The in vivo evaluation of colon-targeting tablets was conducted in six healthy male volunteers. A pectin-hydroxypropyl methylcellulose coating was compressed onto core tablets labelled with 4MBq (99m)Tc-DTPA. The tablets released in the colon in all subjects; three in the ascending colon (AC) and three in the transverse colon (TC). Tablets that released in the TC had reached the AC before or just after food (Group A). The other three tablets released immediately upon AC entry at least 1.5h post-meal (Group B). Release onset for Group B was earlier than Group A (343min vs 448min). Group B tablets exhibited a clear residence period at the ileocaecal junction (ICJ) which was not observed in Group A. Prolonged residence at the ICJ is assumed to have increased hydration of the hydrogel layer surrounding the core tablet. Forces applied as the tablets progressed through the ICJ may have disrupted the hydrogel layer sufficiently to initiate radiolabel release. Conversely, Group A tablets moved rapidly through the AC to the TC, possibly minimising contact times with water pockets. Inadequate prior hydration of the hydrogel layer preventing access of pectinolytic enzymes and reduced fluid availability in the TC may have retarded tablet disintegration and radiolabel diffusion. PMID:19114096

  20. Molecular mobility in glassy dispersions.

    PubMed

    Mehta, Mehak; McKenna, Gregory B; Suryanarayanan, Raj

    2016-05-28

    Dielectric spectroscopy was used to characterize the structural relaxation in pharmaceutical dispersions containing nifedipine (NIF) and either poly(vinyl) pyrrolidone (PVP) or hydroxypropyl methylcellulose acetate succinate (HPMCAS). The shape of the dielectric response (permittivity versus log time) curve was observed to be independent of temperature. Thus, for the pure NIF as well as the dispersions, the validity of the time-temperature superposition principle was established. Furthermore, though the shape of the full dielectric response varied with polymer concentration, the regime related to the α- or structural relaxation was found to superimpose for the dispersions, though not with the response of the NIF itself. Hence, there is a limited time-temperature-concentration superposition for these systems as well. Therefore, in this polymer concentration range, calculation of long relaxation times in these glass-forming systems becomes possible. We found that strong drug-polymer hydrogen bonding interactions improved the physical stability (i.e., delayed crystallization) by reducing the molecular mobility. The strength of hydrogen bonding, structural relaxation time, and crystallization followed the order: NIF-PV P>NIF-HPMCAS>NIF. With an increase in polymer concentration, the relaxation times were longer indicating a decrease in molecular mobility. The temperature dependence of relaxation time, in other words fragility, was independent of polymer concentration. This is the first application of the superposition principle to characterize structural relaxation in glassy pharmaceutical dispersions. PMID:27250315

  1. Influence of enteric citric acid on the release profile of 4-aminopyridine from HPMC matrix tablets.

    PubMed

    Martínez González, Ilona; Villafuerte Robles, Leopoldo

    2003-01-30

    A weakly basic experimental drug, 4-aminopyridine (4-AP), was taken as a model to study the influence of enteric citric acid (ECA) on the release profile from hydroxypropyl methylcellulose (HPMC) matrices, to set up a system bringing about gradual release of the drug. For this purpose, powder mixtures were wet granulated with water and compressed with a hydraulic press at 55 MPa. Dissolution studies were made using first 900 ml HCl 0.1 N, and then phosphate buffer pH 7.4. Dissolution curves were described by M(t)/M(inf)=kt(n). As physically expected, increasing proportions (2-9%) of the in acid insoluble ECA decreased the release rate. In an acid medium, ECA acts as a physical barrier obstructing the diffusion path, dissolving after the pH change to 7.4. Both circumstances flattening the release profile. Apparent zero order release was observed at ECA concentrations of about 10%. The presence of ECA compensates the effect of decreased solubility of 4-AP at pH 7.4. Unexpectedly, higher ECA proportions (10-50%) act increasing the dissolution rate. This is attributed to a void space formation around the insoluble ECA, after HPMC hydration, which percolates after a critical ECA proportion of approximately 10%. Moreover, decreasing release constant values (k) show a logarithmic relationship with increasing values of the exponent (n). This indicates that an apparent zero-order release can be obtained at a given release constant. PMID:12527188

  2. Influence of enteric-coated lactose on the release profile of 4-aminopyridine from HPMC matrix tablets.

    PubMed

    Martínez-González, Ilona; Villafuerte-Robles, Leopoldo

    2004-01-01

    A weakly basic experimental drug, 4-aminopyridine, was taken as a model to study the influence of enteric-coated lactose (EL) on the release profile from hydroxypropyl methylcellulose matrices. Powder mixtures were wet-granulated with water. The dried granulation was compressed with a hydraulic press at 85 MPa. Dissolution studies were made using HCl 0.1 N and then phosphate buffer pH 7.4. Dissolution curves were described by M(t)/M(inf) = k*t(N). A trend toward increasing exponent (n) and decreasing release constant (k) values is observed with increasing EL concentrations up to 9%; this is attributed to an increasing obstruction of the diffusion path by isolated EL particles that are insoluble in HCl and are surrounded by a water-filled space. After a critical EL concentration, the water-filled spaces surrounding EL particles percolate, producing the opposite effect, increasing the release constant and decreasing the exponent (n) values as the EL proportion increases from 10% to 50%. EL particles (2% to 9%) decrease the drug and water transport in matrices dissolving in HCl. Thereafter, at pH 7.4, the pores formed by dissolution of EL particles produce the opposite. Both processes contribute to flattening the release profile. Release profiles with decreasing release constant values show a logarithmic trend toward increasing values of the exponent (n), changing from diffusion toward relaxation-erosion-controlled processes. PMID:15202573

  3. Influence of admixed citric acid on the release profile of pelanserin hydrochloride from HPMC matrix tablets.

    PubMed

    Espinoza, R; Hong, E; Villafuerte, L

    2000-05-25

    Pelanserin is a weakly basic experimental drug with a short half-life and a prolonged release formulation was developed using hydroxypropyl methylcellulose (HPMC) and citric acid to set up a system bringing about gradual release of this drug. For this purpose powder mixtures were wet granulated with water and compressed with a hydraulic press at 55 MPa. Dissolution studies were made using 900 ml HCl 0.1 N, the first 3 h, and phosphate buffer pH 7.4, h 3-8. Dissolution curves were described by M(t)/M(inf)=kt(n), applied separately for each dissolution medium. The dissolution mechanism involved a coupled diffusion/relaxation with a trend favoring the diffusion mechanism with increasing citric acid concentrations. Increasing concentrations of citric acid produced increasing values of the kinetic constants, in a cubic relationship. Higher HPMC proportions produced slower dissolution rates but with a citric acid compensating more clearly a decreased solubility of pelanserin at pH 7.4. Individually calculated dissolution curves showed experimental 8 h pelanserin dissolution in a range of 65-99% for matrices with 100 mg HPMC/tab., while those with 200 mg HPMC/tab. were in the range 57-73%. PMID:10878323

  4. Formulation and optimization of mucoadhesive buccal patches of losartan potassium by using response surface methodology

    PubMed Central

    Ikram, Md.; Gilhotra, Neeraj; Gilhotra, Ritu Mehra

    2015-01-01

    Background: This study was undertaken with an aim to systematically design a model of factors that would yield an optimized sustained release dosage form of an anti-hypertensive agent, losartan potassium, using response surface methodology (RSM) by employing 32 full factorial design. Materials and Methods: Mucoadhesive buccal patches were prepared using different grades of hydroxypropyl methylcellulose (HPMC) (K4M and K100M) and polyvinylpyrrolidone-K30 by solvent casting method. The amount of the release retardant polymers – HPMC K4M (X1) and HPMC K100M (X2) was taken as an independent variable. The dependent variables were the burst release in 30 min (Y1), cumulative percentage release of drug after 8 h (Y2) and swelling index (Y3) of the patches. In vitro release and swelling studies were carried out and the data were fitted to kinetic equations. Results: The physicochemical, bioadhesive, and swelling properties of patches were found to vary significantly depending on the viscosity of the polymers and their combination. Patches showed an initial burst release preceding a more gradual sustained release phase following a nonfickian diffusion process. Discussion: The results indicate that suitable bioadhesive buccal patches with desired permeability could be prepared, facilitated with the RSM. PMID:26682205

  5. Modulated dissolution rate from the inclusion complex of antichagasic benznidazole and cyclodextrin using hydrophilic polymer.

    PubMed

    Sá-Barreto, Lívia C L; Gustmann, Pricila C; Garcia, Felipe S; Maximiano, Flávia P; Novack, Kátia M; Cunha-Filho, Marcílio S S

    2013-01-01

    Benznidazole (BNZ) is the primary chemotherapeutic agent for treating Chagas' disease; however, its poor water solubility and irregular oral absorption lead to the treatment failure in the chronic phase. The aim of this work was to investigate the utility of the polymer hydroxypropyl methylcellulose (HPMC) in controlling the release of BNZ from solid inclusion complexes with cyclodextrin to overcome the problem of its bioavailability. Preliminary studies of solubility were conducted in solution using selected β-cyclodextrin derivatives according to an experimental mixture design. The best cyclodextrin composition was used to produce solid-state systems by kneading in the presence or absence of HPMC. The formulations were characterized by different physico-chemical techniques, including the dissolution rate. Hydroxypropyl-β-cyclodextrin (HPβCD) produced the greatest improvement in drug solubility and was selected for the development of solid systems. Assays confirmed the production of true inclusion complexes between BNZ and HPβCD. The dissolution rate of the BNZ-HPβCD system was markedly increased, while the presence of HPMC retarded drug release. An optimal formulation obtained by the combination of kneading systems developed in appropriate ratios could be a promising drug delivery system with a prolonged therapeutic effect coupled with more balanced bioavailability. The produced systems present interesting perspectives for Chagas' therapy. PMID:22200091

  6. Molecular mobility in glassy dispersions

    NASA Astrophysics Data System (ADS)

    Mehta, Mehak; McKenna, Gregory B.; Suryanarayanan, Raj

    2016-05-01

    Dielectric spectroscopy was used to characterize the structural relaxation in pharmaceutical dispersions containing nifedipine (NIF) and either poly(vinyl) pyrrolidone (PVP) or hydroxypropyl methylcellulose acetate succinate (HPMCAS). The shape of the dielectric response (permittivity versus log time) curve was observed to be independent of temperature. Thus, for the pure NIF as well as the dispersions, the validity of the time-temperature superposition principle was established. Furthermore, though the shape of the full dielectric response varied with polymer concentration, the regime related to the α- or structural relaxation was found to superimpose for the dispersions, though not with the response of the NIF itself. Hence, there is a limited time-temperature-concentration superposition for these systems as well. Therefore, in this polymer concentration range, calculation of long relaxation times in these glass-forming systems becomes possible. We found that strong drug-polymer hydrogen bonding interactions improved the physical stability (i.e., delayed crystallization) by reducing the molecular mobility. The strength of hydrogen bonding, structural relaxation time, and crystallization followed the order: NIF-PV P>NIF-HPMCAS>NIF. With an increase in polymer concentration, the relaxation times were longer indicating a decrease in molecular mobility. The temperature dependence of relaxation time, in other words fragility, was independent of polymer concentration. This is the first application of the superposition principle to characterize structural relaxation in glassy pharmaceutical dispersions.

  7. Transdermal delivery system for zidovudine: in vitro, ex vivo and in vivo evaluation.

    PubMed

    Narishetty, Sunil Thomas Kumar; Panchagnula, Ramesh

    2004-01-01

    The objective of this study was to prepare a transdermal delivery system (TDS) for zidovudine (AZT) with a combination of menthol and oleic acid as penetration enhancers incorporated in hydroxypropyl methylcellulose, and to evaluate ex vivo as well as in vivo permeation across rat skin. It was found that AZT in gel formulation was stable in both refrigerated as well as accelerated stability conditions for 3 months and further, the gel did not significantly retard the permeability of AZT across the skin in comparison with solution formulation. Ex vivo steady state flux of AZT across rat skin from gel was 2.26 mg cm(-2) h(-1), which is sufficient to achieve therapeutic plasma concentrations. Intravenous pharmacokinetic parameters of AZT in rats were determined and used together with ex vivo flux data to generate theoretical plasma profiles of AZT and compared with plasma concentrations achieved after application of TDS. Further, steady state plasma concentrations of drug following multiple applications of TDS were determined and good correlations between ex vivo and in vivo data were observed. In addition, the combination of penetration enhancers used at 2.5% w/w in this study proved efficient in achieving sufficient enhancement in the transdermal permeability of AZT across rat skin with reduced skin irritation potential when compared with individual penetration enhancers at higher concentrations. PMID:14716748

  8. Design and Evaluation of Ocular Controlled Delivery System for Diclofenac Sodium

    PubMed Central

    Jafariazar, Zahra; Jamalinia, Nasim; Ghorbani-Bidkorbeh, Fatemeh; Mortazavi, Seyed Alireza

    2015-01-01

    Diclofenac sodium as ophthalmic dosage form is used for the treatment of the pain, swelling and redness of patients’ eyes recovering from cataract surgery; however, it faces the bioavailability limitation of eye drops due to effective protective mechanisms and corneal barrier functions in the eyes. Therefore, this investigation was aimed to develop ocular film formulations to achieve controlled drug release. Drug films were prepared using polymers, namely hydroxypropyl methylcellulose (HPMC) and polyvinyl pyrrolidone (PVP), Eudragit RL PO, and Eudragit RS PO by solvent casting method considering parameters such as drug: polymer ratio, different polymer combinations as well as plasticizer effect. Ocular films were evaluated for various physicochemical parameters such as physical characters, film thickness, uniformity of weight, drug content, swelling index, mucoadhesion time and in-vitro release study. Ocular films complied with all physicochemical parameters underwent in-vitro release study. Finally, the film formulation with HPMC: Eudragit RS PO 1:1 ratio, Drug: Polymer ratio 1:45 and glycerin as plasticizer showed controlled and prolonged release following the zero order and non-Fickian transport. PMID:26185502

  9. Fast drying of biocompatible polymer films loaded with poorly water-soluble drug nano-particles via low temperature forced convection.

    PubMed

    Susarla, Ramana; Sievens-Figueroa, Lucas; Bhakay, Anagha; Shen, Yueyang; Jerez-Rozo, Jackeline I; Engen, William; Khusid, Boris; Bilgili, Ecevit; Romañach, Rodolfo J; Morris, Kenneth R; Michniak-Kohn, Bozena; Davé, Rajesh N

    2013-10-15

    Fast drying of nano-drug particle laden strip-films formed using water-soluble biocompatible polymers via forced convection is investigated in order to form films having uniform drug distribution and fast dissolution. Films were produced by casting and drying a mixture of poorly water soluble griseofulvin (GF) nanosuspensions produced via media milling with aqueous hydroxypropyl methylcellulose (HPMC E15LV) solutions containing glycerin as a plasticizer. The effects of convective drying parameters, temperature and air velocity, and film-precursor viscosity on film properties were investigated. Two major drying regimes, a constant rate period as a function of the drying conditions, followed by a single slower falling rate period, were observed. Films dried in an hour or less without any irreversible aggregation of GF nanoparticles with low residual water content. Near-infrared chemical imaging (NIR-CI) and the content uniformity analysis indicated a better drug particle distribution when higher viscosity film-precursors were used. Powder X-ray diffraction showed that the GF in the films retained crystallinity and the polymorphic form. USP IV dissolution tests showed immediate release (~20 min) of GF. Overall, the films fabricated from polymer-based suspensions at higher viscosity dried at different conditions exhibited similar mechanical properties, improved drug content uniformity, and achieved fast drug dissolution. PMID:23911341

  10. Water-mediated solid-state transformation of a polymorphic drug during aqueous-based drug-layer coating of pellets.

    PubMed

    Lust, Andres; Lakio, Satu; Vintsevits, Julia; Kozlova, Jekaterina; Veski, Peep; Heinämäki, Jyrki; Kogermann, Karin

    2013-11-01

    During aqueous drug-layer coating, drug substance(s) are exposed to water and elevated temperatures which can lead to water-mediated process induced transformations (PITs). The effects of aqueous drug-layer coating of pellets (Cellets(®)) on the anhydrous piroxicam, PRX, were investigated in the miniaturized coating equipment and with free films. Hydroxypropyl methylcellulose (HPMC) was used as a carrier coating polymer. Free films were prepared by using an in-house small-scale rotating plate system equipped with an atomization air nozzle. Raman spectroscopy, X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) were used to characterize the solid-state properties and surface morphology of the pellets and free films. The results showed that anhydrous PRX form I (AH) and monohydrate (MH) were stable during drug-layer coating, but amorphous PRX in solid dispersion (SD) crystallized as MH already after 10 min of coating. Furthermore, the increase in a dissolution rate was achieved from the drug-layer coated inert pellets compared to powder forms. In conclusion, water-mediated solid-state PITs of amorphous PRX is evident during aqueous-based drug-layer coating of pellets, and solid-state change can be verified using Raman spectroscopy. PMID:23994016

  11. Pharmaceutical and pharmacokinetic evaluation of a novel fast dissolving film formulation of flupentixol dihydrochloride.

    PubMed

    Abdelbary, Ahmed; Bendas, Ehab R; Ramadan, Afaf A; Mostafa, Dalia A

    2014-12-01

    The objective of the present study was to develop fast dissolving oral film of the antipsychotic drug, flupentixol dihydrochloride, to enhance its bioavailability, optimize its therapeutic effect when used to treat depression with anxiety, and increase the convenience and compliance by the mentally ill, developmentally disable, elderly, and pediatric patients. Six formulae were prepared with different concentrations of water-soluble polymers vis. hydroxypropyl methylcellulose (HPMC E5) and carboxymethyl cellulose (CMC) by solvent casting technique. The prepared films were subjected to characterization for folding endurance, weight variations, thickness, disintegration time, drug release pattern, and drug content. Physical compatibility between the drug and excipients was guaranteed in the selected formulation (2% HPMC) by means of differential scanning calorimetry analysis and Fourier-transform infrared spectroscopy. This formulation revealed high stability after testing according to the International Conference on Harmonisation guidelines. In vivo studies based on single phase parallel design were carried out for the optimized formulation in healthy human volunteers. The concentration of flupentixol dihydrochloride in plasma samples was analyzed by a developed validated LC-MS/MS assay method and the pharmacokinetic parameters of the established formulation were compared with the commercially available oral tablets. Faster rate of absorption of flupentixol could be obtained from the oral film formulation and the relative bioavailability was found to be 151.06% compared to the marketed product. PMID:25142820

  12. Development of matrix controlled transdermal delivery systems of pentazocine: In vitro/in vivo performance.

    PubMed

    Prasad Verma, Priya Ranjan; Chandak, Ashok R

    2009-06-01

    The present study aimed to develop hydroxypropyl methylcellulose based transdermal delivery of pentazocine. In formulations containing lower proportions of polymer, the drug released followed the Higuchi kinetics while, with an increase in polymer content, it followed the zero-order release kinetics. Release exponent (n) values imply that the release of pentazocine from matrices was non-Fickian. FT-IR, DSC and XRD studies indicated no interaction between drug and polymer.The in vitro dissolution rate constant, dissolution half-life and pharmacokinetic parameters (C(max), t(max), AUC(s), t(1/2), Kel, and MRT) were evaluated statistically by two-way ANOVA. A significant difference was observed between but not within the tested products. Statistically, a good correlation was found between per cent of drug absorbed from patches vs. C(max) and AUC(s). A good correlation was also observed when per cent drug released was correlated with the blood drug concentration obtained at the same time point. The results of this study indicate that the polymeric matrix films of pentazocine hold potential for transdermal drug delivery. PMID:19564142

  13. Newly Developed Topical Cefotaxime Sodium Hydrogels: Antibacterial Activity and In Vivo Evaluation

    PubMed Central

    Zakaria, Azza S.; Afifi, Samar A.; Elkhodairy, Kadria A.

    2016-01-01

    In an attempt to reach better treatment of skin infections, gel formulations containing Cefotaxime (CTX) were prepared. The gel was formulated using Carbopol 934 (C934), Hydroxypropyl Methylcellulose 4000 (HPMC 4000), Carboxymethylcellulose Sodium (Na CMC), Pectin (PEC), Xanthan Gum (XG), or Guar Gum (GG). Thirteen different formulas were prepared and characterized physically in terms of color, syneresis, spreadability, pH, drug content, and rheological properties. Drug-excipients compatibility studies were confirmed by FTIR and then in vitro drug release study was conducted. In vitro and in vivo antibacterial activities of CTX were studied against wound pathogens such as, Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and Pseudomonas aeruginosa (P. aeruginosa), using either pure drug or Fucidin® cream as control. F13 provides better spreadability compared to F1 (XG) or F11 (HPMC). Moreover, the release of the drug from hydrogel F13 containing C934 was slower and sustained for 8 h. Stability study revealed that, upon storage, there were no significant changes in pH, drug content, and viscosity of the gels. Also, F13 showed the larger inhibition zone and highest antibacterial activity among other formulations. Histological analysis demonstrated that after single treatment with F13 gel formulation, a noticeable reduction in microbial bioburden occurred in case of both Gram positive and Gram negative bacterial isolates. PMID:27314033

  14. Isolation of Murine Embryonic Hemogenic Endothelial Cells.

    PubMed

    Fang, Jennifer S; Gritz, Emily C; Marcelo, Kathrina L; Hirschi, Karen K

    2016-01-01

    The specification of hemogenic endothelial cells from embryonic vascular endothelium occurs during brief developmental periods within distinct tissues, and is necessary for the emergence of definitive HSPC from the murine extra embryonic yolk sac, placenta, umbilical vessels, and the embryonic aorta-gonad-mesonephros (AGM) region. The transient nature and small size of this cell population renders its reproducible isolation for careful quantification and experimental applications technically difficult. We have established a fluorescence-activated cell sorting (FACS)-based protocol for simultaneous isolation of hemogenic endothelial cells and HSPC during their peak generation times in the yolk sac and AGM. We demonstrate methods for dissection of yolk sac and AGM tissues from mouse embryos, and we present optimized tissue digestion and antibody conjugation conditions for maximal cell survival prior to identification and retrieval via FACS. Representative FACS analysis plots are shown that identify the hemogenic endothelial cell and HSPC phenotypes, and describe a methylcellulose-based assay for evaluating their blood forming potential on a clonal level. PMID:27341393

  15. A novel solubilization technique for poorly soluble drugs through the integration of nanocrystal and cocrystal technologies.

    PubMed

    Karashima, Masatoshi; Kimoto, Kouya; Yamamoto, Katsuhiko; Kojima, Takashi; Ikeda, Yukihiro

    2016-10-01

    The aim of the present study was to develop a novel solubilization technique consisting of a nano-cocrystal suspension by integrating cocrystal and nanocrystal formulation technologies to maximize solubilization over current solubilizing technologies. Monodisperse carbamazepine-saccharin, indomethacin-saccharin, and furosemide-caffeine nano-cocrystal suspensions, as well as a furosemide-cytosine nano-salt suspension, were successfully prepared with particle sizes of less than 300nm by wet milling with the stabilizers hydroxypropyl methylcellulose and sodium dodecyl sulfate. Interestingly, the properties of resultant nano-cocrystal suspensions were dramatically changed depending on the physicochemical and structural properties of the cocrystals. In the formulation optimization, the concentration and ratio of the stabilizers also influenced the zeta potentials and particles sizes of the resultant nano-cocrystal suspensions. Raman spectroscopic analysis revealed that the crystalline structures of the cocrystals were maintained in the nanosuspensions, and were physically stable for at least one month. Furthermore, their dissolution profiles were significantly improved over current solubilization-enabling technologies, nanocrystals, and cocrystals. In the present study, we demonstrated that nano-cocrystal formulations can be a new promising option for solubilization techniques to improve the absorption of poorly soluble drugs, and can expand the development potential of poorly soluble candidates in the pharmaceutical industry. PMID:27393561

  16. Transmucosal delivery of metformin- a comprehensive study.

    PubMed

    Sushma, M; Raju, Y Prasanna; Sundaresan, C R; Vandana, K R; Kumar, N Vijay; Chowdary, V Harini

    2014-01-01

    Discovered in the 1920s, the biguanide metformin hydrochloride is still the first line drug in the management of Type 2 diabetes mellitus. Metformin hydrochloride is absorbed slowly and incompletely from the gastrointestinal tract. The present research work was undertaken with the aim of developing a fast dissolving film of metformin hydrochloride, suitable for oral trans mucosal administration. Fast dissolving films allow rapid drug dissolution in the oral cavity, ensuring bypass of first pass metabolism resulting in rapid absorption. Films of metformin were prepared by solvent casting method using Hydroxypropyl methylcellulose K15 (HPMC). Six formulations (F1-F6) of metformin hydrochloride were prepared and evaluated for their physical characteristics such as tackiness, thickness, tensile strength, elongation, weight variation, folding endurance, drug content and surface pH. The compatibility of the drug with HPMC was confirmed by FTIR studies. The formulations were subjected to disintegration, in-vitro drug release and the optimised formulation was evaluated for pharmacodynamic studies in diabetic rats. Among the formulations (F1-F6) F4 was found to be the best formulation which contained Hydroxypropyl methyl cellulose K15 at weight ratios of 1:4 and showed excellent film forming characteristics such as disintegration time at 42 sec and percentage drug release of 94.2% within 5 minutes. Pharmacodynamic assessment in diabetes induced rats demonstrated that the fast dissolving films of metformin had a quicker onset of action compared to conventional formulation. PMID:23848354

  17. Stability of dry coated solid dosage forms.

    PubMed

    Kablitz, Caroline Désirée; Urbanetz, Nora Anne

    2009-01-01

    The dry coating process was evaluated in terms of storage stability investigating drug release and agglomeration tendency of the different coated oral dosage forms; hydroxypropyl methylcellulose acetate succinate (HPMCAS) was used with triethylcitrate (TEC) as plasticizer and acetylated monoglyceride (Myvacet) as wetting agent. Talc or colloidal silicon dioxide (Aerosil) was used as anti-tacking agents. In contrast to coating formulations consisting of HPMCAS and Myvacet all formulations containing TEC showed enteric resistance and no agglomeration tendency after preparation. After storage at 10% RH +/- 5% enteric resistance is increased slightly. This increase is more pronounced at 60% RH +/- 5%. The formulations without anti-tacking agents showed higher drug releases after 12 and 24 months due to the damage of the film's integrity during sample preparation caused by the high tackiness of the film. Tackiness is not affected by storing if samples are stored at low relative humidity. At high relative humidity tackiness increases upon storage especially for formulations without anti-tacking agents. The sieving results of the agglomeration measurements after storage can be confirmed by ring shear measurements performed immediately after preparation and approved to be a tool, which is able to predict the agglomeration during storage. PMID:19883250

  18. Enhanced physical stabilization of fenofibrate nanosuspensions via wet co-milling with a superdisintegrant and an adsorbing polymer.

    PubMed

    Azad, Mohammad; Afolabi, Afolawemi; Bhakay, Anagha; Leonardi, Jonathan; Davé, Rajesh; Bilgili, Ecevit

    2015-08-01

    Drug nanoparticles in suspensions can form aggregates leading to physical instability, which is traditionally mitigated using soluble polymers and surfactants. The aim of this paper was to explore common superdisintegrants, i.e., sodium starch glycolate (SSG), croscarmellose sodium (CCS), and crospovidone (CP), as novel class of dispersants for enhanced stabilization of fenofibrate (FNB), a model BCS Class II drug, suspensions. FNB was wet-milled with superdisintegrants along with hydroxypropyl methylcellulose (HPMC), a soluble adsorbing polymer, in a stirred media mill. For comparison, FNB was also milled in the presence of HPMC and/or SDS (sodium dodecyl sulfate) without superdisintegrants. Laser diffraction, scanning electron microscopy, viscometry, differential scanning calorimetry, and powder X-ray diffraction were used to characterize the suspensions. The results show that 2% HPMC along with 1% SSG or 1% CCS mitigated the aggregation of FNB nanoparticles significantly similar to the use of either 5% HPMC or 1% HPMC-0.075% SDS, whereas CP was not effective due to its low swelling capacity. CCS/SSG enhanced steric-kinetic stabilization of the FNB suspensions owing to their high swelling capacity, viscosity enhancement, and physical barrier action. Overall, this study provides a mechanistic basis for a novel method of formulating surfactant-free drug nanosuspensions with co-milled superdisintegrants. PMID:26079832

  19. Development and evaluation of in situ gel of pregabalin

    PubMed Central

    Madan, Jyotsana R; Adokar, Bhushan R; Dua, Kamal

    2015-01-01

    Aim and Background: Pregabalin (PRG), an analog of gamma-aminobutyric acid, reduces the release of many neurotransmitters, including glutamate, and noradrenaline. It is used for the treatment of epilepsy; simple and complex partial convulsion. The present research work aims to ensure a high drug absorption by retarding the advancement of PRG formulation through the gastrointestinal tract. The work aims to design a controlled release PRG formulation which is administered as liquid and further gels in the stomach and floats in gastric juice. Materials and Methods: In situ gelling formulations were prepared using sodium alginate, calcium chloride, sodium citrate, hydroxypropyl methylcellulose (HPMC) K100M, and sodium bicarbonate. The prepared formulations were evaluated for solution viscosity, drug content, in vitro gelling studies, gel strength, and in vitro drug release. The final formulation was optimized using a 32 full factorial design. Results: The formulation containing 2.5% w/v sodium alginate and 0.2% w/v calcium chloride were considered optimum since it showed minimum floating lag time (18 s), optimum viscosity (287.3 cps), and gel strength (4087.17 dyne/cm2). The optimized formulation follows Korsmeyer-Peppas kinetic model with n value 0.3767 representing Fickian diffusion mechanism of drug release. Conclusion: Floating in situ gelling system of PRG can be formulated using sodium alginate as a gelling polymer and calcium chloride as a complexing agent to control the drug release for about 12 h for the treatment of epilepsy. PMID:26682193

  20. Development and Characterization of In Situ Oral Gel of Spiramycin

    PubMed Central

    Sharma, Avinash; Sharma, Jyoti; Kaur, Rupinder; Saini, Vinay

    2014-01-01

    The present investigation deals with the optimization, formulation, and characterization of oral in situ gel of spiramycin. Sodium alginate and hydroxypropyl methylcellulose were used as cross-linking and viscosifying agents, respectively. Sodium bicarbonate was used as a floating agent. In preformulation studies, the melting point, pH, and partition coefficient were found to be 133°C, 9.5, and 0.193, respectively. The drug had retention time at around 2.65 minutes in high performance liquid chromatography (HPLC). During compatibility studies of drug with all polymers, we observed that there were no changes in the FTIR spectra of a mixture of drug and polymers. All the formulations showed good pourability. Floating time and total floating time were ~30 sec and >12 hours, respectively. During in vitro drug release studies, the drug was released from the formulation around 80–100% for 12–16 hrs. In TEM analysis, we found that the drug molecules were well entrapped in the polymer and the drug was released slowly for up to 12 hrs. In these studies, we found that the concentration of sodium alginate and HPMC had significant influence on floating lag time, gelling capacity, and cumulative percentage drug release. During antimicrobial studies, we found that the formulation containing spiramycin showed good zone of inhibition against different microbial strains (Staphylococcus aureus and Escherichia coli). PMID:25050376

  1. Design, Development and Optimization of S (-) Atenolol Floating Sustained Release Matrix Tablets Using Surface Response Methodology

    PubMed Central

    Gunjal, P. T.; Shinde, M. B.; Gharge, V. S.; Pimple, S. V.; Gurjar, M. K.; Shah, M. N.

    2015-01-01

    The objective of this present investigation was to develop and formulate floating sustained release matrix tablets of s (-) atenolol, by using different polymer combinations and filler, to optimize by using surface response methodology for different drug release variables and to evaluate the drug release pattern of the optimized product. Floating sustained release matrix tablets of various combinations were prepared with cellulose-based polymers: Hydroxypropyl methylcellulose, sodium bicarbonate as a gas generating agent, polyvinyl pyrrolidone as a binder and lactose monohydrate as filler. The 32 full factorial design was employed to investigate the effect of formulation variables on different properties of tablets applicable to floating lag time, buoyancy time, % drug release in 1 and 6 h (D1 h,D6 h) and time required to 90% drug release (t90%). Significance of result was analyzed using analysis of non variance and P < 0.05 was considered statistically significant. S (-) atenolol floating sustained release matrix tablets followed the Higuchi drug release kinetics that indicates the release of drug follows anomalous (non-Fickian) diffusion mechanism. The developed floating sustained release matrix tablet of improved efficacy can perform therapeutically better than a conventional tablet. PMID:26798171

  2. Preparation and Characterization of a Gastric Floating Dosage Form of Capecitabine

    PubMed Central

    Taghizadeh Davoudi, Ehsan; Ibrahim Noordin, Mohamed; Kadivar, Ali; Kamalidehghan, Behnam; Farjam, Abdoreza Soleimani; Akbari Javar, Hamid

    2013-01-01

    Gastrointestinal disturbances, such as nausea and vomiting, are considered amongst the main adverse effects associated with oral anticancer drugs due to their fast release in the gastrointestinal tract (GIT). Sustained release formulations with proper release profiles can overcome some side effects of conventional formulations. The current study was designed to prepare sustained release tablets of Capecitabine, which is approved by the Food and Drug Administration (FDA) for the treatment of advanced breast cancer, using hydroxypropyl methylcellulose (HPMC), carbomer934P, sodium alginate, and sodium bicarbonate. Tablets were prepared using the wet granulation method and characterized such that floating lag time, total floating time, hardness, friability, drug content, weight uniformity, and in vitro drug release were investigated. The sustained release tablets showed good hardness and passed the friability test. The tablets' floating lag time was determined to be 30–200 seconds, and it floated more than 24 hours and released the drug for 24 hours. Then, the stability test was done and compared with the initial samples. In conclusion, by adjusting the right ratios of the excipients including release-retarding gel-forming polymers like HPMC K4M, Na alginate, carbomer934P, and sodium bicarbonate, sustained release Capecitabine floating tablet was formulated. PMID:24288681

  3. Composite alginate hydrogel microparticulate delivery system of zidovudine hydrochloride based on counter ion induced aggregation

    PubMed Central

    Roy, Harekrishna; Rao, P. Venkateswar; Panda, Sanjay Kumar; Biswal, Asim Kumar; Parida, Kirti Ranjan; Dash, Jharana

    2014-01-01

    Aim: The present study deals with preparation of zidovudine loaded microparticle by counter ion induced aggregation method. During this study effect of polyacrylates and hypromellose polymers on release study were investigated. Materials and Methods: The ion induced aggregated alginate based microparticles were characterized for surface morphology, particle size analysis, drug entrapment study, in-vitro study, Fourier-transform infrared (FTIR) spectroscopy, and differential scanning calorimetry (DSC) study. Results and Discussion: The result showed Eudragit RL-100 (ERL) based formulations had smoother surface as well as their mean particle sizes were found greater compared with Eudragit RS-100 (ERS) microparticles. Furthermore, drug entrapments were found to be more in ERL formulae as compared with ERS. RL3 released 101.05% drug over a period of 8th h and followed Higuchi profile and Fickian diffusion. Moreover, data obtained illustrated that, higher amount of quaternary ammonium group, alkali value, and glass transition temperature may be possible reason for improving permeability of ERL based formulations. It was also noticed, hyroxypropyl methylcellulose (HPMC) K4M premium grade polymer sustained drug release more than HPMC K15M. In addition, drug-excipient interaction study was carried out by FTIR and DSC study. PMID:25298940

  4. Formulation and Evaluation of Controlled Release Floating Microballoons of Stavudine

    PubMed Central

    Vidyadhara, Suryadevara; Sasidhar, Reddyvalam Lankapalli; Balakrishna, Talamanchi; Balaji, Boyapati; Amrutha, Ravi

    2015-01-01

    The aim of this study was to formulate and evaluate stavudine floating microballoons for controlled drug release. Initially, the drug-loaded low-density granular pellets were prepared with hydroxypropyl methylcellulose E5 grade and by using isopropyl alcohol as a granulating fluid. Further, the low-density granular pellets were subjected to microencapsulation by an emulsion evaporation technique using ethyl cellulose 7 cps and Eudragit S 100 as coating polymers and 1% w/v polyethylene glycol 400 as aqueous phase. The prepared microballoons were characterized for their particle size analysis, angle of repose, and compressibility index. The in vitro release studies were performed in 0.1 N HCl as medium. The prepared microballoons were free-flowing and spherical in shape. From all the formulations, F5E and F5F can be considered as promising controlled release floating microballoons of stavudine providing first-order release over a period of 12 hours, with a minimum floating lag time of 1 minute. It was found that the ratio of the drug & polymer, stirring speed, and concentration of surfactant were the most significant variables which influenced the size of the stavudine microballoons under the applied experimental conditions. PMID:26839847

  5. Floating matrix dosage form for propranolol hydrochloride based on gas formation technique: development and in vitro evaluation.

    PubMed

    Chaturvedi, Kiran; Umadevi, S; Vaghani, Subhash

    2010-01-01

    Gastroretentive tablets of propranolol hydrochloride were developed by direct compression method using citric acid and sodium bicarbonate as the effervescent base. Hydroxypropyl methylcellulose; HPMC K15M was used to prepare the floating tablets to retard the drug release for 12h in stomach. Na-carboxymethyl cellulose (NaCMC) or carbopol 934P was added to alter the drug release profile or the dimensional stability of the formulation. Dicalcium phosphate (DCP) was used as filler. Formulations were evaluated for floating lag time, duration of floating, dimensional stability, drug content and in vitro drug release profile. The formulations were found to have floating lag time less than 1min. It was found that the dimensional stability of the formulations increase with increasing concentration of the swelling agent. The release mechanism of propranolol hydrochloride from floating tablets was evaluated on the basis of Peppas and Higuchi model. The ânâ value of the formulations ranged from 0.5201 to 0.7367 (0.5

  6. Novel sustained release and swellable gastroretentive dosage form for ciprofloxacin hydrochloride

    PubMed Central

    Gaikwad, Vinay Dhananjay; Yadav, Vishal Dadasaheb; Gaikwad, Manish Dhananjay

    2014-01-01

    Introduction: The present study aims at developing a gastroretentive swellable and floating matrix tablet formulation of ciprofloxacin hydrochloride (HCl) for the effective treatment of infections caused by susceptible organisms. Ciprofloxacin HCl is a fluoroquinoline antibiotic drug. Ciprofloxacin HCl is more stable in acidic medium and it has a narrow absorption window which is sited at the stomach and proximal portions of the small intestine, so it covers the required criteria for selection of drug for gastroretentive dosage form. Materials and Methods: Ciprofloxacin HCl gastroretentive tablets were formulated by using direct compression method and different grades of hydroxypropyl methylcellulose as suspending and stabilizing agent (polymer), sodium starch glycolate (SSG), crospovidone as disintegrates, sodium bicarbonate as alkalizing agent and magnesium stearate as lubricant. Results: The tablets were evaluated for post compression parameters. All the parameters were within the pharmacopoeial limits. Conclusion: The in vitro dissolution studies showed that the drug release was fast in formulations F2, F4 and F6 containing SSG as super disintegrant when compared with all other formulations. In SEM study of F2 formulation shows maximum swelling and porosity observed after 12 h. Hence, formulation F2 shows the best formulation among the six formulations containing different binders and super disintegrants. PMID:25006553

  7. Porous carrier based floating granular delivery system of repaglinide.

    PubMed

    Jain, Sunil K; Agrawal, Govind P; Jain, Narendra K

    2007-04-01

    A floating granular delivery system consisting of calcium silicate (CS) as porous carrier; repaglinide (Rg), an oral hypoglycemic agent; and hydroxypropyl methylcellulose K4M (HPMC K4M), ethyl cellulose (EC) and carbopol 940 (CP940) as matrix forming polymers was prepared and evaluated for its gastro-retentive and controlled release properties. The effect of various formulation and process variables on the particle morphology, micromeritic properties, in vitro floating behavior, drug content (%) and in vitro drug release was studied. The transit of floating granules of optimized formulation in the gastrointestinal (GI) tract was monitored by gamma scintigraphy in albino rabbits. The optimized formulation was compared in vivo with lactose granules (RgSCLG) prepared from identical polymers with their optimized composition ratio. Repaglinide-loaded optimized formulation was orally administered to albino rabbits and blood samples collected were used to determine pharmacokinetic parameters of Rg from floating granular formulation. Results were compared with pharmacokinetic parameters of marketed tablet formulation of Rg. The optimized formulation (RgSCG4) demonstrated favorable in vitro floating and release characteristics. Prolonged gastric residence time (GRT) of over 6 hr was achieved in all subjects for calcium silicate based floating granules of Rg. The relative bioavailability of Rg-loaded floating granules increased 3.8-fold in comparison to that of its marketed capsule. The designed system, combining excellent buoyant ability and suitable drug release pattern, offered clear advantages in terms of increased bioavailability of repaglinide. PMID:17523003

  8. Controlled growth and applications of complex metal oxide ZnSn(OH)6 polyhedra.

    PubMed

    Yin, Jingzhou; Gao, Feng; Wei, Chengzhen; Lu, Qingyi

    2012-10-15

    We successfully controlled the crystallographic surface of ZnSn(OH)(6) crystals and systematically obtained ZnSn(OH)(6) crystals in different shapes including cubes, truncated cubes, cuboctahedrons, truncated octahedrons, and octahedrons using a simple solvothermal method in a methylcellulose (MC) ethanol/water solution. By simply adjusting the amount of the NaOH solution added to the reaction system, we observed the shape evolution of ZnSn(OH)(6) particles from cube to octahedron, with the sizes gradually increasing from about 200 nm to 1-2 μm. These results not only provide ZnSn(OH)(6) polyhedra bound by different lattice planes, but also make it possible to investigate the morphology-property relationship of ZnSn(OH)(6) particles with different morphologies obtained under similar conditions. The antibacterial activities of the as-prepared ZnSn(OH)(6) polyhedral particles were studied. It was found that the antibacterial activities of ZnSn(OH)(6) particles against Escherichia coli depend on the shape of the ZnSn(OH)(6) particles, demonstrating that the surface structure of nanocrystals affects the antibacterial activity. Additionally, the obtained ZnSn(OH)(6) polyhedra can be applied as precursors for Zn(2)SnO(4)/SnO(2) composites with different morphologies by calcining at 600 °C. PMID:23030801

  9. The in vitro and in vivo effects of a fast-dissolving mucoadhesive bi-layered strip as topical anesthetics.

    PubMed

    Roh, Jiyeon; Han, Mira; Kim, Kyoung-Nam; Kim, Kwang-Mahn

    2016-01-01

    To overcome pain on injection, the dentist can apply a topical anesthetic spray. Despite the convenience, it is not easy to apply it locally. So, we developed an oral mucoadhesive bi-layer film containing an anesthetic. We used polyvinylpyrrolidone (PVP)/hydroxypropyl methylcellulose (HPMC) and HPMC-only layer as the drug-containing layer and ethyl cellulose (EC) as the backing layer. The lidocaine released was tested in vitro together with the adhesion time and cytotoxicity of the film. Mucosa permeability was tested in vivo. Statistical analysis was performed, with p at 0.05 taken to be significant. The lidocaine was released significantly faster in the PVP/HPMC than HPMC-only group and 80% of the drug was released within 1 min (p<0.05) and they attached at least 3 h. The test groups showed no toxicity and the drug effectively permeated the mucosa (p<0.05). We suggest this new mucoadhesive anesthetic may reduce dental phobia. PMID:27477225

  10. A three dimensional anchorage independent in vitro system for the prolonged growth of embryoid bodies to study cancer cell behaviour and anticancer agents.

    PubMed

    Fong, Chui-Yee; Chak, Li-Ling; Subramanian, Arjunan; Tan, Jee-Hian; Biswas, Arijit; Gauthaman, Kalamegam; Choolani, Mahesh; Chan, Woon-Khiong; Bongso, Ariff

    2009-12-01

    We describe a three dimensional (3D) anchorage independent in vitro protocol for the prolonged growth of human embryoid bodies (EBs) up to 90 days. We grew hESCs (46XX) in methylcellulose (MC) in motion culture in the presence of EB medium (EB), EB medium with Matrigel (EB + MAT), bulk culture medium (BCM), and BCM medium with Matrigel (BCM + MAT). All four experimental groups produced embryoid bodies (EBs) which with prolonged growth to 90 days acquired blood vessels and tissues from all three germ layers. Based on histology, microarray gene expression profiles and the definition for experimental teratomas, we could classify the EBs into early EBs, mature EBs and teratomas. The EB + MAT group produced the highest number of teratomas and their microarray data suggested the presence of inductive microenvironment niches and activation of pathways for self-organization, morphogenesis and growth. When we microinjected hepatocarcinoma-Green Fluorescent Protein cells (HepG2-GFP) (46XY) into the teratomas, after 10 days the HepG2-GFP cells had grown inside the teratoma as confirmed by confocal microscopy and SRY gene analysis. This 3D-MC-(EB + MAT) in vitro system requires few cells to produce many teratomas, can be used to test pluripotency of potential human embryonic and induced pluripotent stem cell lines (hESC, hiPSC), and is an experimental humanized platform to study cancer cell behavior. PMID:20058203

  11. Refinement of nano-structured fibroin thin films by near-IR pulsed laser deposition from targets consolidated with autogenous binder.

