WorldWideScience

Sample records for controlled release formulations

  1. Controlled-release tablet formulation of isoniazid.

    Science.gov (United States)

    Jain, N K; Kulkarni, K; Talwar, N

    1992-04-01

    Guar (GG) and Karaya gums (KG) alone and in combination with hydroxy-propylmethylcellulose (HPMC) were evaluated as release retarding materials to formulate a controlled-release tablet dosage form of isoniazid (1). In vitro release of 1 from tablets followed non-Fickian release profile with rapid initial release. Urinary excretion studies in normal subjects showed steady-state levels of 1 for 13 h. In vitro and in vivo data correlated (r = 0.9794). The studies suggested the potentiality of GG and KG as release retarding materials in formulating controlled-release tablet dosage forms of 1.

  2. Controlled Release Formulations of Auxinic Herbicides

    Science.gov (United States)

    Kowalski, Witold J.; Siłowiecki, Andrzej.; Romanowska, Iwona; Glazek, Mariola; Bajor, Justyna; Cieciwa, Katarzyna; Rychter, Piotr

    2013-04-01

    Controlled release formulations are applied extensively for the release of active ingredients such as plant protection agents and fertilizers in response to growing concern for ecological problems associated with increased use of plant protection chemicals required for intensive agricultural practices [1]. We synthesized oligomeric mixtures of (R,S)-3-hydroxy butyric acid chemically bonded with 2,4-D, Dicamba and MCPA herbicides (HBA) respectively, and determined their molecular structure and molecular weight dispersion by the size exclusion chromatography, proton magnetic resonance spectrometry and electro-spray ionization mass spectrometry. Further we carried out bioassays of herbicidal effectiveness of the HBA herbicides vs. series of dicotyledonous weeds and crop injury tests [2, 3, 4]. Field bioassays were accomplished according to the EPPO standards [5]. Groups of representative weeds (the development stages in the BCCH scale: 10 - 30) were selected as targets. Statistical variabilities were assessed by the Fisher LSD test for plants treated with the studied herbicides in form of HBA oligomers, the reference herbicides in form of dimethyl ammonium salts (DMA), and untreated plants. No statistically significant differences in the crop injuries caused by the HBA vs. the DMA reference formulation were observed. The effectiveness of the HBA herbicides was lower through the initial period (ca. 2 weeks) relative to the DMA salts, but a significant increase in the effectiveness of the HBA systems followed during the remaining fraction of each assay. After 6 weeks all observed efficiencies approached 100%. The death of weeds treated with the HBA herbicides was delayed when compared with the DMA reference herbicides. The delayed uptake observed for the HBA oligomers relative to the DMA salts was due to controlled release phenomena. In case of the DMA salts the total amount of active ingredients was available at the target site. By contrast, the amount of an active

  3. Controlled Release Formulation of Indomethacin Prepared With Bee ...

    African Journals Online (AJOL)

    Erah

    2010-12-27

    Dec 27, 2010 ... Results: The results show that, although the release rate of formulations F1 - F7 did not show any ... Keywords: Propolis (bee glue), Indomethacin, Controlled release, Zero order kinetics, Waxy materials ... focus of interest.

  4. Design of a controlled release liquid formulation of lamotrigine

    Directory of Open Access Journals (Sweden)

    V Kumar

    2011-05-01

    Full Text Available "n  "n  Background and the purpose of the study: Lamotrigine is a broad spectrum anticonvulsant drug widely used as mono- or adjunct- therapy in adults and children. The aim of this study was to develop controlled release liquid formulation of lamotrigine to improve bioavailability and compliance of pediatric and geriatric epileptic patients. "n  Methods: Multiple (w/o/w emulsion was prepared using one step emulsification technique. It was evaluated for entrapment efficiency (EE, morphology, zeta potential (ZP, polydispersity index (PI, rheology, thermal property, in vitro drug release behavior and stability. In vivo studies in albino mice were carried out using maximal electroshock seizure (MES test and strychnine induced seizure (SIS pattern test and results were compared with marketed formulation. "n  Results: The EE of the formulations varied from 84.37% to 98.11%. The ZP and PI values of the prepared batches were in the range of +23.46 to +28.07 and 0.256 and 0.365, respectively. Microscopic observation clearly indicated the stability of the emulsions during the storage period. All batches exhibited controlled in vitro drug release up to 12 hrs. Batch C11 exhibited significantly longer duration of protection of seizure in mice against MES and exhibited comparable efficacy in SIS as compared to the marketed formulation. "n  Major Conclusion: Multiple emulsion of lamotrigine compared to the marketed tablet showed plasma drug concentration within therapeutic range for longer time and comparable efficacy.

  5. Formulation and Pharmacokinetic Evaluation of Controlled-Release ...

    African Journals Online (AJOL)

    A coating layer was then applied with a mixture of HPMC, ethylcellulose, shellac, and HPMC phthalate. The effect of several formulation variables on in vitro drug release was studied; furthermore, the drug release kinetics of the optimized formulation was evaluated. The in vivo pharmacokinetics of the optimized formulation ...

  6. Agricultural production - Phase 2. Indonesia. Controlled release pesticide formulations

    International Nuclear Information System (INIS)

    Vollner, L.

    1992-01-01

    At the request of the Government of Indonesia, an IAEA expert undertook a two weeks mission from 2 to 15 April 1991, and continued it from the 9 to 22 November 1991 at the Center for Application of Isotopes and Radiation (CAIR) of the National Atomic Energy Agency, BATAN in Jakarta. Expert discussed the project and carried out experiments together with the staff of the center, introducing shellac (description in part II) as a candidate for controlled release formulations. Formulations of carbofuran, butachlor, 2,4-D and diazinon were carried out, using sand and cocconut shells as carriers. Release rates of a.i. into water have been checked and further work has been discussed. Expert assessed further needs for supply of instruments, accessories and chemicals. (author)

  7. Formulation and Pharmacokinetic Evaluation of Controlled-Release ...

    African Journals Online (AJOL)

    The effect of several formulation variables on in ... The in vivo pharmacokinetics of the optimized formulation was compared ... Results: The core tablets exhibited extended release consisting of drug release from the embedded ... important factor in medical treatment with respect ... The solvents for high-performance liquid.

  8. Newly developed controlled release subcutaneous formulation for tramadol hydrochloride

    Directory of Open Access Journals (Sweden)

    Mostafa Mabrouk

    2018-05-01

    Full Text Available This study presents a drug delivery system of poly (Ɛ-caprolactone (PCL ribbons to optimize the pharmaceutical action of tramadol for the first time according to our knowledge. PCL ribbons were fabricated and loaded with tramadol HCl. Ribbons were prepared by slip casting technique and coated with dipping technique with β-cyclodextrin. The chemical integrity and surface morphology of the ribbons were confirmed using FTIR and SEM coupled with EDX. In addition, thermodynamic behavior of the fabricated ribbons was investigated using DSC/TGA. Tramadol loading into PCL ribbons, biodegradation of ribbons and tramadol release kinetics were studied in PBS.The results revealed that the formulated composition did not affect the chemical integrity of the drug. Furthermore, SEM/EDX confirmed the inclusion of tramadol into the PCL matrix in homogenous distribution pattern without any observation of porous structure. The particle size of loaded tramadol was found to be in the range of (2–4 nm. The formulated composition did not affect the chemical integrity of the drug and should be further investigated for bioavailability. Tramadol exhibited controlled release behavior from PCL ribbons up to 45 days governed mainly by diffusion mechanism. The fabricated ribbons have a great potentiality to be implemented in the long term subcutaneous delivery of tramadol. Keywords: Tramadol, Polycaprolcatone, Subcutaneous membrane, Ribbons, β-Cyclodextrin, Controlled release

  9. Agricultural production - Phase 2. Indonesia. Controlled release pesticide formulations

    International Nuclear Information System (INIS)

    Vollner, L.

    1991-01-01

    At the request of the Government of Indonesia, an IAEA expert undertook a two weeks (of one month) mission from 2 to 15 April 1991 to the Center for Application of Isotopes and Radiation (CAIR) of BATAN in Jakarta. Expert held a seminar, discussed and carried out experiments on Controlled Release Formulations (CRF). Discussed further experiments, cleaned and reinstalled an ECD of the Shimadzu gas chromatograph and optimized the analytical conditions for chlorinated pesticides. He also developed a project for possible submission to the Government of Germany, to allow the staff of CAIR to undertake a more intensive research and to be able to set up training facilities in his research center in Munich/Germany. He furthermore assessed needs for supply of instruments, accessories and radiolabelled pesticides. An agreement for continuing the scientific and technical mission was obtained with the staff of CAIR, in connection with the DDT-RCM at the end of November 1991, provided approval by IAEA

  10. Controlled Release Formulation of Indomethacin Prepared With Bee ...

    African Journals Online (AJOL)

    Abstract. Purpose: To prepare and evaluate new sustained release formulations of indomethacin based on extracts of propolis (bee glue). Methods: Standardization of propolis (bee glue) extracts was performed by high performance liquid chromatography (HPLC) and determination of the values of fat and fixed oils. Several ...

  11. Cardiovascular safety of the oral controlled absorption system (OCAS) formulation of tamsulosin compared to the modified release (MR) formulation

    NARCIS (Netherlands)

    Michel, M. C.; Korstanje, C.; Klauwinkel, W.; Shear, M.; Davies, J.; Quartel, A.

    2005-01-01

    Objective: The potential to interfere with efferent adrenergic drive in the cardiovascular system was tested in elderly healthy subjects for the new oral controlled absorption system (OCAS) 0.4 mg tablet formulation of tamsulosin compared to the modified release (MR) 0.4 mg capsule formulation of

  12. A REVIEW ON CONTROLLED DRUG RELEASE FORMULATION: SPANSULES

    OpenAIRE

    Rinky Maurya; Dr. Pramod Kumar Sharma; Rishabha Malviya

    2014-01-01

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

  13. Controlled release of diuron from an alginate-bentonite formulation: water release kinetics and soil mobility study.

    Science.gov (United States)

    Fernández-Pérez, M; Villafranca-Sánchez, M; González-Pradas, E; Flores-Céspedes, F

    1999-02-01

    The herbicide diuron was incorporated in alginate-based granules to obtain controlled release (CR) properties. The standard formulation (alginate-herbicide-water) was modified by the addition of different sorbents. The effect on diuron release rate caused by incorporation of natural and acid-treated bentonites in alginate formulation was studied by immersion of the granules in water under static conditions. The release of diuron was diffusion-controlled. The time taken for 50% release of active ingredient to be released into water, T(50), was calculated for the comparison of formulations. The addition of bentonite to the alginate-based formulation produced the higher T(50) values, indicating slower release of the diuron. The mobility of technical and formulated diuron was compared by using soil columns. The use of alginate-based CR formulations containing bentonite produced a less vertical distribution of the active ingredient as compared to the technical product and commercial formulation. Sorption capacities of the various soil constituents for diuron were also determined using batch experiments.

  14. Controlled release hydrophilic matrix tablet formulations of isoniazid: design and in vitro studies.

    Science.gov (United States)

    Hiremath, Praveen S; Saha, Ranendra N

    2008-01-01

    The aim of the present investigation was to develop oral controlled release matrix tablet formulations of isoniazid using hydroxypropyl methylcellulose (HPMC) as a hydrophilic release retardant polymer and to study the influence of various formulation factors like proportion of the polymer, polymer viscosity grade, compression force, and release media on the in vitro release characteristics of the drug. The formulations were developed using wet granulation technology. The in vitro release studies were performed using US Pharmacopoeia type 1 apparatus (basket method) in 900 ml of pH 7.4 phosphate buffer at 100 rpm. The release kinetics was analyzed using Korsmeyer-Peppas model. The release profiles were also analyzed using statistical method (one-way analysis of variance) and f (2) metric values. The release profiles found to follow Higuchi's square root kinetics model irrespective of the polymer ratio and the viscosity grade used. The results in the present investigation confirm that the release rate of the drug from the HPMC matrices is highly influenced by the drug/HPMC ratio and viscosity grade of the HPMC. Also, the effect of compression force and release media was found to be significant on the release profiles of isoniazid from HPMC matrix tablets. The release mechanism was found to be anomalous non-Fickian diffusion in all the cases. In the present investigation, a series of controlled release formulations of isoniazid were developed with different release rates and duration so that these formulations could further be assessed from the in vivo bioavailability studies. The formulations were found to be stable and reproducible.

  15. Controlled release of isoproturon, imidacloprid, and cyromazine from alginate-bentonite-activated carbon formulations.

    Science.gov (United States)

    Garrido-Herrera, F J; Gonzalez-Pradas, E; Fernandez-Pérez, M

    2006-12-27

    Different alginate-based systems of isoproturon, imidacloprid, and cyromazine have been investigated in order to obtain controlled release (CR) properties. The basic formulation [sodium alginate (1.50%), pesticide (0.30%), and water] was modified using different amounts of bentonite and activated carbon. The higher values of encapsulation efficiency corresponded to those formulations prepared with higher percentages of activated carbon, showing higher encapsulation efficiency values for isoproturon and imidacloprid than for cyromazine, which has a higher water solubility. The kinetic experiments of imidacloprid/isoproturon release in water have shown us that the release rate is higher in imidacloprid systems than in those prepared with isoproturon. Moreover, it can be deduced that the use of bentonite and/or activated carbon sorbents reduces the release rate of the isoproturon and imidacloprid in comparison with the technical product and with alginate formulation without modifying agents. The highest decrease in release rate corresponds to the formulations prepared with the highest percentage of activated carbon. The water uptake, permeability, and time taken for 50% of the active ingredient to be released into water, T50, were calculated to compare the formulations. On the basis of a parameter of an empirical equation used to fit the pesticide release data, the release of isoproturon and imidacloprid from the various formulations into water is controlled by a diffusion mechanism. The sorption capacity of the sorbents and the permeability of the formulations were the most important factors modulating pesticide release. Finally, a linear correlation of the T50 values and the content of activated carbon in formulations were obtained.

  16. The Experiment of Carbofuran Controlled Release Formulation Insecticide Application on Rice Plants

    International Nuclear Information System (INIS)

    Sulistyati, M.; Ulfa TS; Sofnie M Ch; Kuswadi AN

    2004-01-01

    Field test of carbofuran insecticide (2,3-dihydro-2,2-dimethyl-7-benzofuranyl-N-methylcarbamate) controlled release formulation on rice plants of IR-64 variety was carried out in Pusakanegara, West Java. This insecticide formulation was made by using the mixture of activated charcoal, tapioca, kaolin, Na-alginate as a filler matrix. Insecticide formulation was applied one week after transplanting. The observations were conducted on the number of tillers, damage level caused by Orseolia oryzae (Wood/Mason), Chilo suppressalis (Walker), and Cnaphalocrosis medinalis (Guen) on new young plants. The observation were carried out on three weeks after application of carbofuran insecticide formulation then every two weeks until harvest. The number of tillers were occurred at the treatments of controlled release formulation of 20kg/ha, 30kg/ha, and 40kg/ha dose rate on the third weeks, it was showed significant difference compared with commercial carbofuran, and the following weeks were no significant difference between the treatments. The attack of Orseolia oryzae was occurred at the treatments of controlled release formulation with dose rate of 30 kg/ha and 40 kg/ha on the seventh weeks, ninth weeks, and eleventh weeks, those attacks were significantly difference found compared with commercial carbofuran. The attack of Chilo suppressalis was occurred at the treatments of controlled release formulation of 40kg/ha dose rate on the fifth weeks, it was showed significant difference which was compared to untreated carbofuran. The attack of Cnaphalocrosis medinalis was occurred on the ninth weeks, three dose rate of controlled released formulation were showed significant differences which compared with commercial carbofuran and were showed 50% less than commercial carbofuran, while the grains dry weight were no significant difference between the treatments. (author)

  17. Formulation and evaluation of novel controlled release of topical pluronic lecithin organogel of mefenamic acid.

    Science.gov (United States)

    Jhawat, Vikas; Gupta, Sumeet; Saini, Vipin

    2016-11-01

    In the present study, pluronic lecithin based organogels (PLO gels) were formulated as topical carrier for controlled delivery of mefenamic acid. Ten organogel formulations were prepared by a method employing lecithin as lipophilic phase and pluronic F-127 as hydrophilic phase in varying concentrations to study various parameters using in vitro diffusion study and in vivo studies. All formulations were found to be off-white, homogenous, and reluctant to be washed easily and have pH value within the range of 5.56-5.80 which is nonirritant. Polymer concentration increased in formulations of F1 to F5 (lecithin) and F6 to F10 (pluronic) resulted in decrease of the gelation temperature, increase of viscosity and reduction of spreadability of gels having polymer tendency to form rigid 3D network. Organogels with higher viscosity were found to be more stable and retard the drug release from the gel. The formulations of F2 and F3 were selected for kinetic studies and stability studies, as they found to have all physical parameters within acceptable limits, highest percent drug content and exhibited highest drug release in eight hours. The order of drug release from various formulations was found to be F2 > F3 > F10 > F4 > F1 > F9 > F8 > F5 > F7 > F6. The optimized formulation F2 was found to follow zero order rate kinetics showing controlled release of the drug from the formulations. In vivo anti-inflammatory activity of optimized mefenamic acid organogel (F2) against a standard marketed preparation (Volini gel) was found satisfactory and significant.

  18. Pharmacokinetics and Pharmacodynamics of Tamsulosin in its Modified-Release and Oral Controlled Absorption System Formulations

    NARCIS (Netherlands)

    Franco-Salinas, Gabriela; de La Rosette, Jean J. M. C. H.; Michel, Martin C.

    2010-01-01

    Tamsulosin is an alpha(1)-adrenoceptor antagonist used for the treatment of lower urinary tract symptoms that are suggestive of benign prostatic hyperplasia. It is mostly used in a modified-release (M R) Formulation. but an oral controlled absorption system (OCAS) and a 'without-water' tablet

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

    Science.gov (United States)

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

    2013-01-01

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

  20. Formulation and evaluation of controlled release matrix mucoadhesive tablets of domperidone using Salvia plebeian gum

    Directory of Open Access Journals (Sweden)

    Gurpreet Arora

    2011-01-01

    Full Text Available The aim of study was to prepare controlled release matrix mucoadhesive tablets of domperidone using Salvia plebeian gum as natural polymer. Tablets were formulated by direct compression technology employing the natural polymer in different concentrations (5, 10, 15 and 20% w/w. The prepared batches were evaluated for drug assay, diameter, thickness, hardness and tensile strength, swelling index, mucoadhesive strength (using texture analyzer and subjected to in vitro drug release studies. Real-time stability studies were also conducted on prepared batches. In vitro drug release data were fitted in various release kinetic models for studying the mechanism of drug release. Tensile strength was found to increase from 0.808 ± 0.098 to 1.527 ± 0.10 mN/cm 2 and mucoadhesive strength increased from 13.673 ± 1.542 to 40.378 ± 2.345 N, with an increase in the polymer concentration from 5 to 20% (A1 to A4. Swelling index was reported to increase with both increase in the concentration of gum and the time duration. The in vitro drug release decreased from 97.76 to 83.4% (A1 to A4 with the increase in polymer concentration. The drug release from the matrix tablets was found to follow zero-order and Higuchi models, indicating the matrix-forming potential of natural polymer. The value of n was found to be between 0.5221 and 0.8992, indicating the involvement of more than one drug release mechanism from the formulation and possibly the combination of both diffusion and erosion. These research findings clearly indicate the potential of S. plebeian gum to be used as binder, release retardant and mucoadhesive natural material in tablet formulations.

  1. Multi-unit dosage formulations of theophylline for controlled release applications.

    Science.gov (United States)

    Uhumwangho, Michael U; Okor, Roland S

    2007-01-01

    The study was carried out to investigate the drug release profiles of multi-unit dosage formulations of theophylline consisting of both the fast and slow release components in a unit dose. The fast release component consisted of conventional granules of theophylline formed by mixing the drug powder with starch mucilage (20% w/v) while the slow release component consisted of wax granulations of theophylline formed by triturating the drug powder with a melted Carnauba wax (drug:wax ratio, 4:1). The granules were either filled into capsules or tabletted. In the study design, the drug release characteristics of the individual fast or slow release particles were first determined separately and then mixed in various proportions for the purpose of optimizing the drug release profiles. The evaluating parameters were the prompt release in the first 1 h (mp), the maximum release (m infinity) and the time to attain it (t infinity). Total drug content in each capsule or tablet was 300 mg and two of such were used in dissolution studies. The release kinetics and hence the release mechanism was confirmed by measuring the linear regression coefficient (R2 values) of the release data. The release kinetics was generally most consistent with the Higuchi square root of time relationship (R2 = 0.95). indicating a diffusion-controlled mechanism. The mp (mg) and t infinity (h) values for capsules and tablets of the conventional granules were (420 mg, 3 h) and (348 mg, 5 h), respectively, while for the capsules and tablets of the wax granulations mp and t infinity values were (228 mg, 9 h) and (156 mg, 12 h), respectively, indicating that a combination of wax granulation and tableting markedly retarded drug release. In the multi-unit dose formulations where the conventional and wax granulations were mixed in the ratios 2:1, 1:1 and 1:2 (conventional: matrix), the m infinity and t infinity values for the capsules were (378 mg, 6 h), (326 mg, 6 h) and (272 mg, 7 h), reSpectively. The

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

    Science.gov (United States)

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

    2018-04-01

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

  3. Light-triggerable formulations for the intracellular controlled release of biomolecules.

    Science.gov (United States)

    Lino, Miguel M; Ferreira, Lino

    2018-05-01

    New therapies based on the use of biomolecules [e.g., proteins, peptides, and non-coding (nc)RNAs] have emerged during the past few years. Given their instability, adverse effects, and limited ability to cross cell membranes, delivery systems are required to fully reveal their biological potential. Sophisticated nanoformulations responsive to light offer an excellent opportunity for the controlled release of these biomolecules, enabling the control of timing, duration, location, and dosage. In this review, we discuss the design principles for the delivery of biomolecules, in particular proteins and RNA-based therapeutics, by light-triggerable formulations. We further discuss the opportunities offered by these formulations in terms of endosomal escape, as well as their limitations. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Oral matrix tablet formulations for concomitant controlled release of anti-tubercular drugs: design and in vitro evaluations.

    Science.gov (United States)

    Hiremath, Praveen S; Saha, Ranendra N

    2008-10-01

    The aim of the present investigation was to develop controlled release (C.R.) matrix tablet formulations of rifampicin and isoniazid combination, to study the design parameters and to evaluate in vitro release characteristics. In the present study, a series of formulations were developed with different release rates and duration using hydrophilic polymers hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC). The duration of rifampicin and isoniazid release could be tailored by varying the polymer type, polymer ratio and processing techniques. Further, Eudragit L100-55 was incorporated in the matrix tablets to compensate for the pH-dependent release of rifampicin. Rifampicin was found to follow linear release profile with time from HPMC formulations. In case of formulations with HPC, there was an initial higher release in simulated gastric fluid (SGF) followed by zero order release profiles in simulated intestinal fluid (SIFsp) for rifampicin. The release of isoniazid was found to be predominantly by diffusion mechanism in case of HPMC formulations, and with HPC formulations release was due to combination of diffusion and erosion. The initial release was sufficiently higher for rifampicin from HPC thus ruling out the need to incorporate a separate loading dose. The initial release was sufficiently higher for isoniazid in all formulations. Thus, with the use of suitable polymer or polymer combinations and with the proper optimization of the processing techniques it was possible to design the C.R. formulations of rifampicin and isoniazid combination that could provide the sufficient initial release and release extension up to 24h for both the drugs despite of the wide variations in their physicochemical properties.

  5. Methods and predictors of tampering with a tamper-resistant controlled-release oxycodone formulation.

    Science.gov (United States)

    Peacock, Amy; Degenhardt, Louisa; Hordern, Antonia; Larance, Briony; Cama, Elena; White, Nancy; Kihas, Ivana; Bruno, Raimondo

    2015-12-01

    In April 2014, a tamper-resistant controlled-release oxycodone formulation was introduced into the Australian market. This study aimed to identify the level and methods of tampering with reformulated oxycodone, demographic and clinical characteristics of those who reported tampering with reformulated oxycodone, and perceived attractiveness of original and reformulated oxycodone for misuse (via tampering). A prospective cohort of 522 people who regularly tampered with pharmaceutical opioids and had tampered with the original oxycodone product in their lifetime completed two interviews before (January-March 2014: Wave 1) and after (May-August 2014: Wave 2) introduction of reformulated oxycodone. Four-fifths (81%) had tampered with the original oxycodone formulation in the month prior to Wave 1; use and attempted tampering with reformulated oxycodone amongst the sample was comparatively low at Wave 2 (29% and 19%, respectively). Reformulated oxycodone was primarily swallowed (15%), with low levels of recent successful injection (6%), chewing (2%), drinking/dissolving (1%), and smoking (word-of-mouth or the internet). Participants rated reformulated oxycodone as more difficult to prepare and inject and less pleasant to use compared to the original formulation. Current findings suggest that the introduction of the tamper-resistant product has been successful at reducing, although not necessarily eliminating, tampering with the controlled-release oxycodone formulation, with lower attractiveness for misuse. Appropriate, effective treatment options must be available with increasing availability of abuse-deterrent products, given the reduction of oxycodone tampering and use amongst a group with high rates of pharmaceutical opioid dependence. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Comparison of vascular alpha(1)-adrenoceptor antagonism of tamsulosin in oral controlled absorption system (OCAS) and modified release (MR) formulations

    NARCIS (Netherlands)

    Michel, M. C.; Korstanje, C.; Krauwinkel, W.; Shear, M.; Davies, J.; Quartel, A.

    2005-01-01

    Objective: The cardiovascular a-l-adrenoceptor (AR) antagonism of the new oral controlled absorption system (OCAS) 0.4 mg tablet formulation of tamsulosin was compared with that of the modified release (MR) 0.4 mg capsule formulation in healthy male volunteers after a single dose in the fasted

  7. Dry elixir formulations of dexibuprofen for controlled release and enhanced oral bioavailability.

    Science.gov (United States)

    Kim, Seo-Ryung; Kim, Jin-Ki; Park, Jeong-Sook; Kim, Chong-Kook

    2011-02-14

    The objective of this study was to achieve an optimal formulation of dexibuprofen dry elixir (DDE) for the improvement of dissolution rate and bioavailability. To control the release rate of dexibuprofen, Eudragit(®) RS was employed on the surface of DDE resulting in coated dexibuprofen dry elixir (CDDE). Physicochemical properties of DDE and CDDE such as particle size, SEM, DSC, and contents of dexibuprofen and ethanol were characterized. Pharmacokinetic parameters of dexibuprofen were evaluated in the rats after oral administration. The DDE and CDDE were spherical particles of 12 and 19 μm, respectively. The dexibuprofen and ethanol contents in the DDE were dependent on the amount of dextrin and maintained for 90 days. The dissolution rate and bioavailability of dexibuprofen loaded in dry elixir were increased compared with those of dexibuprofen powder. Moreover, coating DDE with Eudragit(®) RS retarded the dissolution rate of dexibuprofen from DDE without reducing the bioavailability. Our results suggest that CDDE may be potential oral dosage forms to control the release and to improve the bioavailability of poorly water-soluble dexibuprofen. Copyright © 2010 Elsevier B.V. All rights reserved.

  8. Residue and bio-efficacy evaluation of controlled release formulations of imidacloprid against pests in soybean (Glycine max).

    Science.gov (United States)

    Adak, Totan; Kumar, Jitendra; Dey, Debjani; Shakil, N A; Walia, S

    2012-01-01

    Controlled release (CR) formulations of imidacloprid (1-(6 chloro-3-pyridinyl methyl)-N- nitro imidazolidin-2- ylideneamine) were prepared using novel amphiphilic polymers synthesized from polyethylene glycol and aliphatic diacids employing encapsulation technique. The bioefficacy of the prepared CR formulations was evaluated against major pests of soybean, namely stem fly, Melanagromyza sojae Zehntmer and white fly, Bemisia tabaci Gennadius along with a commercial formulation at the experimental farm of Indian Agricultural Research Institute (IARI), New Delhi during kharif 2009 and 2010. Most of the CR formulations of imidacloprid gave significantly better control of the pests compare to its commercial formulations, however the CR formulations, Poly [poly (oxyethylene-1000)-oxy suberoyl] amphiphilic polymer based formulation performed better over others for controlling of both stem fly incidence and Yellow Mosaic Virus (YMV) infestation transmitted by white fly. Some of the developed CR formulations recorded higher yield over commercial formulation and control. Nodulation pattern of soybean was not affected due to treatment of CR and commercial formulations of imidacloprid. Also the residues of imidacloprid in seed and soil at harvest were not detectable for both CR and commercial formulations.

  9. Development of controlled release formulations of azadirachtin-A employing poly(ethylene glycol) based amphiphilic copolymers.

    Science.gov (United States)

    Kumar, Jitendra; Shakil, Najam A; Singh, Manish K; Singh, Mukesh K; Pandey, Alka; Pandey, Ravi P

    2010-05-01

    Controlled release (CR) formulations of azadirachtin-A, a bioactive constituent derived from the seed of Azadirachta indica A. Juss (Meliaceae), have been prepared using commercially available polyvinyl chloride, polyethylene glycol (PEG) and laboratory synthesized poly ethylene glycol-based amphiphilic copolymers. Copolymers of polyethylene glycol and various dimethyl esters, which self assemble into nano micellar aggregates in aqueous media, have been synthesized. The kinetics of azadirachtin-A, release in water from the different formulations was studied. Release from the commercial polyethylene glycol (PEG) formulation was faster than the other CR formulations. The rate of release of encapsulated azadirachtin-A from nano micellar aggregates is reduced by increasing the molecular weight of PEG. The diffusion exponent (n value) of azadirachtin-A, in water ranged from 0.47 to 1.18 in the tested formulations. The release was diffusion controlled with a half release time (t(1/2)) of 3.05 to 42.80 days in water from different matrices. The results suggest that depending upon the polymer matrix used, the application rate of azadirachtin-A can be optimized to achieve insect control at the desired level and period.

  10. Controlled-release, pegylation, liposomal formulations: new mechanisms in the delivery of injectable drugs.

    Science.gov (United States)

    Reddy, K R

    2000-01-01

    To review recent developments in novel injectable drug delivery mechanisms and outline the advantages and disadvantages of each. A MEDLINE (1995-January 2000) search using the terms polyethylene glycol, liposomes, polymers, polylactic acid, and controlled release was conducted. Additional references were identified by scanning bibliographies. All articles were considered for inclusion. Abstracts were included only if they were judged to add critical information not otherwise available in the medical literature. A number of systems that alter the delivery of injectable drugs have been developed in attempts to improve pharmacodynamic and pharmacokinetic properties of therapeutic agents. New drug delivery systems can be produced either through a change in formulation (e.g., continuous-release products, liposomes) or an addition to the drug molecule (e.g., pegylation). Potential advantages of new delivery mechanisms include an increased or prolonged duration of pharmacologic activity, a decrease in adverse effects, and increased patient compliance and quality of life. Injectable continuous-release systems deliver drugs in a controlled, predetermined fashion and are particularly appropriate when it is important to avoid large fluctuations in plasma drug concentrations. Encapsulating a drug within a liposome can produce a prolonged half-life and a shift of distribution toward tissues with increased capillary permeability (e.g., tumors, infected tissue). Pegylation provides a method for modification of therapeutic proteins to minimize many of the limitations (e.g., poor stability, short half-life, immunogenicity) associated with these agents. Pegylation of therapeutic proteins is an established process with new applications. However, not all pegylated proteins are alike, and each requires optimization on a protein-by-protein basis to derive maximum clinical benefit. The language required to describe each pegylated therapeutic protein must be more precise to accurately

  11. Studies on the controlled release pesticide formulation for pest control in cotton using isotope technique

    International Nuclear Information System (INIS)

    Jamil, F.F.; Qureshi, M.J.; Naqvi, S.H.M.

    1989-06-01

    Cotton plants were treated with 14C-carbofuran, cold carbofuran formulation and granular carbofuran pesticides. Sampling of soil and formulation pieces from the field was done at the end of experiment. Data for insect attack was also recorded throughout the crop season. Cotton plants treated with cold carbofuran formulation and granular carbofuran, their soil samples and residual cold formulation pieces were analyzed by HPLC. (A.B)

  12. Application Test OF Carbofuran Insecticide Controlled Release Formulation On Rice Plants Of Cilosari Variety Have Been Carried Out

    International Nuclear Information System (INIS)

    Sulisyati, M.; Ulfa, T.S. et all

    2000-01-01

    this formulation was made by using a mixture of activated charcoal, tapioca, kaolin, Na-alginate as filter matrix and the second formulation using zeolite with couted shelak. The observation were done on the damage level caused by Orseo;ia oryzae (wood/mason), Chilo suppressalis (walker), and cnaphalocrosis medinalis (Guen) on new young plants. The observation were done every two weeks after transplanting until harvest. Both formulation have the same results showed that new young plants on the early stage growth showed no differences among the treatments, then becoming more different between controlled release formulation and commercial formulation or untreated plants. The attack of orseolia oryzae could be observed on every week of the observation but only on the fifth weeks were significant difference found. The attack of Chilo suppressalis on the seventh week showed significant difference, while the attack of cnaphalocrosis medinalis appeared on the seventh and ninth weeks showing no differences

  13. Formulation and in vitro evaluation of mucoadhesive controlled release matrix tablets of flurbiprofen using response surface methodology

    Directory of Open Access Journals (Sweden)

    Ikrima Khalid

    2014-09-01

    Full Text Available The objective of the current study was to formulate mucoadhesive controlled release matrix tablets of flurbiprofen and to optimize its drug release profile and bioadhesion using response surface methodology. Tablets were prepared via a direct compression technique and evaluated for in vitro dissolution parameters and bioadhesive strength. A central composite design for two factors at five levels each was employed for the study. Carbopol 934 and sodium carboxymethylcellulose were taken as independent variables. Fourier transform infrared (FTIR spectroscopy studies were performed to observe the stability of the drug during direct compression and to check for a drug-polymer interaction. Various kinetic models were applied to evaluate drug release from the polymers. Contour and response surface plots were also drawn to portray the relationship between the independent and response variables. Mucoadhesive tablets of flurbiprofen exhibited non-Fickian drug release kinetics extending towards zero-order, with some formulations (F3, F8, and F9 reaching super case II transport, as the value of the release rate exponent (n varied between 0.584 and 1.104. Polynomial mathematical models, generated for various response variables, were found to be statistically significant (P<0.05. The study also helped to find the drug's optimum formulation with excellent bioadhesive strength. Suitable combinations of two polymers provided adequate release profile, while carbopol 934 produced more bioadhesion.

  14. Formulation and evaluation of controlled-release of telmisartan microspheres: In vitro/in vivo study

    Directory of Open Access Journals (Sweden)

    Praveen Kumar Gaur

    2014-12-01

    Full Text Available The aim of this work was to design a controlled-release drug-delivery system for the angiotensin-II receptor antagonist drug telmisartan. Telmisartan was encapsulated with different EUDRAGIT polymers by an emulsion solvent evaporation technique and the physicochemical properties of the formulations were characterized. Using a solvent evaporation method, white spherical microspheres with particle sizes of 629.9–792.1 μm were produced. The in vitro drug release was studied in three different pH media (pH 1.2 for 2 hours, pH 6.8 for 4 hours, and pH 7.4 for 18 hours. The formulations were then evaluated for their pharmacokinetic parameters. The entrapment efficiency of these microspheres was between 58.6% and 90.56%. The obtained microspheres showed good flow properties, which were evaluated in terms of angle of repose (15.29–26.32, bulk and tapped densities (0.37–0.53 and 0.43–0.64, respectively, Carr indices and Hausner ratio (12.94–19.14% and 1.14–1.23, respectively. No drug release was observed in the simulated gastric medium up to 2 hours; however, a change in pH from 1.2 to 6.8 increased the drug release. At pH 7.4, formulations with EUDRAGIT RS 100 showed a steady drug release. The microsphere formulation TMRS-3 (i.e., microspheres containing 2-mg telmisartan gave the highest Cmax value (6.8641 μg/mL at 6 hours, which was three times higher than Cmax for telmisartan oral suspension (TOS. Correspondingly, the area under the curve for TMRS-3 was 8.5 times higher than TOS. Particle size and drug release depended on the nature and content of polymer used. The drug release mechanism of the TMRS-3 formulation can be explained using the Higuchi model. The controlled release of drug from TMRS-3 also provides for higher plasma drug content and improved bioavailability.

  15. The effect of rainy and dry seasons upon the application of controlled release of dimethoate formulation on soybean plant

    International Nuclear Information System (INIS)

    Syahrir, Ulfa T.; Rahayu, Ali; Sulistyati, M.; Sofnie M CH; Sumatra, Made

    1998-01-01

    Controlled release formulation of dimethoate (o,o-dimetil s-(metil karbonil metil) fosforoditioate) was applicated on soybean varieties Willis, G-58, G-7, and G-55. The observation was made on damage leaves pod, and residue on seed and soil. The residue of dimethoate was determined using Gas Chromatography with Flame Photometric Detector. The result on rainy season that damage leaves pod and small and soybean grain 7% more than dry season. (authors)

  16. Effect of controlled release formulations of diuron and alachlor herbicides on the biochemical activity of agricultural soils.

    Science.gov (United States)

    Tejada, Manuel; Morillo, Esmeralda; Gómez, Isidoro; Madrid, Fernando; Undabeytia, Tomás

    2017-01-15

    The use of pesticides in agriculture is essential because it reduces the economic losses caused by pests, improving crop yields. In spite of the growing number of studies concerning the development and application of controlled release formulations (CRFs) of pesticides in agricultural soils, there are no studies about the effects of such formulations on the biochemical properties. In this paper the dissipation of diuron and alachlor in three agricultural soils for 127days, applied either as commercial or CRFs, was determined as well as their concomitant effects on soil biochemical properties. Dehydrogenase, urease, β-glucosidase and phosphatase activities were measured thought the experimental period. The application of alachlor as CRF increases its half-life time in soils, whereas no differences were noticed between diuron formulations due to its slower degradation, which takes longer than its release from the CRF. At the end of the incubation period, the enzymatic activities were the same after the use of diuron either as commercial or CRF, recovering the soil previous status. For alachlor formulations, no differences in enzymatic activities were again observed between both formulations, but their levels in soils were enhanced. Therefore, the use of these CRFs does not adversely affect the soil biochemical properties. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    Verma, Sanjay; Rudraraju, Varma S

    2015-02-01

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

  18. Aerosol-Assisted Fast Formulating Uniform Pharmaceutical Polymer Microparticles with Variable Properties toward pH-Sensitive Controlled Drug Release

    Directory of Open Access Journals (Sweden)

    Hong Lei

    2016-05-01

    Full Text Available Microencapsulation is highly attractive for oral drug delivery. Microparticles are a common form of drug carrier for this purpose. There is still a high demand on efficient methods to fabricate microparticles with uniform sizes and well-controlled particle properties. In this paper, uniform hydroxypropyl methylcellulose phthalate (HPMCP-based pharmaceutical microparticles loaded with either hydrophobic or hydrophilic model drugs have been directly formulated by using a unique aerosol technique, i.e., the microfluidic spray drying technology. A series of microparticles of controllable particle sizes, shapes, and structures are fabricated by tuning the solvent composition and drying temperature. It is found that a more volatile solvent and a higher drying temperature can result in fast evaporation rates to form microparticles of larger lateral size, more irregular shape, and denser matrix. The nature of the model drugs also plays an important role in determining particle properties. The drug release behaviors of the pharmaceutical microparticles are dependent on their structural properties and the nature of a specific drug, as well as sensitive to the pH value of the release medium. Most importantly, drugs in the microparticles obtained by using a more volatile solvent or a higher drying temperature can be well protected from degradation in harsh simulated gastric fluids due to the dense structures of the microparticles, while they can be fast-released in simulated intestinal fluids through particle dissolution. These pharmaceutical microparticles are potentially useful for site-specific (enteric delivery of orally-administered drugs.

  19. Formulation and Characterization of Sustained Release Floating ...

    African Journals Online (AJOL)

    Purpose: To formulate sustained release gastroretentive microballoons of metformin hydrochloride with the objective of improving its bioavailability. Methods: Microballoons of metformin hydrochloride were formulated by solvent evaporation and diffusion method using varying mixtures of hydroxypropyl methylcellulose ...

  20. Chitosan-carboxymethylcellulose based microcapsules formulation for controlled release of active ingredients from cosmeto textile

    Science.gov (United States)

    Roy, J. C.; Ferri, A.; Salaün, F.; Giraud, S.; Chen, G.; Jinping, G.

    2017-10-01

    Chitosan-based emulsions were prepared at pH from 4.0 to 6.0. The zeta potential and droplet size were monitored at different pH. Double emulsions (wateroil- water) were observed due to the stiff conformation of chitosan at pH 4.0. At pH 5.0, the emulsion droplets were the smallest (2.9 μm) of the experimental pH range. The emulsion droplets were well dispersed due to high surface charge of chitosan (for example, +50 mV at pH 5.5) in entire pH range. The emulsion was treated with carboxymethyl cellulose (CMC) for neutralizing the charged chitosan on the surface of emulsion droplets. Above 10×10-2 mg/ml of CMC, no change in zeta potential was observed indicating no more free chitosan existed after neutralization with CMC. The emulsion was then crosslinked with different amount of glutaraldehyde. Upon increasing the amount of glutaraldehyde, the amount of core content inside the microcapsule and encapsulation efficiency of shell materials decreased gradually. The Dynamic Scanning Calorimetry data confirmed no interaction between core and shell material in the microencapsulation process. The thermal degradation of the microcapsules was examined by thermogravimetric analysis and a gradual decrease in the degradation temperature upon increasing glutaraldehyde concentration was found. The tuning of CMC concentration can provide valuable information regarding stable emulsion and efficient microcapsule formulation via coacervation.

  1. Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS): A rapid test for enteric coating thickness and integrity of controlled release pellet formulations.