    PubMed

    Nakayama, S; Nozaki, R; Senna, M

    2008-01-01

    Silk fibroin (SF) powders were mixed with an autogenous binder from a natural cocoon after degumming with Na(2)CO(3) and liquefied with LiBr. An all-fibroin ablation target, SLT, obtained from the mixture after compression at ambient temperature, was compared with those without autogenous binder, SWT, or with a simple, non-autogenous binder, hydroxypropyl methylcellulose, SHT. The targets were then irradiated by a 1064 nm laser beam to obtain nano-structured thin films of fibroin by pulsed laser deposition (PLD) on Si (100). The properties of PLD films were examined mainly by atomic force microscope (AFM) or scanning electron microscope (SEM) for microstructures and morphology. By using an autogenous binder, significant increase was observed in the rate of nanofilm deposition with simultaneous decrease in the fraction of large debris. Size reduction of smallest protein units (SPUs) was also recognized by AFM. The autogenous binder turned out to be significantly superior over conventional, non-autogenous ones. PMID:18544238

  12. Management of Constipation in Older Adults.

    PubMed

    Mounsey, Anne; Raleigh, Meghan; Wilson, Anthony

    2015-09-15

    Chronic constipation is common in adults older than 60 years, and symptoms occur in up to 50% of nursing home residents. Primary constipation is also referred to as functional constipation. Secondary constipation is associated with chronic disease processes, medication use, and psychosocial issues. Fecal impaction should be treated with mineral oil or warm water enemas. Most patients are initially treated with lifestyle modifications, such as scheduled toileting after meals, increased fluid intake, and increased dietary fiber intake. Additional fiber intake in the form of polycarbophil, methylcellulose, or psyllium may improve symptoms. Fiber intake should be slowly increased over several weeks to decrease adverse effects. The next step in the treatment of constipation is the use of an osmotic laxative, such as polyethylene glycol, followed by a stool softener, such as docusate sodium, and then stimulant laxatives. Long-term use of magnesium-based laxatives should be avoided because of potential toxicity. If symptoms do not improve, a trial of linaclotide or lubiprostone may be appropriate, or the patient may be referred for further diagnostic evaluation. Peripherally acting mu-opioid antagonists are effective for opioid-induced constipation but are expensive. PMID:26371734

  13. Physicochemical and microbiological properties of selected rice flour-based batters for fried chicken drumsticks.

    PubMed

    Mukprasirt, A; Herald, T J; Boyle, D L; Boyle, E A

    2001-07-01

    Rice flour-based batter (RFBB) formulations for chicken drumstick coating were developed as an alternative for traditional wheat flour-based batter (WFBB). Physicochemical properties and storage stability of selected RFBB were evaluated and compared to WFBB. Batter pickup of RFBB formulated in combination with oxidized corn starch and methylcellulose (MC) was not significantly different from that of WFBB. In contrast, batters with only rice and corn flour (60:40% flour weight) exhibited significantly higher pickup. Rice flour batter with 15% oxidized corn starch had the lowest batter pickup. All RFBB exhibited (P < 0.05) lower oil absorption than WFBB. The TBA values of RFBB and WFBB increased (P < 0.05) with increased frozen storage time at -40 C for 90 d. The RFBB with MC exhibited the lowest TBA values, whereas WFBB had the highest values. Microstructural analysis revealed that freezing caused structural deterioration of all batters, but the RFBB with MC exhibited less freezing tolerance than other samples. The total plate counts of immediately fried or frozen fried chicken stored for 90 d were less than 1 log cfu/g sample. The RFBB with 5% oxidized corn starch and MC can replace WFBB on fried drumsticks. Additionally, RFBB results in a healthier product due to lower fat absorption. PMID:11469667

  14. Formulation, preparation, and evaluation of novel orally disintegrating tablets containing taste-masked naproxen sodium granules and naratriptan hydrochloride.

    PubMed

    Stange, Ulrike; Führling, Christian; Gieseler, Henning

    2014-04-01

    The purpose of this study was to develop and manufacture novel freeze-dried orally disintegrating tablets (ODTs) for migraine therapy containing taste-masked naproxen sodium and naratriptan hydrochloride. The formulation was optimized based on freeze-drying of sucrose solutions with different binders (hydroxyethylstarch, sodium alginate, methylcellulose, and gelatin) and varying amounts of Eudragit® E-coated naproxen sodium granules. Excellent product performance of the ODTs in terms of hardness and disintegration time (<10 s) independent of the mass of particles embedded was found for the solution consisting of sucrose and hydroxyethylstarch. Poloxamer 188, menthol flavor, naratriptan hydrochloride, and taste-masked naproxen sodium granules corresponding to 200 mg of naproxen were then added, and the final batches of ODTs for migraine therapy were produced. The ODTs were fully characterized, and subsequently stored for 1 month at room temperature and at 40°C. The amount of free naproxen sodium after freeze-drying and storage was below the threshold bitterness value, and the coating remained intact. Additionally, the particle size distribution of taste-masked granules was preserved, and more than 90 % naproxen sodium was released after 30 min. Naratriptan hydrochloride was dissolved immediately after disintegration, hence facilitating buccal absorption of the active pharmaceutical ingredient. PMID:24532095

  15. Orodispersible films and tablets with prednisolone microparticles.

    PubMed

    Brniak, Witold; Maślak, Ewelina; Jachowicz, Renata

    2015-07-30

    Orodispersible tablets (ODTs) and orodispersible films (ODFs) are solid oral dosage forms disintegrating or dissolving rapidly when placed in the mouth. One of the main issues related to their preparation is an efficient taste masking of a bitter drug substance. Therefore, the aim of this study was to prepare and evaluate the microparticles intended to mask a bitter taste of the prednisolone and use them in further preparation of two orodispersible dosage forms. Microparticles based on the Eudragit E PO or E 100 as a taste-masking agent were prepared with spray-drying technique. Tablets containing microparticles, co-processed ODT excipient Pharmaburst, and lubricant were directly compressed with single-punch tablet press. Orodispersible films were prepared by casting polymeric solutions of hydroxypropyl methylcellulose containing uniformly dispersed microparticles. Physicochemical properties of microparticles were evaluated, as well as mechanical properties analysis, disintegration time measurements and dissolution tests were performed for prepared dosage forms. Both formulations showed good mechanical resistance while maintaining excellent disintegration properties. The dissolution studies showed good masking properties of microparticles with Eudragit E 100. The amount of prednisolone released during the first minute in phosphate buffer 6.8 was around 0.1%. After incorporation into the orodispersible forms, the amount of released prednisolone increased significantly. It was probably the effect of faster microparticles wetting in orodispersible forms and their partial destruction by compression force during tableting process. PMID:25889975

  16. Formulation and evaluation of mucoadhesive tablets containing eugenol for the treatment of periodontal diseases.

    PubMed

    Jadhav, Bhimrao K; Khandelwal, Kishanchandra R; Ketkar, Anant R; Pisal, Sambhaji S

    2004-02-01

    Eugenol is the principle chemical constituent of clove oil and has been used to cure dental problems for ages. Eugenol is an integral part of the dentist's kit due to its analgesic, local anesthetic, anti-inflammatory, and antibacterial effects. It is used in the form of a paste or mixture as dental cement, filler, and restorative material. This study reports the development and evaluation of controlled-release mucoadhesive tablets for gingival application, containing eugenol, which are prepared by taking carbopol 934 P and Hydroxypropyl methylcellulose (HPMC) K4M in the ratio of 1:2, 1:1, and 2:1. Incorporation of eugenol (10 mg) in a mucoadhesive formulation provides controlled release for a period of 8 hours, which is advantageous over conventional use. In vitro mucoadhesion measured as detachment force in grams and the formulations show good correlation in vivo. The release study indicates that increase in carbopol increases the release rate of eugenol from the formulation whereas HPMC retards it. Increased in vitro bioadhesion is related to HPMC content of the formulation. The release kinetics of eugenol in vitro correlates with the in vivo results. This indicates the increased potential of eugenol as antibacterial, local analgesic, and anaesthetic treatment. PMID:15089054

  17. Enhancement of bioavailability of cefpodoxime proxetil using different polymeric microparticles.

    PubMed

    Khan, Fahim; Katara, Rajesh; Ramteke, Suman

    2010-09-01

    Poorly water-soluble drugs such as cefpodoxime proxetil (400 μg/ml) offer a challenging problem in drug formulation as poor solubility is generally associated with poor dissolution characteristics and thus poor oral bioavailability. According to these characteristics, preparation of cefpodoxime proxetil microparticle has been achieved using high-speed homogenization. Polymers (methylcellulose, sodium alginate, and chitosan) were precipitated on the surface of cefpodoxime proxetil using sodium citrate and calcium chloride as salting-out agents. The pure drug and the prepared microparticles with different concentrations of polymer (0.05-1.0%) were characterized in terms of solubility, drug content, particle size, thermal behavior (differential scanning calorimeter), surface morphology (scanning electron microscopy), in vitro drug release, and stability studies. The in vivo performance was assessed by pharmacokinetic study. The dissolution studies demonstrate a marked increase in the dissolution rate in comparison with pure drug. The considerable improvement in the dissolution rate of cefpodoxime proxetil from optimized microparticle was attributed to the wetting effect of polymers, altered surface morphology, and micronization of drug particles. The optimized microparticles exhibited excellent stability on storage at accelerated condition. The in vivo studies revealed that the optimized formulations provided improved pharmacokinetic parameter in rats as compared with pure drug. The particle size of drug was drastically reduced during formulation process of microparticles. PMID:20821175

  18. Regulation of mir-196b by MLL and its overexpression by MLL fusions contributes to immortalization

    PubMed Central

    Popovic, Relja; Riesbeck, Laurie E.; Velu, Chinavenmeni S.; Chaubey, Aditya; Zhang, Jiwang; Achille, Nicholas J.; Erfurth, Frank E.; Eaton, Katherine; Lu, Jun; Grimes, H. Leighton; Chen, Jianjun; Rowley, Janet D.

    2009-01-01

    Chromosomal translocations involving the Mixed Lineage Leukemia (MLL) gene produce chimeric proteins that cause abnormal expression of a subset of HOX genes and leukemia development. Here, we show that MLL normally regulates expression of mir-196b, a hematopoietic microRNA located within the HoxA cluster, in a pattern similar to that of the surrounding 5′ Hox genes, Hoxa9 and Hoxa10, during embryonic stem (ES) cell differentiation. Within the hematopoietic lineage, mir-196b is most abundant in short-term hematopoietic stem cells and is down-regulated in more differentiated hematopoietic cells. Leukemogenic MLL fusion proteins cause overexpression of mir-196b, while treatment of MLL-AF9 transformed bone marrow cells with mir-196–specific antagomir abrogates their replating potential in methylcellulose. This demonstrates that mir-196b function is necessary for MLL fusion-mediated immortalization. Furthermore, overexpression of mir-196b was found specifically in patients with MLL associated leukemias as determined from analysis of 55 primary leukemia samples. Overexpression of mir-196b in bone marrow progenitor cells leads to increased proliferative capacity and survival, as well as a partial block in differentiation. Our results suggest a mechanism whereby increased expression of mir-196b by MLL fusion proteins significantly contributes to leukemia development. PMID:19188669

  19. In vitro assays misrepresent in vivo lineage potentials of murine lymphoid progenitors.

    PubMed

    Richie Ehrlich, Lauren I; Serwold, Thomas; Weissman, Irving L

    2011-03-01

    The identity of T-cell progenitors that seed the thymus has remained controversial, largely because many studies differ over whether these progenitors retain myeloid potential. Contradictory reports diverge in their use of various in vitro and in vivo assays. To consolidate these discordant findings, we compared the myeloid potential of 2 putative thymus seeding populations, common lymphoid progenitors (CLPs) and multipotent progenitors (MPPs), and the earliest intrathymic progenitor (DN1), using 2 in vitro assays and in vivo readouts. These assays gave contradictory results: CLP and DN1 displayed surprisingly robust myeloid potential on OP9-DL1 in vitro stromal cocultures but displayed little myeloid potential in vivo, as well as in methylcellulose cultures. MPP, on the other hand, displayed robust myeloid potential in all settings. We conclude that stromal cocultures reveal cryptic, but nonphysiologic, myeloid potentials of lymphoid progenitors, providing an explanation for contradictory findings in the field and underscoring the importance of using in vivo assays for the determination of physiologic lineage potentials. PMID:21163922

  20. A novel floating controlled release drug delivery system prepared by hot-melt extrusion.

    PubMed

    Vo, Anh Q; Feng, Xin; Morott, Joseph T; Pimparade, Manjeet B; Tiwari, Roshan V; Zhang, Feng; Repka, Michael A

    2016-01-01

    Floating dosage forms are an important formulation strategy for drugs with a narrow absorption window and low intestinal solubility, and for localized gastric treatment. Novel floating pellets were prepared using the hot-melt extrusion (HME) technology. Uniformly foamed strands were created by liquid injection pumping and screw configuration modification. The ammonio methacrylate copolymer (Eudragit® RSPO) foaming structure was formed by a liquid-vapor phase transition inside the strand upon die exiting resulting from the sudden decrease in external pressure, vaporizing the liquid ethanol and vacating the extruded material. This generated uniform vacuous regions in the extrudate. The pellets' internal structure was investigated using scanning electron microscopy (SEM). The formulation constituents' and processing parameters' effects on the drug release profiles, floating force, and the pellets' micromeritic properties were evaluated by design of experiments: all formulations showed zero lag time and excellent floating strength, indicating immediate-floating pellet formation. The pellets' drug release profiles were controlled by multiple independent variables at different time points (⩽ 24 h). Drug loading significantly affected drug release within the first hour, the hydroxypropyl methylcellulose (HPMC) content thereafter. Understanding the variables' effects on the formulations allows for the tailoring of this delivery system to obtain various drug release profiles. PMID:26643801

  1. Ion-activated In Situ Gelling Ophthalmic Delivery Systems of Azithromycin

    PubMed Central

    Vijaya, C.; Goud, K. Swetha

    2011-01-01

    Gelation of pectin caused by divalent cations especially calcium ions has been applied to develop an ophthalmic formulation of azithromycin in the present study. Rapid elimination of drug on instillation into cul de sac would be minimal with in situ gelling ophthalmic solution leading to increased precorneal contact time and prolonged drug delivery. In the formulation development studies pectin was used in different concentrations (1-5% w/v) and different proportions of the hydrocolloids hydroxypropyl methylcellulose and sodium carboxymethyl cellulose of different grades of viscosity were used. The primary criteria for formulation optimization were gelling capacity and rheological behaviour. In addition, formulations were evaluated for pH, and antimicrobial efficacy and drug release. The clarity, pH, gelation in simulated tear fluid and rheological properties of the optimized formulations were satisfactory. The formulations inhibited the growth of Staphylococcus aureus effectively in cup–plate method and were proved to be safe and non irritant on rabbit eyes. The results indicate that pectin based in situ gels can be successfully used to prolong the duration of action of azithromycin. PMID:23112394

  2. The fate of free radicals in a cellulose based hydrogel: detection by electron paramagnetic resonance spectroscopy.

    PubMed

    Basumallick, Lipika; Ji, J Andrea; Naber, Nariman; Wang, Y John

    2009-07-01

    Cellulose derivatives are commonly used as gelling agents in topical and ophthalmic drug formulations. During the course of manufacturing, cellulose derivatives are believed to generate free radicals. These free radicals may degrade the gelling agent, leading to lower viscosity. Free radicals also may react with the active ingredient in the product. The formation of radicals in a 3% hydrogel of hypromellose (hydroxypropyl methylcellulose) was monitored by electron paramagnetic resonance (EPR) spectroscopy and spin trapping techniques. Radicals were trapped with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and quantitated by comparing the EPR intensity with 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy (TEMPOL), a stable free radical. Typically, the hydrogels showed an initial increase in the radical concentration within 2 days after autoclaving, followed by a drop in radical concentration in 7 days. EDTA prevented the formation of free radicals in the hypromellose (HPMC) hydrogel, suggesting the involvement of metal ions in the generation of free radicals. The oxidizing potential of the hydrogel was estimated by measuring the rate at which methionine (a model for the protein active pharmaceutical ingredient) was degraded, and was consistent with the amount of radicals present in the gel. This study is the first report investigating the application of EPR spectroscopy in detecting and estimating free radical concentration in cellulose based hydrogels. PMID:19090570

  3. Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia

    PubMed Central

    Christoph, Sandra; Lee-Sherick, Alisa B.; Sather, Susan; DeRyckere, Deborah; Graham, Douglas K.

    2013-01-01

    Receptor tyrosine kinases have been implicated in the development and progression of many cancers, including both leukemia and solid tumors, and are attractive druggable therapeutic targets. Here we describe an efficient four-step strategy for pre-clinical evaluation of tyrosine kinase inhibitors (TKIs) in the treatment of acute leukemia. Initially, western blot analysis is used to confirm target inhibition in cultured leukemia cells. Functional activity is then evaluated using clonogenic assays in methylcellulose or soft agar cultures. Experimental compounds that demonstrate activity in cell culture assays are evaluated in vivo using NOD-SCID-gamma (NSG) mice transplanted orthotopically with human leukemia cell lines. Initial in vivo pharmacodynamic studies evaluate target inhibition in leukemic blasts isolated from the bone marrow. This approach is used to determine the dose and schedule of administration required for effective target inhibition. Subsequent studies evaluate the efficacy of the TKIs in vivo using luciferase expressing leukemia cells, thereby allowing for non-invasive bioluminescent monitoring of leukemia burden and assessment of therapeutic response using an in vivo bioluminescence imaging system. This strategy has been effective for evaluation of TKIs in vitro and in vivo and can be applied for identification of molecularly-targeted agents with therapeutic potential or for direct comparison and prioritization of multiple compounds. PMID:24084362

  4. Stimuli-responsive lipid nanotubes in gel formulations for the delivery of doxorubicin.

    PubMed

    Ilbasmis-Tamer, Sibel; Unsal, Hande; Tugcu-Demiroz, Fatmanur; Kalaycioglu, Gokce Dicle; Degim, Ismail Tuncer; Aydogan, Nihal

    2016-07-01

    Lipid nanotubes (LNTs) are one of the most advantageous structures for drug delivery and targeting. LNTs formed by a specially designed molecule called AQUA (AQ-NH-(CH2)10COOH (AQ: anthraquinone group) is used for drug delivery, and doxorubicin (DOX) is the drug selected. DOX and AQUA have some similarities in their molecular structures, so a significant amount of DOX can be loaded to LNTs. The AQUA LNTs are pH responsive, and drug loading increased almost linearly by increasing the pH, reaching a maximum value (96%) at pH 9.0. In terms of drug release, lower pHs are preferred. Drug-loaded LNTs are also mixed with four different gels (chitosan, alginate, hydroxypropyl methylcellulose and polycarbophil) to use the advantages of these gels. The drug release efficiency is studied using a Franz diffusion cell in which sheep colon membranes and dialysis membranes are utilized. The amount of released DOX from the chitosan gel formulations was quite high. Sodium alginate gels had lower release and slower diffusion of DOX. The cytotoxic effect of DOX-loaded AQUA LNTs has also been determined on cell cultures. Our new lipid nanotubes are a non-toxic, effective, biodegradable, biocompatible, stable and promising system for drug delivery and can be used for colonic administration of DOX for the treatment of colorectal cancer (CRC). PMID:27037777

  5. Floating mucoadhesive alginate beads of amoxicillin trihydrate: A facile approach for H. pylori eradication.

    PubMed

    Dey, Sanjoy Kumar; De, Pintu Kumar; De, Arnab; Ojha, Souvik; De, Ronita; Mukhopadhyay, Asish Kumar; Samanta, Amalesh

    2016-08-01

    This study investigates the design of sunflower oil entrapped floating and mucoadhesive beads of amoxicillin trihydrate using sodium alginate and hydroxypropyl methylcellulose as matrix polymers and chitosan as coating polymer to localize the antibiotic at the stomach site against Helicobacter pylori. Beads prepared by ionotropic gellation technique were evaluated for different physicochemical, in-vitro and in-vivo properties. Beads of all batches were floated for >24h with a maximum lag time of 46.3±3.2s. Scanning electron microscopy revealed that the beads were spherical in shape with few oil filled channels distributed throughout the surfaces and small pocket structures inside the matrix confirming oil entrapment. Prepared beads showed good mucoadhesiveness of 75.7±3.0% to 85.0±5.5%. The drug release profile was best fitted to Higuchi model with non fickian driven mechanism. The optimized batch showed 100% Helicobacter pylori growth inhibition in 15h in in-vitro culture. Furthermore, X-ray study in rabbit stomach confirmed the gastric retention of optimized formulation. The results exhibited that formulated beads may be preferred to localize the antibiotic in the gastric region to allow more availability of antibiotic at gastric mucus layer acting on Helicobacter pylori, thereby improving the therapeutic efficacy. PMID:27177460

  6. In vitro/in vivo evaluation of HPMC/alginate based extended-release matrix tablets of cefpodoxime proxetil.

    PubMed

    Mujtaba, Ali; Kohli, Kanchan

    2016-08-01

    The purpose of this research was to assessment of antimicrobial activity and in vitro/in vivo evaluation of cefpodoxime proxetil extended-release (ER) tablet for once daily administration. The tablets were prepared using combination of biodegradable polysaccharides including hydroxypropyl methylcellulose and sodium alginate as matrix material to achieve pH-independent ER release. The tablets were found within the permissible limits for various physicochemical parameters. The in vitro drug release showed that the drug was released over a period of 24h in a sustained release manner. The drug release followed Higuchi kinetics as these plots showed the highest linearity (R(2)=0.9833), but a close relationship was also observed with zero-order kinetics (R(2)=0.9088) and the drug release mechanism was found to be of anomalous or non-Fickian type. Further, in vitro drug release was assessed by antimicrobial assay and it revealed that drug release through 24h periods was above the MIC. In vivo investigation in rabbits showed ER pharmacokinetic profile of cefpodoxime from the matrix tablets. A good correlation of drug absorption in vivo and drug release in vitro (R(2)=0.9785) was observed. These results suggested that the investigated CFP matrix tablets have a potential for extended-release dosage forms. PMID:27155235

  7. PBPK Model for Atrazine and Its Chlorotriazine Metabolites in Rat and Human.

    PubMed

    Campbell, Jerry L; Andersen, Melvin E; Hinderliter, Paul M; Yi, Kun Don; Pastoor, Timothy P; Breckenridge, Charles B; Clewell, Harvey J

    2016-04-01

    The previously-published physiologically based pharmacokinetic model for atrazine (ATZ), deisopropylatrazine (DIA), deethylatrazine (DEA), and diaminochlorotriazine (DACT), which collectively comprise the total chlorotriazines (TCT) as represented in this study, was modified to allow for scaling to humans. Changes included replacing the fixed dose-dependent oral uptake rates with a method that represented delayed absorption observed in rats administered ATZ as a bolus dose suspended in a methylcellulose vehicle. Rate constants for metabolism of ATZ to DIA and DEA, followed by metabolism of DIA and DEA to DACT were predicted using a compartmental model describing the metabolism of the chlorotriazines by rat and human hepatocytesin vitro Overall, the model successfully predicted both the 4-day plasma time-course data in rats administered ATZ by bolus dose (3, 10, and 50 mg/kg/day) or in the diet (30, 100, or 500 ppm). Simulated continuous daily exposure of a 55-kg adult female to ATZ at a dose of 1.0 µg/kg/day resulted in steady-state urinary concentrations of 0.6, 1.4, 2.5, and 6.0 µg/L for DEA, DIA, DACT, and TCT, respectively. The TCT (ATZ + DEA + DIA + DACT) human urinary biomonitoring equivalent concentration following continuous exposure to ATZ at the chronic point of departure (POD = 1.8 mg/kg/day) was 360.6 μg/L. PMID:26794140

  8. Films loaded with insulin-coated nanoparticles (ICNP) as potential platforms for peptide buccal delivery.

    PubMed

    Morales, Javier O; Huang, Siyuan; Williams, Robert O; McConville, Jason T

    2014-10-01

    The goal of this investigation was to develop films containing insulin-coated nanoparticles and evaluate their performance in vitro as potential peptide delivery systems. To incorporate insulin into the films, a new antisolvent co-precipitation fabrication process was adapted to obtain insulin-coated nanoparticles (ICNPs). The ICNPs were embedded in polymeric films containing a cationic polymethacrylate derivative (ERL) or a combination of ERL with hydroxypropyl methylcellulose (HPMC). ICNP-loaded films were characterized for morphology, mucoadhesion, and insulin release. Furthermore, in vitro insulin permeation was evaluated using a cultured tridimensional human buccal mucosa model. The antisolvent co-precipitation method was successfully adapted to obtain ICNPs with 40% (w/w) insulin load, achieving 323±8nm particles with a high zeta potential of 32.4±0.8mV, indicating good stability. High yields were obtained after manufacture and the insulin content did not decrease after one month storage. ICNP-embedded films using ERL as the polymer matrix presented excellent mucoadhesive and insulin release properties. A high permeation enhancement effect was observed for ICNP-loaded ERL films in comparison with ICNP-loaded ERL-HPMC films and a control insulin solution. ICNP-loaded ERL formulations were found to be more effective in terms of film performance and insulin permeation through the human buccal mucosa model, and thus are a promising delivery system for buccal administration of a peptide such as insulin. PMID:25016543

  9. Modifying release characteristics from 3D printed drug-eluting products.

    PubMed

    Boetker, Johan; Water, Jorrit Jeroen; Aho, Johanna; Arnfast, Lærke; Bohr, Adam; Rantanen, Jukka

    2016-07-30

    This work describes an approach to modify the release of active compound from a 3D printed model drug product geometry intended for flexible dosing and precision medication. The production of novel polylactic acid and hydroxypropyl methylcellulose based feed materials containing nitrofurantoin for 3D printing purposes is demonstrated. Nitrofurantoin, Metolose® and polylactic acid were successfully co-extruded with up to 40% Metolose® content, and subsequently 3D printed into model disk geometries (ø10mm, h=2mm). Thermal analysis with differential scanning calorimetry and solid phase identification with Raman spectroscopy showed that nitrofurantoin remained in its original solid form during both hot-melt extrusion and subsequent 3D printing. Rheological measurements of the different compositions showed that the flow properties were sensitive to the amount of undissolved particles present in the formulation. Release of nitrofurantoin from the disks was dependent on Metolose® loading, with higher accumulated release observed for higher Metolose® loads. This work shows the potential of custom-made, drug loaded feed materials for 3D printing of precision drug products with tailored drug release characteristics. PMID:26987609

  10. The physicodynamic properties of mucoadhesive polymeric films developed as female controlled drug delivery system.

    PubMed

    Yoo, Jin-Wook; Dharmala, Kiran; Lee, Chi H

    2006-02-17

    To develop an efficient female controlled drug delivery system (FcDDS) against sexually transmitted diseases (STDs), the polymeric films containing sodium dodecyl sulfate (SDS) were prepared with various compositions of Carbopol 934P, hydroxypropyl methylcellulose (HPMC) and polyethylene glycol (PEG). The physicochemical properties of mucoadhesive polymeric films, such as tensile strength, contact angle, swelling ratio and erosion rate in a vaginal fluid stimulant (VFS), were characterized. In addition, the drug release profile of SDS from the films and mucosal residence time were evaluated using a simulated dynamic vaginal system. It was demonstrated that the films made of Carbopol, HPMC and PEG were colorless, thin and soft and had proper physicodynamic properties for FcDDS. An increase in Carbopol content elevated tensile strength and swelling ratio but decreased the contact angle, erosion rate and the SDS release rate from the films. The films containing 0.25% (w/v) PEG as well as 0.75% (w/v) of combining Carbopol and HPMC remained on the vaginal tissue for up to 6h. The films containing the ratio of Carbopol:HPMC:PEG=1.5:1.5:1 and 1:2:1 seem to be optimal compositions for FcDDS, as they showed good peelability, relatively high swelling index and moderate tensile strength, and achieved the target release rate of SDS for 6h. PMID:16376036

  11. Predicting the diffusion coefficient of water vapor through glassy HPMC films at different environmental conditions using the free volume additivity approach.

    PubMed

    Laksmana, Fesia Lestari; Hartman Kok, Paul Jean Antoine; Vromans, Herman; Van der Voort Maarschalk, Kees

    2009-07-12

    Prediction of diffusion coefficient of polymer materials is important in the pharmaceutical research and becomes the aim of this paper. This paper bases the prediction method on the estimation of the polymer fractional free volume at different environmental conditions. Focussing on glassy polymers, the free volumes of polymer films were estimated using the model of Vrentas et al. [J.S. Vrentas, J.L. Duda, H.-C. Ling, Antiplasticization and volumetric behavior in glassy polymers, Macromolecules 21 (1988) 1470-1475]. The required data are the moisture sorption and glass transition temperature data, which were measured on various hydroxypropyl methylcellulose (used as a model material) free films at different water activities. The temperature and molecular weight particularly determine the free volume of the polymer, while the sorbed water can either decrease or increase the specific free volume of the polymer. At high water activity, the amount of water sorbed in the film increases to such level that the direct free volume addition by water becomes proportional to the contribution of the polymer itself. This confirms the importance of considering the environmental effect on the diffusivity of polymer during coating material selection. The presented approach enables the prediction of the diffusivity at any given relevant material variable and therefore has the potency to be used as a formulation development tool. PMID:19409985

  12. Floating Matrix Tablets of Domperidone Formulation and Optimization Using Simplex Lattice Design

    PubMed Central

    Prajapati, Shailesh; Patel, Laxmanbhai; Patel, Chhaganbhai

    2011-01-01

    The purpose of this research was to prepare a floating matrix tablet containing domperidone as a model drug. Polyethylene oxide (PEO) and hydroxypropyl methylcellulose (HPMC) were evaluated for matrix-forming properties. A simplex lattice design was applied to systemically optimize the drug release profile. The amounts of PEO WSR 303, HPMC K15M and sodium bicarbonate were selected as independent variables and floating lag time, time required to release 50% of drug (t50) and 80% of drug (t80), diffusion coefficient (n) and release rate (k) as dependent variables. The amount of PEO and HPMC both had significant influence on the dependent variables. It was found that the content of PEO had dominating role as drug release controlling factor, but using suitable concentration of sodium bicarbonate, one can tailor the desired drug release from hydrophilic matrixes. The linear regression analysis and model fitting showed that all these formulations followed Korsmeyer and Peppas model, which had a higher value of correlation coefficient (r). The tablets of promising formulation were found to be stable for 3 months under accelerated (40°C / 75% RH) stability testing. PMID:24250376

  13. Development of orodispersible polymer films containing poorly water soluble active pharmaceutical ingredients with focus on different drug loadings and storage stability.

    PubMed

    Woertz, Christina; Kleinebudde, Peter

    2015-09-30

    The aim of this work was the development of orodispersible films containing different film forming polymers with focus on different drug loadings of two poorly water soluble APIs. Furthermore, physical stability of films was examined at two different storage conditions. Loperamide hydrochloride (LPH) and ibuprofen (IBU) were used as model drugs. Hydroxypropyl methylcellulose (HPMC) and three different types of hydroxypropyl cellulose (HPC) were used as film forming polymers. Suspensions were characterized with respect to their viscosity and particle sedimentation and films regarding their content uniformity, thickness, mass and stability. Principal component analysis (PCA) was used to evaluate the correlation between the wet film thickness, dry film thickness, mass of the films, API fraction in the suspension and the viscosity of the suspensions. The viscosity of the suspensions was dependent on the drug load and the polymer fraction but less so on the type of the utilized polymer. A correlation between the wet film thickness, the solid fraction and the mass of the films was established with an increase in mass by increasing the wet film thickness or the solid fraction. Films containing 50 mg IBU/6 cm(2) film led to acceptable films. Storage experiments did not lead to an AV below 15 in all cases after storage for three and six months, attributed to the storage conditions and the quality of the films. Nevertheless, the development and production of flexible and homogeneous films of LPH and IBU was successfully achieved. PMID:26216415

  14. Polymeric coatings for a multiple-unit pulsatile delivery system: preliminary study on free and applied films.

    PubMed

    Maroni, Alessandra; Del Curto, Maria Dorly; Cerea, Matteo; Zema, Lucia; Foppoli, Anastasia; Gazzaniga, Andrea

    2013-01-20

    In order to adapt a previously described swellable/erodible pulsatile delivery system to a multiple-unit configuration, insoluble films with adequate permeability and flexibility were proposed for application to its functional hydroxypropyl methylcellulose (HPMC) layer. By slowing down the penetration of water into the system, such films would be expected to improve the relevant effectiveness in delaying the onset of release without possibly impacting on the mechanism involved. Free films of Eudragit(®)NE containing differing amounts (10-20%) of a superdisintegrant, i.e. Explotab(®)V17, Ac-Di-Sol(®), Kollidon(®)CL or Kollidon(®)CL-M, were prepared by spraying technique and evaluated for hydration, permeability and tensile properties. The hydration and permeability characteristics were enhanced by the addition of the superdisintegrants, generally as a function of their concentration. Explotab(®)V17 was shown particularly useful to increase the film permeability. Moreover, it exerted a minor impact on the advantageous tensile properties of the acrylic polymer, especially in the wet state. Based on these results and on a preliminary release study performed with two-layer devices, the Eudragit(®)NE film with Explotab(®)V17 at the highest investigated percentage was identified as a potential formulation candidate for being applied to HPMC-coated cores thus allowing the onset of release to effectively be delayed by coatings of reduced thickness. PMID:22688248

  15. Particle-Induced X-Ray Emission (PIXE) Of Silicate Coatings On High Impact Resistance Polycarbonates

    NASA Astrophysics Data System (ADS)

    Xing, Qian; Hart, M. A.; Culbertson, R. J.; Bradley, J. D.; Herbots, N.; Wilkens, Barry J.; Sell, David A.; Watson, Clarizza Fiel

    2011-06-01

    Particle-Induced X-ray Emission (PIXE) analysis was employed to characterize hydroxypropyl methylcellulose (HPMC) C32H60O19 polymer film via areal density measurement on silicon-based substrates utilizing the differential PIXE concept, and compared with Rutherford backscattering spectrometry (RBS) results. It is demonstrated in this paper that PIXE and RBS measurements both yield comparable results for areal densities ranging from 1018 atom/cm2 to several 1019 atom/cm2. A collection of techniques including PIXE, RBS, tapping mode atomic force microscopy (TMAFM), and contact angle analysis were used to compute surface free energy, analyze surface topography and roughness parameters, determine surface composition and areal density, and to predict the water affinity and condensation behaviors of silicates and other compounds used for high impact resistance vision ware coatings. The visor surface under study is slightly hydrophilic, with root mean square of surface roughness on the order of one nm, and surface wavelength between 200 nm and 300 nm. Water condensation can be controlled on such surfaces via polymers adsorption. HPMC polymer areal density measurement supports the analysis of the surface water affinity and topography and the subsequent control of condensation behavior. HPMC film between 1018 atom/cm2 and 1019 atom/cm2 was found to effectively alter the water condensation pattern and prevents fogging by forming a wetting layer during condensation.

  16. Mechanical properties and water vapour permeability of film from Haruan (Channa striatus) and fusidic acid spray for wound dressing and wound healing.

    PubMed

    Febriyenti; Noor, Azmin Mohd; Bai, Saringat Bin

    2010-04-01

    Aerosol is a new dosage form for wound dressing and wound healing. Concentrate of aerosols which were prepared for wound dressing and wound healing will produced films after sprayed onto the surface of wounds. The aim of this study is to evaluate the mechanical and water vapour permeability properties of the films from the aerosol concentrates. Film forming dispersions contained Haruan extract and Fusidic acid as the active ingredients, hydroxypropyl methylcellulose (HPMC) as polymer and polyethylene glycol (PEG) 400, glycerin and propylene glycol as plasticizers. Haruan extract is used to promote healing and Fusidic acid is added in formula as antibiotic to prevent the infections. The films were prepared by using casting technique. Based on the results, it is concluded that films produced from Formula E1, E2 and F4 possessed good elongation at break but low tensile strength. All Formula E, Formula F4 and F5 were permeable but Formula F5 was brittle and would peel off by themselves from the Petri dish. PMID:20363692

  17. Time-dependent mechanical properties of polymeric coatings used in rupturable pulsatile release dosage forms.

    PubMed

    Bussemer, T; Peppas, N A; Bodmeier, R

    2003-07-01

    The mechanical properties of polymer films used in pharmaceutical coatings of pulsatile drug delivery systems were evaluated in the dry and the wet state by a newly developed puncture test, which allowed the time-dependent measurement of the mechanical properties on the same film specimen. Force, puncture strength, energy at break, modulus, and strain were investigated as a function of water exposure time with respect to the type of polymer and the type and concentration of plasticizer and pore former (hydroxypropyl methylcellulose, HPMC). Eudragit RS films were very flexible, had a high strain, and broke upon puncture with only small cracks. In contrast, ethylcellulose films were more brittle with a lower strain and showed complete film rupture. Increased amounts of the hydrophilic pore former, HPMC, resulted in a reduced puncture strength and in an increase in water uptake and weight loss of the films. The puncture strength decreased with increasing plasticizer concentration and was lower with the lipophilic dibutyl sebacate than with the hydrophilic triethyl citrate. PMID:12889780

  18. Development and characterization of an orodispersible film containing drug nanoparticles.

    PubMed

    Shen, Bao-de; Shen, Cheng-ying; Yuan, Xu-dong; Bai, Jin-xia; Lv, Qing-yuan; Xu, He; Dai, Ling; Yu, Chao; Han, Jin; Yuan, Hai-long

    2013-11-01

    In this study, a novel orodispersible film (ODF) containing drug nanoparticles was developed with the goal of transforming drug nanosuspensions into a solid dosage form and enhancing oral bioavailability of drugs with poor water solubility. Nanosuspensions were prepared by high pressure homogenization and then transformed into ODF containing drug nanoparticles by mixing with hydroxypropyl methylcellulose solution containing microcrystalline cellulose, low substituted hydroxypropylcellulose and PEG-400 followed by film casting and drying. Herpetrione, a novel and potent antiviral agent with poor water solubility that extracted from Herpetospermum caudigerum, was chosen as a model drug and studied systematically. The uniformity of dosage units of the preparation was acceptable according to the criteria of Japanese Pharmacopoeia 15. The ODF was disintegrated in water within 30s with reconstituted nanosuspensions particle size of 280 ± 11 nm, which was similar to that of drug nanosuspensions, indicating a good redispersibility of the fast dissolving film. Result of X-ray diffraction showed that HPE in the ODF was in the amorphous state. In the in vitro dissolution test, the ODF containing HPE nanoparticles showed an increased dissolution velocity markedly. In the pharmacokinetics study in rats, compared to HPE coarse suspensions, the ODF containing HPE nanoparticles exhibited significant increase in AUC0-24h, Cmax and decrease in Tmax, MRT. The result revealed that the ODF containing drug nanoparticles may provide a potential opportunity in transforming drug nanosuspensions into a solid dosage form as well as enhancing the dissolution rate and oral bioavailability of poorly water-soluble drugs. PMID:24103635

  19. Characterization and optimization of orodispersible mosapride film formulations.

    PubMed

    ElMeshad, Aliaa N; El Hagrasy, Arwa S

    2011-12-01

    Orodispersible film (ODF) technology offers new possibilities for drug delivery by providing the advantages of oral delivery coupled with the enhanced onset of action and convenience to special patient categories such as pediatrics and geriatrics. In this study, mosapride (MOS) was formulated in an ODF preparation that can be used for treatment of patients who suffer from gastrointestinal disorders, especially difficulty in swallowing due to gastroesophageal reflux disease. Poloxamer 188 was used to solubilize MOS to allow its incorporation into the film matrix. The films were prepared by solvent-casting method using different polymer ratios of maltodextrin and hydroxypropyl methylcellulose and plasticizer levels of glycerol and propylene glycol. A D-optimal design was utilized to study the effect of polymer ratio, plasticizer type, and level on film mechanical properties, disintegration time, and dissolution rate. Statistical analysis of the experimental design showed that the increase of maltodextrin fraction and plasticizer level conferred optimum attributes to the prepared films in terms of film elasticity, film disintegration time, and MOS release rate. The ODF formulations were further tested for moisture sorption capacity, with formulations containing a higher ratio of maltodextrin and percent plasticizer showing more moisture uptake. The optimum film composition was also tested in vivo for film palatability and disintegration time. An optimized mosapride orodispersible film formulation was achieved that could be of benefit to patients suffering from gastrointestinal disorders. PMID:22009305

  20. Protection of moisture-sensitive drugs with aqueous polymer coatings: importance of coating and curing conditions.

    PubMed

    Bley, O; Siepmann, J; Bodmeier, R

    2009-08-13

    The aim of this study was to better understand the importance of coating and curing conditions of moisture-protective polymer coatings. Tablets containing freeze-dried garlic powder were coated with aqueous solutions/dispersions of hydroxypropyl methylcellulose (HPMC), poly(vinyl alcohol), ethyl cellulose and poly(methacrylate-methylmethacrylates). The water content of the tablets during coating and during storage at different temperatures and relative humidities (RH) was determined gravimetrically. In addition, changes in the allicin (active ingredient in garlic powder) content were monitored. During the coating process, the water uptake was below 2.7% and no drug degradation was detectable. Thermally induced drug degradation occurred only at temperatures above the coating temperatures. Different polymer coatings effectively decreased the rate, but not the extent of water uptake during open storage at room temperature and 75% RH. Tablets coated with poly(vinyl alcohol) and poly(methacrylate-methylmethacrylates) showed the lowest moisture uptake rates (0.49 and 0.57%/d, respectively). Curing at elevated temperature after coating did not improve the moisture-protective ability of the polymeric films, but reduced the water content of the tablets. Drug stability was significantly improved with tablets coated with poly(vinyl alcohol) and poly(methacrylate-methylmethacrylates). PMID:19477253

  1. Characterization of moisture-protective polymer coatings using differential scanning calorimetry and dynamic vapor sorption.

    PubMed

    Bley, O; Siepmann, J; Bodmeier, R

    2009-02-01

    The aim of this study was to evaluate the moisture-protective ability of different polymeric coatings. Free films and film-coated tablets (with cores containing freeze-dried garlic powder) were prepared using aqueous solutions/dispersions of hydroxypropyl methylcellulose (HPMC), Opadry AMB [a poly(vinylalcohol)-based formulation] and Eudragit E PO [a poly(methacrylate-methylmethacrylate)]. The water content of the systems upon open storage at 75% relative humidity (RH) and 22 degrees C (room temperature) was followed gravimetrically. Furthermore, polymer powders, free films and coated tablets were analyzed by differential scanning calorimetry (DSC) and dynamic vapor sorption (DVS). The type of polymer strongly affected the resulting water uptake kinetics of the free films and coated tablets. DSC analysis revealed whether or not significant physical changes occurred in the coatings during storage, and whether the water vapor permeability was water concentration dependent. Using DVS analysis the critical glass transition RH of Opadry AMB powder and Opadry AMB-coated tablets at 25 degrees C could be determined: 44.0% and 72.9% RH. Storage below these threshold values significantly reduces water penetration. Thus, DVS and DSC measurements can provide valuable information on the nature of polymers used for moisture protection. PMID:18481311

  2. Controlled release floating multiparticulates of metoprolol succinate by hot melt extrusion.

    PubMed

    Malode, Vilas N; Paradkar, Anant; Devarajan, Padma V

    2015-08-01

    We present hot melt extrusion (HME) for the design of floating multiparticulates. Metoprolol succinate was selected as the model drug. Our foremost objective was to optimize the components Eudragit(®) RS PO, polyethylene oxide (PEO) and hydroxypropyl methylcellulose (HPMC) to balance both buoyancy and controlled release. Gas generated by sodium bicarbonate in acidic medium was trapped in the polymer matrix to enable floating. Eudragit(®) RS PO and PEO with sodium bicarbonate resulted in multiparticulates which exhibited rapid flotation within 3 min but inadequate total floating time (TFT) of 3h. Addition of HPMC to the matrix did not affect floating lag time (FLT), moreover TFT increased to more than 12h with controlled release of metoprolol succinate. Floating multiparticulates exhibited t50% of 5.24h and t90% of 10.12h. XRD and DSC analysis revealed crystalline state of drug while FTIR suggested nonexistence of chemical interaction between the drug and the other excipients. The assay, FLT, TFT and the drug release of the multiparticulates were unchanged when stored at 40°C/75%RH for 3 months confirming stability. We present floating multiparticulates by HME which could be extrapolated to a range of other drugs. Our approach hence presents platform technology for floating multiparticulates. PMID:26142246

  3. FORMULATION AND EVALUATION OF ENTERIC COATED TABLETS OF PROTON PUMP INHIBITOR

    PubMed Central

    Nair, Anroop B; Gupta, Rachna; Kumria, Rachna; Jacob, Shery; Attimarad, Mahesh

    2010-01-01

    The present study was an attempt to formulate and evaluate enteric coated tablets for esomeprazole magnesium trihydrate. Different core tablets were prepared and formulation (F-1) was selected for further enteric coating, based on the disintegration time. Seal coating was applied to achieve 3% weight gain using opadry®. Enteric coating was carried out using different polymers like Eudragit L-30 D-55, hydroxy propyl methylcellulose phthalate, cellulose acetate phthalate and Acryl-EZE® to achieve 5% weight gain. Disintegration studies showed that the formulations failed in 0.1 N HCl media. Hence the quantity of enteric coating was increased to 8% w/w. In vitro analysis of the developed tablets was carried out. Results from disintegration time and dissolution rate studies indicate that all the esomeprazole enteric tablets prepared possess good integrity, desirable for enteric coated tablets. Among the polymers studied, the methacrylic polymers exhibited better dissolution rate than the cellulose polymers. Stability studies indicate that the prepared formulations were stable for a period of three months. This study concluded that enteric coated tablets of esomeprazole can be prepared using any of the enteric coating polymer studied using a minimal weight gain of 8%. PMID:24825991

  4. Preparation and evaluation of an ispaghula based directly compressible matrixing agent for controlled release.

    PubMed

    Lalwani, Anita N; Parikh, Jolly R

    2008-09-01

    The objective of the present investigation was to prepare and evaluate an ispaghula husk based directly compressible (DC) adjuvant that can be used as matrixing agent using an agglomeration technique. Addition of hydroxypropyl methylcellulose was found necessary to improve cohesion. Lactose (X1), calcium hydrogen phosphate dihydrate (X2) and Avicel PH101 (X3), used along with ispaghula in preparation of agglomerates, were selected as three independent variables in a simplex lattice design affecting compressional and dissolution characteristics of the drug from the DC adjuvant. The agglomerates were evaluated for their flow properties. Tablets were prepared using 70% agglomerates and 30% acetaminophen, a poorly compressible drug, and were subjected to in vitro drug release study. Amounts of the drug released at the end of 60 min (Y60), 300 min (Y300) and 480 min (Y480) were selected as dependent variables in a simplex lattice design. Batch IH05 that contained lactose and calcium hydrogen phosphate dihydrate in a 1:2 ratio could control the release for 12 hours and thus form the basis for twice a-day-dosing. PMID:19103567

  5. Preparation and evaluation of gastroretentive floating tablets of Silymarin.

    PubMed

    Garg, Rajeev; Gupta, Ghanshyam Das

    2009-06-01

    The present study performed by preparation and evaluation of floating tablets of Silymarin as model drug for prolongation of gastric residence time. Floating effervescent tablets were formulated by various materials like hydroxypropyl methylcellulose (HPMC) K 4M, K 15M, psyllium husk, swelling agent as crospovidone and microcrystalline cellulose and gas generating agent like sodium bicarbonate and citric acid and evaluated for floating properties, swelling characteristics and in vitro drug release studies. Floating noneffervescent tablets were prepared by polypropylene foam powder and different matrix forming polymers like HPMC K 4M, Carbopol 934P, xanthan gum and sodium alginate. In vitro drug release studies were performed and drug release kinetics evaluated using the linear regression method was found to follow both the Higuchi and the Korsemeyer and Peppas equation. The drug release mechanism was found fickian type in most of the formulations. The developed floating tablets of Silymarin may be used in clinic for prolonged drug release for at least 24 h, thereby improving the bioavailability and patient compliance. PMID:19483331

  6. The effect of moisture on the flowability of pharmaceutical excipients.

    PubMed

    Crouter, Allison; Briens, Lauren

    2014-02-01

    The effect of moisture content on flowability of six pharmaceutical powders (microcrystalline cellulose (MCC), hydroxypropyl methylcellulose (HPMC), carboxymethyl cellulose (CMC), polyvinylpyrrolidone (PVP), corn starch, and potato starch) was investigated. Powder flowability was measured using established static techniques and emerging dynamic avalanche behavior measurements. Static techniques did not provide enough resolution to clearly identify changes in flowability due to increasing powder moisture content. Avalanche time and its standard deviation showed that flowability of MCC, CMC, PVP, and potato starch decreased after a critical moisture content, flowability of corn starch increased and flowability did not significantly change for HPMC. The moisture decreased flowability by forming stronger interparticle liquid bridges and increased flowability by acting as a lubricant. The dynamic density of the celluloses and PVP decreased linearly with increasing moisture content as the particles swelled with water. The starches also swelled and decreased in dynamic density, but only after a moisture content corresponding to monolayer coverage of water around the particles was reached. As flowability and dynamic density change with moisture content, to ensure consistent production of high-quality tablets, the moisture content of the powders must be measured and controlled. PMID:24092523

  7. Globin chain synthesis in single erythroid bursts from cord blood: studies on gamma leads to beta and G gamma leads to A gamma switches.