    Science.gov (United States)

    Alfarsi, Anas; Dillon, Amy; McSweeney, Seán; Krüse, Jacob; Griffin, Brendan; Devine, Ken; Sherry, Patricia; Henken, Stephan; Fitzpatrick, Stephen; Fitzpatrick, Dara

    2018-04-12

    There are no rapid dissolution based tests for determining coating thickness, integrity and drug concentration in controlled release pellets either during production or post-production. The manufacture of pellets requires several coating steps depending on the formulation. The sub-coating and enteric coating steps typically take up to six hours each followed by additional drying steps. Post production regulatory dissolution testing also takes up to six hours to determine if the batch can be released for commercial sale. The thickness of the enteric coating is a key factor that determines the release rate of the drug in the gastro-intestinal tract. Also, the amount of drug per unit mass decreases with increasing thickness of the enteric coating. In this study, the coating process is tracked from start to finish on an hourly basis by taking samples of pellets during production and testing those using BARDS (Broadband Acoustic Resonance Dissolution Spectroscopy). BARDS offers a rapid approach to characterising enteric coatings with measurements based on reproducible changes in the compressibility of a solvent due to the evolution of air during dissolution. This is monitored acoustically via associated changes in the frequency of induced acoustic resonances. A steady state acoustic lag time is associated with the disintegration of the enteric coatings in basic solution. This lag time is pH dependent and is indicative of the rate at which the coating layer dissolves. BARDS represents a possible future surrogate test for conventional USP dissolution testing as its data correlates directly with the thickness of the enteric coating, its integrity and also with the drug loading as validated by HPLC. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Review of levetiracetam, with a focus on the extended release formulation, as adjuvant therapy in controlling partial-onset seizures

    Directory of Open Access Journals (Sweden)

    Carol M Ulloa

    2009-09-01

    Full Text Available Carol M Ulloa, Allen Towfigh, Joseph SafdiehDepartment of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY, USAAbstract: Levetiracetam is a second-generation antiepileptic drug (AED with a unique chemical structure and mechanism of action. The extended release formulation of levetiracetam (Keppra XR™; UCB Pharma was recently approved by the Food and Drug Administration for adjunctive therapy in the treatment of partial-onset seizures in patients 16 years of age and older with epilepsy. This approval is based on a double-blind, randomized, placebo-controlled, multicenter, multinational trial. Levetiracetam XR allows for once-daily dosing, which may increase compliance and, given the relatively constant plasma concentrations, may minimize concentration-related adverse effects. Levetiracetam’s mode of action is not fully elucidated, but it has been found to target high-voltage, N-type calcium channels as well as the synaptic vesicle protein 2A (SV2A. Levetiracetam has nearly ideal pharmacokinetics. It is rapidly and almost completely absorbed after oral ingestion, is ‹10% protein-bound, demonstrates linear kinetics, is minimally metabolized through a pathway independent of the cytochrome P450 system, has no significant drug–drug interactions, and has a wide therapeutic index. The most common reported adverse events with levetiracetam XR were somnolence, irritability, dizziness, nausea, influenza, and nasopharyngitis. Levetiracetam XR provides an efficacious and well-tolerated treatment option for adjunctive therapy in the treatment of partial-onset seizures.Keywords: levetiracetam, partial-onset seizures, antiepileptic drugs

  3. TURVA-2012: Formulation of radionuclide release scenarios

    International Nuclear Information System (INIS)

    Marcos, Nuria; Hjerpe, Thomas; Snellman, Margit; Ikonen, Ari; Smith, Paul

    2014-01-01

    TURVA-2012 is Posiva's safety case in support of the Preliminary Safety Analysis Report (PSAR) and application for a construction licence for a repository for disposal of spent nuclear fuel at the Olkiluoto site in south-western Finland. This paper gives a summary of the scenarios and the methodology followed in formulating them as described in TURVA-2012: Formulation of Radionuclide Release Scenarios (Posiva, 2013). The scenarios are further analysed in TURVA-2012: Assessment of Radionuclide Release Scenarios for the Repository System and TURVA-2012: Biosphere Assessment (Posiva, 2012a, 2012b). The formulation of scenarios takes into account the safety functions of the main barriers of the repository system and the uncertainties in the features, events, and processes (FEP) that may affect the entire disposal system (i.e. repository system plus the surface environment) from the emplacement of the first canister until the far future. In the report TURVA-2012: Performance Assessment (2012d), the performance of the engineered and natural barriers has been assessed against the loads expected during the evolution of the repository system and the site. Uncertainties have been identified and these are taken into account in the formulation of radionuclide release scenarios. The uncertainties in the FEP and evolution of the surface environment are taken into account in formulating the surface environment scenarios used ultimately in estimating radiation exposure. Formulating radionuclide release scenarios for the repository system links the reports Performance Assessment and Assessment of Radionuclide Release Scenarios for the Repository System. The formulation of radionuclide release scenarios for the surface environment brings together biosphere description and the surface environment FEP and is the link to the assessment of the surface environment scenarios summarised in TURVA-2012: Biosphere Assessment. (authors)

  4. Eco-friendly PEG-based controlled release nano-formulations of Mancozeb: Synthesis and bioefficacy evaluation against phytopathogenic fungi Alternaria solani and Sclerotium rolfsii.

    Science.gov (United States)

    Majumder, Sujan; Shakil, Najam A; Kumar, Jitendra; Banerjee, Tirthankar; Sinha, Parimal; Singh, Braj B; Garg, Parul

    2016-12-01

    Controlled release (CR) nano-formulations of Mancozeb (manganese-zinc double salt of N,N-bisdithiocarbamic acid), a protective fungicide, have been prepared using laboratory-synthesized poly(ethylene glycols) (PEGs)-based functionalized amphiphilic copolymers without using any surfactants or external additives. The release kinetics of the developed Mancozeb CR formulations were studied and compared with that of commercially available 42% suspension concentrate and 75% wettable powder. Maximum amount of Mancozeb was released on 42nd day for PEG-600 and octyl chain, PEG-1000 and octyl chain, and PEG-600 and hexadecyl chain, on 35th day for PEG-1000 and hexadecyl chain, on 28th day for PEG-1500 and octyl chain, PEG-2000 and octyl chain, PEG-1500 and hexadecyl chain, and PEG-2000 and hexadecyl chain in comparison to both commercial formulations (15th day). The diffusion exponent (n value) of Mancozeb in water ranged from 0.42 to 0.62 in tested formulations. The half-release (t 1/2 ) values ranged from 17.35 to 35.14 days, and the period of optimum availability of Mancozeb ranged from 18.54 to 35.42 days. Further, the in vitro bioefficacy evaluation of developed formulations was done against plant pathogenic fungi Alternaria solani and Sclerotium rolfsii by poison food technique. Effective dose for 50% inhibition in mgL -1 (ED 50 ) values of developed formulations varied from 1.31 to 2.79 mg L -1 for A. solani, and 1.60 to 3.14 mg L -1 for S. rolfsii. The present methodology is simple, economical, and eco-friendly for the development of environment-friendly CR formulations of Mancozeb. These formulations can be used to optimize the release of Mancozeb to achieve disease control for the desired period depending upon the matrix of the polymer used. Importantly, the maximum amount of active ingredient remains available for a reasonable period after application. In addition, the developed CR formulations were found to be suitable for fungicidal applications, allowing

  5. Controlled-release of Bacillus thurigiensis formulations encapsulated in light-resistant colloidosomal microcapsules for the management of lepidopteran pests of Brassica crops.

    Science.gov (United States)

    Bashir, Oumar; Claverie, Jerome P; Lemoyne, Pierre; Vincent, Charles

    2016-01-01

    Bacillus thuringiensis ( B. t. ) based formulations have been widely used to control lepidopteran pests in agriculture and forestry. One of their weaknesses is their short residual activity when sprayed in the field. Using Pickering emulsions, mixtures of spores and crystals from three B. t. serovars were successfully encapsulated in colloïdosomal microparticles (50 μm) using innocuous chemicals (acrylic particles, sunflower oil, iron oxide nanoparticles, ethanol and water). A pH trigger mechanism was incorporated within the particles so that B. t. release occurred only at pH > 8.5 which corresponds to the midgut pH of the target pests. Laboratory assays performed on Trichoplusia ni ( T. ni ) larvae demonstrated that the microencapsulation process did not impair B. t. bioactivity. The best formulations were field-tested on three key lepidopteran pests that attack Brassica crops, i.e., the imported cabbageworm, the cabbage looper and the diamondback moth. After 12 days, the mean number of larvae was significantly lower in microencapsulated formulations than in a commercial B. t. formulation, and the effect of microencapsulated formulations was comparable to a chemical pesticide (lambda-cyhalothrin). Therefore, colloïdosomal microcapsule formulations successfully extend the bioactivity of B. t. for the management of lepidopteran pests of Brassica crops.

  6. Controlled-release of Bacillus thurigiensis formulations encapsulated in light-resistant colloidosomal microcapsules for the management of lepidopteran pests of Brassica crops

    Directory of Open Access Journals (Sweden)

    Oumar Bashir

    2016-10-01

    Full Text Available Bacillus thuringiensis (B. t. based formulations have been widely used to control lepidopteran pests in agriculture and forestry. One of their weaknesses is their short residual activity when sprayed in the field. Using Pickering emulsions, mixtures of spores and crystals from three B. t. serovars were successfully encapsulated in colloïdosomal microparticles (50 μm using innocuous chemicals (acrylic particles, sunflower oil, iron oxide nanoparticles, ethanol and water. A pH trigger mechanism was incorporated within the particles so that B. t. release occurred only at pH > 8.5 which corresponds to the midgut pH of the target pests. Laboratory assays performed on Trichoplusia ni (T. ni larvae demonstrated that the microencapsulation process did not impair B. t. bioactivity. The best formulations were field-tested on three key lepidopteran pests that attack Brassica crops, i.e., the imported cabbageworm, the cabbage looper and the diamondback moth. After 12 days, the mean number of larvae was significantly lower in microencapsulated formulations than in a commercial B. t. formulation, and the effect of microencapsulated formulations was comparable to a chemical pesticide (lambda-cyhalothrin. Therefore, colloïdosomal microcapsule formulations successfully extend the bioactivity of B. t. for the management of lepidopteran pests of Brassica crops.

  7. Formulation and in-vitro evaluation of directly compressed controlled release matrices of Losartan Potassium using Ethocel Grade 100 as rate retarding agent.

    Science.gov (United States)

    Khan, Kamran Ahmad; Khan, Gul Majid; Zeeshan Danish, Muhammad; Akhlaq; Khan, Haroon; Rehman, Fazal; Mehsud, Saifullah

    2015-12-30

    Current study was aimed to develop 200mg controlled release matrix tablets of Losartan Potassium using Ethocel 100 Premium and Ethocel 100 FP Premium as rate controlling polymer. In-vitro studies were performed according to USP Method-I in phosphate buffer (PH 6.8) using pharma test dissolution apparatus. The temperature of the dissolution medium was kept constant at 37±0.5°C at 100rpm. Flow properties, physical quality control tests, effect of polymer size and drug-to-polymers ratios were studied using different kinetics models such as 1st-order, zero-order, Hixon Crowell model, Highuchi model and Power law. Difference factor f1 and similarity factor f2 were applied for dissolution profiles against Cardaktin® tablets used as a reference formulation. The matrices with polymer ethocel 100 FP Premiums have prolonged the drug release rate as compared to polymer ethocel 100 Premiums. The n values matrices with polymer ethocel grade 100 ranged from 0.603 to 0.857 indicating that the drug release occurred by anomalous non fickian diffusion kinetics while then value of reference Cardaktin® tablet was measured as 0.125 indicating that these tablets do not follow power law. The dissolution profiles of test formulations were different than that of reference Cardaktin®. This suggests the polymer Ethocel grade 100 can be proficiently incorporated in fabrication and development of once a day controlled release matrix tablets. Copyright © 2015. Published by Elsevier B.V.

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

    Science.gov (United States)

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

    2016-07-25

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

  9. Novel electrospun nanofibrous matrices prepared from poly(lactic acid)/poly(butylene adipate) blends for controlled release formulations of an anti-rheumatoid agent.

    Science.gov (United States)

    Siafaka, Panoraia I; Barmbalexis, Panagiotis; Bikiaris, Dimitrios N

    2016-06-10

    In the present work, a series of novel formulations consisting of poly(lactic acid)/poly(butylene adipate) (PLA/PBAd) electrospun blends was examined as controlled release matrices for Leflunomide's active metabolite, Teriflunomide (TFL). The mixtures were prepared using different ratios of PLA and PBAd in order to produce nanofibrous matrices with different characteristics. Miscibility studies of the blended polymeric fibers were performed through differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). Hydrolytic degradation in the prepared fibers was evaluated at 37°C using a phosphate buffered saline solution. Different concentrations of (TFL) (5, 10, 15wt.%) were incorporated into nanofibers for examining the drug release behavior in simulated body fluids (SBF), at 37°C. The drug-loaded nanofibrous formulations were further characterized by Fourier Transform Infrared Spectroscopy (FTIR) spectroscopy, DSC and XRD. Gel permeation chromatography (GPC) analysis was used to evaluate the mechanism of TFL release. Artificial neural networks (ANN) and multi-linear-regression (MLR) models were used to evaluate the effect of % content of PBAd (X1) and TFL (X2) on an initial burst effect and a dissolution behavior. It was found that PLA/PBAd nanofibers have different diameters depending on the ratio of used polyesters and added drug. TFL was incorporated in an amorphous form inside the polymeric nanofibers. In vitro release studies reveal that a drug release behavior is correlated with the size of the nanofibers, drug loading and matrix degradation after a specific time. ANN dissolution modeling showed increased correlation efficacy compared to MLR. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Formulation of Sustained-Release Diltiazem Matrix Tablets Using ...

    African Journals Online (AJOL)

    Erah

    surface, their drug release behavior appears simple, but ... matrix material for the formulation of ..... formulation F5 (,) and reference formulations. ( , □). 0. 50. 100. 150. 200. 250. 300. 0. 3. 6 .... Coviello T, Matricardi P, Marianecci C, Alhaique F.

  11. Effect of a controlled-release drug delivery system made of oleanolic acid formulated into multivesicular liposomes on hepatocellular carcinoma in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Luo YL

    2016-07-01

    Full Text Available Yuling Luo, Zhongbing Liu, Xiaoqin Zhang, Juan Huang, Xin Yu, Jinwei Li, Dan Xiong, Xiaoduan Sun, Zhirong Zhong Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan,People’s Republic of ChinaAbstract: The aim of the present study was to develop a novel dosage form of multivesicular liposomes for oleanolic acid (OA to overcome its poor solubility, prolong therapeutic drug levels in the blood, and enhance the antitumor effect on hepatocellular carcinoma. OA-encapsulated multivesicular liposomes (OA-MVLs were prepared by a double-emulsion method, and the formulation was optimized by the central composite design. The morphology, particle size, and drug-loading efficiency of OA-MVLs were investigated. Furthermore, OA-MVLs were also characterized both in vitro and in vivo. The results showed that OA-MVLs were spherical particles with an average particle size of 11.57 µm and an encapsulation efficiency of 82.3%±0.61%. OA-MVLs exhibited a sustained-release pattern in vitro, which was fitted to Ritger–Peppas equation. OA-MVLs inhibited the growth of human HepG2 cells which was confirmed by the MTT assay and fluorescence microscopy detection. The in vivo release of OA from OA-MVLs exhibited a sustained manner, indicating a longer circulation time compared to OA solution. The in vivo toxicity study indicated that medium-dose OA-MVLs exerted no toxic effect on the hosts. Importantly, OA-MVLs suppressed the growth of murine H22 hepatoma and prolonged the survival of tumor-bearing mice. In conclusion, the poorly soluble OA could be encapsulated into MVLs to form a novel controlled-release drug delivery system. The present study may hold promise for OA-MVLs as a new dosage form for sustained-release drug delivery in cancer therapy.Keywords: oleanolic acid, multivesicular liposomes, murine hepatocellular carcinoma, controlled release, cancer therapy

  12. Pharmacokinetic comparison of controlled-release and immediate-release oral formulations of simvastatin in healthy Korean subjects: a randomized, open-label, parallel-group, single- and multiple-dose study.

    Science.gov (United States)

    Jang, Seong Bok; Lee, Yoon Jung; Lim, Lay Ahyoung; Park, Kyung-Mi; Kwon, Bong-Ju; Woo, Jong Soo; Kim, Yong-Il; Park, Min Soo; Kim, Kyung Hwan; Park, Kyungsoo

    2010-01-01

    A controlled-release (CR) formulation of simvastatin was recently developed in Korea. The formulation is expected to yield a lower C(max) and similar AUC values compared with the immediate-release (IR) formulation. The goal of this study was to compare the pharmacokinetics of the new CR formulation and an IR formulation of simvastatin after single- and multiple-dose administration in healthy Korean subjects. This study was developed as part of a product development project at the request of the Korean regulatory agency. This was a randomized, open-label, parallelgroup, 2-part study. Eligible subjects were healthy male or female volunteers between the ages of 19 and 55 years and within 20% of their ideal weight. In part I, each subject received a single dose of the CR or IR formulation of simvastatin 40 mg orally (20 mg x 2 tablets) after fasting. In part II, each subject received the same dose of the CR or IR formulation for 8 consecutive days. Blood samples were obtained for 48 hours after the dose in part I and after the first and the last dose in part II. Pharmacokinetic parameters were determined for both simvastatin (the inactive prodrug) and simvastatin acid (the active moiety). An adverse event (AE) was defined as any unfavorable sign (including an abnormal laboratory finding) or symptom, regardless of whether it had a causal relationship with the study medication. Serious AEs were defined as any events that are considered life threatening, require hospitalization or prolongation of existing hospitalization, cause persistent or significant disability or incapacity, or result in congenital abnormality, birth defect, or death. AEs were determined based on patient interviews and physical examinations. Twenty-four healthy subjects (17 men, 7 women; mean [SD] age, 29 [7] years; age range, 22-50 years) were enrolled in part I, and 29 subjects (17 men, 12 women; mean age, 33 [9] years; age range, 19-55 years) were enrolled in part II. For simvastatin acid, C

  13. Extended release formulations for local anaesthetic agents.

    Science.gov (United States)

    Weiniger, C F; Golovanevski, L; Domb, A J; Ickowicz, D

    2012-08-01

    Systemic toxicity through overdose of local anaesthetic agents is a real concern. By encapsulating local anaesthetics in biodegradable carriers to produce a system for prolonged release, their duration of action can be extended. This encapsulation should also improve the safety profile of the local anaesthetic as it is released at a slower rate. Work with naturally occurring local anaestheticss has also shown promise in the area of reducing systemic and neurotoxicity. Extended duration local anaesthetic formulations in current development or clinical use include liposomes, hydrophobic based polymer particles such as Poly(lactic-co-glycolic acid) microspheres, pasty injectable and solid polymers like Poly(sebacic-co-ricinoleic acid) P(SA:RA) and their combination with synthetic and natural local anaesthetic. Their duration of action, rationale and limitations are reviewed. Direct comparison of the different agents is limited by their chemical properties, the drug doses encapsulated and the details of in vivo models described. Anaesthesia © 2012 The Association of Anaesthetists of Great Britain and Ireland.

  14. Formulation of porous poly(lactic-co-glycolic acid) microparticles by electrospray deposition method for controlled drug release

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Shilei; Wang, Yazhou; Wang, Bochu, E-mail: wangbc2000@126.com; Deng, Jia; Zhu, Liancai; Cao, Yang

    2014-06-01

    In the present study, the electrospray deposition was successfully applied to prepare the porous poly(lactic-co-glycolic acid) (PLGA) microparticles by one-step processing. Metronidazole was selected as the model drug. The porous PLGA microparticles had high drug loading and low density, and the porous structure can be observed by scanning electron microscope (SEM) and transmission electron microscopy (TEM). The production time has been shortened considerably compared with that of the traditional multi-emulsion method. In addition, no chemical reaction occurred between the drug and polymer in the preparation of porous microparticles, and the crystal structure of drug did not change after entrapment into the porous microparticles. The porous microparticles showed a sustained release in the simulated gastric fluid, and the release followed non-Fickian or case II transport. Furthermore, porous microparticles showed a slight cytotoxicity in vitro. The results indicated that electrospray deposition is a good technique for preparation of porous microparticles, and the low-density porous PLGA microparticles has a potential for the development of gastroretentive systems or for pulmonary drug delivery. - Highlights: • The porous PLGA microparticles were successfully prepared by the electrospray deposition method at one step. • The porous microparticles had high loading capacity and low density. • The microparticle showed a sustained release in the simulated gastric liquid. • The microparticles showed a slight cytotoxicity in vitro.

  15. Formulation of porous poly(lactic-co-glycolic acid) microparticles by electrospray deposition method for controlled drug release

    International Nuclear Information System (INIS)

    Hao, Shilei; Wang, Yazhou; Wang, Bochu; Deng, Jia; Zhu, Liancai; Cao, Yang

    2014-01-01

    In the present study, the electrospray deposition was successfully applied to prepare the porous poly(lactic-co-glycolic acid) (PLGA) microparticles by one-step processing. Metronidazole was selected as the model drug. The porous PLGA microparticles had high drug loading and low density, and the porous structure can be observed by scanning electron microscope (SEM) and transmission electron microscopy (TEM). The production time has been shortened considerably compared with that of the traditional multi-emulsion method. In addition, no chemical reaction occurred between the drug and polymer in the preparation of porous microparticles, and the crystal structure of drug did not change after entrapment into the porous microparticles. The porous microparticles showed a sustained release in the simulated gastric fluid, and the release followed non-Fickian or case II transport. Furthermore, porous microparticles showed a slight cytotoxicity in vitro. The results indicated that electrospray deposition is a good technique for preparation of porous microparticles, and the low-density porous PLGA microparticles has a potential for the development of gastroretentive systems or for pulmonary drug delivery. - Highlights: • The porous PLGA microparticles were successfully prepared by the electrospray deposition method at one step. • The porous microparticles had high loading capacity and low density. • The microparticle showed a sustained release in the simulated gastric liquid. • The microparticles showed a slight cytotoxicity in vitro

  16. Predicting release and transport of pesticides from a granular formulation during unsaturated diffusion in porous media

    DEFF Research Database (Denmark)

    Paradelo Pérez, Marcos; Soto-Gómez, Diego; Pérez-Rodrígez, Paula

    2014-01-01

    The release and transport of active ingredients (AIs) from controlled-release formulations (CRFs) have potential to reduce groundwater pesticide pollution. These formulations have a major effect on the release rate and subsequent transport to groundwater. Therefore the influence of CRFs should be...

  17. Cetirizine release from cyclodextrin formulated compressed chewing gum

    DEFF Research Database (Denmark)

    Stojanov, Mladen; Larsen, Kim Lambertsen

    2012-01-01

    release patterns, but with variations in the total amount released. Chewing gum formulated with cetirizine alone, demonstrated a release of 75% after 8 min of chewing. The presence of CDs resulted in increased cetirizine release. The analysis of variance (ANOVA) demonstrated that parameters with the most...... the statistical analysis (ANOVA) demonstrated significance in the release (P

  18. Preparation and characterization of Slow Release Formulations of ...

    African Journals Online (AJOL)

    alginate beads and characterize the resulting slow release formulations (SRFs) using scanning electron microscopy (SEM), and Fourier Transform infrared spectroscopy (FTIR). Two sets of formulations were made by extrusion into 0.25 M calcium ...

  19. Formulation and Release Characteristics of Zidovudine- Loaded ...

    African Journals Online (AJOL)

    Drug Delivery Research Unit, Department of Pharmaceutics, Faculty of ... The results show that drug content has influence on drug release from the SLMs, but not ... poor bioavailability [1, 2]. ..... et al [21] this initial in vitro burst release could be.

  20. Continuous-release formulation for environmental doses to moving receptors

    International Nuclear Information System (INIS)

    Piepho, M.G.

    1981-01-01

    Atmospheric dispersion models frequently assume a puff release or several puff releases, each of which are described separately. A dispersion model should better describe a continuous release as more puffs are assumed, but the computational cost and bookkeeping difficulty increases with additional puffs. A new formulism is derived in this work which replaces the puff approximation. With the new continuous release formulation, radioactive dose calculations to moving receptors are more accurately calculated without any great additional computation. There are several advantages of a continuous release formulation. With this formulation, a dose rate to a moving receptor is calculated as a function of time. The dose-rate will increase (decrease) as the bulk of the release gets closer (farther) to (from) the receptor which is at position x(t), y(t). The receptor may follow any x, y trajectory as a function of time, and the dose rate will be calculated along the path

  1. Preparation and Characterization of Azadirachtin Alginate-Biosorbent Based Formulations: Water Release Kinetics and Photodegradation Study.

    Science.gov (United States)

    Flores-Céspedes, Francisco; Martínez-Domínguez, Gerardo P; Villafranca-Sánchez, Matilde; Fernández-Pérez, Manuel

    2015-09-30

    The botanical insecticide azadirachtin was incorporated in alginate-based granules to obtain controlled release formulations (CRFs). The basic formulation [sodium alginate (1.47%) - azadirachtin (0.28%) - water] was modified by the addition of biosorbents, obtaining homogeneous hybrid hydrogels with high azadirachtin entrapment efficiency. The effect on azadirachtin release rate caused by the incorporation of biosorbents such as lignin, humic acid, and olive pomace in alginate formulation was studied by immersion of the granules in water under static conditions. The addition of the biosorbents to the basic alginate formulation reduces the rate of release because the lignin-based formulation produces a slower release. Photodegradation experiments showed the potential of the prepared formulations in protecting azadirachtin against simulated sunlight, thus improving its stability. The results showed that formulation prepared with lignin provided extended protection. Therefore, this study provides a new procedure to encapsulate the botanical insecticide azadirachtin, improving its delivery and photostability.

  2. Release Properties of Paracetamol Granulationa Formulated with ...

    African Journals Online (AJOL)

    Theobroma cacao gum, TCG was derived as a dry powder from fresh fruits of Theobroma cacao. Various granulations of paracetamol were prepared with TCG at the concentrations of 0.5 – 4% w/w. Similar formulations were prepared using sodium carboxymethyl cellulose, SCMC and acacia gums as standards. In each ...

  3. Formulation and Study of Some Controlled Release Tablets with Pentoxifylline Based on Hydroxypropylcellulose Matrix Obtained by Wet Granulation Method with PEG 6000

    Directory of Open Access Journals (Sweden)

    Gabriel Hancu

    2011-01-01

    Full Text Available In this work three formulations of modified release tablets
    containing pentoxifylline 400 mg/tablet were obtained. Hydroxypropylcellulose (HPC in di®erent ratios was used as hydrophilic matrix agent. The pentoxifylline inclusion in the matrix has been carried out by water granulation, using PEG 6000 as binder. Tablets were obtained with a single station
    tablet machine (Korsch, using standard pressure, and obtaining tablets with 13 mm diameter, 800 mg weight and 400 mg pentoxifylline per tablet. The weight uniformity, friability, hardness, thickness and disintegration of tablets were determined according to the stipulations of the 2001 Supplement of the Romanian Pharmacopoeia Xth edition. The experimental formulations with 400 mg pentoxifylline/tablet were studied by comparing them to the industrial reference product, Trental 400 mg (Aventis Pharma and in according
    to the stipulations of Romanian Pharmacopoeia Xth edition, USP 27 and European Pharmacopoeia 5th edition. Every determination was performed using 20 tablets. We followed the comparison between dissolution profiles of slow release tablets containing pentoxifylline based on hydrophilic matrix. The dissolution studies were performed using the method from USP 24, using the paddle apparatus, and water as medium of dissolution at 37+/-0,5 Celsius degrees, at a rotation speed of 50 rpm. The determination was performed by spectrofotometric as say in UV at 274 nm. It was noticeable that regarding the weight uniformity, friability, hardness, thickness and disintegration the proposed formulations are comparable with the industrial reference product (Trental, 400 mg and are in agreement with the stipulations of the Romanian Pharmacopoeia Xth edition and European Pharmacopoeia 5th edition. The analysis of dissolution profiles showed that all formulations exhibit slow release.

  4. Continuous production of controlled release dosage forms based on hot-melt extruded gum arabic: Formulation development, in vitro characterization and evaluation of potential application fields.

    Science.gov (United States)

    Kipping, Thomas; Rein, Hubert

    2016-01-30

    Controlled release matrices based on gum arabic are prepared by applying a continuous hot-melt extrusion technology: the pre-mixture consisting of gum arabic and the incorporated API is plasticized by a co-rotating twin-screw extruder, an intermediate strand is formed by a round nozzle. Single dosed matrices are prepared by cutting the semi elastic strand with a rotary fly cutter. Paracetamol and phenazone are used as model drug substances. High drug loadings up to 70% can be realized. Matrices are characterized concerning their crystalline structure, in vitro dissolution, disintegration time and various physical parameters including glass transition temperature (Tg). Release characteristic behavior is mainly influenced by erosion of the matrices. At higher drug loadings also diffusion based transport gain importance. The solubility of the API shows an influence on the erosion rate of the matrix and should therefore be considered during formulation development. Tg is mainly influenced by the solubility of the API in the surrounding matrix. High soluble phenazone shows a decrease, whereas paracetamol addition has nearly no influence on the Tg of the polymeric system. Activation energy (EA) of the glass transition is determined via dynamic mechanical analysis. The addition of APIs leads to a reduction of EA indicating an increased molecular movement at Tg region compared to placebo extrudates. X-ray diffraction is used to determine the crystalline state of the extruded matrices and interaction between matrix and incorporated APIs. The production of thin layer matrices is an interesting option to provide a fast drug delivery to the oral cavity. High mechanical strength combined with fast disintegration times can be a great advantage for the development of oro-dispersible tablets. A great benefit of the evaluated processing technology is the simple adaption of the final dose by varying either the cutting length or the diameter of the nozzle resulting in a cost

  5. Investigation of the effects of certain formulation factors on release ...

    African Journals Online (AJOL)

    Objective: To study the effects of three formulation variables (PVP, stearic acid and Avicel PH101) on disintegration time and release properties of paracetamol tablets using a 23 factorial experimental design. Methodology: Three formulation variables; Polyvinyl pyrrolidone (factor A), Stearic acid (factor B) and Avicel PH 101 ...

  6. Formulation of Sustained-Release Diltiazem Matrix Tablets Using ...

    African Journals Online (AJOL)

    Formulation of Sustained-Release Diltiazem Matrix Tablets Using Hydrophilic Gum Blends. A Moin, H.G Shivakumar. Abstract. Purpose: To develop sustained release matrix tablets of diltiazem hydrochloride (DTZ) using karaya gum (K) alone or in combination with locust bean gum (LB) and hydroxypropyl methylcellulose ...

  7. Formulation of Extended-Release Metformin Hydrochloride Matrix ...

    African Journals Online (AJOL)

    Methods: Various metformin hydrochloride formulations containing a hydrophobic carrier (stearic acid) and a hydrophilic polymer (polyethylene oxide) were prepared using a 32 factorial design. ... The release data were subjected to various release kinetic models and also compared with those of a commercial brand.

  8. Intermediate release formulations of diclofenac potassium tablets for IVIVC.

    Science.gov (United States)

    Ali, Huma; Shoaib, Muhammad Harris; Zafar, Farya; Bushra, Rabia; Yasmin, Riffat; Siddiqui, Shehla; Alam, Zafar M

    2016-07-01

    In recent days response surface methodology (RSM) has widely been applied for development and optimization of cost effective formulations with required quality. Study comprised of three steps including micromeritic comparison of different powder blends of placebo and diclofenac potassium (DP), formulation designing with CCRD (Design Expert, version 7.0.0), and stability testing of selected formulations by using R Gui. Ten formulations (F11-F20) were developed using microcrystalline cellulose (Avicel PH-102) (X1) (13-72%), methocel K15M (X2) (6.59-23.4%) and magnesium stearate (X3) (1.32-4.68%), while responses were % friability and % drug release. Blending rate constant was determined at 3, 6, 9 and 12 minutes. The results of physicochemical parameters were found within acceptable limits. After in vitro testing at pH 1.2, pH 4.5 and pH 6.8, mechanism of drug release, kinetic analysis and statistical evaluation were carried out by model - independent, model-dependent and one-way ANOVA methods. Most formulations followed zero order kinetics at higher pH. Fickian release (0.326 ≤ n ≤0.449) was observed with β greater than 0.5 and less than 1. ANOVA indicated no significant variation within and between formulations as p-values were found to be > 0.05.

  9. Formulation and characterization of modified release tablets containing isoniazid using swellable polymers.

    Science.gov (United States)

    Akhtar, M F; Rabbani, M; Sharif, A; Akhtar, B; Saleem, A; Murtaza, G

    2011-01-01

    The aim of this work was to develop swellable modified release (MR) isoniazid tablets using different combinations of polyvinyl acetate (PVAc) and sodium-carboxymethylcellulose (Na-CMC). Granules were prepared by moist granulation technique and then compressed into tablets. In vitro release studies for 12 hr were carried out in dissolution media of varying pH i.e. pH 1.2, 4.5, 7.0 and 7.5. Tablets of all formulations were found to be of good physical quality with respect to appearance (width and thickness), content uniformity, hardness, weight variation and friability. In vitro release data showed that increasing total polymer content resulted in more retarding effect. Formulation with 35% polymer content exhibited zero order release profile and it released 35% of the drug in first hr, later on, controlled drug release was observed upto the 12(th) hour. Formulations with PVAc to Na-CMC ratio 20:80 exhibited zero order release pattern at levels of studied concentrations, which suggested that this combination can be used to formulate zero order release tablets of water soluble drugs like isoniazid. Korsmeyer-Peppas modeling of drug release showed that non-Fickian transport is the primary mechanism of isoniazid release from PVAc and Na-CMC based tablets. The value of mean dissolution time decreased with the increase in the release rate of drug clearly showing the retarding behavior of the swellable polymers. The application of a mixture of PVAc to Na-CMC in a specific ratio may be feasible to formulate zero order release tablets of water soluble drugs like isoniazid.

  10. Mydriatics release from solid and semi-solid ophthalmic formulations using different in vitro methods.

    Science.gov (United States)

    Pescina, Silvia; Macaluso, Claudio; Gioia, Gloria Antonia; Padula, Cristina; Santi, Patrizia; Nicoli, Sara

    2017-09-01

    The aim of the present paper was the development of semi-solid (hydrogels) and solid (film) ophthalmic formulations for the controlled release of two mydriatics: phenylephrine and tropicamide. The formulations - based on polyvinylalcohol and hyaluronic acid - were characterized, and release studies were performed with three different in vitro set-ups, i.e. Franz-type diffusion cell, vial method and inclined plane; for comparison, a solution and a commercial insert, both clinically used to induce mydriasis, were evaluated. Both gels and film allowed for a controlled release of drugs, appearing a useful alternative for mydriatics administration. However, the release kinetic was significantly influenced by the method used, highlighting the need for optimization and standardization of in vitro models for the evaluation of drug release from ophthalmic dosage forms.

  11. The influence of polymeric excipients on the process of pharmaceutical availability of therapeutic agents from a model drug form. Part I. In formulations with controlled disintegration and release time.

    Science.gov (United States)

    Nachajski, Michal Jakub; Zgoda, Marian Mikołaj

    2010-01-01

    Pre-formulation research was conducted on the application of Ex. Echinaceae aq. siccum in the production of a quickly disintegrating suspension tablet, a lozenge with kariostatic sugar alcohols (mannitol, sorbitol), and, above all, a solid drug form with controlled release of therapeutic agents included in the extract. Morphological parameters of tablets obtained in the course of experiment were estimated and the profiles of the release (diffusion) ofhydrophilic therapeutic agents into model receptor fluids with varying values of osmolarity (0.1 mol HCl approximately 200 mOsm/l, hypotonic hydrating fluid approximately 143 mOsm/l, and compensatory paediatric fluid approximately 272 mOsm/l) were examined. The study focused on the technological problem of determining the effect of hydrogel Carbopol structure on the ordering of diffusion ofhydrophilic therapeutic agents from a model drug form (a tablet) into model fluids with variable osmolarity.

  12. An innovative method for the preparation of high API-loaded hollow spherical granules for use in controlled-release formulation.

    Science.gov (United States)

    Asada, Takumi; Kobiki, Mitsuaki; Ochiai, Yasushi; Iwao, Yasunori; Itai, Shigeru

    2017-05-15

    The aim of this study was to prepare controlled-release (CR) granules with suitable particle strength, flowability, particle size distribution (PSD) and density characteristics for blending with other excipients. We also wanted these CR granules to contain large quantities of active pharmaceutical ingredient (API). A high shear mixer was used to mix an API with various polymers at various feed ratios, and the resulting granulated materials were sprayed with solvent. The wet granules were dried using a fluidized bed dryer to give CR granules. The API content of the granules was determined to be 95wt%. The granules were found to be spherical in shape with smooth surfaces by scanning electron microscopy. The inner structure of each granule was determined to be hollow by X-ray computed tomography, highlighting the unusual mechanism of this granulation process. The PSD of the granules was found to be dependent on that of the constituent polymer, and a narrow PSD was obtained by adjusting the PSD of the polymer. The dissolution profile of the granules was also dependent on the constituent polymer. Taken together, these results show that we have successfully developed a new manufacturing technology for the simple and low-cost preparation of ideal CR granules. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Formulation of Dipyridamole Sustained Release Tablet Using Floating System

    Directory of Open Access Journals (Sweden)

    Lenny Mauilida Valentina

    2011-06-01

    Full Text Available Dipyridamole is a drug for prevention of postoperative thromboembolic complication of heart valve replacement and long term therapy of angina pectoris will be well absorbed in stomach. To maintain therapeutic plasma concentration in long time and to increase bioavalaibility is needed a sustained release dosage form having the long residence time in the stomach. The objective of this research was to make floating sustained release tablet of dipyridamole conforming to the requirement that was set up by dipyridamol therapeutic concentration. Tablets were made by wet granulation method using aquadest as a liquid binder, HPMC K4M, Ac-di-sol, Avicel PH 102, talk, and Mg stearat. Dissolution assay was carried out using type 2 release tester at rotation speed of 50 rpm in medium 900 mL HCl 0.1 N at 37 ± 0.5 °C for 8 hours. The formulation containing of 50 mg dipirydamole, HPMC K4M (30%, Ac-di-sol (20%, Avicel PH 102 (37%, talk (2%, and Mg stearat (1% released 59.61 ± 6.73% and 89.34 ± 5.87% of dipyridamole respectively after 4 and 8 hours that conformed to the requirement.

  14. Sustained release of intravitreal flurbiprofen from a novel drug-in-liposome-in-hydrogel formulation.

    Science.gov (United States)

    Pachis, K; Blazaki, S; Tzatzarakis, M; Klepetsanis, P; Naoumidi, E; Tsilimbaris, M; Antimisiaris, S G

    2017-11-15

    A novel Flurbiprofen (FLB)-in-liposome-in-hydrogel formulation was developed, as a method to sustain the release and increase the ocular bioavailability of FLB following intravitreal injection. For this, FLB loading into liposomes was optimized and liposomes were entrapped in thermosensitive hydrogels consisted of Pluronic F-127 (P). FLB solution, liposomes, and FLB dissolved in hydrogel were also used as control formulations. Actively loaded liposomes were found to be optimal for high FLB loading and small size, while in vitro studies revealed that P concentration of 18% (w/v) was best to retain the integrity of the hydrogel-dispersed liposome, compared to a 20% concentration. The in vitro release of FLB was significantly sustained when FLB-liposomes were dispersed in the hydrogel compared to hydrogel dissolved FLB, as well as the other control formulations. In vivo studies were carried out in pigmented rabbits which were injected through a 27G needle with 1mg/mL FLB in the different formulation-types. Ophthalmic examinations after intravitreal injection of all FLB formulations, revealed no evidence of inflammation, hemorrhage, uveitis or endophthalmitis. Pharmacokinetic analysis results confirm that the hybrid drug delivery system increases the bioavailability (by 1.9 times compared to solution), and extends the presence of the drug in the vitreous cavity, while liposome and hydrogel formulations demonstrate intermediate performance. Furthermore the hybrid system increases MRT of FLB in aqueous humor and retina/choroid tissues, compared to all the control formulations. Currently the potential therapeutic advances of FLB sustained release formulations for IVT administration are being evaluated. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Formulation And Evaluation Of Bilayer Tablet for Bimodal Release of Venlafaxine Hydrochloride

    Directory of Open Access Journals (Sweden)

    Munira eMomin

    2015-07-01

    Full Text Available The aim of the present research was to develop a bilayer tablet of venlafexine hydrochloride for bimodal drug release. In the present investigation authors have tried to explore Fenugreek Mucilage (FNM for bioadhesive sustained release layer. The attempt has been made to combine FNM with well studied bioahesive polymers like Hydroxy Propyl Methyl Cellulose, Carbopol and Xanthan Gum. The formulations were evaluated for swelling Index, ex-vivo bioadhesion, water uptake studies, in-vitro drug release and dissolution kinetics was studied. Substantial bioadhesion force (2.4±0.023 gms and tablet adhesion retention time (24±2 hrs was observed with FNM and HPMC combination at 80:20 ratio. The dissolution kinetics followed the Higuchi model (R2 =0.9913 via a non-Fickian diffusion controlled release mechanism after the initial burst. The 32 full factorial design was employed in the present study. The type of polymers used in combination with FNM (X1 and percent polymer replaced with FNM (X2 were taken as independent formulations variables. The selected responses, bioadhesion force (0.11-0.25±0.023gm, amount of drug released in 10 h, Y10 (78.20–95.78±1.24 % and bioadhesive strength, (19-24±2hrs presented good correlation with the selected independent variables. Statistical analysis (ANOVA of the optimized bilayer formulations showed no significant difference in the cumulative amount of drug release after 15 min, but significant difference (p < 0.05 in the amount of drug released after 1 hr till 12 h from optimized formulations was observed. The natural mucilage like FNM could be successfully incorporated into tablet with only 20% replacement with HPMC and it showed good bioadhesiveness and sustained drug release.