    PubMed

    Comi, P; Giglioni, B; Ottolenghi, S; Gianni, A M; Polli, E; Barba, P; Covelli, A; Migliaccio, G; Condorelli, M; Peschle, C

    1980-01-01

    Erythroid bursts from cord or adult blood were grown in methylcellulose cultures (3 international units of erythropoietin per plate). On day 13, single bursts were picked up and reincubated for 16-24 hr with [3H]leucine. Radioactive globin chains [alpha,beta,G gamma, and A gamma (Ala-136)] were analyzed by either isoelectric focusing on polyacrylamide gels and fluorography or carboxymethylcellulose chromatography. In all cases, alpha to non-alpha globin radioactivity ratios were close to 1. In single cord blood bursts, the values of both gamma-to-beta and G gamma-to-A gamma ratios were spread over a large spectrum and further characterized by a continuous rather than a bimodal distribution. Morever, the G gamma-to-A gamma ratios demonstrated in single bursts appeared to be directly correlated with the respective gamma-to-beta ratios. These data suggest that both the gamma leads to beta and the G gamma leads to A gamma switches are mediated via mechanisms modulating the relative activities of the different genes in the non-alpha globin gene cluster rather than via selection of clones committed to the preferential synthesis of beta and A gamma globins. In contrast with the results obtained with cord blood, individual adult blood bursts synthesize a lower and hence relatively more uniform amount of gamma globin chains. PMID:6153796

  8. Systematic review of the mechanisms and evidence behind the hypocholesterolaemic effects of HPMC, pectin and chitosan in animal trials.

    PubMed

    van der Gronde, Toon; Hartog, Anita; van Hees, Charlotte; Pellikaan, Hubert; Pieters, Toine

    2016-05-15

    Dietary fibres have diverse mechanisms in reducing plasma cholesterol, which could be useful for treating high levels of low-density lipoprotein cholesterol (LDL-C). The objective of this review is to determine the state of the evidence for the cholesterol-lowering effects of three selected fibres and their mechanisms, using the most recent animal trials. Therefore, a systematic review was conducted for hydroxypropyl methylcellulose (HPMC), pectin and chitosan in Pubmed, Embase and the Cochrane Library. All fibres reviewed reduced total cholesterol, very low-density lipoprotein cholesterol (VLDL-C) and LDL-C. Pectin gave a small, and chitosan an impressive rise in high-density lipoprotein cholesterol (HDL-C). A limitation of this study is the variety of animal models, each with distinct cholesterol profiles. Possible publication bias was also detected. In conclusion, chitosan seems to be the most promising of the studied fibres. A dietary fibre could be designed that yields the best cholesterol-lowering effect, using experiences in tailoring physicochemical properties and primarily exploiting the biophysical mechanisms of action. PMID:26776032

  9. Fractal analysis of extra-embryonic vessels of chick embryos under the effect of glucosamine and chondroitin sulfates.

    PubMed

    de Souza Lins Borba, Fernanda Katharine; Felix, Giovanni Loos Queiroz; Costa, Edbhergue Ventura Lola; Silva, Lisie; Dias, Paulo Fernando; de Albuquerque Nogueira, Romildo

    2016-05-01

    Like heparan sulfate proteoglycans, some monosaccharides and glycosaminoglycans, such as sulfated glucosamine (GS) and chondroitin (CS), integrate the vascular extracellular matrix and may influence vascular endothelial cell growth. To assess the effects of these substances on blood vessel formation, we used the chick yolk sac membrane (YSM) model and fractal geometry quantification, which provided an objective in vivo method for testing potential agents that promote vasculogenesis and angiogenesis. An image processing method was developed to evaluate YSM capillary vessels after they were implanted in a methylcellulose disk of GS or CS at a concentration between 0.001-0.1mg/disk (performed on 2-day old embryos). This method resulted in a binary image of the microvascular network (white vessels on a black background). Fractal box-counting (DBC) and information (DINF) dimensions were used to quantify the activity of GS and CS in vasculogenesis and angiogenesis. YSM treated with GS (0.001-0.1mg) and CS (0.03-0.1mg) showed an increase in fractal dimensions that corresponded to vitelline vessel growth compared to the control group (vehicle), with GS displaying higher fractal dimension values. PMID:26873109

  10. Benznidazole Extended-Release Tablets for Improved Treatment of Chagas Disease: Preclinical Pharmacokinetic Study.

    PubMed

    Davanço, Marcelo Gomes; Campos, Michel Leandro; Rosa, Talita Atanazio; Padilha, Elias Carvalho; Alzate, Alejandro Henao; Rolim, Larissa Araújo; Rolim-Neto, Pedro José; Peccinini, Rosângela Gonçalves

    2016-04-01

    Benznidazole (BNZ) is the first-line drug for the treatment of Chagas disease. The drug is available in the form of immediate-release tablets for 100-mg (adult) and 12.5-mg (pediatric) doses. The drug is administered two or three times daily for 60 days. The high frequency of daily administrations and the long period of treatment are factors that significantly contribute to the abandonment of therapy, affecting therapeutic success. Accordingly, this study aimed to evaluate the preclinical pharmacokinetics of BNZ administered as extended-release tablets (200-mg dose) formulated with different types of polymers (hydroxypropyl methylcellulose K4M and K100M), compared to the tablets currently available. The studies were conducted with rabbits, and BNZ quantification was performed in plasma and urine by ultraperformance liquid chromatography methods previously validated. The bioavailability of BNZ was adequate in the administration of extended-release tablets; however, with the administration of the pediatric tablet, the bioavailability was lower than with other tablets, which showed that the clinical use of this formulation should be monitored. The pharmacokinetic parameters demonstrated that the extended-release tablets prolonged drug release from the pharmaceutical matrix and provided an increase in the maintenance of the drug concentrationin vivo, which would allow the frequency of administration to be reduced. Thus, a relative bioavailability study in humans will be planned for implementation of a new product for the treatment of Chagas disease. PMID:26883698

  11. Erodible time-dependent colon delivery systems with improved efficiency in delaying the onset of drug release.

    PubMed

    Del Curto, Maria Dorly; Palugan, Luca; Foppoli, Anastasia; Zema, Lucia; Gazzaniga, Andrea; Maroni, Alessandra

    2014-11-01

    To prepare swellable/erodible time-dependent colon delivery systems with improved efficiency in delaying drug release, the application of an outer Eudragit® NE film, which contained the superdisintegrant Explotab® V17 as a pore former, was attempted. Tablet cores were successively spray-coated with a hydroxypropyl methylcellulose (HPMC) solution and diluted Eudragit® NE 30 D, wherein fixed amounts of Explotab® V17 were present. The resulting two-layer systems yielded lag phases of extended duration as compared with formulations provided with the HPMC layer only. By raising the thickness of the outer film, longer lag times were generally observed, whereas the effectiveness in deferring the drug liberation was reduced by increasing the pore former content, which, however, also resulted in a lower data variability. The films containing 20% of Explotab® V17 effectively and consistently prolonged the in vitro lag phase imparted by HPMC as a function of their thickness. Stored for 3 years under ambient conditions, a two-layer system with this outer film composition pointed out unmodified release patterns. The same system proved to meet gastroresistance criteria when enteric coated. The results obtained indicated that the proposed strategy would enable the preparation of erodible delivery systems with reduced size, possibly suitable as multiple-unit dosage forms. PMID:25213173

  12. Spectrophotometric and AAS determination of ramipril and enalapril through ternary complex formation.

    PubMed

    Ayad, Magda M; Shalaby, Abdalla A; Abdellatef, Hisham E; Hosny, Mervat M

    2002-04-15

    Two sensitive, spectrophotometric and atomic absorption spectrometric procedures are developed for the determination of two antihypertensive agents (enalapril maleate and ramipril). The spectrophotometric procedures for the two cited drugs are based on ternary complex formation. The first ternary complex (copper(II), eosin, and enalapril) was estimated by two methods; the first depends on its extraction with chloroform measuring at 533.4 nm. Beer's law was obeyed in concentration range from 56 to 112 microg ml(-1). The second method for the same complex depends on its direct measurement after addition of methylcellulose as surfactant at the pH value 5 at 558.8 nm. The concentration range is from 19 to 32 microg ml(-1). The second ternary complex (iron(III), thiocyanate, and ramipril) was extracted with methylene chloride, measuring at 436.6 nm, with a concentration range 60-132 microg ml(-1). The direct atomic absorption spectrometric method through the quantitative determination of copper or iron content of the complex was also investigated for the purpose of enhancing the sensitivity of the determination. The spectrophotometric and atomic absorption spectrometric procedures hold their accuracy and precision well when applied to the determination of ramipril and enalapril dosage forms. PMID:11929674

  13. Development of the novel coating formulations for skin vaccination using stainless steel microneedle.

    PubMed

    Kim, Seong-Jin; Shin, Ju-Hyung; Noh, Jin-Yong; Song, Chang-Seon; Kim, Yeu-Chun

    2016-10-01

    This study focused on the development of novel coating formulations for stainless steel microneedles against influenza A virus. With in vitro studies, various viscosity enhancers and stabilizers were screened based on the hemagglutination activity of the vaccine, which was coated and dried onto a stainless steel chip at room temperature for 1 day. Following the long-term storage test, the hemagglutination activity and particle size of the vaccine, which was formulated with conventional or methylcellulose or hydroxyethyl cellulose and dried onto the microneedle, were monitored. Next, to evaluate the in vivo immunogenicity and protection effect of each dried vaccine formulation, mice were immunized by the antigen-coated microneedle, which had either the conventional or the proposed formulation. Two novel formulations were chosen in the preliminary screening, and in further evaluations, they exhibited a 20 % higher HA activity during storage for 3 months, and no aggregation was observed during storage after drying. In a mouse model, the microneedle with the novel formulation elicited a higher level of IgG and IgG2a was more prevalent in the IgG isotype profile. In addition, mice immunized with the HEC-coated microneedle survived with small weight loss (>90 %) against lethal challenge infection. Overall, the novel formulation hydroxyethyl cellulose preserved significantly higher HA activity during the production and storage of the microneedle as well as improved the in vivo immunogenicity of the vaccine. PMID:27519363

  14. Welding of silver nanowire networks via flash white light and UV-C irradiation for highly conductive and reliable transparent electrodes

    PubMed Central

    Chung, Wan-Ho; Kim, Sang-Ho; Kim, Hak-Sung

    2016-01-01

    In this work, silver nanowire inks with hydroxypropyl methylcellulose (HPMC) binders were coated on polyethylene terephthalate (PET) substrates and welded via flash white light and ultraviolet C (UV-C) irradiation to produce highly conductive transparent electrodes. The coated silver nanowire films were firmly welded and embedded into PET substrate successfully at room temperature and under ambient conditions using an in-house flash white light welding system and UV-C irradiation. The effects of light irradiation conditions (light energy, irradiation time, pulse duration, and pulse number) on the silver nanowire networks were studied and optimized. Bending fatigue tests were also conducted to characterize the reliability of the welded transparent conductive silver nanowire films. The surfaces of the welded silver nanowire films were analyzed via scanning electron microscopy (SEM), while the transmittance of the structures was measured using a spectrophotometer. From the results, a highly conductive and transparent silver nanowire film with excellent reliability could be achieved at room temperature under ambient conditions via the combined flash white light and UV-C irradiation welding process. PMID:27553755

  15. Regulation of heme metabolism in normal and sideroblastic bone marrow cells in culture

    SciTech Connect

    Ibraham, N.G.; Lutton, J.D.; Hoffman, R.; Levere, R.D.

    1985-05-01

    Heme metabolism was examined in developing in vitro erythroid colonies (CFUE) and in bone marrow samples taken directly from four normal donors and four patients with sideroblastic anemia. Maximum activities of delta-aminolevulinic acid synthase (ALAS), ALA dehydratase (ALAD), and /sup 14/C-ALA incorporation into heme were achieved in normal marrow CFUE after 8 days of culture, whereas heme oxygenase progressively decreased to low levels of activity during the same period. Assays on nucleated bone marrow cells taken directly from patients revealed that ALAS activity was considerably reduced in idiopathic sideroblastic anemia (IASA) and X-linked sideroblastic anemia (X-SA) bone marrow specimens, whereas the activity increased more than twofold (normal levels) when cells were assayed from 8-day CFUE. In all cases, ALAD activity appeared to be within normal levels. Measurement of heme synthesis revealed that normal levels of /sup 14/C-ALA incorporation into heme were achieved in IASA cells but were reduced in X-SA cells. In marked contrast to levels in normal cells, heme oxygenase was found to be significantly elevated (two- to fourfold) in bone marrow cells taken directly from patients with IASA and X-SA. Results from this study demonstrate that IASA and X-SA bone marrow cells have disturbances in ALAS and heme metabolism, and that erythropoiesis (CFUE) can be restored to normal levels when cells are cultured in methylcellulose.

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

    PubMed

    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. PMID:12554071

  17. Characterization of nanoscale spatial distribution of small molecules in amorphous polymer matrices

    NASA Astrophysics Data System (ADS)

    Ricarte, Ralm; Hillmyer, Marc; Lodge, Timothy

    Hydroxypropyl methylcellulose acetate succinate (HPMCAS) can significantly enhance the efficacy of active pharmaceutical ingredients (APIs). Yet, the interactions between species in HPMCAS-API blends are not understood. Elucidating these interactions is difficult because the spatial distributions of HPMCAS and API in the blends are ambiguous; the polymer and drug may be molecularly mixed or the species may form phase separated domains. As these phase separated domains may be less than 100 nm in size, traditional characterization techniques may not accurately evaluate the spatial distribution. To address this challenge, we explore the use of electron energy-loss spectroscopy (EELS) for detecting the model API phenytoin in an HPMCAS-phenytoin blend. Using EELS, we directly measured with high accuracy and precision the phenytoin concentrations in several blends. We present evidence that suggests phase separation occurs in blends that have a phenytoin loading of approximately 50 wt percent. Finally, we demonstrate that this technique achieves a sub-100 nm spatial resolution and can detect several other APIs.

  18. Evaluation of Skin Permeation and Analgesic Activity Effects of Carbopol Lornoxicam Topical Gels Containing Penetration Enhancer

    PubMed Central

    Al-Suwayeh, Saleh A.; Taha, Ehab I.; Al-Qahtani, Fahad M.; Ahmed, Mahrous O.; Badran, Mohamed M.

    2014-01-01

    The current study was designed to develop a topical gel formulation for improved skin penetration of lornoxicam (LOR) for enhancement of its analgesic activity. Moreover, the effect of different penetration enhancers on LOR was studied. The LOR gel formulations were prepared by using hydroxylpropyl methylcellulose (HPMC) and carbopol. The carbopol gels in presence of propylene glycol (PG) and ethanol were developed. The formulated gels were characterized for pH, viscosity, and LOR release using Franz diffusion cells. Also, in vitro skin permeation of LOR was conducted. The effect of hydroxypropyl β-cyclodextrin (HP β-CD), beta-cyclodextrin (β-CD), Tween 80, and oleic acid on LOR permeation was evaluated. The optimized LOR gel formulation (LORF8) showed the highest flux (14.31 μg/cm2/h) with ER of 18.34 when compared to LORF3. Incorporation of PG and HP β-CD in gel formulation (LORF8) enhanced the permeation of LOR significantly. It was observed that LORF3 and LORF8 show similar analgesic activity compared to marketed LOR injection (Xefo). This work shows that LOR can be formulated into carbopol gel in presence of PG and HP β-CD and may be promising in enhancing permeation. PMID:25045724

  19. The fate of ritonavir in the presence of darunavir.

    PubMed

    Nguyen, D N; Van den Mooter, G

    2014-11-20

    This study was the first investigation into the potential of a fixed dose combination of ritonavir and darunavir in the form of dispersible powders prepared by spray drying. A common polymer (hydroxypropyl methylcellulose, polyvinylpyrrolidone, and polyvinylpyrrolidone-vinyl acetate 64) was formulated with either ritonavir or darunavir or a combination of ritonavir and darunavir. The influence of these polymers on the supersaturation level of ritonavir and darunavir was investigated. The concentration levels of ritonavir and darunavir during these tests dropped instantly to a plateau which could be considered as amorphous solubility. Besides, the presence of darunavir always decreased the supersaturation level of ritonavir and vice versa no matter which polymers were used. Moreover, the rate and extent of release of both ritonavir and darunavir from ternary spray-dried powders were less than the releases from binary spray-dried powders. Intermolecular interaction between ritonavir and darunavir was ruled out by (1)H NMR study which means that the decrease in supersaturation level or release must be at least partially attributed to the mediated solvent process. In order to restrict the mutual influence between darunavir and ritonavir, a complex of both ritonavir and darunavir with (2-hydroxypropyl)-β-cyclodextrin was prepared and improved the dissolution rate of both ritonavir and darunavir. PMID:25180992

  20. Stimulation of proliferation, differentiation, and function of human cells by primate interleukin 3

    SciTech Connect

    Lopez, A.F.; To, L.B.; Yang, Y.C.; Gamble, J.R.; Shannon, M.F.; Burns, G.F.; Dyson, P.G.; Juttner, C.A.; Clark, S.; Vadas, M.A.

    1987-05-01

    Cloned gibbon interleukin 3 (gIL-3) was found to stimulate the proliferation and differentiation of human bone marrow cells to produce day-14 granulocyte, macrophage, granulocyte-macrophage, and eosinophil colonies in semisolid agar. In the presence of normal human plasma, gIL-3 stimulated megakaryocytes. In methylcellulose cultures, it stimulated erythroid colonies in the presence, but not in the absence, of erythropoietin. When mature human leukocytes were used, gIL-3 stimulated the function of purified mature eosinophils as measured by the capacity to kill /sup 51/Cr-labeled antibody-coated target cells, to produce superoxide anions, and to phagocytize opsonized yeast particles in a manner similar to recombinant human granulocyte-macrophage colony-stimulating factor. In contrast, gIL-3 did not significantly stimulate any of the neutrophil functions tested, whereas human recombinant granulocyte-macrophage colony-stimulating factor was active in these assay. Among cytokines that are active on human hematopoietic cells, gIL-3 thus has a distinct set of functions and may predict the range of actions of the human molecule.

  1. Nanoscale Concentration Quantification of Pharmaceutical Actives in Amorphous Polymer Matrices by Electron Energy-Loss Spectroscopy.

    PubMed

    Ricarte, Ralm G; Lodge, Timothy P; Hillmyer, Marc A

    2016-07-26

    We demonstrated the use of electron energy-loss spectroscopy (EELS) to evaluate the composition of phenytoin:hydroxypropyl methylcellulose acetate succinate (HPMCAS) spin-coated solid dispersions (SDs). To overcome the inability of bright-field and high-angle annular dark-field TEM imaging to distinguish between glassy drug and polymer, we used the π-π* transition peak in the EELS spectrum to detect phenytoin within the HPMCAS matrix of the SD. The concentration of phenytoin within SDs of 10, 25, and 50 wt % drug loading was quantified by a multiple least-squares analysis. Evaluating the concentration of 50 different regions in each SD, we determined that phenytoin and HPMCAS are intimately mixed at a length scale of 200 nm, even for drug loadings up to 50 wt %. At length scales below 100 nm, the variance of the measured phenytoin concentration increases; we speculate that this increase is due to statistical fluctuations in local concentration and chemical changes induced by electron irradiation. We also performed EELS analysis of an annealed 25 wt % phenytoin SD and showed that the technique can resolve concentration differences between regions that are less than 50 nm apart. Our findings indicate that EELS is a useful tool for quantifying, with high accuracy and sub-100 nm spatial resolution, the composition of many pharmaceutical and soft matter systems. PMID:27419264

  2. Influence of hydroxypropylmethylcellulose addition and homogenization conditions on properties and ageing of corn starch based films.

    PubMed

    Jiménez, Alberto; Fabra, María José; Talens, Pau; Chiralt, Amparo

    2012-06-20

    Edible films based on corn starch, hydroxypropyl methylcellulose (HPMC) and their mixtures were prepared by using two different procedures to homogenize the film forming dispersions (rotor-stator and rotor-stator plus microfluidizer). The influence of both HPMC-starch ratio and the homogenization method on the structural, optical, tensile and barrier properties of the films was analysed. The ageing of the films was also studied by characterizing them after 5 weeks' storage. Starch re-crystallization in newly prepared and stored films was analysed by means of X-ray diffraction. HPMC-corn starch films showed phase separation of polymers, which was enhanced when microfluidization was applied to the film forming dispersion. Nevertheless, HPMC addition inhibited starch re-crystallization during storage, giving rise to more flexible films at the end of the period. Water barrier properties of starch films were hardly affected by the addition of HPMC, although oxygen permeability increased due to its poorer oxygen barrier properties. PMID:24750773

  3. HP55-coated capsule containing PLGA/RS nanoparticles for oral delivery of insulin.

    PubMed

    Wu, Zhi Min; Zhou, Liying; Guo, Xin Dong; Jiang, Wei; Ling, Li; Qian, Yu; Luo, Kathy Qian; Zhang, Li Juan

    2012-04-01

    In this work, we designed and developed a two-stage delivery system composed of enteric capsule and cationic nanoparticles for oral delivery of insulin. The enteric capsule was coated with pH-sensitive hydroxypropyl methylcellulose phthalate (HP55), which could selectively release insulin from nanoparticles in the intestinal tract, instead of stomach. The biodegradable poly(lactic-co-glycolic acid) (PLGA) was selected as the matrix for loading insulin. Eurdragit(®) RS (RS) was also introduced to the nanoparticles for enhancing the penetration of insulin across the mucosal surface in the intestine. The nanoparticles were prepared with the multiple emulsions solvent evaporation method via ultrasonic emulsification. The optimized nanoparticles have a mean size of 285nm, a positive zeta potential of 42mV. The encapsulation efficiency was up to 73.9%. In vitro results revealed that the initial burst release of insulin from nanoparticles was markedly reduced at pH 1.2, which mimics the stomach environment. In vivo effects of the capsule containing insulin PLGA/RS nanoparticles were also investigated in diabetic rat models. The oral delivered capsules induced a prolonged reduction in blood glucose levels. The pharmacological availability was found to be approximately 9.2%. All the results indicated that the integration of HP55-coated capsule with cationic nanoparticles may be a promising platform for oral delivery of insulin with high bioavailability. PMID:22248666

  4. Solvent mediated microstructures and release behavior of insulin from pH-sensitive nanoparticles.

    PubMed

    Wu, Zhi Min; Guo, Xin Dong; Zhang, Li Juan; Jiang, Wei; Ling, Li; Qian, Yu; Chen, Yun

    2012-06-01

    The insulin loaded nanoparticles composed of poly (lactic-co-glycolic acid) (PLGA) and hydroxypropyl methylcellulose phthalate (HP55) were prepared via the emulsions solvent diffusion method with two different solvents, namely, DMSO and acetone/water. The microstructures of the nanoparticles were studied by the solubility parameters theory, DSC, FTIR, and the nitrogen adsorption technique. Phase-separated PLGA domains were observed from the nanoparticles prepared with both types of solvents. Mesopores were observed from the nanoparticles prepared with DMSO as the solvent and almost did not exist with acetone/water. An in vitro drug release study showed that the pH-sensitivity of nanoparticles was not only attributed to the pH-dependent dissolubility of HP55 but also to the internal microstructure. The formation of mesopores accelerated the release of insulin, leading to no obvious pH-sensitivity of the nanoparticles prepared with DMSO. However, for the nanoparticles prepared with acetone/water, the release of insulin was pH-dependent. The results demonstrated that solvents played an important role in affecting the microstructures of nanoparticles, which influenced markedly the insulin release behavior. PMID:22356870

  5. Preparation and characterization of tablet formulation based on solid dispersion of glimepiride and poly(ester amide) hyperbranched polymer.

    PubMed

    Reven, Sebastjan; Homar, Miha; Peternel, Luka; Kristl, Julijana; Žagar, Ema

    2013-01-01

    The feasibility of incorporating a solid dispersion containing poorly soluble antidiabetic drug glimepiride and poly(ester amide) hyperbranched polymer into a tablet using a direct-compression tabletting technique was investigated. Tablet cores were additionally coated with hydroxypropyl methylcellulose phthalate in order to protect the extremely hygroscopic solid dispersion from atmospheric moisture. Preliminary stability studies show that glimepiride, which is in amorphous form within solid dispersion, is chemically stable, even if tablets are exposed to elevated temperature and/or moisture. In-vitro dissolution studies show some impact of storage conditions on the tablet cores disintegration time and, consequently, drug release rate. Glimepiride solubility also deteriorates somewhat, most probably due to its partial recrystallization. Storage conditions much less affect the physical stability of coated tablets, which was ascribed to reduced tablet hygroscopicity due to the presence of protecting coating. The hyperbranched polymers are rather new and complex macromolecules. Therefore, we addressed also the biocompatibility of hyperbranched polymer, i.e., its impact on haemolysis of the red blood cells. The concentration required for the haemolytic effect on the red blood cells is around 100-times higher than its expected gastrointestinal luminal concentration, which makes the occurrence of hyperbranched polymer mediated cytotoxicity very unlikely. PMID:21812524

  6. Effects of combined treatments of irradiation and antimicrobial coatings on reduction of food pathogens in broccoli florets

    NASA Astrophysics Data System (ADS)

    Takala, P. N.; Salmieri, S.; Vu, K. D.; Lacroix, M.

    2011-12-01

    The effect of combined treatment of antimicrobial coatings and γ-radiation on reduction of food pathogens such as Listeria monocytogenes, Escherichia coli, and Salmonella Typhimurium was evaluated in broccoli florets. Broccoli florets were inoculated with pathogenic bacteria at 10 6 CFU/g. Inoculated florets were then coated with methylcellulose-based coating containing various mixtures of antimicrobial agents: organic acids (OAs) plus lactic acid bacteria metabolites (LABs), OA plus citrus extract (CE), OA plus CE plus spice mixture (SM), and OA plus rosemary extract (RE). Coated florets were irradiated with various doses (0-3.3 kGy), and microbial analyses were used to calculate the D10 value and radiosensitive relative. The coating containing OA plus CE was the most effective formulation for increasing the sensitization of Escherichia coli by 2.4 times as compared to the control without the antimicrobial coating. For Salmonella Typhimurium, coating containing OA plus LAB was the most effective formulation, increasing radiosensitivity by 2.4 times as well. All antimicrobial coatings had almost the same effect of increasing the sensitivity of Listeria monocytogenes (from 1.31 to 1.45 times) to γ-irradiation.

  7. Suberin fatty acids isolated from outer birch bark improve moisture barrier properties of cellulose ether films intended for tablet coatings.

    PubMed

    Heinämäki, Jyrki; Halenius, Anna; Paavo, Maaja; Alakurtti, Sami; Pitkänen, Pauliina; Pirttimaa, Minni; Paaver, Urve; Kirsimäe, Kalle; Kogermann, Karin; Yliruusi, Jouko

    2015-07-15

    We showed that the addition of suberin fatty acids (SFAs) even at small concentrations significantly improves the water vapor barrier properties of hydroxypropyl methylcellulose (HPMC) films. SFAs were isolated from the outer birch bark using extractive hydrolysis. The effects of SFAs on the film formation of aqueous HPMC were investigated with free films plasticized with polyethylene glycol (PEG 400). Special attention was paid on the physical solid-state, moisture barrier and mechanical stress-strain properties of films intended for tablet film coatings. Topography and surface morphology, glass transition temperature (Tg), tensile strength, Young's modulus, and water vapor permeation (WVP) of films were studied. The addition of SFAs lowered the Tg of films suggesting partial enhancement in film plasticization. The WVP of films decreased with increasing SFAs concentration up to 15% (calculated as a % w/w from a polymer weight). The WVP value for a non-suberized reference film and suberized film plasticized with PEG 400 was 2.13×10(-6) and 0.69[×10(-6) g/(mm(2)×h)×mm/Pa], respectively. The addition of SFAs impaired the mechanical stress-strain properties of HPMC films by reducing the deformation capacity of film. In conclusion, the film properties and performance of aqueous HPMC can be modified by including SFAs in the films. PMID:25936623

  8. Fabrication and evaluation of valsartan–polymer– surfactant composite nanoparticles by using the supercritical antisolvent process

    PubMed Central

    Kim, Min-Soo; Baek, In-hwan

    2014-01-01

    The aim of this study was to fabricate valsartan composite nanoparticles by using the supercritical antisolvent (SAS) process, and to evaluate the correlation between in vitro dissolution and in vivo pharmacokinetic parameters for the poorly water-soluble drug valsartan. Spherical composite nanoparticles with a mean size smaller than 400 nm, which contained valsartan, were successfully fabricated by using the SAS process. X-ray diffraction and thermal analyses indicated that valsartan was present in an amorphous form within the composite nanoparticles. The in vitro dissolution and oral bioavailability of valsartan were dramatically enhanced by the composite nanoparticles. Valsartan–hydroxypropyl methylcellulose–poloxamer 407 nanoparticles exhibited faster drug release (up to 90% within 10 minutes under all dissolution conditions) and higher oral bioavailability than the raw material, with an approximately 7.2-fold higher maximum plasma concentration. In addition, there was a positive linear correlation between the pharmacokinetic parameters and the in vitro dissolution efficiency. Therefore, the preparation of composite nanoparticles with valsartan–hydroxypropyl methylcellulose and poloxamer 407 by using the SAS process could be an effective formulation strategy for the development of a new dosage form of valsartan with high oral bioavailability. PMID:25404856

  9. Optimizing novel implant formulations for the prolonged release of biopharmaceuticals using in vitro and in vivo imaging techniques.

    PubMed

    Beyer, Susanne; Xie, Li; Schmidt, Mike; de Bruin, Natasja; Ashtikar, Mukul; Rüschenbaum, Sabrina; Lange, Christian M; Vogel, Vitali; Mäntele, Werner; Parnham, Michael J; Wacker, Matthias G

    2016-08-10

    As a rapidly growing class of therapeutics, biopharmaceuticals have conquered the global market. Despite the great potential from a therapeutic perspective, such formulations often require frequent injections due to their short half-life. Aiming to establish a parenteral dosage form with prolonged release properties, a biodegradable implant was developed, based on a combination of nanoencapsulation of protein-heparin complexes, creation of a slow release matrix by freeze-drying, and compression using hyaluronan and methylcellulose. In order to investigate this novel delivery system, formulations containing IFN-β-1a and trypsinogen as model proteins were developed. No degradation of the proteins was observed at any stage of the formulation processing. The potential of the delivery system was evaluated in vivo and in vitro after fluorescence-labeling of the biopharmaceuticals. An optimized agarose gel was utilized as in vitro release medium to simulate the subcutaneous environment in a biorelevant manner. In addition, the formulations were administered to female SJL mice and release was innovatively tracked by fluorescence imaging, setting up an in vitro-in vivo correlation. A prolonged time of residence of approximately 12days was observed for the selected formulation design. PMID:27288876

  10. Inhibition of MerTK increases chemosensitivity and decreases oncogenic potential in T-cell acute lymphoblastic leukemia.

    PubMed

    Brandao, L N; Winges, A; Christoph, S; Sather, S; Migdall-Wilson, J; Schlegel, J; McGranahan, A; Gao, D; Liang, X; Deryckere, D; Graham, D K

    2013-01-01

    Pediatric leukemia survival rates have improved dramatically over the past decades. However, current treatment protocols are still largely ineffective in cases of relapsed leukemia and are associated with a significant rate of chronic health conditions. Thus, there is a continued need for new therapeutic options. Here, we show that mer receptor tyrosine kinase (MerTK) was abnormally expressed in approximately one half of pediatric T-cell leukemia patient samples and T-cell acute lymphoblastic leukemia (T-ALL) cell lines. Stimulation of MerTK by the ligand Gas6 led to activation of the prosurvival proteins Erk 1/2 and Stat5, and MerTK-dependent activation of the STAT pathway in leukemia represents a novel finding. Furthermore, inhibition of MerTK expression increased the sensitivity of T-ALL cells to treatment with chemotherapeutic agents and decreased the oncogenic potential of the Jurkat T-ALL cell line in a methylcellulose colony-forming assay. Lastly, inhibition of MerTK expression significantly increased median survival in a xenograft mouse model of leukemia (30.5 days vs 60 days, P<0.0001). These results suggest that inhibition of MerTK is a promising therapeutic strategy for the treatment of leukemia and may allow for dose reduction of currently used chemotherapeutics resulting in decreased rates of therapy-associated toxicities. PMID:23353780

  11. Inhibition of MerTK increases chemosensitivity and decreases oncogenic potential in T-cell acute lymphoblastic leukemia

    PubMed Central

    Brandao, L N; Winges, A; Christoph, S; Sather, S; Migdall-Wilson, J; Schlegel, J; McGranahan, A; Gao, D; Liang, X; DeRyckere, D; Graham, D K

    2013-01-01

    Pediatric leukemia survival rates have improved dramatically over the past decades. However, current treatment protocols are still largely ineffective in cases of relapsed leukemia and are associated with a significant rate of chronic health conditions. Thus, there is a continued need for new therapeutic options. Here, we show that mer receptor tyrosine kinase (MerTK) was abnormally expressed in approximately one half of pediatric T-cell leukemia patient samples and T-cell acute lymphoblastic leukemia (T-ALL) cell lines. Stimulation of MerTK by the ligand Gas6 led to activation of the prosurvival proteins Erk 1/2 and Stat5, and MerTK-dependent activation of the STAT pathway in leukemia represents a novel finding. Furthermore, inhibition of MerTK expression increased the sensitivity of T-ALL cells to treatment with chemotherapeutic agents and decreased the oncogenic potential of the Jurkat T-ALL cell line in a methylcellulose colony-forming assay. Lastly, inhibition of MerTK expression significantly increased median survival in a xenograft mouse model of leukemia (30.5 days vs 60 days, P<0.0001). These results suggest that inhibition of MerTK is a promising therapeutic strategy for the treatment of leukemia and may allow for dose reduction of currently used chemotherapeutics resulting in decreased rates of therapy-associated toxicities. PMID:23353780

  12. Design, Development and Optimization of S (-) Atenolol Floating Sustained Release Matrix Tablets Using Surface Response Methodology.

    PubMed

    Gunjal, P T; Shinde, M B; Gharge, V S; Pimple, S V; Gurjar, M K; Shah, M N

    2015-01-01

    The objective of this present investigation was to develop and formulate floating sustained release matrix tablets of s (-) atenolol, by using different polymer combinations and filler, to optimize by using surface response methodology for different drug release variables and to evaluate the drug release pattern of the optimized product. Floating sustained release matrix tablets of various combinations were prepared with cellulose-based polymers: Hydroxypropyl methylcellulose, sodium bicarbonate as a gas generating agent, polyvinyl pyrrolidone as a binder and lactose monohydrate as filler. The 3(2) full factorial design was employed to investigate the effect of formulation variables on different properties of tablets applicable to floating lag time, buoyancy time, % drug release in 1 and 6 h (D1 h,D6 h) and time required to 90% drug release (t90%). Significance of result was analyzed using analysis of non variance and P < 0.05 was considered statistically significant. S (-) atenolol floating sustained release matrix tablets followed the Higuchi drug release kinetics that indicates the release of drug follows anomalous (non-Fickian) diffusion mechanism. The developed floating sustained release matrix tablet of improved efficacy can perform therapeutically better than a conventional tablet. PMID:26798171

  13. Formulation and evaluation of novel coated floating tablets of bergenin and cetirizine dihydrochloride for gastric delivery.

    PubMed

    He, Shuang; Li, Feng; Zhou, Dan; Du, Junrong; Huang, Yuan

    2012-10-01

    A novel coated gastric floating drug-delivery system (GFDDS) of bergenin (BN) and cetirizine dihydrochloride (CET) was developed. First, the pharmacodynamic studies were performed and the results revealed that the new compounds of bergenin/cetirizine dihydrochloride had comparative efficacy as commercial products (bergenin/chlorphenamine maleate) but with fewer side effects on central nervous system (CNS). Subsequently, bergenin was formulated as an extended-release core tablet while cetirizine dihydrochloride was incorporated into the gastric coating film for immediate release. The formulation of GFDDS was optimized by CET content uniformity test, in vitro buoyancy and drug release. Herein, the effects of sodium bicarbonate (effervescent), hydroxypropyl methylcellulose (HPMC, matrix polymer) and coating weight gain were investigated respectively. The optimized GFDDS exhibited good floating properties (buoyancy lag time < 2 min; floating duration > 10 h) and satisfactory drug-release profiles (immediate release of CET in 10 min and sustained release of BN for 12 h). In vivo gamma scintigraphy proved that the optimized GFDDS could retain in the stomach with a prolonged gastric retention time (GRT) of 5 h, and the coating layer showed no side effect for gastric retention. The novel coated gastric floating drug-delivery system offers a new approach to enhance BN's absorption at its absorption site and the efficacy of both CET and BN. PMID:22206469

  14. Development of dengue virus plaques under serum-free overlay medium.

    PubMed Central

    Malewicz, B; Jenkin, H M

    1979-01-01

    An improved plaque assay for dengue virus was developed utilizing baby hamster kidney (BHK-21) cells initially grown in shaker culture. Different media preparations were tested for uniform and fast formation of BHK-21 cell sheets. Several overlay formulas were tested to develop a rapid plaque assay in 6- and 24-well plastic plates. The best results were obtained utilizing Eagle minimal essential medium (pH 7.2 to 7.4) supplemented with 1 mg of NaHCO3 per ml and 5% newborn calf serum for the formation of cell monolayers after 8 to 24 h of incubation at 37 degrees C. Serum-free Eagle minimal essential medium supplemented with 1% methylcellulose and buffered with 10 mM N-2-hydroxyethyl piperazine-N'-2-ethanesulfonic acid (pH 7.4 to 7.6) was used as an overlay medium. This system allowed for plaque formation after 3 days of incubation of dengue type 2 virus and after 4 days for dengue type 1 and 4 viruses. Images PMID:39085

  15. Inhibitory effect of gels loaded with a low concentration of antibiotics against biofilm formation by Enterococcus faecalis and Porphyromonas gingivalis.

    PubMed

    A Algarni, Amnah; H Yassen, Ghaeth; L Gregory, Richard

    2015-09-01

    We explored longitudinally the inhibitory effect of gels loaded with 1 mg/mL modified triple antibiotic paste (MTAP) or double antibiotic paste (DAP) against biofilm formation by Enterococcus faecalis and Porphyromonas gingivalis. Methylcellulose-based antibiotic gels of MTAP (ciprofloxacin, metronidazole and clindamycin) and DAP (ciprofloxacin and metronidazole) were prepared at a concentration of 1 mg/mL. Individually cultured E. faecalis and P. gingivalis bacterial suspensions were treated with MTAP, DAP, or placebo (vehicle only) gels at different dilutions and allowed to grow in 96-well microtiter plates. Untreated bacterial suspensions served as a negative control. Crystal violet assays were used to evaluate biofilm formation after 48 h. The ability of the gels to inhibit biofilm formation was determined immediately, and at 1 month and 3 months after the gels had been prepared. Data were analyzed using a mixed-model ANOVA. The MTAP and DAP gels significantly reduced biofilm formation by both bacterial species at all time points, regardless of the tested dilution. No-significant differences in biofilm-inhibitory effects between MTAP and DAP gels were observed at the majority of the tested dilutions through various time points. Gels loaded with 1 mg/mL MTAP and DAP demonstrated a significant antibiofilm effect against E.faecalis and P. gingivalis. PMID:26369485

  16. Interplay between type IV pili activity and exopolysaccharides secretion controls motility patterns in single cells of Myxococcus xanthus

    PubMed Central

    Hu, Wei; Gibiansky, Maxsim L.; Wang, Jing; Wang, Chuandong; Lux, Renate; Li, Yuezhong; Wong, Gerard C. L.; Shi, Wenyuan

    2016-01-01

    Myxococcus xanthus performs coordinated social motility of cell groups through the extension and retraction of type IV pili (TFP) on solid surfaces, which requires both TFP and exopolysaccharides (EPS). By submerging cells in a liquid medium containing 1% methylcellulose, M. xanthus TFP-driven motility was induced in isolated cells and independently of EPS. We measured and analyzed the movements of cells using community tracking algorithms, which combine single-cell resolution with statistics from large sample populations. Cells without significant multi-cellular social interactions have surprisingly complex behaviors: EPS− cells exhibited a pronounced increase in the tendency to stand vertically and moved with qualitatively different characteristics than other cells. A decrease in the EPS secretion of cells correlates with a higher instantaneous velocity, but with lower directional persistence in trajectories. Moreover, EPS− cells do not adhere to the surface as strongly as wild-type and EPS overproducing cells, and display a greater tendency to have large deviations between the direction of movement and the cell axis, with cell velocity showing only minimal dependence on the direction of movement. The emerging picture is that EPS does not simply provide rheological resistance to a single mechanism but rather that the availability of EPS impacts motility pattern. PMID:26821939

  17. Dry coating in a rotary fluid bed.

    PubMed

    Kablitz, Caroline Désirée; Harder, Kim; Urbanetz, Nora Anne

    2006-02-01

    A highly efficient dry coating process was developed to obtain an enteric film avoiding completely the use of organic solvents and water. Using hydroxypropyl methylcellulose acetate succinate (HPMCAS) an enteric coat should be obtained without adding talc as anti-tacking agent because of problems arising from microbiological contamination. Further on, a method was developed preparing isolated films in order to determine the glass transition temperature (T(g)) and the required process temperature. The process was conducted in the rotary fluid bed with a gravimetric powder feeder achieving an exact dosage in contrast to volumetric powder feeder. A three way nozzle was aligned tangential to the pellet bed movement feeding simultaneously powder and plasticizer into the rotary fluid bed. The determined coating efficiency of the talc-free formulation was high with 94% and storage stability regarding tacking could be achieved using colloidal silicium dioxide as top powder. The T(g) of the enteric coat could be determined analyzing the T(g) of isolated films obtained by coating celluloid spheres instead of pellets using the dry coating process in rotary fluid bed. The dry coating process has been demonstrated to be a serious alternative to conventional solvent or water based coating processes. PMID:16290285

  18. Hot-melt extruded filaments based on pharmaceutical grade polymers for 3D printing by fused deposition modeling.

    PubMed

    Melocchi, Alice; Parietti, Federico; Maroni, Alessandra; Foppoli, Anastasia; Gazzaniga, Andrea; Zema, Lucia

    2016-07-25

    Fused deposition modeling (FDM) is a 3D printing technique based on the deposition of successive layers of thermoplastic materials following their softening/melting. Such a technique holds huge potential for the manufacturing of pharmaceutical products and is currently under extensive investigation. Challenges in this field are mainly related to the paucity of adequate filaments composed of pharmaceutical grade materials, which are needed for feeding the FDM equipment. Accordingly, a number of polymers of common use in pharmaceutical formulation were evaluated as starting materials for fabrication via hot melt extrusion of filaments suitable for FDM processes. By using a twin-screw extruder, filaments based on insoluble (ethylcellulose, Eudragit(®) RL), promptly soluble (polyethylene oxide, Kollicoat(®) IR), enteric soluble (Eudragit(®) L, hydroxypropyl methylcellulose acetate succinate) and swellable/erodible (hydrophilic cellulose derivatives, polyvinyl alcohol, Soluplus(®)) polymers were successfully produced, and the possibility of employing them for printing 600μm thick disks was demonstrated. The behavior of disks as barriers when in contact with aqueous fluids was shown consistent with the functional application of the relevant polymeric components. The produced filaments were thus considered potentially suitable for printing capsules and coating layers for immediate or modified release, and, when loaded with active ingredients, any type of dosage forms. PMID:27215535

  19. Local Delivery of Neurotrophin-3 and Anti-NogoA Promotes Repair After Spinal Cord Injury.

    PubMed

    Elliott Donaghue, Irja; Tator, Charles H; Shoichet, Molly S

    2016-05-01

    Tissue and functional repair after spinal cord injury (SCI) continue to elude researchers. Neurotrophin-3 (NT-3) and anti-NogoA have been shown to promote axonal regeneration in animal models of SCI; however, localized and sustained delivery to the central nervous system (CNS) remains a critical challenge for these and other macromolecular therapeutics. An injectable drug delivery system (DDS) has previously been developed, which can provide safe local delivery to the spinal cord. This DDS, composed of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (nps) dispersed in a hyaluronan methylcellulose hydrogel, was adapted for the tunable bioactive delivery of NT-3 and anti-NogoA. Furthermore, the combined delivery of NT-3 and anti-NogoA from the DDS in an impact/compression model of SCI increases axon density and improves locomotor function. The benefits of this np/hydrogel DDS observed for NT-3 and anti-NogoA demonstrate the utility of the DDS as a local delivery strategy for protein therapeutics to the CNS. PMID:27056081

  20. Dynamic scaling analysis of two-dimensional cell colony fronts in a gel medium: A biological system approaching a quenched Kardar-Parisi-Zhang universality

    NASA Astrophysics Data System (ADS)

    Huergo, M. A. C.; Muzzio, N. E.; Pasquale, M. A.; González, P. H. Pedro; Bolzán, A. E.; Arvia, A. J.