  16. Bioavailability of immediate and controlled release formulations of lithium carbonate Biodisponibilidade de formulações de liberação imediata e controlada de carbonato de lítio

    Directory of Open Access Journals (Sweden)

    Luciana Vismari

    2002-06-01

    Full Text Available INTRODUCTION/OBJECTIVES: Controlled-release lithium formulations were developed to minimize elevated blood peaks, related to side-effects and intoxications. However, there is little information about the bioavailability of the only controlled-release lithium formulation available in Brazil. The objective of this study was to compare the bioavailability of controlled-release and immediate-release lithium formulations, after single and multiple doses. METHODS: Twelve healthy volunteers received 900 mg of immediate-release or controlled-release lithium carbonate in single or multiple doses during 9 days. After single dose administration, the following parameters were analyzed for each formulation: maximum lithium concentration (Cmax; time to reach Cmax (t max; area under the curve of serum concentration versus time (AUC0-12 and AUC0-¥ and the elimination half-life (t1/2 elim.. After multiple doses, Cmax; t max; AUC0-12; mean (Cmean and minimum drug concentration (Cmin and degree of fluctuation (DF were analyzed. A 90% confidence interval (90%CI for the ratio between the AUCs for each formulation was constructed. RESULTS/DISCUSSION: Following single dose, the two formulations were bioequivalent; however, they were not after multiple doses. This fact could be a consequence of methodological limitations of lithium level's measurements since, following single dose, these levels could not be detected at time periods 24 and 48h in many volunteers, compromising the calculation of t1/2 elim ,and consequently of the AUC0-¥ and the 90%CI to the ratio of these areas. Therefore, the bioequivalence found after single dose may be an unreliable result.INTRODUÇÃO/OBJETIVO: Formulações de liberação controlada de lítio foram produzidas para minimizar picos sangüíneos elevados relacionados a efeitos colaterais e intoxicações. No entanto, o único produto com liberação controlada de lítio disponível no Brasil possui poucas informações a respeito de

  17. Formulation and release of alaptide from cellulose-based hydrogels

    Directory of Open Access Journals (Sweden)

    Zbyněk Sklenář

    2012-01-01

    Full Text Available The modern drug alaptide, synthetic dipeptide, shows regenerative effects and effects on the epitelisation process. A commercial product consisting of 1% alaptide hydrophilic cream is authorised for use in veterinary practice. This study focuses on the formulation of alaptide into semi-synthetic polymer-based hydrogels. The aim of the present study is to prepare hydrogels and to evaluate the liberation of alaptide from hydrogels. The hydrogels were prepared on the basis of three gel-producing substances: methylcellulose, hydroxyethylcellulose and hydroxypropylcellulose. To enhance the drug release from hydrogel humectants, glycerol, propylene glycol and ethanol in various concentrations were evaluated. The permeation of the alaptide from gels into the acceptor solution was evaluated with the use of the permeable membrane neprophane. The amount of drug released from prepared hydrogels was determined spectrophotometrically. Hydrogels with optimal alaptide liberation properties were subjected to the study of rheological properties in the next phase. The optimal composition of hydrogel as established in this study was 1% alaptide + 3% hydroxyethylcellulose with the addition of 10% glycerol as humectant. Due to the advantageous properties of hydrogels in wounds, alaptide could be incorporated into a hydrogel base for use in veterinary medicine.

  18. Employment-based reinforcement of adherence to an FDA approved extended release formulation of naltrexone in opioid-dependent adults: a randomized controlled trial.

    Science.gov (United States)

    DeFulio, Anthony; Everly, Jeffrey J; Leoutsakos, Jeannie-Marie S; Umbricht, Annie; Fingerhood, Michael; Bigelow, George E; Silverman, Kenneth

    2012-01-01

    Naltrexone provides excellent opioid blockade, but its clinical utility is limited because opioid-dependent patients typically refuse it. An injectable suspension of naltrexone for extended release (XR-NTX) was recently approved by the FDA for treatment of opioid dependence. XR-NTX treatment may require concurrent behavioral intervention to maximize adherence and effectiveness, thus we sought to evaluate employment-based reinforcement as a method of improving adherence to XR-NTX in opiate dependent adults. Opioid-dependent adults (n=38) were detoxified and inducted onto oral naltrexone, then randomly assigned to contingency or prescription conditions. Participants received up to six doses of XR-NTX at four-week intervals. All participants could earn vouchers for attendance and performance at a therapeutic workplace. Contingency participants were required to accept XR-NTX injections to access the workplace and earn vouchers. Prescription participants could earn vouchers independent of their acceptance of XR-NTX injections. Contingency participants accepted significantly more naltrexone injections than prescription participants (87% versus 52%, p=.002), and were more likely to accept all injections (74% versus 26%, p=.004). Participants in the two conditions provided similar percentages of samples negative for opiates (72% versus 65%) and for cocaine (58% versus 54%). Opiate positivity was significantly more likely when samples were also cocaine positive, independent of naltrexone blockade (p=.002). Long-term adherence to XR-NTX in unemployed opiate dependent adults is low under usual care conditions. Employment-based reinforcement can maintain adherence to XR-NTX. Ongoing cocaine use appears to interfere with the clinical effectiveness of XR-NTX on opiate use. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  19. Formulation and evaluation of sustained release matrix tablets of pioglitazone hydrochloride using processed Aloe vera mucilage as release modifier

    Directory of Open Access Journals (Sweden)

    Manoj Choudhary

    2015-01-01

    Full Text Available Background: Natural gums and mucilage which hydrates and swells on contact with aqueous media are used as additives in the formulation of hydrophilic drug delivery system. Aim: The purpose of this study was to develop a new monolithic matrix system for complete delivery of Pioglitazone hydrochloride (HCl, in a zero-order manner over an extended time period using processed Aloe vera gel mucilage (PAG as a release modifier. Materials and Methods: The matrices were prepared by dry blending of selected ratios of polymer and ingredients using direct compression technique. Physicochemical properties of dried powdered mucilage of A. vera were studied. Various formulations of pioglitazone HCl and A. vera mucilage were prepared using different drug: Polymer ratios viz., 1:1, 1:2, 1:3, 1:4, 1:5 for PAG by direct compression technique. Results: The formulated matrix tablets were found to have better uniformity of weight and drug content with low statistical deviation. The swelling behavior and in vitro release rate characteristics were also studied. Conclusion: The study proved that the dried A. vera mucilage can be used as a matrix forming material for controlled release of Pioglitazone HCl matrix tablets.

  20. Workload Control with Continuous Release

    NARCIS (Netherlands)

    Phan, B. S. Nguyen; Land, M. J.; Gaalman, G. J. C.

    2009-01-01

    Workload Control (WLC) is a production planning and control concept which is suitable for the needs of make-to-order job shops. Release decisions based on the workload norms form the core of the concept. This paper develops continuous time WLC release variants and investigates their due date

  1. Absorption of controlled-release iron

    International Nuclear Information System (INIS)

    Cook, J.D.; Lipschitz, D.A.; Skikne, B.S.

    1982-01-01

    A multiple-dose double radioiron technic was used to compare absorption of iron administered as a controlled release (CR) capsule and as an elixir; both formulations contained 50 mg elemental iron as ferrous sulfate. When taken by normal subjects in the fasting state, mean absorption from the elixir and CR capsule averaged 4.92% and 4.38%, which gave a CR capsule:elixir ratio of 0.89. This difference was not significant, but when taken with meals that inhibit absorption of dietary iron by different degrees, absorption of the CR formulation was superior. CR capsule:elixir absorption ratios averaged 1.70 from a meal that is mildly inhibitory and 3.13 from a meal that causes more marked inhibition. It is concluded that CR iron formulations may offer a therapeutic advantage to patients who take oral iron with meals to avoid gastrointestinal side effects

  2. Birth control - slow release methods

    Science.gov (United States)

    Contraception - slow-release hormonal methods; Progestin implants; Progestin injections; Skin patch; Vaginal ring ... might want to consider a different birth control method. SKIN PATCH The skin patch is placed on ...

  3. Formulation, Development and Evaluation of delayed release capsules of Duloxetine Hydrochloride made of different Enteric Polymers

    OpenAIRE

    Pallavi Yerramsetty; J. Vijaya Ratna; Venkata Ramana Reddy; Praveen Kumar

    2012-01-01

    Delayed release systems have acquired a centre stage in the arena of pharmaceutical research and development. The present study involves formulation and evaluation of Duloxetine Hydrochloride delayed release capsules. Duloxetine Hydrochloride is an acid labile drug. It degrades in the acidic environment of the stomach thus leading to therapeutic inefficacy. Therefore it is necessary to bypass the acidic pH of the stomach which can be achieved by formulating delayed release dosage form by usin...

  4. Controlled Release from Recombinant Polymers

    Science.gov (United States)

    Price, Robert; Poursaid, Azadeh; Ghandehari, Hamidreza

    2014-01-01

    Recombinant polymers provide a high degree of molecular definition for correlating structure with function in controlled release. The wide array of amino acids available as building blocks for these materials lend many advantages including biorecognition, biodegradability, potential biocompatibility, and control over mechanical properties among other attributes. Genetic engineering and DNA manipulation techniques enable the optimization of structure for precise control over spatial and temporal release. Unlike the majority of chemical synthetic strategies used, recombinant DNA technology has allowed for the production of monodisperse polymers with specifically defined sequences. Several classes of recombinant polymers have been used for controlled drug delivery. These include, but are not limited to, elastin-like, silk-like, and silk-elastinlike proteins, as well as emerging cationic polymers for gene delivery. In this article, progress and prospects of recombinant polymers used in controlled release will be reviewed. PMID:24956486

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

    Science.gov (United States)

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

    2015-01-01

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

  6. Formulation and in vitro evaluation of sustained release matrix tablets using cross-linked natural gum.

    Science.gov (United States)

    Jamil, Qurratul Ain; Masood, Muhammad Irfan; Jamil, Muhammad Nauman; Masood, Imran; Iqbal, Shahid Muhammad

    2017-03-01

    Polysaccharide gums because of their biocompatibility, biodegradability and non-immunogenic properties are considered as the best choice for preparing sustained release tablets as compared to their synthetic counterpart. The cross linking of natural gums in matrix tablets increase the sustained release property of matrix tablets. Isoniazid is a first line therapy of tuberculosis, belongs to BCS I with half-life of 3-4 hours. These characteristics make isoniazid a good candidate for sustained release dosage form. Karaya gum crossed linked with trisodium tri metaphosphate was used as release rate retardant for preparing isoniazid cross-linked matrix tablet. Total 8 sustained release formulations were prepared. Both granules and tablets were evaluated under in vitro condition against different parameters. Dissolution studies were performed with all eight formulations for 12 hours using USP apparatus I. Four formulations designated as F1, F2, F3, F4 have drug and karaya gum while other four formulations F5, F6, F7, F8 have drug and crossed linked polymer in ratios of 1:1, 1:2, 1:3 and 1:4 respectively. Dissolution data was analyzed by using different kinetic models. Best fit model for most efficient formulation was zero order while release mechanism was super case I. Formulation 8 showed sufficiently slow release kinetics and about 83% of drug was released in 10 hours, indicating that cross-linked karaya gum proved efficient in preparing sustained release tablets.

  7. Meticulous Overview on the Controlled Release Fertilizers

    Directory of Open Access Journals (Sweden)

    Siafu Ibahati Sempeho

    2014-01-01

    Full Text Available Owing to the high demand for fertilizer formulations that will exhaust the possibilities of nutrient use efficiency (NUE, regulate fertilizer consumption, and lessen agrophysicochemical properties and environmental adverse effects instigated by conventional nutrient supply to crops, this review recapitulates controlled release fertilizers (CRFs as a cutting-edge and safe way to supply crops’ nutrients over the conventional ways. Essentially, CRFs entail fertilizer particles intercalated within excipients aiming at reducing the frequency of fertilizer application thereby abating potential adverse effects linked with conventional fertilizer use. Application of nanotechnology and materials engineering in agriculture particularly in the design of CRFs, the distinctions and classification of CRFs, and the economical, agronomical, and environmental aspects of CRFs has been revised putting into account the development and synthesis of CRFs, laboratory CRFs syntheses and testing, and both linear and sigmoid release features of CRF formulations. Methodical account on the mechanism of nutrient release centring on the empirical and mechanistic approaches of predicting nutrient release is given in view of selected mathematical models. Compositions and laboratory preparations of CRFs basing on in situ and graft polymerization are provided alongside the physical methods used in CRFs encapsulation, with an emphasis on the natural polymers, modified clays, and superabsorbent nanocomposite excipients.

  8. Formulation of Sustained-Release Matrix Tablets Using Cross ...

    African Journals Online (AJOL)

    MK and the formulations were also characterized by scanning electron microscopy (SEM), Fourier transform infra-red spectroscopy (FTIR) and differential scanning calorimetry (DSC). Results: Tablets with MK showed higher mean dissolution time (MDT) and lower dissolution efficiency than those prepared with karaya gum.

  9. Formulation and In Vitro Evaluation of Release Retardant Diclofenac ...

    African Journals Online (AJOL)

    Development of release retardant matrix tablets of diclofenac sodium for 24 h by wet granulation technique using different combinations and ratios of hydroxypropylmethylcellulose (HPMC), sodium carboxymethylcellulose (sodium CMC), sodium alginate and cetostearyl alcohol was carried out. The tablets were evaluated ...

  10. Slow diuron release formulations based on clay-phosphatidylcholine complexes

    Czech Academy of Sciences Publication Activity Database

    Undabeytia, T.; Recio, E.; Maqueda, C.; Sanchez-Verdejo, T.; Balek, Vladimír

    2012-01-01

    Roč. 55, JAN (2012), s. 53-61 ISSN 0169-1317 R&D Projects: GA MŠk(CZ) LC523 Institutional support: RVO:61388980 Keywords : Diuron * Phosphatidylcholine * Clay mineral * Leaching * Bioactivity * Slow release Subject RIV: CA - Inorganic Chemistry OBOR OECD: Inorganic and nuclear chemistry Impact factor: 2.342, year: 2012

  11. Effect of Formulation Methods on the Mechanical and Release ...

    African Journals Online (AJOL)

    The mechanical properties of the tablets were assessed using the crushing strength (CS), friability(F) and crushing strength-friability ratio (CSFR) of the tablets, while drug release properties were assessed using disintegration time and dissolution profile. The granules possessed better flow properties than the powder ...

  12. Quality evaluation of extemporaneous delayed-release liquid formulations of lansoprazole.

    Science.gov (United States)

    Melkoumov, Alexandre; Soukrati, Amina; Elkin, Igor; Forest, Jean-Marc; Hildgen, Patrice; Leclair, Grégoire

    2011-11-01

    The quality attributes of extemporaneous delayed-release liquid formulations of lansoprazole for oral administration were evaluated. A novel liquid formulation (3 mg/mL) of Prevacid FasTab in an Ora-Blend vehicle was prepared and compared with the Prevacid FasTab 30 mg and Prevacid-sodium bicarbonate 1 M formulation (3 mg/mL). The latter formulation was combined with hydrochloric acid 0.1 N, and the remaining lansoprazole content was assayed by high-performance liquid chromatography (HPLC). A batch of delayed-release liquid formulation was prepared to evaluate content uniformity. For content assay, three samples were prepared for each evaluated condition and each sample was analyzed in triplicate by HPLC. The lansoprazole in the sodium bicarbonate formulation was extensively degraded by quantities of hydrochloric acid 0.1 N in excess of 100 mL. Storage time and temperature had a significant effect on lansoprazole stability in the Ora-Blend formulation. The drug remained stable for seven days when the formulation was stored at 4.5-5.5 °C, but storage at 21-22 °C or the reduction of pH with citric acid accelerated lansoprazole degradation. The amount of lansoprazole released from the Ora-Blend formulation during the buffer stage of the dissolution test decreased with increases in formulation storage time, in formulation storage temperature, and in the amount of lansoprazole released and degraded during the acid stage of the test. An extemporaneous formulation consisting of lansoprazole microgranules in Ora-Blend maintained acceptable quality attributes when stored for three days at 4.5-5.5 °C.

  13. Formulation and In vitro/In vivo Evaluation of Sustained Release ...

    African Journals Online (AJOL)

    HP

    ISSN: 1596-5996 (print); 1596-9827 (electronic). © Pharmacotherapy ... (DHL). Methods: DHL tablets were prepared by direct compression and consisted of .... subjected to 3D response surface methodology to determine the .... Table 3: Release of diltiazem HCl from the test formulations as per factorial design. Formulation ...

  14. Sustained release formulations of citronella oil nanoemulsion using cavitational techniques.

    Science.gov (United States)

    Agrawal, Naveen; Maddikeri, Ganesh L; Pandit, Aniruddha B

    2017-05-01

    Nanoemulsion synthesis has proven to be an effective way for transportation of immobile, insoluble bioactive compounds. Citronella Oil (lemongrass oil), a natural plant extract, can be used as a mosquito repellent and has less harmful effects compared to its available market counterpart DEET (N, N-Diethyl-meta-toluamide). Nanoemulsion of citronella oil in water was prepared using cavitation-assisted techniques while investigating the effect of system parameters like HLB (Hydrophilic Lipophilic Balance), surfactant concentration, input energy density and mode of power input on emulsion quality. The present work also examines the effect of emulsification on release rate to understand the relationship between droplet size and the release rate. Minimum droplet size (60nm) of the emulsion was obtained at HLB of 14, S/O 1 ratio of 1.0, ultrasound amplitude of 50% and irradiation time of 5min. This study revealed that hydrodynamic cavitation-assisted emulsification is more energy efficient compared to ultrasonic emulsification. It was also found that the release rate of nanoemulsion enhanced as the droplet size of emulsion reduced. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Formulation and Evaluation of Extended- Release Tablet of Zolpidem Tartrate by Wet Granulation Technique

    OpenAIRE

    Fatemeh Pourhashem; Mohammad Reza Avadi

    2016-01-01

    The goal of this study was to design and evaluate extended - release system of the hypnotic agent, Zolpidem tartrate usefulness for the treatment of insomnia. The half-life of this drug is about 1.9 - 3 hours that indicating it a candidate for the extended release formulation. Our investigation relates to development of extended drug delivery system based on Hydroxy propyl methyl cellulose (HPMCK4M) as release retardant, polyvinyl pyrrolidone (PVP k30) as binder and Magnesium S...

  16. Review of extended-release formulations of Tramadol for the management of chronic non-cancer pain: focus on marketed formulations

    Science.gov (United States)

    Kizilbash, Arshi; Ngô-Minh, Cường

    2014-01-01

    Patients with chronic non-malignant pain report impairments of physical, social, and psychological well-being. The goal of pain management should include reducing pain and improving quality of life. Patients with chronic pain require medications that are able to provide adequate pain relief, have minimum dosing intervals to maintain efficacy, and avoid breakthrough pain. Tramadol has proven efficacy and a favourable safety profile. The positive efficacy and safety profile has been demonstrated historically in numerous published clinical studies as well as from post-marketing experience. It is a World Health Organization “Step 2” opioid analgesic that has been shown to be effective, well-tolerated, and valuable, where treatment with strong opioids is not required. A number of extended release formulations of Tramadol are available in Canada and the United States. An optimal extended release Tramadol formulation would be expected to provide consistent pain control with once daily dosing, few sleep interruptions, flexible dosing schedules, and no limitation on taking with meals. Appropriate treatment options should be based on the above proposed attributes. A comparative review of available extended release Tramadol formulations shows that these medications are not equivalent in their pharmacokinetic profile and this may have implications for selecting the optimal therapy for patients with pain syndromes where Tramadol is an appropriate analgesic agent. Differences in pharmacokinetics amongst the formulations may also translate into varied clinical responses in patients. Selection of the appropriate formulation by the health care provider should therefore be based on the patient’s chronic pain condition, needs, and lifestyle. PMID:24711710

  17. Formulation and Evaluation of Extended- Release Tablet of Zolpidem Tartrate by Wet Granulation Technique

    Directory of Open Access Journals (Sweden)

    Fatemeh Pourhashem

    2016-06-01

    Full Text Available The goal of this study was to design and evaluate extended - release system of the hypnotic agent, Zolpidem tartrate usefulness for the treatment of insomnia. The half-life of this drug is about 1.9 - 3 hours that indicating it a candidate for the extended release formulation. Our investigation relates to development of extended drug delivery system based on Hydroxy propyl methyl cellulose (HPMCK4M as release retardant, polyvinyl pyrrolidone (PVP k30 as binder and Magnesium Stearate using Factorial design. In vitro release study of matrix tablets was carried out in 0.01N HCl for 2 hours. All prepared matrix tablets were evaluated for physicochemical evaluation and drug content. The formulation that had release profile according to United State Pharmacopoeia selected for stability study according to ICH guidelines.

  18. Formulation and evaluation of sustained release matrix tablet of rabeprazole using wet granulation technique

    Directory of Open Access Journals (Sweden)

    Ruqaiyah Khan

    2014-01-01

    Full Text Available Introduction: Rabeprazole, a member of substituted benzimidazoles, inhibits the final step in gastric acid secretions. This drug claims to cause fastest acid separation (due to higher pKa, and more rapidly converts to the active species to aid gastric mucin synthesis. The most significant pharmacological action of Rabeprazole is dose dependent suppression of gastric acid secretion; without anticholinergic or H2-blocking action. It completely abolishes the hydrochloric acid secretion as it is powerful inhibitor of gastric acid. Rabeprazole is acid labile and hence commonly formulated as an enteric coated tablet. The absorption of rabeprazole occurs rapidly as soon as tablet leaves the stomach. Aim: In the present study an attempt was made to formulate and evaluate Rabeprazole sustained release matrix tablet using wet granulation technique incorporating various polymers like HPMC-E15, Carbopol934, and sodium carboxymethyl cellulose (CMC. Materials and Methods: The Formulated tablets were evaluated for different physicochemical properties like rheological properties, weight variation, thickness, hardness, % friability, in vitro release studies and drug content. Results: Studies revealed that all the physicochemical parameters comply with the official standards. The in vitro release studies exhibits the release up to 90%, over a prolonged period of time which confirms the extended release profile of formulation, having better bioavailability as well as decreased dosing frequency with reduced doses. Conclusion: The sustained release matrix tablets of rabiprazole shown better bioavailability, efficacy and potency, when compared with official standards.

  19. Formulation and evaluation of a sustained-release tablets of metformin hydrochloride using hydrophilic synthetic and hydrophobic natural polymers.

    Science.gov (United States)

    Wadher, K J; Kakde, R B; Umekar, M J

    2011-03-01

    Metformin hydrochloride has relatively short plasma half-life, low absolute bioavailability. The need for the administration two to three times a day when larger doses are required can decrease patient compliance. Sustained release formulation that would maintain plasma level for 8-12 h might be sufficient for daily dosing of metformin. Sustained release products are needed for metformin to prolong its duration of action and to improve patient compliances. The overall objective of this study was to develop an oral sustained release metformin hydrochloride tablet by using hydrophilic Eudragit RSPO alone or its combination with hydrophobic natural polymers Gum copal and gum damar as rate controlling factor. The tablets were prepared by wet granulation method. The in vitro dissolution study was carried out using USP 22 apparatus I, paddle method and the data was analysed using zero order, first order, Higuchi, Korsmeyer and Hixson-Crowell equations. The drug release study revealed that Eudragit RSPO alone was unable to sustain the drug release. Combining Eudragit with gum Copal and gum Damar sustained the drug release for more than 12 h. Kinetic modeling of in vitro dissolution profiles revealed the drug release mechanism ranges from diffusion controlled or Fickian transport to anomalous type or non-Fickian transport. Fitting the in vitro drug release data to Korsmeyer equation indicated that diffusion along with erosion could be the mechanism of drug release.

  20. Sintering of wax for controlling release from pellets

    OpenAIRE

    Singh, Reena; Poddar, S. S.; Chivate, Amit

    2007-01-01

    The purpose of the present study was to investigate incorporation of hydrophobic (ie, waxy) material into pellets using a thermal sintering technique and to evaluate the pellets in vitro for controlled release. Pellets prepared by extrusion-spheronization technology were formulated with a water-soluble drug, microcrystalline cellulose, and carnauba wax. Powdered carnauba wax (4%–20%) prepared by grinding or by emulsification was studied with an attempt to retard the drug release. The inclusio...

  1. pH-independent immediate release polymethacrylate formulations--an observational study.

    Science.gov (United States)

    Claeys, Bart; Vandeputte, Reinout; De Geest, Bruno G; Remon, Jean Paul; Vervaet, Chris

    2016-01-01

    Using Eudragit® E PO (EudrE) as a polymethacrylate carrier, the aim of the study was to develop a pH-independent dosage form containing ibuprofen (IBP) as an active compound via chemical modification of the polymer (i.e. quaternization of amine function) or via the addition of dicarboxylic acids (succinic, glutaric and adipic acid) to create a pH micro-environment during dissolution. Biconvex tablets (diameter: 10 mm; height: 5 mm) were produced via hot melt extrusion and injection molding. In vitro dissolution experiments revealed that a minimum of 25% of quaternization was sufficient to partially (up to pH 5) eliminate the pH-dependent effect of the EudrE/IBP formulation. The addition of dicarboxylic acids did not alter IBP release in a pH 1 and 3 medium as the dimethyl amino groups of EudrE are already fully protonated, while in a pH 5 solvent IBP release was significantly improved (cf. from 0% to 92% release after 1 h dissolution experiments upon the addition of 20 wt.% succinic acid). Hence, both approaches resulted in a pH-independent (up to pH 5) immediate release formulation. However, the presence of a positively charged polymer induced stability issues (recrystallization of API) and the formulations containing dicarboxylic acids were classified as mechanically unstable. Hence, further research is needed to obtain a pH-independent immediate release formulation while using EudrE as a polmethacrylate carrier.

  2. Evaluation of olibanum and its resin as rate controlling matrix for controlled release of diclofenac

    OpenAIRE

    Chowdary KPR; Mohapatra P; Murali Krishna M

    2006-01-01

    Olibanum and its resin and carbohydrate fractions were evaluated as rate controlling matrix materials in tablets for controlled release of diclofenac. Diclofenac matrix tablets were formulated employing olibanum and its resin and carbohydrate fractions in different concentrations and the tablets were evaluated for various tablet characters including drug release kinetics and mechanism. Olibanum and its resin component exhibited excellent retarding effect on drug release from the matrix tablet...

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

    Science.gov (United States)

    Varma, Chekuri Ashok Kumar; Jayaram Kumar, K

    2018-04-30

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

  4. Comparative steady-state pharmacokinetic study of an extended-release formulation of itopride and its immediate-release reference formulation in healthy volunteers.

    Science.gov (United States)

    Yoon, Seonghae; Lee, Howard; Kim, Tae-Eun; Lee, SeungHwan; Chee, Dong-Hyun; Cho, Joo-Youn; Yu, Kyung-Sang; Jang, In-Jin

    2014-01-01

    This study was conducted to compare the oral bioavailability of an itopride extended-release (ER) formulation with that of the reference immediate-release (IR) formulation in the fasting state. The effect of food on the bioavailability of itopride ER was also assessed. A single-center, open-label, randomized, multiple-dose, three-treatment, three-sequence, crossover study was performed in 24 healthy male subjects, aged 22-48 years, who randomly received one of the following treatments for 4 days in each period: itopride 150 mg ER once daily under fasting or fed conditions, or itopride 50 mg IR three times daily in the fasting state. Steady-state pharmacokinetic parameters of itopride, including peak plasma concentration (Cmax) and area under the plasma concentration versus time curve over 24 hours after dosing (AUC(0-24h)), were determined by noncompartmental analysis. The geometric mean ratio of the pharmacokinetic parameters was derived using an analysis of variance model. A total of 24 healthy Korean subjects participated, 23 of whom completed the study. The geometric mean ratio and its 90% confidence interval of once-daily ER itopride versus IR itopride three times a day for AUC(0-24h) were contained within the conventional bioequivalence range of 0.80-1.25 (0.94 [0.88-1.01]), although Cmax was reached more slowly and was lower for itopride ER than for the IR formulation. Food delayed the time taken to reach Cmax for itopride ER, but AUC(0-24h) was not affected. There were no serious adverse events and both formulations were generally well tolerated. At steady state, once-daily itopride ER at 150 mg has a bioavailability comparable with that of itopride IR at 50 mg given three times a day under fasting conditions. Food delayed the absorption of itopride ER, with no marked change in its oral bioavailability.

  5. Pharmacological and clinical evidence of nevirapine immediate- and extended-release formulations

    Directory of Open Access Journals (Sweden)

    Ena J

    2012-11-01

    Full Text Available Javier Ena, Concepción Amador, Conxa Benito, Francisco PasquauHIV Unit, Hospital Marina Baixa, Villajoyosa, SpainAbstract: We reviewed the current information available on nevirapine immediate- and extended-release formulations and its role in single-dose and combination antiretroviral therapy. Nevirapine was approved in 1996 and was the first non-nucleoside reverse-transcriptase inhibitor available for the treatment of HIV-1 infection. Nevirapine has demonstrated good efficacy and a well-characterized safety profile. A major drawback is the low genetic barrier, allowing the emergence of resistance in the presence of single mutations in the reverse-transcriptase gene. This shortcoming is particularly relevant when nevirapine is administered in a single dose to prevent mother-to-child transmission of HIV-1 infection, compromising the efficacy of future non-nucleoside reverse transcriptase–inhibitor regimens. Studies published recently have probed the noninferiority of nevirapine compared to ritonavir-boosted atazanavir with both tenofovir disoproxil fumarate and emtricitabine in antiretroviral treatment–naïve patients. In 2011, a new formulation of nevirapine (nevirapine extended release that allowed once-daily dosing was approved by the Food and Drug Administration and by the European Medicines Agency. VERxVe, a study comparing nevirapine extended release with nevirapine immediate release in antiretroviral treatment–naïve patients, and TRANxITION, a study carried out in antiretroviral treatment–experienced patients who switched therapy from nevirapine immediate release to nevirapine extended release, provided data on the noninferiority of the new formulation of nevirapine compared with nevirapine immediate release in terms of efficacy and safety. Nevirapine extended release will further increase the durability and persistence of nevirapine-containing antiretroviral therapy, allowing once-daily dosing regimens.Keywords: nevirapine

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

    Science.gov (United States)

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

    2015-01-01

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

  7. Formulation and In vitro/In vivo Evaluation of Sustained Release ...

    African Journals Online (AJOL)

    Conclusion: A fair correlation between in vitro dissolution and in vivo data was found. The results obtained indicate successful development of a sustained release formulation of diltiazem. Keywords: Diltiazem, Matrix tablet, Hydroxypropyl methylcellulose Eudragit, In vitro/in vivo correlation, Optimization ...

  8. Prolonged release matrix tablet of pyridostigmine bromide: formulation and optimization using statistical methods.

    Science.gov (United States)

    Bolourchian, Noushin; Rangchian, Maryam; Foroutan, Seyed Mohsen

    2012-07-01

    The aim of this study was to design and optimize a prolonged release matrix formulation of pyridostigmine bromide, an effective drug in myasthenia gravis and poisoning with nerve gas, using hydrophilic - hydrophobic polymers via D-optimal experimental design. HPMC and carnauba wax as retarding agents as well as tricalcium phosphate were used in matrix formulation and considered as independent variables. Tablets were prepared by wet granulation technique and the percentage of drug released at 1 (Y(1)), 4 (Y(2)) and 8 (Y(3)) hours were considered as dependent variables (responses) in this investigation. These experimental responses were best fitted for the cubic, cubic and linear models, respectively. The optimal formulation obtained in this study, consisted of 12.8 % HPMC, 24.4 % carnauba wax and 26.7 % tricalcium phosphate, had a suitable prolonged release behavior followed by Higuchi model in which observed and predicted values were very close. The study revealed that D-optimal design could facilitate the optimization of prolonged release matrix tablet containing pyridostigmine bromide. Accelerated stability studies confirmed that the optimized formulation remains unchanged after exposing in stability conditions for six months.

  9. Comparative steady-state pharmacokinetic study of an extended-release formulation of itopride and its immediate-release reference formulation in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Yoon S

    2014-01-01

    Full Text Available Seonghae Yoon,1,* Howard Lee,2,* Tae-Eun Kim,1 SeungHwan Lee,1 Dong-Hyun Chee,3 Joo-Youn Cho,1 Kyung-Sang Yu,1 In-Jin Jang1 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 2Clinical Trials Center, Seoul National University Hospital, 3AbbVie Ltd., Seoul, Republic of Korea *These authors contributed equally to this work Background: This study was conducted to compare the oral bioavailability of an itopride extended-release (ER formulation with that of the reference immediate-release (IR formulation in the fasting state. The effect of food on the bioavailability of itopride ER was also assessed. Methods: A single-center, open-label, randomized, multiple-dose, three-treatment, three-sequence, crossover study was performed in 24 healthy male subjects, aged 22–48 years, who randomly received one of the following treatments for 4 days in each period: itopride 150 mg ER once daily under fasting or fed conditions, or itopride 50 mg IR three times daily in the fasting state. Steady-state pharmacokinetic parameters of itopride, including peak plasma concentration (Cmax and area under the plasma concentration versus time curve over 24 hours after dosing (AUC0–24h, were determined by noncompartmental analysis. The geometric mean ratio of the pharmacokinetic parameters was derived using an analysis of variance model. Results: A total of 24 healthy Korean subjects participated, 23 of whom completed the study. The geometric mean ratio and its 90% confidence interval of once-daily ER itopride versus IR itopride three times a day for AUC0–24h were contained within the conventional bioequivalence range of 0.80–1.25 (0.94 [0.88–1.01], although Cmax was reached more slowly and was lower for itopride ER than for the IR formulation. Food delayed the time taken to reach Cmax for itopride ER, but AUC0–24h was not affected. There were no serious adverse events and both formulations were

  10. In-vitro release of diclofenac diethylammonium from lipid-based formulations.

    Science.gov (United States)

    Parsaee, Siamak; Sarbolouki, Mohammad N; Parnianpour, Mohamad

    2002-07-08

    This article presents the preparation and topical performance of some new lipid-based formulations of diclofenac, namely (a) a diclofenac aqueous gel containing mixed micelles (sodium cholate:egg lecithin molar ratio 0.55); (b) diclofenac lotion that contains soya lecithin, ethanol and buffer; and (c) diclofenac lipogel containing egg lecithin, isopropyl myristate, propylene glycol and ethanol. Gel formulations were prepared using Carbomer 934. Release of diclofenac from all formulations was monitored via dialysis through Spectra/por membrane into phosphate buffer (0.2 M pH=7.4) using a Franz cell. Drug release profile and diffusion coefficients were compared with brand formulation (Geigy's Vlotaren Emulgel). Statistical analysis of data show that the diffusion coefficient of the drug from these formulations rank according to the following order: Diclofenac lotion (D=5.308x10(-7) cm(2)/s) >lipogel (D=2.102 x 10(-7) cm(2)/s) >Voltaren Emulgel (1.518 x 10(-7) cm(2)/s) >aqueous gel mixed micelle (0.966 x 10(-7) cm(2)/s). These results show that diclofenac lotion and lipogel maybe more suitable formulations than the conventional topical dosage form.

  11. Formulation and In Vitro, In Vivo Evaluation of Effervescent Floating Sustained-Release Imatinib Mesylate Tablet

    Science.gov (United States)

    Kadivar, Ali; Kamalidehghan, Behnam; Javar, Hamid Akbari; Davoudi, Ehsan Taghizadeh; Zaharuddin, Nurul Dhania; Sabeti, Bahareh; Chung, Lip Yong; Noordin, Mohamed Ibrahim

    2015-01-01

    Introduction Imatinib mesylate is an antineoplastic agent which has high absorption in the upper part of the gastrointestinal tract (GIT). Conventional imatinib mesylate (Gleevec) tablets produce rapid and relatively high peak blood levels and requires frequent administration to keep the plasma drug level at an effective range. This might cause side effects, reduced effectiveness and poor therapeutic management. Therefore, floating sustained-release Imatinib tablets were developed to allow the tablets to be released in the upper part of the GIT and overcome the inadequacy of conventional tablets. Methodology Floating sustained-release Imatinib mesylate tablets were prepared using the wet granulation method. Tablets were formulated using Hydroxypropyl Methylcellulose (HPMC K4M), with Sodium alginate (SA) and Carbomer 934P (CP) as release-retarding polymers, sodium bicarbonate (NaHCO3) as the effervescent agent and lactose as a filler. Floating behavior, in vitro drug release, and swelling index studies were conducted. Initial and total drug release duration was compared with a commercial tablet (Gleevec) in 0.1 N HCl (pH 1.2) at 37 ± 0.5°C for 24 hours. Tablets were then evaluated for various physical parameters, including weight variation, thickness, hardness, friability, and drug content. Consequently, 6 months of physical stability studies and in vitro gastro-retentive studies were conducted. Results and Discussion Statistical data analysis revealed that tablets containing a composition of 14.67% w/w HPMC K4M, 10.67%, w/w Na alginate, 1.33%, w/w Carbomer 934P and 9.33%, w/w NaHCO3 produced the most favorable formulation to develop 24-hour sustained-release tablets with optimum floating behavior and satisfactory physicochemical characteristics. Furthermore, in vitro release study revealed that the formulated SR tablet had significantly lower Cmax and higher Tmax compared to the conventional tablet (Gleevec). Thus, formulated SR tablets preserved persistent

  12. Formulation and in vitro, in vivo evaluation of effervescent floating sustained-release imatinib mesylate tablet.

    Directory of Open Access Journals (Sweden)

    Ali Kadivar

    Full Text Available Imatinib mesylate is an antineoplastic agent which has high absorption in the upper part of the gastrointestinal tract (GIT. Conventional imatinib mesylate (Gleevec tablets produce rapid and relatively high peak blood levels and requires frequent administration to keep the plasma drug level at an effective range. This might cause side effects, reduced effectiveness and poor therapeutic management. Therefore, floating sustained-release Imatinib tablets were developed to allow the tablets to be released in the upper part of the GIT and overcome the inadequacy of conventional tablets.Floating sustained-release Imatinib mesylate tablets were prepared using the wet granulation method. Tablets were formulated using Hydroxypropyl Methylcellulose (HPMC K4M, with Sodium alginate (SA and Carbomer 934P (CP as release-retarding polymers, sodium bicarbonate (NaHCO3 as the effervescent agent and lactose as a filler. Floating behavior, in vitro drug release, and swelling index studies were conducted. Initial and total drug release duration was compared with a commercial tablet (Gleevec in 0.1 N HCl (pH 1.2 at 37 ± 0.5°C for 24 hours. Tablets were then evaluated for various physical parameters, including weight variation, thickness, hardness, friability, and drug content. Consequently, 6 months of physical stability studies and in vitro gastro-retentive studies were conducted.Statistical data analysis revealed that tablets containing a composition of 14.67% w/w HPMC K4M, 10.67%, w/w Na alginate, 1.33%, w/w Carbomer 934P and 9.33%, w/w NaHCO3 produced the most favorable formulation to develop 24-hour sustained-release tablets with optimum floating behavior and satisfactory physicochemical characteristics. Furthermore, in vitro release study revealed that the formulated SR tablet had significantly lower Cmax and higher Tmax compared to the conventional tablet (Gleevec. Thus, formulated SR tablets preserved persistent concentration of plasma up to 24 hours

  13. Characterization of new functionalized calcium carbonate-polycaprolactone composite material for application in geometry-constrained drug release formulation development.

    Science.gov (United States)

    Wagner-Hattler, Leonie; Schoelkopf, Joachim; Huwyler, Jörg; Puchkov, Maxim

    2017-10-01

    A new mineral-polymer composite (FCC-PCL) performance was assessed to produce complex geometries to aid in development of controlled release tablet formulations. The mechanical characteristics of a developed material such as compactibility, compressibility and elastoplastic deformation were measured. The results and comparative analysis versus other common excipients suggest efficient formation of a complex, stable and impermeable geometries for constrained drug release modifications under compression. The performance of the proposed composite material has been tested by compacting it into a geometrically altered tablet (Tablet-In-Cup, TIC) and the drug release was compared to commercially available product. The TIC device exhibited a uniform surface, showed high physical stability, and showed absence of friability. FCC-PCL composite had good binding properties and good compactibility. It was possible to reveal an enhanced plasticity characteristic of a new material which was not present in the individual components. The presented FCC-PCL composite mixture has the potential to become a successful tool to formulate controlled-release dosage solid forms.

  14. Compressional, mechanical and release properties of a novel gum in paracetamol tablet formulations

    Directory of Open Access Journals (Sweden)

    Adedokun Musiliu O.

    2014-09-01

    Full Text Available The binding properties of Eucalyptus gum obtained from the incised trunk of Eucalyptus tereticornis, were evaluated in paracetamol tablet formulations, in comparison with that of Gelatin B.P. In so doing, the compression properties were analyzed using density measurements and the compression equations of Heckel, Kawakita and Gurham. In our work, the mechanical properties of the tablets were assessed using the crushing strength and friability of the tablets, while the drug release properties of the tablets were assessed using disintegration and dissolution times. The results of the study reveal that tablet formulations incorporating Eucalyptus gum as binder, exhibited faster onset and higher amount of plastic deformation during compression than those containing gelatin. What is more, the Gurnham equation could be used as a substitute for the Kawakita equation in describing the compression properties of pharmaceutical tablets. Furthermore, the crushing strength, disintegration and dissolution times of the tablets increased with binder concentration, while friability values decreased. We noted that no significant differences in properties exist between formulations derived from the two binders (p > 0.05 exist. While tablets incorporating gelatin exhibited higher values for mechanical properties, Eucalyptus gum tablets had better balance between mechanical and release properties - as seen from the CSFR/Dt values. Tablets of good mechanical and release properties were prepared using Eucalyptus gum as a binder, and, therefore, it could serve as an alternative binder in producing tablets with good mechanical strength and fast drug release.

  15. Acrylic injectable and self-curing formulations for the local release of bisphosphonates in bone tissue.

    Science.gov (United States)

    Rodríguez-Lorenzo, L M; Fernández, M; Parra, J; Vázquez, B; López-Bravo, A; Román, J San

    2007-11-01

    Two bisphosphonates (BPs), namely 1-hydroxy-2-[4-aminophenyl]ethane-1,1-diphosphonic acid (APBP) and 1-hydroxy-2-[3-indolyl]ethane-1,1-diphosphonic acid (IBP), have been synthesized and incorporated to acrylic injectable and self-curing formulations. Alendronic acid monosodium trihydrated salt (ALN) containing cement was formulated as control. These systems have potential applications in low density hard tissues affected by ailments characterized by a high osteoclastic resorption, i.e. osteoporosis and osteolysis. Values of curing parameters of APBP and IBP were acceptable to obtain pastes with enough fluency to be injected through a biopsy needle into the bone cavity. Working times ranged between 8 and 15 min and maximum temperature was around 50 degrees C. Cured systems stored for a month in synthetic body fluid had compressive strengths between 90 and 96 MPa and modulus between 1.2 and 1.3 GPa, which suggest mechanical stabilization after setting and in the short time. BPs were released in PBS at an initial rate depending on the corresponding chemical structure in the order ALN > APBP > IBP to give final concentrations in PBS of 2.21, 0.44, and 0.19 mol/mL for ALN, APBP, and IBP, respectively. Cytotoxicities of bisphosphonates were evaluated, IC(50) values being in the order APBP > ALN > IBP. Absence of cytotoxicity coming from leachables of the cured systems was observed in all cases independently of the BP. An improved cell growth and proliferation for the systems loaded with APBP and IBP compared with that loaded with ALN was observed, as assessed by measuring cell adhesion and proliferation, and total DNA content.