    2014-08-01

    The interfacial two-dimensional spreading dynamics of quasilinear Vero cell colony fronts in methylcellulose (MC)-containing culture medium, under a constant average front displacement velocity regime, was investigated. Under comparable experimental conditions, the average colony front displacement velocity becomes lower than that reported for a standard culture medium. Initially, the presence of MC in the medium hinders both the colony spreading, due to a gradual change in the average size and shape of cells and their distribution in the colony, and the cell motility in the gelled medium. Furthermore, at longer culture times enlarged cells appear at random in the border region of the colony. These cells behave as obstacles (pinning sites) for the displacement of smaller cells towards the colony front. The dynamic scaling analysis of rough fronts yields the set of exponents α =0.63±0.04,β =0.75±0.05, and z =0.84±0.05, which is close to that expected for a quenched Kardar-Parisi-Zhang model.

  1. Foam granulation: new developments in pharmaceutical solid oral dosage forms using twin screw extrusion machinery.

    PubMed

    Thompson, M R; Weatherley, S; Pukadyil, R N; Sheskey, P J

    2012-07-01

    This paper investigates foam granulation in a twin screw extruder as a new continuous wet granulation technique for pharmaceutical powder drug formulations. Foamed aqueous binder has a reportedly lower soak-to-spread ratio than drop or spray liquid addition in batch granulation. This work demonstrates a twin screw extruder configuration for foam granulation and subsequently compares the new approach against liquid injection in the granulation of α-lactose monohydrate with a methylcellulose binder. Trials were conducted at high powder output rates (20-40 kg/h) and high screw speeds (220-320 RPM) with two screw configurations. Process stability improved with the new technique allowing granulation with less binder. The extruded mass maintained a low exit temperature, being insensitive to operating conditions unlike the liquid injection approach, where temperatures rose significantly as flow rate increased. The particle size distribution by foam granulation reflected a more uniformly wetted mass with larger granule growth noted even for conditions where dry powder exited by liquid injection. Other factors were found similar between the two binder delivery methods such as consumed mechanical energy, as well as fracture strength and compressibility of produced granules. PMID:22085462

  2. Solid lipid nanoparticles for topical administration of Kaempferia parviflora extracts.

    PubMed

    Sutthanut, Khaetthareeya; Lu, Xiuling; Jay, Michael; Sripanidkulchai, Bungorn

    2009-04-01

    Extracts of Kaempferia parviflora (KP) were formulated in solid lipid nanoparticles (SLNs) in order to enhance their transdermal permeability. The KP extracts were entrapped within SLNs by adding them to a melted mixture of oils, surfactants and PEGylating agents and subsequently forming an oil-in-water microemulsion at an elevated temperature. Cooling of this microemulsion resulted in the formation of SLNs. The formulation with the optimum properties was composed of stearyl alcohol as the nanoparticle matrix and Tocopheryl Polyethylene Glycol Succinate (TPGS) as the surfactant. Particle sizes of 82-108 nm were obtained with entrapment efficiencies as high as 87%. The release of the flavonoids from the SLN matrix was measured after suspending them in a Phosphate Buffered Saline (PBS)/Tween 80 solution and demonstrated biphasic patterns. Permeability studies using a skin model composed of human-derived epidermal keratinocytes were conducted in which a topically applied KP extract-loaded SLN was compared to a KP-hydroxypropyl methylcellulose/Tween 80 gel formulation containing KP extract. The amount of total KP flavonoids in the SLNs and gel that had permeated through the skin after 25 hours (95.57 +/- 9.08 and 81.04 +/- 5.82 g, respectively) were found to be significantly different (P < 0.05). In addition, the flux values of three of the flavonoids were greater when incorporated in SLNs. PMID:20055101

  3. Mechanistic analysis of PLGA/HPMC-based in-situ forming implants for periodontitis treatment.

    PubMed

    Do, M P; Neut, C; Metz, H; Delcourt, E; Siepmann, J; Mäder, K; Siepmann, F

    2015-08-01

    In-situ forming implant formulations based on poly(lactic-co-glycolic acid) (PLGA), acetyltributyl citrate (ATBC), minocycline HCl, N-methyl pyrrolidone (NMP) and optionally hydroxypropyl methylcellulose (HPMC) were prepared and thoroughly characterized in vitro. This includes electron paramagnetic resonance (EPR), nuclear magnetic resonance ((1)H NMR), mass change and drug release measurements under different conditions, optical microscopy, size exclusion chromatography (SEC) as well as antibacterial activity tests using gingival crevicular fluid samples from periodontal pockets of periodontitis patients. Based on these results, deeper insight into the physico-chemical phenomena involved in implant formation and the control of drug release could be gained. For instance, the effects of adding HPMC to the formulations, resulting in improved implant adherence and reduced swelling, could be explained. Importantly, the in-situ formed implants effectively hindered the growth of bacteria present in the patients' periodontal pockets. Interestingly, the systems were more effectively hindering the growth of pathogenic bacterial strains (e.g., Fusobacterium nucleatum) than that of strains with a lower pathogenic potential (e.g., Streptococcus salivarius). In vivo, such a preferential action against the pathogenic bacteria can be expected to give a chance to the healthy flora to re-colonize the periodontal pockets. PMID:26047797

  4. Viscoelastic interactions between polydeoxyribonucleotide and ophthalmic excipients.

    PubMed

    Kim, Iksoo; Kim, Hyeongmin; Park, Kyunghee; Karki, Sandeep; Khadka, Prakash; Jo, Kanghee; Kim, Seong Yeon; Ro, Jieun; Lee, Jaehwi

    2016-01-01

    This study investigated the interaction between polydeoxyribonucleotide (PDRN) and several ionic and nonionic isotonic agents, thickeners and a preservative that were employed as excipients in ophthalmic preparations. Interaction of each individual excipient and PDRN aqueous solution was evaluated by analyzing their rheological properties. Rheological properties of PDRN solutions were evaluated by dynamic oscillatory shear tests and values of elastic modulus (G'), viscous modulus (G″) and loss tangent (tan δ) were used to assess the relative changes in viscoelastic properties. At given concentrations, sodium chloride was found to show alteration in viscoelastic properties of PDRN solution while nonionic isotonic agents like d-glucose and d-sorbitol did not alter them. Similarly, nonionic water soluble polymers like polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose (HPMC) also did not interact with PDRN to alter the viscoelastic properties. However, there were changes observed when carbopol 940 was used as a thickener. Therefore, PDRN was found to interact with ionic excipients and the interactions were negligible when nonionic materials were examined, which suggests that nonionic excipients are suitable to be formulated with PDRN. PMID:26023993

  5. Crystallization of progesterone polymorphs using polymer-induced heteronucleation (PIHn) method.

    PubMed

    Araya-Sibaja, Andrea Mariela; Soldi, Valdir; Campos, Carlos Eduardo Maduro; Cardoso, Simone Gonçalves; Cuffini, Silvia Lucia

    2015-05-01

    Progesterone is a natural hormone steroid used in humans for several treatments and in livestock for artificial insemination, which exhibits two polymorphic forms at ambient conditions: form 1 and form 2. Form 2 is metastable and more soluble than form 1; however, it is not suitable to use as powder raw material because it transforms into form 1 by the effects of grinding. A polymorphic screening of progesterone based on polymer-induced heteronucleation method was performed as an alternative to prepare the metastable form. Polyvinyl alcohol, hydroxypropyl methylcellulose (HPMC), dextran, gelatin, polyisoprene (PI) and acrylonitrile-butadiene (NBR) copolymer were used. Crystals were prepared from 0.5, 10 and 40 mg/mL solutions in acetone at room temperature by solvent evaporation. The samples were characterized by X-ray powder diffraction, differential scanning calorimetry (DSC), scanning electron microcopy and attenuated total reflectance infrared Fourier transform spectroscopy. Form 1 was nucleated from 40 mg/mL solutions on the six polymers and from 10 mg/mL solutions on PI and NBR. The mixture of form 1 and form 2 was obtained from 10 mg/mL solution on HPMC, dextran and gelatin and from 0.5 mg/mL solution crystallizations. Therefore, the polymeric devices, which crystallized the metastable and more soluble polymorph (2) of progesterone, would be a promissory alternative for the pharmaceutical applications. PMID:24758712

  6. Electrospun nanofibers as a potential controlled-release solid dispersion system for poorly water-soluble drugs.

    PubMed

    Paaver, Urve; Heinämäki, Jyrki; Laidmäe, Ivo; Lust, Andres; Kozlova, Jekaterina; Sillaste, Elen; Kirsimäe, Kalle; Veski, Peep; Kogermann, Karin

    2015-02-01

    Electrospinning was introduced as a novel technique for preparing controlled-release (CR) amorphous solid dispersions (SD) and polymeric nanofibers of a poorly water-soluble drug. Piroxicam (PRX) was used as a low-dose poorly-soluble drug and hydroxypropyl methylcellulose (HPMC) as an amorphous-state stabilising carrier polymer in nanofibers. Raman spectroscopy, X-ray powder diffraction (XPRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) were used in the physical characterisation of the CR-SD nanofibers. Special attention was paid on the effects of a polymer and solvent system on the solid-state properties and physical stability of nanofibers. The average dry diameter of the electrospun CR-SD nanofibers ranged from 400 to 600 nm (SEM). PRX existed in amorphous form in the nanofibers immediately after fabrication and after a short-term (3-month) aging at low temperature (6-8 °C/0% RH) and ambient room temperature (22 °C/0% RH). At higher temperature and humidity (30 °C/85% RH), however, amorphous PRX in the nanofibers tended to slowly recrystallise to PRX form III. The electrospun CR-SD nanofibers exhibited a short lag-time, the absence of initial burst release and zero-order linear CR dissolution kinetics. In conclusion, electrospinning can be used to fabricate supersaturating CR-SD nanofibers of PRX and HPMC, and to stabilise the amorphous state of PRX. PMID:25549852

  7. Porous networks derived from synthetic polymer-clay complexes

    SciTech Connect

    Carrado, K.A.; Thiyagarajan, P.; Elder, D.L.

    1995-05-12

    Synthetic hectorites were hydrothermally crystallized with direct incorporation of a cationic polymer poly(dimethyl diallyl ammonium chloride) (PDDA), and two neutral cellulosic polymers hydroxypropyl methylcellulose (HPMC) and hydroxyethyl cellulose (HEC). Synthetic PDDA-hectorite displays the lowest d-spacing at 15.8 {Angstrom} along with less polymer incorporation (7.8 wt % organic) than the neutral polymers (18--22 wt % organic). Thermal analysis and small angle neutron scattering were used to further examine the polymer-clay systems. Clay platelets of the largest size and best stacking order occur when cationic PDDA polymer is used. PDDA also enhances these properties over the crystallites prepared for a control mineral, where no polymer is used. HEC acts to aggregate the silica, leaving less to react to form clay. The clay platelets which result from HEC are small, not stacked to a large degree, and oriented randomly. Neutral HPMC acts more like cationic PDDA in that larger clay platelets are allowed to form. The extended microstructure of the clay network remains undisturbed after polymer is removed by calcination. When no polymer is used, the synthetic hectorite has a N{sub 2} BET surface area of 200 M{sup 2}/gm, even after calcination. This increases by 20--50% for the synthetic polymer-hectorites after the polymer is removed by calcination.

  8. Intravenous Administration of Cilostazol Nanoparticles Ameliorates Acute Ischemic Stroke in a Cerebral Ischemia/Reperfusion-Induced Injury Model

    PubMed Central

    Nagai, Noriaki; Yoshioka, Chiaki; Ito, Yoshimasa; Funakami, Yoshinori; Nishikawa, Hiroyuki; Kawabata, Atsufumi

    2015-01-01

    It was reported that cilostazol (CLZ) suppressed disruption of the microvasculature in ischemic areas. In this study, we have designed novel injection formulations containing CLZ nanoparticles using 0.5% methylcellulose, 0.2% docusate sodium salt, and mill methods (CLZnano dispersion; particle size 81 ± 59 nm, mean ± S.D.), and investigated their toxicity and usefulness in a cerebral ischemia/reperfusion-induced injury model (MCAO/reperfusion mice). The pharmacokinetics of injections of CLZnano dispersions is similar to that of CLZ solutions prepared with 2-hydroxypropyl-β-cyclodextrin, and no changes in the rate of hemolysis of rabbit red blood cells, a model of cell injury, were observed with CLZnano dispersions. In addition, the intravenous injection of 0.6 mg/kg CLZnano dispersions does not affect the blood pressure and blood flow, and the 0.6 mg/kg CLZnano dispersions ameliorate neurological deficits and ischemic stroke in MCAO/reperfusion mice. It is possible that the CLZnano dispersions will provide effective therapy for ischemic stroke patients, and that injection preparations of lipophilic drugs containing drug nanoparticles expand their therapeutic usage. PMID:26690139

  9. Effect of source variation on drug release from HPMC tablets: linear regression modeling for prediction of drug release.

    PubMed

    Piriyaprasarth, Suchada; Sriamornsak, Pornsak

    2011-06-15

    The aim of this study was to investigate the effect of source variation of hydroxypropyl methylcellulose (HPMC) raw material on prediction of drug release from HPMC matrix tablets. To achieve this objective, the flow ability (i.e., angle of repose and Carr's compressibility index) and apparent viscosity of HPMC from 3 sources was investigated to differentiate HPMC source variation. The physicochemical properties of drug and manufacturing process were also incorporated to develop the linear regression model for prediction of drug release. Specifically, the in vitro release of 18 formulations was determined according to a 2 × 3 × 3 full factorial design. Further regression analysis provided a quantitative relationship between the response and the studied independent variables. It was found that either apparent viscosity or Carr's compressibility index of HPMC powders combining with solubility and molecular weight of drug had significant impact on the release behavior of drug. The increased drug release was observed when a greater in drug solubility and a decrease in the molecular weight of drug were applied. Most importantly, this study has shown that the HPMC having low viscosity or high compressibility index resulted in an increase of drug release, especially in the case of poorly soluble drugs. PMID:21420475

  10. Formulation and Evaluation of Omeprazole Tablets for Duodenal Ulcer

    PubMed Central

    Choudhury, A.; Das, S.; Bahadur, S.; Saha, S.; Roy, A.

    2010-01-01

    Omeprazole pellets containing mucoadhesive tablets were developed by direct punch method. Three mucoadhesive polymers namely hydroxypropylemethylcellulose K4M, sodium carboxy methylcellulose, carbopol-934P and ethyl cellulose were used for preparation of tablets which intended for prolong action may be due to the attachment with intestinal mucosa for relief from active duodenal ulcer. Mucoadhesive tablets were coated with respective polymer and coated with Eudragit L100 to fabricate enteric coated tablets. The prepared tablets were evaluated for different physical parameters and dissolution study were performed in three dissolution mediums like 0.1N hydrochloric acid for 2h, pH 6.5 and pH 7.8 phosphate buffer solution for 12hr. Sodium carboxymethylcellulose showed above 95% release within 10 h where as carbopol-934P showed slow release about 88% to 92% over a period of 12 h. having excellent mucoadhesive strength but ethyl cellulose containing tablets showed less than 65% release. The release mechanism of all formulation was diffusion controlled confirmed from Higuchi’s plot. Thus, the present study concluded that, carbopol-934P containing mucoadhesive tablets of omeprazole pellets can be used for local action in the ulcer disease as well as for oral controlled release drug delivery. PMID:21218061

  11. Gluten-free sorghum bread improved by sourdough fermentation: biochemical, rheological, and microstructural background.

    PubMed

    Schober, Tilman J; Bean, Scott R; Boyle, Daniel L

    2007-06-27

    This study was conducted to improve the quality and theoretical understanding of gluten-free sorghum bread. The addition of 2% hydroxypropyl methylcellulose improved bread based on 105% water, 70% sorghum flour, and 30% potato starch. Nevertheless, a flat top and tendency toward a hole in the crumb remained. Sourdough fermentation of the total sorghum flour eliminated these problems. Size-exclusion high-performance liquid chromatography demonstrated that during sourdough fermentation, proteins from the dough liquid were degraded to peptides smaller than kafirin monomers (<19 kDa). Laser scanning confocal microscopy showed aggregated protein in bread crumb without sourdough fermentation, whereas with sourdough fermentation, only small isolated patches of protein bodies embedded in matrix protein remained. In oscillatory temperature sweeps, sourdough fermentation caused a significantly higher resistance to deformation (|G*|) after gelatinization of the above batter relative to batters without sourdough. Results suggest that a strong starch gel, without interference of aggregated protein, is desirable for this type of bread. PMID:17536829

  12. An innovative antisolvent precipitation process as a promising technique to prepare ultrafine rifampicin particles

    NASA Astrophysics Data System (ADS)

    Viçosa, Alessandra; Letourneau, Jean-Jacques; Espitalier, Fabienne; Inês Ré, Maria

    2012-03-01

    Many existing and new drugs fail to be fully utilized because of their limited bioavailability due to poor solubility in aqueous media (BCS drug classes II and IV). In this work, for accelerating dissolution of this kind of poorly water-soluble drugs, an antisolvent precipitation method that does not require the use of conventional volatile organic solvents is proposed. To demonstrate this technique, ultrafine particles of rifampicin were prepared using a room temperature ionic liquid (1-ethyl 3- methyl imidazolium methyl-phosphonate) as an alternative solvent and a phosphate buffer as an antisolvent. Rifampicin solubility was measured in various solvents (1-ethyl 3-methyl imidazolium methylphosphonate, water and phosphate buffer), showing the RTIL good solvency for the model drug: rifampicin solubility was found to be higher than 90 mg/g in RTIL at 30 °C and lower than 1 mg/g in water at 25 °C. Additionally, it was demonstrated that introduction of rifampicin solution in 1-ethyl 3- methyl imidazolium methyl-phosphonate into the aqueous solution antisolvent can produce particles in the submicron range with or without hydroxypropyl methylcellulose as the stabilizer. The ultrafine particles (280-360 nm) are amorphous with enhanced solubility and faster dissolution rate. To our knowledge, this is the first published work examining the suitability of using RTILs for ultrafine drug nanoparticles preparation by an antisolvent precipitation process.

  13. Investigation of the effects of hydroalcoholic solutions on textural and rheological properties of various controlled release grades of hypromellose.

    PubMed

    Missaghi, Shahrzad; Fegely, Kurt A; Rajabi-Siahboomi, Ali R

    2009-01-01

    Hypromellose (hydroxypropyl methylcellulose, HPMC) matrices are widely used in the formulation of sustained release dosage forms. The integrity and performance of an HPMC matrix formulation depends on rapid hydration and gel formation upon ingestion. Due to the recent alert issued by the Food and Drug Administration regarding the potential negative influence of alcoholic beverages on extended release (ER) formulations, several researchers have evaluated the potential influence of hydroalcoholic media on drug release from ER dosage forms. It has been reported that HPMC matrix formulations do not show "dose dumping" in hydroalcoholic media. The purpose of this study was a fundamental investigation on the effect of hydroalcoholic solutions (0-40% v/v ethanol) on textural and rheological properties of different viscosity grades of neat HPMC, as the functional ingredient within a hydrophilic matrix. In general, hydroalcoholic solutions had little effect on gel formation and mechanical properties of hydrated compacts, while the rheological behavior of HPMC showed dependency on the ethanol content of such solutions. PMID:19148758

  14. Evaluation of models for predicting spray mist diameter for scaling-up of the fluidized bed granulation process.

    PubMed

    Fujiwara, Maya; Dohi, Masafumi; Otsuka, Tomoko; Yamashita, Kazunari; Sako, Kazuhiro

    2012-01-01

    We evaluated models for predicting spray mist diameter suitable for scaling-up the fluidized bed granulation process. By precise selection of experimental conditions, we were able to identify a suitable prediction model that considers changes in binder solution, nozzle dimension, and spray conditions. We used hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), or polyvinylpyrrolidone (PVP) binder solutions, which are commonly employed by the pharmaceutical industry. Nozzle dimension and spray conditions for oral dosing were carefully selected to reflect manufacturing and small (1/10) scale process conditions. We were able to demonstrate that the prediction model proposed by Mulhem optimally estimated spray mist diameter when each coefficient was modified. Moreover, we developed a simple scale-up rule to produce the same spray mist diameter at different process scales. We confirmed that the Rosin-Rammler distribution could be applied to this process, and that its distribution coefficient was 1.43-1.72 regardless of binder solution, spray condition, or nozzle dimension. PMID:23124561

  15. Leflunomide biodegradable microspheres intended for intra-articular administration: Development, anti-inflammatory activity and histopathological studies.

    PubMed

    El-Setouhy, Doaa Ahmed; Abdelmalak, Nevine Shawky; Anis, Shady E; Louis, Dina

    2015-11-30

    Leflunomide, the disease-modifying anti-rheumatic drug was formulated as microspheres for prolonged drug release in the form of intraarticular injection. Eight formulations were developed using three biodegradable PDLG polymers (lactide/glycolide copolymer) and polycaprolactone (PLC) at two drug:polymer ratios (1:2 and 1:4). Solvent evaporation method was employed using polyvinyl alcohol or hydropxypropyl methylcellulose as stabilizers. Formulations were assessed for encapsulation efficiency, yield, particle size, release pattern and SEM. F6 (PDLG 5010), with appropriate particle size and prolonged drug release, was chosen for in-vivo studies using arthritis induced rats, which were intrarticularly injected with F6 or took oral Avara(®). Nuclear factor-kappa B measurements and histopathologic studies were conducted. There was significant reduction of inflammation caused by both F6 and oral Avara(®). Histopathologic studies showed minimal infiltration by chronic inflammatory cells and no angiogenesis in F6 compared to Avara(®). Results also revealed biocompatibility of the polymer used. PMID:26392248

  16. Formulation and Evaluation of Controlled Release Floating Microballoons of Stavudine.

    PubMed

    Vidyadhara, Suryadevara; Sasidhar, Reddyvalam Lankapalli; Balakrishna, Talamanchi; Balaji, Boyapati; Amrutha, Ravi

    2015-01-01

    The aim of this study was to formulate and evaluate stavudine floating microballoons for controlled drug release. Initially, the drug-loaded low-density granular pellets were prepared with hydroxypropyl methylcellulose E5 grade and by using isopropyl alcohol as a granulating fluid. Further, the low-density granular pellets were subjected to microencapsulation by an emulsion evaporation technique using ethyl cellulose 7 cps and Eudragit S 100 as coating polymers and 1% w/v polyethylene glycol 400 as aqueous phase. The prepared microballoons were characterized for their particle size analysis, angle of repose, and compressibility index. The in vitro release studies were performed in 0.1 N HCl as medium. The prepared microballoons were free-flowing and spherical in shape. From all the formulations, F5E and F5F can be considered as promising controlled release floating microballoons of stavudine providing first-order release over a period of 12 hours, with a minimum floating lag time of 1 minute. It was found that the ratio of the drug & polymer, stirring speed, and concentration of surfactant were the most significant variables which influenced the size of the stavudine microballoons under the applied experimental conditions. PMID:26839847

  17. A physicochemical study of the morphology of progesterone-loaded microspheres fabricated from poly(D,L-lactide-co-glycolide).

    PubMed

    Rosilio, V; Benoit, J P; Deyme, M; Thies, C; Madelmont, G

    1991-05-01

    Progesterone-loaded microspheres are fabricated by a solvent evaporation process from a poly(D,L-lactide-co-glycolide) (85/15 PLG) and from alpha-progesterone. Methylene chloride is used as solvent and polyvinyl alcohol and methylcellulose are used as surfactants. The microspheres are characterized by scanning electron microscopy, differential scanning calorimetry, and x-ray powder diagrams. Our study shows that the morphology and the thermal behavior of PLG microspheres can vary significantly with progesterone loading and sample thermal history. Below and at 16.5% loading the microspheres exhibit a smooth outer surface. Above 23% loading, the surface becomes rough, embedded by copolymer particles or well-defined crystals. Pores and cracks can also be observed. Below 35% the progesterone is molecularly dispersed. At 35% and above crystal domains of the steroid appear and two crystalline forms are found: alpha- and beta-progesterone. The physical state of progesterone and the nature of its crystal domains dispersed in the PLG matrix can change during storage. Also a progressive development of an endothermic peak at the Tg event of the copolymer is observed during storage. No well defined relationship of peak size to progesterone loading can be shown. PMID:1869581

  18. Bringing comfort to the masses: a novel evaluation of comfort agent solution properties.

    PubMed

    White, Charles J; Thomas, Calvin R; Byrne, Mark E

    2014-04-01

    Ocular comfort agents are molecules that relieve ocular discomfort by augmenting characteristics of the tear film to stabilize and retain tear volume and lubricate the ocular surface. While a number of clinical comparisons between ocular comfort agent solutions are available, very little work has been done correlating the properties of specific comfort agents (species, molecular weight, and water retention) and solution properties (concentration, viscosity, zero shear viscosity, and surface tension) to the performance and effectiveness of comfort agent solutions. In this work, comfort-promoting properties related strongly to comfort agent concentration and molecular weight, the first objective demonstration of this relationship across diverse comfort agent species and molecular weights. The comfort agents with the greatest comfort property contributions (independent of specific molecular weight and concentration considerations) were hyaluronic acid (HA), hydroxypropyl methylcellulose (HPMC), and carboxymethylcellulose (CMC), respectively. The observed, empirical relationships between comfort property contribution and comfort agent species, solution properties, comfort agent molecular weight, and solution concentration was used to develop novel comfort agent index values. The comfort agent index values provided much insight and understanding into the results of experimental studies and/or clinical trials and offer potential resolution to numerous conflicting reports within the literature by accounting for the difference in comfort agent performance due to molecular weight and concentration of comfort agents. The index values provide the first objective, experimental validation and explanation of numerous general trends suggested by clinical data. PMID:23999507

  19. T-lymphocyte colonies in the lymphoproliferative disorders.

    PubMed Central

    Dao, C; Marie, J P; Bernadou, A; Bilski-Pasquier, G

    1978-01-01

    Human lymphocytes from peripheral blood, bone marrow spleen and lymph nodes were cultured. Continuous phytoheamagglutinin (PHA) stimulation was used, first during a 24 h liquid preincubation, then during a 5 day culture in methylcellulose. In normal donors a rapid colony formation took place, with a mean of 124+/-82 colonies per 1 times 10(5) preincubated lymphocytes. Cells from such colonies were studied by cytology, scanning electron microscopy and rosette formation techniques; arguments favour the hypothesis that these could be T lymphocytes. Neither granulocytes nor macrophages could be grown, and no lymphoid colony formation occurred without PHA stimulation. The same technique was applied to patients with various lymphoproliferative disorders. Significant colony suppression was observed in nearly every case of chronic lymphatic leukaemia; the number of colonies was reduced in some patients with acute lymphatic leukaemia, lymphosarcoma, dysglobulinaemia and Hodgkin's disease. This lymphoid culture method should be applied to a larger number of patients to determine whether it has a classification value and/or prognostic significance. When colonies were grown in pathological states, rosette formation was identical to that of normal donors; colony formation could be due to persisting normal lymphocytes. Images Figure 2 Figure 3 PMID:309852

  20. Formulation and evaluation of gastroretentive controlled release tablets of alfuzosin hydrochloride.

    PubMed

    Rudraswamy-Math, Nijaguni Revansiddayya; Gupta, Vankdari Rama-Mohan

    2015-11-01

    Alfuzosin hydrochloride is a novel drug used in the treatment of urinary incontinency. The purpose of this research was to develop controlled release floating matrix formulations of Alfuzosin HCl. Floating matrix tablets of Alfuzosin HCl were prepared using hydroxypropyl methylcellulose (HPMC), Polyethylene oxide (PEO), Carbopol 971P NF polymer (Direct compressible) and Blend of Polyvinyl Acetate and Povidone 30 (80:19:1(0.8% sodium laury sulfate and 0.2% silica)). Combination of citric acid and sodium bicarbonate were also used as gas forming agent. Matrix formulations were prepared by direct compression method and evaluated for floating, in vitro drug release profile and swelling characteristics. The mechanism of drug release was found to follow non-Fickian or anomalous type. The data obtained from the invitro release studies demonstrated that the floating matrix tablets containing HPMC 100K CR (controlled-release) and carbopol along with sodium CMC were found to sustain the release of drug over a period of 12 hours. Formulations containing 25% PEO 303WSR was also capable of sustaining delivery the release of Alfuzosin HCl. PMID:26639508

  1. Natural Micronized Progesterone Sustained Release (SR) and Luteal Phase: Role Redefined!!

    PubMed Central

    Malik, Sonia

    2016-01-01

    Role of progesterone in reproductive medicine is evolving with its suggested clinical role for the hormonal and nonhormonal actions in reproductive medicine. The main function of progesterone is to induce ‘secretory’ changes in endometrium that is further complimented by its immunomodulatory and anti-inflammatory actions. It positively modulates PIBF, NK cells and HOXA 10 genes for better implantation. MHRA recommends Serum Progesterone levels ≥14ng/ml in the mid-luteal phase for supporting pregnancy adequately. Oral Natural Micronized Progesterone SR formulation represents a therapeutic advance in this direction offering ‘therapeutic compliance’ with oral formulation while avoiding the local side effects related to long-term patient compliance in reproductive disorders. The formulation offers round the clock efficiency and efficacy with single dose administration thereby improving patient convenience and compliance. This formulation has been marketed globally since 1986 utilizing the well validated drug delivery system involving Methylcellulose base. The clinical utility of this formulation is further suggested especially in various conditions related with luteal phase insufficiency and Bad obstetric history (BOH) or luteal phase support in ART. The level of evidence has been quite robust with several clinical studies including Prescription Event Monitoring and Investigator initiated studies supporting the clinical role of oral NMP SR formulation especially in ‘Real world’ clinic settings for Luteal phase insufficiency that may be physiological or iatrogenic. PMID:27042538

  2. Itraconazole solid dispersion prepared by a supercritical fluid technique: preparation, in vitro characterization, and bioavailability in beagle dogs

    PubMed Central

    Yin, Xuezhi; Daintree, Linda Sharon; Ding, Sheng; Ledger, Daniel Mark; Wang, Bing; Zhao, Wenwen; Qi, Jianping; Wu, Wei

    2015-01-01

    This research aimed to develop a supercritical fluid (SCF) technique for preparing a particulate form of itraconazole (ITZ) with good dissolution and bioavailability characteristics. The ITZ particulate solid dispersion was formulated with hydroxypropyl methylcellulose, Pluronic F-127, and L-ascorbic acid. Aggregated particles showed porous structure when examined by scanning electron microscopy. Powder X-ray diffraction and Fourier transform infrared spectra indicated an interaction between ITZ and excipients and showed that ITZ existed in an amorphous state in the composite solid dispersion particles. The solid dispersion obtained by the SCF process improved the dissolution of ITZ in media of pH 1.0, pH 4.5, and pH 6.8, compared with a commercial product (Sporanox®), which could be ascribed to the porous aggregated particle shape and amorphous solid state of ITZ. While the solid dispersion did not show a statistical improvement (P=0.50) in terms of oral bioavailability of ITZ compared with Sporanox®, the Cmax (the maximum plasma concentration of ITZ in a pharmacokinetic curve) of ITZ was raised significantly (P=0.03) after oral administration. Thus, the SCF process has been shown to be an efficient, single step process to form ITZ-containing solid dispersion particles with good dissolution and oral bioavailability characteristics. PMID:26060397

  3. Augmentation of erythroid burst formation by the addition of thymocytes and other myelo-lymphoid cells.

    PubMed

    Kanamaru, A; Durban, E; Gallagher, M T; Miller, S C; Trentin, J J

    1980-08-01

    Bone marrow from barrier-sustained specific pathogen-free (SPF) CBA and C57BL/6 mice gave relatively low numbers of BFU-E colonies in methylcellulose culture, as compared to conventional mice. Addition of thymocytes to the marrow cultures increased the yield of BFU-E colonies more than fourfold in SPF mice but only 1.5-fold in conventional mice. Colony size was also increased. Increased yield of BFU-E colonies was also obtained by co-culture of bone marrow with lymph node cells or with bone marrow or spleen cells from 900R whole-body irradiated mice. The effect appeared to be cellular rather than humoral. It was not reproduced by conditioned medium from thymus or pokeweed mitogen stimulated spleen cells. The helper effect of thymus cells was eliminated or reduced by freezing and thawing, or by 48 hours of incubation after irradiation. Treatment of bone marrow cells in vitro with anti-theta serum and complement did not decrease the number of BFU-E colonies. The putative helper cells appear not to be T cells, were non-adherent to the plastic culture dish, and were cortisone resistant and radioresistant. The low BFU-E colony yield from SPF mouse marrow is presumed to be largely the result of deficiency of these non-T helper cells in SPF bone marrow, rather than of BFU-E progenitor cells. PMID:6447706

  4. Modelling drug degradation in a spray dried polymer dispersion using a modified Arrhenius equation.

    PubMed

    Patterson, Adele; Ferreira, Ana P; Banks, Elizabeth; Skeene, Kirsty; Clarke, Graham; Nicholson, Sarah; Rawlinson-Malone, Clare

    2015-01-15

    The Pharmaceutical industry is increasingly utilizing amorphous technologies to overcome solubility challenges. A common approach is the use of drug in polymer dispersions to prevent recrystallization of the amorphous drug. Understanding the factors affecting chemical and physical degradation of the drug within these complex systems, e.g., temperature and relative humidity, is an important step in the selection of a lead formulation, and development of appropriate packaging/storage control strategies. The Arrhenius equation has been used as the basis of a number of models to predict the chemical stability of formulated product. In this work, we investigate the increase in chemical degradation seen for one particular spray dried dispersion formulation using hydroxypropyl methylcellulose acetate succinate (HPMC-AS). Samples, prepared using polymers with different substitution levels, were placed on storage for 6 months under a range of different temperature and relative humidity conditions and the degradant level monitored using high-performance liquid chromatography (HPLC). While the data clearly illustrates the impact of temperature and relative humidity on the degradant levels detected, it also highlighted that these terms do not account for all the variability in the data. An extension of the Arrhenius equation to include a term for the polymer chemistry, specifically the degree of succinoyl substitution on the polymer backbone, was shown to improve the fit of the model to the data. PMID:25450477

  5. Synthesis and characterization of novel bactericidal Cu/HPMC BNCs using chemical reduction method for food packaging.

    PubMed

    Ebrahimiasl, Saeideh; Rajabpour, Ataollah

    2015-09-01

    In this research copper nanoparticles (Cu NPs) were incorporated in the biodegradable hydroxypropyl methylcellulose (HPMC) matrix using the simple and low cost chemical reduction method for application as food packaging material. The properties of Cu/HPMC bionanocomposites (BNCs) were studied as a function of the CuSO4 concentration. Surface morphology of the film was investigated by scanning electron microscopy. Mechanical analysis and water vapor barrier properties of HPMC/Cu nanocomposites were analyzed. It was observed that mechanical and water vapor barrier properties of the films were improved by the concentration of CuSO4. The antibacterial activity of HPMC/Cu thin films were evaluated based on the diameter of inhibition zone in a disk diffusion test against Gram positive bacteria, ie, Streptococus A., S. epidermidis, S.aureus , B.cereus and Gram negative bacteria, ie, E. coli, E. faecalis, Salmonella, P. aeruginosa using Mueller Hinton agar at different concentration of CuSO4. The results revealed a greater bactericidal effectiveness for nanocomposite films containing 5 % of CuSO4. Packages prepared from HPMC/Cu nanocomposite films were used for meat packaging. The films were filled with meat and then stored at 4 °C. Microbial stability of the meat was evaluated after 3, 7, 10 and 15 days of storage. The results showed that microbial growth rate significantly reduced as a result of using this nanocomposite packaging material. PMID:26345017

  6. Continuous twin-screw granulation for enhancing the dissolution of poorly water soluble drug.

    PubMed

    Maniruzzaman, Mohammed; Nair, Arun; Renault, Maxcene; Nandi, Uttom; Scoutaris, Nicholaos; Farnish, Richard; Bradley, Michael S A; Snowden, Martin J; Douroumis, Dennis

    2015-12-30

    The article describes the application of a twin-screw granulation process to enhance the dissolution rate of the poorly water soluble drug, ibuprofen (IBU). A quality-by-design (QbD) approach was used to manufacture IBU loaded granules via hot-melt extrusion (HME) processing. For the purpose of the study, a design of experiment (DoE) was implemented to assess the effect of the formulation compositions and the processing parameters. This novel approach allowed the use of, polymer/inorganic excipients such as hydroxypropyl methylcellulose (HPMC) and magnesium aluminometasilicate (Neusilin(®)-MAS) with polyethylene glycol 2000 (PEG) as the binder without requiring a further drying step. IBU loaded batches were processed using a twin screw extruder to investigate the effect of MAS/polymer ratio, PEG amount (binder) and liquid to solid (L/S) ratios on the dissolution rates, mean particle size and the loss on drying (LoD) of the extruded granules. The DoE analysis showed that the defined independent variables of the twin screw granulation process have a complex effect on the measured outcomes. The solid state analysis showed the existence of partially amorphous IBU state which had a significant effect on the dissolution enhancement in acidic media. Furthermore, the analysis obtained from the surface mapping by Raman proved the homogenous distribution of the IBU in the extruded granulation formulations. PMID:26387621

  7. The effect of HPMCAS functional groups on drug crystallization from the supersaturated state and dissolution improvement.

    PubMed

    Ueda, Keisuke; Higashi, Kenjirou; Yamamoto, Keiji; Moribe, Kunikazu

    2014-04-10

    The inhibitory effect on drug crystallization in aqueous solution was evaluated using various forms of hydroxypropyl methylcellulose acetate succinate (HPMCAS). HPMCAS suppressed crystallization of carbamazepine (CBZ), nifedipine (NIF), mefenamic acid, and dexamethasone. The inhibition of drug crystallization mainly derived from molecular level hydrophobic interactions between the drug and HPMCAS. HPMCAS with a lower succinoyl substituent ratio strongly suppressed drug crystallization. The inhibition of crystallization was affected by pH, with the CBZ crystallization being inhibited at a higher pH due to the hydrophilization of HPMCAS derived from succinoyl ionization. The molecular mobility of CBZ in an HPMCAS solution was evaluated by 1D-(1)H NMR and relaxation time measurements. CBZ mobility was strongly suppressed in the HPMCAS solutions where strong inhibitory effects on CBZ crystallization were observed. The mobility suppression of CBZ in the HPMCAS solution was derived from intermolecular interactions between CBZ and HPMCAS leading to an inhibition of crystallization. The effect of HPMCAS on the drug dissolution rate was evaluated using an NIF/HPMCAS solid dispersion. The dissolution rate of NIF was increased when HPMCAS with a higher succinoyl substituent ratio was used. PMID:24440403

  8. Understanding and managing the impact of HPMC variability on drug release from controlled release formulations.

    PubMed

    Zhou, Deliang; Law, Devalina; Reynolds, Judie; Davis, Lynn; Smith, Clifford; Torres, Jose L; Dave, Viraj; Gopinathan, Nishanth; Hernandez, Daniel T; Springman, Mary Kay; Zhou, Casey Chun

    2014-06-01

    The purpose of this study is to identify critical physicochemical properties of hydroxypxropyl methylcellulose (HPMC) that impact the dissolution of a controlled release tablet and develop a strategy to mitigate the HPMC lot-to-lot and vendor-to-vendor variability. A screening experiment was performed to evaluate the impacts of methoxy/hydroxypropyl substitutions, and viscosity on drug release. The chemical diversity of HPMC was explored by nuclear magnetic resonance (NMR), and the erosion rate of HPMC was investigated using various dissolution apparatuses. Statistical evaluation suggested that the hydroxypropyl content was the primary factor impacting the drug release. However, the statistical model prediction was not robust. NMR experiments suggested the existence of structural diversity of HPMC between lots and more significantly between vendors. Review of drug release from hydrophilic matrices indicated that erosion is a key aspect for both poorly soluble and soluble drugs. An erosion rate method was then developed, which enabled the establishment of a robust model and a meaningful HPMC specification. The study revealed that the overall substitution level is not the unique parameter that dictates its release-controlling properties. Fundamental principles of polymer chemistry and dissolution mechanisms are important in the development and manufacturing of hydrophilic matrices with consistent dissolution performance. PMID:24652662

  9. A nanosystem for water-insoluble drugs prepared by a new technology, nanoparticulation using a solid lipid and supercritical fluid.

    PubMed

    Park, Joo Won; Yun, Jeong Min; Lee, Eun Seong; Youn, Yu Seok; Kim, Kab Sig; Oh, Young Taik; Oh, Kyung Teak

    2013-11-01

    While the number and diversity of lead compounds has increased with the development of science technologies, ca. 90 % of new chemical entities under development have shown low aqueous solubility, classified as class II or IV of the biopharmaceutics classification system (BCS). The low aqueous solubility hinders their clinical translations due to low bioavailability and dissolution-limited absorption of orally-administered drugs. Several technologies have been employed to improve the solubility of poorly water-soluble drugs. In this paper, a new method of nanoparticulation using fat and a supercritical fluid (NUFS) for the formulation of hydrophobic drugs was applied to solve the low solubility problem. A typical BCS class II drug, itraconazole, was selected and formulated with hydroxypropyl methylcellulose, emulsification, and anticoagulating agents for NUFS. The non-spherical itraconazole nanoparticles prepared by NUFS were ~300-500 nm in size with a ~15-fold improved dissolution rate compared to non-nanoparticles of itraconazole (i.e., raw itraconazole). In addition, a high drug content of ~46 % by weight and a drug loading efficiency greater than 85 % were achieved. Therefore, the new technology for nano-platforms could be a promising solution for solubilization of poorly water-soluble drugs, resulting in improved bioavailability. PMID:23780798

  10. Study the effect of formulation variables on drug release from hydrophilic matrix tablets of milnacipran and prediction of in-vivo plasma profile.