  16. Formulation, release characteristics, and bioavailability study of gastroretentive floating matrix tablet and floating raft system of Mebeverine HCl.

    Science.gov (United States)

    El Nabarawi, Mohamed A; Teaima, Mahmoud H; Abd El-Monem, Rehab A; El Nabarawy, Nagla A; Gaber, Dalia A

    2017-01-01

    To prolong the residence time of dosage forms within the gastrointestinal tract until all drug is released at the desired rate is one of the real challenges for oral controlled-release drug delivery systems. This study was designed to develop a controlled-release floating matrix tablet and floating raft system of Mebeverine HCl (MbH) and evaluate different excipients for their floating behavior and in vitro controlled-release profiles. Oral pharmacokinetics of the optimum matrix tablet, raft system formula, and marketed Duspatalin ® 200 mg retard as reference were studied in beagle dogs. The optimized tablet formula (FT-10) and raft system formula (FRS-11) were found to float within 34±5 sec and 15±7 sec, respectively, and both remain buoyant over a period of 12 h in simulated gastric fluid. FT-10 (Compritol/HPMC K100M 1:1) showed the slowest drug release among all prepared tablet formulations, releasing about 80.2% of MbH over 8 h. In contrast, FRS-11 (Sodium alginate 3%/HPMC K100M 1%/Precirol 2%) had the greatest retardation, providing sustained release of 82.1% within 8 h. Compared with the marketed MbH product, the C max of FT-10 was almost the same, while FRS-11 maximum concentration was higher. The t max was 3.33, 2.167, and 3.0 h for marketed MbH product, FT-10, and FRS-11, respectively. In addition, the oral bioavailability experiment showed that the relative bioavailability of the MbH was 104.76 and 116.01% after oral administration of FT-10 and FRS-11, respectively, compared to marketed product. These results demonstrated that both controlled-released floating matrix tablet and raft system would be promising gastroretentive delivery systems for prolonging drug action.

  17. Differential scanning calorimetry as a screening technique in compatibility studies of acyclovir extended release formulations

    International Nuclear Information System (INIS)

    Barboza, Fernanda M.; Vecchia, Debora D.; Tagliari, Monika P.; Ferreira, Andrea Granada; Silva, Marcos A.S.; Stulzer, Hellen K.

    2009-01-01

    Acyclovir (ACV) has been investigated during the past years, mainly due to its antiviral activity. Assessment of possible incompatibility between an active component and different excipients along with the evaluation of thermal stability are crucial parts of a normal study prior to the final formulation setting of a medicine. Thermal analysis studies were used as important and complementary tools during pre-formulation to determine the compatibility of drug excipients with the purpose of developing an acyclovir extended release formulation. Fourier transform infrared spectroscopy and X-ray powder diffraction analyses were also realized. The results showed that ACV only exhibited interaction which could influence the stability of the product in the binary mixtures of ACV/magnesium stearate. (author)

  18. Development of a new esomeprazole delayed release gastro-resistant pellet formulation with improved storage stability.

    Science.gov (United States)

    Barmpalexis, Panagiotis; Grypioti, Agni

    2018-06-01

    This study describes the development of a new esomeprazole (ESO) delayed release gastro-resistant formulation with improved storage stability. A three-step (drug-, sub(seal)- and enteric-) coating process was employed with the aid of a fluid bed coater. Several formulation factors (namely, size and quantity of starting non-pareil sugar spheres, binder quantity during drug-layering, sub(seal)-coating polymer type, and quantity and enteric coating quantity) were evaluated and the whole process was modeled with the aid of feed-forward back-propagation artificial neural networks (ANNs). Results showed that the selection of small-sized starting spheres (45/60 mesh size) leads to pellet agglomeration, while as sub(seal)-coating weight gain increases a reduction in ESO dissolution rate is observed. The enteric-coating applied (Eudragit L30D-55) showed good gastro-resistant performance in both 0.1 N HCl and pH 4.5 media, while immediate release profiles with more than 85% of ESO being released in less than 30 min were obtained. The effect of cellulose-based sub(seal)-coating polymers, (namely, hydroxypropyl cellulose and hydroxypropylmethyl cellulose) on formulation's storage stability at 40 ± 2 °C/75 ± 5%RH indicated that only hydroxypropylmethyl cellulose was able to stabilize ESO delayed-release formulations in terms of assay, dissolution, impurities, and gastro-resistance performance. Finally, scanning electron microscopy (SEM) analysis revealed smooth and homogeneous external surface/coating layers in all three levels (drug-, sub(seal)-, and enteric- coating), while x-ray diffraction showed no polymorphic transformations.

  19. Design and characterization of controlled release tablet of metoprolol

    Directory of Open Access Journals (Sweden)

    Gautam Singhvi

    2012-01-01

    Full Text Available Metoprolol succinate is a selective beta-adrenergic receptor blocker useful in treatment of hypertension, angina and heart failure. The purpose of the present work was to design and evaluate controlled release matrix type tablet of Metoprolo succinate using HPMC K15M and Eudragit (RLPO and RSPO as a matrix forming agents. Effect of various polymer alone and combinations were studied in pH 1.2 buffer using USP type II paddle at 50 rpm. HPMC was used to form firm gel with Eudragit polymer. Formulation with Equal proportion (1:1 of Eudragit RSPO and RLPO showed optimum drug release t50 =7 hrs and t100 =16 hrs indicate optimum permeability for drug release from matrix. The drug release mechanism was predominantly found to be Non-Fickian diffusion controlled.

  20. Role of In Vitro Release Methods in Liposomal Formulation Development: Challenges and Regulatory Perspective.

    Science.gov (United States)

    Solomon, Deepak; Gupta, Nilesh; Mulla, Nihal S; Shukla, Snehal; Guerrero, Yadir A; Gupta, Vivek

    2017-11-01

    In the past few years, measurement of drug release from pharmaceutical dosage forms has been a focus of extensive research because the release profile obtained in vitro can give an indication of the drug's performance in vivo. Currently, there are no compendial in vitro release methods designed for liposomes owing to a range of experimental challenges, which has created a major hurdle for both development and regulatory acceptance of liposome-based drug products. In this paper, we review the current techniques that are most often used to assess in vitro drug release from liposomal products; these include the membrane diffusion techniques (dialysis, reverse dialysis, fractional dialysis, and microdialysis), the sample-and-separate approach, the in situ method, the continuous flow, and the modified United States Pharmacopeia methods (USP I and USP IV). We discuss the principles behind each of the methods and the criteria that assist in choosing the most appropriate method for studying drug release from a liposomal formulation. Also, we have included information concerning the current regulatory requirements for liposomal drug products in the United States and in Europe. In light of increasing costs of preclinical and clinical trials, applying a reliable in vitro release method could serve as a proxy to expensive in vivo bioavailability studies. Graphical Abstract Appropriate in-vitro drug release test from liposomal products is important to predict the in-vivo performance.

  1. Risk based In Vitro Performance Assessment of Extended Release Abuse Deterrent Formulations

    Science.gov (United States)

    Xu, Xiaoming; Gupta, Abhay; Al-Ghabeish, Manar; Calderon, Silvia N.; Khan, Mansoor A.

    2016-01-01

    High strength extended release opioid products, which are indispensable tools in the management of pain, are associated with serious risks of unintentional and potentially fatal overdose, as well as of misuse and abuse that might lead to addiction. The issue of drug abuse becomes increasingly prominent when the dosage forms can be readily manipulated to release a high amount of opioid or to extract the drug in certain products or solvents. One approach to deter opioid drug abuse is by providing novel abuse deterrent formulations (ADF), with properties that may be viewed as barriers to abuse of the product. However, unlike regular extended release formulations, assessment of ADF technologies are challenging, in part due to the great variety of formulation designs available to achieve deterrence of abuse by oral, parenteral, nasal and respiratory routes. With limited prior history or literature information, and lack of compendial standards, evaluation and regulatory approval of these novel drug products become increasingly difficult. The present article describes a risk-based standardized in-vitro approach that can be utilized in general evaluation of abuse deterrent features for all ADF products. PMID:26784976

  2. PLGA biodegradable nanoparticles containing perphenazine or chlorpromazine hydrochloride: effect of formulation and release.

    Science.gov (United States)

    Halayqa, Mohammed; Domańska, Urszula

    2014-12-22

    In our study, poly(dl-lactide-co-glycolide) (PLGA) nanoparticles loaded with perphenazine (PPH) and chlorpromazine hydrochloride (CPZ-HCl) were formulated by emulsion solvent evaporation technique. The effect of various processing variables, including PLGA concentration, theoretical drug loading, poly(vinyl alcohol) (PVA) concentration and the power of sonication were assessed systematically to obtain higher encapsulation efficiency and to minimize the nanoparticles size. By the optimization formulation process, the nanoparticles were obtained in submicron size from 325.5 ± 32.4 to 374.3 ± 10.1 nm for nanoparticles loaded with PPH and CPZ-HCl, respectively. Nanoparticles observed by scanning electron microscopy (SEM) presented smooth surface and spherical shape. The encapsulation efficiency of nanoparticles loaded with PPH and CPZ-HCl were 83.9% and 71.0%, respectively. The drug loading were 51.1% and 39.4% for PPH and CPZ-HCl, respectively. Lyophilized nanoparticles with different PLGA concentration 0.8%, 1.3% and 1.6% (w/v) in formulation process were evaluated for in vitro release in phosphate buffered saline (pH = 7.4) by using dialysis bags. The release profile for both drugs have shown that the rate of PPH and CPZ-HCl release were dependent on a size and amount of drugs in the nanoparticles.

  3. PLGA Biodegradable Nanoparticles Containing Perphenazine or Chlorpromazine Hydrochloride: Effect of Formulation and Release

    Directory of Open Access Journals (Sweden)

    Mohammed Halayqa

    2014-12-01

    Full Text Available In our study, poly(dl-lactide-co-glycolide (PLGA nanoparticles loaded with perphenazine (PPH and chlorpromazine hydrochloride (CPZ-HCl were formulated by emulsion solvent evaporation technique. The effect of various processing variables, including PLGA concentration, theoretical drug loading, poly(vinyl alcohol (PVA concentration and the power of sonication were assessed systematically to obtain higher encapsulation efficiency and to minimize the nanoparticles size. By the optimization formulation process, the nanoparticles were obtained in submicron size from 325.5 ± 32.4 to 374.3 ± 10.1 nm for nanoparticles loaded with PPH and CPZ-HCl, respectively. Nanoparticles observed by scanning electron microscopy (SEM presented smooth surface and spherical shape. The encapsulation efficiency of nanoparticles loaded with PPH and CPZ-HCl were 83.9% and 71.0%, respectively. The drug loading were 51.1% and 39.4% for PPH and CPZ-HCl, respectively. Lyophilized nanoparticles with different PLGA concentration 0.8%, 1.3% and 1.6% (w/v in formulation process were evaluated for in vitro release in phosphate buffered saline (pH = 7.4 by using dialysis bags. The release profile for both drugs have shown that the rate of PPH and CPZ-HCl release were dependent on a size and amount of drugs in the nanoparticles.

  4. Stimuli responsive nanomaterials for controlled release applications

    KAUST Repository

    Li, Song

    2012-01-01

    The controlled release of therapeutics has been one of the major challenges for scientists and engineers during the past three decades. Coupled with excellent biocompatibility profiles, various nanomaterials have showed great promise for biomedical applications. Stimuli-responsive nanomaterials guarantee the controlled release of cargo to a given location, at a specific time, and with an accurate amount. In this review, we have combined the major stimuli that are currently used to achieve the ultimate goal of controlled and targeted release by "smart" nanomaterials. The most heavily explored strategies include (1) pH, (2) enzymes, (3) redox, (4) magnetic, and (5) light-triggered release.

  5. Lignin based controlled release coatings

    NARCIS (Netherlands)

    Mulder, W.J.; Gosselink, R.J.A.; Vingerhoeds, M.H.; Harmsen, P.F.H.; Eastham, D.

    2011-01-01

    Urea is a commonly used fertilizer. Due to its high water-solubility, misuse easily leads to excess nitrogen levels in the soil. The aim of this research was to develop an economically feasible and biodegradable slow-release coating for urea. For this purpose, lignin was selected as coating

  6. Controlled Release from Zein Matrices

    NARCIS (Netherlands)

    Bouman, Jacob; Belton, Peter; Venema, Paul; Linden, Van Der Erik; Vries, De Renko; Qi, Sheng

    2016-01-01

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

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

    Science.gov (United States)

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

    2011-04-01

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

  8. Polymeric materials and formulation technologies for modified-release tablet development.

    Science.gov (United States)

    Zarate, J; Igartua, M; Hernández, R M; Pedraz, J L

    2009-11-01

    Over the last years significant advances have been made in the area of drug delivery with the development of modified-release (MR) dosage forms. The present review is divided into two parts, one dealing with technologies for the design of modified-release drug delivery tablets and the other with the use of synthetic and natural polymers that are capable of controlling drug release.

  9. Effect of xanthan gum on the release of strawberry flavor in formulated soy beverage.

    Science.gov (United States)

    Xu, Jiao; He, Zhiyong; Zeng, Maomao; Li, Bingbing; Qin, Fang; Wang, Linxiang; Wu, Shengfang; Chen, Jie

    2017-08-01

    The effects of xanthan gum on the release of strawberry flavor compounds in formulated soy protein isolate (SPI) beverage were investigated by headspace gas chromatography (GC). Seven strawberry flavor compounds (limonene, ethyl hexanoate, (Z)-3-hexenyl acetate, ethyl 2-methylbutanoate, ethyl butanoate, (Z)-3-hexen-1-ol and diacetyl) could be detected by GC and hence analyzed the gas-matrix partition coefficients (K). The release of flavor compounds was restrained in SPI and/or xanthan gum solution. The retention of (Z)-3-hexen-1-ol, limonene and diacetyl significantly changed (pfuraneol) accelerated the release of ester compounds to some extent in different matrices. The above results demonstrated that presence of SPI and xanthan gum could bring about an imbalance in the strawberry flavor. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. A novel experimental design method to optimize hydrophilic matrix formulations with drug release profiles and mechanical properties.

    Science.gov (United States)

    Choi, Du Hyung; Lim, Jun Yeul; Shin, Sangmun; Choi, Won Jun; Jeong, Seong Hoon; Lee, Sangkil

    2014-10-01

    To investigate the effects of hydrophilic polymers on the matrix system, an experimental design method was developed to integrate response surface methodology and the time series modeling. Moreover, the relationships among polymers on the matrix system were studied with the evaluation of physical properties including water uptake, mass loss, diffusion, and gelling index. A mixture simplex lattice design was proposed while considering eight input control factors: Polyethylene glycol 6000 (x1 ), polyethylene oxide (PEO) N-10 (x2 ), PEO 301 (x3 ), PEO coagulant (x4 ), PEO 303 (x5 ), hydroxypropyl methylcellulose (HPMC) 100SR (x6 ), HPMC 4000SR (x7 ), and HPMC 10(5) SR (x8 ). With the modeling, optimal formulations were obtained depending on the four types of targets. The optimal formulations showed the four significant factors (x1 , x2 , x3 , and x8 ) and other four input factors (x4 , x5 , x6 , and x7 ) were not significant based on drug release profiles. Moreover, the optimization results were analyzed with estimated values, targets values, absolute biases, and relative biases based on observed times for the drug release rates with four different targets. The result showed that optimal solutions and target values had consistent patterns with small biases. On the basis of the physical properties of the optimal solutions, the type and ratio of the hydrophilic polymer and the relationships between polymers significantly influenced the physical properties of the system and drug release. This experimental design method is very useful in formulating a matrix system with optimal drug release. Moreover, it can distinctly confirm the relationships between excipients and the effects on the system with extensive and intensive evaluations. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  11. Time-oriented experimental design method to optimize hydrophilic matrix formulations with gelation kinetics and drug release profiles.

    Science.gov (United States)

    Shin, Sangmun; Choi, Du Hyung; Truong, Nguyen Khoa Viet; Kim, Nam Ah; Chu, Kyung Rok; Jeong, Seong Hoon

    2011-04-04

    A new experimental design methodology was developed by integrating the response surface methodology and the time series modeling. The major purposes were to identify significant factors in determining swelling and release rate from matrix tablets and their relative factor levels for optimizing the experimental responses. Properties of tablet swelling and drug release were assessed with ten factors and two default factors, a hydrophilic model drug (terazosin) and magnesium stearate, and compared with target values. The selected input control factors were arranged in a mixture simplex lattice design with 21 experimental runs. The obtained optimal settings for gelation were PEO, LH-11, Syloid, and Pharmacoat with weight ratios of 215.33 (88.50%), 5.68 (2.33%), 19.27 (7.92%), and 3.04 (1.25%), respectively. The optimal settings for drug release were PEO and citric acid with weight ratios of 191.99 (78.91%) and 51.32 (21.09%), respectively. Based on the results of matrix swelling and drug release, the optimal solutions, target values, and validation experiment results over time were similar and showed consistent patterns with very small biases. The experimental design methodology could be a very promising experimental design method to obtain maximum information with limited time and resources. It could also be very useful in formulation studies by providing a systematic and reliable screening method to characterize significant factors in the sustained release matrix tablet. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Use of partial AUC to demonstrate bioequivalence of Zolpidem Tartrate Extended Release formulations.

    Science.gov (United States)

    Lionberger, Robert A; Raw, Andre S; Kim, Stephanie H; Zhang, Xinyuan; Yu, Lawrence X

    2012-04-01

    FDA's bioequivalence recommendation for Zolpidem Tartrate Extended Release Tablets is the first to use partial AUC (pAUC) metrics for determining bioequivalence of modified-release dosage forms. Modeling and simulation studies were performed to aid in understanding the need for pAUC measures and also the proper pAUC truncation times. Deconvolution techniques, In Vitro/In Vivo Correlations, and the CAT (Compartmental Absorption and Transit) model were used to predict the PK profiles for zolpidem. Models were validated using in-house data submitted to the FDA. Using dissolution profiles expressed by the Weibull model as input for the CAT model, dissolution spaces were derived for simulated test formulations. The AUC(0-1.5) parameter was indicative of IR characteristics of early exposure and effectively distinguished among formulations that produced different pharmacodynamic effects. The AUC(1.5-t) parameter ensured equivalence with respect to the sustained release phase of Ambien CR. The variability of AUC(0-1.5) is higher than other PK parameters, but is reasonable for use in an equivalence test. In addition to the traditional PK parameters of AUCinf and Cmax, AUC(0-1.5) and AUC(1.5-t) are recommended to provide bioequivalence measures with respect to label indications for Ambien CR: onset of sleep and sleep maintenance.

  13. Controlled drug release for tissue engineering.

    Science.gov (United States)

    Rambhia, Kunal J; Ma, Peter X

    2015-12-10

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

  14. A Bayesian Formulation of Behavioral Control

    Science.gov (United States)

    Huys, Quentin J. M.; Dayan, Peter

    2009-01-01

    Helplessness, a belief that the world is not subject to behavioral control, has long been central to our understanding of depression, and has influenced cognitive theories, animal models and behavioral treatments. However, despite its importance, there is no fully accepted definition of helplessness or behavioral control in psychology or…

  15. Development of a CO2 releasing co-formulation 1 based on starch, Saccharomyces cerevisiae and Beauveria bassiana attractive towards western corn rootworm larvae

    Science.gov (United States)

    CO2 is known as an attractant for many soil-dwelling pests. To implement an attract-and-kill strategy for soil pest control, CO2 emitting formulations need to be developed. This work aimed at the development of a slow release bead system in order to bridge the gap between application and hatching of...

  16. A Novel Approach to Flurbiprofen Pulsatile Colonic Release: Formulation and Pharmacokinetics of Double-Compression-Coated Mini-Tablets.

    Science.gov (United States)

    Vemula, Sateesh Kumar

    2015-12-01

    A significant plan is executed in the present study to study the effect of double-compression coating on flurbiprofen core mini-tablets to achieve the pulsatile colonic delivery to deliver the drug at a specific time as per the patho-physiological need of the disease that results in improved therapeutic efficacy. In this study, pulsatile double-compression-coated tablets were prepared based on time-controlled hydroxypropyl methylcellulose K100M inner compression coat and pH-sensitive Eudragit S100 outer compression coat. Then, the tablets were evaluated for both physical evaluation and drug-release studies, and to prove these results, in vivo pharmacokinetic studies in human volunteers were conducted. From the in vitro drug-release studies, F6 tablets were considered as the best formulation, which retarded the drug release in the stomach and small intestine (3.42 ± 0.12% in 5 h) and progressively released to the colon (99.78 ± 0.74% in 24 h). The release process followed zero-order release kinetics, and from the stability studies, similarity factor between dissolution data before and after storage was found to be 88.86. From the pharmacokinetic evaluation, core mini-tablets producing peak plasma concentration (C max) was 14,677.51 ± 12.16 ng/ml at 3 h T max and pulsatile colonic tablets showed C max = 12,374.67 ± 16.72 ng/ml at 12 h T max. The area under the curve for the mini and pulsatile tablets was 41,238.52 and 72,369.24 ng-h/ml, and the mean resident time was 3.43 and 10.61 h, respectively. In conclusion, development of double-compression-coated tablets is a promising way to achieve the pulsatile colonic release of flurbiprofen.

  17. Formulation and in vivo evaluation of diclofenac sodium sustained release matrix tablet: effect of compression force.

    Science.gov (United States)

    Taha, Ehab Ibrahim; Shazly, Gamal Abdel-Ghany; Harisa, Gamaleldin Ibrahim; Barakat, Nahla Sedik; Al-Enazi, Fouza Kayem; Elbagory, Ibrahim Mostafa

    2015-03-01

    In the present study, Diclofenac Sodium (DS) matrix tablets were prepared by direct compression method under different compression forces (5, 10, 15 and 20 KN), using ethylcellulose as matrix forming material. The produced tablets were characterized on the foundation of satisfactory tablet properties such as hardness, friability, drug content, weight variations and in vitro drug release rate. Differential scanning calorimetry (DSC), Fourier Transform Infrared (FT-IR) spectroscopy and X-ray diffraction have been used to investigate any incompatibilities of the tablet's ingredients. Additionally, in vivo bioavailability has been investigated on beagle dogs. Data obtained revealed that, upon increasing compression force the in vitro drug release was sustained and the T(max) value was four hours (for formulations compressed at 15 and 20 kN) compared to the conventional voltarine(®) 50 tablets (T(max) value of 2 hours).

  18. Analgesic Efficacy of a New Immediate-Release/Extended-Release Formulation of Ibuprofen: Results From Single- and Multiple-Dose Postsurgical Dental Pain Studies.

    Science.gov (United States)

    Christensen, Steven; Paluch, Ed; Jayawardena, Shyamalie; Daniels, Stephen; Meeves, Suzanne

    2017-05-01

    Analgesic effects of ibuprofen immediate-release/extended-release (IR/ER) 600-mg tablets were evaluated in 2 randomized, double-blind, placebo-controlled dental pain studies. Patients 16-40 years old with moderate-severe pain following third-molar extraction received single-dose ibuprofen 600 mg IR/ER (formulation A or B), naproxen sodium 220 mg, or placebo (2:2:2:1; study 1) or 4 doses of ibuprofen 600 mg IR/ER (formulation A) or placebo (1:1; study 2). In study 1 (n = 196), mean (standard deviation [SD]) time-weighted sum of pain intensity difference scores for placebo, ibuprofen IR/ER A, ibuprofen IR/ER B, and naproxen, respectively, were 0.05 (9.2), 16.87 (9.4), 17.34 (10.5), and 12.66 (10.0) over 0-12 hours and -0.03 (4.1), 6.57 (4.4), 7.14 (5.2), and 5.14 (5.0) over 8-12 hours (all P ibuprofen IR/ER, respectively (P ibuprofen. Gastrointestinal adverse events predominated with placebo both after study medication administration and after rescue medication use, if applicable. Ibuprofen 600 mg IR/ER provided safe and effective analgesia after single and multiple doses. © 2016, The American College of Clinical Pharmacology.

  19. The impact of new partial AUC parameters for evaluating the bioequivalence of prolonged-release formulations.

    Science.gov (United States)

    Boily, Michaël; Dussault, Catherine; Massicotte, Julie; Guibord, Pascal; Lefebvre, Marc

    2015-01-23

    To demonstrate bioequivalence (BE) between two prolonged-release (PR) drug formulations, single dose studies under fasting and fed state as well as at least one steady-state study are currently required by the European Medicines Agency (EMA). Recently, however, there have been debates regarding the relevance of steady-state studies. New requirements in single-dose investigations have also been suggested by the EMA to address the absence of a parameter that can adequately assess the equivalence of the shape of the curves. In the draft guideline issued in 2013, new partial area under the curve (pAUC) pharmacokinetic (PK) parameters were introduced to that effect. In light of these potential changes, there is a need of supportive clinical evidence to evaluate the impact of pAUCs on the evaluation of BE between PR formulations. In this retrospective analysis, it was investigated whether the newly defined parameters were associated with an increase in discriminatory ability or a change in variability compared to the conventional PK parameters. Among the single dose studies that met the requirements already in place, 20% were found unable to meet the EMA's new requirements in regards to the pAUC PK parameters. When pairing fasting and fed studies for a same formulation, the failure rate increased to 40%. In some cases, due to the high variability of these parameters, an increase of the sample size would be required to prove BE. In other cases however, the pAUC parameters demonstrated a robust ability to detect differences between the shapes of the curves of PR formulations. The present analysis should help to better understand the impact of the upcoming changes in European regulations on PR formulations and in the design of future BE studies. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Formulation and In Vitro Release Kinetics of Mucoadhesive Blend Gels Containing Matrine for Buccal Administration.

    Science.gov (United States)

    Chen, Xiaojin; Yan, Jun; Yu, Shuying; Wang, Pingping

    2018-01-01

    Enterovirus 71 (EV71) is a pathogenic factor of severe hand, foot, and mouth disease (HFMD). No vaccine or specific treatment is currently available for EV71 infection. Hence, we developed a buccal mucoadhesive gel containing matrine to protect against HFMD. Mucoadhesive gels were prepared by Carbopol 974P and were combined with Carbopol 971P, sodium carboxymethyl cellulose (CMC-Na), or hydroxypropylmethy cellulose (HPMC K100M). The formulations were characterized in terms of tensile testing and continuous flow techniques for mucoadhesion. The rheological studies and in vitro drug release characteristics were also investigated. The results showed that combinations of two polymers significantly improved mucoadhesion, especially Carbopol 974P blended with HPMC. Carbopol 974P to HPMC blend ratios of 1:1 and 2:1 induced better mucoadhesion in the tensile test and continuous flow method, respectively. The most sustained release was obtained at a Carbopol 974P to HPMC ratio of 2.5:1. A predominantly non-Fickian diffusion release mechanism was obtained. The gel containing 2.5% Carbopol 974P combined with 1% HPMC showed good mucoadhesion properties and sustained drug release.

  1. Massive radiological releases profoundly differ from controlled releases

    International Nuclear Information System (INIS)

    Pascucci-Cahen, Ludivine; Patrick, Momal

    2012-11-01

    Preparing for a nuclear accident implies understanding potential consequences. While many specialized experts have been working on different particular aspects, surprisingly little effort has been dedicated to establishing the big picture and providing a global and balanced image of all major consequences. IRSN has been working on the cost of nuclear accidents, an exercise which must strive to be as comprehensive as possible since any omission obviously underestimates the cost. It therefore provides (ideally) an estimate of all cost components, thus revealing the structure of accident costs, and hence sketching a global picture. On a French PWR, it appears that controlled releases would cause an 'economical' accident with limited radiological consequences when compared to other costs; in contrast, massive releases would trigger a major crisis with strong radiological consequences. The two types of crises would confront managers with different types of challenges. (authors)

  2. Slow release formulations of Bacillus thuringiensis israelensis (AM 65-52 and spinosyns: effectiveness against the West Nile vector Culex pipiens in Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Alaa Sulaiman Alsobhi

    2016-07-01

    Full Text Available Objective: To investigate the effectiveness of slow release formulations of Bacillus thuringiensis israelensis (AM 65-52 (B. thuringiensis israelensis and spinosyns against the West Nile vector Culex pipiens (Cx. pipiens in Saudi Arabia. Methods: We tested slow release insecticide formulations of Natular DT, Tap 60 and VectoBac granule against II instars of Cx. pipiens larvae in 50 L laboratory arenas. Results: Slow release formulations of B. thuringiensis israelensis and spinosyns gave continuous control against Cx. pipiens for several weeks. Natular DT was more effective over Tap 60 and VectoBac granule of about 1.3 and 5.8 times, respectively. Variations in the durations of effective control among the tested slow release formulations may reflect differences in their active ingredients and the mode of action. Conclusions: Our results highlighted the effectiveness of B. thuringiensis israelensis and spinosyns against an important West Nile vector, providing baseline data to develop ecofriendly mosquito control programs in Saudi Arabia.

  3. Sintering of wax for controlling release from pellets.

    Science.gov (United States)

    Singh, Reena; Poddar, S S; Chivate, Amit

    2007-09-14

    The purpose of the present study was to investigate incorporation of hydrophobic (ie, waxy) material into pellets using a thermal sintering technique and to evaluate the pellets in vitro for controlled release. Pellets prepared by extrusion-spheronization technology were formulated with a water-soluble drug, microcrystalline cellulose, and carnauba wax. Powdered carnauba wax (4%-20%) prepared by grinding or by emulsification was studied with an attempt to retard the drug release. The inclusion of ground or emulsified carnauba wax did not sustain the release of theophylline for more than 3 hours. Matrix pellets of theophylline prepared with various concentrations of carnauba wax were sintered thermally at various times and temperatures. In vitro drug release profiles indicated an increase in drug release retardation with increasing carnauba wax concentration. Pellets prepared with ground wax showed a higher standard deviation than did those prepared with emulsified wax. There was incomplete release at the end of 12 hours for pellets prepared with 20% ground or emulsified wax. The sintering temperature and duration were optimized to allow for a sustained release lasting at least 12 hours. The optimized temperature and duration were found to be 100 degrees C and 140 seconds, respectively. The sintered pellets had a higher hydrophobicity than did the unsintered pellets. Scanning electron micrographs indicated that the carnauba wax moved internally, thereby increasing the surface area of wax within the pellets.

  4. The Multimedia Environmental Pollutant Assessment System (MEPAS)reg-sign: Source-term release formulations

    International Nuclear Information System (INIS)

    Streile, G.P.; Shields, K.D.; Stroh, J.L.; Bagaasen, L.M.; Whelan, G.; McDonald, J.P.; Droppo, J.G.; Buck, J.W.

    1996-11-01

    This report is one of a series of reports that document the mathematical models in the Multimedia Environmental Pollutant Assessment System (MEPAS). Developed by Pacific Northwest National Laboratory for the US Department of Energy, MEPAS is an integrated impact assessment software implementation of physics-based fate and transport models in air, soil, and water media. Outputs are estimates of exposures and health risk assessments for radioactive and hazardous pollutants. Each of the MEPAS formulation documents covers a major MEPAS component such as source-term, atmospheric, vadose zone/groundwater, surface water, and health exposure/health impact assessment. Other MEPAS documentation reports cover the sensitivity/uncertainty formulations and the database parameter constituent property estimation methods. The pollutant source-term release component is documented in this report. MEPAS simulates the release of contaminants from a source, transport through the air, groundwater, surface water, or overland pathways, and transfer through food chains and exposure pathways to the exposed individual or population. For human health impacts, risks are computed for carcinogens and hazard quotients for noncarcinogens. MEPAS is implemented on a desktop computer with a user-friendly interface that allows the user to define the problem, input the required data, and execute the appropriate models for both deterministic and probabilistic analyses

  5. A formulation to encapsulate nootkatone for tick control.

    Science.gov (United States)

    Behle, Robert W; Flor-Weiler, Lina B; Bharadwaj, Anuja; Stafford, Kirby C

    2011-11-01

    Nootkatone is a component of grapefruit oil that is toxic to the disease-vectoring tick, Ixodes scapularis Say, but unfortunately causes phytotoxicity to treated plants and has a short residual activity due to volatility. We prepared a lignin-encapsulated nootkatone formulation to compare with a previously used emulsifiable formulation for volatility, plant phytotoxicity, and toxicity to unfed nymphs of I. scapularis. Volatility of nootkatone was measured directly by trapping nootkatone vapor in a closed system and indirectly by measuring nootkatone residue on treated filter paper after exposure to simulated sunlight (Xenon). After 24 h in the closed system, traps collected only 15% of the nootkatone applied as the encapsulated formulation compared with 40% applied as the emulsifiable formulation. After a 1-h light exposure, the encapsulated formulation retained 92% of the nootkatone concentration compared with only 26% retained by the emulsifiable formulation. For plant phytotoxicity, cabbage, Brassica oleracea L., leaves treated with the encapsulated formulation expressed less necrosis, retaining greater leaf weight compared with leaves treated with the emusifiable formulation. The nootkatone in the emulsifiable formulation was absorbed by cabbage and oat, Avena sativa L., plants (41 and 60% recovered 2 h after application, respectively), as opposed to 100% recovery from the plants treated with encapsulated nootkatone. Using a treated vial technique, encapsulated nootkatone was significantly more toxic to I. scapularis nymphs (LC50 = 20 ng/cm2) compared with toxicity of the emulsifiable formulation (LC50 = 35 ng/cm2). Thus, the encapsulation of nootkatone improved toxicity for tick control, reduced nootkatone volatility, and reduced plant phytotoxicity.

  6. Controlled release of glaucocalyxin - a self-nanoemulsifying system from osmotic pump tablets with enhanced bioavailability.

    Science.gov (United States)

    Yanfei, Miao; Guoguang, Chen; Lili, Ren; Pingkai, Ouyang

    2017-03-01

    The purpose of this study was to develop a new formulation to enhance the bioavailability simultaneously with controlled release of glaucocalyxin A (GLA). In this study, controlled release of GLA was achieved by the osmotic release strategy taking advantage of the bioavailability enhancing capacity of self-nanoemulsifying drug delivery systems (SNEDDS). The formulation of GLA-SNEDDS was selected by the solubility and pseudoternary-phase diagrams studies. The prepared GLA-SNEDDS formulations were characterized for self-emulsification time, effect of pH and robustness to dilution, droplet size analysis and zeta potential. The optimized GLA-SNEDDS were used to prepare GLA-SNEDDS osmotic pump tablet via direct powder compression method. The effect of formulation variables on the release characteristic was investigated. GLA-SNEDDS osmotic pump tablets were administered to beagle dogs and their pharmacokinetics were compared to GLA and GLA-SNEDDS as a control. In vitro drug release studies indicated that the GLA-SNEDDS osmotic pump tablet showed sustained release profiles with 90% released within 12 h. Pharmacokinetic study showed steady blood GLA with prolonged T max and mean residence time (MRT), and enhanced bioavailability for GLA-SNEDDS osmotic pump tablet. It was concluded that simultaneous controlling on GLA release and enhanced bioavailability had been achieved by a combination of osmotic pump tablet and SNEDDS.

  7. Local control of striatal dopamine release

    Directory of Open Access Journals (Sweden)

    Roger eCachope

    2014-05-01

    Full Text Available The mesolimbic and nigrostriatal dopamine (DA systems play a key role in the physiology of reward seeking, motivation and motor control. Importantly, they are also involved in the pathophysiology of Parkinson’s and Huntington’s disease, schizophrenia and addiction. Control of DA release in the striatum is tightly linked to firing of DA neurons in the ventral tegmental area (VTA and the substantia nigra (SN. However, local influences in the striatum affect release by exerting their action directly on axon terminals. For example, endogenous glutamatergic and cholinergic activity is sufficient to trigger striatal DA release independently of cell body firing. Recent developments involving genetic manipulation, pharmacological selectivity or selective stimulation have allowed for better characterization of these phenomena. Such termino-terminal forms of control of DA release transform considerably our understanding of the mesolimbic and nigrostriatal systems, and have strong implications as potential mechanisms to modify impaired control of DA release in the diseased brain. Here, we review these and related mechanisms and their implications in the physiology of ascending DA systems.

  8. New polymeric formulation for control of biomphalaria Alexandria based on pharmaceutical waste gelatin

    International Nuclear Information System (INIS)

    Kenawy, E.; El-Maghraby, A.

    2005-01-01

    In the recent years, important new areas of application for plastics have emerged in medicine such as devices for the controlled release of drugs. The increases in the use of plastic materials in all sectors of industry have led to a continuous increase in the generation of plastic wastes. Recycling allow the waste to be reintroduced into the consumption cycle. Pharmaceutical companies which manufacture soft gels with different shapes, sizes and colors based mainly on gelatin formulations produce huge amount of gelatin waste. Schistosomiasis is one of the most important public health problems in our country. We now report the utilization of gelatin scrap by incorporating them in biodegradable films containing the molluscicide niclosamide for control of Biomphalaria Alexandrina snails. The preparation of the gelatin films will be described. The release of niclosamide from the prepared blends was investigated. The prepared formulations proved to be useful compared with free niclosamide

  9. Spironolactone release from liquisolid formulations prepared with Capryol™ 90, Solutol® HS-15 and Kollicoat® SR 30 D as non-volatile liquid vehicles.

    Science.gov (United States)

    Elkordy, Amal Ali; Tan, Xin Ning; Essa, Ebtessam Ahmed

    2013-02-01

    The purpose of the study is to enhance dissolution of spironolactone as a model hydrophobic drug through application of liquisolid technology. Spironolactone is prepared as liquisolid formulations, and its dissolution property is evaluated and compared to that of conventional spironolactone tablets and pure spironolactone. Three non-volatile liquid vehicles were used in the design of spironolactone liquisolid formulations, Capryol™ 90, Synperonic® PE/L61 in combination with Solutol® HS-15 at a ratio of 1:1, and Kollicoat® SR 30 D. Spironolactone liquisolid formulations were tested according to British Pharmacopoeia (BP) quality control tests. Furthermore, the prepared liquisolid powder formulations were evaluated via differential scanning calorimetry (DSC), Fourier transform infrared (FT-IR) and scanning electron microscopy. Also, liquisolid formulations were subjected to testing of storage stability at high relative humidity. The results indicated that most of liquisolid tablets met the BP requirements. Dissolution results indicate that release of spironolactone was significantly increased (PSolutol® HS-15 showed highest dissolution. DSC thermograms from liquisolid formulations revealed that drug endothermic peak was disappeared after processing. Dissolution, DSC and FT-IR data after storage demonstrated that there were no significant changes in the formulations after storage. In conclusion, the liquid vehicles used within spironolactone liquisolid formulations enhanced drug dissolution rate. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Cubic phase nanoparticles for sustained release of ibuprofen: formulation, characterization, and enhanced bioavailability study

    Science.gov (United States)

    Dian, Linghui; Yang, Zhiwen; Li, Feng; Wang, Zhouhua; Pan, Xin; Peng, Xinsheng; Huang, Xintian; Guo, Zhefei; Quan, Guilan; Shi, Xuan; Chen, Bao; Li, Ge; Wu, Chuanbin

    2013-01-01

    In order to improve the oral bioavailability of ibuprofen, ibuprofen-loaded cubic nanoparticles were prepared as a delivery system for aqueous formulations. The cubic inner structure was verified by cryogenic transmission electron microscopy. With an encapsulation efficiency greater than 85%, the ibuprofen-loaded cubic nanoparticles had a narrow size distribution around a mean size of 238 nm. Differential scanning calorimetry and X-ray diffraction determined that ibuprofen was in an amorphous and molecular form within the lipid matrix. The in vitro release of ibuprofen from cubic nanoparticles was greater than 80% at 24 hours, showing sustained characteristics. The pharmacokinetic study in beagle dogs showed improved absorption of ibuprofen from cubic nanoparticles compared to that of pure ibuprofen, with evidence of a longer half-life and a relative oral bioavailability of 222% (P ibuprofen-loaded cubic nanoparticles provide a promising carrier candidate with an efficient drug delivery for therapeutic treatment. PMID:23468008

  11. Pharmacokinetics of an oral extended-release formulation of doxycycline hyclate containing acrylic acid and polymethacrylate in dogs.

    Science.gov (United States)

    Ruiz, Sara Melisa Arciniegas; Olvera, Lilia Gutiérrez; Chacón, Sara del Carmen Caballero; Estrada, Dinorah Vargas

    2015-04-01

    To determine the pharmacokinetics of doxycycline hyclate administered orally in the form of experimental formulations with different proportions of acrylic acid-polymethacrylate-based matrices. 30 healthy adult dogs. In a crossover study, dogs were randomly assigned (in groups of 10) to receive a single oral dose (20 mg/kg) of doxycycline hyclate without excipients (control) or extended-release formulations (ERFs) containing doxycycline, acrylic acid polymer, and polymethacrylate in the following proportions: 1:0.5:0.0075 (ERF1) or 1:1:0.015 (ERF2). Serum concentrations of doxycycline were determined for pharmacokinetic analysis before and at several intervals after each treatment. Following oral administration to the study dogs, each ERF resulted in therapeutic serum doxycycline concentrations for 48 hours, whereas the control treatment resulted in therapeutic serum doxycycline concentrations for only 24 hours. All pharmacokinetic parameters for ERF1 and ERF2 were significantly different; however, findings for ERF1 did not differ significantly from those for the control treatment. Results indicated that both ERFs containing doxycycline, acrylic acid polymer, and polymethacrylate had an adequate pharmacokinetic-pharmacodynamic relationship for a time-dependent drug and a longer release time than doxycycline alone following oral administration in dogs. Given the minimum effective serum doxycycline concentration of 0.26 μg/mL, a dose interval of 48 hours can be achieved for each tested ERF. This minimum inhibitory concentration has the potential to be effective against several susceptible bacteria involved in important infections in dogs. Treatment of dogs with either ERF may have several benefits over treatment with doxycycline alone.

  12. Controlled release studies of calcium alginate hydrogels

    International Nuclear Information System (INIS)

    Rendevski, S.; Andonovski, A.; Mahmudi, N.

    2012-01-01

    Controlled release of substances in many cases may be achieved from calcium alginate hydrogels. In this research, the time dependence of the mass of released model substance bovine serum albumin (BSA) from calcium alginate spherical hydrogels of three different types (G/M ratio) have been investigated. The hydrogels were prepared with the drop-wise method of sodium alginate aqueous solutions with concentration of 0.02 g/cm 3 with 0.01 g/cm 3 BSA and a gelling water bath of chitosan in 0.2 M CH 3 COOH/0.4 M CH 3 COONa with added 0.2 M CaCl 2 .The hydrogel structures were characterized by dynamic light scattering and scanning electron microscopy. The controlled release studies were conducted by UV-Vis spectrophotometry of the released medium with p H=7 at 37 °C. The results showed that the model of osmotic pumping is the dominant mechanism of the release. Also, large dependences of the release profile on the homogeneity of the hydrogels were found. (Author)

  13. Electrosprayed nanoparticle delivery system for controlled release

    Energy Technology Data Exchange (ETDEWEB)

    Eltayeb, Megdi, E-mail: megdi.eltayeb@sustech.edu [Department of Biomedical Engineering, Sudan University of Science and Technology, PO Box 407, Khartoum (Sudan); Stride, Eleanor, E-mail: eleanor.stride@eng.ox.ac.uk [Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Old Road Campus Research Building, Headington OX3 7DQ (United Kingdom); Edirisinghe, Mohan, E-mail: m.edirisinghe@ucl.ac.uk [Department of Mechanical Engineering, University College London, Torrington Place, London WC1E 7JE (United Kingdom); Harker, Anthony, E-mail: a.harker@ucl.ac.uk [London Centre for Nanotechnology, Gordon Street, London WC1H 0AH (United Kingdom); Department of Physics & Astronomy, University College London, Gower Street, London WC1E 6BT (United Kingdom)

    2016-09-01

    This study utilises an electrohydrodynamic technique to prepare core-shell lipid nanoparticles with a tunable size and high active ingredient loading capacity, encapsulation efficiency and controlled release. Using stearic acid and ethylvanillin as model shell and active ingredients respectively, we identify the processing conditions and ratios of lipid:ethylvanillin required to form nanoparticles. Nanoparticles with a mean size ranging from 60 to 70 nm at the rate of 1.37 × 10{sup 9} nanoparticles per minute were prepared with different lipid:ethylvanillin ratios. The polydispersity index was ≈ 21% and the encapsulation efficiency ≈ 70%. It was found that the rate of ethylvanillin release was a function of the nanoparticle size, and lipid:ethylvanillin ratio. The internal structure of the lipid nanoparticles was studied by transmission electron microscopy which confirmed that the ethylvanillin was encapsulated within a stearic acid shell. Fourier transform infrared spectroscopy analysis indicated that the ethylvanillin had not been affected. Extensive analysis of the release of ethylvanillin was performed using several existing models and a new diffusive release model incorporating a tanh function. The results were consistent with a core-shell structure. - Highlights: • Electrohydrodynamic spraying is used to produce lipid-coated nanoparticles. • A new model is proposed for the release rates of active components from nanoparticles. • The technique has potential applications in food science and medicine. • Electrohydrodynamic processing controlled release lipid nanoparticles.

  14. Massive radiological releases profoundly differ from controlled releases

    International Nuclear Information System (INIS)

    Pascucci-Cahen, Ludivine; Patrick, Momal

    2013-01-01

    In this article, the authors report identification and assessment of different types of costs associated with nuclear accidents. They first outline that these cost assessments must be as exhaustive or comprehensive as possible. While referring to past accidents, they define the different categories of costs: on-site costs (decontamination and dismantling, electricity not produced on the site), off-site costs (health costs, psychological costs, farming losses), image-related costs (impact on food and farm product exports, decrease of other exports), costs related to energy production, costs related to contaminated areas (refugees, lands). They give an assessment of a severe nuclear accident (i.e. an accident with important but controlled radiological releases) in France and outline that it would be a national catastrophe which could be however managed. They discuss the possible variations of the estimated costs. Then, they show that a major accident (i.e. an accident with massive radiological releases) in France would be an unmanageable European catastrophe because of the radiological consequences, of high economic costs, and of huge losses

  15. Investigation of in situ gelling alginate formulations as a sustained release vehicle for co-precipitates of dextromethrophan and Eudragit S 100

    Directory of Open Access Journals (Sweden)

    Maghraby Gamal Mohamed El

    2014-03-01

    Full Text Available Alginate vehicles are capable of forming a gel matrix in situ when they come into contact with gastric medium in the presence of calcium ions. However, the gel structure is pH dependent and can break after gastric emptying, leading to dose dumping. The aim of this work was to develop modified in situ gelling alginate formulations capable of sustaining dextromethorphan release throughout the gastrointestinal tract. Alginate solution (2 %, m/m was used as a vehicle for the tested formulations. Solid matrix of the drug and Eudragit S 100 was prepared by dissolving the drug and polymer in acetone. The organic solvent was then evaporated and the deposited solid matrix was micronized, sieved and dispersed in alginate solution to obtain candidate formulations. The release behavior of dextromethorphan was monitored and evaluated in a medium simulating the gastric and intestinal pH. Drug-polymer compatibility and possible solid-state interactions suggested physical interaction through hydrogen bonding between the drug and the polymer. A significant decrease in the rate and extent of dextromethorphan release was observed with increasing Eudragit S 100 concentration in the prepared particles. Most formulations showed sustained release profiles similar to that of a commercial sustained-release liquid based on ion exchange resin. The release pattern indicated strict control of drug release both under gastric and intestinal conditions, suggesting the potential advantage of using a solid dispersion of drug-Eudragit S 100 to overcome the problem of dose dumping after the rupture of the pH dependent alginate gels

  16. Sustained release biodegradable solid lipid microparticles: Formulation, evaluation and statistical optimization by response surface methodology

    Directory of Open Access Journals (Sweden)

    Hanif Muhammad

    2017-12-01

    Full Text Available For preparing nebivolol loaded solid lipid microparticles (SLMs by the solvent evaporation microencapsulation process from carnauba wax and glyceryl monostearate, central composite design was used to study the impact of independent variables on yield (Y1, entrapment efficiency (Y2 and drug release (Y3. SLMs having a 10-40 μm size range, with good rheological behavior and spherical smooth surfaces, were produced. Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffractometry pointed to compatibility between formulation components and the zeta-potential study confirmed better stability due to the presence of negative charge (-20 to -40 mV. The obtained outcomes for Y1 (29-86 %, Y2 (45-83 % and Y3 (49-86 % were analyzed by polynomial equations and the suggested quadratic model were validated. Nebivolol release from SLMs at pH 1.2 and 6.8 was significantly (p 0.85 value (Korsmeyer- Peppas suggested slow erosion along with diffusion. The optimized SLMs have the potential to improve nebivolol oral bioavailability.

  17. Sustained release biodegradable solid lipid microparticles: Formulation, evaluation and statistical optimization by response surface methodology.

    Science.gov (United States)

    Hanif, Muhammad; Khan, Hafeez Ullah; Afzal, Samina; Mahmood, Asif; Maheen, Safirah; Afzal, Khurram; Iqbal, Nabila; Andleeb, Mehwish; Abbas, Nazar

    2017-12-20

    For preparing nebivolol loaded solid lipid microparticles (SLMs) by the solvent evaporation microencapsulation process from carnauba wax and glyceryl monostearate, central composite design was used to study the impact of independent variables on yield (Y1), entrapment efficiency (Y2) and drug release (Y3). SLMs having a 10-40 μm size range, with good rheological behavior and spherical smooth surfaces, were produced. Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray diffractometry pointed to compatibility between formulation components and the zeta-potential study confirmed better stability due to the presence of negative charge (-20 to -40 mV). The obtained outcomes for Y1 (29-86 %), Y2 (45-83 %) and Y3 (49-86 %) were analyzed by polynomial equations and the suggested quadratic model were validated. Nebivolol release from SLMs at pH 1.2 and 6.8 was significantly (p 0.85 value (Korsmeyer- Peppas) suggested slow erosion along with diffusion. The optimized SLMs have the potential to improve nebivolol oral bioavailability.

  18. Formulating entompathogens for control of boring beetles in avocado orchards

    Science.gov (United States)

    A foam formulation of Beauveria bassiana was adapted to control boring beetles in avocado orchards. The two geographically independent avocado growing areas in the United States are threatened by emerging diseases vectored by boring beetles. In the California growing region, Fusarium dieback is vect...

  19. Stimuli responsive nanomaterials for controlled release applications

    KAUST Repository

    Li, Song; Li, Wengang; Khashab, Niveen M.

    2012-01-01

    applications. Stimuli-responsive nanomaterials guarantee the controlled release of cargo to a given location, at a specific time, and with an accurate amount. In this review, we have combined the major stimuli that are currently used to achieve the ultimate

  20. Bioadhesive Controlled Release Clotrimazole Vaginal Tablets | Bhat ...

    African Journals Online (AJOL)

    Conclusion: This study indicates the possible use of suitable mixtures of natural and semi-synthetic cellulosic polymers for the preparation of clotrimazole mucoadhesive tablets for application as a vaginal controlled delivery system. Keywords: Clotrimazole, Swelling, Cellulosic polymers, Guar gum, Bioadhesion, Release ...

  1. Controlled-Release Personal Use Arthropod Repellent Formulation. Phase 2

    Science.gov (United States)

    1986-09-15

    damage, pitting M - Hypopyon N - Corneal neovascularization P - Pannus R - Unable to visualize due to severe opacity S - Granulation scar tissue POS...M - Hypopyon N - Corneal neovascularization P - Pannus R - Unable to visualize due to severe opacity S - Granulation scar tissue POS -Positive...Corneal epithelial damage, piling L - Corneal epithelial damage, pitting M - Hypopyon N - Corneal neovascularization P - Pannus R - Unable to

  2. Quality control of an antipsoriatic ayurvedic herbal Formulation: Lajjalu Keram

    Directory of Open Access Journals (Sweden)

    M T Athar

    2016-01-01

    Full Text Available Background: Psoriasis is an autoimmune disorder, which affects a large group of human population of world (3%. Till date, there is no treatment for psoriasis except some herbal drugs and its constituents. Since Ayurveda is the main traditional system of medicine in India, here, we have selected one ayurvedic formulation - Lajjalu Keram, which has been used since long for their quality control. Methods: Total microbial load of formulations were carried out for total fungal count and total bacterial count. Lajjalu Keram was also tested by high-performance liquid chromatographic (HPLC for aflatoxins (B1, B2, G1, and G2, which showed its presence below the permissible limit; similarly, pesticides residues were analyzed using gas chromatography/mass spectrometry for organophosphates and organochlorides, which showed that pesticides were below detection limit (0.1 ppb. The content of heavy metals was analyzed using AAS, which demonstrated the presence of cadmium, lead, and arsenic below permissible limit, whereas mercury was found absent. Results: The result of quality control analysis showed the presence of alkaloids, tannins, carbohydrate, saponins, proteins and amino acids, lipid/fats, phenolic compounds, and flavonoids in formulation. The dermal toxicity (LD50 of Lajjalu Keram in Wistar rats was found more than 2000 mg/kg (safe for the management of psoriasis. Formulation was also analyzed for their composition of fatty acids. It was found to have 13 fatty acids, out of which, seven were saturated fatty acids (95.2% and the rest were unsaturated fatty acids (3.27%. A rapid HPLC method for quantification of mimosine (an unusual amino acid present in formulation has been developed and validated. The mimosine content in Lajjalu Keram was found to be 0.0070% w/w with % relative standard deviation of 0.41. Conclusion: The formulation afforded significant and better protection of carrageenan-induced rat paw edema (72.11% inhibition as compared to

  3. Controlled release systems containing solid dispersions: strategies and mechanisms.

    Science.gov (United States)

    Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh; Park, Jun Bom; Lee, Beom-Jin

    2011-10-01

    In addition to a number of highly soluble drugs, most new chemical entities under development are poorly water-soluble drugs generally characterized by an insufficient dissolution rate and a small absorption window, leading to the low bioavailability. Controlled-release (CR) formulations have several potential advantages over conventional dosage forms, such as providing a uniform and prolonged therapeutic effect to improve patient compliance, reducing the frequency of dosing, minimizing the number of side effects, and reducing the strength of the required dose while increasing the effectiveness of the drug. Solid dispersions (SD) can be used to enhance the dissolution rate of poorly water-soluble drugs and to sustain the drug release by choosing an appropriate carrier. Thus, a CR-SD comprises both functions of SD and CR for poorly water-soluble drugs. Such CR dosage forms containing SD provide an immediately available dose for an immediate action followed by a gradual and continuous release of subsequent doses to maintain the plasma concentration of poorly water-soluble drugs over an extended period of time. This review aims to summarize all currently known aspects of controlled release systems containing solid dispersions, focusing on the preparation methods, mechanisms of action and characterization of physicochemical properties of the system.

  4. EPICS application source/release control

    International Nuclear Information System (INIS)

    Zieman, B.; Anderson, J.; Kraimer, M.

    1995-01-01

    This manual describes a set of Application Source/Release Control tools (appSR) that can be used to develop software for EPICS based control systems. The Application Source/Release Control System (appSR) has been unbundled from base EPICS and is now available as an EPICS extension. Due to this unbundling, two new directories must be added to a user's path (see section ''Environment'' on page 3 for more information) and a new command getapp must be issued after the getrel command to get a specific version of appSR (see section ''Creating The Initial Application System Area'' on page 7 for more information). It is now required that GNU make version 3.71 or later be used for makes instead of SUN make. Users should now type gmake instead of make

  5. Extended‐Release Once‐Daily Formulation of Tofacitinib: Evaluation of Pharmacokinetics Compared With Immediate‐Release Tofacitinib and Impact of Food

    Science.gov (United States)

    Wang, Rong; Fletcher, Tracey; Alvey, Christine; Kushner, Joseph; Stock, Thomas C.

    2016-01-01

    Abstract Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. An extended‐release (XR) formulation has been designed to provide a once‐daily (QD) dosing option to patients to achieve comparable pharmacokinetic (PK) parameters to the twice‐daily immediate‐release (IR) formulation. We conducted 2 randomized, open‐label, phase 1 studies in healthy volunteers. Study A characterized single‐dose and steady‐state PK of tofacitinib XR 11 mg QD and intended to demonstrate equivalence of exposure under single‐dose and steady‐state conditions to tofacitinib IR 5 mg twice daily. Study B assessed the effect of a high‐fat meal on the bioavailability of tofacitinib from the XR formulation. Safety and tolerability were monitored in both studies. In study A (N = 24), the XR and IR formulations achieved time to maximum plasma concentration at 4 hours and 0.5 hours postdose, respectively; terminal half‐life was 5.9 hours and 3.2 hours, respectively. Area under plasma concentration‐time curve (AUC) and maximum plasma concentration (Cmax) after single‐ and multiple‐dose administration were equivalent between the XR and IR formulations. In study B (N = 24), no difference in AUC was observed for fed vs fasted conditions. Cmax increased by 27% under the fed state. On repeat administration, negligible accumulation (Tofacitinib administration as an XR or IR formulation was generally well tolerated in these studies. PMID:26970526

  6. Formulation of a poorly water-soluble drug in sustained-release hollow granules with a high viscosity water-soluble polymer using a fluidized bed rotor granulator.

    Science.gov (United States)

    Asada, Takumi; Yoshihara, Naoki; Ochiai, Yasushi; Kimura, Shin-Ichiro; Iwao, Yasunori; Itai, Shigeru

    2018-04-25

    Water-soluble polymers with high viscosity are frequently used in the design of sustained-release formulations of poorly water-soluble drugs to enable complete release of the drug in the gastrointestinal tract. Tablets containing matrix granules with a water-soluble polymer are preferred because tablets are easier to handle and the multiple drug-release units of the matrix granules decreases the influences of the physiological environment on the drug. However, matrix granules with a particle size of over 800 μm sometimes cause a content uniformity problem in the tableting process because of the large particle size. An effective method of manufacturing controlled-release matrix granules with a smaller particle size is desired. The aim of this study was to develop tablets containing matrix granules with a smaller size and good controlled-release properties, using phenytoin as a model poorly water-soluble drug. We adapted the recently developed hollow spherical granule granulation technology, using water-soluble polymers with different viscosities. The prepared granules had an average particle size of 300 μm and sharp particle size distribution (relative width: 0.52-0.64). The values for the particle strength of the granules were 1.86-1.97 N/mm 2 , and the dissolution profiles of the granules were not affected by the tableting process. The dissolution profiles and the blood concentration levels of drug released from the granules depended on the viscosity of the polymer contained in the granules. We succeeded in developing the desired controlled-release granules, and this study should be valuable in the development of sustained-release formulations of poorly water-soluble drugs. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Formulation and Evaluation of a Sustained-Release Tablets of Metformin Hydrochloride Using Hydrophilic Synthetic and Hydrophobic Natural Polymers

    OpenAIRE

    Wadher, K. J.; Kakde, R. B.; Umekar, M. J.

    2011-01-01

    Metformin hydrochloride has relatively short plasma half-life, low absolute bioavailability. The need for the administration two to three times a day when larger doses are required can decrease patient compliance. Sustained release formulation that would maintain plasma level for 8-12 h might be sufficient for daily dosing of metformin. Sustained release products are needed for metformin to prolong its duration of action and to improve patient compliances. The overall objective of this study ...

  8. Single Layer Extended Release Two-in-One Guaifenesin Matrix Tablet: Formulation Method, Optimization, Release Kinetics Evaluation and Its Comparison with Mucinex® Using Box-Behnken Design.

    Science.gov (United States)

    Morovati, Amirhosein; Ghaffari, Alireza; Erfani Jabarian, Lale; Mehramizi, Ali

    2017-01-01

    Guaifenesin, a highly water-soluble active (50 mg/mL), classified as a BCS class I drug. Owing to its poor flowability and compressibility, formulating tablets especially high-dose one, may be a challenge. Direct compression may not be feasible. Bilayer tablet technology applied to Mucinex®, endures challenges to deliver a robust formulation. To overcome challenges involved in bilayer-tablet manufacturing and powder compressibility, an optimized single layer tablet prepared by a binary mixture (Two-in-one), mimicking the dual drug release character of Mucinex ® was purposed. A 3-factor, 3-level Box-Behnken design was applied to optimize seven considered dependent variables (Release "%" in 1, 2, 4, 6, 8, 10 and 12 h) regarding different levels of independent one (X 1 : Cetyl alcohol, X 2 : Starch 1500 ® , X 3 : HPMC K100M amounts). Two granule portions were prepared using melt and wet granulations, blended together prior to compression. An optimum formulation was obtained (X 1 : 37.10, X 2 : 2, X 3 : 42.49 mg). Desirability function was 0.616. F2 and f1 between release profiles of Mucinex® and the optimum formulation were 74 and 3, respectively. An n-value of about 0.5 for both optimum and Mucinex® formulations showed diffusion (Fickian) control mechanism. However, HPMC K100M rise in 70 mg accompanied cetyl alcohol rise in 60 mg led to first order kinetic (n = 0.6962). The K values of 1.56 represented an identical burst drug releases. Cetyl alcohol and starch 1500 ® modulated guaifenesin release from HPMC K100M matrices, while due to their binding properties, improved its poor flowability and compressibility, too.

  9. Safety case for the disposal of spent nuclear fuel at Olkiluoto. Formulation of radionuclide release scenarios 2012

    International Nuclear Information System (INIS)

    2013-04-01

    TURVA-2012 is Posiva's safety case in support of the Preliminary Safety Analysis Report (PSAR) and application for a construction licence for a repository for disposal of spent nuclear fuel at the Olkiluoto site in south-western Finland. This report presents the radionuclide release scenarios and the methodology followed in formulating them. The formulation of scenarios takes into account the regulatory framework, the knowledge acquired in the present safety case as well as in previous safety assessments, the safety functions of the barriers of the repository system and the uncertainties in the features, events, and processes (FEPs) that may affect the entire disposal system (i.e. repository system plus the surface environment) from the emplacement of the first canister until the far future. In the report Performance Assessment, the performance of the engineered and natural barriers has been assessed against the loads expected during the evolution of the repository system and the site. Uncertainties have been identified and these are taken into account in the formulation of radionuclide release scenarios. The uncertainties in the FEPs affecting the characteristics and evolution of the surface environment are taken into account in formulating the surface environment scenarios used ultimately for assessing radiation exposure. Formulating radionuclide release scenarios for the repository system links the reports Performance Assessment and Assessment of Radionuclide Release Scenarios for the Repository System. The formulation of radionuclide release scenarios for the surface environment brings together Biosphere Description and the surface environment FEPs and is the link to the assessment of the surface environment scenarios analysed in Biosphere Assessment. (orig.)

  10. Effect of thermal and chemical modifications on the mechanical and release properties of paracetamol tablet formulations containing corn, cassava and sweet potato starches as filler-binders

    Directory of Open Access Journals (Sweden)

    Mariam Vbamiunomhene Lawal

    2015-07-01

    Conclusions: Modification of the experimental starches improved the mechanical and release properties of directly compressed paracetamol tablet formulations. Thus, they can be developed for use as pharmaceutical excipients in specific formulations.

  11. Controlling Release of Integral Lipid Nanoparticles Based on Osmotic Pump Technology.

    Science.gov (United States)

    Tian, Zhiqiang; Yu, Qin; Xie, Yunchang; Li, Fengqian; Lu, Yi; Dong, Xiaochun; Zhao, Weili; Qi, Jianping; Wu, Wei

    2016-08-01

    To achieve controlled release of integral nanoparticles by the osmotic pump strategy using nanostructured lipid carriers (NLCs) as model nanoparticles. NLCs was prepared by a hot-homogenization method, transformed into powder by lyophilization, and formulated into osmotic pump tablets (OPTs). Release of integral NLCs was visualized by live imaging after labeling with a water-quenching fluorescent probe. Effects of formulation variables on in vitro release characteristics were evaluated by measuring the model drug fenofibrate. Pharmacokinetics were studied in beagle dogs using the core tablet and a micronized fenofibrate formulation as references. NLCs are released through the release orifices of the OPTs as integral nanoparticles. Near zero-order kinetics can be achieved by optimizing the influencing variables. After oral administration, decreased C max and steady drug levels for as long as over 24 h are observed. NLC-OPTs show an oral bioavailability of the model drug fenofibrate similar to that of the core tablets, which is about 1.75 folds that of a fast-release formulation. Controlled release of integral NLCs is achieved by the osmotic pump strategy.

  12. Meltable magnetic biocomposites for controlled release

    Energy Technology Data Exchange (ETDEWEB)

    Müller, R., E-mail: robert.mueller@ipht-jena.de [Leibniz Institute of Photonic Technology (IPHT), P.O.B. 100239, Jena, D-07702 Germany (Germany); Zhou, M. [Institute of Organic Chemistry and Macromolecular Chemistry, Friedrich Schiller University of Jena, Humboldtstrasse 10, Jena, D-07743 Germany (Germany); Dellith, A. [Leibniz Institute of Photonic Technology (IPHT), P.O.B. 100239, Jena, D-07702 Germany (Germany); Liebert, T.; Heinze, T. [Institute of Organic Chemistry and Macromolecular Chemistry, Friedrich Schiller University of Jena, Humboldtstrasse 10, Jena, D-07743 Germany (Germany)

    2017-06-01

    New biocompatible composites with adjustable melting point in the range of 30–140 °C, consisting of magnetite nanoparticles embedded into a matrix of meltable dextran fatty acid ester are presented which can be softened under an induced alternating magnetic field (AMF). The chosen thermoplastic magnetic composites have a melting range close to human body temperature and can be easily shaped into disk or coating film under melting. The composite disks were loaded with green fluorescent protein (GFP) as a model protein. Controlled release of the protein was realized with high frequent alternating magnetic field of 20 kA/m at 400 kHz. These results showed that under an AMF the release of GFP from magnetic composite was accelerated compared to the control sample without exposure to AMF. Furthermore a texturing of particles in the polymer matrix by a static magnetic field was investigated. - Highlights: • Thermoplastic biocomposite are prepared from dextran ester and magnetite particles. • The composite can be heated by an AC magnetic field above the melting temperature. • In molten state texturing of particles is possible and improves the heating ability. • The biopolymer could be used as a remote controlled matrix for protein release.

  13. Simultaneous Intercalation of 1-Naphthylacetic Acid and Indole-3-butyric Acid into Layered Double Hydroxides and Controlled Release Properties

    Directory of Open Access Journals (Sweden)

    Shifeng Li

    2014-01-01

    Full Text Available Controlled release formulations have been shown to have potential in overcoming the drawbacks of conventional plant growth regulators formulations. A controlled-release formulation of 1-naphthylacetic acid (NAA and indole-3-butyric acid (IBA simultaneous intercalated MgAl-layered double hydroxides (LDHs was prepared. The synthetic nanohybrid material was characterized by various techniques, and release kinetics was studied. NAA and IBA anions located in the gallery of MgAl-LDHs with bilayer arrangement, and the nanohybrids particles were of typical plate-like shape with the lateral size of 50–100 nm. The results revealed that NAA and IBA have been intercalated into the interlayer spaces of MgAl-LDHs. The release of NAA and IBA fits pseudo-second-order model and is dependent on temperature, pH value, and release medium. The nanohybrids of NAA and IBA simultaneously intercalated in LDHs possessed good controlled release properties.

  14. Controlled drug release from bifunctionalized mesoporous silica

    Science.gov (United States)

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

    2008-10-01

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

  15. Formulation development and optimization of sustained release matrix tablet of Itopride HCl by response surface methodology and its evaluation of release kinetics.

    Science.gov (United States)

    Bose, Anirbandeep; Wong, Tin Wui; Singh, Navjot

    2013-04-01

    The objective of this present investigation was to develop and formulate sustained release (SR) matrix tablets of Itopride HCl, by using different polymer combinations and fillers, to optimize by Central Composite Design response surface methodology for different drug release variables and to evaluate drug release pattern of the optimized product. Sustained release matrix tablets of various combinations were prepared with cellulose-based polymers: hydroxy propyl methyl cellulose (HPMC) and polyvinyl pyrolidine (pvp) and lactose as fillers. Study of pre-compression and post-compression parameters facilitated the screening of a formulation with best characteristics that underwent here optimization study by response surface methodology (Central Composite Design). The optimized tablet was further subjected to scanning electron microscopy to reveal its release pattern. The in vitro study revealed that combining of HPMC K100M (24.65 MG) with pvp(20 mg)and use of LACTOSE as filler sustained the action more than 12 h. The developed sustained release matrix tablet of improved efficacy can perform therapeutically better than a conventional tablet.

  16. A double-blind placebo-controlled study of controlled release fluvoxamine for the treatment of generalized social anxiety disorder

    NARCIS (Netherlands)

    Westenberg, HGM; Stein, DJ; Yang, HC; Li, D; Barbato, LM

    This was a randomized double-blind placebo-controlled multicenter study to assess the efficacy, safety, and tolerability of fluvoxamine in a controlled release (CR) formulation for treatment of generalized social anxiety disorder (GSAD). A total of 300 subjects with GSAD were randomly assigned to

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

    Science.gov (United States)

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

    2012-01-01

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

  18. Are Branded and Generic Extended-Release Ropinirole Formulations Equally Efficacious? A Rater-Blinded, Switch-Over, Multicenter Study

    Directory of Open Access Journals (Sweden)

    Edit Bosnyák

    2014-01-01

    Full Text Available The aim of this study was to compare the efficacy of the branded and a generic extended-release ropinirole formulation in the treatment of advanced Parkinson’s disease (PD. Of 22 enrolled patients 21 completed the study. A rater blinded to treatment evaluated Unified Parkinson’s Disease Rating Scale, Fahn-Tolosa-Marin Tremor Rating Scale, Nonmotor Symptoms Assessment Scale, and a structured questionnaire on ropinirole side effects. Besides, the patients self-administered EQ-5D, Parkinson’s Disease Sleep Scale (PDSS-2, and Beck Depression Inventories. Branded and generic ropinirole treatment achieved similar scores on all tests measuring severity of motor symptoms (primary endpoint, UPDRS-III: 27.0 versus 28.0 points, P=0.505. Based on patient diaries, the lengths of “good time periods” were comparable (10.5 and 10.0 hours for branded and generic ropinirole, resp., P=0.670. However, generic ropinirole therapy achieved almost 3.0 hours shorter on time without dyskinesia (6.5 versus. 9.5 hours, P<0.05 and 2.5 hours longer on time with slight dyskinesia (3.5 versus. 1.0 hours, P<0.05 than the branded ropinirole did. Except for gastrointestinal problems, nonmotor symptoms were similarly controlled. Patients did not prefer either formulation. Although this study has to be interpreted with limitations, it demonstrated that both generic and branded ropinirole administration can achieve similar control on most symptoms of PD.

  19. Investigation of an artificial intelligence technology--Model trees. Novel applications for an immediate release tablet formulation database.

    Science.gov (United States)

    Shao, Q; Rowe, R C; York, P

    2007-06-01

    This study has investigated an artificial intelligence technology - model trees - as a modelling tool applied to an immediate release tablet formulation database. The modelling performance was compared with artificial neural networks that have been well established and widely applied in the pharmaceutical product formulation fields. The predictability of generated models was validated on unseen data and judged by correlation coefficient R(2). Output from the model tree analyses produced multivariate linear equations which predicted tablet tensile strength, disintegration time, and drug dissolution profiles of similar quality to neural network models. However, additional and valuable knowledge hidden in the formulation database was extracted from these equations. It is concluded that, as a transparent technology, model trees are useful tools to formulators.

  20. The impact of manufacturing variables on in vitro release of clobetasol 17-propionate from pilot scale cream formulations.

    Science.gov (United States)

    Fauzee, Ayeshah Fateemah Beebee; Khamanga, Sandile Maswazi; Walker, Roderick Bryan

    2014-12-01

    The purpose of the study was to evaluate the effect of different homogenization speeds and times, anchor speeds and cooling times on the viscosity and cumulative % clobetasol 17-propionate released per unit area at 72 h from pilot scale cream formulations. A 2(4) full factorial central composite design for four independent variables were investigated. Thirty pilot scale batches of cream formulations were manufactured using a Wintech® cream/ointment plant. The viscosity and in vitro release of CP were monitored and compared to an innovator product that is commercially available on the South African market, namely, Dermovate® cream. Contour and three-dimensional response surface plots were produced and the viscosity and cumulative % CP released per unit area at 72 h were found to be primarily dependent on the homogenization and anchor speeds. An increase in the homogenization and anchor speeds appeared to exhibit a synergistic effect on the resultant viscosity of the cream whereas an antagonistic effect was observed for the in vitro release of CP from the experimental cream formulations. The in vitro release profiles were best fitted to a Higuchi model and diffusion proved to be the dominant mechanism of drug release that was confirmed by use of the Korsmeyer-Peppas model. The research was further validated and confirmed by the high prognostic ability of response surface methodology (RSM) with a resultant mean percentage error of (±SD) 0.17 ± 0.093 suggesting that RSM may be an efficient tool for the development and optimization of topical formulations.

  1. Effect of Nisin's Controlled Release on Microbial Growth as Modeled for Micrococcus luteus.

    Science.gov (United States)

    Balasubramanian, Aishwarya; Lee, Dong Sun; Chikindas, Michael L; Yam, Kit L

    2011-06-01

    The need for safe food products has motivated food scientists and industry to find novel technologies for antimicrobial delivery for improving food safety and quality. Controlled release packaging is a novel technology that uses the package to deliver antimicrobials in a controlled manner and sustain antimicrobial stress on the targeted microorganism over the required shelf life. This work studied the effect of controlled release of nisin to inhibit growth of Micrococcus luteus (a model microorganism) using a computerized syringe pump system to mimic the release of nisin from packaging films which was characterized by an initially fast rate and a slower rate as time progressed. The results show that controlled release of nisin was strikingly more effective than instantly added ("formulated") nisin. While instant addition experiments achieved microbial inhibition only at the beginning, controlled release experiments achieved complete microbial inhibition for a longer time, even when as little as 15% of the amount of nisin was used as compared to instant addition.

  2. Formulation and quality control of a poly herbal tranquilizer syrup

    Directory of Open Access Journals (Sweden)

    2017-11-01

    Full Text Available Background and objectives: Herbal drugs are rapidly becoming popular in recent years as alternative therapies. Numerous poly herbal formulations, which are combinations of different herbal materials/extracts are being used for prevention or treatment of various disorders. The present research has been undertaken to formulate and evaluate the quality of a tranquilizing syrup based on Iranian traditional medicine references. Methods: A decoction containing Echium amoenum L., Lavandula spp. L., Melissa officinalis L., Cuscuta chinensis Lam, Vitis venifera L.,Prunus domestica and Alhagi camelorum Fisch.was prepared and then filtered. The filtrate was concentrated and different sweeteners and flavoring agents including, brown sugar, honey, masking flavor, sucralose, lemon and orange essential oil were examined to cover the unpleasant taste of the product caused by Cuscuta chinensis. Finally,sucralose was found to be beneficent to cover the unpleasant taste. The final product was evaluated physicochemically and microbiologically according to standard protocols. Results: The results of the quality control assessments demonstrated that the color, odor, microbial and physicochemical characteristics of the syrup were acceptable. Conclusion: The formulated syrup can be examined in in vivo and clinical studies as a tranquilizer with respect to its tranquilizing herbal content.

  3. A New Environmentally Safe Formulation and of Low Cost for Prolonged Release System of Atrazine and Diuron

    Directory of Open Access Journals (Sweden)

    Gracy karla da Rocha Cortes

    2017-07-01

    Full Text Available Diuron and atrazine were incorporated in new formulations developed with the purpose to improve herbicides action through release systems, as well as to reduce the environmental toxicity. A low cost formulation (ALG/ESC was obtained by combining sodium alginate (ALG with fish scales of the Piau fish (ESC from the Leporinus elongatus species. From the crosslinking of ALG/ESC with CaCl2, the formulation ALG/ESC-CaCl2 was obtained. For ALG/ESC-CaCl2, the results are successful, showing a prolonged release of 3.5 and 4.5 days for atrazine and diuron, respectively. Based on parameters of an empirical equation used to fit the herbicide release data, it appears that the release systems of diuron and atrazine from ALG/ESC-CaCl2 are by diffusion processes due to anomalous transport, which did not follow Fick’s laws of diffusion. DOI: http://dx.doi.org/10.17807/orbital.v9i3.994

  4. Comparative steady-state pharmacokinetic study of an extended-release formulation of itopride and its immediate-release reference formulation in healthy volunteers

    OpenAIRE

    Yoon, Seonghae; Lee, Howard; Kim, Tae-Eun; Lee, SeungHwan; Chee, Dong-Hyun; Cho, Joo-Youn; Yu, Kyung-Sang; Jang, In-Jin

    2014-01-01

    Seonghae Yoon,1,* Howard Lee,2,* Tae-Eun Kim,1 SeungHwan Lee,1 Dong-Hyun Chee,3 Joo-Youn Cho,1 Kyung-Sang Yu,1 In-Jin Jang1 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 2Clinical Trials Center, Seoul National University Hospital, 3AbbVie Ltd., Seoul, Republic of Korea *These authors contributed equally to this work Background: This study was conducted to compare the oral bioavailability of an itopride extended-release (ER...

  5. Extended-Release Once-Daily Formulation of Tofacitinib: Evaluation of Pharmacokinetics Compared With Immediate-Release Tofacitinib and Impact of Food.

    Science.gov (United States)

    Lamba, Manisha; Wang, Rong; Fletcher, Tracey; Alvey, Christine; Kushner, Joseph; Stock, Thomas C

    2016-11-01

    Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. An extended-release (XR) formulation has been designed to provide a once-daily (QD) dosing option to patients to achieve comparable pharmacokinetic (PK) parameters to the twice-daily immediate-release (IR) formulation. We conducted 2 randomized, open-label, phase 1 studies in healthy volunteers. Study A characterized single-dose and steady-state PK of tofacitinib XR 11 mg QD and intended to demonstrate equivalence of exposure under single-dose and steady-state conditions to tofacitinib IR 5 mg twice daily. Study B assessed the effect of a high-fat meal on the bioavailability of tofacitinib from the XR formulation. Safety and tolerability were monitored in both studies. In study A (N = 24), the XR and IR formulations achieved time to maximum plasma concentration at 4 hours and 0.5 hours postdose, respectively; terminal half-life was 5.9 hours and 3.2 hours, respectively. Area under plasma concentration-time curve (AUC) and maximum plasma concentration (C max ) after single- and multiple-dose administration were equivalent between the XR and IR formulations. In study B (N = 24), no difference in AUC was observed for fed vs fasted conditions. C max increased by 27% under the fed state. On repeat administration, negligible accumulation (Tofacitinib administration as an XR or IR formulation was generally well tolerated in these studies. © 2016, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

  6. 28 CFR 541.50 - Release from a control unit.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Release from a control unit. 541.50... INMATE DISCIPLINE AND SPECIAL HOUSING UNITS Control Unit Programs § 541.50 Release from a control unit. (a) Only the Executive Panel may release an inmate from a control unit. The following factors are...

  7. Fabrication of ketoprofen controlled-release tablets using biopolymeric hydrophilic matrices: in-vitro studies

    International Nuclear Information System (INIS)

    Rashid, S.; Khan, B.A.; Khan, G.M.

    2017-01-01

    Ketoprofen is propionic acid derivative and belongs to the Non-Steroidal anti-inflammatory group of drugs. Due to the short half-life, dosage frequency, patient non-compliance and side effects such as gastrointestinal disturbance, peptic ulceration and gastro intest inal bleeding, it is considered to be good candidate for formulation into controlled release dosage forms. Directly compressed controlled released ( CR) tablets using Acrylic acid derivatives were prepared and evaluated. In-Vitro Physicochemical assessment of the formulated tablets were performed using different physicochemical, dimensional and quality control tests such as weight variation, thickness and diameter, hardness test, friability test, content uniformity, disintegration and dissolution testing. Results of all these tests were formed within acceptable range. The effect of carbomer polymers on the tablet characteristics, drug release rates, release patterns and release kinetics were investigated. The F2-metric technique was applied to compare dissolution profiles of ketoprofen and carbopol tablets with ketoprofen SR - tablets taken as standard preparation. Acrylic acid derivatives when used as polymers resulted in an extended release profile of about 12 h. Using Higuchi's model and the Korsmeyer equation, the drug release mechanism from the tablets was found to be an anomalous type involving diffusion and erosion. Controlled- release Ketoprofen tablets appear to be a good choice for the symptomatic treatment of rheumatoid arthritis and osteoarthritis. Convenient once-daily administration may help improve patient's compliance. (author)

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

    Science.gov (United States)

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

    2013-11-01

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

  9. [Abpm and duration of the antihypertensive effect: a study with a new formulation of sustained release losartan (CRONOS)].

    Science.gov (United States)

    Bendersky, Mario; Juncos, Luis; Waisman, Gabriel Dario; Piskorz, Daniel; Lopez-Santi, Ricardo; Montaña, Oscar; Caruso, Gustavo; Kotetzky, Martin; Penna, Maria; Gomez, Roberto

    2012-01-01

    Antihypertensive drugs action should last at least 24 h in order to enhance adherence, with positive impact on CV morbimortality. ABPM allow us to evaluate duration of action of drugs, against placebo, using Trough:Peak Ratio, antihypertensive effect in the last 4 h interdosis, and calculating the rate of BP morning surge. Losartán is an Antagonist At1 with good antihypertensive efficacy and renal, cardiac and cerebrovascular protection. Some studies shows less than 24 hs of action, that suggest twice a day dosing. The merge of a new formulation, Losartan Cronos, a bilayer tablet containing 50 mg of Losartan immediate release (IR) and 50 mg extended release (ER) would allow 24 h coverage, maintaining the previous advantages. To assess antihypertensive duration of action of Losartán Cronos in patients with essential hypertension throughout a 24-h dosing interval, using ABPM and response rates, AASI and Smoothness Index. 97 essential hypertensives, where included and received a single morning dose of Losartán Cronos (50 mg of regular release and 50 mg of controlled and retarded release) during 8 weeks. Performed valid ABPM post placebo and post active treatment. Results Mean age 58 (26-86), 60% women. 63% treatment naïve. The mean reduction in BP from baseline to week 8 (end of treatment) was statistically significant for all times analyzed (24 hours, daytime, night-time, and last 4 hours monitoring). There were no significant changes in 24h heart rate. BP morning surge (mmHg/hour) decreased from 4.53 to 3,68 (p=0.03).T:P Ratio was 0.91 for SBP and 1.14 for DBP. Smoothness Index: SBP 2.86 (95% CI 1.84-3.7) - DBP 3.17 (95% CI 2.03-3.9) 19 patients had adverse events, no-one cough, all mild, without discontinuations. Conclusion Losartán Cronos demonstrated efficacy and safety, decreases BP without significant effects in heart rate, it reduces the pulse pressure, and its effect lasts for 24 hs, assessed by T:P ratio, last 4 hours effects, decreasing morning surge

  10. The effect of additives on release and in vitro skin retention of flavonoids from emulsion and gel semisolid formulations.