    PubMed

    Singhvi, Gautam; Shah, Abhishek; Yadav, Nilesh; Saha, Ranendra N

    2014-09-01

    The objective of this study was to design oral controlled release (CR) matrix tablets of Milnacipran using hydroxypropyl methylcellulose (HPMC) as the retardant polymer and to study the effect of various formulation factors such as polymer proportion, polymer viscosity, compression force and also the pH of dissolution medium on the in-vitro release of drug. Two viscosity grade of HPMC (15 K and 100 K) were used in the proportion of 50, 100, 150 and 200 mg per CR tablet. In-vitro release rate was characterized using various model dependent approaches and model independent dissolution parameters [T50% and T80% dissolution time, mean dissolution time (MDT), mean residence time (MRT), dissolution efficiency (DE)]. The statistical analysis was performed on all the model independent approaches using student t test and ANOVA. Results were found that as polymer concentration (50 mg to 200 mg) and viscosity (15 K to 100 K) increases, the MDT, MRT, T50% and T80% extended significantly. Drug release rate was found to be significantly different at different hardness. In-vivo human plasma concentration--time profile was predicted from in-vitro release data using convolution method. Predicted human pharmacokinetic parameters shows that the design CR formulation has capability to sustained the plasma drug level of milnacipran. PMID:23931031

  11. Synthesis of cellulose-based superabsorbent hydrogels by high-energy irradiation in the presence of crosslinking agent

    NASA Astrophysics Data System (ADS)

    Fekete, Tamás; Borsa, Judit; Takács, Erzsébet; Wojnárovits, László

    2016-01-01

    Superabsorbent hydrogels were prepared from aqueous solutions of four cellulose derivatives (carboxymethylcellulose Na-salt - CMC, methylcellulose - MC, hydroxyethylcellulose - HEC and hydroxypropylcellulose - HPC) by gamma irradiation initiated crosslinking. CMC was used for the majority of the measurements. N,N'-methylene-bis-acrylamide (MBA) crosslinking agent was used to modify the gel properties. The crosslink density increased with the MBA concentration, leading to an improved gel fraction and lower water uptake. The crosslinking efficiency was the highest up to 1 w/wpolymer% MBA concentration. Very high MBA content (10 w/wpolymer%) led to a heterogeneous gel structure. Gelation also occurred under milder conditions in the presence of MBA: good gel properties were achieved at significantly lower doses and solute concentrations as compared to crosslinker-free solutions. The time required to reach maximum water uptake increased with the degree of swelling in equilibrium. Swelling properties of CMC gels with lower water uptake showed lower sensitivity to the ionic strength of the solvent.

  12. Comparison of Gavage, Water Bottle, and a High-Moisture Diet Bolus as Dosing Methods for Quantitative D-xylose Administration to B6D2F1 (Mus musculus) Mice

    NASA Technical Reports Server (NTRS)

    Zimmer, J. Paul; Lewis, Sherry M.; Moyer, Jerry L.

    1993-01-01

    Gavage, water bottle, and diet incorporation are 3 dosing methods used orally to administer test compounds to rodents. These 3 methods were compared in mice to determine which represented the most quantitative delivery system. For dietary incorporation, a high-moisture bolus form of NIH-31 rodent meal was developed using hydroxypropyl methylcellulose as an autoclave-stable binding agent. A high-moisture bolus were selected to increase the acceptability of the dosed diet and to promote quantitative consumption through reduced wastage. The test compound used was D-xylose, a pentose sugar that may be quantitatively detected, colorimetrically, in urine following oral dosing. Six male and 6 female B6D2FI mice were placed in metabolism cages and dosed with a known quantity of D-xylose by each of the 3 methods. Urine was collected before and after each method of administration and analysed for total D-xylose; the per cent recovery was based upon the amount of D-xylose consumed. Quantitative consumption was apparently greatest for water bottle dosing with an average recovery of 56.0% of the original D-xylose dose. High-moisture bolus incorporation ranked second with 50.0% D-xylose recovery, and gavage was third with 41.0% D-xylose recovery.

  13. The multiple myeloma–associated MMSET gene contributes to cellular adhesion, clonogenic growth, and tumorigenicity

    PubMed Central

    Abukhdeir, Abde M.; Konishi, Hiroyuki; Garay, Joseph P.; Gustin, John P.; Wang, Qiuju; Arceci, Robert J.; Matsui, William

    2008-01-01

    Multiple myeloma (MM) is an incurable hematologic malignancy characterized by recurrent chromosomal translocations. Patients with t(4;14)(p16;q32) are the worst prognostic subgroup in MM, although the basis for this poor prognosis is unknown. The t(4;14) is unusual in that it involves 2 potential target genes: fibroblast growth factor receptor 3 (FGFR3) and multiple myeloma SET domain (MMSET). MMSET is universally overexpressed in t(4;14) MM, whereas FGFR3 expression is lost in one-third of cases. Nonetheless, the role of MMSET in t(4;14) MM has remained unclear. Here we demonstrate a role for MMSET in t(4;14) MM cells. Down-regulation of MMSET expression in MM cell lines by RNA interference and by selective disruption of the translocated MMSET allele using gene targeting dramatically reduced colony formation in methylcellulose but had only modest effects in liquid culture. In addition, MMSET knockdown led to cell-cycle arrest of adherent MM cells and reduced the ability of MM cells to adhere to extracellular matrix. Finally, MMSET knockdown and knockout reduced tumor formation by MM xenografts. These results provide the first direct evidence that MMSET plays a significant role in t(4;14) MM and suggest that therapies targeting this gene could impact this particular subset of poor-prognosis patients. PMID:17942756

  14. Astringency reduction in red wine by whey proteins.

    PubMed

    Jauregi, Paula; Olatujoye, Jumoke B; Cabezudo, Ignacio; Frazier, Richard A; Gordon, Michael H

    2016-05-15

    Whey is a by-product of cheese manufacturing and therefore investigating new applications of whey proteins will contribute towards the valorisation of whey and hence waste reduction. This study shows for the first time a detailed comparison of the effectiveness of gelatin and β-lactoglobulin (β-LG) as fining agents. Gelatin was more reactive than whey proteins to tannic acid as shown by both the astringency method (with ovalbumin as a precipitant) and the tannins determination method (with methylcellulose as a precipitant). The two proteins showed similar selectivity for polyphenols but β-LG did not remove as much catechin. The fining agent was removed completely or to a trace level after centrifugation followed by filtration which minimises its potential allergenicity. In addition, improved understanding of protein-tannin interactions was obtained by fluorescence, size measurement and isothermal titration calorimetry (ITC). Overall this study demonstrates that whey proteins have the potential of reducing astringency in red wine and can find a place in enology. PMID:26776007

  15. Formulation, physicochemical characterization, and in vitro study of chitosan/HPMC blends-based herbal blended patches.

    PubMed

    Suksaeree, Jirapornchai; Monton, Chaowalit; Madaka, Fameera; Chusut, Tun; Saingam, Worawan; Pichayakorn, Wiwat; Boonme, Prapaporn

    2015-02-01

    The current work prepared chitosan/hydroxypropyl methylcellulose (HPMC) blends and studied the possibility of chitosan/HPMC blended patches for Zingiber cassumunar Roxb. The blended patches without/with crude Z. cassumunar oil were prepared by homogeneously mixing the 3.5% w/v of chitosan solution and 20% w/v of HPMC solution, and glycerine was used as plasticizer. Then, they were poured into Petri dish and produced the blended patches in hot air oven at 70 ± 2°C. The blended patches were tested and evaluated by the physicochemical properties: moisture uptake, swelling ratio, erosion, porosity, Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction, and photographed the surface and cross-section morphology under SEM technique. Herbal blended patches were studied by the in vitro release and skin permeation of active compound D. The blended patches could absorb the moisture and became hydrated patches that occurred during the swelling of blended patches. They were eroded and increased by the number of porous channels to pass through out for active compound D. In addition, the blended patches indicated the compatibility of the blended ingredients and homogeneous smooth and compact. The blended patches made from chitosan/HPMC blends provide a controlled release and skin permeation behavior of compound D. Thus, the blended patches could be suitably used for herbal medicine application. PMID:25233803

  16. Matrix effects in nilotinib formulations with pH-responsive polymer produced by carbon dioxide-mediated precipitation.

    PubMed

    Colombo, Stefano; Brisander, Magnus; Haglöf, Jakob; Sjövall, Peter; Andersson, Per; Østergaard, Jesper; Malmsten, Martin

    2015-10-15

    Factors determining the pH-controlled dissolution kinetics of nilotinib formulations with the pH-titrable polymer hydroxypropyl methylcellulose phthalate, obtained by carbon dioxide-mediated precipitation, were mechanistically examined in acid and neutral environment. The matrix effect, modulating the drug dissolution, was characterized with a battery of physicochemical methodologies, including ToF-SIMS for surface composition, SAXS/WAXS and modulated DSC for crystallization characterization, and simultaneous UV-imaging and Raman spectroscopy for monitoring the dissolution process in detail. The hybrid particle formulations investigated consisted of amorphous nilotinib embedded in a polymer matrix in single continuous phase, displaying extended retained amorphicity also under wet conditions. It was demonstrated by Raman and FTIR spectroscopy that the efficient drug dispersion and amorphization in the polymer matrix were mediated by hydrogen bonding between the drug and the phthalate groups on the polymer. Simultaneous Raman and UV-imaging studies of the effect of drug load on the swelling and dissolution of the polymer matrix revealed that high nilotinib load prevented matrix swelling on passage from acid to neutral pH, thereby preventing re-precipitation and re-crystallization of incorporated nilotinib. These findings provide a mechanistic foundation of formulation development of nilotinib and other protein kinase inhibitors, which are now witnessing an intense therapeutic and industrial attention due to the difficulty in formulating these compounds so that efficient oral bioavailability is reached. PMID:26276256

  17. Skin permeation profile and anti-inflammatory effect of anemonin extracted from weilingxian.

    PubMed

    Ning, Yuming; Rao, Yuefeng; Yu, Zhenwei; Liang, Wenquan; Li, Fanzhu

    2016-03-01

    The aim of this study was to evaluate the skin permeability of anemonin, which was extracted from the Chinese herb weilingxian, and its potency of relieving the inflammation caused by rheumatoid arthritis (RA). To optimize the formulation, the solubility of anemonin in water and selected concentration of ethanol-water vehicles was determined. The effect of ethanol on the permeation of anemonin through human skin was then studied. Additionally, the influences of hydroxypropyl methylcellulose E50 (HPMC) and Carbomer 934 in different concentrations on the permeation of drug were investigated. Finally, the anti-inflammatory effect of the optimized formulation was assessed by murine model of xylene-induced ear edema. The results showed that the solubility and transdermal permeation of anemonin in ethanol-water vehicles linearly depended on the ethanol concentration. The combination of 30% ethanol and 3% Azone had a synergistic enhancement effect and was therefore selected for gel preparation. The 0.14% anemonin gel prepared with 1% HPMC exhibited the highest transdermal flux. The xylene-induced ear edema inhibitory rate of the optimized formulation was 48.85%. The results indicated that transdermal administration of anemonin is a potential modality for combating inflammation caused by RA. PMID:27183707

  18. Carboxymethyl cellulose wafers containing antimicrobials: a modern drug delivery system for wound infections.

    PubMed

    Ng, Shiow-Fern; Jumaat, Nafisah

    2014-01-23

    Lyophilised wafers have been shown to have potential as a modern dressing for mucosal wound healing. The wafer absorbs wound exudates and transforms into a gel, thus providing a moist environment which is essential for wound healing. The objective of this study was to develop a carboxymethyl cellulose wafer containing antimicrobials to promote wound healing and treat wound infection. The pre-formulation studies began with four polymers, sodium carboxymethyl cellulose (NaCMC), methylcellulose (MC), sodium alginate and xanthan gum, but only NaCMC and MC were chosen for further investigation. The wafers were characterised by physical assessments, solvent loss, microscopic examination, swelling and hydration properties, drug content uniformity, drug release and efficacy of antimicrobials. Three of the antimicrobials, neomycin trisulphate salt hydrate, sulphacetamide sodium and silver nitrate, were selected as model drugs. Among the formulations, NaCMC wafer containing neomycin trisulphate exhibited the most desirable wound dressing characteristics (i.e., flexibility, sponginess, uniform wafer texture, high content drug uniformity) with the highest in vitro drug release and the greatest inhibition against both Gram positive and Gram negative bacteria. In conclusion, we successfully developed a NaCMC lyophilised wafer containing antimicrobials, and this formulation has potential for use in mucosal wounds infected with bacteria. PMID:24076463

  19. In vitro sustained release of bioactive anti-NogoA, a molecule in clinical development for treatment of spinal cord injury.

    PubMed

    Stanwick, Jason C; Baumann, M Douglas; Shoichet, Molly S

    2012-04-15

    Anti-NogoA is a promising anti-inhibitory molecule that has been shown to enhance functional recovery after spinal cord injury when delivered in rat and primate models over the span of weeks. To achieve this sustained release, anti-NogoA is typically delivered by osmotic minipumps; however, external minipumps are susceptible to infection. To address this issue, we developed a drug delivery system that consists of anti-NogoA-loaded poly(lactic-co-glycolic acid) nanoparticles dispersed in a hydrogel of hyaluronan and methylcellulose (composite HAMC). To optimize in vitro release, we screened formulations for improved anti-NogoA bioactivity and sustained release based on combinations of co-encapsulated trehalose, hyaluronan, MgCO(3), and CaCO(3). Co-encapsulated MgCO(3) and CaCO(3) slowed the rate of anti-NogoA release and did not influence anti-NogoA bioactivity. Co-encapsulated trehalose significantly improved anti-NogoA bioactivity at early release time points by stabilizing the protein during lyophilization. Co-encapsulated trehalose with hyaluronan improved bioactivity up to 28d and dramatically increased the rate and duration of sustained delivery. The sustained release of bioactive anti-NogoA from composite HAMC is a compelling formulation for in vivo evaluation in a model of spinal cord injury. PMID:22306041

  20. Edible oleogels based on water soluble food polymers: preparation, characterization and potential application.

    PubMed

    Patel, Ashok R; Cludts, Nick; Sintang, Mohd Dona Bin; Lesaffer, Ans; Dewettinck, Koen

    2014-11-01

    Oil structuring using food-approved polymers is an emerging strategy and holds significant promise in the area of food and nutrition. In the current study, edible oleogels (containing >97 wt% of sunflower oil) were prepared using a combination of water soluble food polymers (methylcellulose and xanthan gum) and further evaluated for potential application as a shortening alternative. Microstructure studies (including cryo-SEM) and rheology measurements were conducted to gain more insights into the properties of these new types of oleogels. In addition, the functionality of oleogel as a shortening alternative was studied in terms of batter properties and the texture analysis of cakes and compared to the reference batches made using either oil, commercial shortening or cake margarine. Interestingly, while the batter properties (air incorporation, rheology and microstructure) of the oleogel batch were more close to the oil batch, the textural properties of cakes were significantly better than oil and resembled more to the cakes prepared using shortening and margarine. PMID:25214474

  1. Improved oral absorption of tacrolimus by a solid dispersion with hypromellose and sodium lauryl sulfate.

    PubMed

    Jung, Hyuck Jun; Ahn, Hye In; Park, Ji Yeon; Ho, Myoung Jin; Lee, Dae Ro; Cho, Ha Ra; Park, Jun Seo; Choi, Yong Seok; Kang, Myung Joo

    2016-02-01

    A novel surfactant-incorporated hydroxypropyl methylcellulose (HPMC) solid dispersion (SD) system was constructed in order to facilitate the release rate and oral absorption of tacrolimus (FK506), a poorly water-soluble immunosuppressant. Several emulsifiers including sodium lauryl sulfate (SLS), as drug release promotors, were employed with HPMC to fabricate SD using the solvent wetting method. The solid state characteristics using differential scanning calorimetry and X-ray powder diffraction, revealed that FK506 was molecularly distributed within all dispersions in amorphous form. The dissolution rates of FK506 in SLS-incorporated SDs were much higher than those in SDs prepared with HPMC alone, and even with stearoyl polyoxyl-32 glycerides or tocopheryl polyethylene glycol 1000 succinate. In particular, the greatest dissolution enhancement was obtained from the SD consisting of the drug, HPMC, and SLS in a weight ratio of 1:1:3, providing a 50-fold higher drug concentration within 15 min, compared with HPMC SD. In vivo absorption study in rats demonstrates that the optimized formula remarkably increased the oral absorption of FK506, providing about 4.0-fold greater bioavailability (p<0.05) compared with the marketed product (Prograf®, Astellas Pharma). These data suggest that a novel SLS/HPMC SD may be an advantageous dosage form of FK506, boosting the dissolution and absorption in gastrointestinal tract. PMID:26642839

  2. Effect of methanol extract of Basella alba L. (Basellaceae) on the fecundity and testosterone level in male rats exposed to flutamide in utero.

    PubMed

    Nantia, E A; Manfo, P F T; Beboy, N E; Travert, C; Carreau, S; Monsees, T K; Moundipa, P F

    2012-02-01

    We evaluated the effect of the methanol extract of Basella alba (MEBa) on testosterone level and fecundity/fertility in male rats exposed in utero to flutamide - an androgen receptor antagonist. For this purpose, 1.5- and 2.5 -month-old male rats exposed in utero to flutamide were treated with the MEBa (1 mg kg(-1) ) for 2 and 1 month respectively. Five days before the end of treatment, rats were housed with females to assess their fecundity/fertility. Thereafter, rats were sacrificed and blood collected for the quantification of testosterone. Flutamide-exposed male rats showed a decrease in their ano-genital distance (AGD, P < 0.05) and were infertile. In normal (methylcellulose-exposed) animals, MEBa provoked an increase in testosterone level in 1.5- (P < 0.008) and 2.5 -month-old rats (P < 0.01) concomitantly with the improvement in their fecundity by 25%. In flutamide-exposed male rats, MEBa increased testosterone level in 1.5 -month-old rats (P < 0.001) without any effect on their fecundity; while in 2.5- month-old rats, MEBa did not affect the testosterone level but improved fecundity (by 25%) and fertility (P < 0.001). This study demonstrated the positive effect of MEBa to enhance fecundity/fertility in normal male rats and in rats exposed to the antiandrogen flutamide during their foetal life. PMID:21592171

  3. Determination of ephedrine and pseudoephedrine by field-amplified sample injection capillary electrophoresis.

    PubMed

    Deng, Dongli; Deng, Hao; Zhang, Lichun; Su, Yingying

    2014-04-01

    A simple and rapid capillary electrophoresis method was developed for the separation and determination of ephedrine (E) and pseudoephedrine (PE) in a buffer solution containing 80 mM of NaH2PO4 (pH 3.0), 15 mM of β-cyclodextrin and 0.3% of hydroxypropyl methylcellulose. The field-amplified sample injection (FASI) technique was applied to the online concentration of the alkaloids. With FASI in the presence of a low conductivity solvent plug (water), an approximately 1,000-fold improvement in sensitivity was achieved without any loss of separation efficiency when compared to conventional sample injection. Under these optimized conditions, a baseline separation of the two analytes was achieved within 16 min and the detection limits for E and PE were 0.7 and 0.6 µg/L, respectively. Without expensive instruments or labeling of the compounds, the limits of detection for E and PE obtained by the proposed method are comparable with (or even lower than) those obtained by capillary electrophoresis laser-induced fluorescence, liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry. The method was validated in terms of precision, linearity and accuracy, and successfully applied for the determination of the two alkaloids in Ephedra herbs. PMID:23619557

  4. Gastrointestinal and Systemic Monitoring of Posaconazole in Humans After Fasted and Fed State Administration of a Solid Dispersion.

    PubMed

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

    2016-09-01

    The purpose of this study was to explore the intraluminal behavior and systemic exposure of posaconazole in humans after oral intake of a novel delayed-release tablet (Noxafil(®)), containing posaconazole dispersed in a matrix of hydroxypropyl methylcellulose acetate succinate. Five healthy volunteers were asked to ingest the tablet in the fasted and fed state condition, after positioning one aspiration catheter in the stomach and one in the jejunum. Subsequently, gastric and jejunal fluids were aspirated and analyzed for posaconazole. In parallel, blood samples were collected. In gastric aspirates, dissolved concentrations were negligible regardless of the test condition, confirming the delayed-release properties of the tablet. In fasted state jejunal aspirates, sustained supersaturation was observed during an average period of time of 93 ± 78.2 min, with a mean maximum degree of supersaturation of 7.28 ± 8.81. In the fed state condition, supersaturation was negligible in the jejunum with a pronounced presence of solid posaconazole, suggesting the importance of more distal intestinal regions for posaconazole absorption. PMID:27178739

  5. Influence of neutron activation factors on matrix tablets for site specific delivery to the colon.

    PubMed

    Ahrabi, S F; Heinämäki, J; Sande, S A; Graffner, C

    2000-05-01

    The impact of the neutron activation procedure, i.e. incorporation of samarium oxide (Sm(2)O(3)) and neutron irradiation, on the compression properties (including the crushing strength) and in vitro dissolution of potential colonic delivery systems based on matrix tablets of amidated pectin (Am.P) or two types of hydroxypropyl methylcellulose (HPMC) was investigated. The neutron activation factors did not influence the compression properties of the tablets. Replacement of magnesium stearate with samarium stearate in directly compressed Am.P tablets to achieve both radiolabelling and lubrication resulted in a greater extent of concentration-dependent reduction of the crushing strength. Dissolution tests demonstrated that irradiation increased the release of the model drug ropivacaine from the tablets. The extent of this increase was unexpectedly low considering the previously observed degradation of the polymer expressed as an irradiation-induced viscosity reduction in solutions prepared from the polymers. Delayed-release coating with Eudragit L 100 protected the HPMC tablets against the release-increasing effect of irradiation until the late phases of release. Sm(2)O(3) retarded the release to a varying extent depending on particle characteristics. Incorporation of Sm(2)O(3) in the coating layer did not influence the release. However, one-third of the radioactivity leached from the coating within 60 min in 0.1 M HCl. PMID:10767600

  6. Endogenously elevated bilirubin modulates kidney function and protects from circulating oxidative stress in a rat model of adenine-induced kidney failure

    PubMed Central

    Boon, Ai-Ching; Lam, Alfred K.; Gopalan, Vinod; Benzie, Iris F.; Briskey, David; Coombes, Jeff S.; Fassett, Robert G.; Bulmer, Andrew C.

    2015-01-01

    Mildly elevated bilirubin is associated with a reduction in the presence and progression of chronic kidney disease and related mortality, which may be attributed to bilirubin’s antioxidant properties. This study investigated whether endogenously elevated bilirubin would protect against adenine-induced kidney damage in male hyperbilirubinaemic Gunn rats and littermate controls. Animals were orally administered adenine or methylcellulose solvent (vehicle) daily for 10 days and were then monitored for 28 days. Serum and urine were assessed throughout the protocol for parameters of kidney function and antioxidant/oxidative stress status and kidneys were harvested for histological examination upon completion of the study. Adenine-treated animals experienced weight-loss, polyuria and polydipsia; however, these effects were significantly attenuated in adenine-treated Gunn rats. No difference in the presence of dihydroadenine crystals, lymphocytic infiltration and fibrosis were noted in Gunn rat kidneys versus controls. However, plasma protein carbonyl and F2-isoprostane concentrations were significantly decreased in Gunn rats versus controls, with no change in urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine or kidney tissue F2-isoprostane concentrations. These data indicated that endogenously elevated bilirubin specifically protects from systemic oxidative stress in the vascular compartment. These data may help to clarify the protective relationship between bilirubin, kidney function and cardiovascular mortality in clinical investigations. PMID:26498893

  7. Nano-pulverization of poorly water soluble compounds with low melting points by a rotation/revolution pulverizer.

    PubMed

    Yuminoki, K; Takeda, M; Kitamura, K; Numata, S; Kimura, K; Takatsuka, T; Hashimoto, N

    2012-08-01

    We report a method for pulverizing poorly water soluble compounds with low melting points to nanoparticles without producing an amorphous phase using a rotation/revolution pulverizer. Fenofibrate, flurbiprofen, and probucol were used as crystalline model compounds. They were suspended in a methylcellulose aqueous solution and pulverized with zirconia balls by the rotation/revolution pulverizer. Beeswax, an amorphous compound, was also examined to investigate whether nano-pulverization of a compound with a low melting point was possible. Beeswax was suspended in ethyl alcohol cooled with liquid nitrogen and pulverized with zirconia balls by the rotation/revolution pulverizer. By optimizing the pulverization parameters, nanoparticles (D50 < 0.15 microm) of the crystalline compounds were obtained with narrow particle size distributions at a rotation/revolution speed of 1000 rpm and a rotation/revolution ratio of 1.0 when the vessel was 0 degrees C. Amorphous fenofibrate and flurbiprofen were not detected by differential scanning calorimetry or powder X-ray diffraction, whereas small amounts of amorphous probucol were detected. Beeswax was pulverized to nanoparticles (D50 = 0.14 microm) with ethyl alcohol cooled with liquid nitrogen. Fine nanoparticles of these poorly water soluble compounds with low melting points were obtained by controlling the rotation/revolution speed and reducing the vessel temperature. PMID:22957432

  8. Nitric oxide suppression of human hematopoiesis in vitro. Contribution to inhibitory action of interferon-gamma and tumor necrosis factor-alpha.

    PubMed Central

    Maciejewski, J P; Selleri, C; Sato, T; Cho, H J; Keefer, L K; Nathan, C F; Young, N S

    1995-01-01

    IFN-gamma and TNF-alpha, potent inhibitors of hematopoiesis, induce nitric oxide synthase (NOS) in various cell types. When normal human bone marrow (BM) or CD34+ cells were exposed to NO, inhibition of colony formation was dose dependent and direct. NO induced apoptosis in BM progenitors, as shown by electrophoretic detection of DNA degradation and deoxynucleotidyl transferase assay. Using PCR and immunoprecipitation, we found inducible NOS (iNOS) mRNA and iNOS protein in BM after stimulation with IFN-gamma or TNF-alpha. iNOS mRNA was also detected by PCR in highly purified CD34+ cells; TNF-alpha or IFN-gamma increased iNOS expression. The presence of iNOS in CD34+ cells was confirmed in single cells by immunochemical staining. NG-Monomethyl-L-arginine (MM-Arg), an NOS inhibitor, partially reversed the effects of TNF-alpha and, to a lesser extent, IFN-gamma in methylcellulose culture of total BM and CD34+ cells, and inhibited apoptosis of BM cells induced by these cytokines. When the effects of competitive iNOS inhibition were tested on more immature progenitors, MM-Arg increased the number of long-term BM culture-initiating cells in control cultures but failed to protect these cells from the inhibitory action of IFN-gamma and TNF-alpha. Our results suggest that NO may be one mediator of cytokine-induced hematopoietic suppression. Images PMID:7543491

  9. Encapsulation and Delivery of Crystalline Hydrophobic Nutraceuticals using Nanoemulsions: Factors Affecting Polymethoxyflavone Solubility.

    PubMed

    Li, Yan; Xiao, Hang; McClements, David Julian

    2012-12-01

    Polymethoxyflavones (PMF) isolated from citrus peel have potent anti-cancer activity, however their utilization as functional ingredients in foods is currently limited because of their high melting point and poor water-solubility. The influence of oil type and concentration, hydrophilic polymer addition, and simulated intestinal conditions on PMF (5-hydroxytangeretin) solubility in solutions and nanoemulsions was examined. The saturation concentration of PMF in water was relatively low (0.93 µM), but could be increased appreciably by adding certain hydrophilic polymers: polyethylene glycol (PEG) and β-cyclodextrin (CD) were ineffective at increasing solubility, but poly(vinyl alcohol) (PVA) and hydroxypropyl methylcellulose (HPMC) greatly enhanced solubility (e.g., > 6 µM for 0.5 % polymer). PMF was more soluble in medium chain triglycerides (MCT, 6.1 mM) than long chain triglycerides (LCT, 4.2 mM). The encapsulation efficiency of PMF in oil-in-water nanoemulsions was higher when MCT was used as the oil phase rather than LCT, and could be increased by increasing the oil droplet content. The solubility of PMF in simulated small intestinal fluids was increased by solubilization in bile micelles and mixed micelles formed during lipid digestion. These results have important implications for the development of functional foods fortified with bioactive hydrophobic components aimed at improving human health and wellness. PMID:23646037

  10. PBPK Model for Atrazine and Its Chlorotriazine Metabolites in Rat and Human

    PubMed Central

    Campbell, Jerry L.; Andersen, Melvin E.; Hinderliter, Paul M.; Yi, Kun Don; Pastoor, Timothy P.; Breckenridge, Charles B.; Clewell, Harvey J.

    2016-01-01

    The previously-published physiologically based pharmacokinetic model for atrazine (ATZ), deisopropylatrazine (DIA), deethylatrazine (DEA), and diaminochlorotriazine (DACT), which collectively comprise the total chlorotriazines (TCT) as represented in this study, was modified to allow for scaling to humans. Changes included replacing the fixed dose-dependent oral uptake rates with a method that represented delayed absorption observed in rats administered ATZ as a bolus dose suspended in a methylcellulose vehicle. Rate constants for metabolism of ATZ to DIA and DEA, followed by metabolism of DIA and DEA to DACT were predicted using a compartmental model describing the metabolism of the chlorotriazines by rat and human hepatocytes in vitro. Overall, the model successfully predicted both the 4-day plasma time-course data in rats administered ATZ by bolus dose (3, 10, and 50 mg/kg/day) or in the diet (30, 100, or 500 ppm). Simulated continuous daily exposure of a 55-kg adult female to ATZ at a dose of 1.0 µg/kg/day resulted in steady-state urinary concentrations of 0.6, 1.4, 2.5, and 6.0 µg/L for DEA, DIA, DACT, and TCT, respectively. The TCT (ATZ + DEA + DIA + DACT) human urinary biomonitoring equivalent concentration following continuous exposure to ATZ at the chronic point of departure (POD = 1.8 mg/kg/day) was 360.6 μg/L. PMID:26794140

  11. Dynamic scaling analysis of two-dimensional cell colony fronts in a gel medium: a biological system approaching a quenched Kardar-Parisi-Zhang universality.

    PubMed

    Huergo, M A C; Muzzio, N E; Pasquale, M A; Pedro González, P H; Bolzán, A E; Arvia, A J

    2014-08-01

    The interfacial two-dimensional spreading dynamics of quasilinear Vero cell colony fronts in methylcellulose (MC)-containing culture medium, under a constant average front displacement velocity regime, was investigated. Under comparable experimental conditions, the average colony front displacement velocity becomes lower than that reported for a standard culture medium. Initially, the presence of MC in the medium hinders both the colony spreading, due to a gradual change in the average size and shape of cells and their distribution in the colony, and the cell motility in the gelled medium. Furthermore, at longer culture times enlarged cells appear at random in the border region of the colony. These cells behave as obstacles (pinning sites) for the displacement of smaller cells towards the colony front. The dynamic scaling analysis of rough fronts yields the set of exponents α=0.63±0.04,β=0.75±0.05, and z=0.84±0.05, which is close to that expected for a quenched Kardar-Parisi-Zhang model. PMID:25215757

  12. Nanometer depth resolution in 3D topographic analysis of drug-loaded nanofibrous mats without sample preparation.

    PubMed

    Paaver, Urve; Heinämäki, Jyrki; Kassamakov, Ivan; Hæggström, Edward; Ylitalo, Tuomo; Nolvi, Anton; Kozlova, Jekaterina; Laidmäe, Ivo; Kogermann, Karin; Veski, Peep

    2014-02-28

    We showed that scanning white light interferometry (SWLI) can provide nanometer depth resolution in 3D topographic analysis of electrospun drug-loaded nanofibrous mats without sample preparation. The method permits rapidly investigating geometric properties (e.g. fiber diameter, orientation and morphology) and surface topography of drug-loaded nanofibers and nanomats. Electrospun nanofibers of a model drug, piroxicam (PRX), and hydroxypropyl methylcellulose (HPMC) were imaged. Scanning electron microscopy (SEM) served as a reference method. SWLI 3D images featuring 29 nm by 29 nm active pixel size were obtained of a 55 μm × 40 μm area. The thickness of the drug-loaded non-woven nanomats was uniform, ranging from 2.0 μm to 3.0 μm (SWLI), and independent of the ratio between HPMC and PRX. The average diameters (n=100, SEM) for drug-loaded nanofibers were 387 ± 125 nm (HPMC and PRX 1:1), 407 ± 144 nm (HPMC and PRX 1:2), and 290 ± 100 nm (HPMC and PRX 1:4). We found advantages and limitations in both techniques. SWLI permits rapid non-contacting and non-destructive characterization of layer orientation, layer thickness, porosity, and surface morphology of electrospun drug-loaded nanofibers and nanomats. Such analysis is important because the surface topography affects the performance of nanomats in pharmaceutical and biomedical applications. PMID:24378328

  13. The antimicrobial agent C31G is effective for therapy for HSV-1 ocular keratitis in the rabbit eye model.

    PubMed

    Hill, James M; Stern, Ethan M; Bhattacharjee, Partha S; Malamud, Daniel; Clement, Christian; Rodriguez, Paulo; Lukiw, Walter J; Ochoa, Augusto C; Foster, Timothy P; Velasco, Cruz; McFerrin, Harris E

    2013-10-01

    The amphoteric C31G solution contains equimolar alkyl dimethlyglycine and alkyl dimethyl amine oxide buffered with citric acid. C31G acts as a broad spectrum antiviral and an antibacterial. No previous in vivo studies have been done to test C31G in an animal model of HSV-1 ocular keratitis. We assessed the anti-herpetic activity of C31G in the rabbit eye model using three treatment groups: (1) 1% trifluorothymidine (TFT); (2) 0.25% C31G plus 0.5% hydroxypropyl methylcellulose (HPMC); and (3) vehicle, 0.5% HPMC. Scarified rabbit corneas were inoculated with the HSV-1 strain McKrae. On post inoculation (PI) day 3, rabbits were placed in three balanced groups based on slit-lamp examination (SLE) scores. Treatment began on PI day 3, five times a day for five consecutive days. In addition to the daily, masked SLE scoring, the eyes were assessed daily for stromal opacity, scleral inflammation, neovascularization, eyelid inflammation, inflammatory discharge, and epiphora. C31G and TFT were very effective in reducing the lesions and pathogenesis associated with HSV-1 ocular keratitis. The vehicle control scores were significantly higher and did not effectively treat HSV-1 keratitis. C31G has the potential to be used to treat herpetic keratitis as well as other herpetic topical lesions in humans. PMID:23860013

  14. Roles of the ITAM and PY motifs of Epstein-Barr virus latent membrane protein 2A in the inhibition of epithelial cell differentiation and activation of {beta}-catenin signaling.

    PubMed

    Morrison, Jennifer A; Raab-Traub, Nancy

    2005-02-01

    Epstein-Barr virus (EBV) latent membrane protein 2A (LMP2A) is important for maintenance of latency in infected B lymphocytes. Through its immunoreceptor tyrosine-based activation motif (ITAM) and PY motifs, LMP2A is able to block B-cell receptor (BCR) signaling, bind BCR-associated kinases, and manipulate the turnover of itself and these kinases via a PY-mediated interaction with the Nedd4 family of ubiquitin ligases. In epithelial cells, LMP2A has been shown to activate the phosphatidylinositol 3'-OH kinase/Akt and beta-catenin signaling pathways. In the present study, the biological consequences of LMP2A expression in the normal human foreskin keratinocyte (HFK) cell line were investigated and the importance of the ITAM and PY motifs for LMP2A signaling effects in HFK cells was ascertained. The ITAM was essential for the activation of Akt by LMP2A in HFK cells, while both the ITAM and PY motifs contributed to LMP2A-mediated accumulation and nuclear translocation of the oncoprotein beta-catenin. LMP2A inhibited induction of differentiation in an assay conducted with semisolid methylcellulose medium, and the PY motifs were critical for this inhibition. LMP2A is expressed in the EBV-associated epithelial malignancies nasopharyngeal carcinoma and gastric carcinoma, and these data indicate that LMP2A affects cellular processes that likely contribute to carcinogenesis. PMID:15681438

  15. Drug release kinetics from tablet matrices based upon ethylcellulose ether-derivatives: a comparison between different formulations.

    PubMed

    Khan, Gul Majid; Meidan, Victor M

    2007-06-01

    The present study involved the preparation of ibuprofen-containing controlled release tablets formulated from either the established granular product, Ethocel Standard Premium, or the novel finely-milled product, Ethocel Standard FP Premium. The tablets were prepared by either direct compression or wet granulation. The aim was to explore the influence of different parameters on the kinetics and mechanisms of ibuprofen release from the tablets. These parameters were; polymer particle size, polymer molecular weight, drug : polymer ratio, preparation methodology and partial replacement of lactose with the coexcipient-hydroxypropyl methylcellulose (HPMC). The derived drug release data were analyzed with reference to various established mathematical models while the f2-metric technique was used in order to determine profile equivalency. It was found that drug release was mostly modulated by several interactive factors apparently exhibiting crosstalk. Nevertheless, it was possible to identify some simple rules. Incorporation of Ethocel FP polymers and application of the wet granulation technique facilitated greater efficiency in controlling ibuprofen release behavior from the matrices. Furthermore, drug release profiles could be modulated by partial substitution of the primary excipient with HPMC. Polymer concentrations and particle sizes, rather than viscosity grade, were found to be decisive factors in controlling drug release rates. PMID:17613027

  16. Development and evaluation of diltiazem hydrochloride controlled-release pellets by fluid bed coating process

    PubMed Central

    Prasad, Mikkilineni Bhanu; Vidyadhara, Suryadevara; Sasidhar, Reddyvalam Lankapalli C.; Balakrishna, Talamanchi; Trilochani, Pavuluri

    2013-01-01

    The aim of the present study was to develop controlled-release pellets of diltiazem HCl with ethyl cellulose and hydroxylpropyl methylcellulose phthalate as the release rate retarding polymers by fluid bed coating technique. The prepared pellets were evaluated for drug content, particle size, subjected to Scanning Electron Microscopy (SEM) and Differential Scanning Calori metry (DSC), and evaluated for in vitro release. Stability studies were carried out on the optimized formulations for a period of 3 months. The drug content was in the range of 97%-101%. The mean particle size of the drug-loaded pellets was in the range 700-785 μm. The drug release rate decreased as the concentration of ethyl cellulose increased in the pellet formulations. Among the prepared formulations, FDL10 and FDL11 showed 80% drug release in 16 h, matching with USP dissolution test 6 for diltiazem HCl extended-release capsules. SEM photographs confirmed that the prepared formulations were spherical in nature with a smooth surface. The compatibility between drug and polymers in the drug-loaded pellets was confirmed by DSC studies. Stability studies indicated that the pellets were stable. PMID:23833750

  17. [Oral health care by utilizing food function].

    PubMed

    Taguchi, Yuuki

    2014-01-01

    We examined the effects of spices and herbs on Candida albicans to develop therapeutic tools against oral diseases such as oral candidiasis. C. albicans, a dimorphic fungus, is a component of the healthy human microbial flora. However, the excessive overgrowth of C. albicans causes oral candidiasis, and the symptoms, accompanied by severe inflammation, reduce the quality of life of elderly people. We found that spices such as clove (Syzygium aromaticum) and cassia (Cinnamomum aromaticum) exhibit inhibitory activity against Candida mycelial growth and show therapeutic efficacy in a murine oral candidiasis model. Our studies also demonstrated that the inhibitory activity of cinnamaldehyde was strengthened in parallel with a prolonged treatment time. Furthermore, when cinnamaldehyde in combination with methylcellulose was administered to the model mice, the therapeutic effect was potentiated. Here, we summarize up-to-date findings on how to use spices and herbs on a daily basis to improve or prevent oral problems such as oral candidiasis with the presentation of our recent data. PMID:25742994

  18. Constipation in people prescribed opioids

    PubMed Central

    2010-01-01

    Introduction Constipation is reported in 52% of people with advanced malignancy. This figure rises to 87% in people who are terminally ill and taking opioids. Constipation may be the most common adverse effect of opioids. There is no reason to believe that people with chronic non-malignant disease who take opioids will be any less troubled by this adverse effect. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of: oral laxatives, rectally applied medications, and opioid antagonists for constipation in people prescribed opioids? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2009 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 23 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: arachis oil enemas, bisacodyl, co-danthrusate/co-danthramer, docusate, glycerol suppositories, ispaghula husk, lactulose, liquid paraffin, macrogols plus electrolyte solutions, magnesium salts, methylcellulose, opioid antagonists, phosphate enemas, senna, sodium citrate micro-enema, and sodium picosulfate. PMID:21718572

  19. Human adipose CD34+ CD90+ stem cells and collagen scaffold constructs grafted in vivo fabricate loose connective and adipose tissues.

    PubMed

    Ferraro, Giuseppe A; De Francesco, Francesco; Nicoletti, Gianfranco; Paino, Francesca; Desiderio, Vincenzo; Tirino, Virginia; D'Andrea, Francesco

    2013-05-01

    Stem cell based therapies for the repair and regeneration of various tissues are of great interest for a high number of diseases. Adult stem cells, instead, are more available, abundant and harvested with minimally invasive procedures. In particular, mesenchymal stem cells (MSCs) are multi-potent progenitors, able to differentiate into bone, cartilage, and adipose tissues. Human adult adipose tissue seems to be the most abundant source of MSCs and, due to its easy accessibility; it is able to give a considerable amount of stem cells. In this study, we selected MSCs co-expressing CD34 and CD90 from adipose tissue. This stem cell population displayed higher proliferative capacity than CD34(-) CD90(-) cells and was able to differentiate in vitro into adipocytes (PPARγ(+) and adiponectin(+)) and endothelial cells (CD31(+) VEGF(+) Flk1(+)). In addition, in methylcellulose without VEGF, it formed a vascular network. The aim of this study was to investigate differentiation potential of human adipose CD34(+) /CD90(+) stem cells loaded onto commercial collagen sponges already used in clinical practice (Gingistat) both in vitro and in vivo. The results of this study clearly demonstrate that human adult adipose and loose connective tissues can be obtained in vivo, highlighting that CD34(+) /CD90 ASCs are extremely useful for regenerative medicine. PMID:23129214

  20. The importance of binder moisture content in Metformin HCL high-dose formulations prepared by moist aqueous granulation (MAG)

    PubMed Central

    Takasaki, Hiroshi; Yonemochi, Etsuo; Ito, Masanori; Wada, Koichi; Terada, Katsuhide

    2015-01-01

    The aim of this study was to evaluate binders to improve the flowability of granulates and compactibility of Metformin HCL (Met) using the moist aqueous granulation (MAG) process. The effect of the binder moisture content on granulate and tablet quality was also evaluated. Vinylpyrrolidone–vinyl acetate copolymer (Kollidon VA64 fine: VA64), polyvidone (Povidone K12: PVP), hydroxypropyl cellulose (HPC SSL SF: HPC) and hydroxypropyl methylcellulose (Methocel E5 LV: HPMC) were evaluated as binders. These granulates, except for HPMC, had a lower yield pressure than Met active pharmaceutical ingredient (API). HPMC Met was not sufficiently granulated with low water volume. No problems were observed with the VA64 Met granulates during the tableting process. However, HPC Met granulates had a bowl-forming tendency, and PVP Met granulates had the tendency to stick during the tableting process. These bowl-forming and sticking tendencies may have been due to the low moisture absorbency of HPC and the high volume of bound water of PVP, respectively. VA64 Met granulates had the highest ambient moisture content (bulk water, bound water) and moisture absorbency. It was concluded that the type of binder used for the Met MAG process has an impact on granulate flow and compactibility, as well as moisture absorbency and maintenance of moisture balance. PMID:26779418

  1. Optimization of aceclofenac solid dispersion using Box-Behnken design: in-vitro and in-vivo evaluation.

    PubMed

    Maulvi, Furqan A; Thakkar, Vaishali T; Soni, Tejal G; Gandhi, Tejal R

    2014-01-01

    The study investigates the combined influence of three independent variables in preparation of aceclofenac ternary solid dispersion (SD) by kneading method. A 3-factor, 3-level Box-Behnken design was used. Independent variables selected were microcrystalline cellulose (Avicel 200 = X1), hydroxypropyl methylcellulose-5 cps (HPMC E-5 = X2), and ratio of drug to polymer mixture (X3). Fifteen batches were prepared and evaluated for angle of repose and percentage drug release at 5 minutes (Q5). The transformed values of variables were subjected to multiple regression analysis to establish a second-order polynomial equation. Contour plots were constructed to evaluate the effects of X1, X2 and X3 on Q5 and angle of repose. Model was validated for accurate prediction of Q5 and angle of repose (AR) by performing checkpoint analysis. The computer optimization process and contour plots predict the levels of independent variables as X1= +0.5, X2 = -1 and X3 = +0.35 for maximized response of Q5 with better flow property. The stability study during 6 months confirms that aceclofenac exhibits high stability in solid dispersion. In vivo studies indicate that optimized ternary solid dispersion provides rapid pharmacological responses in mice and rats compared to marketed formulation. PMID:24611664

  2. Use of Propranolol-Magnesium Aluminium Silicate Intercalated Complexes as Drug Reservoirs in Polymeric Matrix Tablets

    PubMed Central

    Pongjanyakul, T.; Rojtanatanya, S.

    2012-01-01

    The objective of the present study was to investigate the use of propranolol–magnesium aluminium silicate intercalated complexes as drug reservoirs in hydroxypropylmethylcellulose tablets. The matrix tablets containing the complexes were prepared and characterised with respect to propranolol release and were subsequently compared with those loading propranolol or a propranolol–magnesium aluminium silicate physical mixture. Additionally, the effects of varying viscosity grades of hydroxypropyl methylcellulose, compression pressures and calcium acetate incorporation on the drug release characteristics of the complex-loaded tablets were also examined. The results showed that the complex-loaded tablets have higher tablet hardness than those containing propranolol or a physical mixture. The drug release from the complex-loaded tablets followed a zero-order release kinetic, whereas an anomalous transport was found in the propranolol or physical mixture tablets. The drug release rate of the complex tablet significantly decreased with increasing hydroxypropylmethylcellulose viscosity grade. Increase in the compression pressure caused a decrease in the drug release rate of the tablets. Furthermore, the incorporation of calcium ions could accelerate propranolol release, particularly in acidic medium, because calcium ions could be exchanged with propranolol molecules intercalated in the silicate layers of magnesium aluminium silicate. These findings suggest that propranolol-magnesium aluminium silicate intercalated complexes show strong potential for use as drug reservoirs in matrix tablets intended for modifying drug release. PMID:23626384

  3. Ibuprofen effects on behavioral thermoregulation with microwave radiation in albino rats.

    PubMed

    Vitulli, W F; Nemeth, Y M; Conte, C T

    2001-04-01

    This study determined whether ibuprofen causes a disruptive behavior pattern similar to aspirin yet contrary to acetaminophen regarding thermoregulatory effects. 8 Sprague-Dawley rats (3 males and 5 females) were drawn from a population of rats which had been conditioned to press a lever for food reinforcement in an undergraduate course in operant conditioning. Animals were conditioned in a refrigerated Skinner Box on a fixed-interval 2-min. (FI-2 min.) schedule of microwave radiation (5 sec. of radiation per exposure occasion) in a repeated-measures reversal (within-subjects) design. The rats were injected intraperitoneally with doses of ibuprofen in amounts of 10-50 mg/kg or methyl-cellulose control vehicle of equal volume over 8-hr. daily sessions. A multivariate analysis of variance showed significant differences due to doses (mg/kg) of ibuprofen for number of microwave heat reinforcers per hour and rate of responding (ns) both measures of which were significantly higher during the first 2 hours of the session. Comparative differences in behavioral thermoregulation in humans reflect the likelihood of underlying biochemical mechanisms based on research by Murphy, Badia, Myers, Boecker, and Wright in 1994. PMID:11361298

  4. Part II: bioavailability in beagle dogs of nimodipine solid dispersions prepared by hot-melt extrusion.

    PubMed

    Zheng, Xin; Yang, Rui; Zhang, Yu; Wang, Zhijun; Tang, Xing; Zheng, Liangyuan

    2007-07-01

    The aim of the present work was to investigate the in vitro dissolution properties and oral bioavailability of three solid dispersions of nimodipine. The solid dispersions were compared with pure nimodipine, their physical mixtures, and the marketed drug product Nimotop. Nimodipine solid dispersions were prepared by a hot-melt extrusion process with hydroxypropyl methylcellulose (HPMC, Methocel E5), polyvinylpyrrolidone/vinyl acetate copolymer (PVP/VA, Plasdone S630), and ethyl acrylate, methyl methacrylate polymer (Eudragit EPO). Previous studies of XRPD and DSC data showed that the crystallinity was not observed in hot-melt extrudates, two T(g)s were observed in the 30% and 50% NMD-HPMC samples, indicating phase separation. The weakening and shift of the N-H stretching vibration of the secondary amine groups of nimodipine as determined by FT-IR proved hydrogen bonding between the drug and polymers in the solid dispersion. The dissolution profiles of the three dispersion systems showed that the release was improved compared with the unmanipulated drug. Drug plasma concentrations were determined by HPLC, and pharmacokinetic parameters were calculated after orally administering each preparation containing 60 mg of nimodipine. The mean bioavailability of nimodipine was comparable after administration of the Eudragit EPO solid dispersion and Nimotop, but the HPMC and PVP/VA dispersions exhibited much lower bioavailability. However, the AUC(0-12 hr) values of all three solid dispersions were significantly higher than physical mixtures with the same carriers and nimodipine powder. PMID:17654027

  5. Preparation and characterization of a gastric floating dosage form of capecitabine.

    PubMed

    Taghizadeh Davoudi, Ehsan; Ibrahim Noordin, Mohamed; Kadivar, Ali; Kamalidehghan, Behnam; Farjam, Abdoreza Soleimani; Akbari Javar, Hamid

    2013-01-01

    Gastrointestinal disturbances, such as nausea and vomiting, are considered amongst the main adverse effects associated with oral anticancer drugs due to their fast release in the gastrointestinal tract (GIT). Sustained release formulations with proper release profiles can overcome some side effects of conventional formulations. The current study was designed to prepare sustained release tablets of Capecitabine, which is approved by the Food and Drug Administration (FDA) for the treatment of advanced breast cancer, using hydroxypropyl methylcellulose (HPMC), carbomer934P, sodium alginate, and sodium bicarbonate. Tablets were prepared using the wet granulation method and characterized such that floating lag time, total floating time, hardness, friability, drug content, weight uniformity, and in vitro drug release were investigated. The sustained release tablets showed good hardness and passed the friability test. The tablets' floating lag time was determined to be 30-200 seconds, and it floated more than 24 hours and released the drug for 24 hours. Then, the stability test was done and compared with the initial samples. In conclusion, by adjusting the right ratios of the excipients including release-retarding gel-forming polymers like HPMC K4M, Na alginate, carbomer934P, and sodium bicarbonate, sustained release Capecitabine floating tablet was formulated. PMID:24288681

  6. Long-term evaluation of the degradation behavior of three apatite-forming calcium phosphate cements.

    PubMed

    An, Jie; Liao, Hongbing; Kucko, Nathan W; Herber, Ralf-Peter; Wolke, Joop G C; van den Beucken, Jeroen J J P; Jansen, John A; Leeuwenburgh, Sander C G

    2016-05-01

    Calcium phosphate cements (CPCs) are injectable bone substitutes with a long clinical history because of their biocompatibility and osteoconductivity. Nevertheless, their cohesion upon injection into perfused bone defects as well as their long-term degradation behavior remain major clinical challenges. Therefore, the long-term degradation behavior of two types of α-tricalcium phosphate-based, apatite-forming CPCs was compared to a commercially available apatite-forming cement, that is HydroSet(TM) . Carboxyl methylcellulose (CMC) was used as cohesion promotor to improve handling properties of the two experimental cements, whereas poly (d, l-lactic-co-glycolic) acid (PLGA) microparticles were added to introduce macroporosity and stimulate CPC degradation. All three CPCs were injected into defects drilled into rabbit femoral condyles and explanted after 4, 12, or 26 weeks, after which the bone response was assessed both qualitatively and quantitatively. CPCs without PLGA microparticles degraded only at the periphery of the implants, while the residual CPC volume was close to 90%. On the contrary, bone ingrowth was observed not only at the periphery of the CPC, but also throughout the center of the implants after 26 weeks of implantation for the PLGA-containing CPCs with a residual CPC volume of approximately 55%. In conclusion, it was shown that CPC containing CMC and PLGA was able to induce partial degradation of apatite-forming CPCs and concomitant replacement by bone tissue. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1072-1081, 2016. PMID:26743230

  7. Isolation of Murine Embryonic Hemogenic Endothelial Cells

    PubMed Central

    Marcelo, Kathrina L.; Hirschi, Karen K.

    2016-01-01

    The specification of hemogenic endothelial cells from embryonic vascular endothelium occurs during brief developmental periods within distinct tissues, and is necessary for the emergence of definitive HSPC from the murine extra embryonic yolk sac, placenta, umbilical vessels, and the embryonic aorta-gonad-mesonephros (AGM) region. The transient nature and small size of this cell population renders its reproducible isolation for careful quantification and experimental applications technically difficult. We have established a fluorescence-activated cell sorting (FACS)-based protocol for simultaneous isolation of hemogenic endothelial cells and HSPC during their peak generation times in the yolk sac and AGM. We demonstrate methods for dissection of yolk sac and AGM tissues from mouse embryos, and we present optimized tissue digestion and antibody conjugation conditions for maximal cell survival prior to identification and retrieval via FACS. Representative FACS analysis plots are shown that identify the hemogenic endothelial cell and HSPC phenotypes, and describe a methylcellulose-based assay for evaluating their blood forming potential on a clonal level. PMID:27341393

  8. Analysis of results of ASTP experiment in electrophoresis

    NASA Technical Reports Server (NTRS)

    Vanderhoff, J. W.; Micale, F. J.; Krumrine, P. H.

    1977-01-01

    The Apollo-Soyuz Test Project (ASTP) included an electrophoretic separation experiment of biological cells. The nature separation results of aldehyde-fixed rabbit, human and horse red blood cells, which were taken in the form of photographs taken at three-minute intervals, are the subject of this report. The electrophoretic separation was successful in that fractionation according to mobility did occur and was found in the sliced samples. Photographic evidence indicates that the low electroosmotic methylcellulose coating was successful in reducing the electroosmosis to a near zero value. Also, the flight film shows that the bands migrated down the column as theory would predict, producing two bands of high cell concentration separated and surrounded by regions of lower cell concentration. However, most likely some clumping of cells occurred to cause the trailing band to be larger than expected from theory. Overall, the experiment was a success in demonstrating a static electrophoresis separation under microgravity conditions with a resolution not possible on earth.

  9. ¹³C solid-state NMR analysis of the most common pharmaceutical excipients used in solid drug formulations Part II: CP kinetics and relaxation analysis.

    PubMed

    Pisklak, Dariusz Maciej; Zielińska-Pisklak, Monika; Szeleszczuk, Łukasz; Wawer, Iwona

    2016-04-15

    Excipients used in the solid drug formulations differ in their NMR relaxation and (13)C cross-polarization (CP) kinetics parameters. Therefore, experimental parameters like contact time of cross-polarization and repetition time have a major impact on the registered solid state NMR spectra and in consequence on the results of the NMR analysis. In this work the CP kinetics and relaxation of the most common pharmaceutical excipients: anhydrous α-lactose, α-lactose monohydrate, mannitol, sucrose, sorbitol, sodium starch glycolate type A and B, starch of different origin, microcrystalline cellulose, hypromellose, ethylcellulose, methylcellulose, hydroxyethylcellulose, sodium alginate, magnesium stearate, sodium laurilsulfate and Kollidon(®) were analyzed. The studied excipients differ significantly in their optimum repetition time (from 5 s to 1200 s) and T(1ρ)(I) parameters (from 2 ms to 73 ms). The practical use of those differences in the excipients composition analysis was demonstrated on the example of commercially available tablets containing indapamide as an API. The information presented in this article will help to choose the correct acquisition parameters and also will save the time and effort needed for their optimization in the NMR analysis of the solid drug formulations. PMID:26836362

  10. Multiple-unit tablet of probiotic bacteria for improved storage stability, acid tolerability, and in vivo intestinal protective effect

    PubMed Central

    Park, Hee Jun; Lee, Ga Hyeon; Jun, Joonho; Son, Miwon; Kang, Myung Joo

    2016-01-01

    The aim of this study was to formulate probiotics-loaded pellets in a tablet form to improve storage stability, acid tolerability, and in vivo intestinal protective effect. Bacteria-loaded pellets primarily prepared with hydroxypropyl methylcellulose acetate succinate were compressed into tablets with highly compressible excipients and optimized for flow properties, hardness, and disintegration time. The optimized probiotic tablet consisted of enteric-coated pellets (335 mg), microcrystalline cellulose (Avicel PH102, 37.5 mg), and porous calcium silicate (25 mg) and allowed whole survival of living bacteria during the compaction process with sufficient tablet hardness (13 kp) and disintegration time (14 minutes). The multiple-unit tablet showed remarkably higher storage stability under ambient conditions (25°C/60% relative humidity) over 6 months and resistance to acidic medium compared to uncoated strains or pellets. Repeated intake of this multiple-unit tablet significantly lowered plasma level of endotoxin, a pathogenic material, compared to repeated intake of bare probiotics or marketed products in rats. These results, therefore, suggest that the multiple-unit tablet is advantageous to better bacterial viability and gain the beneficial effects on the gut flora, including the improvement of intestinal barrier function. PMID:27103789

  11. ¹³C solid-state NMR analysis of the most common pharmaceutical excipients used in solid drug formulations, Part I: Chemical shifts assignment.

    PubMed

    Pisklak, Dariusz Maciej; Zielińska-Pisklak, Monika Agnieszka; Szeleszczuk, Łukasz; Wawer, Iwona

    2016-04-15

    Solid-state NMR is an excellent and useful method for analyzing solid-state forms of drugs. In the (13)C CP/MAS NMR spectra of the solid dosage forms many of the signals originate from the excipients and should be distinguished from those of active pharmaceutical ingredient (API). In this work the most common pharmaceutical excipients used in the solid drug formulations: anhydrous α-lactose, α-lactose monohydrate, mannitol, sucrose, sorbitol, sodium starch glycolate type A and B, starch of different origin, microcrystalline cellulose, hypromellose, ethylcellulose, methylcellulose, hydroxyethylcellulose, sodium alginate, magnesium stearate, sodium laurilsulfate and Kollidon(®) were analyzed. Their (13)C CP/MAS NMR spectra were recorded and the signals were assigned, employing the results (R(2): 0.948-0.998) of GIPAW calculations and theoretical chemical shifts. The (13)C ssNMR spectra for some of the studied excipients have not been published before while for the other signals in the spectra they were not properly assigned or the assignments were not correct. The results summarize and complement the data on the (13)C ssNMR analysis of the most common pharmaceutical excipients and are essential for further NMR studies of API-excipient interactions in the pharmaceutical formulations. PMID:26845204

  12. Multiple-unit tablet of probiotic bacteria for improved storage stability, acid tolerability, and in vivo intestinal protective effect.

    PubMed

    Park, Hee Jun; Lee, Ga Hyeon; Jun, Joonho; Son, Miwon; Kang, Myung Joo

    2016-01-01

    The aim of this study was to formulate probiotics-loaded pellets in a tablet form to improve storage stability, acid tolerability, and in vivo intestinal protective effect. Bacteria-loaded pellets primarily prepared with hydroxypropyl methylcellulose acetate succinate were compressed into tablets with highly compressible excipients and optimized for flow properties, hardness, and disintegration time. The optimized probiotic tablet consisted of enteric-coated pellets (335 mg), microcrystalline cellulose (Avicel PH102, 37.5 mg), and porous calcium silicate (25 mg) and allowed whole survival of living bacteria during the compaction process with sufficient tablet hardness (13 kp) and disintegration time (14 minutes). The multiple-unit tablet showed remarkably higher storage stability under ambient conditions (25°C/60% relative humidity) over 6 months and resistance to acidic medium compared to uncoated strains or pellets. Repeated intake of this multiple-unit tablet significantly lowered plasma level of endotoxin, a pathogenic material, compared to repeated intake of bare probiotics or marketed products in rats. These results, therefore, suggest that the multiple-unit tablet is advantageous to better bacterial viability and gain the beneficial effects on the gut flora, including the improvement of intestinal barrier function. PMID:27103789

  13. Predictable pulsatile release of tramadol hydrochloride for chronotherapeutics of arthritis.

    PubMed

    Dabhi, Chandu; Randale, Shivsagar; Belgamwar, Veena; Gattani, Surendra; Tekade, Avinash

    2010-07-01

    The present investigation deals with the development of a pH and time-dependent press-coated pulsatile drug delivery system for delivering drugs into the colon. The system consists of a drug containing core, coated by a combination of natural polymer Delonix regia gum (DRG) and hydroxypropyl methylcellulose (HPMC K4M) in various proportions, which controls the onset of release. The whole system was coated with methacrylic acid copolymers, which not only prevents the drug release in the stomach, but also prolongs the lag time. Tramadol HCl was used as a model drug and varying combinations of DRG and HPMC K4M were used to achieve the desired lag time before rapid and complete release of the drug in the colon. It was observed that the lag time depends on the coating ratio of DRG to HPMC and also on press coating weight. Drug release was found to be increased by 15-30% in the presence of colonic microbial flora. The results showed the capability of the system in achieving pulsatile release for a programmable period of time and pH-dependent release to attain colon-targeted delivery. PMID:20524906

  14. Preparation and clinical evaluation of nano-transferosomes for treatment of erectile dysfunction

    PubMed Central

    Ali, Maha Fadel M; Salem, Heba F; Abdelmohsen, Hany F; Attia, Sameh K

    2015-01-01

    Objective The goal of the present study was to formulate topical nanocarriers of the low-cost vasodilator, papaverine hydrochloride (PH), as an alternative to the painful penile injections. The injections are used for both diagnosis and treatment of erectile dysfunction. Transdermal nano-transferosome (T), the ultraflexible nanoliposome, was used as a nanocarrier to enhance the penetration of the papaverine to the penis. Methods Different nano formulas were prepared and characterized for their encapsulation efficiency, particle size, zeta potential, and cumulative drug release. The formula acquired the best characteristics was incorporated into 2% (w/v) hydroxypropyl methylcellulose hydrogel base. The gel containing transferosomal papaverine hydrochloride (PH) and that containing free PH were clinically compared using color flow Doppler measurements. Results The results revealed that transferosome 3 (T3) had the highest entrapment efficiency approaching 72%, low particle size of 220 nm, and zeta potential of −33.4 mV. The formula released 73% of its initial drug content within 2 hours. The clinical evaluation showed the increase in the cavernous artery diameter from 0.53 mm to 0.78 mm and the increase in the peak systolic flow velocity from 5.95 cm/second to 12.2 cm/second, both of which were found to be significant at P<0.05. Conclusion It is evident from the study that the transferosomes can be used as a carrier of papaverine hydrochloride for both diagnosis and treatment of the erectile dysfunction. This new strategy could be used successfully in the treatment of erectile dysfunction and in male impotency. PMID:25995616

  15. Development of a zero-order sustained-release tablet containing mesalazine and budesonide intended to treat the distal gastrointestinal tract in inflammatory bowel disease.

    PubMed

    Gareb, Bahez; Eissens, Anko C; Kosterink, Jos G W; Frijlink, Hendrik W

    2016-06-01

    Ulcerative colitis (UC) and Crohn's disease (CD) are diseases affecting the gastrointestinal tract. Treatment depends on the severity of the disease, site of inflammation, and patient's response. The aim of this study was to develop a zero-order sustained-release tablet containing both the anti-inflammatory drugs mesalazine and budesonide as a new treatment option for ileo-colonic CD and UC. Tablets were attained by wet granulation with hydroxypropyl methylcellulose and direct compression. Our newly developed tablet core was coated with different ColoPulse® coating thicknesses and the mesalazine and budesonide release profiles were investigated in a 600-min gastrointestinal simulation system (GISS) experiment, together with commercially available MMX®-mesalazine and MMX®-budesonide. Lag-time, release rate (k0), completeness of release, and zero-order correlation coefficient (R(2)0) could be manipulated by varying ColoPulse® coating thickness. Our newly developed combination preparation (C[4.92]) complied with all conducted European Pharmacopoeia tests as well as an accelerated 6-month stability test and had a lag-time of 250min (simulated ileum targeted), a linear release profile (mesalazine R(2)0=0.9002; budesonide R(2)0=0.9481), and drug release of 100% mesalazine and 77% budesonide. Like C[4.92], MMX®-mesalazine had a linear (R(2)0=0.9883) and complete release profile (96%). However, C[4.92] lag-time was longer (250 vs. 210min), assuring simulated ileum specificity. Remarkably, MMX®-budesonide lag-time was 480min and release was only 7% with a linear character (R(2)0=0.9906). The in vitro results suggest that MMX®-budesonide effectiveness may be improved if budesonide release in the aqueous phase would be increased and that C[4.92] is a potential, new treatment option for ileo-colonic CD and UC. PMID:27000751

  16. Evaluating effects of penicillin treatment on the metabolome of rats.

    PubMed

    Sun, Jinchun; Schnackenberg, Laura K; Khare, Sangeeta; Yang, Xi; Greenhaw, James; Salminen, William; Mendrick, Donna L; Beger, Richard D

    2013-08-01

    Penicillin (PEN) V, a well-known antibiotic widely used in the treatment of Gram-positive bacterial infections, was evaluated in this study. LC/MS- and NMR-based metabolic profiling were employed to examine the effects of PEN on the host's metabolic phenotype. Male Sprague Dawley rats were randomly divided into groups that were orally administered either 0.5% methylcellulose vehicle, 100 or 2400mg PEN/kg body weight once daily for up to 14 consecutive days. Urine, plasma and tissue were collected from groups sacrificed at 6h, 24h or 14d. The body fluids were subjected to clinical chemistry and metabolomics analysis; the tissue samples were processed for histopathology. The only notable clinical chemistry observation was that gamma glutamyltransferase (GGT) significantly decreased at 24h for both dose groups, and significantly decreased at 14d for the high-dose groups. Partial least squares discriminant analysis scores plots of the metabolomics data from urine and plasma samples showed dose- and time-dependent grouping patterns. Time- and dose-dependent decreases in urinary metabolites including indole-containing metabolites (such as 3-methyldioxyindole sulfate generated from bacterial metabolism of tryptophan), organic acids containing phenyl groups (such as hippuric acid, phenyllactic acid and 3-hydroxyanthranilic acid), and metabolites conjugated with sulfate or glucuronide (such as cresol sulfate and aminophenol sulfate) indicated that the gut microflora population was suppressed. Decreases in many host-gut microbiota urinary co-metabolites (indole- and phenyl-containing metabolites, amino acids, vitamins, nucleotides and bile acids) suggested gut microbiota play important roles in the regulation of host metabolism, including dietary nutrient absorption and reprocessing the absorbed nutrients. Decreases in urinary conjugated metabolites (sulfate, glucuronide and glycine conjugates) implied that gut microbiota might have an impact on chemical detoxification

  17. Formulation and evaluation of fast dissolving films of levocitirizine di hydrochloride

    PubMed Central

    Prabhu, Prabhakara; Malli, Ravi; Koland, Marina; Vijaynarayana, K; D’Souza, Ullas; Harish, NM; Shastry, CS; Charyulu, RN

    2011-01-01

    Introduction: Levocetirizine dihydrochloride is an orally active, third-generation non-sedative antihistamine used in the symptomatic relief of seasonal and perennial allergic rhinitis. The present work aimed at preparing quick release films of levocetirizine with the purpose of developing a dosage form for a very quick onset of action, which is beneficial in managing severe conditions of allergies, aiding in the enhancement of bioavailability, and is very convenient for administration, without the problem of swallowing and using water. Materials and Methods: The films of levocetirizine dihydrochloride were prepared by using polymers such as hydroxypropyl methylcellulose (HPMC) and polyvinyl alcohol (PVA), as either single polymer or in combination of two, by a solvent casting method. They were evaluated for physical characteristics such as uniformity of weight, thickness, folding endurance, drug content uniformity, surface pH, percentage elongation, and tensile strength, and gave satisfactory results. The formulations were subjected to disintegration, in vitro drug release tests, and in vivo studies on rats. Results: A marked increase in the dissolution rate was exhibited by fast-dissolving films of levocetirizine dihydrochloride containing HPMC as a polymer, when compared to conventional tablets. The haloperidol-induced catalepsy, milk-induced leukocytosis, and nasal provocation in vivo studies in rats proved that the fast-dissolving films of levocetirizine dihydrochloride produced a faster onset of action compared to the conventional tablets. Conclusions: Fast dissolving films of levocetirizine dihydrochloride can be considered suitable for clinical use in the treatment of allergic rhinitis and other conditions of allergies, where a quicker onset of action for a dosage form is desirable along with the convenience of administration. PMID:23071928

  18. Mechanistic differences in permeation behavior of supersaturated and solubilized solutions of carbamazepine revealed by nuclear magnetic resonance measurements.

    PubMed

    Ueda, Keisuke; Higashi, Kenjirou; Limwikrant, Waree; Sekine, Shuichi; Horie, Toshiharu; Yamamoto, Keiji; Moribe, Kunikazu

    2012-11-01

    A solid dispersion (SPD) of carbamazepine (CBZ) with hydroxypropyl methylcellulose acetate succinate (HPMC-AS) was prepared by the spray drying method. The apparent solubility (37 °C, pH 7.4) of CBZ observed with the SPD was over 3 times higher than the solubility of unprocessed CBZ. The supersaturated solution was stable for 7 days. A higher concentration of CBZ in aqueous medium was also achieved by mixing with Poloxamer 407 (P407), a solubilizing agent. From permeation studies of CBZ using Caco-2 monolayers and dialysis membranes, we observed improved CBZ permeation across the membrane in the supersaturated solution of CBZ/HPMC-AS SPD. On the contrary, the CBZ-solubilized P407 solution exhibited poor permeation by CBZ. The chemical shifts of CBZ on the (1)H NMR spectrum from CBZ/HPMC-AS SPD solution were not altered significantly by coexistence with HPMC-AS. In contrast, an upfield shift of CBZ was observed in the CBZ/P407 solution. The spin-lattice relaxation time (T(1)) over spin-spin relaxation time (T(2)) indicated that the mobility of CBZ in the HPMC-AS solution was much lower than that in water. Meanwhile, the mobility of CBZ in P407 solution was significantly higher than that in water. NMR data indicate that CBZ does not strongly interact with HPMC-AS. CBZ mobility was suppressed due to self-association and microviscosity around CBZ, which do not affect permeation behavior. Most of the CBZ molecules in the CBZ/P407 solution were solubilized in the hydrophobic core of P407, and a few were free to permeate the membrane. The molecular state of CBZ, as evaluated by NMR measurements, directly correlated with permeation behavior. PMID:22970935

  19. Growth and differentiation of circulating hemopoietic stem cells with atomic bomb irradiation-induced chromosome abnormalities

    SciTech Connect

    Amenomori, T.; Honda, T.; Otake, M.; Tomonaga, M.; Ichimaru, M.

    1988-11-01

    The effects of atomic bomb irradiation on hemopoietic stem cells were studied cytogenetically using single colonies derived from hemopoietic progenitor cells. The subjects studied were 21 healthy atomic bomb survivors (10 males and 11 females) in the high dose exposure group (100+ rad) with a known high incidence (10% or more) of radiation-induced chromosome abnormalities in their peripheral blood lymphocytes (stimulated with phytohemagglutinin), and 11 nonexposed healthy controls (5 males and 6 females). Colony formation by circulating granulocyte-macrophage (GM-CFC) and erythroid (BFU-E) progenitor cells was made by the methylcellulose method using peripheral blood mononuclear cells. Chromosome specimens were prepared from single colonies by our micromethod. The total number of colonies analyzed in the exposed group was 131 for GM-CFC and 75 for BFU-E. Chromosome abnormalities were observed in 15 (11.5%) and 9 (12.0%) colonies, respectively. In the control group, the total number of colonies analyzed was 61 for GM-CFC and 41 for BFU-E. None of these colonies showed chromosome abnormalities. The difference in incidence of chromosome abnormalities was highly significant by an exact test; p = 0.003 for GM-CFC and 0.017 for BFU-E. The karyotypes of chromosome abnormalities obtained from the colonies in the exposed group were mostly translocations, but deletion and marker chromosomes were also observed. In two individuals, such karyotypic abnormalities as observed in the peripheral lymphocytes were also seen in the myeloid progenitor cells. This finding suggests that atomic bomb irradiation produced a chromosome aberration on multipotent hemopoietic stem cells common to myeloid and lymphoid lineages.

  20. Drug release-modulating mechanism of hydrophilic hydroxypropylmethylcellulose matrix tablets: distribution of atoms and carrier and texture analysis.

    PubMed

    Park, Jun-Bom; Lim, Jisung; Kang, Chin-Yang; Lee, Beom-Jin

    2013-12-01

    Although release profiles of drug from hydrophilic matrices have been well recognized, the visual distribution of hydroxypropylmethylcellulose (HPMC) and atoms inside of internal structures of hydrophilic HPMC matrices has not been characterized. In this paper, drug release mechanism from HPMC matrix tablet was investigated based on the release behaviors of HPMC, physical properties of gelled HPMC tablet and atomic distributions of formulation components using diverse instruments. A matrix tablet consisting of hydroxypropyl methylcellulose (HPMC 6, 4,000 and 100,000 mPa·s), chlorpheniramine maleate (CPM) as a model and fumed silicon dioxide (Aerosil(®) 200) was prepared via direct compression. The distribution of atoms and HPMC imaging were characterized using scanning electron microscope (SEM)/ energy-dispersive X-ray spectroscopy (EDX), and near-infrared (NIR) analysis, respectively as a function of time. A texture analyzer was also used to characterize the thickness and maintenance of gel layer of HPMC matrix tablet. The HPMC matrix tablets showed Higuchi release kinetics with no lag time against the square root of time. High viscosity grades of HPMC gave retarded release rate because of the greater swelling and gel thickness as characterized by texture analyzer. According to the NIR imaging, low-viscosity-grade HPMC (6 mPa·s) quickly leached out onto the surface of the tablet, while the high-viscosity-grade HPMC (4000 mPa·s) formed much thicker gel layer around the tablet and maintained longer via slow erosion, resulting in retarded drug release. The atomic distribution of the drug (chlorine, carbon, oxygen), HPMC (carbon, oxygen) and silicon dioxide (silica, oxygen) and NIR imaging of HPMC corresponded with the dissolution behaviors of drug as a function of time. The use of imaging and texture analyses could be applicable to explain the release- modulating mechanism of hydrophilic HPMC matrix tablets. PMID:23855499

  1. In Vivo Assessment of Phage and Linezolid Based Implant Coatings for Treatment of Methicillin Resistant S. aureus (MRSA) Mediated Orthopaedic Device Related Infections.

    PubMed

    Kaur, Sandeep; Harjai, Kusum; Chhibber, Sanjay

    2016-01-01

    Staphylococcus comprises up to two-thirds of all pathogens in orthopaedic implant infections with two species respectively Staphylococcus aureus and Staphylococcus epidermidis, being the predominate etiological agents isolated. Further, with the emergence of methicillin-resistant S. aureus (MRSA), treatment of S. aureus implant infections has become more difficult, thus representing a devastating complication. Use of local delivery system consisting of S.aureus specific phage along with linezolid (incorporated in biopolymer) allowing gradual release of the two agents at the implant site represents a new, still unexplored treatment option (against orthopaedic implant infections) that has been studied in an animal model of prosthetic joint infection. Naked wire, hydroxypropyl methylcellulose (HPMC) coated wire and phage and /or linezolid coated K-wire were surgically implanted into the intra-medullary canal of mouse femur bone of respective groups followed by inoculation of S.aureus ATCC 43300(MRSA). Mice implanted with K-wire coated with both the agents i.e phage as well as linezolid (dual coated wires) showed maximum reduction in bacterial adherence, associated inflammation of the joint as well as faster resumption of locomotion and motor function of the limb. Also, all the coating treatments showed no emergence of resistant mutants. Use of dual coated implants incorporating lytic phage (capable of self-multiplication) as well as linezolid presents an attractive and aggressive early approach in preventing as well as treating implant associated infections caused by methicillin resistant S. aureus strains as assessed in a murine model of experimental joint infection. PMID:27333300

  2. In vitro characterization of a novel polymeric system for preparation of amorphous solid drug dispersions.

    PubMed

    Mahmoudi, Zahra N; Upadhye, Sampada B; Ferrizzi, David; Rajabi-Siahboomi, Ali R

    2014-07-01

    Preparation of amorphous solid dispersions using polymers is a commonly used formulation strategy for enhancing the solubility of poorly water-soluble drugs. However, often a single polymer may not bring about a significant enhancement in solubility or amorphous stability of a poorly water-soluble drug. This study describes application of a unique and novel binary polymeric blend in preparation of solid dispersions. The objective of this study was to investigate amorphous solid dispersions of glipizide, a BCS class II model drug, in a binary polymeric system of polyvinyl acetate phthalate (PVAP) and hypromellose (hydroxypropyl methylcellulose, HPMC). The solid dispersions were prepared using two different solvent methods: rotary evaporation (rotavap) and fluid bed drug layering on sugar spheres. The performance and physical stability of the dispersions were evaluated with non-sink dissolution testing, powder X-ray diffraction (PXRD), and modulated differential scanning calorimetry (mDSC). PXRD analysis demonstrated an amorphous state for glipizide, and mDSC showed no evidence of phase separation. Non-sink dissolution testing in pH 7.5 phosphate buffer indicated more than twofold increase in apparent solubility of the drug with PVAP-HPMC system. The glipizide solid dispersions demonstrated a high glass transition temperature (Tg) and acceptable chemical and physical stability during the stability period irrespective of the manufacturing process. In conclusion, the polymeric blend of PVAP-HPMC offers a unique formulation approach for developing amorphous solid dispersions with the flexibility towards the use of these polymers in different ratios and combined quantities depending on drug properties. PMID:24789531

  3. Evaluation of the composition of the binder bridges in matrix granules prepared with a small-scale high-shear granulator.

    PubMed

    Bajdik, János; Baki, Gabriella; Szent-Királlyi, Zsuzsanna; Knop, Klaus; Kleinebudde, Peter; Pintye-Hódi, Klára

    2008-11-01

    The aim of this work was to evaluate the binder bridges which can form in hydrophilic matrix granules prepared with a small-scale high-shear granulator. Matrices contained hydroxypropyl methylcellulose (HPMC) as a matrix-forming agent, together with lactose monohydrate and microcrystalline cellulose as filler. Water was used as granulating liquid. A 2(4) full factorial design was used to evaluate the effects of the operational parameters (impeller speed, chopper speed, dosing speed and wet massing time) on the granulation process. The temperature of the sample increased relevantly during the preparation in the small-scale apparatus. The same setup induced different temperature increases for different amounts of powder. This alteration enhances the solubility of lactose and decreases that of HPMC, and thus the quantities of the dissolved components can vary. Accordingly, changes in composition of the binder bridge can occur. Since exact determination of the dissolution of these materials during granulation is difficult, the consequences of the changes in solubility were examined. Differential scanning calorimetry (DSC), thermomechanical analysis (TMA) and X-ray diffraction (XRD) measurements were made to evaluate the films prepared from liquids with different ratios of soluble materials. The DSC and XRD measurements confirmed that the lactose lost its crystalline state in the film. The TMA tests revealed that increase of the quantity of lactose in the film decreased the glass transition temperature of the film; this may be attributed to the interaction of the additives. At a lactose content of 37.5%, a second glass transition appeared. This phenomenon may be indicative of a separate amorphous lactose phase. PMID:18774256

  4. Gastroretentive Matrix Tablets of Boswellia Oleogum Resin: Preparation, Optimization, In Vitro Evaluation, and Cytoprotective Effect on Indomethacin-Induced Gastric Ulcer in Rabbits.

    PubMed

    Yusif, Rehab Mohammad; Abu Hashim, Irhan Ibrahim; Mohamed, Elham Abdelmonem; Badria, Farid Abd-Elreheim

    2016-04-01

    Currently available anti-ulcer drugs suffer from serious side effects which limited their uses and prompted the need to search for a safe and efficient new anti-ulcer agent. Boswellia gum resin (BR) emerged as a safe, efficient, natural, and economic potential cytoprotective agent. Thus, it is of medical importance to develop gastroretentive (GR) formulations of BR to enhance its bioavailability and anti-ulcer efficacy. Early attempts involved the use of organic solvents and non-applicability to large-scale production. In this study, different tablet formulations were prepared by simple direct compression combining floating and bioadhesion mechanisms employing hydroxypropyl methylcellulose (HPMC), sodium carboxymethyl cellulose (SCMC), pectin (PC), and/or carbopol (CP) as bioadhesive polymers and sodium bicarbonate (SB) as a gas former. The prepared tablets were subjected for assessment of swelling, floating, bioadhesion, and drug release in 0.1 N HCl. The optimized GR formulation was examined for its protective effect on the gastric ulcer induced by indomethacin in albino rabbits compared with lactose tablets. The obtained results disclosed that swelling, floating, bioadhesion, and drug release of the GR tablets of BR depend mainly on the nature of the matrix and the ratio of polymer combinations. Moreover, a combination of SCMC-CP in a ratio of 2:1 (SCP21) exhibited desirable floating, bioadhesion, swelling, and extended drug release. Also, a 6-h pretreatment with SCP21 tablets decreased the severity of inflammation and number of bleeding spots among ulcer-induced rabbits in comparison to those treated with lactose tablets. PMID:26092303

  5. A Neutral Thermostable β-1,4-Glucanase from Humicola insolens Y1 with Potential for Applications in Various Industries

    PubMed Central

    Zhang, Wei; Huang, Huoqing; Shi, Pengjun; Luo, Huiying; Liu, Bo; Zhang, Yuhong; Zhang, Zhifang; Fan, Yunliu; Yao, Bin

    2015-01-01

    We cloned a new glycoside hydrolase family 6 gene, Hicel6C, from the thermophilic fungus Humicola insolens Y1 and expressed it in Pichia pastoris. Using barley β-glucan as a substrate, recombinant HiCel6C protein exhibited neutral pH (6.5) and high temperature (70°C) optima. Distinct from most reported acidic fungal endo-β-1,4-glucanases, HiCel6C was alkali-tolerant, retaining greater than 98.0, 61.2, and 27.6% of peak activity at pH 8.0, 9.0, and 10.0, respectively, and exhibited good stability over a wide pH range (pH 5.0−11.0) and at temperatures up to 60°C. The Km and Vmax values of HiCel6C for barley β-glucan were 1.29 mg/mL and 752 μmol/min·mg, respectively. HiCel6C was strictly specific for the β-1,4-glucoside linkage exhibiting activity toward barley β-glucan, lichenan, and carboxy methylcellulose sodium salt (CMC-Na), but not toward laminarin (1,3-β-glucan). HiCel6C cleaved the internal glycosidic linkages of cellooligosaccharides randomly and thus represents an endo-cleaving enzyme. The predominant product of polysaccharide hydrolysis by HiCel6C was cellobiose, suggesting that it functions by an endo-processive mechanism. The favorable properties of HiCel6C make it a good candidate for basic research and for applications in the textile and brewing industries. PMID:25909505

  6. Glutathione attenuates ethanol-induced alveolar macrophage oxidative stress and dysfunction by downregulating NADPH oxidases.

    PubMed

    Yeligar, Samantha M; Harris, Frank L; Hart, C Michael; Brown, Lou Ann S

    2014-03-01

    Chronic alcohol abuse increases lung oxidative stress and susceptibility to respiratory infections by impairing alveolar macrophage (AM) function. NADPH oxidases (Nox) are major sources of reactive oxygen species in AMs. We hypothesized that treatment with the critical antioxidant glutathione (GSH) attenuates chronic alcohol-induced oxidative stress by downregulating Noxes and restores AM phagocytic function. Bronchoalveolar lavage (BAL) fluid and AMs were isolated from male C57BL/6J mice (8-10 wk) treated ± ethanol in drinking water (20% wt/vol, 12 wk) ± orally gavaged GSH in methylcellulose vehicle (300 mg x kg(-1) x day(-1), during week 12). MH-S cells, a mouse AM cell line, were treated ± ethanol (0.08%, 3 days) ± GSH (500 μM, 3 days or last 1 day of ethanol). BAL and AMs were also isolated from ethanol-fed and control mice ± inoculated airway Klebsiella pneumoniae (200 colony-forming units, 28 h) ± orally gavaged GSH (300 mg/kg, 24 h). GSH levels (HPLC), Nox mRNA (quantitative RT-PCR) and protein levels (Western blot and immunostaining), oxidative stress (2',7'-dichlorofluorescein-diacetate and Amplex Red), and phagocytosis (Staphylococcus aureus internalization) were measured. Chronic alcohol decreased GSH levels, increased Nox expression and activity, enhanced oxidative stress, impaired phagocytic function in AMs in vivo and in vitro, and exacerbated K. pneumonia-induced oxidative stress. Although how oral GSH restored GSH pools in ethanol-fed mice is unknown, oral GSH treatments abrogated the detrimental effects of chronic alcohol exposure and improved AM function. These studies provide GSH as a novel therapeutic approach for attenuating alcohol-induced derangements in AM Nox expression, oxidative stress, dysfunction, and risk for pneumonia. PMID:24441868

  7. Characterization of the Murine Myeloid Precursor Cell Line MuMac-E8

    PubMed Central

    Fricke, Stephan; Riemschneider, Sina; Kohlschmidt, Janine; Hilger, Nadja; Fueldner, Christiane; Knauer, Jens; Sack, Ulrich; Emmrich, Frank; Lehmann, Jörg

    2014-01-01

    Starting point for the present work was the assumption that the cell line MuMac-E8 represents a murine cell population with stem cell properties. Preliminary studies already pointed to the expression of stem-cell associated markers and a self-regenerative potential of the cells. The cell line MuMac-E8 should be examined for their differential stage within stem cell hierarchy. MuMac-E8 cells were derived from a chimeric mouse model of arthritis. It could be shown that MuMac-E8 cells express mRNA of some genes associated with pluripotent stem cells (Nanog, Nucleostemin), of genes for hematopoietic markers (EPCR, Sca-1, CD11b, CD45), for the mesenchymal marker CD105 and of genes for the neural markers Pax-6 and Ezrin. In methylcellulose and May-Grünwald-Giemsa staining, hematopoietic colonies were obtained but the hematopoietic system of lethally irradiated mice could not be rescued. Osteogenic differentiation was not detectable. Thus, it became evident that MuMac-E8 represents not a stem cell line. However, MuMac-E8 cells expressed several myeloid surface markers (i.e. CD11b, F4/80, CD14, CD64), showed phagocytosis and is capable of producing nitric oxide. Thus, this cell line seems to be arrested an advanced stage of myeloid differentiation. Adherence data measured by impedance-based real-time cell analysis together with cell morphology data suggested that MuMac-E8 represents a new macrophage precursor cell line exhibiting weak adherence. This cell line is suitable as an in-vitro model for testing of macrophage functions. Moreover, it might be also useful for differentiation or reprogramming studies. PMID:25546418

  8. Dissolution of ibuprofen enantiomers from coprecipitates and suspensions containing chiral excipients.

    PubMed

    Janjikhel, R K; Adeyeye, C M

    1999-01-01

    The purpose of this research was to evaluate the stereospecific interaction of ibuprofen with chiral excipients such as hydroxypropyl-beta-cyclodextrin (HPCD), tartaric acid, sucrose, hydroxypropylmethylcellulose (HPMC), methylcellulose (MC), and a nonchiral excipient, citric acid. Coprecipitates of ibuprofen were prepared in molar ratios ranging between 1:0.5 and 1:10 by a solvent evaporation method and characterized using x-ray diffraction, Fourier-transform infrared (FTIR) spectroscopy, and dissolution testing. Phase solubility studies of ibuprofen were carried out by adding excess amount of ibuprofen to aqueous excipient solutions of varying concentrations. Interaction was studied in suspensions of ibuprofen with HPMC, MC, and sucrose stored at room temperature and 60 degrees C for 12 weeks. Solubility of ibuprofen in HPCD solutions increased 10-fold, whereas solubility decreased in the tartaric and citric acid solutions, a result of decreased pH with increased amount of the acids in which ibuprofen (pKa 4.8) is less soluble. Phase solubility diagrams of ibuprofen in aqueous HPCD, citric acid, and tartaric acid solutions showed no stereospecific differences in solubility of the two enantiomers. X-ray diffraction studies showed that ibuprofen exists in a crystalline form at low ibuprofen-to-excipient ratios, whereas at the higher ratios, it exists in an amorphous form. FTIR spectroscopy for HPCD coprecipitates showed a shift of the carbonyl stretching band of ibuprofen to a higher wavelength with a markedly decreased intensity, probably because of a breakdown in the intermolecular hydrogen bonding with ibuprofen and restriction of the drug molecule in the HPCD cavity, respectively. Dissolution profiles of the coprecipitates demonstrated higher dissolution rates than those of pure ibuprofen. The presence of chiral excipients did not appear to cause stereoselective release of the drug from the coprecipitates and the suspensions. PMID:10027208

  9. Effect of technical settings and semen handling upon motility characteristics of dog spermatozoa measured using computer-aided sperm analysis.