    Science.gov (United States)

    Dyja, R; Jankowski, A

    2017-08-01

    To assess the effect of two different additives (propylene glycol (PG) and polyethylene glycol 400 (PEG 400)) on release and in vitro skin retention of quercetin and chrysin from semisolid bases (amphiphilic creams and acidic carbomer gels). For obtaining semisolid formulations, flavonoids were pre-dissolved in the liquid (PG or PEG 400) or directly suspended in the semisolid base. Three chrysin formulations ('cream 0', 'PG-cream' and 'PEG 400-cream') and five quercetin formulations ('cream 0', 'PG cream', 'PEG 400 cream', 'gel 0' and 'PG gel') were prepared. The release studies were carried out in Franz diffusion cells by means of a cellulose membrane. The porcine ear skin was used in in vitro skin retention studies. The dissolution was a prerequisite to increase the release rates of tested flavonoids from obtained semisolid formulations. The cumulative amount of chrysin released after 6 h from 'PEG 400 cream' containing partly dissolved form of that flavonoid was higher than that from 'cream 0' or 'PG cream' containing its suspended form. The formulations containing quercetin dissolved in PG ('PG cream', 'PG gel') or PEG 400 ('PEG 400 cream') exhibited higher release rates of that flavonoid than corresponding semisolid suspensions ('cream 0' or 'gel 0'). The effects of both liquid additives (PG and PEG 400) on the cumulative amount of quercetin released after 6 h were comparable. However, there was no correlation between the release rate and the skin retention. The amounts of the flavonoids found in the skin were strongly affected by the type of the used solvent. While PG increased the skin retention of both flavonoids, PEG 400 had no effect on chrysin skin retention and delayed quercetin skin absorption. The proper choice of the solvent added to the semisolid base is crucial for enhanced skin delivery of the tested flavonoids. PG is more efficient absorption promoter than PEG 400 of both chrysin and quercetin. © 2017 Society of Cosmetic Scientists and the Soci

  11. Development and evaluation of diltiazem hydrochloride controlled-release pellets by fluid bed coating process

    Directory of Open Access Journals (Sweden)

    Mikkilineni Bhanu Prasad

    2013-01-01

    Full Text Available 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.

  12. [The use of natural and synthetic hydrophilic polymers in the formulation of metformin hydrochloride tablets with different profile release].

    Science.gov (United States)

    Kołodziejczyk, Michał Krzysztof; Kołodziejska, Justyna; Zgoda, Marian Mikołaj

    2012-01-01

    Metformin hydrochloride after buformin and phenformin belongs to the group of biguanid derivatives used as oral anti-diabetic drugs. The object of the study is the technological analysis and the potential effect of biodegradable macromolecular polymers on the technological and therapeutic parameters of oral anti-diabetic medicinal products with metformin hydrochloride: Siofor, Formetic, Glucophage, Metformax in doses of 500mg and 1000mg and Glucophage XR in a dose of 500 mg of modified release. Market therapeutic products containing 500 and 1000 mg of metformin hydrochloride in a normal formulation and 500 mg of metformin hydrochloride in a formulation of modified release were analyzed. Following research methods were used: technological analysis of tablets, study of disintegration time of tablets, evaluation of pharmaceutical availability of metformin hydrochloride from tested therapeutic products, mathematical and kinetic analysis of release profiles of metformin hydrochloride, statistical analysis of mean differences of release coefficients. The percentage of excipients in the XR formulation is higher and constitutes 50.5% of a tablet mass. However, in standard formulations the percentage is lower, between 5.5% and 12.76%. On the basis of the results of disintegration time studies, the analysed therapeutic products can be divided into two groups, regardless the dose. The first one are preparations with faster (not fast!) disintegration: Glucophage i Metformax. The second group are preparations with slower disintegration, more balanced in the aspect of a high dose of the biologically active substance: Formetic and Siofor. Products with a lower content of excipients (Metformax, Glucophage) disintegrate in a faster way. The disintegration rate of the products with a higher content of excipients (Formetic, Siofor) is slower. The appearance of metformin hydrochloride concentration in the gastrointestinal contents, balanced in time, caused by a slower disintegration

  13. Synthesis of hydrogels of alginate for system controlled release of progesterone

    International Nuclear Information System (INIS)

    Abreu, Marlon de F.; Rodriguez, Ruben J.S.; Silva, Ester C.C. da; Barreto, Gabriela N.S.

    2015-01-01

    The chemical modifications of natural polymers like alginate, has allowed the development of new formulations for controlled release systems. In this work we report the synthesis of a derivative of the amidic alginate with alkyl chain. The polymer was characterized by spectroscopic techniques: Nuclear Magnetic Resonance and Fourier Transform Infrared. (author)

  14. Poly lactic acid based injectable delivery systems for controlled release of a model protein, lysozyme.

    Science.gov (United States)

    Al-Tahami, Khaled; Meyer, Amanda; Singh, Jagdish

    2006-02-01

    The objective of this study was to evaluate the critical formulation parameters (i.e., polymer concentration, polymer molecular weight, and solvent nature) affecting the controlled delivery of a model protein, lysozyme, from injectable polymeric implants. The conformational stability and biological activity of the released lysozyme were also investigated. Three formulations containing 10%, 20%, and 30% (w/v) poly lactic acid (PLA) in triacetin were investigated. It was found that increasing polymer concentration in the formulations led to a lower burst effect and a slower release rate. Formulation with a high molecular weight polymer showed a greater burst effect as compared to those containing low molecular weight. Conformational stability and biological activity of released samples were studied by differential scanning calorimeter and enzyme activity assay, respectively. The released samples had significantly (P solution kept at same conditions). Increasing polymer concentration increased both the conformational stability and the biological activity of released lysozyme. In conclusion, phase sensitive polymer-based delivery systems were able to deliver a model protein, lysozyme, in a conformationally stable and biologically active form at a controlled rate over an extended period.

  15. Calcium modified edible Canna (Canna edulis L) starch for controlled released matrix

    Science.gov (United States)

    Putri, A. P.; Ridwan, M.; Darmawan, T. A.; Darusman, F.; Gadri, A.

    2017-07-01

    Canna edulis L starch was modified with calcium chloride in order to form controlled released matrix. Present study aim to analyze modified starch characteristic. Four different formulation of ondansetron granules was used to provide dissolution profile of controlled released, two formula consisted of 15% and 30% modified starch, one formula utilized matrix reference standards and the last granules was negative control. Methocel-hydroxypropyl methyl cellulose was used as controlled released matrix reference standards in the third formula. Calcium starch was synthesized in the presence of sodium hydroxide to form gelatinized mass and calcium chloride as the cross linking agent. Physicochemical and dissolution properties of modified starch for controlled released application were investigated. Modified starch has higher swelling index, water solubility and compressibility index. Three of four different formulation of granules provide dissolution profile of controlled released. The profiles indicate granules which employed calcium Canna edulis L starch as matrix are able to resemble controlled drug released profile of matrix reference, however their bigger detain ability lead to lower bioavailability.

  16. Pharmacokinetics of a Sustained-release Formulation of Meloxicam After Subcutaneous Administration to Hispaniolan Amazon Parrots (Amazona ventralis).

    Science.gov (United States)

    Guzman, David Sanchez-Migallon; Court, Michael H; Zhu, Zhaohui; Summa, Noémie; Paul-Murphy, Joanne R

    2017-09-01

    Meloxicam has been shown to have a safe and favorable pharmacodynamic profile with individual variability in Hispaniolan Amazon parrots (Amazona ventralis). In the current study, we determined the pharmacokinetics of a sustained-release formulation of meloxicam after subcutaneous administration to Hispaniolan Amazon parrots. Twelve healthy adult parrots, 6 males and 6 females, were used in the study. Blood samples were collected before (time 0) and at 0.5, 1, 2, 6, 12, 24, 48, 72, 96, and 120 hours after a single dose of the sustained-release meloxicam formulation (3 mg/kg SC). Plasma meloxicam concentrations were measured by high-pressure liquid chromatography. Pharmacokinetic parameters were determined by noncompartmental analysis. Plasma concentrations reached a mean C max of 23.4 μg/mL (range, 14.7-46.0 μg/mL) at 1.8 hours (range, 0.5-6 hours), with a terminal half-life of 7.4 hours (range, 1.4-40.9 hours). Individual variation was noticeable, such that some parrots (4 of 12 birds) had very low plasma meloxicam concentrations, similar to the high variability reported in a previous pharmacokinetic study of the standard meloxicam formulation in the same group of birds. Two birds developed small self-resolving scabs at the injection site. On the basis of these results, the sustained-release meloxicam formulation could be administered every 12 to 96 hours in Hispaniolan Amazon parrots to manage pain. Because of these highly variable results, the use of this formulation in this species cannot be recommended until further pharmacokinetic, safety, and pharmacogenomic evaluations are performed to establish accurate dosing recommendations and to understand the high pharmacokinetic variability.

  17. Formulation strategy towards minimizing viscosity mediated negative food effect on disintegration and dissolution of immediate release tablets.

    Science.gov (United States)

    Zaheer, Kamran; Langguth, Peter

    2018-03-01

    Food induced viscosity can delay disintegration and subsequent release of API from solid dosage form which may lead to severe reduction in the bioavailability of BCS type III compounds. Formulations of such tablets need to be optimized in view of this postprandial viscosity factor. In this study, three super disintegrants, croscarmellose sodium (CCS), cross-linked polyvinylpolypyrrolidone (CPD), and sodium starch glycolate (SSG) were assessed for their efficiency under simulated fed state. Tablets containing these disintegrants were compressed at 10 and 30 KN, while taking lactose as a soluble filler. In addition to other compendial tests, disintegration force of these formulations was measured by texture analysis. Comparison of parameters derived from force - time curves revealed a direct relation of maximum disintegration force (F max ) and disintegration force development rate (DFDR) with compressional force in fasted state, whereas an inverse relationship of F max and DFDR with compressional force was observed in fed state. The gelling tendency of disintegrants influenced the rate of release of API in simulated fed and fasted states when compressional force was changed. These observations recommend the evaluation of formulations in simulated fed state, in the development stage, with an objective of minimizing the negative impact of food induced viscosity on disintegration. Use of disintegrants that act without gelling or can counteract the effect of gelling is recommended for tablet formulations with reduced disintegration time (DT) and mean dissolution time (MDT) in fed state, respectively.

  18. Advances in Targeted Pesticides with Environmentally Responsive Controlled Release by Nanotechnology

    Directory of Open Access Journals (Sweden)

    Bingna Huang

    2018-02-01

    Full Text Available Pesticides are the basis for defending against major biological disasters and important for ensuring national food security. Biocompatible, biodegradable, intelligent, and responsive materials are currently an emerging area of interest in the field of efficient, safe, and green pesticide formulation. Using nanotechnology to design and prepare targeted pesticides with environmentally responsive controlled release via compound and chemical modifications has also shown great potential in creating novel formulations. In this review, special attention has been paid to intelligent pesticides with precise controlled release modes that can respond to micro-ecological environment changes such as light-sensitivity, thermo-sensitivity, humidity sensitivity, soil pH, and enzyme activity. Moreover, establishing intelligent and controlled pesticide release technologies using nanomaterials are reported. These technologies could increase pesticide-loading, improve the dispersibility and stability of active ingredients, and promote target ability.

  19. Use of hydrophilic and hydrophobic polymers for the development of controlled release tizanidine matrix tablets

    Directory of Open Access Journals (Sweden)

    Tariq Ali

    2014-12-01

    Full Text Available The aim of the present study was to develop tizanidine controlled release matrix. Formulations were designed using central composite method with the help of design expert version 7.0 software. Avicel pH 101 in the range of 14-50% was used as a filler, while HPMC K4M and K100M in the range of 25-55%, Ethylcellulose 10 ST and 10FP in the range of 15 - 45% and Kollidon SR in the range of 25-60% were used as controlled release agents in designing different formulations. Various physical parameters including powder flow for blends and weight variation, thickness, hardness, friability, disintegration time and in-vitro release were tested for tablets. Assay of tablets were also performed as specified in USP 35 NF 32. Physical parameters of both powder blend and compressed tablets such as compressibility index, angle of repose, weight variation, thickness, hardness, friability, disintegration time and assay were evaluated and found to be satisfactory for formulations K4M2, K4M3, K4M9, K100M2, K100M3, K100M9, E10FP2, E10FP9, KSR2, KSR3 & KSR9. In vitro dissolution study was conducted in 900 ml of 0.1N HCl, phosphate buffer pH 4.5 and 6.8 medium using USP Apparatus II. In vitro release profiles indicated that formulations prepared with Ethocel 10 standard were unable to control the release of drug while formulations K4M2, K100M9, E10FP2 & KSR2 having polymer content ranging from 40-55% showed a controlled drug release pattern in the above mentioned medium. Zero-order drug release kinetics was observed for formulations K4M2, K100M9, E10FP2 & KSR2. Similarity test (f2 results for K4M2, E10FP2 & KSR2 were found to be comparable with reference formulation K100M9. Response Surface plots were also prepared for evaluating the effect of independent variable on the responses. Stability study was performed as per ICH guidelines and the calculated shelf life was 24-30 months for formulation K4M2, K100M9 and E10FP2.

  20. Development and characterization of controlled release polar lipid microparticles of candesartan cilexetil by solid dispersion

    Science.gov (United States)

    Kamalakkannan, V; Puratchikody, A; Ramanathan, L

    2013-01-01

    Candesartan cilexetil (CC) is a newer class of angiotensin II receptor antagonist used for the treatment of hypertension. The solubility of the CC is very poor and its oral bioavailability is only 15%. The controlledrelease polar lipid microparticles of CC (formulations F1, F2, F3 and F4) were prepared using variable erodible lipophilic excipients like hydrogenated castor oil, stearic acid, cetostearyl alcohol and carnauba wax by fusion method. The particle sizes of polar lipid microparticles were less than 50 microns and they were irregular in shape. Drug content ranged between 98.96 ± 2.1 and 101.9 ± 1.6% were present in all the formulations. The formulation F3 showed better drug release throughout the study period in a controlled release manner. Moreover, the in vitro release showed that all the formulations were best fitted to Higuchi model. Accelerated stability studies indicated that there was no significant changes in the chemical and physical characteristics of the formulated drug product during initial and at the end of the study period. The FTIR and DSC studies showed that there was no interaction between the drug and lipophilic excipients and no polymorphic transitions in all formulations. The X-ray diffraction peak of solid dispersion indicated that the crystalline nature of CC disappeared and no new peaks could be observed, suggesting the absence of interaction between drug and excipients. PMID:24019822

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

    Science.gov (United States)

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

    2004-02-11

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

  2. BIOMASS PRODUCTION AND FORMULATION OF Bacillus subtilis FOR BIOLOGICAL CONTROL

    Directory of Open Access Journals (Sweden)

    Amran Muis

    2016-10-01

    Full Text Available Bacillus subtilis is a widespread bacterium found in soil, water, and air. It controls the growth of certain harmful bacteria and fungi, presumably by competing for nutrients, growth sites on plants, and by directly colonizing and attaching to fungal pathogens. When applied to seeds, it colonizes the developing root system of the plants and continues to live on the root system and provides protection throughout the growing season. The study on biomass production and formulation of B. subtilis for biological control was conducted in the laboratory of Department of Plant Pathology, College of Agriculture, University of the Philippines Los Baños (UPLB-CA, College, Laguna from May to July 2005. The objective of the study was to determine the optimum pH and a good carbon source for biomass production of B. subtilis and to develop a seed treatment formulation of B. subtilis as biological control agent. Results showed that the optimum pH for growth of B. subtilis was pH 6 (1.85 x 109 cfu/ml. In laboratory tests for biomass production using cassava flour, corn flour, rice flour, and brown sugar as carbon sources, it grew best in brown sugar plus yeast extract medium (6.8 x 108 cfu ml-1 in sterile distilled water and 7.8 x 108 cfu ml-1 in coconut water. In test for bacterial biomass carriers, talc proved to be the best in terms of number of bacteria recovered from the seeds (3.98 x 105 cfu seed-1.

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

    Science.gov (United States)

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

    2006-01-01

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

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

    Science.gov (United States)

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

    2014-10-01

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

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

    Science.gov (United States)

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

    2008-06-24

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

  6. Effluent release limits, sources and control

    International Nuclear Information System (INIS)

    Swindell, G.E.

    1977-01-01

    Objectives of radiation protection in relation to releases. Environmental transfer models for radionuclides. Relationship between releases, environmental levels and doses to persons. Establishment of release limits: Limits based on critical population group concept critical pathway analysis and identification of critical group. Limits based on optimization of radiation protection individual dose limits, collective doses and dose commitments 1) differential cost benefit analysis 2) authorized and operational limits taking account of future exposures. Monitoring of releases to the environment: Objectives of effluent monitoring. Typical sources and composition of effluents; design and operation of monitoring programmes; recording and reporting of monitoring results; complementary environmental monitoring. (orig.) [de

  7. Sustained-release microsphere formulation containing an agrochemical by polyurethane polymerization during an agitation granulation process.

    Science.gov (United States)

    Terada, Takatoshi; Tagami, Manabu; Ohtsubo, Toshiro; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru

    2016-07-25

    In this report, a new solventless microencapsulation method by synthesizing polyurethane (PU) from polyol and isocyanate during an agglomeration process in a high-speed mixing apparatus was developed. Clothianidin (CTD), which is a neonicotinoid insecticide and highly effective against a wide variety of insect pests, was used as the model compound. The microencapsulated samples covered with PU (CTD microspheres) had a median diameter of <75μm and sustained-release properties. The CTD microspheres were analyzed by synchrotron X-ray computed tomography measurements. Multiple cores of CTD and other solid excipient were dispersed in PU. Although voids appeared in the CTD microspheres after CTD release, the spherical shape of the microspheres remained stable and no change in its framework was observed. The experimental release data were highly consistent with the Baker-Lonsdale model derived from drug release of spherical monolithic dispersions and consistent with the computed tomography measurements. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Formulation and In vitro/In vivo Evaluation of Sustained Release ...

    African Journals Online (AJOL)

    HP

    applied to study the effect of polymers used on drug release from the DHL. The tablets were ... A fair correlation between the dissolution profile and bioavailability for ... The results also indicate that the approach used could lead to a successful.

  9. Lyophilized sustained release mucoadhesive chitosan sponges for buccal buspirone hydrochloride delivery: formulation and in vitro evaluation.

    Science.gov (United States)

    Kassem, Mohamed A A; ElMeshad, Aliaa N; Fares, Ahmed R

    2015-06-01

    This work aims to prepare sustained release buccal mucoadhesive lyophilized chitosan sponges of buspirone hydrochloride (BH) to improve its systemic bioavailability. Chitosan sponges were prepared using simple casting/freeze-drying technique according to 3(2) factorial design where chitosan grade was set at three levels (low, medium, and high molecular weight), and concentration of chitosan solution at three levels (0.5, 1, and 2%). Mucoadhesion force, ex vivo mucoadhesion time, percent BH released after 8 h (Q8h), and time for release of 50% BH (T50%) were chosen as dependent variables. Additional BH cup and core buccal chitosan sponge were prepared to achieve uni-directional BH release toward the buccal mucosa. Sponges were evaluated in terms of drug content, surface pH, scanning electron microscopy, swelling index, mucoadhesion strength, ex vivo mucoadhesion time, and in vitro drug release. Cup and core sponge (HCH 0.5E) were able to adhere to the buccal mucosa for 8 h. It showed Q8h of 68.89% and exhibited a uni-directional drug release profile following Higuchi diffusion model.

  10. Core/shell PLGA microspheres with controllable in vivo release profile via rational core phase design.

    Science.gov (United States)

    Yu, Meiling; Yao, Qing; Zhang, Yan; Chen, Huilin; He, Haibing; Zhang, Yu; Yin, Tian; Tang, Xing; Xu, Hui

    2018-02-27

    Highly soluble drugs tend to release from preparations at high speeds, which make them need to be taken at frequent intervals. Additionally, some drugs need to be controlled to release in vivo at certain periods, so as to achieve therapeutic effects. Thus, the objective of this study is to design injectable microparticulate systems with controllable in vivo release profile. Biodegradable PLGA was used as the matrix material to fabricate microspheres using the traditional double emulsification-solvent evaporation method as well as improved techniques, with gel (5% gelatine or 25% F127) or LP powders as the inner phases. Their physicochemical properties were systemically investigated. Microspheres prepared by modified methods had an increase in drug loading (15.50, 16.72, 15.66%, respectively) and encapsulation efficiencies (73.46, 79.42, 74.40%, respectively) when compared with traditional methods (12.01 and 57.06%). The morphology of the particles was characterized by optical microscope (OM) and scanning electron microscopy (SEM), and the amorphous nature of the encapsulated drug was confirmed by differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis. To evaluate their release behaviour, the in vitro degradation, in vitro release and in vivo pharmacodynamics were subsequently studied. Traditional microspheres prepared in this study with water as the inner phase had a relatively short release period within 16 d when compared with modified microspheres with 5% gelatine as the inner phase, which resulted in a smooth release profile and appropriate plasma LP concentrations over 21 d. Thus this type of modified microspheres can be better used in drugs requiring sustained release. The other two formulations containing 25% F127 and LP micropowders presented two-stage release profiles, resulting in fluctuant plasma LP concentrations which may be suitable for drugs requiring controlled release. All the results suggested that drug release rates from

  11. Influence of different test parameters on in vitro drug release from topical diclofenac formulations in a vertical diffusion cell setup.

    Science.gov (United States)

    Klein, S

    2013-07-01

    In the past decades, the vertical diffusion cell has emerged as a useful device for testing drug release of topical dosage forms. However, to date neither a general USP method nor formulation-related monographs have been published in international pharmacopoeia. The purpose of the present work was to examine the influence of different test parameters in a vertical diffusion cell setup on in vitro drug release from semi-solid preparations for cutaneous application. Diclofenac was selected as the model compound. Release experiments were performed in a 7 ml Microett vertical diffusion cell system. Various test parameters, including the media composition and pH, degassing, membrane material and pore size, stirring speed and stirrer type, were varied. Results obtained with different test parameter settings clearly indicate that both drug properties and instrumental details can have a huge impact on the outcome of in vitro diffusion/drug release studies with the vertical diffusion cell. Thus, the selection of adequate test parameters is crucial for the success of the release experiments and, as shown in the present study, optimal test parameters/conditions need to be established and validated on a case by case study.

  12. Controlled-release oxycodone-induced seizures.

    Science.gov (United States)

    Klein, Moti; Rudich, Zvia; Gurevich, Boris; Lifshitz, Matityahu; Brill, Silviu; Lottan, Michael; Weksler, Natan

    2005-11-01

    The use of the opioid oxycodone hydrochloride in the management of chronic pain is gaining popularity principally because of its tolerability. However, opioid-related seizure in patients with epilepsy or other conditions that may decrease seizure threshold has been described in the literature; in particular, oxycodone has been associated with seizure in a patient with acute renal failure. The aim of this article was to report a patient with a history of seizures but normal renal and hepatic function who developed seizure on 2 occasions after oxycodone ingestion. A 54-year-old male patient presented with a history of tonic-clonic seizures that developed immediately after intracranial surgery. Long-term treatment with carbamazepine 400 mg QD was started, and the patient was free of convulsions for approximately 7 years. The patient presented to us with severe headache that was nonresponsive to an NSAID and the opiate agonist tramadol. Treatment with controlled-release (CR) oxycodone and tramadol drops (50 mg QID if necessary) was started, and tonic-clonic seizures developed 3 days later. Based on laboratory analysis, the patient had normal renal and hepatic function. On discontinuation of oxycodone treatment, the seizures resolved. However, due to effective pain relief with oxycodone, the patient decided to continue treatment, and seizures recurred. Carbamazepine was then administered 4 hours before oxycodone dosing, which allowed continuation of treatment without seizure. A patient with a history of seizures controlled with long-term carbamazepine therapy developed seizures when he started treatment with oxycodone CR at recommended doses. Oxycodone CR should be used with extreme caution in patients with epilepsy or other conditions that may decrease seizure threshold.

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

    Science.gov (United States)

    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. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Microgels produced using microfluidic on-chip polymer blending for controlled released of VEGF encoding lentivectors.

    Science.gov (United States)

    Madrigal, Justin L; Sharma, Shonit N; Campbell, Kevin T; Stilhano, Roberta S; Gijsbers, Rik; Silva, Eduardo A

    2018-03-15

    Alginate hydrogels are widely used as delivery vehicles due to their ability to encapsulate and release a wide range of cargos in a gentle and biocompatible manner. The release of encapsulated therapeutic cargos can be promoted or stunted by adjusting the hydrogel physiochemical properties. However, the release from such systems is often skewed towards burst-release or lengthy retention. To address this, we hypothesized that the overall magnitude of burst release could be adjusted by combining microgels with distinct properties and release behavior. Microgel suspensions were generated using a process we have termed on-chip polymer blending to yield composite suspensions of a range of microgel formulations. In this manner, we studied how alginate percentage and degradation relate to the release of lentivectors. Whereas changes in alginate percentage had a minimal impact on lentivector release, microgel degradation led to a 3-fold increase, and near complete release, over 10 days. Furthermore, by controlling the amount of degradable alginate present within microgels the relative rate of release can be adjusted. A degradable formulation of microgels was used to deliver vascular endothelial growth factor (VEGF)-encoding lentivectors in the chick chorioallantoic membrane (CAM) assay and yielded a proangiogenic response in comparison to the same lentivectors delivered in suspension. The utility of blended microgel suspensions may provide an especially appealing platform for the delivery of lentivectors or similarly sized therapeutics. Genetic therapeutics hold considerable potential for the treatment of diseases and disorders including ischemic cardiovascular diseases. To realize this potential, genetic vectors must be precisely and efficiently delivered to targeted regions of the body. However, conventional methods of delivery do not provide sufficient spatial and temporal control. Here, we demonstrate how alginate microgels provide a basis for developing systems for

  15. Accelerated dissolution testing for controlled release microspheres using the flow-through dissolution apparatus.

    Science.gov (United States)

    Collier, Jarrod W; Thakare, Mohan; Garner, Solomon T; Israel, Bridg'ette; Ahmed, Hisham; Granade, Saundra; Strong, Deborah L; Price, James C; Capomacchia, A C

    2009-01-01

    Theophylline controlled release capsules (THEO-24 CR) were used as a model system to evaluate accelerated dissolution tests for process and quality control and formulation development of controlled release formulations. Dissolution test acceleration was provided by increasing temperature, pH, flow rate, or adding surfactant. Electron microscope studies on the theophylline microspheres subsequent to each experiment showed that at pH values of 6.6 and 7.6 the microspheres remained intact, but at pH 8.6 they showed deterioration. As temperature was increased from 37-57 degrees C, no change in microsphere integrity was noted. Increased flow rate also showed no detrimental effect on integrity. The effect of increased temperature was determined to be the statistically significant variable.

  16. Formulation and In vitro/In vivo Evaluation of Sustained Release ...

    African Journals Online (AJOL)

    HP

    2013-07-15

    Jul 15, 2013 ... They are generally used to treat high blood pressure ... extending drug release for highly water-soluble drugs is limited ..... by the high water permeability of Kollidon SR while the ... due to the extremely low water solubility of.

  17. Pharmacokinetics of a once-daily extended-release formulation of pramipexole in healthy male volunteers: three studies.

    Science.gov (United States)

    Jenner, Peter; Könen-Bergmann, Michael; Schepers, Cornelia; Haertter, Sebastian

    2009-11-01

    Pramipexole is a dopamine agonist used in the treatment of Parkinson's disease. The currently available immediate-release (IR) formulation is taken orally 3 times daily. These studies were conducted to evaluate the pharmacokinetic properties of a variety of prototypes for a once-daily extended-release (ER) formulation of pramipexole and to further characterize the prototype whose pharmacokinetics best matched those of the IR formulation. Three Phase I studies were conducted, all in healthy adult men aged food effect. In the third study, steady-state pharmacokinetics of the optimal ER formulation were assessed across a range of pramipexole doses (0.375-4.5 mg/d), including investigation of the food effect at steady state for the highest dose. Tolerability was assessed throughout all studies based on physical examinations, laboratory measurements, and adverse events (AEs). The 3 studies included 18, 15, and 39 subjects, respectively. Among the ER prototypes tested at 0.75 mg once daily in study 1, a matrix tablet had the optimal pharmacokinetic resemblance to IR pramipexole 0.25 mg TID, with a geometric mean AUC(0-24h,ss) of 17.4 ng.h/mL (vs 16.0 ng.h/mL for the IR formulation), C(max,ss) of 0.967 ng/mL (vs 1.09 ng/mL), and C(min,ss) of 0.455 ng/mL (vs 0.383 ng/mL). For single-dose ER 0.375 mg administered in the fasted state in study 2, in vivo bioavailability was predictable from in vitro dissolution data, with internal mean absolute percent prediction errors of 3.18% for AUC(0-30h) and 4.87% for C(max), and external mean absolute prediction errors of 6.61% and 3.34%, respectively, satisfying current guidelines for a level A IVIVC. For single-dose ER 0.375 mg administered in the fed state, the upper bound of the 90% CI for fed:fasted values was 119.8 for AUC(0-30h) (within the bioequivalence limits of 80%-125%) and 134.1 for C(max). At steady state in study 3 (subjects' 5th treatment day), dosing at 0.375 to 4.5 mg in the fasted state was associated with a linear

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

    Science.gov (United States)

    Kim, Yang-Hee; Tabata, Yasuhiko

    2015-11-01

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

  19. Piroxicam immediate release formulations: A fasting randomized open-label crossover bioequivalence study in healthy volunteers.

    Science.gov (United States)

    Helmy, Sally A; El-Bedaiwy, Heba M

    2014-11-01

    Piroxicam is a NSAID with analgesic and antipyretic properties, used for the treatment of rheumatoid diseases. The aim of this study was to evaluate the bioequivalence of two brands of piroxicam capsules (20 mg) in 24 Egyptian volunteers. The in vivo study was established according to a single-center, randomized, single-dose, laboratory-blinded, 2-period, 2-sequence, crossover study with a washout period of 3 weeks. Under fasting conditions, 24 healthy male volunteers were randomly selected to receive a single oral dose of one capsule (20 mg) of either test or reference product. Plasma samples were obtained over a 144-hour interval and analyzed for piroxicam by HPLC with UV detection. The pharmacokinetic parameters Cmax , tmax , AUC0-t , AUC0-∞ , Vd /F, Cl/F, and t1/2 were determined from plasma concentration-time profiles. The 90% confidence intervals for the ratio of log transformed values of Cmax , AUC0-t , and AUC0-∞ of the two treatments were within the acceptable range (0.8-1.25) for bioequivalence. From PK perspectives, the two piroxicam formulations were considered bioequivalent, based on the rate and extent of absorption. No adverse events occurred or were reported after a single 20-mg piroxicam and both formulations were well-tolerated. © 2014, The American College of Clinical Pharmacology.

  20. Development of modified release diltiazem HCl tablets using composite index to identify optimal formulation.

    Science.gov (United States)

    Gohel, M C; Patel, M M; Amin, A F

    2003-05-01

    This article reports the preparation of tartaric acid treated ispaghula husk powder for the development of modified release tablets of diltiazem HCl by adopting direct compression technique and a 32 full factorial design. The modified ispaghula husk powder showed superior swelling and gelling as compared to untreated powder. Addition of compaction augmenting agent such as dicalcium phosphate was found to be essential for obtaining tablets with adequate crushing strength. In order to improve the crushing strength of diltiazem HCl tablets, to modulate drug release pattern, and to obtain similarity of dissolution profiles in distilled water and simulated gastric fluid (pH 1.2), modified guar gum was used along with modified ispaghula husk powder and tartaric acid. A novel composite index, which considers a positive or a negative deviation from an ideal value, was calculated considering percentage drug release in 60, 300, and 540 min as dependent variables for the selection of a most appropriate batch. Polynomial equation and contour plots are presented. The concept of similarity factor (f2) was used to prove similarity of dissolution in water and simulated gastric fluid (pH 1.2).

  1. Environmental Release Prevention and Control Plan

    International Nuclear Information System (INIS)

    Mamatey, A.; Arnett, M.

    1997-01-01

    During the history of SRS, continual improvements in facilities, process, and operations, and changes in the site''s mission have reduced the amount of radioactive liquid releases. In the early years of SRS (1958 to 1965), the amount of tritium discharged to the Savannah River averaged approximately 61,000 curies a year. During the mid-1980''s (1983 to 1988), liquid releases of tritium averaged 27,000 curies a year. By 1996, liquid releases of tritium are projected to be just 3000 curies for the year. This large projected decrease is the result of the planned shut-down of all reactors and the anticipated significant decline in the amount of tritium migrating from the site seepage basins and the Solid Waste Disposal Facility

  2. Nanocomposites for controlled release of nitrogen fertilizer

    International Nuclear Information System (INIS)

    Silva, Viviane J.M. da; Visconte, Leila L.Y.; Nascimento, Regina Sandra V.

    2009-01-01

    The study aimed at the development of nano structured materials capable of reducing the rate of release of nitrogen in the soil from an agricultural nitrogen fertilizer. Four different systems of polymer composites were prepared: (1) montmorillonite clay/fertilizer, (2) montmorillonite clay/thermoplastic starch and fertilizer, (3) montmorillonite clay/fertilizer, thermoplastic starch and low-density polyethylene (LDPE) and also (4) montmorillonite clay/fertilizer, thermoplastic starch and polycaprolactone. It was confirmed the formation of nano structured materials by elemental analysis (CHN) and X-ray diffraction (XRD). The kinetics of nitrogen release was detected by enzymatic colorimetric analysis and spectroscopy in the ultraviolet/visible. The results showed that all materials evaluated were able to reduce the rate of release of nitrogen in the fertilizers. (author)

  3. Development of controlled release spheroids using Buchananiacochinchinesis gum

    Directory of Open Access Journals (Sweden)

    Narayan Babulal Gaikwad

    2013-03-01

    Full Text Available Chirauli nut gum was isolated from the bark of Buchanania cochinchinesis (fam. Anacadiacea and was used as a release modifier for the preparation of Diclofenac sodium spheroids using the extrusion spheronization technique. The process was studied for the effects on variables when making spheroids with satisfactory particle shape, size and size distribution. The prepared spheroids were characterized for surface morphology, qualitative surface porosity, friability, bulk density and flow properties. In vitro studies demonstrated that the release exhibited Fickian diffusion kinetics which was confirmed by the Higuchi and the Korsmeyer-Peppas models. The physico-chemical parameters of the gum could be correlated to the in vitro dissolution profile of the spheroids. The spheroids were not able to sustain the drug releases over 12 hours. A greater concentration of Chirauli nut gum and a process that can accommodate such greater concentrations may produce a formulation capable of significant sustained release.

  4. Controlled release of insect sex pheromones from paraffin wax and emulsions.

    Science.gov (United States)

    Atterholt, C A; Delwiche, M J; Rice, R E; Krochta, J M

    1999-02-22

    Paraffin wax and aqueous paraffin emulsions can be used as controlled release carriers for insect sex pheromones for mating disruption of orchard pests. Paraffin can be applied at ambient temperature as an aqueous emulsion, adheres to tree bark or foliage, releases pheromone for an extended period of time, and will slowly erode from bark and biodegrade in soil. Pheromone emulsions can be applied with simple spray equipment. Pheromone release-rates from paraffin were measured in laboratory flow-cell experiments. Pheromone was trapped from an air stream with an adsorbent, eluted periodically, and quantified by gas chromatography. Pheromone release from paraffin was partition-controlled, providing a constant (zero-order) release rate. A typical paraffin emulsion consisted of 30% paraffin, 4% pheromone, 4% soy oil, 1% vitamin E, 2% emulsifier, and the balance water. Soy oil and vitamin E acted as volatility suppressants. A constant release of oriental fruit moth pheromone from paraffin emulsions was observed in the laboratory for more than 100 days at 27 degreesC, with release-rates ranging from 0.4 to 2 mg/day, depending on the concentration and surface area of the dried emulsion. The use of paraffin emulsions is a viable method for direct application of insect pheromones for mating disruption. Sprayable formulations can be designed to release insect pheromones to the environment at a rate necessary for insect control by mating disruption. At temperatures below 38 degreesC, zero-order release was observed. At 38 degreesC and higher, pheromone oxidation occurred. A partition-controlled release mechanism was supported by a zero-order pheromone release-rate, low air/wax partition coefficients, and pheromone solubility in paraffin.

  5. Toxicological evaluation of a dietary supplement formulated for male sexual health prior to market release.

    Science.gov (United States)

    Clewell, A; Qureshi, I; Endres, J; Horváth, J; Financsek, I; Neal-Kababick, J; Jade, K; Schauss, A G

    2010-06-01

    The dietary supplement, 112 Degrees, was formulated with the goal of supporting sexual functioning in men. Due to rampant problems with drug adulteration for this category of products, a comprehensive screening for active pharmaceutical agents, with an emphasis on drugs prescribed for erectile dysfunction such as type 5 phosphodiesterase (PDE-5) inhibitors, and known unapproved PDE-5 drug analogues, was performed along with preclinical toxicology studies prior to the introduction of this product into the marketplace. 112 Degrees was found to be free of all pharmaceutical adulterants tested, and was not mutagenic, clastogenic, or genotoxic as demonstrated by the Ames test, chromosomal aberration assay, and mouse micronucleus assay, respectively. The LD(50) in the 14-day acute oral toxicity study was greater than 5000 mg/kg, the highest dose tested. (c) 2009 Elsevier Inc. All rights reserved.

  6. Phenolic excipients of insulin formulations induce cell death, pro-inflammatory signaling and MCP-1 release

    Directory of Open Access Journals (Sweden)

    Claudia Weber

    2015-01-01

    Insulin solutions displayed cytotoxic and pro-inflammatory potential caused by phenol or m-cresol. We speculate that during insulin pump therapy phenol and m-cresol might induce cell death and inflammatory reactions at the infusion site in vivo. Inflammation is perpetuated by release of MCP-1 by activated monocytic cells leading to enhanced recruitment of inflammatory cells. To minimize acute skin complications caused by phenol/m-cresol accumulation, a frequent change of infusion sets and rotation of the infusion site is recommended.

  7. Overview study of LNG release prevention and control systems

    Energy Technology Data Exchange (ETDEWEB)

    Pelto, P.J.; Baker, E.G.; Holter, G.M.; Powers, T.B.

    1982-03-01

    The liquefied natural gas (LNG) industry employs a variety of release prevention and control techniques to reduce the likelihood and the consequences of accidental LNG releases. A study of the effectiveness of these release prevention and control systems is being performed. Reference descriptions for the basic types of LNG facilities were developed. Then an overview study was performed to identify areas that merit subsequent and more detailed analyses. The specific objectives were to characterize the LNG facilities of interest and their release prevention and control systems, identify possible weak links and research needs, and provide an analytical framework for subsequent detailed analyses. The LNG facilities analyzed include a reference export terminal, marine vessel, import terminal, peakshaving facility, truck tanker, and satellite facility. A reference description for these facilities, a preliminary hazards analysis (PHA), and a list of representative release scenarios are included. The reference facility descriptions outline basic process flows, plant layouts, and safety features. The PHA identifies the important release prevention operations. Representative release scenarios provide a format for discussing potential initiating events, effects of the release prevention and control systems, information needs, and potential design changes. These scenarios range from relatively frequent but low consequence releases to unlikely but large releases and are the principal basis for the next stage of analysis.

  8. Construction of a controlled-release delivery system for pesticides using biodegradable PLA-based microcapsules.

    Science.gov (United States)

    Liu, Baoxia; Wang, Yan; Yang, Fei; Wang, Xing; Shen, Hong; Cui, Haixin; Wu, Decheng

    2016-08-01

    Conventional pesticides usually need to be used in more than recommended dosages due to their loss and degradation, which results in a large waste of resources and serious environmental pollution. Encapsulation of pesticides in biodegradable carriers is a feasible approach to develop environment-friendly and efficient controlled-release delivery system. In this work, we fabricated three kinds of polylactic acid (PLA) carriers including microspheres, microcapsules, and porous microcapsules for controlled delivery of Lambda-Cyhalothrin (LC) via premix membrane emulsification (PME). The microcapsule delivery system had better water dispersion than the other two systems. Various microcapsules with a high LC contents as much as 40% and tunable sizes from 0.68 to 4.6μm were constructed by manipulating the process parameters. Compared with LC technical and commercial microcapsule formulation, the microcapsule systems showed a significantly sustained release of LC for a longer period. The LC release triggered by LC diffusion and matrix degradation could be optimally regulated by tuning LC contents and particle sizes of the microcapsules. This multi-regulated release capability is of great significance to achieve the precisely controlled release of pesticides. A preliminary bioassay against plutella xylostella revealed that 0.68μm LC-loaded microcapsules with good UV and thermal stability exhibited an activity similar to a commercial microcapsule formulation. These results demonstrated such an aqueous microcapsule delivery system had a great potential to be further explored for developing an effective and environmentally friendly pesticide-release formulation. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Preparation and characterization of controlled-release fertilizers coated with marine polysaccharide derivatives

    Science.gov (United States)

    Wang, Jing; Liu, Song; Qin, Yukun; Chen, Xiaolin; Xing, Rong'e.; Yu, Huahua; Li, Kecheng; Li, Pengcheng

    2017-09-01

    Encapsulation of water-soluble nitrogen fertilizers by membranes can be used to control the release of nutrients to maximize the fertilization effect and reduce environmental pollution. In this research, we formulated a new double-coated controlled-release fertilizer (CRF) by using food-grade microcrystalline wax (MW) and marine polysaccharide derivatives (calcium alginate and chitosan-glutaraldehyde copolymer). The pellets of water-soluble nitrogen fertilizer were coated with the marine polysaccharide derivatives and MW. A convenient and eco-friendly method was used to prepare the CRF. Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) were used to characterize the morphology and composition of the products. The nitrogen-release properties were determined in water using UV-Vis spectrophotometry. The controlled-release properties of the fertilizer were improved dramatically after coating with MW and the marine polysaccharide derivatives. The results show that the double-coated CRFs can release nitrogen in a controlled manner, have excellent controlled-release features, and meet the European Standard for CRFs.