    PubMed

    Smith, S C; England, G C

    2001-01-01

    Technical aspects of computer-aided sperm analysis and the influence of semen preparation were investigated for their effect on the measured motility characteristics of dog spermatozoa. Altering the internal image settings significantly influenced the measured motility by changing the ability of the computer to recognize spermatozoa. Similarly, the use of a longer minimum track point (the minimum length of sperm track detected before analysis) resulted in failure to detect some of the faster moving spermatozoa. There was a clear interaction between the search radius (the threshold distance below which objects are linked together) and the minimum track point. A 1 min analysis period was required to eliminate reduced motility as a result of sample deterioration upon the microscope stage. The dilution of semen to between 1:10 and 1:20 was necessary to allow accurate detection of sperm motility; however, such dilution significantly altered the motility characteristics of spermatozoa. The influence of viscosity and ionic composition of the media was confirmed by comparing dilution in seminal plasma with dilution in iso-viscous methylcellulose and iso-osmotic saline, respectively. Analysis temperature had a significant influence on sperm motility, although values were most constant within the range of 25-45 degrees C. Extremes of temperature had marked deleterious effects. Careful selection of internal image settings, the minimal track point and search radius, and the analysis time are essential for accurate detection of sperm motility. Moreover, dilution of spermatozoa per se, and dilution with media of different viscosities and ionic compositions can alter the sperm motility. Once these aspects of computer image analysis are determined for each system, the method can achieve a high degree of repeatability with interanalysis coefficients of variation of < 12%, and intra-analysis coefficients of variation of < 3% for most parameters. PMID:11787144

  10. Effect of non-Newtonian fluid properties on bovine sperm motility.

    PubMed

    Hyakutake, Toru; Suzuki, Hiroki; Yamamoto, Satoru

    2015-09-18

    The swimming process by which mammal spermatozoa progress towards an egg within the reproductive organs is important in achieving successful internal fertilization. The viscosity of oviductal mucus is more than two orders of magnitude greater than that of water, and oviductal mucus also has non-Newtonian properties. In this study, we experimentally observed sperm motion in fluids with various fluid rheological properties and investigated the influence of varying the viscosity and whether the fluid was Newtonian or non-Newtonian on the sperm motility. We selected polyvinylpyrrolidone and methylcellulose as solutes to create solutions with different rheological properties. We used the semen of Japanese cattle and investigated the following parameters: the sperm velocity, the straight-line velocity and the amplitude from the trajectory, and the beat frequency from the fragellar movement. In a Newtonian fluid environment, as the viscosity increased, the motility of the sperm decreased. However, in a non-Newtonian fluid, the straight-line velocity and beat frequency were significantly higher than in a Newtonian fluid with comparable viscosity. As a result, the linearity of the sperm movement increased. Additionally, increasing the viscosity brought about large changes in the sperm flagellar shape. At low viscosities, the entire flagellum moved in a curved flapping motion, whereas in the high-viscosity, only the tip of the flagellum flapped. These results suggest that the bovine sperm has evolved to swim toward the egg as quickly as possible in the actual oviduct fluid, which is a high-viscosity non-Newtonian fluid. PMID:26277700

  11. Transdermal iontophoretic delivery of celecoxib from gel formulation.

    PubMed

    Tavakoli, Naser; Minaiyan, Mohsen; Heshmatipour, Mojtaba; Musavinasab, Ruholla

    2015-01-01

    Celecoxib is used in the treatment of osteoarthritis, rheumatoid arthritis, acute pain, joint inflammation and sport injuries. Long term administration of the drug results in such complications as gastrointestinaland renal disturbances and cardio-vascular complications. The main objective of the present study was to investigate the feasibility of delivering celecoxib incorporated in gel formulations by iontophoresis. Sodium alginate, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose (HPMC) and carbopol 934P were used to develop topical gel formulations of celecoxib. The gel formulations were evaluated for macroscopic and microscopic properties, pH determination, spreadability, rheological behaviour, and drug release characteristics both in vitro and ex vivo. Drug release was evaluated in the presence of iontophoresis field (0.1 to 0.5 mA/cm(2)) or without electrical current (passive diffusion) and celecoxib was measured spectrophotometrically at 252 nm. Most gel formulations showed acceptable physicochemical properties. Amongst formulations, gel formulation containing HPMC K4M which indicated greater performance in drug release behaviour was selected for further in vivo studies. The cumulative percent of drug released in vitro at the end of each experiment was 36%, 63%, and 89.7% for passive diffusion, direct electric current (DC) current density of 0.3 mA/cm(2), and 0.5 mA/cm(2), respectively. The findings of ex vivo drug transport across rat skin also showed a significantly higher release of celecoxib compared to passive flux for both AC and DC currents. A 0.5 mA/cm(2) of DC current increased drug flux to 73% compared to 41.5% of passive diffusion. It can be concluded from the results of this study that the application of iontophoresis enhances the flux of celecoxib, as compared to the passive diffusion. PMID:26752990

  12. The colonic response to genotoxic carcinogens in the rat: regulation by dietary fibre.

    PubMed

    Hu, Y; Martin, J; Le Leu, R; Young, G P

    2002-07-01

    The apoptotic response to DNA damage appears to be an innate biological mechanism for protection against tumourigenesis. It is possible that agents that protect against colorectal cancer act by enhancing the apoptotic deletion of cells suffering DNA damage, with consequent removal of those with tumourigenic mutations. We examined the acute apoptotic response to genotoxic carcinogens ("AARGC") in colonic epithelium and the possibility that dietary fibres of different fermentability might regulate AARGC. To fully define the time-course and nature of AARGC in response to the carcinogen azoxymethane (AOM), a single injection of AOM (10 mg/kg) was given to rats and apoptosis monitored in the colon by light microscopy and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling staining over a 72 h period. Having defined the site and time of maximum response, two groups of eight rats were fed diets containing 10% wheat bran fibre (WB; fermentable) or 10% methylcellulose (MC; poorly fermentable) for 4 weeks. Colonic AARGC was compared by light microscopy; lumenal short chain fatty acids (SCFAs) and pH were measured as indicators of the fermentative environment. AOM-induced AARGC was maximal at 8 h and greater in distal compared with proximal colon. Apoptotic cells were situated predominantly in the lower half of the crypt, with the median at position 9 indicating involvement of daughter as well as stem cells. There was no "second wave" of apoptosis within 72 h as follows irradiation in small intestine. Distal colonic AARGC in rats fed WB was twice that in rats fed MC (P < 0.01). Compared with MC, WB significantly lowered lumenal pH and increased all SCFAs including butyrate, while proliferation did not differ between the fibres. Certainly, dietary fibres can regulate AARGC and further studies are warranted to determine if this biological effect is the way in which dietary factors regulate tumourigenesis. Lumenal generation of butyrate may enhance

  13. Topical Delivery of Interferon Alpha by Biphasic Vesicles: Evidence for a Novel Nanopathway across the Stratum Corneum

    SciTech Connect

    Foldvari, M.; Badea, B; Wettig, S; Baboolal, D; Kumar, P; Creagh, A; Haynes, C

    2010-01-01

    Noninvasive delivery of macromolecules across intact skin is challenging but would allow for needle-free administration of many pharmaceuticals. Biphasic vesicles, a novel lipid-based topical delivery system, have been shown to deliver macromolecules into the skin. Investigation of the delivery mechanism of interferon alpha (IFN {alpha}), as a model protein, by biphasic vesicles could improve understanding of molecular transport through the stratum corneum and allow for the design of more effective delivery systems. The interaction of biphasic vesicles with human skin and isolated stratum corneum membrane was investigated by confocal microscopy, differential scanning calorimetry (DSC) and small- and wide-angle X-ray scattering (SAXS and WAXS). Confocal microscopy revealed that biphasic vesicles delivered IFN {alpha} intercellularly, to a depth of 70 {micro}m, well below the stratum corneum and into the viable epidermis. DSC and SAXS/WAXS data suggest that the interaction of biphasic vesicles with SC lipids resulted in the formation of a three-dimensional cubic Pn3m polymorphic phase by the molecular rearrangement of intercellular lipids. This cubic phase could be an intercellular permeation nanopathway that may explain the increased delivery of IFN {alpha} by biphasic vesicles. Liposomes and submicrometer emulsion (the individual building blocks of biphasic vesicles) separately and methylcellulose gel, an alternative topical vehicle, did not induce a cubic phase and delivered low amounts of IFN {alpha} below the stratum corneum. Molecular modeling of the cubic Pn3m phase and lamellar-to-cubic phase transitions provides a plausible mechanism for transport of IFN {alpha}. It is hypothesized that induction of a Pn3m cubic phase in stratum corneum lipids could make dermal and transdermal delivery of other macromolecules also possible.

  14. Two- and three-dimensional imaging of multicomponent systems using scanning thermal microscopy and localized thermomechanical analysis.

    PubMed

    Harding, Ljiljana; Wood, John; Reading, Mike; Craig, Duncan Q M

    2007-01-01

    The aim of this study was to develop a novel approach to the spatial characterization of multicomponent samples, based on the emergent technique of microthermal analysis. More specifically, we present an assessment of the use of scanning thermal microscopy as a means of component mapping via thermal conductivity; we include a new statistical approach to data handling, which allows reduction of topographic effects. We also introduce a novel three-dimensional mapping technique based on localized thermomechanical analysis. Tablets of paracetamol and hyproxypropyl methylcellulose (HPMC) and 50:50 mixes of the two were prepared and the materials characterized in scanning and localized modes using a TA Instruments 2990 microthermal analyzer with a Thermomicroscopes Explorer AFM head and Wollaston wire thermal probe. L-TMA studies of the pure components indicated markedly differing thermal responses, with the paracetamol showing a sharp melting accompanied by a probe pull-in effect, while HPMC showed only thermal expansion over the temperature range studied. Thermal conductivity and topographic images indicated that two-dimensional differentiation between the components was possible in scanning mode. A means of delineating the relative contribution of the topographic and conductivity effects was developed based on a regression analysis of the thermal conductivity measurements on a set of terms representing the local surface curvature. The results of three-dimensional imaging using a grid of L-TMA measurements is presented. This technique utilized the distinct thermal responses of the two components to allow the probe to melt through the paracetamol down to the underlying HPMC. The advantages and limitations of this novel imaging method are discussed in the context of pharmaceutical and broader uses of the approach. PMID:17194130

  15. Oral buccoadhesive films of ondansetron: Development and evaluation

    PubMed Central

    Kumria, Rachna; Gupta, Vishant; Bansal, Sanjay; Wadhwa, Jyoti; Nair, Anroop B

    2013-01-01

    Introduction: Difficulty or inability in swallowing tablets/capsules during or after chemotherapy is common due to chemotherapy induced nausea and vomiting in patients. Buccoadhesive films of ondansetron hydrochloride were prepared for the prevention and treatment of chemotherapy-induced emesis. Films of varying polymeric composition were prepared in order to facilitate initial as well as prolonged drug release that could take care of acute as well as delayed emesis. Materials and Methods: Mucoadhesive films were prepared using polymers such as hydroxypropyl methylcellulose (HPMC) E5, HPMC K100, and Eudragit® NE 30 D. The effect of concentration of these polymers on physical properties and drug release were studied. All the films were prepared by solvent casting method. In another part of the study, the effect of drug concentration on physical and mucoadhesive properties of film were assessed, keeping the polymer concentration fixed. Results: Films containing HPMC showed good mucoadhesion. Increasing the concentration of Eudragit® NE 30 D in the films retarded drug release and increased residence time, however, reduced mucoadhesion. At a fixed polymer concentration and ratio, films prepared using an increased drug content showed an increased mucoadhesion. Conclusion: Films prepared using HPMC E5 (1000 mg), HPMC K100 (500 mg), and Eudragit® NE 30 D (750 mg) provided initial rapid followed by sustained drug release over a period of 6 h. Given the promising results, the study concluded that the developed buccal films have the potential to release ondansetron required for chemotherapy induced acute and delayed emesis. PMID:24015383

  16. Development and In Vivo Evaluation of a Novel Histatin-5 Bioadhesive Hydrogel Formulation against Oral Candidiasis

    PubMed Central

    Kong, Eric F.; Tsui, Christina; Boyce, Heather; Ibrahim, Ahmed; Hoag, Stephen W.; Karlsson, Amy J.; Meiller, Timothy F.

    2015-01-01

    Oral candidiasis (OC), caused by the fungal pathogen Candida albicans, is the most common opportunistic infection in HIV+ individuals and other immunocompromised populations. The dramatic increase in resistance to common antifungals has emphasized the importance of identifying unconventional therapeutic options. Antimicrobial peptides have emerged as promising candidates for therapeutic intervention due to their broad antimicrobial properties and lack of toxicity. Histatin-5 (Hst-5) specifically has exhibited potent anticandidal activity indicating its potential as an antifungal agent. To that end, the goal of this study was to design a biocompatible hydrogel delivery system for Hst-5 application. The bioadhesive hydroxypropyl methylcellulose (HPMC) hydrogel formulation was developed for topical oral application against OC. The new formulation was evaluated in vitro for gel viscosity, Hst-5 release rate from the gel, and killing potency and, more importantly, was tested in vivo in our mouse model of OC. The findings demonstrated a controlled sustained release of Hst-5 from the polymer and rapid killing ability. Based on viable C. albicans counts recovered from tongues of treated and untreated mice, three daily applications of the formulation beginning 1 day postinfection with C. albicans were effective in protection against development of OC. Interestingly, in some cases, Hst-5 was able to clear existing lesions as well as associated tissue inflammation. These findings were confirmed by histopathology analysis of tongue tissue. Coupled with the lack of toxicity as well as anti-inflammatory and wound-healing properties of Hst-5, the findings from this study support the progression and commercial feasibility of using this compound as a novel therapeutic agent. PMID:26596951

  17. UNC569, a novel small molecule Mer inhibitor with efficacy against acute lymphoblastic leukemia in vitro and in vivo

    PubMed Central

    Christoph, Sandra; DeRyckere, Deborah; Schlegel, Jennifer; Frazer, J. Kimble; Batchelor, Lance A.; Trakhimets, Alesia Y.; Sather, Susan; Hunter, Debra M.; Cummings, Christopher; Liu, Jing; Yang, Chao; Kireev, Dmitri; Simpson, Catherine; Norris-Drouin, Jacqueline; Hull-Ryde, Emily A.; Janzen, William P.; Johnson, Gary L.; Wang, Xiaodong; Frye, Stephen V.; Earp, H. Shelton; Graham, Douglas K.

    2013-01-01

    Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Although survival rates have improved, patients with certain biological subtypes still have suboptimal outcomes. Current chemotherapeutic regimens are associated with short- and long-term toxicities and novel, less toxic therapeutic strategies are needed. Mer receptor tyrosine kinase is ectopically expressed in ALL patient samples and cell lines. Inhibition of Mer expression reduces pro-survival signaling, increases chemosensitivity, and delays development of leukaemia in vivo suggesting that Mer tyrosine kinase inhibitors are excellent candidates for targeted therapies. Brain and spinal tumors are the second most common malignancies in childhood. Multiple chemotherapy approaches and radiation have been attempted, yet overall survival remains dismal. Mer is also abnormally expressed in atypical teratoid/rhabdoid tumors (ATRT), providing a rationale for targeting Mer as a therapeutic strategy. We have previously described UNC569, the first small molecule Mer inhibitor. This manuscript describes the biochemical and biological effects of UNC569 in ALL and ATRT. UNC569 inhibited Mer activation and downstream signaling through ERK1/2 and AKT, determined by western blot analysis. Treatment with UNC569 reduced proliferation/survival in liquid culture, decreased colony formation in methylcellulose/soft agar, and increased sensitivity to cytotoxic chemotherapies. MYC transgenic zebrafish with T-ALL were treated with UNC569 (4 µM for 2 weeks). Fluorescence was quantified as indicator of the distribution of lymphoblasts, which express Mer and enhanced green fluorescent protein. UNC569 induced >50% reduction in tumor burden compared to vehicle- and mock-treated fish. These data support further development of Mer inhibitors as effective therapies in ALL and ATRT. PMID:23997116

  18. Nanoscale Infrared, Thermal, and Mechanical Characterization of Telaprevir-Polymer Miscibility in Amorphous Solid Dispersions Prepared by Solvent Evaporation.

    PubMed

    Li, Na; Taylor, Lynne S

    2016-03-01

    Miscibility is of great interest for pharmaceutical systems, in particular, for amorphous solid dispersions, as phase separation can lead to a higher tendency to crystallize, resulting in a loss in solubility, decreased dissolution rate, and compromised bioavailability. The purpose of this study was to investigate the miscibility behavior of a model poorly water-soluble drug, telaprevir (TPV), with three different polymers using atomic force microscopy-based infrared, thermal, and mechanical analysis. Standard atomic force microscopy (AFM) imaging together with nanoscale infrared spectroscopy (AFM-IR), nanoscale thermal analysis (nanoTA), and Lorentz contact resonance (LCR) measurements were used to evaluate the miscibility behavior of TPV with three polymers, hydroxypropyl methylcellulose (HPMC), HPMC acetate succinate (HPMCAS), and poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA), at different drug to polymer ratios. Phase separation was observed with HPMC and PVPVA at drug loadings above 10%. For HPMCAS, a smaller miscibility gap was observed, with phase separation being observed at drug loadings higher than ∼30-40%. The domain size of phase-separated regions varied from below 50 nm to a few hundred nanometers. Localized infrared spectra, nano-TA measurements, images from AFM-based IR, and LCR measurements showed clear contrast between the continuous and discrete domains for these phase-separated systems, whereby the discrete domains were drug-rich. Fluorescence microscopy provided additional evidence for phase separation. These methods appear to be promising to evaluate miscibility in drug-polymer systems with similar Tgs and submicron domain sizes. Furthermore, such findings are of obvious importance in the context of contributing to a mechanistic understanding of amorphous solid dispersion phase behavior. PMID:26859046

  19. Ion Beam Analysis Of Silicon-Based Surfaces And Correlation With Surface Energy Measurements

    NASA Astrophysics Data System (ADS)

    Xing, Qian; Herbots, N.; Hart, M.; Bradley, J. D.; Wilkens, B. J.; Sell, D. A.; Sell, Clive H.; Kwong, Henry Mark; Culbertson, R. J.; Whaley, S. D.

    2011-06-01

    The water affinity of Si-based surfaces is quantified by contact angle measurement and surface free energy to explain hydrophobic or hydrophilic behavior of silicone, silicates, and silicon surfaces. Surface defects such as dangling bonds, surface free energy including Lewis acid-base and Lifshitz-van der Waals components are discussed. Water nucleation and condensation is further explained by surface topography. Tapping mode atomic force microscopy (TMAFM) provides statistical analysis of the topography of these Si-based surfaces. The correlation of the above two characteristics describes the behavior of water condensation at Si-based surfaces. Surface root mean square roughness increasing from several Å to several nm is found to provide nucleation sites that expedite water condensation visibly for silica and silicone. Hydrophilic surfaces have a condensation pattern that forms puddles of water while hydrophobic surfaces form water beads. Polymer adsorption on these surfaces alters the water affinity as well as the surface topography, and therefore controls condensation on Si-based surfaces including silicone intraocular lens (IOL). The polymer film is characterized by Rutherford backscattering spectrometry (RBS) in conjunction with 4.265 MeV 12C(α, α)12C, 3.045 MeV 16O(α,α)16O nuclear resonance scattering (NRS), and 2.8 MeV elastic recoil detection (ERD) of hydrogen for high resolution composition and areal density measurements. The areal density of hydroxypropyl methylcellulose (HPMC) film ranges from 1018 atom/cm2 to 1019 atom/cm2 gives the silica or silicone surface a roughness of several Å and a wavelength of 0.16±0.02 μm, and prevents fogging by forming a complete wetting layer during water condensation.

  20. Evaluation of conjunctival bacterial flora in patients with Stevens-Johnson Syndrome

    PubMed Central

    Frizon, Luciana; Araújo, Marília Cavalcante; Andrade, Larissa; Yu, Maria Cecília Zorat; Wakamatsu, Tais Hitomi; Höfling-Lima, Ana Luisa; Gomes, José Álvaro Pereira

    2014-01-01

    OBJECTIVE: To determine the conjunctival bacterial flora present in patients with Stevens-Johnson syndrome. METHODS: A prospective study of the conjunctival bacterial flora was performed in 41 eyes of 22 patients with Stevens-Johnson syndrome. The information gathered included the patient's sex and age, the duration of disease, the cause of Stevens-Johnson syndrome, and treatments. Scrapings of the inferior conjunctival fornix were performed in both eyes. Fourteen days before scraping, the patients were asked to interrupt all topical medication and start using 0.5% nonpreserved methylcellulose. The microbiological evaluation included microorganism identification and determination of antibiotic sensitivity. RESULTS: Of 22 patients (41 eyes), 14 (64%) were females, and eight (36%) were males. The mean age was 33.2 years, and the mean duration of disease was 15.6 years. Visual acuity ranged from light perception to 20/25 (1.57 logMar). The treatment received by most patients consisted of tear substitutes, topical antibiotics, and contact lenses. Bacterial identification was positive in 39 eyes (95%) and negative in two eyes (5%). Gram-positive cocci accounted for 55.5% of the microorganisms, whereas gram-positive bacilli and gram-negative bacilli accounted for 19% and 25.5%, respectively. Half of the patients (54%) had multiple bacterial species in their flora, and only one bacterial species was identified in the other half. Resistant bacteria were isolated from four eyes. The antibiotic sensitivity results for the Streptococcus group showed the lowest sensitivity and the highest microbial resistance identified. CONCLUSION: Patients with Stevens-Johnson syndrome have a diverse conjunctival flora that includes many pathogenic species. PMID:24626941

  1. A sustained release gel formulation of doramectin for control of lone star ticks (Acari: Ixodidae) and horn flies (Diptera: Muscidae) on cattle.

    PubMed

    Lohmeyer, K H; Miller, J A; Pound, J M; Klavons, J A

    2009-04-01

    A gel formulation formed by incorporating technical doramectin into a 10% hydroxypropyl methylcellulose aqueous solution was used to subcutaneously inject steers at varying dosages. Doramectin serum concentration of steers receiving 600 microg (AI)/kg body weight declined from 21.9 ppb at 0.5 wk to below detectable at 8 wk postinjection. The 1,200 microg (AI)/kg injection resulted in serum concentrations of 29.1 ppb at 0.5 wk and declined to 0.5 ppb at 8 wk postinjection. Both the 600 and 1,200 microg (AI)/kg injections provided 100% inhibition of index of fecundity (IF) in adult lone star ticks, Amblyomma americanum L. (Acari: Ixodidae) through week 8, after which inhibition declined to 79.4 and 45.3%, respectively, during the 12th week posttreatment. For steers treated at 600 microg (AI)/kg, mortality of adult horn flies, Hematobia irritans L. (Diptera: Muscidae), declined from 16.9% during week 2 to 3.1% during week 7 postinjection. The blood from steers treated at 1,200 microg (AI)/kg resulted in a similar decline in mortality of blood fed adult horn flies from 29.4% during week 1 to 4.0% during week 7. The 600 microg (AI)/kg treatment provided complete control of larval horn flies in the manure for 9 wk, whereas the 1,200 microg (AI)/kg injection gave complete control for 14 wk posttreatment. The doramectin gel formulation provided long-lasting delivery of doramectin to cattle and extended control of lone star ticks and larval horn flies. Such a simple and inexpensive formulation could be useful in tick eradication programs by reducing the frequency of gathering cattle. PMID:19449664

  2. Evaluation of Multifunctional Polysaccharide Hydrogels with Varying Stiffness for Bone Tissue Engineering

    PubMed Central

    Zuidema, Jonathan M.; Venuto, Kathryn N.; Macione, James; Dai, Guohao; Gilbert, Ryan J.; Kotha, Shiva P.

    2013-01-01

    The use of hydrogels for bone regeneration has been limited due to their inherent low modulus to support cell adhesion and proliferation as well as their susceptibility to bacterial infections at the wound site. To overcome these limitations, we evaluated multifunctional polysaccharide hydrogels of varying stiffness to obtain the optimum stiffness at which the gels (1) induce proliferation of human dermal fibroblasts, human umbilical vascular endothelial cells (HUVECs), and murine preosteoblasts (MC3T3-E1), (2) induce osteoblast differentiation and mineralization, and (3) exhibit an antibacterial activity. Rheological studies demonstrated that the stiffness of hydrogels made of a polysaccharide blend of methylcellulose, chitosan, and agarose was increased by crosslinking the chitosan component to different extents with increasing amounts of genipin. The gelation time decreased (from 210 to 60 min) with increasing genipin concentrations. Proliferation of HUVECs decreased by 10.7 times with increasing gel stiffness, in contrast to fibroblasts and osteoblasts, where it increased with gel stiffness by 6.37 and 7.8 times, respectively. At day 14 up to day 24, osteoblast expression of differentiation markers—osteocalcin, osteopontin—and early mineralization marker—alkaline phosphatase, were significantly enhanced in the 0.5% (w/v) crosslinked gel, which also demonstrated enhanced mineralization by day 25. The antibacterial efficacy of the hydrogels decreased with the increasing degree of crosslinking as demonstrated by biofilm formation experiments, but gels crosslinked with 0.5% (w/v) genipin still demonstrated significant bacterial inhibition. Based on these results, gels crosslinked with 0.5% (w/v) genipin, where 33% of available groups on chitosan were crosslinked, exhibited a stiffness of 502±64.5 Pa and demonstrated the optimal characteristics to support bone regeneration. PMID:23724786

  3. The homeodomain transcription factor Prep1 (pKnox1) is required for hematopoietic stem and progenitor cell activity.

    PubMed

    Di Rosa, Patrizia; Villaescusa, J Carlos; Longobardi, Elena; Iotti, Giorgio; Ferretti, Elisabetta; Diaz, Victor M; Miccio, Annarita; Ferrari, Giuliana; Blasi, Francesco

    2007-11-15

    Most of the hypomorphic Prep1(i/i) embryos (expressing 3-10% of the Prep1 protein), die between E17.5 and P0, with profound anemia, eye malformations and angiogenic anomalies [Ferretti, E., Villaescusa, J.C., Di Rosa, P., Fernandez-Diaz, L.-C., Longobardi, E., Mazzieri, R., Miccio, A., Micali, N., Selleri, L., Ferrari G., Blasi, F. (2006). Hypomorphic mutation of the TALE gene Prep1 (pKnox1) causes a major reduction of Pbx and Meis proteins and a pleiotropic embryonic phenotype. Mol. Cell. Biol. 26, 5650-5662]. We now report on the hematopoietic phenotype of these embryos. Prep1(i/i) fetal livers (FL) are hypoplastic, produce less common myeloid progenitors colonies (CFU-GEMM) in cytokine-supplemented methylcellulose and have an increased number of B-cells precursors that differentiate poorly. Prep1(i/i) FL is able to protect lethally irradiated mice only at high cell doses but the few protected mice show major anomalies in all hematopoietic lineages in both bone marrow (BM) and peripheral organs. Prep1(i/i) FL cells compete inefficiently with wild type bone marrow in competitive repopulation experiments, suggesting that the major defect lies in long-term repopulating hematopoietic stem cells (LTR-HSC). Indeed, wt embryonic expression of Prep1 in the aorta-gonad-mesonephros (AGM) region, fetal liver (FL), cKit(+)Sca1(+)Lin(-)AA4.1(+) (KSLA) cells and B-lymphocytes precursors agrees with the observed phenotype. We therefore conclude that Prep1 is required for a correct and complete hematopoiesis. PMID:17904118

  4. Short-term treatment with VEGF receptor inhibitors induces retinopathy of prematurity-like abnormal vascular growth in neonatal rats.

    PubMed

    Nakano, Ayuki; Nakahara, Tsutomu; Mori, Asami; Ushikubo, Hiroko; Sakamoto, Kenji; Ishii, Kunio

    2016-02-01

    Retinal arterial tortuosity and venous dilation are hallmarks of plus disease, which is a severe form of retinopathy of prematurity (ROP). In this study, we examined whether short-term interruption of vascular endothelial growth factor (VEGF) signals leads to the formation of severe ROP-like abnormal retinal blood vessels. Neonatal rats were treated subcutaneously with the VEGF receptor (VEGFR) tyrosine kinase inhibitors, KRN633 (1, 5, or 10 mg/kg) or axitinib (10 mg/kg), on postnatal day (P) 7 and P8. The retinal vasculatures were examined on P9, P14, or P21 in retinal whole-mounts stained with an endothelial cell marker. Prevention of vascular growth and regression of some preformed capillaries were observed on P9 in retinas of rats treated with KRN633. However, on P14 and P21, density of capillaries, tortuosity index of arterioles, and diameter of veins significantly increased in KRN633-treated rats, compared to vehicle (0.5% methylcellulose)-treated animals. Similar observations were made with axitinib-treated rats. Expressions of VEGF and VEGFR-2 were enhanced on P14 in KRN633-treated rat retinas. The second round of KRN633 treatment on P11 and P12 completely blocked abnormal retinal vascular growth on P14, but thereafter induced ROP-like abnormal retinal blood vessels by P21. These results suggest that an interruption of normal retinal vascular development in neonatal rats as a result of short-term VEGFR inhibition causes severe ROP-like abnormal retinal vascular growth in a VEGF-dependent manner. Rats treated postnatally with VEGFR inhibitors could serve as an animal model for studying the mechanisms underlying the development of plus disease. PMID:26500193

  5. Identification of a population of cells with hematopoietic stem cell properties in mouse aorta-gonad-mesonephros cultures

    SciTech Connect

    Nobuhisa, Ikuo; Ohtsu, Naoki; Okada, Seiji; Nakagata, Naomi; Taga, Tetsuya . E-mail: taga@kaiju.medic.kumamoto-u.ac.jp

    2007-03-10

    The aorta-gonad-mesonephros (AGM) region is a primary source of definitive hematopoietic cells in the midgestation mouse embryo. In cultures of dispersed AGM regions, adherent cells containing endothelial cells are observed first, and then non-adherent hematopoietic cells are produced. Here we report on the characterization of hematopoietic cells that emerge in the AGM culture. Based on the expression profiles of CD45 and c-Kit, we defined three cell populations: CD45{sup low} c-Kit{sup +} cells that had the ability to form hematopoietic cell colonies in methylcellulose media and in co-cultures with stromal cells; CD45{sup low} c-Kit{sup -} cells that showed a granulocyte morphology; CD45{sup high} c-Kit{sup low/-} that exhibited a macrophage morphology. In co-cultures of OP9 stromal cells and freshly prepared AGM cultures, CD45{sup low} c-Kit{sup +} cells from the AGM culture had the abilities to reproduce CD45{sup low} c-Kit{sup +} cells and differentiate into CD45{sup low} c-Kit{sup -} and CD45{sup high} c-Kit{sup low/-} cells, whereas CD45{sup low} c-Kit{sup -} and CD45{sup high} c-Kit{sup low/-} did not produce CD45{sup low} c-Kit{sup +} cells. Furthermore, CD45{sup low} c-Kit{sup +} cells displayed a long-term repopulating activity in adult hematopoietic tissue when transplanted into the liver of irradiated newborn mice. These results indicate that CD45{sup low} c-Kit{sup +} cells from the AGM culture have the potential to reconstitute multi-lineage hematopoietic cells.

  6. Mutations in the Borrelia burgdorferi Flagellar Type III Secretion System Genes fliH and fliI Profoundly Affect Spirochete Flagellar Assembly, Morphology, Motility, Structure, and Cell Division

    PubMed Central

    Gao, Lihui; Zhao, Xiaowei; Liu, Jun; Norris, Steven J.

    2015-01-01

    ABSTRACT The Lyme disease spirochete Borrelia burgdorferi migrates to distant sites in the tick vectors and mammalian hosts through robust motility and chemotaxis activities. FliH and FliI are two cytoplasmic proteins that play important roles in the type III secretion system (T3SS)-mediated export and assembly of flagellar structural proteins. However, detailed analyses of the roles of FliH and FliI in B. burgdorferi have not been reported. In this study, fliH and fliI transposon mutants were utilized to dissect the mechanism of the Borrelia type III secretion system. The fliH and fliI mutants exhibited rod-shaped or string-like morphology, greatly reduced motility, division defects (resulting in elongated organisms with incomplete division points), and noninfectivity in mice by needle inoculation. Mutants in fliH and fliI were incapable of translational motion in 1% methylcellulose or soft agar. Inactivation of either fliH or fliI resulted in the loss of the FliH-FliI complex from otherwise intact flagellar motors, as determined by cryo-electron tomography (cryo-ET). Flagellar assemblies were still present in the mutant cells, albeit in lower numbers than in wild-type cells and with truncated flagella. Genetic complementation of fliH and fliI mutants in trans restored their wild-type morphology, motility, and flagellar motor structure; however, full-length flagella and infectivity were not recovered in these complemented mutants. Based on these results, disruption of either fliH or fliI in B. burgdorferi results in a severe defect in flagellar structure and function and cell division but does not completely block the export and assembly of flagellar hook and filament proteins. PMID:25968649

  7. Brinzolamide nanocrystal formulations for ophthalmic delivery: reduction of elevated intraocular pressure in vivo.

    PubMed

    Tuomela, Annika; Liu, Peng; Puranen, Jooseppi; Rönkkö, Seppo; Laaksonen, Timo; Kalesnykas, Giedrius; Oksala, Olli; Ilkka, Jukka; Laru, Johanna; Järvinen, Kristiina; Hirvonen, Jouni; Peltonen, Leena

    2014-06-01

    Nanocrystal-based drug delivery systems provide important tools for ocular formulation development, especially when considering poorly soluble drugs. The objective of the study was to formulate ophthalmic, intraocular pressure (IOP) reducing, nanocrystal suspensions from a poorly soluble drug, brinzolamide (BRA), using a rapid wet milling technique, and to investigate their IOP reducing effect in vivo. Different stabilizers for the nanocrystals were screened (hydroxypropyl methylcellulose (HPMC), poloxamer F127 and F68, polysorbate 80) and HPMC was found to be the only successful stabilizer. In order to investigate both the effect of an added absorption enhancer (polysorbate 80) and the impact of the free drug in the nanocrystal suspension, formulations in phosphate buffered saline (PBS) at pH 7.4 and pH 4.5 were prepared. Particle size, polydispersity (PI), solid state (DSC), morphology (SEM) as well as dissolution behavior and the uniformity of the formulations were characterized. There was rapid dissolution of BRA (in PBS pH 7.4) from all the nanocrystal formulations; after 1 min 100% of the drug was fully dissolved. The effect was significantly pronounced at pH 4.5, where the dissolved fraction of drug was the highest. The cytotoxicity of nanocrystal formulations to human corneal epithelial cell (HCE-T) viability was tested. The effects of the nanocrystal formulations and the commercial product on the cell viability were comparable. The intraocular pressure (IOP) lowering effect was investigated in vivo using a modern rat ocular hypertensive model and elevated IOP reduction was seen in vivo with all the formulations. Notably, the reduction achieved in experimentally elevated IOP was comparable to that obtained with a marketed product. In conclusion, various BRA nanocrystal formulations, which all showed advantageous dissolution and absorption behavior, were successfully formulated. PMID:24680962

  8. Preparation and pharmaceutical evaluation of glibenclamide slow release mucoadhesive buccal film

    PubMed Central

    Bahri-Najafi, R.; Tavakoli, N.; Senemar, M.; Peikanpour, M.

    2014-01-01

    Buccal mucoadhesive systems among novel drug delivery systems have attracted great attention in recent years due to their ability to adhere and remain on the oral mucosa and to release their drug content gradually. Buccal mucoadhesive films can improve the drug therapeutic effect by enhancement of drug absorption through oral mucosa increasing the drug bioavailability via reducing the hepatic first pass effect. The aim of the current study was to formulate the drug as buccal bioadhesive film, which releases the drug at sufficient concentration with a sustain manner reducing the frequency of the dosage form administration. One of the advantagees of this formulation is better patient compliances due to the ease of administration with no water to swallow the product. The mucoadhesive films of glibenclamide were prepared using hydroxypropyl methylcellulose (HPMC) K4M, K15M and Eudragit RL100 polymers and propylene glycol as plasticizer and co-solvent. Films were prepared using solvent casting method, and were evaluated with regard to drug content, thickness, weight variations, swelling index, tensile strength, ex vivo adhesion force and percentage of in vitro drug release. Films with high concentrations of HPMC K4M and K15M did not have favorable appearance and uniformity. The formulations prepared from Eudragit were transparent, uniform, flexible, and without bubble. The highest and the lowest percentages of swelling were observed for the films containing HPMC K15M and Eudragit RL100, respectively. Films made of HPMC K15M had adhesion force higher than those containing Eudragit RL100. Formulations with Eudragit RL100 showed the highest mean dissolution time (MDT). Drug release kinetics of all formulations followed Higuchi's model and the mechanism of diffusion was considered non-Fickian type. It was concluded that formulations containing Eudragit RL100 were more favorable than others with regard to uniformity, flexibility, rate and percentage of drug release. PMID

  9. Human Cardiac Progenitor Spheroids Exhibit Enhanced Engraftment Potential

    PubMed Central

    Colangelo, Donato; Gregoletto, Luca; Reano, Simone; Pietronave, Stefano; Merlin, Simone; Talmon, Maria; Novelli, Eugenio; Diena, Marco; Nicoletti, Carmine; Musarò, Antonio; Filigheddu, Nicoletta; Follenzi, Antonia; Prat, Maria

    2015-01-01

    A major obstacle to an effective myocardium stem cell therapy has always been the delivery and survival of implanted stem cells in the heart. Better engraftment can be achieved if cells are administered as cell aggregates, which maintain their extra-cellular matrix (ECM). We have generated spheroid aggregates in less than 24 h by seeding human cardiac progenitor cells (hCPCs) onto methylcellulose hydrogel-coated microwells. Cells within spheroids maintained the expression of stemness/mesenchymal and ECM markers, growth factors and their cognate receptors, cardiac commitment factors, and metalloproteases, as detected by immunofluorescence, q-RT-PCR and immunoarray, and expressed a higher, but regulated, telomerase activity. Compared to cells in monolayers, 3D spheroids secreted also bFGF and showed MMP2 activity. When spheroids were seeded on culture plates, the cells quickly migrated, displaying an increased wound healing ability with or without pharmacological modulation, and reached confluence at a higher rate than cells from conventional monolayers. When spheroids were injected in the heart wall of healthy mice, some cells migrated from the spheroids, engrafted, and remained detectable for at least 1 week after transplantation, while, when the same amount of cells was injected as suspension, no cells were detectable three days after injection. Cells from spheroids displayed the same engraftment capability when they were injected in cardiotoxin-injured myocardium. Our study shows that spherical in vivo ready-to-implant scaffold-less aggregates of hCPCs able to engraft also in the hostile environment of an injured myocardium can be produced with an economic, easy and fast protocol. PMID:26375957

  10. Application of a binary polymer system in drug release rate modulation. 1. Characterization of release mechanism.

    PubMed

    Kim, H; Fassihi, R

    1997-03-01

    A new binary polymer matrix tablet for oral administration was developed. The system will deliver drug at variable rates according to zero-order kinetics for total drug content and is manufactured by direct compression technology. Highly methoxylated pectin and hydroxypropyl methylcellulose (HPMC) at different ratios were used as major formulation components, and prednisolone was used as the drug model. The results indicate that by increasing pectin:HPMC ratios, release rates are increased, but zero-order kinetics prevail throughout the dissolution period (e.g., 3-22 h). Different pectin:HPMC ratios provide a range of viscosities that modulates drug release and results in rapid hydration/gelation in both axial and radial directions, as evidenced by photomicrographic pictures. This hydration-gelation contributes to the development of swelling/erosion boundaries and consequently to constant drug release. Combination of these particular polymers facilitates rapid formation of necessary boundaries (i.e., gel layer and solid core boundaries) to control overall mass transfer processes. The drug fraction released (Mt/M infinity), release kinetics, and mechanism of release were analyzed by applying the simple power law expression Mt/M infinity = kt(n), where k is a kinetic constant and the exponent n is indicative of the release mechanism. The calculated n values for pectin:HPMC ratios of 4:5, 3:6, and 2:7 were >0.95, which is indicative of a Case II transport mechanism (polymer relaxation/dissolution). The achievement of total zero-order kinetics is due to the predictable swelling/erosion and final polymer chain deaggregation and dissolution that is regulated by the gelling characteristics of polymers in the formulation. PMID:9050799

  11. Shear rheology and filament stretching behaviour of xanthan gum and carboxymethyl cellulose solution in presence of saliva

    PubMed Central

    Choi, Hyejung; Mitchell, John R.; Gaddipati, Sanyasi R.; Hill, Sandra E.; Wolf, Bettina

    2014-01-01

    The objective of the work reported in this paper is to determine if saliva addition has an effect on the rheology of xanthan gum solutions. The reasons for the interest was that it has been previously reported that flavour release from high viscosity xanthan thickened foods is not reduced in the same way as foods thickened by other hydrocolloids at comparable viscosities. It was previously postulated that this could be due to an interaction between saliva and xanthan that could change the microstructure and rheology of xanthan solutions. In this work the effect of saliva on the rheology of CMC and xanthan solutions was compared. Solutions of molecularly dissolved xanthan gum and CMC mixed with water or human whole saliva at a ratio of 5:1 showed little impact of the presence of saliva on steady shear or dynamic viscosity for the two hydrocolloids. In filament thinning experiments saliva addition significantly increased filament break-up time for xanthan gum while it had little effect on the break-up time of the CMC filament. Also, filament thinning appeared a lot less even and was not as reproducible in the case of xanthan gum. Addition of CMC and hydroxypropyl methylcellulose (HPMC) to xanthan gum solutions showed a similar increase in break-up time to saliva, but to see this effect the viscosity of the added CMC or HPMC solution had to be very much higher than the viscosity of saliva. The results are discussed in the context of the structure of xanthan gum and the reported extensional rheology of saliva. PMID:25284950

  12. Shear rheology and filament stretching behaviour of xanthan gum and carboxymethyl cellulose solution in presence of saliva.

    PubMed

    Choi, Hyejung; Mitchell, John R; Gaddipati, Sanyasi R; Hill, Sandra E; Wolf, Bettina

    2014-10-01

    The objective of the work reported in this paper is to determine if saliva addition has an effect on the rheology of xanthan gum solutions. The reasons for the interest was that it has been previously reported that flavour release from high viscosity xanthan thickened foods is not reduced in the same way as foods thickened by other hydrocolloids at comparable viscosities. It was previously postulated that this could be due to an interaction between saliva and xanthan that could change the microstructure and rheology of xanthan solutions. In this work the effect of saliva on the rheology of CMC and xanthan solutions was compared. Solutions of molecularly dissolved xanthan gum and CMC mixed with water or human whole saliva at a ratio of 5:1 showed little impact of the presence of saliva on steady shear or dynamic viscosity for the two hydrocolloids. In filament thinning experiments saliva addition significantly increased filament break-up time for xanthan gum while it had little effect on the break-up time of the CMC filament. Also, filament thinning appeared a lot less even and was not as reproducible in the case of xanthan gum. Addition of CMC and hydroxypropyl methylcellulose (HPMC) to xanthan gum solutions showed a similar increase in break-up time to saliva, but to see this effect the viscosity of the added CMC or HPMC solution had to be very much higher than the viscosity of saliva. The results are discussed in the context of the structure of xanthan gum and the reported extensional rheology of saliva. PMID:25284950

  13. Atrazine-induced reproductive tract alterations after transplacental and/or lactational exposure in male Long-Evans rats

    SciTech Connect

    Rayner, Jennifer L.; Enoch, Rolondo R.; Wolf, Douglas C.; Fenton, Suzanne E. . E-mail: fenton.suzanne@epa.gov

    2007-02-01

    Studies showed that early postnatal exposure to the herbicide atrazine (ATR) delayed preputial separation (PPS) and increased incidence of prostate inflammation in adult Wistar rats. A cross-fostering paradigm was used in this study to determine if gestational exposure to ATR would also result in altered puberty and reproductive tissue effects in the male rat. Timed-pregnant Long-Evans (LE) rats were dosed by gavage on gestational days (GD) 15-19 with 100 mg ATR/kg body weight (BW) or 1% methylcellulose (controls, C). On postnatal day (PND)1, half litters were cross-fostered, creating 4 treatment groups; C-C, ATR-C, C-ATR, and ATR-ATR (transplacental-milk as source, respectively). On PND4, male offspring in the ATR-ATR group weighed significantly less than the C-C males. ATR-ATR male pups had significantly delayed preputial separation (PPS). BWs at PPS for C-ATR and ATR-ATR males were reduced by 6% and 9%, respectively, from that of C-C. On PND120, lateral prostate weights of males in the ATR-ATR group were significantly increased over C-C. Histological examination of lateral and ventral prostates identified an increased distribution of inflammation in the lateral prostates of C-ATR males. By PND220, lateral prostate weights were significantly increased for ATR-C and ATR-ATR, but there were no significant changes in inflammation in either the lateral or ventral prostate. These results suggest that in LE rats, gestational ATR exposure delays PPS when male offspring suckle an ATR dam, but leads to increased lateral prostate weight via transplacental exposure alone. Inflammation present at PND120 does not increase in severity with time.