  10. Formulation of criteria for pollution control on cement products produced from solid wastes in China.

    Science.gov (United States)

    Yang, Yufei; Huang, Qifei; Yang, Yu; Huang, Zechun; Wang, Qi

    2011-08-01

    The process of producing cement products from solid waste can increase the level of pollutants in the cement products. Therefore, it is very important to establish a pollution control standard for cement products to protect the environment and human health. This paper presents acceptance limits for the availability of heavy metals in cement products which have been produced from solid wastes and explains how the limits have been calculated. The approach and method used to formulate these criteria were based on EN 12920. The typical exposure scenarios used in this paper involve concrete being used for drinking water supply pipelines and concrete pavements and are based on an analysis of typical applications of cement in China, and the potential for contact with water. The parameters of a tank test which was based on NEN 7375 were set in accordance with the environmental conditions of typical scenarios in China. Mechanisms controlling the release of heavy metals in concrete and a model for that release were obtained using the leaching test. Finally, based on acceptance criteria for drinking water and groundwater quality in China, limit values for the availability of heavy metals in concrete were calculated. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. STUDIES ON NATURAL AND SYNTHETIC POLYMERS FOR CONTROLLED RELEASE MATRIX TABLET OF ACECLOFENAC

    OpenAIRE

    Abhishek S. Joshi *, Deepak A. Joshi , Avinash V. Dhobale , Sandhya S. Bundel , Vijay R. Chakote, Gunesh N. Dhembre

    2018-01-01

    The present study was aimed to design new oral controlled release matrix tablets of new NSAID Aceclofenac for once a day by using 10, 15, 20 and 25% of GG:HPMC and XG:HPMC mixture in the ratio 1:1 by wet granulation method. The prepared tablets subjected to in vitro drug release studies in pH 7.4 buffer solution. All the formulation meets the pre-compression and compression characteristics. All the tablets prepared with 10, 15, 20 and 25% of HPMC: XG mixture in the ratio 1:1 fails to meet the...

  12. Formulation and evaluation of a bilayer tablet comprising of diclofenac potassium as orodispersible layer and diclofenac sodium as sustained release core

    OpenAIRE

    Abbas, Jabbar; Bashir, Sajid; Samie, Muhammad; Laghari, Sadaf

    2017-01-01

    Diclofenac a phenylacetic acid derivative has long been used as an anti-inflammatory and analgesic drug to treat certain conditions however its sustained release formulation with immediate release loading dose is desirable. The rationale of the current work was to develop and evaluate bilayer tablets with diclofenac potassium as orodispersible layer and diclofenac sodium as sustained release core. The diclofenac sodium core was prepared by wet granulation method while the...

  13. A comparative histological study of alginate beads as a promising controlled release delivery for mefenamic acid.

    Science.gov (United States)

    Sevgi, Ferhan; Kaynarsoy, Buket; Ozyazici, Mine; Pekcetin, Cetin; Ozyurt, Dogan

    2008-01-01

    The new mefenamic acid-alginate bead formulation prepared by ionotropic gelation method using 3 x 2(2) factorial design has shown adequate controlled release properties in vitro. In the present study, the irritation effects of mefenamic acid (MA), a prominent non-steroidal anti-inflammatory (NSAI) drug, were evaluated on rat gastric and duodenal mucosa when suspended in 0.5% (w/v) sodiumcarboxymethylcellulose (NaCMC) solution and loaded in alginate beads. Wistar albino rats weighing 200 +/- 50 g were used during in vivo animal studies. In this work, biodegradable controlled release MA beads and free MA were evaluated according to the degree of gastric or duodenal damage following oral administration in rats. The gastric and duodenal mucosa was examined for any haemorrhagic changes. Formulation code A10 showing both Case II transport and zero order drug release and t(50) % value of 5.22 h was chosen for in vivo animal studies. For in vivo trials, free MA (100 mgkg(-1)), blank and MA (100 mgkg(-1)) loaded alginate beads (formulation code A10) were suspended in 0.5% (w/v) NaCMC solution and each group was given to six rats orally by gavage. NaCMC solution was used as a control in experimental studies. In vivo data showed that the administration of MA in alginate beads prevented the gastric lesions.

  14. Plasma methylphenidate concentrations in youths treated with high-dose osmotic release oral system formulation.

    Science.gov (United States)

    Stevens, Jonathan R; George, Robert A; Fusillo, Steven; Stern, Theodore A; Wilens, Timothy E

    2010-02-01

    Children and adolescents are being treated increasingly for attention-deficit/hyperactivity disorder (ADHD) with a variety of stimulants in higher than Food and Drug Administration (FDA)-approved doses and in combination with other medications. We sought to determine methylphenidate (MPH) concentrations in children and adolescents treated with high-dose, extended-release osmotic release oral system (OROS) MPH plus concomitant medications, and to examine MPH concentrations with respect to the safety and tolerability of treatment. Plasma MPH concentrations were measured by liquid chromatography-mass spectrometry 4-5 hours after administration of medication in a sample of youths diagnosed with ADHD. These youths were treated naturalistically with higher than FDA-approved doses of OROS MPH in addition to their concomitant medications. Markers of safety and tolerability (e.g., measures of blood pressure and heart rate) were also examined. Among the 17 patients (with a mean age of 16.2 +/- 2 years and a mean number of concurrent medications of 2.23 +/- 0.94), the mean plasma MPH concentration was 28 +/- 9.1 ng/mL, despite a mean daily dose of OROS MPH of 169 +/- 5 mg (3.0 +/- 0.8 mg/kg per day). No patient had a plasma MPH level >or=50 ng/mL or clinical signs of stimulant toxicity. No correlation was found between plasma MPH concentrations and OROS MPH dose or changes in vital signs. High-dose OROS MPH, used in combination with other medications, was not associated with either unusually elevated plasma MPH concentrations or with clinically meaningful changes in vital signs. Study limitations include a single time-point sampling of MPH concentrations, a small sample size, and a lack of outcome measures to address treatment effectiveness.

  15. A formulation to encapusulate nootkatone oil for tick control

    Science.gov (United States)

    Nootkatone is a component of grapefruit oil that is toxic to the disease vectoring tick, Ixodes scapularis Say, but unfortunately causes phytotoxicity to treated plants and has a short residual activity due to volatility. We prepared an encapsulated formulation of nootkatone using lignin to compare...

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

    Science.gov (United States)

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

    2018-01-01

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

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

    African Journals Online (AJOL)

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

  18. Geometry of modified release formulations during dissolution--influence on performance of dosage forms with diclofenac sodium.

    Science.gov (United States)

    Dorożyński, Przemysław; Kulinowski, Piotr; Jamróz, Witold; Juszczyk, Ewelina

    2014-12-30

    The objectives of the work included: presentation of magnetic resonance imaging (MRI) and fractal analysis based approach to comparison of dosage forms of different composition, structure, and assessment of the influence of the compositional factors i.e., matrix type, excipients etc., on properties and performance of the dosage form during drug dissolution. The work presents the first attempt to compare MRI data obtained for tablet formulations of different composition and characterized by distinct differences in hydration and drug dissolution mechanisms. The main difficulty, in such a case stems from differences in hydration behavior and tablet's geometry i.e., swelling, cracking, capping etc. A novel approach to characterization of matrix systems i.e., quantification of changes of geometrical complexity of the matrix shape during drug dissolution has been developed. Using three chosen commercial modified release tablet formulations with diclofenac sodium we present the method of parameterization of their geometrical complexity on the base of fractal analysis. The main result of the study is the correlation between the hydrating tablet behavior and drug dissolution - the increase of geometrical complexity expressed as fractal dimension relates to the increased variability of drug dissolution results. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Drug release control and system understanding of sucrose esters matrix tablets by artificial neural networks.

    Science.gov (United States)

    Chansanroj, Krisanin; Petrović, Jelena; Ibrić, Svetlana; Betz, Gabriele

    2011-10-09

    Artificial neural networks (ANNs) were applied for system understanding and prediction of drug release properties from direct compacted matrix tablets using sucrose esters (SEs) as matrix-forming agents for controlled release of a highly water soluble drug, metoprolol tartrate. Complexity of the system was presented through the effects of SE concentration and tablet porosity at various hydrophilic-lipophilic balance (HLB) values of SEs ranging from 0 to 16. Both effects contributed to release behaviors especially in the system containing hydrophilic SEs where swelling phenomena occurred. A self-organizing map neural network (SOM) was applied for visualizing interrelation among the variables and multilayer perceptron neural networks (MLPs) were employed to generalize the system and predict the drug release properties based on HLB value and concentration of SEs and tablet properties, i.e., tablet porosity, volume and tensile strength. Accurate prediction was obtained after systematically optimizing network performance based on learning algorithm of MLP. Drug release was mainly attributed to the effects of SEs, tablet volume and tensile strength in multi-dimensional interrelation whereas tablet porosity gave a small impact. Ability of system generalization and accurate prediction of the drug release properties proves the validity of SOM and MLPs for the formulation modeling of direct compacted matrix tablets containing controlled release agents of different material properties. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Qualitative analysis of controlled release ciprofloxacin/carbopol 934 mucoadhesive suspension

    Directory of Open Access Journals (Sweden)

    Subhashree Sahoo

    2011-01-01

    Full Text Available Mucoadhesive polymeric (carbopol 934 suspension of ciprofloxacin was prepared by ultrasonication and optimized with the aim of developing an oral controlled release gastro-retentive dosage form. The qualitative analysis of the formulation was performed by fourier transform infrared spectroscopy (FTIR, Raman spectroscopy, X-ray powder diffraction (XRD, and scanning electron microscopy (SEM analyses. FTIR (400 cm-1 to 4000 cm-1 region and Raman (140 to 2400 cm-1 region Spectroscopic studies were carried out and the spectra were used for interpretation. XRD data of pure drug, polymer and the formulation were obtained using a powder diffractometer scanned from a Bragg′s angle (2q of 10° to 70°. The dispersion of the particle was observed using SEM techniques. The particle size distribution and aspect ratio of particles in the polymeric suspension were obtained from SEM image analysis. The results from FTIR and Raman spectroscopic analyses suggested that, in formulation, the carboxylic groups of ciprofloxacin and hydroxyl groups of C934 undergo a chemical interaction leading to esterification and hydrogen bonding. The XRD data suggested that the retention of crystalline nature of ciprofloxacin in the formulation would lead to increase in stability and drug loading; decrease in solubility; and delay in release of the drug from polymeric suspension with better bioavailability and penetration capacity. The SEM image analysis indicated that, in the formulation maximum particles were having aspect ratio from 2 to 4 and standard deviation was very less which provided supporting evidences for homogeneous, uniformly dispersed, stable controlled release ciprofloxacin suspension which would be pharmaceutically acceptable.

  1. A new formulation of Bacillus thuringiensis: UV protection and sustained release mosquito larvae studies

    Czech Academy of Sciences Publication Activity Database

    Zhang, L.; Zhang, X.; Zhang, Y.; Wu, S.; Gelbič, Ivan; Xu, L.; Guan, X.

    2016-01-01

    Roč. 6, DEC 22 (2016), č. článku 39425. ISSN 2045-2322 Institutional support: RVO:60077344 Keywords : Bacillus thuringiensis * pest control * UV protection Subject RIV: EE - Microbiology, Virology Impact factor: 4.259, year: 2016 http://www.nature.com/articles/srep39425

  2. How controlled release technology can aid gene delivery.

    Science.gov (United States)

    Jo, Jun-Ichiro; Tabata, Yasuhiko

    2015-01-01

    Many types of gene delivery systems have been developed to enhance the level of gene expression. Controlled release technology is a feasible gene delivery system which enables genes to extend the expression duration by maintaining and releasing them at the injection site in a controlled manner. This technology can reduce the adverse effects by the bolus dose administration and avoid the repeated administration. Biodegradable biomaterials are useful as materials for the controlled release-based gene delivery technology and various biodegradable biomaterials have been developed. Controlled release-based gene delivery plays a critical role in a conventional gene therapy and genetic engineering. In the gene therapy, the therapeutic gene is released from biodegradable biomaterial matrices around the tissue to be treated. On the other hand, the intracellular controlled release of gene from the sub-micro-sized matrices is required for genetic engineering. Genetic engineering is feasible for cell transplantation as well as research of stem cells biology and medicine. DNA hydrogel containing a sequence of therapeutic gene and the exosome including the individual specific nucleic acids may become candidates for controlled release carriers. Technologies to deliver genes to cell aggregates will play an important role in the promotion of regenerative research and therapy.

  3. Antimicrobial beeswax coated polylactide films with silver control release capacity.

    Science.gov (United States)

    Martínez-Abad, Antonio; Lagarón, Jose Maria; Ocio, María Jose

    2014-03-17

    Although the application of silver based antimicrobial systems is a widespread technology, its implementation in areas such as food packaging is still challenging. The present paper describes the fabrication of poly(lactic acid) (PLA) coated with beeswax with controlled release properties for sustained antimicrobial performance. Release of silver ions from the polymers was monitored voltammetrically under various conditions (surface contact, immersion in various liquid media and at different pH values) throughout at least 7days. A higher release was noted with decreasing pH while surface release was much slower than the release when immersed in liquid medium. While uncoated films demonstrated a high burst release which in some instances implied surpassing some current migration restrictions (food), the addition of a beeswax layer allowed a sustained release of the antimicrobial compound. Increasing the thickness of the beeswax layer resulted in an increase in the water barrier properties of the films while reducing the relatively constant values of sustained release. Antimicrobial performance was correlated with the release of silver ions, indicating threshold concentrations for biocide action of films displayed a strong bactericidal effect against Salmonella enterica. The application of this functional barrier thus offers the possibility of tuning the release profiles of the films to suit a specific application and puts forth the possible suitability of these materials for food packaging or other migration sensitive applications. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Photoresponsive lipid-polymer hybrid nanoparticles for controlled doxorubicin release

    Science.gov (United States)

    Yao, Cuiping; Wu, Ming; Zhang, Cecheng; Lin, Xinyi; Wei, Zuwu; Zheng, Youshi; Zhang, Da; Zhang, Zhenxi; Liu, Xiaolong

    2017-06-01

    Currently, photoresponsive nanomaterials are particularly attractive due to their spatial and temporal controlled drug release abilities. In this work, we report a photoresponsive lipid-polymer hybrid nanoparticle for remote controlled delivery of anticancer drugs. This hybrid nanoparticle comprises three distinct functional components: (i) a poly(D,L-lactide-co-glycolide) (PLGA) core to encapsulate doxorubicin; (ii) a soybean lecithin monolayer at the interface of the core and shell to act as a molecular fence to prevent drug leakage; (iii) a photoresponsive polymeric shell with anti-biofouling properties to enhance nanoparticle stability, which could be detached from the nanoparticle to trigger the drug release via a decrease in the nanoparticle’s stability under light irradiation. In vitro results revealed that this core-shell nanoparticle had excellent light-controlled drug release behavior (76% release with light irradiation versus 10% release without light irradiation). The confocal microscopy and flow cytometry results also further demonstrated the light-controlled drug release behavior inside the cancer cells. Furthermore, a CCK8 assay demonstrated that light irradiation could significantly improve the efficiency of killing cancer cells. Meanwhile, whole-animal fluorescence imaging of a tumor-bearing mouse also confirmed that light irradiation could trigger drug release in vivo. Taken together, our data suggested that a hybrid nanoparticle could be a novel light controlled drug delivery system for cancer therapy.

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

    Science.gov (United States)

    Streubel, A; Siepmann, J; Bodmeier, R

    2003-01-01

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

  6. Stimuli-Responsive Materials for Controlled Release Applications

    KAUST Repository

    Li, Song

    2015-01-01

    The controlled release of therapeutics has been one of the major challenges for scientists and engineers during the past three decades. To address this outstanding problem, the design and fabrication of stimuli-responsive materials are pursued

  7. Natural gum as mucoadhesive controlled release carriers: evaluation of cefpodoxime proxetil by D-optimal design technique.

    Science.gov (United States)

    Patil, Satish H; Talele, Gokul S

    2014-03-01

    The present study deals with the development of mucoadhesive controlled release tablets of Cefpodoxime Proxetil to increase the gastric residence time and thus prolong drug release, reduce dosing frequency and improve oral bioavailability. Tablets were prepared using sodium alginate and karaya gum, a natural polymer, with a synthetic polymer hydroxypropylmethylcellulose (K100LV) and Karaya gum with HPMC K100LV in various ratios to optimize the drug release profile using D-Optimal technique. Pre- and post-compression parameters of tablets prepared with various formulations (S1-S9, C1-C9) were evaluated. The FTIR and DSC studies revealed that no physiochemical interaction between excipients and drug. The formulation S7 showed prolonged drug release, and the mechanism of drug release from the optimized formulation was confirmed using the Korsmeyer-Peppas model to be non-Fickian release transport and n value was found 0.605 indicating both diffusion and erosion mechanism from these natural gums. The optimized formulation showed mucoadhesive strength >35 g. An in vivo study was performed on rabbits using an X-ray imaging technique. The radiological evidence suggests that the tablets adheres (more than 10 hours) to a rabbit's stomach. No significant changes were found in the physical appearance, drug content, mucoadhesive study and in vitro dissolution pattern after storage at 40 °C/75% relative humidity for 3 months.

  8. Chemical controls on abiotic and biotic release of geogenic arsenic from Pleistocene aquifer sediments to groundwater.

    Science.gov (United States)

    Gillispie, Elizabeth C; Andujar, Erika; Polizzotto, Matthew L

    2016-08-10

    Over 150 million people in South and Southeast Asia consume unsafe drinking water from arsenic-rich Holocene aquifers. Although use of As-free water from Pleistocene aquifers is a potential mitigation strategy, such aquifers are vulnerable to geogenic As pollution, placing millions more people at potential risk. The goal of this research was to define chemical controls on abiotic and biotic release of geogenic As to groundwater. Batch incubations of sediments with natural chemical variability from a Pleistocene aquifer in Cambodia were conducted to evaluate how interactions among arsenic, manganese and iron oxides, and dissolved and sedimentary organic carbon influenced As mobilization from sediments. The addition of labile dissolved organic carbon produced the highest concentrations of dissolved As after >7 months, as compared to sediment samples incubated with sodium azide or without added carbon, and the extent of As release was positively correlated with the percent of initial extractable Mn released from the sediments. The mode of As release was impacted by the source of DOC supplied to the sediments, with biological processes responsible for 81% to 85% of the total As release following incubations with lactate and acetate but only up to 43% to 61% of the total As release following incubations with humic and fulvic acids. Overall, cycling of key redox-active elements and organic-carbon reactivity govern the potential for geogenic As release to groundwater, and results here may be used to formulate better predictions of the arsenic pollution potential of aquifers in South and Southeast Asia.

  9. Simulation and parametric study of a film-coated controlled-release pharmaceutical.

    Science.gov (United States)

    Borgquist, Per; Zackrisson, Gunnar; Nilsson, Bernt; Axelsson, Anders

    2002-04-23

    Pharmaceutical formulations can be designed as Multiple Unit Systems, such as Roxiam CR, studied in this work. The dose is administrated as a capsule, which contains about 100 individual pellets, which in turn contain the active drug remoxipride. Experimental data for a large number of single pellets can be obtained by studying the release using microtitre plates. This makes it possible to study the release of the individual subunits making up the total dose. A mathematical model for simulating the release of remoxipride from single film-coated pellets is presented including internal and external mass transfer hindrance apart from the most important film resistance. The model can successfully simulate the release of remoxipride from single film-coated pellets if the lag phase of the experimental data is ignored. This was shown to have a minor influence on the release rate. The use of the present model is demonstrated by a parametric study showing that the release process is film-controlled, i.e. is limited by the mass transport through the polymer coating. The model was used to fit the film thickness and the drug loading to the experimental release data. The variation in the fitted values was similar to that obtained in the experiments.

  10. In vitro solubility, dissolution and permeability studies combined with semi-mechanistic modeling to investigate the intestinal absorption of desvenlafaxine from an immediate- and extended release formulation

    DEFF Research Database (Denmark)

    Franek, F; Jarlfors, A; Larsen, F.

    2015-01-01

    Desvenlafaxine is a biopharmaceutics classification system (BCS) class 1 (high solubility, high permeability) and biopharmaceutical drug disposition classification system (BDDCS) class 3, (high solubility, poor metabolism; implying low permeability) compound. Thus the rate-limiting step...... not imply low intestinal permeability, as indicated by the BDDCS, merely low duodenal/jejunal permeability....... for desvenlafaxine absorption (i.e. intestinal dissolution or permeation) is not fully clarified. The aim of this study was to investigate whether dissolution and/or intestinal permeability rate-limit desvenlafaxine absorption from an immediate-release formulation (IRF) and Pristiq®, an extended release formulation...

  11. Development and validation of an in vitro–in vivo correlation (IVIVC model for propranolol hydrochloride extended-release matrix formulations

    Directory of Open Access Journals (Sweden)

    Chinhwa Cheng

    2014-06-01

    Full Text Available The objective of this study was to develop an in vitro–in vivo correlation (IVIVC model for hydrophilic matrix extended-release (ER propranolol dosage formulations. The in vitro release characteristics of the drug were determined using USP apparatus I at 100 rpm, in a medium of varying pH (from pH 1.2 to pH 6.8. In vivo plasma concentrations and pharmacokinetic parameters in male beagle dogs were obtained after administering oral, ER formulations and immediate-release (IR commercial products. The similarity factor f2 was used to compare the dissolution data. The IVIVC model was developed using pooled fraction dissolved and fraction absorbed of propranolol ER formulations, ER-F and ER-S, with different release rates. An additional formulation ER-V, with a different release rate of propranolol, was prepared for evaluating the external predictability. The results showed that the percentage prediction error (%PE values of Cmax and AUC0–∞ were 0.86% and 5.95%, respectively, for the external validation study. The observed low prediction errors for Cmax and AUC0–∞ demonstrated that the propranolol IVIVC model was valid.

  12. Formulation, quality control and shelf life of the experimental cytostatic drug cyclopentenyl cytosine

    NARCIS (Netherlands)

    Schimmel, Kirsten; Guchelaar, Henk-Jan; van Kan, Erik

    2006-01-01

    This paper describes the formulation and quality control of an aqueous sterilized formulation of the experimental cytostatic drug cyclopentenyl cytosine (CPEC) to be used in Phase I/II clinical trials. The raw drug substance was extensively tested. A High Pressure Liquid Chromotography (HPLC) method

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

    Science.gov (United States)

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

    2012-05-01

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

  14. Stimuli-Responsive Materials for Controlled Release Applications

    KAUST Repository

    Li, Song

    2015-04-01

    The controlled release of therapeutics has been one of the major challenges for scientists and engineers during the past three decades. To address this outstanding problem, the design and fabrication of stimuli-responsive materials are pursued to guarantee the controlled release of cargo at a specific time and with an accurate amount. Upon applying different stimuli such as light, magnetic field, heat, pH change, enzymes or redox, functional materials change their physicochemical properties through physical transformation or chemical reactions, allowing the release of payload agents on demand. This dissertation studied three stimuli-responsive membrane systems for controlled release from films of macro sizes to microcapsules of nano sizes. The first membrane system is a polymeric composite film which can decrease and sustain diffusion upon light irradiation. The photo-response of membranes is based on the photoreaction of cinnamic derivatives. The second one is composite membrane which can improve diffusion upon heating. The thermo-response of membranes comes from the volume phase transition ability of hydrogels. The third one is microcapsule which can release encapsulated agents upon light irradiation. The photo-response of capsules results from the photoreaction of nitrobenzyl derivatives. The study on these membrane systems reveals that stimuli-responsive release can be achieved by utilizing different functional materials on either macro or micro level. Based on the abundant family of smart materials, designing and fabricating stimuli-responsive systems shall lead to various advanced release processes on demand for biomedical applications.

  15. Research and development of controlled release technology for agrochemicals using isotopes

    International Nuclear Information System (INIS)

    1986-01-01

    In recent years, increasing investment has been made into development of measures to reduce pesticide contamination of food and the environment while at the same time protecting crops and livestock from pest attack. Studies to develop controlled-release technology are frequently carried out with labelled compounds. Radiotracer techniques provide a unique tool in measuring the release rate of the chemical, the stability of the chemical within the formulation and evaluating the effect of environmental factors on the release rate. These technologies and pesticide residue problems were the theme of the Seminar. The Seminar has illustrated the potential value of isotope techniques and has reviewed information on current developments in this field and their relevance to agriculture in developing countries

  16. Controlled release of tocopherols from polymer blend films

    Science.gov (United States)

    Obinata, Noe

    Controlled release packaging has great potential to increase storage stability of foods by releasing active compounds into foods continuously over time. However, a major limitation in development of this technology is the inability to control the release and provide rates useful for long term storage of foods. Better understanding of the factors affecting active compound release is needed to overcome this limitation. The objective of this research was to investigate the relationship between polymer composition, polymer processing method, polymer morphology, and release properties of active compounds, and to provide proof of principle that compound release is controlled by film morphology. A natural antioxidant, tocopherol was used as a model active compound because it is natural, effective, heat stable, and soluble in most packaging polymers. Polymer blend films were produced from combination of linear low density polyethylene (LLDPE) and high density polyethylene (HDPE), polypropylene (PP), or polystyrene (PS) with 3000 ppm mixed tocopherols using conventional blending method and innovative blending method, smart blending with a novel mixer using chaotic advection. Film morphologies were visualized with scanning electron microscopy (SEM). Release of tocopherols into 95% ethanol as a food simulant was measured by UV/Visible spectrophotometry or HPLC, and diffusivity of tocopherols in the polymers was estimated from this data. Polymer composition (blend proportions) and processing methods have major effects on film morphology. Four different types of morphologies, dispersed, co-continuous, fiber, and multilayer structures were developed by either conventional extrusion or smart blending. With smart blending of fixed polymer compositions, different morphologies were progressively developed with fixed polymer composition as the number of rod rotations increased, providing a way to separate effects of polymer composition and morphology. The different morphologies

  17. Microchips and controlled-release drug reservoirs.

    Science.gov (United States)

    Staples, Mark

    2010-01-01

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

  18. Controlled release of curcumin from poly(HEMA-MAPA) membrane.

    Science.gov (United States)

    Caka, Müşerref; Türkcan, Ceren; Aktaş Uygun, Deniz; Uygun, Murat; Akgöl, Sinan; Denizli, Adil

    2017-05-01

    In this work, poly(HEMA-MAPA) membranes were prepared by UV-polymerization technique. These membranes were characterized by SEM, FTIR, and swelling studies. Synthesized membranes had high porous structure. These membranes were used for controlled release of curcumin which is already used as folk remedy and used as drug for some certain diseases and cancers. Curcumin release was investigated for various pHs and temperatures. Optimum drug release yield was found to be as 70% at pH 7.4 and 37 °C within 2 h period. Time-depended release of curcumin was also investigated and its slow release from the membrane demonstrated within 48 h.

  19. Electrospray synthesis and properties of hierarchically structured PLGA TIPS microspheres for use as controlled release technologies.

    Science.gov (United States)

    Malik, Salman A; Ng, Wing H; Bowen, James; Tang, Justin; Gomez, Alessandro; Kenyon, Anthony J; Day, Richard M

    2016-04-01

    Microsphere-based controlled release technologies have been utilized for the long-term delivery of proteins, peptides and antibiotics, although their synthesis poses substantial challenges owing to formulation complexities, lack of scalability, and cost. To address these shortcomings, we used the electrospray process as a reproducible, synthesis technique to manufacture highly porous (>94%) microspheres while maintaining control over particle structure and size. Here we report a successful formulation recipe used to generate spherical poly(lactic-co-glycolic) acid (PLGA) microspheres using the electrospray (ES) coupled with a novel thermally induced phase separation (TIPS) process with a tailored Liquid Nitrogen (LN2) collection scheme. We show how size, shape and porosity of resulting microspheres can be controlled by judiciously varying electrospray processing parameters and we demonstrate examples in which the particle size (and porosity) affect release kinetics. The effect of electrospray treatment on the particles and their physicochemical properties are characterized by scanning electron microscopy, confocal Raman microscopy, thermogravimetric analysis and mercury intrusion porosimetry. The microspheres manufactured here have successfully demonstrated long-term delivery (i.e. 1week) of an active agent, enabling sustained release of a dye with minimal physical degradation and have verified the potential of scalable electrospray technologies for an innovative TIPS-based microsphere production protocol. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2012-05-30

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

  1. Magnetic molecularly imprinted polymer for aspirin recognition and controlled release

    Energy Technology Data Exchange (ETDEWEB)

    Kan Xianwen; Geng Zhirong; Zhao Yao; Wang Zhilin; Zhu Junjie [State Key Laboratory of Coordination Chemistry, MOE Key Lab of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, 22 Hankou Road, Nanjing 210093 (China)], E-mail: wangzl@nju.edu.cn, E-mail: jjzhu@nju.edu.cn

    2009-04-22

    Core-shell structural magnetic molecularly imprinted polymers (magnetic MIPs) with combined properties of molecular recognition and controlled release were prepared and characterized. Magnetic MIPs were synthesized by the co-polymerization of methacrylic acid (MAA) and trimethylolpropane trimethacrylate (TRIM) around aspirin (ASP) at the surface of double-bond-functionalized Fe{sub 3}O{sub 4} nanoparticles in chloroform. The obtained spherical magnetic MIPs with diameters of about 500 nm had obvious superparamagnetism and could be separated quickly by an external magnetic field. Binding experiments were carried out to evaluate the properties of magnetic MIPs and magnetic non-molecularly imprinted polymers (magnetic NIPs). The results demonstrated that the magnetic MIPs had high adsorption capacity and selectivity to ASP. Moreover, release profiles and release rate of ASP from the ASP-loaded magnetic MIPs indicated that the magnetic MIPs also had potential applications in drug controlled release.

  2. Magnetic molecularly imprinted polymer for aspirin recognition and controlled release

    International Nuclear Information System (INIS)

    Kan Xianwen; Geng Zhirong; Zhao Yao; Wang Zhilin; Zhu Junjie

    2009-01-01

    Core-shell structural magnetic molecularly imprinted polymers (magnetic MIPs) with combined properties of molecular recognition and controlled release were prepared and characterized. Magnetic MIPs were synthesized by the co-polymerization of methacrylic acid (MAA) and trimethylolpropane trimethacrylate (TRIM) around aspirin (ASP) at the surface of double-bond-functionalized Fe 3 O 4 nanoparticles in chloroform. The obtained spherical magnetic MIPs with diameters of about 500 nm had obvious superparamagnetism and could be separated quickly by an external magnetic field. Binding experiments were carried out to evaluate the properties of magnetic MIPs and magnetic non-molecularly imprinted polymers (magnetic NIPs). The results demonstrated that the magnetic MIPs had high adsorption capacity and selectivity to ASP. Moreover, release profiles and release rate of ASP from the ASP-loaded magnetic MIPs indicated that the magnetic MIPs also had potential applications in drug controlled release.

  3. Once-Daily Tacrolimus Extended-Release Formulation: 1 Year after Conversion in Stable Pediatric Kidney Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Lars Pape

    2011-01-01

    Full Text Available It is speculated that a once-daily dosage of immunosuppression can increase adherence and thereby graft survival. Until now, there have been no studies on once-daily use of Tacrolimus extended-release formulation (TAC-ER in children following pediatric kidney transplantation. In 11 stable pediatric kidney recipients >10 years, efficacy, safety, and tolerability of a switch to TAC-ER were observed over one year. Adherence was determined by use of the BAASIS-Scale Interview and comparison of individual variability of Tacrolimus trough levels. Over the observation period, two acute rejections were observed in one girl with nonadherence and repeated Tacrolimus trough levels of 0 ng/m. Beside this, there were no acute rejections in this trial. TAC dose was increased in 3/11 patients and decreased in 2/11 patients within the course of the study. Six patients did not require a dose adjustment. All but one patient had a maximum of 1 dose change during therapy. Mean Tacrolimus dose, trough levels, and Glomerular filtration rates were also stable. Adherence, as measured by BAASIS-Scale Interview and coefficient of variation of Tacrolimus trough levels, was good at all times. It is concluded that conversion to Tac-ER is safe in low-risk children following pediatric kidney transplantation.

  4. Induction of fertile estrus in bitches using a sustained-release formulation of a GnRH agonist (leuprolide acetate).

    Science.gov (United States)

    Inaba, T; Tani, H; Gonda, M; Nakagawa, A; Ohmura, M; Mori, J; Torii, R; Tamada, H; Sawada, T

    1998-04-01

    A single subcutaneous injection of a sustained-release formulation of a potent GnRH agonist, leuprolide acetate (LA; [D-Leu6, Pro9NEt]-GnRH), was evaluated as a method of inducing fertile estrus in 12 mature anestrous and 6 prepubertal beagle bitches. The bitches were treated with microencapsulated LA (100 micrograms/kg, s.c.) at 120 or 150 d post partum, or at 1 yr of age, followed by a GnRH-analogue (fertirelin; [Pro9NEt]-GnRH, 3 micrograms/kg, i.m.) on the first day of induced estrus. Signs of estrus were seen within 10.3 +/- 0.9 d after LA administration in all bitches. The interestrous interval in 120- and 150-d post-partum bitches was shortened (P bitches. All LA treated dogs demonstrated behavioral estrus and mated. Three of 6 (50%) at 120 d post partum, 6 of 6 (100%) at 150 d post partum and 5 of 6 (83%) of prepubertal (1-yr old) bitches then became pregnant and produced a mean litter size of 4.1 +/- 0.8 pups. A normal circulating estrogen and progesterone response pattern was observed in mature anestrous bitches. A prepubertal bitch that failed to become pregnant had a similar estrogen response pattern but an insufficient progesterone profile. The results suggest that microencapsulated LA can be useful in inducing fertile estrus in the domestic dogs.

  5. Formulation of a modified release metformin. HCl matrix tablet: influence of some hydrophilic polymers on release rate and in-vitro evaluation

    Directory of Open Access Journals (Sweden)

    John Rojas

    2011-09-01

    Full Text Available Metformin hydrochloride is an antidiabetic agent which improves glucose tolerance in patients with type 2 diabetes and reduces basal plasma levels of glucose. In this study, a simplex centroid experimental design with 69 runs was used to select the best combination of some hydrophilic polymers that rendered a 24 h in-vitro release profile of metformin.HCl. The Korsmeyer-Peppas model was used to model the dissolution profiles since it presented the best fit to the experimental data. Further, a cubic model predicted the best formulation of metformin.HCl containing polyvinyl pyrrolidone, ethyl cellulose, hydroxypropyl methyl cellulose, carrageenan, sodium alginate, and gum arabic at 6.26, 68.7, 6.26, 6.26, 6.26 and 6.26 % levels, respectively. The validation runs confirmed the accuracy of the cubic model with six components for predicting the best set of components which rendered a once-a-day modified release hydrophilic matrix tablet in compliance with the USP specifications.O cloridrato de metformina é um agente antidiabético que melhora a tolerância à glicose em pacientes com diabetes tipo 2 e reduz os níveis plasmáticos basais de glicose. Neste estudo, um projeto experimental do tipo "centróide simplex" com 69 tomadas foi usado para selecionar a melhor combinação de alguns polímeros hidrofílicos que gerou um perfil de liberação da metformina.HCl de 24 horas. O modelo Korsmeyer-Peppas foi usado para modelar os perfis de dissolução, uma vez que apresentou os melhores ajustes aos dados experimentais. Além disso, um modelo cúbico previu a melhor formulação de metformina.HCl sendo aquela contendo polivinilpirrolidona, etilcelulose, hidroxipropilmetil celulose, carragena, alginato de sódio e goma arábica nos níveis 6.26, 68.7, 6.26, 6.26, 6.26 e 6.26 %, respectivamente. As corridas de validação confirmaram a precisão do modelo cúbico com os seis componentes para prever o melhor conjunto de componentes que originou uma

  6. Release kinetics of tocopherol and quercetin from binary antioxidant controlled-release packaging films.

    Science.gov (United States)

    Chen, Xi; Lee, Dong Sun; Zhu, Xuntao; Yam, Kit L

    2012-04-04

    This paper investigated the feasibility of manipulating packaging polymers with various degrees of hydrophobicity to release two antioxidants, tocopherol and quercetin, at rates suitable for long-term inhibition of lipid oxidation in food. For example, one antioxidant can be released at a fast rate to provide short-term/intermediate protection, whereas the other antioxidant can be released at a slower rate to provide intermediate/long-term protection of lipid oxidation. Controlled-release packaging films containing tocopherol and quercetin were produced using ethylene vinyl alcohol (EVOH), ethylene vinyl acetate (EVA), low-density polyethylene (LDPE), and polypropylene (PP) polymers; the release of these antioxidants to 95% ethanol (a fatty food simulant) was measured using UV-vis spectrophotometry, and Fickian diffusion models with appropriate initial and boundary conditions were used to fit the data. For films containing only quercetin, the results show that the release of quercetin was much faster but lasted for a much shorter time for hydrophilic polymers (EVOH and EVA) than for hydrophobic polymers (LDPE and PP). For binary antioxidant films containing tocopherol and quercetin, the results show that tocopherol released more rapidly but for a shorter period of time than quercetin in LDPE and EVOH films, and the difference is more pronounced for LDPE films than EVOH films. The results also show the presence of tocopherol can accelerate the release of quercetin. Although none of the films produced is acceptable for long-term lipid oxidation inhibition, the study provides encouraging results suggesting that acceptable films may be produced in the future using polymer blend films.

  7. HABIT, Toxic and Radioactive Release Hazards in Reactor Control Room

    International Nuclear Information System (INIS)

    Stage, S.A.

    2005-01-01

    1 - Description of program or function: HABIT is a package of computer codes designed to be used for the evaluation of control room habitability in the event of an accidental release of toxic chemicals or radioactive materials. 2 - Methods: Given information about the design of a nuclear power plant, a scenario for the release of toxic or radionuclides, and information about the air flows and protection systems of the control room, HABIT can be used to estimate the chemical exposure or radiological dose to control room personnel

  8. FERLENT - a controlled release fertilizer produced from a polymer material

    International Nuclear Information System (INIS)

    Gonzalez, Mayra; Arces, Milagros; Cuesta, Ernesto; Corredera, Pilar; Sardina, Carmen; Rieumont, Jacques; Quintana, Patricia; Bartolo, Pascual; Guenther, Bluma

    2011-01-01

    The possibility to use release controlled fertilizers in the agriculture of the tropical countries is more important than in the agriculture of the countries of the template regions. In this context, this work purpose the development of a new Fertilizer of Controlled Release named FERLENT, which was obtained starting from a polymeric material, under controlled conditions which allowed to corroborate the adjustment of the synthesis parameters under the modulate of nutrients liberation. It was characterized by, Scanning Microscopy Electron (SEM), Thermogravimetric analysis (TGA), Nuclear Magnetic Resonance (NMR) and infrared spectroscopy (FTIR). (author)

  9. Design of analog networks in the control theory formulation. Part 2: Numerical results

    OpenAIRE

    Zemliak, A. M.

    2005-01-01

    The paper presents numerical results of design of nonlinear electronic networks based on the problem formulation in terms of the control theory. Several examples illustrate the prospects of the approach suggested in the first part of the work.

  10. The role of hyaluronan as a drug carrier to enhance the bioavailability of extended release ophthalmic formulations. Hyaluronan-timolol ionic complexes as a model case.

    Science.gov (United States)

    Battistini, F D; Tártara, L I; Boiero, C; Guzmán, M L; Luciani-Giaccobbe, L C; Palma, S D; Allemandi, D A; Manzo, R H; Olivera, M E

    2017-07-15

    The aim of this work was to obtain information concerning the properties of ophthalmic formulations based on hyaluronic-drug ionic complexes, to identify the factors that determine the onset, intensity and duration of the pharmacotherapeutic effect. Dispersions of a complex of 0.5% w/v of sodium hyaluronate (HyNa) loaded with 0.5% w/v of timolol maleate (TM) were obtained and presented a counterionic condensation higher than 75%. For comparison a similar complex obtained with hyaluronic acid (HyH) was also prepared. Although the viscosity of HyNa-TM was significantly higher than that of HyH-TM, in vitro release of TM from both complexes showed a similar extended drug release profile (20-31% over 5h) controlled by diffusion and ionic exchange. Ocular pharmacokinetic study performed in normotensive rabbits showed that HyNa-TM complex exhibited attractive bioavailability properties in the aqueous humor (AUC and Cmax significantly higher and later Tmax) compared to commercial TM eye-drops. Moreover, a more prolonged period of lowered intra-ocular pressure (10h) and a more intense hypotensive activity was observed after instillation of a drop of HyNa-TM as compared to the eye-drops. Such behavior was related to the longer pre-corneal residence times (400%) observed with HyNa-TM complex. No significant changes in rabbit transcorneal permeation were detected upon complexation. These results demonstrate that the ability of HyNa to modulate TM release, together with its mucoadhesiveness related to the viscosity, affected both the pharmacokinetic and pharmacodynamic parameters. The HyNa-TM complex is a potentially useful carrier for ocular drug delivery, which could improve the TM efficacy and reduce the frequency of administration to improve patient compliance. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    Fang, Jonathan

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

  12. Economic model predictive control theory, formulations and chemical process applications

    CERN Document Server

    Ellis, Matthew; Christofides, Panagiotis D

    2017-01-01

    This book presents general methods for the design of economic model predictive control (EMPC) systems for broad classes of nonlinear systems that address key theoretical and practical considerations including recursive feasibility, closed-loop stability, closed-loop performance, and computational efficiency. Specifically, the book proposes: Lyapunov-based EMPC methods for nonlinear systems; two-tier EMPC architectures that are highly computationally efficient; and EMPC schemes handling explicitly uncertainty, time-varying cost functions, time-delays and multiple-time-scale dynamics. The proposed methods employ a variety of tools ranging from nonlinear systems analysis, through Lyapunov-based control techniques to nonlinear dynamic optimization. The applicability and performance of the proposed methods are demonstrated through a number of chemical process examples. The book presents state-of-the-art methods for the design of economic model predictive control systems for chemical processes. In addition to being...

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

    International Nuclear Information System (INIS)

    Alizadeh, Naader; Shamaeli, Ehsan

    2014-01-01

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

  14. Evaluation of Ocimum basilicum L. seed mucilage as rate controlling matrix for sustained release of propranolol HCl

    Directory of Open Access Journals (Sweden)

    Majid Saeedi

    2015-01-01

    Full Text Available Polysaccharide mucilage derived from the seeds of Ocimum basilicum L. (family Lamiaceae was investigated for use in matrix formulations containing propranolol hydrochloride. Basil mucilage was extracted and several tablets were formulated. The effect of mucilage on drug release rate was evaluated in comparison with tablets containing two kinds of hydroxypropyl methylcellulose (HPMC K4M and HPMC K100M as standard polymer. The release data were fitted to several models for kinetic evaluation. The results showed that hardness decreased and friability of tablets increased as the concentration of mucilage increased. The rate of release of propranolol HCl from O. basilicm mucilage matrices was mainly controlled by the drug: mucilage ratio. Drug release was slower from the HPMC K4M and HPMCK100M containing tablets compared to the mucilage containing matrices than the drug release from matrices containing O. basilicum seed mucilage in similar ratios.  Formulations containing O. basilicm mucilage were found to exhibit suitable release pattern. The results of kinetic analysis showed that in tablets containing O. basilicm mucilage the highest correlation coefficient was achieved with the zero order model. The swelling and erosion studies revealed that, as the proportion of mucilage in tablets was increased, there was a corresponding increase in percent swelling and a decrease in percent erosion of tablets.