  14. Film coated pellets containing verapamil hydrochloride: enhanced dissolution into neutral medium.

    PubMed

    Munday, Dale L

    2003-05-01

    Weakly basic drugs, such as verapamil hydrochloride, that are poorly soluble in neutral/alkaline medium may have poor oral bioavailability due to reduced solubility in the small intestine and colon. Film coated pellets were prepared using two strategies to enhance drug release at high pH values. Firstly, pellets were coated with Eudragit RS/hydroxypropyl methylcellulose acetate succinate (HMAS) mixtures in proportions of 10:1 and 10:3, respectively. The enteric polymer, HMAS, would dissolve in medium at pH > 6 creating pores through the insoluble Eudragit RS membrane to increase drug release. Secondly, an acidic environment was created within the core by the inclusion of fumaric acid at concentrations of 5 and 10% in order to increase drug solubility. Both strategies enhanced drug release into neutral medium in dissolution studies using the pH change method to simulate GIT transit. Dissolution profiles of samples tested in pH 1.2 for 12 hr were compared with those using the pH change method (pH 1.2 for first 1.5 hr, pH raised to 6.8 for remaining 10.5 hr) using the area under the dissolution curve (AUC), the dissolution half-life (t50%), and the amount of drug released in 3 hr (A3hr) values. Both strategies enhanced drug release into neutral medium although the strategy using HMAS in the film was more effective. The formulation least affected by pH change was a combination of the two strategies, i.e., pellets containing 5% fumaric acid coated with Eudragit RS 12% w/w and HMAS 1.2% w/w. PMID:12779287

  15. Effect of polymer type and drug dose on the in vitro and in vivo behavior of amorphous solid dispersions.

    PubMed

    Knopp, Matthias Manne; Chourak, Nabil; Khan, Fauzan; Wendelboe, Johan; Langguth, Peter; Rades, Thomas; Holm, René

    2016-08-01

    This study investigated the non-sink in vitro dissolution behavior and in vivo performance in rats of celecoxib (CCX) amorphous solid dispersions with polyvinyl acetate (PVA), polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose (HPMC) at different drug doses. Both in vitro and in vivo, the amorphous solid dispersions with the hydrophilic polymers PVP and HPMC led to higher areas under both, the in vitro dissolution and the plasma concentration-time curves (AUC) compared to crystalline and amorphous CCX for all doses. In contrast, the amorphous solid dispersion with the hydrophobic polymer PVA showed a lower AUC both in vitro and in vivo than crystalline CCX. For crystalline CCX and CCX:PVA, the in vitro AUC was limited by the low solubility of the drug and the slow release of the drug from the hydrophobic polymer, respectively. For the supersaturating formulations, amorphous CCX, CCX:PVP and CCX:HPMC, the in vitro performance was mainly dependent on the dissolution rate and precipitation/crystallization inhibition of the polymer. As expected, the crystallization tendency increased with increasing dose, and therefore the in vitro AUCs did not increase proportionally with dose. Even though the in vivo AUC for all formulations increased with increasing dose, the relative bioavailability decreased significantly, indicating that the supersaturating formulations also crystallized in vivo and that the absorption of CCX was solubility-limited. These findings underline the importance of evaluating relevant in vitro doses, in order to rationally assess the performance of amorphous solid dispersions and avoid confusion in early in vivo studies. PMID:27212472

  16. Development and evaluation of in situ nasal gel formulations of loratadine

    PubMed Central

    Sherafudeen, Sheri Peedikayil; Vasantha, Prasanth Viswanadhan

    2015-01-01

    The objective of the present work was to formulate and evaluate mucoadhesive in situ nasal gels of loratadine. This drug delivery system may overcome the first-pass metabolism and subsequently improve the bioavailability of the drug. A total of 16 formulations of in situ nasal gels were prepared using different polymeric ratios of hydroxypropyl methylcellulose (HPMC K-100) and xanthan gum. All formulations had a clear appearance in the sol form, with gelling temperature of the nasal gels ranging between 33.1 ± 0.43 and 34.8 ± 0.82 °C. The gelling time of all the formulations varied from 4.0 ± 0.21 to 11.3 ± 0.22 s; the drug content was >95%. The pH of the formulations ranged between 5.6 ± 0.004 and 6.0 ± 0.003, i.e. no mucosal irritation is expected as the pH was in the acceptable range. Mucoadhesive strength was adequate (3010.89 ± 1.21-6678.89 ± 0.45 dyne/cm2) to provide prolonged adhesion. In vitro drug release studies showed that the prepared formulations could release the drug for up to 10 h with all of them following Higuchi kinetics. The accelerated stability studies indicated that the gels were stable over the six months test period. The DSC and XRD analysis revealed that there was no drug-polymer interaction. From these findings it can be concluded that in situ nasal gels may be potential drug delivery systems for loratadine to overcome first-pass metabolism and thereby to improve the bioavailability. PMID:26779266

  17. Formulation and evaluation of stimuli-sensitive hydrogels of timolol maleate and brimonidine tartrate for the treatment of glaucoma

    PubMed Central

    Dubey, Akhilesh; Prabhu, Prabhakara

    2014-01-01

    Background: Stimuli-sensitive hydrogels are hydrophilic, three-dimensional, polymeric network structure capable of imbibing large amounts of water or biological fluids on stimulation, such as pH, temperature, and ionic change. Owing to the drawback of conventional therapy for ocular delivery, and to provide additive effect on intraocular pressure (IOP) reduction, stimuli sensitive hydrogel membranes containing a combination of timolol maleate and brimonidine tartrate were formulated for the treatment of glaucoma. Materials and Methods: Stimuli-sensitive hydrogel were formulated by timolol maleate and brimonidine tartrate. Poly acrylic acid (carbopol C 934p) is used as a gelling agent, hydroxylpropyl methylcellulose as viscolizer, sodium chloride as tonicity agent. Bezalkonium chloride as preservative. White rabbits of both sexes, weighing between 2 and 3 kg were used for the study. Stirring of ingredients in pH 4 phosphate buffers at high speed was carried out. Result: Viscosity of the prepared hydrogels lies in the optimum range that is, 25-55 cps. Infrared spectroscopy studies show that there is no interaction between the drug and polymer. Drug released up to 90% at the end of 8 h. The hydrogel membranes were found to be sterile, nonirritant to the eye. Marketed formulation showed a decrease in IOP up to 14 mmHg at the end of 5 h and then elimination of drug, F2 and F6 maintain the sustained effect up to 12 h. Conclusion: Stimuli-sensitive hydrogels was successfully formulated and evaluated for rheological studies, drug release studies, drug interaction studies, sterility studies, ocular irritation studies, and in vivo studies. IOP lowering activity of the combination of timolol maleate and brimonidine tartrate in stimuli-sensitive hydrogel was better when compared with alone medication, which shows the additive effect of combination medication. PMID:25126524

  18. Transdermal delivery of Diltiazem HCl from matrix film: Effect of penetration enhancers and study of antihypertensive activity in rabbit model

    PubMed Central

    Parhi, Rabinarayan; Suresh, Padilam

    2015-01-01

    The present investigation focused on the development of Diltiazem HCl (DTH) matrix film and its characterization by in-vitro, ex-vivo and in-vivo methods. Films were prepared by solvent casting method by taking different ratios of hydroxypropyl methylcellulose K4M (HPMC K4M) and Eudragit RS100. Various parameters of the films were analyzed such as mechanical property using tensile tester, interaction study by Fourier transform infrared spectroscopy (FTIR) and Thermogravimetric analysis (TGA), in-vitro drug release through cellulose acetate membrane, ex-vivo permeation study using abdominal skin of rat employing Franz diffusion cell, and in-vivo antihypertensive activity using rabbit model. The FTIR studies confirmed the absence of interaction between DTH and selected polymers. Thermal analysis showed the shifting of endothermic peak of DTH in film, indicating the dispersion of DTH in molecular form throughout the film. Incorporation of 1,8-cineole showed highest flux (89.7 μg/cm2/h) of DTH compared to other penetration enhancers such as capsaicin, dimethyl sulfoxide (DMSO), and N-methyl pyrrolidone (NMP). Photomicrographs of histology study on optimized formulation (DF9) illustrated disruption of stratum corneum (SC) supporting the ex-vivo results. The in-vivo antihypertensive activity results demonstrated that formulation DF9 was effective in reducing arterial blood pressure in normotensive rabbits. SEM analysis of films kept for stability study (40 ± 2 °C/75% ± 5%RH for 3 months) revealed the formation of drug crystals which may be due to higher temperature. The findings of the study provide a better alternative dosage form of DTH for the effective treatment of hypertension with enhanced patient compliance. PMID:27222758

  19. Ram spermatozoa migrating through artificial mucus in vitro have reduced mitochondrial membrane potential but retain their viability.

    PubMed

    Martínez-Rodríguez, Carmen; Alvarez, Mercedes; López-Urueña, Elena; Gomes-Alves, Susana; Anel-López, Luis; Chamorro, Cesar A; Anel, Luis; de Paz, Paulino

    2015-06-01

    Sperm motility in vitro is one of the most common predictors of fertility in male screening. We propose that a mucus-penetration assay can isolate a cellular subpopulation critical to reproductive success. To this end, a device was designed with three modules (sample, test and collection) and its conditions of use evaluated (length of mucus, incubation time, mucus medium, sperm concentration and position in relation to the horizontal). The number of spermatozoa migrating and the viability and acrosomal status of the spermatozoa not migrating were calculated. The second objective was to evaluate the qualitative parameters of the spermatozoa migrating in 1.6% polyacrylamide for 30min. The number of spermatozoa migrating and the sperm motility, viability and the acrosomal and mitochondrial status of three sperm populations (fresh, not migrating and migrating) were determined. A higher number of migrating spermatozoa were observed after 60min of incubation, but this situation adversely affected sperm quality. The methylcellulose-based test showed a significantly lower number of migrating spermatozoa than the polyacrylamide test. The position at an angle of 45° resulted in a higher number of migrating spermatozoa in the polyacrylamide-based test. The sperm counts for three consecutive assays indicated an acceptable repeatability of the method. The viability and acrosomal status of the migrating spermatozoa showed no significant changes with regard to the control when the device was placed at 45°, whereas these parameters showed lower values at 0°. The percentage of high mitochondrial membrane potential spermatozoa was significantly reduced in the population of migrating spermatozoa. PMID:25413445

  20. Improved oral absorption and chemical stability of everolimus via preparation of solid dispersion using solvent wetting technique.

    PubMed

    Jang, Sun Woo; Kang, Myung Joo

    2014-10-01

    The aim of this study was to improve the physicochemical properties and oral absorption of poorly water-soluble everolimus via preparation of a solid dispersion (SD) system using a solvent wetting (SW) technique. The physicochemical properties, drug release profile, and bioavailability of SD prepared by SW process were also compared to SD prepared by the conventional co-precipitation method. Solid state characterizations using scanning electron microscopy, particle size analysis and X-ray powder diffraction indicated that drug homogeneously dispersed and existed in an amorphous state within the intact polymeric carrier. Whereas, a film-like mass was obtained by a co-precipitation method and further pulverization step was needed for tabletization. The drug release from the SD tablet prepared by SW process at a ratio of drug to hydroxypropyl methylcellulose of 1:15 was markedly higher than the drug alone and equivalent to the marketed product (Afinitor(®), Novartis Pharmaceuticals), a SD tablet prepared by co-precipitation method, archiving over 75% the drug release after 30 min. At the accelerated (40°C/75% R.H.) and stress (80°C) stability tests, the novel formula was more stable than drug powder and provided comparable drug stability with the commercially available product, which contains a potentially risky antioxidant, butylated hydroxyl toluene. The pharmacokinetic parameters after single oral administration in beagles showed no significant difference (P>0.01) between the novel SD-based tablet and the marketed product. The results of this study, therefore, suggest that the novel SD system prepared by the solvent wetting process may be a promising approach for improving the physicochemical stability and oral absorption of the sirolimus derivatives. PMID:25003829

  1. Detection of human myeloid progenitor cells in a murine background.

    PubMed

    Carow, C E; Harrington, M A; Broxmeyer, H E

    1993-01-01

    Cell-mixing experiments were performed to determine whether human (hu) peripheral blood plasma would select for the growth of hu myeloid progenitor cells in vitro. Mixtures of hu male umbilical cord blood and murine (mu) female bone marrow (100% hu, 100% mu, 1.0% hu or 10% hu and 50% hu) were plated in methylcellulose cultures that contained either hu plasma or fetal bovine serum (FBS). Cultures were supplemented with recombinant (r) hu erythropoietin (Epo) alone or in combination with rhu granulocyte-macrophage colony stimulating factor (GM-CSF), rmuGM-CSF or rhu steel factor (SLF). DNA was extracted from day 14 colonies and clusters, and the polymerase chain reaction (PCR) was used to detect the hu Y-chromosome satellite DNA sequence. Results of these studies revealed that hu plasma used in combination with hu growth factors selected for the growth of hu progenitor cells. Mu cells grew in hu plasma only at high cell-plating concentrations. This selective effect was due to a heat labile factor or factors, since mu cells grew equally well in heat-inactivated hu plasma and FBS. Cells in individual progenitor cell colonies and clusters cultured in hu plasma contained hu Y-chromosome-specific DNA sequences that were detectable after PCR-mediated amplification, thus eliminating the need for time-consuming Southern transfer. This study describes a method whereby hu/immune-deficient mice can be screened rapidly for hu myeloid engraftment. These results also indicate that the hu identity of colonies and clusters cultured in hu plasma must be genetically confirmed, especially when hu cells may represent a low percentage of the total cells plated. PMID:7678088

  2. Design and in vitro evaluation of a novel controlled onset extended-release delivery system of metoprolol tartrate.

    PubMed

    Emami, Jaber; Kazemali, Mohammad-Reza

    2016-01-01

    Blood pressure rises rapidly upon awakening and maybe responsible, in part, for the increased incidence of myocardial infarction and stroke during the morning hours. The aim of the present study was, therefore, to develop a novel chronotherapeutic formulation of metoprolol tartrate (MT) for night time dosing providing maximum effect in the morning hours. Core tablets contained MT, sodium chloride, lactose, Avicel(®) and starch. Powders were mixed, sieved and directly compressed in to tablets using a single punch tablet machine. Core tablets were then coated with 5 or 10% hydroxypropyl methylcellulose as swelling layer and subsequently outer membrane with the mixture of various ratios of Eudragit(®) RS to RL at different coating levels 5, 10, 15% as semi-permeable water insoluble outer coat by conventional pan-spray method. The best formulation with regard to release behavior was chosen and subjected to further release studies in various rotational speed and pHs. Both lag time and release rate were dependent on the coating levels and the osmotic pressure of dissolution medium. A linear relationship between lag time and outer coating levels was observed. The lag time was prolonged with an increase in the coating levels. Both diffusion and osmotic pumping effect were involved in drug release from the device. Significant increases in drug release behavior was not observed using dissolution medium with various pH and different agitation rates. It was found that the release rate was independent of pH, rotational speed and gastric motility and may not be altered due to changes of pH and peristaltic movement along the GI tract. PMID:27051436

  3. Ethyl cellulose and hydroxypropyl methyl cellulose buoyant microspheres of metoprolol succinate: Influence of pH modifiers

    PubMed Central

    Raut, Neha S; Somvanshi, Sachin; Jumde, Amol B; Khandelwal, Harsha M; Umekar, Milind J; Kotagale, Nandkishor Ramdas

    2013-01-01

    Introduction: Incorporation of pH modifier has been the usual strategy employed to enhance the dissolution of weakly basic drug from floating microspheres. Microspheres prepared using a combination of both ethyl cellulose (EC) and hydroxypropyl methylcellulose (HPMC) which shows highest release were utilize to investigate the effect of fumaric acid (FA), citric acid (CA), ascorbic acid (AA) and tartaric acid (TA) (all 5-20% w/w) incorporation on metoprolol succinate (MS) release. Materials and Methods: EC, HPMC alone or in combination were used to prepare microspheres that floated in simulated gastric fluid and evaluated for a percent yield, drug entrapment, percent buoyancy and drug release. The higher drug release in combination (MS:HPMC:EC, 1:1:2) was selected for the evaluation of influence of pH modifiers on MS release. CA (5-20% w/w), AA (5-20% w/w), FA (5-20% w/w) and TA (5-20% w/w) were added and evaluated for drug release. Present investigation is directed to develop floating drug delivery system of MS by solvent evaporation technique. Results: The microspheres of MS:HPMC:EC (1:1:2) exhibited the highest entrapment (74.36 ± 2.18). The best percentage yield was obtained at MS:HPMC (1:1) (83.96 ± 1.50) and combination of MS:HPMC:EC (1:1:2) (79.23 ± 1.63). Conclusion: MS release from the prepared microspheres was influenced by changing MS-polymer, MS-polymer-polymer ratio and pH modifier. Although significant increment in MS release was observed with CA (20% w/w), TA (20% w/w) and AA (20% w/w), addition of 20% w/w FA demonstrated more pronounced and significant increase in drug entrapment as well as release from MS:HPMC:EC (1:1:2) buoyant microspheres. PMID:24167789

  4. Statistical Design of Experiments on Fabrication of Bilayer Tablet of Narrow Absorption Window Drug: Development and In vitro characterisation

    PubMed Central

    Jivani, R. R.; Patel, C. N.; Jivani, N. P.

    2012-01-01

    The current study involves the fabrication of oral bioadhesive bilayer matrices of narrow absorption window drug baclofen and the optimisation of their in vitro drug release and characterisation. Statistical design of experiments, a computer-aided optimisation technique, was used to identify critical factors, their interactions and ideal process conditions that accomplish the targeted response(s). A central composite design was employed to systematically optimise the drug delivery containing a polymer, filler and compression force. The values of ratio of different grades of hydroxypropyl methylcellulose, microcrystalline cellulose and compression force were varied to be fitted in design. Drug release at 1 h (Q1), 4 h (Q4), 8 h (Q8), 12 h (Q12), and hardness were taken as responses. Tablets were prepared by direct compression methods. The compressed tablets were evaluated for their hardness, weight variation, friability, content uniformity and diameter. Counter plots were drawn and optimum formulation was selected by desirability function. The formulations were checked for their ex vivo mucoadhesion. The experimental value of Q1, Q4, Q8, Q12 and hardness for check-point batch was found to be 31.64, 45.82, 73.27, 98.95% and 4.4 kg/cm2, respectively. The release profile indicates Highuchi kinetics (Fickian transport) mechanism. The results of the statistical analysis of the data demonstrated significant interactions amongst the formulation variables, and the desirability function was demonstrated to be a powerful tool to predict the optimal formulation for the bilayer tablet. PMID:23626385

  5. Design, development and evaluation of clopidogrel bisulfate floating tablets

    PubMed Central

    Rao, K. Rama Koteswara; Lakshmi, K. Rajya

    2014-01-01

    Objective: The objective of the present work was to formulate and to characterize a floating drug delivery system for clopidogrel bisulphate to improve bioavailability and to minimize the side effects of the drug such as gastric bleeding and drug resistance development. Materials and Methods: Clopidogrel floating tablets were prepared by direct compression technique by the use of three polymers xanthan gum, hydroxypropyl methylcellulose (HPMC) K15M and HPMC K4M in different concentrations (20%, 25% and 30% w/w). Sodium bicarbonate (15% w/w) and microcrystalline cellulose (30% w/w) were used as gas generating agent and diluent respectively. Studies were carried out on floating behavior and influence of type of polymer on drug release rate. All the formulations were subjected to various quality control and in-vitro dissolution studies in 0.1 N hydrochloric acid (1.2 pH) and corresponding dissolution data were fitted to popular release kinetic equations in order to evaluate release mechanisms and kinetics. Results and Discussion: All the clopidogrel floating formulations followed first order kinetics, Higuchi drug release kinetics with diffusion as the dominant mechanism of drug release. As per Korsmeyer-Peppas equation, the release exponent “n” ranged 0.452-0.654 indicating that drug release from all the formulations was by non-Fickian diffusion mechanism. The drug release rate of clopidogrel was found to be affected by the type and concentration of the polymer used in the formulation (P < 0.05). As the concentration of the polymer was increased, the drug release was found to be retarded. Conclusion: Based on the results, clopidogrel floating tablets prepared by employing xanthan gum at concentration 25% w/w (formulation F2) was the best formulation with desired in-vitro floating time and drug dissolution. PMID:24678458

  6. Structure and Properties of Polysaccharide Based BioPolymer Gels

    NASA Astrophysics Data System (ADS)

    Prud'Homme, Robert K.

    2000-03-01

    Nature uses the pyranose ring as the basic building unit for a wideclass of biopolymers. Because of their biological origin these biopolymers naturally find application as food additives, rheology modifiers. These polymers range from being rigid skeletal material, such as cellulose that resist dissolution in water, to water soluble polymers, such as guar or carrageenan. The flexibility of the basic pyranose ring structure to provide materials with such a wide range of properties comes from the specific interactions that can be engineered by nature into the structure. We will present several examples of specific interactions for these systems: hydrogen bonding, hydrophobic interactions, and specific ion interactions. The relationship between molecular interations and rheology will be emphasized. Hydrogen bonding mediated by steric interference is used to control of solubility of starch and the rheology of guar gels. A more interesting example is the hydrogen bonding induced by chemical modification in konjac glucomannan that results in a gel that melts upon cooling. Hydrogen bonding interactions in xanthan lead to gel formation at very low polymer concentrations which is a result of the fine tuning of the polymer persistence length and total contour length. Given the function of xanthan in nature its molecular architecture has been optimized. Hydrophobic interactions in methylcellulose show a reverse temperature dependence arising from solution entropy. Carrageenan gelation upon the addition of specific cations will be addressed to show the interplay of polymer secondary structure on chemical reactivity. And finally the cis-hydroxyls on galactomannans permit crosslinking by a variety of metal ions some of which lead to "living gels" and some of which lead to permanently crosslinked networks.

  7. Bone marrow-derived cultured mast cells and peritoneal mast cells as targets of a growth activity secreted by BALB/3T3 fibroblasts

    SciTech Connect

    Jozaki, K.; Kuriu, A.; Hirota, S.; Onoue, H.; Ebi, Y.; Adachi, S.; Ma, J.Y.; Tarui, S.; Kitamura, Y. )

    1991-03-01

    When fibroblast cell lines were cultured in contact with bone marrow-derived cultured mast cells (CMC), both NIH/3T3 and BALB/3T3 cell lines supported the proliferation of CMC. In contrast, when contact between fibroblasts and CMC was prohibited by Biopore membranes or soft agar, only BALB/3T3 fibroblasts supported CMC proliferation, suggesting that BALB/3T3 but not NIH/3T3 cells secreted a significant amount of a mast cell growth activity. Moreover, the BALB/3T3-derived growth activity induced the incorporation of (3H)thymidine by CMC and the clonal growth of peritoneal mast cells in methylcellulose. The mast cell growth activity appeared to be different from interleukin 3 (IL-3) and interleukin 4 (IL-4), because mRNAs for these interleukins were not detectable in BALB/3T3 fibroblasts. Although mast cells are genetically deficient in tissues of W/Wv mice, CMC did develop when bone marrow cells of W/Wv mice were cultured with pokeweed mitogen-stimulated spleen cell-conditioned medium. Because BALB/3T3 fibroblast-conditioned medium (BALB-FCM) did not induce the incorporation of (3H)thymidine by W/Wv CMC, the growth activity in BALB-FCM appeared to be a ligand for the receptor encoded by the W (c-kit) locus. Because CMC and peritoneal mast cells are obtained as homogeneous suspensions rather easily, these cells may be potentially useful as targets for the fibroblast-derived mast cell growth activity.

  8. Changes in numbers and types of mast cell colony-forming cells in the peritoneal cavity of mice after injection of distilled water: evidence that mast cells suppress differentiation of bone marrow-derived precursors

    SciTech Connect

    Kanakura, Y.; Kuriu, A.; Waki, N.; Nakano, T.; Asai, H.; Yonezawa, T.; Kitamura, Y.

    1988-03-01

    Two different types of cells in the peritoneal cavity of mice produce mast cell colonies in methylcellulose. Large mast cell colonies are produced by bone marrow-derived precursors resembling lymphoid cells by light microscopy (L-CFU-Mast), whereas medium and small mast cell colonies are produced by morphologically identifiable mast cells (M-CFU-Mast and S-CFU-Mast, respectively). In the present study we eradicated peritoneal mast cells by intraperitoneal (IP) injection of distilled water. The regeneration process was investigated to clarify the relationship between L-CFU-Mast, M-CFU-Mast, and S-CFU-Mast. After injection of distilled water, M-CFU-Mast and S-CFU-Mast disappeared, but L-CFU-Mast increased, and then M-CFU-Mast and S-CFU-Mast appeared, suggesting the presence of a hierarchic relationship. When purified peritoneal mast cells were injected two days after the water injection, the L-CFU-Mast did not increase. In the peritoneal cavity of WBB6F1-+/+ mice that had been lethally irradiated and rescued by bone marrow cells of C57BL/6-bgJ/bgJ (beige, Chediak-Higashi syndrome) mice, L-CFU-Mast were of bgJ/bgJ type, but M-CFU-Mast and S-CFU-Mast were of +/+ type. The injection of distilled water to the radiation chimeras resulted in the development of bgJ/bgJ-type M-CFU-Mast and then S-CFU-Mast. The presence of mast cells appeared to suppress the recruitment of L-CFU-Mast from the bloodstream and to inhibit the differentiation of L-CFU-Mast to M-CFU-Mast.

  9. Enhanced osteoblast proliferation and collagen gene expression by estradiol

    SciTech Connect

    Ernest, M.; Schmid, Ch.; Froesch, E.R. )

    1988-04-01

    Estrogens play a crucial role in the development of postmenopausal osteoporosis. However, the mechanism by which estrogens exert their effects on bone is unknown. To examine possible direct effects of 17{beta}-estradiol on bone-forming cells, the authors used pure rat osteoblast-like cells in vitro as a model. Osteoblast-like cells prepared from calvaria of newborn rats were cultured serum-free in methylcellulose-containing medium for 21 days. Osteoblast-like cells proliferate selectively into clonally derived cell clusters of spherical morphorlogy. 17{beta}-Estradiol at concentrations of 0.1 nM and 1 nM enhanced osteoblast-like cell proliferation by 41% and 68% above vehicle-treated controls. The biologically inactive stereoisomer 17{alpha}-estradiol (same concentrations) had no effect. Moreover, the antiestrogen tamoxifen abolished the stimulation of osteoblast-like cell proliferation by 17{beta}-estradiol. After 21 days of culture, RNA was prepared and analyzed in a dot-hybridization assay for the abundance of pro{alpha}1(I) collagen mRNA. Steady-state mRNA levels were increased in cultures treated with 17{beta}-estradiol in a dose-dependent manner with maximal stimulation at 1 nM and 10 nM. At the same concentrations, the percentage of synthesized protein (labeled by ({sup 3}H)proline pulse) that was digestible by collagenase was increased, indicating that 17{beta}-estradiol acts as pretranslational levels to enhance synthesis of bone collagen. These data show that the osteoblast is a direct target for 17{beta}-estradiol.

  10. Cloning and Characterization of an Endoglucanase Gene from Actinomyces sp. Korean Native Goat 40

    PubMed Central

    Kim, Sung Chan; Kang, Seung Ha; Choi, Eun Young; Hong, Yeon Hee; Bok, Jin Duck; Kim, Jae Yeong; Lee, Sang Suk; Choi, Yun Jaie; Choi, In Soon; Cho, Kwang Keun

    2016-01-01

    A gene from Actinomyces sp. Korean native goat (KNG) 40 that encodes an endo-β-1,4-glucanase, EG1, was cloned and expressed in Escherichia coli (E. coli) DH5α. Recombinant plasmid DNA from a positive clone with a 3.2 kb insert hydrolyzing carboxyl methyl-cellulose (CMC) was designated as pDS3. The entire nucleotide sequence was determined, and an open-reading frame (ORF) was deduced. The ORF encodes a polypeptide of 684 amino acids. The recombinant EG1 produced in E. coli DH5α harboring pDS3 was purified in one step using affinity chromatography on crystalline cellulose and characterized. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis/zymogram analysis of the purified enzyme revealed two protein bands of 57.1 and 54.1 kDa. The amino terminal sequences of these two bands matched those of the deduced ones, starting from residue 166 and 208, respectively. Putative signal sequences, a Shine–Dalgarno-type ribosomal binding site, and promoter sequences related to the consensus sequences were deduced. EG1 has a typical tripartite structure of cellulase, a catalytic domain, a serine-rich linker region, and a cellulose-binding domain. The optimal temperature for the activity of the purified enzyme was 55°C, but it retained over 90% of maximum activity in a broad temperature range (40°C to 60°C). The optimal pH for the enzyme activity was 6.0. Kinetic parameters, Km and Vmax of rEG1 were 0.39% CMC and 143 U/mg, respectively. PMID:26732336

  11. Obtainment of pellets using the standardized liquid extract of Brosimum gaudichaudii Trécul (Moraceae)

    PubMed Central

    Filho, Omar Paulino Silva; Oliveira, Leandra Almeida Ribeiro; Martins, Frederico Severino; Borges, Leonardo Luiz; de Freitas, Osvaldo; da Conceição, Edemilson Cardoso

    2015-01-01

    Background: The standardized liquid extract of Brosimum gaudichaudii Trécul is an alternative for the treatment of vitiligo. There is a shortage of solid oral dosage forms developed from standardized extracts of this plant specie. Objective: This study is aimed to obtain pellets with a standardized liquid extract of B. gaudichaudii. Results: The standardized liquid extract of B. gaudichaudii was obtained through maceration and percolation with a 55% ethanol-water solution (v/v). Pellets were obtained through a mixture of extract of 500 g of B. gaudichaudii standardized extract, 500 g of microcrystalline cellulose PH101 and 10 g of hydroxypropyl methylcellulose K100. The pellets obtained presented a homogeneity yield of 92%, aspect ratio of 1.16 ± 0.65, shape fator eR of 0.35 ± 0.09 and Feret diammeter of 0.87 ± 0.27. These pellets were coated with a suspension composed of titanium dioxide, aluminum red lacquer, ethyl cellulose, talc and magnesium stearate. Before the photostability test, the uncoated pellets showed psoralen content equal to 0.13 ± 0.01% and to the 5-MOP was 1.40 ± 0.27%. After exposure to one level (3 J.cm-2) of UVB irradiation the uncoated pellets presented a degradation of 2.16% of psoralen and 8.1% of 5-MOP. After exposure to three levels (10, 20 and 30 J.cm-2) of UVA irradiation the uncoated pellets exhibited photodegradation of 9.78, 17.64, 24.21% of psoralen and 18.95, 23.68, 28.48% for 5-MOP. The coated pellets where unaffected after photostability test. Conclusion: Pellets were obtained with the standardized liquid extract of B. gaudichaudii and coating is a technological alternative to ensure the stability of the formula. PMID:25709229

  12. Granulopoiesis requires increased C/EBPα compared to monopoiesis, correlated with elevated Cebpa in immature G-CSF receptor versus M-CSF receptor expressing cells.

    PubMed

    Ma, Ou; Hong, SunHwa; Guo, Hong; Ghiaur, Gabriel; Friedman, Alan D

    2014-01-01

    C/EBPα is required for the formation of granulocyte-monocyte progenitors; however, its role in subsequent myeloid lineage specification remains uncertain. Transduction of murine marrow with either of two Cebpa shRNAs markedly increases monocyte and reduces granulocyte colonies in methylcellulose or the monocyte to neutrophil ratio in liquid culture. Similar findings were found after marrow shRNA transduction and transplantation and with CEBPA knockdown in human marrow CD34+ cells. These results apparently reflect altered myeloid lineage specification, as similar knockdown allowed nearly complete 32Dcl3 granulocytic maturation. Cebpa knockdown also generated lineage-negative blasts with increased colony replating capacity but unchanged cell cycle parameters, likely reflecting complete differentiation block. The shRNA having the greatest effect on lineage skewing reduced Cebpa 3-fold in differentiating cells but 6-fold in accumulating blasts. Indicating that Cebpa is the relevant shRNA target, shRNA-resistant C/EBPα-ER rescued marrow myelopoiesis. Cebpa knockdown in murine marrow cells also increased in vitro erythropoiesis, perhaps reflecting 1.6-fold reduction in PU.1 leading to GATA-1 derepression. Global gene expression analysis of lineage-negative blasts that accumulate after Cebpa knockdown demonstrated reduction in Cebpe and Gfi1, known transcriptional regulators of granulopoiesis, and also reduced Ets1 and Klf5. Populations enriched for immature granulocyte or monocyte progenitor/precursors were isolated by sorting Lin-Sca-1-c-Kit+ cells into GCSFR+MCSFR- or GCSFR-MCSFR+ subsets. Cebpa, Cebpe, Gfi1, Ets1, and Klf5 RNAs were increased in the c-Kit+GCSFR+ and Klf4 and Irf8 in the c-Kit+MCSFR+ populations, with PU.1 levels similar in both. In summary, higher levels of C/EBPα are required for granulocyte and lower levels for monocyte lineage specification, and this myeloid bifurcation may be facilitated by increased Cebpa gene expression in granulocyte

  13. Development of Bioadhesive Transdermal Bupivacaine Gels for Enhanced Local Anesthetic Action

    PubMed Central

    Cho, Cheong-Weon; Kim, Deok-Bae; Shin, Sang-Chul

    2012-01-01

    Topical drug dosage forms such as ointments and creams can be easily removed through wetting, movement and contact. The new bioadhesive formulations with enhanced local anesthetic effects are needed for topical administration. The adhesive capacity of hydroxypropyl methylcellulose (HPMC) was determined by measuring the maximum detachment force and the adhesion work with an auto peeling tester. The release of drug from a HPMC gel was studied according to the drug concentration. Permeation study through the rat skin was performed at 37°C using phosphate buffer solution (pH = 7.4) as a receptor medium. To increase the skin permeation of bupivacaine from the HPMC gels, penetration enhancer such as the saturated and unsaturated fatty acids, the pyrrolidones, the propylene glycol derivatives, the glycerides, and the non-ionic surfactants were incorporated in the bupivacaine-HPMC gels. The local anesthetic effect of the formulated gel preparation was examined using a tail-flick analgesimeter. As the concentration of HPMC increased, the bioadhesive force and viscosity were increased. The rate of drug release was increased with increasing the drug concentration. Among the enhancers used, polyoxyethylene 2-oleyl ether showed the most enhancing effects on drug permeation through the skin. In the rat tail flick test, the area under the efficacy curve of bupivacaine gel containing polyoxyethylene 2-oleyl ether and tetrahydrozoline showed a 2.36-fold increase in anesthetic activity compared to control gel without any additives. The bupivacaine gels containing both penetration enhancer and vasoconstrictor showed enhancement and prolonged efficacy compared to the control gel. To enhance the local anesthetic effects of bupivacaine, the transdermal bupivacaine gel formulation containing penetration enhancer and vasoconstrictor could be developed. PMID:24250466

  14. Efficacy of ipamorelin, a ghrelin mimetic, on gastric dysmotility in a rodent model of postoperative ileus

    PubMed Central

    Greenwood-Van Meerveld, Beverley; Tyler, Karl; Mohammadi, Ehsan; Pietra, Claudio

    2012-01-01

    Background Delayed gastric emptying is a common disorder with few effective therapeutic options. The goal of this study was to investigate whether ipamorelin, a synthetic peptidomimetic that acts on the ghrelin receptor, accelerates gastric emptying in a rodent model of gastroparesis induced by abdominal surgery and intestinal manipulation. Methods Fasted adult male rats were subjected to laparotomy and intestinal manipulation. Following the surgery rats received ipamorelin (0.014–0.14 µmol/kg) or vehicle control via intravenous administration. Gastric emptying was measured by the percent of total recovered radioactivity remaining in the stomach 15 minutes after intragastric gavage of 1.5 mL of 99mTc (technicium-99m) sulfur colloid in 0.5% methylcellulose. In a separate group of rats subjected to laparotomy and intestinal manipulation, the gastric fundus was isolated and tissue segments were suspended in an organ bath to assess the effect of ipamorelin (1 µM) on gastric smooth muscle contractility induced by acetylcholine and electrical field stimulation. Results Abdominal surgery caused a delay in gastric emptying with 78% ± 5% of the meal remaining in the stomach in vehicle controls. Ipamorelin (0.014 µmol/kg intravenous) resulted in a significant acceleration (P < 0.05 vs vehicle-treated rat) of gastric emptying with 52% ± 11% of the meal remaining in the stomach compared to nonsurgical control animals with 44% ± 6%. Following abdominal surgery and intestinal manipulation, isolated preparations of gastric smooth muscle exhibited a marked inhibition of acetylcholine and electrical field stimulation-induced contractile responses, which were reversed by ipamorelin and ghrelin. Conclusion These results suggest that ipamorelin accelerates gastric emptying in a rodent model of postoperative ileus through the stimulation of gastric contractility by activating a ghrelin receptor-mediated mechanism involving cholinergic excitatory neurons.

  15. Cyclodextrin solubilization of benzodiazepines: formulation of midazolam nasal spray.

    PubMed

    Loftsson, T; Gudmundsdóttir, H; Sigurjónsdóttir, J F; Sigurdsson, H H; Sigfússon, S D; Másson, M; Stefánsson, E

    2001-01-01

    The cyclodextrin solubilization of three benzodiazepines, i.e. alprazolam, midazolam and triazolam, was investigated. The cyclodextrin solubilization was enhanced through ring-opening of the benzodiazepine rings and ionization of the ring-open forms. Additional enhancement was obtained through interaction of a water-soluble polymer with the cyclodextrin complexes. The ring-opening was pH-dependent and completely reversible, the ring-open forms dominating at low pH but the ring-closed forms at physiologic pH. The ring-closed forms were rapidly regenerated upon elevation of pH. In freshly collected human serum in vitro at 37 degrees C, the half-life for the first-order rate constant for the ring-closing reaction was estimated to be less than 2 min for both alprazolam and midazolam. Midazolam (17 mg/ml) was solubilized in aqueous pH 4.3 nasal formulation containing 14% (w/v) sulfobutylether beta-cyclodextrin, 0.1% (w/v) hydroxypropyl methylcellulose, preservatives and buffer salts. Six healthy volunteers received 0.06 mg/kg midazolam intranasally and 2 mg intravenously, and blood samples were collected up to 360 min after the administration. Midazolam was absorbed rapidly reaching maximum serum concentrations of 54.3+/-5.0 ng/ml at 15+/-2 min. The elimination half-life of midazolam was 2.2+/-0.3 h and the absolute availability was 73+/-7%. All mean values+/-SEM. PMID:11165818

  16. Preferential eradication of acute myelogenous leukemia stem cells by fenretinide

    PubMed Central

    Zhang, Hui; Mi, Jian-Qing; Fang, Hai; Wang, Zhao; Wang, Chun; Wu, Lin; Zhang, Bin; Minden, Mark; Yang, Wen-Tao; Wang, Huan-Wei; Li, Jun-Min; Xi, Xiao-Dong; Chen, Sai-Juan; Zhang, Ji; Chen, Zhu; Wang, Kan-Kan

    2013-01-01

    Leukemia stem cells (LSCs) play important roles in leukemia initiation, progression, and relapse, and thus represent a critical target for therapeutic intervention. However, relatively few agents have been shown to target LSCs, slowing progress in the treatment of acute myelogenous leukemia (AML). Based on in vitro and in vivo evidence, we report here that fenretinide, a well-tolerated vitamin A derivative, is capable of eradicating LSCs but not normal hematopoietic progenitor/stem cells at physiologically achievable concentrations. Fenretinide exerted a selective cytotoxic effect on primary AML CD34+ cells, especially the LSC-enriched CD34+CD38− subpopulation, whereas no significant effect was observed on normal counterparts. Methylcellulose colony formation assays further showed that fenretinide significantly suppressed the formation of colonies derived from AML CD34+ cells but not those from normal CD34+ cells. Moreover, fenretinide significantly reduced the in vivo engraftment of AML stem cells but not normal hematopoietic stem cells in a nonobese diabetic/SCID mouse xenotransplantation model. Mechanistic studies revealed that fenretinide-induced cell death was linked to a series of characteristic events, including the rapid generation of reactive oxygen species, induction of genes associated with stress responses and apoptosis, and repression of genes involved in NF-κB and Wnt signaling. Further bioinformatic analysis revealed that the fenretinide–down-regulated genes were significantly correlated with the existing poor-prognosis signatures in AML patients. Based on these findings, we propose that fenretinide is a potent agent that selectively targets LSCs, and may be of value in the treatment of AML. PMID:23513221

  17. Combinatorial treatment of tart cherry extract and essential fatty acids reduces cognitive impairments and inflammation in the mu-p75 saporin-induced mouse model of Alzheimer's disease.

    PubMed

    Matchynski, Jessica J; Lowrance, Steven A; Pappas, Colleen; Rossignol, Julien; Puckett, Nicole; Sandstrom, Michael; Dunbar, Gary L

    2013-04-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects more than five million Americans and is characterized by a progressive loss of memory, loss of cholinergic neurons in the basal forebrain, formation of amyloid plaques and neurofibrillary tangles, and an increase in oxidative stress. Recent studies indicate that dietary supplements of antioxidants and omega-3 and omega-6 fatty acids may reduce the cognitive deficits in AD patients. The current study tested a combinatorial treatment of antioxidants from tart cherry extract and essential fatty acids from Nordic fish and emu oils for reducing cognitive deficits in the mu-p75 saporin (SAP)-induced mouse model of AD. Mice were given daily gavage treatments of Cerise(®) Total-Body-Rhythm™ (TBR; containing tart cherry extract, Nordic fish oil, and refined emu oil) or vehicle (methylcellulose) for 2 weeks before intracerebroventricular injections of the cholinergic toxin, mu-p75 SAP, or phosphate-buffered saline. The TBR treatments continued for an additional 17 days, when the mice were tested on a battery of cognitive and motor tasks. Results indicate that TBR decreased the SAP-induced cognitive deficits assessed by the object-recognition, place-recognition, and Morris-water-maze tasks. Histological examination of the brain tissue indicated that TBR protected against SAP-induced inflammatory response and loss of cholinergic neurons in the area around the medial septum. These findings indicate that TBR has the potential to serve as an adjunctive treatment which may help reduce the severity of cognitive deficits in disorders involving cholinergic deficits, such as AD. PMID:23566055

  18. Green tea extract as a local drug therapy on periodontitis patients with diabetes mellitus: A randomized case–control study

    PubMed Central

    Gadagi, Jayaprakash S.; Chava, Vijay K.; Reddy, Venkata Ramesh

    2013-01-01

    Background: The green tea extract is a naturally occurring product having beneficial effects that counteract with the pathobiological features of periodontitis and diabetes mellitus. Hence, the present study was aimed at incorporation of green tea extract into hydroxylpropyl methylcellulose and investigates its efficacy in chronic periodontitis patients associated with and without diabetes mellitus. Materials and Methods: For the in vitro study, formulation of green tea strips and placebo strips, and analysis of drug release pattern from the green tea strips at different time intervals were performed. For the in vivo study, 50 patients (20-65 years), including 25 systemically healthy patients with chronic periodontitis (group 1) and 25 diabetic patients with chronic periodontitis (group 2) were enrolled. In each patient, test and control sites were identified for the placement of green tea and placebo strips, respectively. Gingival Index (GI), Probing Pocket Depth (PPD), and Clinical Attachment Level (CAL) were examined at baseline, first, second, third, and fourth weeks. Microbiological analysis for Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans was performed at baseline and fourth week. Results: The in vitro study showed 10.67% green tea release at 30 min; thereafter, a slow release was noted till 120 min. In vivo study: Both groups showed significant reduction in GI scores at the test sites. Group 1 showed significant (P < 0.001) PPD reduction at different time intervals at the test sites. However, group 2 showed significant reduction from baseline (5.30 ± 0.70) to fourth week (3.5 ± 0.97). Statistically significant gain in CAL at the test sites was observed both in group 1 (1.33 mm) and group 2 (1.43 mm). The prevalence of P. gingivalis in group 1 test sites was significantly reduced from baseline (75%) to fourth week (25%). Conclusions: Local drug delivery using green tea extract could be used as an adjunct in the treatment of chronic

  19. Azithromycin novel drug delivery system for ocular application

    PubMed Central

    Gilhotra, Ritu Mehra; Nagpal, Kalpana; Mishra, Dina Nath

    2011-01-01

    Background: Azithromycin (AZT) is a macrolide antibiotic derived from and similar in structure to erythromycin. Oral administration of AZT is effective for the treatment of trachoma; however, topical formulations are difficult to develop because of the drug's hydrophobicity. The aim of this study is to formulate a novel topical ophthalmic delivery system of AZT. Materials and Methods: In the present study, ocular inserts of AZT are prepared using alginate, carbopol, and hydroxypropyl methylcellulose (HPMC) to solve the said formulation problem of drug and to facilitate ocular bioavailability. Ocular inserts were prepared by film casting method and the prepared films were subjected to investigations for their physical and mechanical properties, swelling behaviors, ex vivo bioadhesion, and in vitro drug release. Ocular irritation of the developed formulation was also checked by hen's egg chorioallantoic membrane test for ocular irritation potential. Results: The physicochemical, bioadhesive, and swelling properties of films were found to vary significantly depending on the type of polymers used and their combinations. The alginate films exhibited greater bioadhesion and showed higher tensile strength and elasticity than the carbopol films. HPMC addition to the films significantly affected the properties of ocular inserts. Carbopol:HPMC (30:70)-based ocular inserts sustained drug release for longest span of 6 h. The release profile of AZT showed that drug release was by both diffusion and swelling. The formulation was found to be practically nonirritant in ocular irritation studies. Conclusion: AZT can therefore be developed as an ocular insert delivery system for the treatment of ocular surface infections. PMID:23071916

  20. Preparation and evaluation of diltiazem hydrochloride diffusion-controlled transdermal delivery system.

    PubMed

    Limpongsa, Ekapol; Umprayn, Kraisri

    2008-01-01

    The objective was to investigate the suitable polymeric films for the development of diltiazem hydrochloride (diltiazem HCl) transdermal drug delivery systems. Hydroxypropyl methylcellulose (HPMC) and ethylcellulose (EC) were used as hydrophilic and hydrophobic film formers, respectively. Effects of HPMC/EC ratios and plasticizers on mechanical properties of free films were studied. Effects of HPMC/EC ratios on moisture uptake, in vitro release and permeation through pig ear skin of diltiazem HCl films were evaluated. Influence of enhancers including isopropyl myristate (IPM), isopropyl palmitate (IPP), N-methyl-2-pyrrolidone, oleic acid, polyethylene glycol 400, propylene glycol, and Tween80 on permeation was evaluated. It was found that addition of EC into HPMC film produced lower ultimate tensile strength, percent elongation at break and Young's modulus, however, addition of EC up to 60% resulted in too hard film. Plasticization with dibutyl phthalate (DBP) produced higher strength but lower elongation as compared to triethyl citrate. The moisture uptake and initial release rates (0-1 h) of diltiazem HCl films decreased with increasing the EC ratio. Diltiazem HCl films (10:0, 8:2 and 6:4 HPMC/EC) were studied for permeation because of the higher release rate. The 10:0 and 8:2 HPMC/EC films showed the comparable permeation-time profiles, and had higher flux values and shorter lag time as compared to 6:4 HPMC/EC film. Addition of IPM, IPP or Tween80 could enhance the fluxes for approx. three times while Tween80 also shorten the lag time. In conclusion, the film composed of 8:2 HPMC/EC, 30% DBP and 10% IPM, IPP or Tween80 loaded with 25% diltiazem HCl should be selected for manufacturing transdermal patch by using a suitable adhesive layer and backing membrane. Further in vitro permeation and in vivo performance studies are required. PMID:18431661