  15. Method and apparatus for controlling accidental releases of tritium

    International Nuclear Information System (INIS)

    Galloway, T.R.

    1980-01-01

    An improvement in a tritium control system based on a catalytic oxidation reactor is provided wherein accidental releases of tritium into room air are controlled by flooding the catalytic oxidation reactor with hydrogen when the tritium concentration in the room air exceeds a specified limit. The sudden flooding with hydrogen heats the catalyst to a high temperature within seconds, thereby greatly increasing the catalytic oxidation rate of tritium to tritiated water vapor. Thus, the catalyst is heated only when needed. In addition to the heating effect, the hydrogen flow also swamps the tritium and further reduces the tritium release

  16. Method and apparatus for controlling accidental releases of tritium

    Science.gov (United States)

    Galloway, Terry R. [Berkeley, CA

    1980-04-01

    An improvement in a tritium control system based on a catalytic oxidation reactor wherein accidental releases of tritium into room air are controlled by flooding the catalytic oxidation reactor with hydrogen when the tritium concentration in the room air exceeds a specified limit. The sudden flooding with hydrogen heats the catalyst to a high temperature within seconds, thereby greatly increasing the catalytic oxidation rate of tritium to tritiated water vapor. Thus, the catalyst is heated only when needed. In addition to the heating effect, the hydrogen flow also swamps the tritium and further reduces the tritium release.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-02-15

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

  18. Clean Photothermal Heating and Controlled Release From Near Infrared Dye Doped Nanoparticles Without Oxygen Photosensitization

    Science.gov (United States)

    Guha, Samit; Shaw, Scott K.; Spence, Graeme T.; Roland, Felicia M.; Smith, Bradley D.

    2015-01-01

    The photothermal heating and release properties of biocompatible organic nanoparticles, doped with a near-infrared croconaine (Croc) dye, were compared with analogous nanoparticles doped with the common near-infrared dyes ICG and IR780. Separate formulations of lipid-polymer-hybrid nanoparticles and liposomes, each containing Croc dye, absorbed strongly at 808 nm and generated clean laser-induced heating (no production of 1O2 and no photobleaching of the dye). In contrast, laser-induced heating of nanoparticles containing ICG or IR780 produced reactive 1O2 leading to bleaching of the dye and also decomposition of co-encapsulated payload such as the drug Doxorubicin. Croc dye was especially useful as a photothermal agent for laser controlled release of chemically sensitive payload from nanoparticles. Solution state experiments demonstrated repetitive fractional release of water soluble fluorescent dye from the interior of thermosensitive liposomes. Additional experiments used a focused laser beam to control leakage from immobilized liposomes with very high spatial and temporal precision. The results indicate that fractional photothermal leakage from nanoparticles doped with Croc dye is a promising method for a range of controlled release applications. PMID:26149326

  19. Granular formulation of Fusarium oxysporum for biological control of faba bean and tomato Orobanche.

    Science.gov (United States)

    Nemat Alla, Mamdouh M; Shabana, Yasser M; Serag, Mamdouh M; Hassan, Nemat M; El-Hawary, Mohamed M

    2008-12-01

    Orobanche spp. represent a serious threat to a wide range of crops. They are difficult targets for herbicides, and biological control could provide a possible solution. This work therefore aimed to formulate mycoherbicides of Fusarium with adequate shelf life and virulence against Orobanche but safe to faba bean and tomato. Only two isolates of Fusarium oxysporum Schlecht. (Foxy I and Foxy II) obtained from diseased Orobanche shoots were found to be pathogenic to Orobanche crenata Forsk. and Orobanche ramosa L. Conidial suspension of both isolates significantly decreased germination, attachments and tubercles of Orobanche. Microconidia and chlamydospores of both isolates were formulated as mycoherbicides encapsulated in a wheat flour-kaolin matrix (four different formulations). All formulations greatly diminished Orobanche emerged shoots, total shoot number, shoot height, attachment of emerged shoots, the germinated seeds that succeeded in emerging above the soil surface and dry weight. Meanwhile, disease incidence and disease severity of emerged shoots were enhanced. The shelf life was adequate, particularly for coarse, freshly prepared, low-temperature-stored, microconidia-rich formulations. The induced growth reduction of Orobanche-infected host plants seemed to be nullified by formulations, particularly at the highest dose. These formulations seemed to destroy Orobanche but appeared harmless to host plants. Hence, they could be efficiently used as mycoherbicides for biological control of Orobanche in faba bean and tomato.

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

    Directory of Open Access Journals (Sweden)

    C. NARENDRA

    2008-03-01

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

  1. Controlled release of biofunctional substances by radiation-induced polymerization

    International Nuclear Information System (INIS)

    Yoshida, M.; Kumakura, M.; Kaetsu, I.

    1978-01-01

    The controlled release of potassium chloride from flat circular matrices made by radiation-induced polymerization of a glass-forming monomer at low temperatures has been studied. The water-particle phase content formed in a poly(diethylene glycol dimethacrylate) matrix was controlled by the addition of polyethylene glycol 600. The dispersed water-particle phase content in the matrix was estimated directly and by scanning electron microscopic observations. The release of potassium chloride from the matrix increased linearly with the square root of time. The water content of the matrix had an important effect on the release rate which increases roughly in proportion to water content. This effect can be attributed to the apparent increase of the rate of drug diffusion. (author)

  2. Commercial formulations of Bacillus thuringiensis for control of Indian meal moth.

    Science.gov (United States)

    Schesser, J H

    1976-10-01

    Doses of four commercial formulations and one experimental formulation of Bacillus thuringiensis Berliner were mixed with the diet used to rear colonies of the Indian meal moth Plodia interpunctella (Hübner). Indian meal moth eggs were introduced to the treated diet, and the resultant adult emergence was tabulated. The experimental formulations ranked as follows in efficacy in controlling the Indian meal moth: Dipel (50% lethal concentration [LC50], 25 mg/kg) greater than Bactospeine WP (LC50, 100 mg/kg) greater than Thuricide (LC50, 150 mg/kg) greater than IMC 90007 (LC30, 180 mg/kg) greater than Bactospeine Flowable (LC50, 440 mg/kg).

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

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  4. Relative bioavailability of diclofenac potassium from softgel capsule versus powder for oral solution and immediate-release tablet formulation.

    Science.gov (United States)

    Bende, Girish; Biswal, Shibadas; Bhad, Prafulla; Chen, Yuming; Salunke, Atish; Winter, Serge; Wagner, Robert; Sunkara, Gangadhar

    2016-01-01

    The oral bioavailability of diclofenac potassium 50 mg administered as a soft gelatin capsule (softgel capsule), powder for oral solution (oral solution), and tablet was evaluated in a randomized, open-label, 3-period, 6-sequence crossover study in healthy adults. Plasma diclofenac concentrations were measured using a validated liquid chromatography-mass spectrometry/mass spectrometry method, and pharmacokinetic analysis was performed by noncompartmental methods. The median time to achieve peak plasma concentrations of diclofenac was 0.5, 0.25, and 0.75 hours with the softgel capsule, oral solution, and tablet formulations, respectively. The geometric mean ratio and associated 90%CI for AUCinf, and Cmax of the softgel capsule formulation relative to the oral solution formulation were 0.97 (0.95-1.00) and 0.85 (0.76-0.95), respectively. The geometric mean ratio and associated 90%CI for AUCinf and Cmax of the softgel capsule formulation relative to the tablet formulation were 1.04 (1.00-1.08) and 1.67 (1.43-1.96), respectively. In conclusion, the exposure (AUC) of diclofenac with the new diclofenac potassium softgel capsule formulation was comparable to that of the existing oral solution and tablet formulations. The peak plasma concentration of diclofenac from the new softgel capsule was 67% higher than the existing tablet formulation, whereas it was 15% lower in comparison with the oral solution formulation. © 2015, The American College of Clinical Pharmacology.

  5. Antifouling efficacy of a controlled depletion paint formulation with acetophenone

    Directory of Open Access Journals (Sweden)

    Sangmok Jung

    2017-12-01

    Full Text Available Biofouling is an inevitable problem that occurs continually on marine fishing vessels and other small crafts. The nature of the antifouling (AF coatings used to prevent biofouling on these small vessels is of great environmental concern. Therefore, the efficacy of a non-toxic AF candidate, acetophenone, was evaluated in preliminary laboratory assays using marine bacteria, diatom and Ulva spores. At a low concentration of 100 μg cm–2 of acetophenone, spore attachment of a green fouling alga was significantly reduced (p < 0.01. Similarly, 40% acetophenone coatings significantly inhibited diatom attachment. This new non-toxic AF agent was incorporated into controlled depletion paint (CDP. Fouling coverage (%, biomass, and fouling resistance (% were estimated. On CDP coatings made with acetophenone (40%, a significant decrease in fouling biomass was estimated (p < 0.01.

  6. CONTROLLED RELEASE, BLIND TEST OF DNAPL REMEDIATION BY ETHANOL FLUSHING

    Science.gov (United States)

    A dense nonaqueous phase liquid (DNAPL) source zone was established within a sheet-pileisolated cell through a controlled release of perchloroethylene (PCE) to evaluate DNAPLremediation by in-situ cosolvent flushing. Ethanol was used as the cosolvent, and the main remedia...

  7. Rectal absorption of morphine from controlled release suppositories

    NARCIS (Netherlands)

    Moolenaar, Frits; Meyler, Pim; Frijlink, Erik; Jauw, Tjoe Hang; Visser, Jan; Proost, Johannes

    1995-01-01

    The absorption profiles and bioavailability of morphine in human volunteers (n = 13) were described after oral administration of MS Contin tablets and rectal administration of a newly developed controlled release suppository. By manipulating the viscosity of fatty suppository base an entirely

  8. Controlled antiseptic release by alginate polymer films and beads.

    Science.gov (United States)

    Liakos, Ioannis; Rizzello, Loris; Bayer, Ilker S; Pompa, Pier Paolo; Cingolani, Roberto; Athanassiou, Athanassia

    2013-01-30

    Biodegradable polymeric materials based on blending aqueous dispersions of natural polymer sodium alginate (NaAlg) and povidone iodine (PVPI) complex, which allow controlled antiseptic release, are presented. The developed materials are either free standing NaAlg films or Ca(2+)-cross-linked alginate beads, which properly combined with PVPI demonstrate antibacterial and antifungal activity, suitable for therapeutic applications, such as wound dressing. Glycerol was used as the plasticizing agent. Film morphology was studied by optical and atomic force microscopy. It was found that PVPI complex forms well dispersed circular micro-domains within the NaAlg matrix. The beads were fabricated by drop-wise immersion of NaAlg/PVPI/glycerol solutions into aqueous calcium chloride solutions to form calcium alginate beads encapsulating PVPI solution (CaAlg/PVPI). Controlled release of PVPI was possible when the composite films and beads were brought into direct contact with water or with moist media. Bactericidal and fungicidal properties of the materials were tested against Escherichia coli bacteria and Candida albicans fungi. The results indicated very efficient antibacterial and antifungal activity within 48 h. Controlled release of PVPI into open wounds is highly desired in clinical applications to avoid toxic doses of iodine absorption by the wound. A wide variety of applications are envisioned such as external and internal wound dressings with controlled antiseptic release, hygienic and protective packaging films for medical devices, and polymer beads as water disinfectants. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Improvement of waste release control in French NPP

    International Nuclear Information System (INIS)

    Samson, T.; Lucquin, E.; Dupin, M.; Florence, D.; Grisot, M.

    2002-01-01

    The new waste release control in French NPP is more restrictive than the old one and needs heavy investment to bring plants to compliance with it. The great evolutions are a chemical follow up on more chemicals with a higher measurement frequency and with lower maximum concentrations and a specific measurement of carbon 14. Regarding radioactive releases, a new counting has been settled and activity of carbon 14 release is now measured and no longer calculated. The evolution of the French regulation leads to develop specific procedures and analytical techniques in chemistry and in radiochemistry (UV spectrometric methods, carbon 14 measurements,..) EDF NPP operators have launched a voluntarist process to reduce their releases since the beginning and before the evolution of the regulation. EDF priorities in terms of environment care lead henceforth to implement a global optimisation of the impact for a better control of releases. The new regulation will help EDF to reach its goals because it covers all the aspects in one administrative document: it is seen as a real simplification and a clarification towards public. In addition, this new regulation fits in with international practices which will allow an easier comparison of results between EDF and foreign NPP. These big environmental concerns lead EDF to create a national dedicated laboratory (LAMEN) in charge of developing specific measurement procedures to be implemented either by NPP or by sub-contractor laboratories. (authors)

  10. Controlled release of ethylene via polymeric films for food packaging

    Science.gov (United States)

    Pisano, Roberto; Bazzano, Marco; Capozzi, Luigi Carlo; Ferri, Ada; Sangermano, Marco

    2015-12-01

    In modern fruit supply chain a common method to trigger ripening is to keep fruits inside special chambers and initiate the ripening process through administration of ethylene. Ethylene is usually administered through cylinders with inadequate control of its final concentration in the chamber. The aim of this study is the development of a new technology to accurately regulate ethylene concentration in the atmosphere where fruits are preserved: a polymeric film, containing an inclusion complex of α-cyclodextrin with ethylene, was developed. The complex was prepared by molecular encapsulation which allows the entrapment of ethylene into the cavity of α-cyclodextrin. After encapsulation, ethylene can be gradually released from the inclusion complex and its release rate can be regulated by temperature and humidity. The inclusion complex was dispersed into a thin polymeric film produced by UV-curing. This method was used because is solvent-free and involves low operating temperature; both conditions are necessary to prevent rapid release of ethylene from the film. The polymeric films were characterized with respect to thermal behaviour, crystalline structure and kinetics of ethylene release, showing that can effectively control the release of ethylene within confined volume.

  11. Improvement of waste release control in French NPP

    Energy Technology Data Exchange (ETDEWEB)

    Samson, T.; Lucquin, E.; Dupin, M. [EDF/GDL (France); Florence, D. [EDF/GENV (France); Grisot, M. [EDF/CNPE Saint Laurent (France)

    2002-07-01

    The new waste release control in French NPP is more restrictive than the old one and needs heavy investment to bring plants to compliance with it. The great evolutions are a chemical follow up on more chemicals with a higher measurement frequency and with lower maximum concentrations and a specific measurement of carbon 14. Regarding radioactive releases, a new counting has been settled and activity of carbon 14 release is now measured and no longer calculated. The evolution of the French regulation leads to develop specific procedures and analytical techniques in chemistry and in radiochemistry (UV spectrometric methods, carbon 14 measurements,..) EDF NPP operators have launched a voluntarist process to reduce their releases since the beginning and before the evolution of the regulation. EDF priorities in terms of environment care lead henceforth to implement a global optimisation of the impact for a better control of releases. The new regulation will help EDF to reach its goals because it covers all the aspects in one administrative document: it is seen as a real simplification and a clarification towards public. In addition, this new regulation fits in with international practices which will allow an easier comparison of results between EDF and foreign NPP. These big environmental concerns lead EDF to create a national dedicated laboratory (LAMEN) in charge of developing specific measurement procedures to be implemented either by NPP or by sub-contractor laboratories. (authors)

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

    Directory of Open Access Journals (Sweden)

    Muhammad Zaman

    2016-01-01

    Full Text Available Oral route of drug administration is considered as the safest and easiest route of drug administration. Control release drug delivery system is the emerging trend in the pharmaceuticals and the oral route is most suitable for such kind of drug delivery system. Oral route is more convenient for It all age group including both pediatric and geriatrics. There are various systems which are adopted to deliver drug in a controlled manner to different target sites through oral route. It includes diffusion controlled drug delivery systems; dissolution controlled drug delivery systems, osmotically controlled drug delivery systems, ion-exchange controlled drug delivery systems, hydrodynamically balanced systems, multi-Particulate drug delivery systems and microencapsulated drug delivery system. The systems are formulated using different natural, semi-synthetic and synthetic polymers. The purpose of the review is to provide information about the orally controlled drug delivery system, polymers which are used to formulate these systems and characterizations of one of the most convenient dosage form which is the tablets. 

  13. Methodology for performing measurements to release material from radiological control

    International Nuclear Information System (INIS)

    Durham, J.S.; Gardner, D.L.

    1993-09-01

    This report describes the existing and proposed methodologies for performing measurements of contamination prior to releasing material for uncontrolled use at the Hanford Site. The technical basis for the proposed methodology, a modification to the existing contamination survey protocol, is also described. The modified methodology, which includes a large-area swipe followed by a statistical survey, can be used to survey material that is unlikely to be contaminated for release to controlled and uncontrolled areas. The material evaluation procedure that is used to determine the likelihood of contamination is also described

  14. The present status of rare gas release control

    International Nuclear Information System (INIS)

    Yamamoto, Hiroshi

    1974-01-01

    Of the rare gases Ar, Kr and Xe released from nuclear facilities, the problem of release control can be confined to 41 Ar, 85 Kr and 133 Xe. The cases of the latter two are described, as 41 Ar is not much significant. 133 Xe, having relatively short half-life, can be dealt sufficiently by holding-up in case of light water reactors. 85 Kr of long half-life must be removed : the methods are low temperature adsorption, liquefaction distillation, absorption and diaphragm method. As for future problem, there is disposal of concentrated rare gas. (Mori, K.)

  15. Bacillus subtilis based-formulation for the control of postbloom fruit drop of citrus.

    Science.gov (United States)

    Klein, Mariana Nadjara; da Silva, Aline Caroline; Kupper, Katia Cristina

    2016-12-01

    Postbloom fruit drop (PFD) caused by Colletotrichum acutatum affects flowers and causes early fruit drop in all commercial varieties of citrus. Biological control with the isolate ACB-69 of Bacillus subtilis has been considered as a potential method for controlling this disease. This study aimed to develop and optimize a B. subtilis based-formulation with a potential for large-scale applications and evaluate its effect on C. acutatum in vitro and in vivo. Bacillus subtilis based-formulations were developed using different carrier materials, and their ability to control PFD was evaluated. The results of the assays led to the selection of the B. subtilis based-formulation with talc + urea (0.02 %) and talc + ammonium molybdate (1 mM), which inhibited mycelial growth and germination of C. acutatum. Studies with detached citrus flowers showed that the formulations were effective in controlling the pathogen. In field conditions, talc + urea (0.02 %) provided 73 % asymptomatic citrus flowers and 56 % of the average number of effective fruit (ANEF), equating with fungicide treatment. On the contrary, non-treated trees had 8.8 % of asymptomatic citrus flowers and 0.83 % ANEF. The results suggest that B. subtilis based-formulations with talc as the carrier supplemented with a nitrogen source had a high potential for PFD control.

  16. Metabolic control of vesicular glutamate transport and release.

    Science.gov (United States)

    Juge, Narinobu; Gray, John A; Omote, Hiroshi; Miyaji, Takaaki; Inoue, Tsuyoshi; Hara, Chiaki; Uneyama, Hisayuki; Edwards, Robert H; Nicoll, Roger A; Moriyama, Yoshinori

    2010-10-06

    Fasting has been used to control epilepsy since antiquity, but the mechanism of coupling between metabolic state and excitatory neurotransmission remains unknown. Previous work has shown that the vesicular glutamate transporters (VGLUTs) required for exocytotic release of glutamate undergo an unusual form of regulation by Cl(-). Using functional reconstitution of the purified VGLUTs into proteoliposomes, we now show that Cl(-) acts as an allosteric activator, and the ketone bodies that increase with fasting inhibit glutamate release by competing with Cl(-) at the site of allosteric regulation. Consistent with these observations, acetoacetate reduced quantal size at hippocampal synapses and suppresses glutamate release and seizures evoked with 4-aminopyridine in the brain. The results indicate an unsuspected link between metabolic state and excitatory neurotransmission through anion-dependent regulation of VGLUT activity. Copyright © 2010 Elsevier Inc. All rights reserved.

  17. 3D printed, controlled release, tritherapeutic tablet matrix for advanced anti-HIV-1 drug delivery.

    Science.gov (United States)

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

    2018-04-12

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

  18. Application of Electrostatic Extrusion – Flavour Encapsulation and Controlled Release

    Science.gov (United States)

    Manojlovic, Verica; Rajic, Nevenka; Djonlagic, Jasna; Obradovic, Bojana; Nedovic, Viktor; Bugarski, Branko

    2008-01-01

    The subject of this study was the development of flavour alginate formulations aimed for thermally processed foods. Ethyl vanilline was used as the model flavour compound. Electrostatic extrusion was applied for the encapsulation of ethyl vanilline in alginate gel microbeads. The obtained microbeads with approx. 10 % w/w of ethyl vanilline encapsulated in about 2 % w/w alginate were uniformly sized spheres of about 450 μm. Chemical characterization by H-NMR spectroscopy revealed that the alginate used in this study had a high content (67 %) of guluronic residues and was rich in GG diad blocks (FGG = 55%) and thus presented a high-quality immobilisation matrix. The thermal behaviour of alginate beads encapsulating ethyl vanilline was investigated by thermogravimetric (TG) and differential scanning calorimetry measurements (TG-DSC) under heating conditions which mimicked usual food processing to provide information about thermal decomposition of alginate matrix and kinetics of aroma release. Two well resolved weight losses were observed. The first one was in the 50-150 °C temperature range with the maximum at approx. 112 °C, corresponding to the dehydration of the polymer network. The second loss in the 220-325 °C temperature range, with a maximum at ∼ 247 °C corresponded to the release of vanilline. The obtained results indicate that up to 230 °C most of the vanilline remained intacta, while prolonged heating at elevated temperatures led to the entire loss of the aroma compound. PMID:27879775

  19. Controlled release of beta-estradiol from PLAGA microparticles: the effect of organic phase solvent on encapsulation and release.

    Science.gov (United States)

    Birnbaum, D T; Kosmala, J D; Henthorn, D B; Brannon-Peppas, L

    2000-04-03

    To determine the effect of the organic solvent used during microparticle preparation on the in vitro release of beta-estradiol, a number of formulations were evaluated in terms of size, shape and drug delivery performance. Biodegradable microparticles of poly(lactide-co-glycolide) were prepared containing beta-estradiol that utilized dichloromethane, ethyl acetate or a mixture of dichloromethane and methanol as the organic phase solvent during the particle preparation. The drug delivery behavior from the microparticles was studied and comparisons were made of their physical properties for different formulations. The varying solubilities of beta-estradiol and poly(lactide-co-glycolide) in the solvents studied resulted in biodegradable microparticles with very different physical characteristics. Microparticles prepared from solid suspensions of beta-estradiol using dichloromethane as the organic phase solvent were similar in appearance to microparticles prepared without drug. Microparticles prepared from dichloromethane/methanol solutions appeared transparent to translucent depending on the initial amount of drug used in the formulation. Microparticles prepared using ethyl acetate appeared to have the most homogeneous encapsulation of beta-estradiol, appearing as solid white spheres regardless of initial drug content. Studies showed that microparticles prepared from either ethyl acetate or a mixture of dichloromethane and methanol gave a more constant release profile of beta-estradiol than particles prepared using dichloromethane alone. For all formulations, an initial burst of release increased with increasing drug loading, regardless of the organic solvent used.

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  1. Highly Efficient Thermoresponsive Nanocomposite for Controlled Release Applications

    KAUST Repository

    Yassine, Omar

    2016-06-23

    Highly efficient magnetic release from nanocomposite microparticles is shown, which are made of Poly (N-isopropylacrylamide) hydrogel with embedded iron nanowires. A simple microfluidic technique was adopted to fabricate the microparticles with a high control of the nanowire concentration and in a relatively short time compared to chemical synthesis methods. The thermoresponsive microparticles were used for the remotely triggered release of Rhodamine (B). With a magnetic field of only 1 mT and 20 kHz a drug release of 6.5% and 70% was achieved in the continuous and pulsatile modes, respectively. Those release values are similar to the ones commonly obtained using superparamagnetic beads but accomplished with a magnetic field of five orders of magnitude lower power. The high efficiency is a result of the high remanent magnetization of the nanowires, which produce a large torque when exposed to a magnetic field. This causes the nanowires to vibrate, resulting in friction losses and heating. For comparison, microparticles with superparamagnetic beads were also fabricated and tested; while those worked at 73 mT and 600 kHz, no release was observed at the low field conditions. Cytotoxicity assays showed similar and high cell viability for microparticles with nanowires and beads.

  2. Highly Efficient Thermoresponsive Nanocomposite for Controlled Release Applications

    KAUST Repository

    Yassine, Omar; Zaher, Amir; Li, Erqiang; Alfadhel, Ahmed; Perez, Jose E.; Kavaldzhiev, Mincho; Contreras, Maria F.; Thoroddsen, Sigurdur T; Khashab, Niveen M.; Kosel, Jü rgen

    2016-01-01

    Highly efficient magnetic release from nanocomposite microparticles is shown, which are made of Poly (N-isopropylacrylamide) hydrogel with embedded iron nanowires. A simple microfluidic technique was adopted to fabricate the microparticles with a high control of the nanowire concentration and in a relatively short time compared to chemical synthesis methods. The thermoresponsive microparticles were used for the remotely triggered release of Rhodamine (B). With a magnetic field of only 1 mT and 20 kHz a drug release of 6.5% and 70% was achieved in the continuous and pulsatile modes, respectively. Those release values are similar to the ones commonly obtained using superparamagnetic beads but accomplished with a magnetic field of five orders of magnitude lower power. The high efficiency is a result of the high remanent magnetization of the nanowires, which produce a large torque when exposed to a magnetic field. This causes the nanowires to vibrate, resulting in friction losses and heating. For comparison, microparticles with superparamagnetic beads were also fabricated and tested; while those worked at 73 mT and 600 kHz, no release was observed at the low field conditions. Cytotoxicity assays showed similar and high cell viability for microparticles with nanowires and beads.

  3. Floating tablets for controlled release of ofloxacin via compression coating of hydroxypropyl cellulose combined with effervescent agent.

    Science.gov (United States)

    Qi, Xiaole; Chen, Haiyan; Rui, Yao; Yang, Fengjiao; Ma, Ning; Wu, Zhenghong

    2015-07-15

    To prolong the residence time of dosage forms within gastrointestinal trace until all drug released at desired rate was one of the real challenges for oral controlled-release drug delivery system. Herein, we developed a fine floating tablet via compression coating of hydrophilic polymer (hydroxypropyl cellulose) combined with effervescent agent (sodium bicarbonate) to achieve simultaneous control of release rate and location of ofloxacin. Sodium alginate was also added in the coating layer to regulate the drug release rate. The effects of the weight ratio of drug and the viscosity of HPC on the release profile were investigated. The optimized formulations were found to immediately float within 30s and remain lastingly buoyant over a period of 12 h in simulated gastric fluid (SGF, pH 1.2) without pepsin, indicating a satisfactory floating and zero-order drug release profile. In addition, the oral bioavailability experiment in New Zealand rabbits showed that, the relative bioavailability of the ofloxacin after administrated of floating tablets was 172.19%, compared to marketed common release tablets TaiLiBiTuo(®). These results demonstrated that those controlled-released floating tables would be a promising gastro-retentive delivery system for drugs acting in stomach. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Delayed release formulation of the somatostatin analog RC-160 inhibits the growth hormone (GH) response to GH-releasing factor-(1-29)NH2 and decreases elevated prolactin levels in rats.

    Science.gov (United States)

    Bokser, L; Schally, A V

    1988-10-01

    Recently, we have developed a long-acting delivery system for our somatostatin (SS) analog RC-160 based on injectable microcapsules in poly-(D,L-lactide-coglycolide). We studied the capacity of this formulation to repeatedly block the GH secretion induced by administration of GRF-(1-29)NH2 (GRF) on different days. Male rats anesthetized with pentobarbital were injected iv with 2.5 micrograms/kg BW GRF-(1-29)NH2 or saline. Five minutes later, blood samples were taken for GH measurement, and the animals were injected im with RC-160 microcapsules at a dose calculated to release 25 micrograms/day of the analog for 7 days or with the vehicle. The GRF stimuli were repeated 48 h, 96 h, and 8 days after administration of SS analog in microcapsules. GRF administration increased GH levels at the four times tested (P less than 0.01) in the control group injected with vehicle, while RC-160 microcapsules inhibited the GH response for more than 96 h (P less than 0.01). The GH levels augmented by pentobarbital were also decreased by the RC-160 microcapsules (P less than 0.01). Animals treated with microcapsules showed smaller increases in their body weight than untreated rats (P less than 0.05). We also investigated the effect of RC-160 microcapsules on hyperprolactinemic female rats implanted with pituitary glands under the kidney capsules. High PRL levels in rats bearing pituitary grafts showed a significant decrease when measured 4 days after the administration of RC-160 microcapsules. These results demonstrate the efficacy of the long-acting delivery system of the SS analog RC-160 and suggest the possible clinical usefulness of this formulation for lowering GH and PRL levels.

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

    Science.gov (United States)

    Dolinina, Ekaterina S; Parfenyuk, Elena V

    2017-01-01

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

  6. Controlled release of agrochemicals intercalated into montmorillonite interlayer space.

    Science.gov (United States)

    Wanyika, Harrison

    2014-01-01

    Periodic application of agrochemicals has led to high cost of production and serious environmental pollution. In this study, the ability of montmorillonite (MMT) clay to act as a controlled release carrier for model agrochemical molecules has been investigated. Urea was loaded into MMT by a simple immersion technique while loading of metalaxyl was achieved by a rotary evaporation method. The successful incorporation of the agrochemicals into the interlayer space of MMT was confirmed by several techniques, such as, significant expansion of the interlayer space, reduction of Barrett-Joyner-Halenda (BJH) pore volumes and Brunauer-Emmett-Teller (BET) surface areas, and appearance of urea and metalaxyl characteristic bands on the Fourier-transform infrared spectra of the urea loaded montmorillonite (UMMT) and metalaxyl loaded montmorillonite (RMMT) complexes. Controlled release of the trapped molecules from the matrix was done in water and in the soil. The results reveal slow and sustained release behaviour for UMMT for a period of 10 days in soil. For a period of 30 days, MMT delayed the release of metalaxyl in soil by more than 6 times. It is evident that MMT could be used to improve the efficiency of urea and metalaxyl delivery in the soil.

  7. Development and validation of stability indicating method for the quantitative determination of venlafaxine hydrochloride in extended release formulation using high performance liquid chromatography

    Directory of Open Access Journals (Sweden)

    Jaspreet Kaur

    2010-01-01

    Full Text Available Objective : Venlafaxine,hydrochloride is a structurally novel phenethyl bicyclic antidepressant, and is usually categorized as a serotonin-norepinephrine reuptake inhibitor (SNRI but it has been referred to as a serotonin-norepinephrine-dopamine reuptake inhibitor. It inhibits the reuptake of dopamine. Venlafaxine HCL is widely prescribed in the form of sustained release formulations. In the current article we are reporting the development and validation of a fast and simple stability indicating, isocratic high performance liquid chromatographic (HPLC method for the determination of venlafaxine hydrochloride in sustained release formulations. Materials and Methods : The quantitative determination of venlafaxine hydrochloride was performed on a Kromasil C18 analytical column (250 x 4.6 mm i.d., 5 μm particle size with 0.01 M phosphate buffer (pH 4.5: methanol (40: 60 as a mobile phase, at a flow rate of 1.0 ml/min. For HPLC methods, UV detection was made at 225 nm. Results : During method validation, parameters such as precision, linearity, accuracy, stability, limit of quantification and detection and specificity were evaluated, which remained within acceptable limits. Conclusions : The method has been successfully applied for the quantification and dissolution profiling of Venlafaxine HCL in sustained release formulation. The method presents a simple and reliable solution for the routine quantitative analysis of Venlafaxine HCL.

  8. Evaluation of alternative Plutella xylostella control by two Isaria fumosorosea conidial formulations - oil-based formulation and wettable powder - combined with Bacillus thuringiensis.

    Science.gov (United States)

    Nian, Xiao-Ge; He, Yu-Rong; Lu, Li-Hua; Zhao, Rui

    2015-12-01

    Entomopathogenic fungi are potential candidates for controlling the diamondback moth Plutella xylostella (L.) (Lepidoptera: Plutellidae). The control efficacy of two Isaria fumosorosea conidial formulations - wettable powder and oil-based formulation - combined with Bacillus thuringiensis against P. xylostella was tested. In the laboratory, the combined application of two pathogens increased larval mortality either in an additive or a synergistic way. P. xylostella larvae treated with oil-based formulation died sooner than larvae infected with wettable powder. For pot and field experiments, each formulation was applied alone or combined with B. thuringiensis 668 µg mL(-1) , and then larval mortality, pupation rate, adult emergence rate, female longevity and fecundity were recorded. In pot experiments there was no evidence of any antagonistic effects between the two pathogens. Combined application of B. thuringiensis and a high concentration of the two I. fumosorosea formulations resulted in higher mortality (84.4 and 86.2%) with minimum pupation (15.6 and 11.9%) and adult emergence rates (8.7 and 7.0%). Female longevity and fecundity were significantly reduced by the two formulations at high concentration compared with the control. Similar results were also observed in field experiments. The combined application of I. fumosorosea and B. thuringiensis is a promising alternative strategy for P. xylostella control. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  9. Reformulation of controlled-release oxycodone and pharmacy dispensing patterns near the US-Canada border.

    Science.gov (United States)

    Gomes, Tara; Paterson, J Michael; Juurlink, David N; Dhalla, Irfan A; Mamdani, Muhammad M

    2012-01-01

    In August 2010, a tamper-resistant formulation of controlled-release oxycodone (OxyContin-OP) was introduced in the United States but not in Canada. Our objective was to determine whether introduction of OxyContin-OP in the United States influenced prescription volumes for the original controlled-release oxycodone formulation (OxyContin) at Canadian pharmacies near the international border. We conducted a population-based, serial, cross-sectional study of prescriptions dispensed from pharmacies in the 3 cities with the highest volume of US-Canada border crossings in Ontario: Niagara Falls, Windsor and Sarnia. We analyzed data on all outpatient prescriptions for OxyContin dispensed by Canadian pharmacies near each border crossing between 2010 Apr. 1 and 2012 Feb. 29. We calculated and compared monthly prescription rates, adjusted per 1000 population and stratified by tablet strength. The number of tablets dispensed near 4 border crossings in the 3 Canadian cities remained stable over the study period. However, the rate of dispensing at pharmacies near the Detroit-Windsor Tunnel increased roughly 4-fold between August 2010 and February 2011, from 505 to 1969 tablets per 1000 population. By April 2011, following warnings to prescribers and pharmacies regarding drug-seeking behaviour, the dispensing rate declined to 1683 tablets per 1000 population in this area. By November 2011, the rate had returned to levels observed in early 2010. Our analyses suggest that 242 075 excess OxyContin tablets were dispensed near the Detroit-Windsor Tunnel between August 2010 and October 2011. Prescribing of the original formulation of controlled-release oxycodone rose substantially near a major international border crossing following the introduction of a tamper-resistant formulation in the United States. It is possible that the restriction of this finding to the area surrounding the Detroit-Windsor Tunnel reflects specific characteristics of this border crossing, including its high

  10. Development and evaluation of controlled-release buccoadhesive verapamil hydrochloride tablets

    Directory of Open Access Journals (Sweden)

    Emami J.

    2008-05-01

    Full Text Available Background and purpose of the study: Verapamil hydrochloride is a calcium channel blocker which is used in the control of supraventricular arrhythmia, hypertension and myocardial infraction. There are considerable inter-individual variations in serum concencentration of verpamil due to variation in the extent of hepatic metabolism. In this study controlled-release buccoadhesive tablets of verapamil hydrochloride (VPH were prepared in order to achieve constant plasma concentrations, to improve the bioavailability by the avoidance of hepatic first-pass metabolism, and to prevent frequent administration. Materials and methods: Tablets containing fixed amount of VPH were prepared by direct compression method using polymers like carbomer (CP, hydroxypropylmethyl cellulose (HPMC and sodium carboxymethyl cellulose (NaCMC in various combination and ratios and evaluated for thickness, weight variation, hardness, drug content uniformity, swelling, mucoadhesive strength, drug release and possible interaction between ingredients. Results: All tablets were acceptable with regard to thickness, weight variation, hardness, and drug content. The maximum bioadhesive strength was observed in tablets formulated with a combination of CP-NaCMC followed by CP-HPMC and NaCMC-HPMC.  Decreasing the content of CP in CP-HPMC tablets or NaCMC in CP-NaCMC or NaCMC-HPMC systems resulted in decrease in detachment forces. Lower release rates were observed by lowering the content of CP in CP-HPMC containing formulations or NaCMC in tablets which contained CP-NaCMC or NaCMC-HPMC. The release behavior was non-Fickian controlled by a combination of diffusion and chain relaxation mechanisms and best fitted zero-order kinetics. Conclusion: The buccoadhesive VPH tablets containing 53% CP and 13.3% HPMC showed suitable release kinetics (n = 0.78, K0 zero order release = 4.11 mg/h, MDT = 5.66 h and adhesive properties and did not show any interaction between polymers and drug based on

  11. pH responsive alginate polymeric rafts for controlled drug release by using box behnken response surface design.

    Science.gov (United States)

    Abbas, Ghulam; Hanif, Muhammad; Khan, Mahtab Ahmad

    2017-01-01

    Aim of the present work was to develop alginate raft forming tablets for controlled release pantoprazole sodium sesquihydrate (PSS). Box behnken design was used to optimize 15 formulations with three independent and three dependent variables. Physical tests of all formulations were within pharmacopoeial limits. Raft was characterized by their strength, thickness, resilience, acid neutralizing capacity, floating lag time and total floating time. Raft strength, thickness and resilience of optimized formulation AR9 were 7.43 ± 0.019 g, 5.8 ± 0.245 cm and greater than 480 min, respectively. Buffering and neutralizing capacity were 11.2 ± 1.01 and 6.5 ± 0.56 meq, respectively. Dissolution studies were performed by using simulated gastric fluid pH 1.2 and cumulative percentage release of optimized formulation AR9 was found 98%. First order release kinetics were followed and non-fickian diffusion was observed as value of n was greater than 0.45 in korsmeyer-peppas model. PSS, polymers, tablets and rafts were further characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffractometry (XRD) and differential scanning calorimetry (DSC). FTIR spectra of PSS, polymers and raft of optimized formulation AR9 showed peaks at 3223.09, 1688.17, 1586.67, 1302.64 and 1027.74 cm -1 due to -OH stretching, ester carbonyl group (C=O) stretching, existence of water and carboxylic group in raft, C-N stretching and -OH bending vibration showed no interaction between them. XRD showed diffraction lines indicates crystalline nature of PSS. DSC thermogram showed endothermic peaks at 250 °C for PSS. The developed raft was suitable for controlled release delivery of PSS.

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

    OpenAIRE

    Kulwant Singh; S. L. HariKumar

    2012-01-01

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

  13. Controlling Object Heat Release Rate using Geometrical Features

    OpenAIRE

    Kraft, Stefan Marc

    2017-01-01

    An experimental study was conducted to determine the effect of complex geometries on the burning rate of materials made using additive manufacturing. Controlling heat release rate has applicability in limiting fire hazards as well as for designing fuels for optimal burning rate. The burning rate of a structure is a function of the material properties as well as the airflow through it, which is dictated by the geometry. This burning rate is generally proportional to the porosity for obj...

  14. SOL-Gel microspheres and nanospheres for controlled release applications

    International Nuclear Information System (INIS)

    Barbe, C.; Beyer, R.; Kong, L.; Blackford, M.; Trautman, R.; Bartlett, J.

    2002-01-01

    We present a novel approach to the synthesis of inorganic sol-gel microspheres for encapsulating organic and bioactive molecules, and controlling their subsequent release kinetics. The bioactive species are incorporated, at ambient temperature, into the inorganic particles using an emulsion gelation process. Independent control of the release rate (by adapting the nanostructure of the internal pore network to the physico-chemical properties of the bioactive molecules) and particle size (by tailoring the emulsion chemistry) is demonstrated. Sol-gel chemistry has been shown to be a flexible technique for producing inorganic silica matrices with tailored microstructures, which can be used for the encapsulation and controlled release of organic and bioactive molecules. The present paper extends this concept by combining sol-gel chemistry with an emulsion approach for producing inorganic particles with controlled dimensions, and demonstrates how the particle size and microstructure can be independently controlled. Sol-Gel Chemistry and Encapsulation of Model Compounds. A stock solution of 4-(2-hydroxy-l-naphthylazo) benzene sulfonic acid (Orange II) was produced by dissolving Orange II in water (0.1 wt%), and adjusting the pH to the required value. Sol-gel solutions were subsequently prepared by mixing the aqueous solution with tetramethylorthosilicate (TMOS) and methanol (MeOH), to achieve H 2 O:TMOS (W] and MeOH:TMOS mole ratios (D) of four. The resulting solution was stirred and left to age at ambient temperature for one day. A transparent emulsion was prepared by mixing selected surfactants and organic solvents. The surfactants used included sorbitan monooleate, sorbitan monolaurate and bis-2-ethylhexylsulfo-succinate (AOT), while the organic phase was typically chosen from the group consisting of kerosene, hexane, heptane, octane, decane, dodecane and cyclohexane. The sol-gel solution was added to the emulsion, and the resulting mixture was stirred at 500 rpm for

  15. Controlled release from bilayer-decorated magnetoliposomes via electromagnetic heating.

    Science.gov (United States)

    Chen, Yanjing; Bose, Arijit; Bothun, Geoffrey D

    2010-06-22

    Nanoscale assemblies that can be activated and controlled through external stimuli represent a next stage in multifunctional therapeutics. We report the formation, characterization, and release properties of bilayer-decorated magnetoliposomes (dMLs) that were prepared by embedding small hydrophobic SPIO nanoparticles at different lipid molecule to nanoparticle ratios within dipalmitoylphosphatidylcholine (DPPC) bilayers. The dML structure was examined by cryogenic transmission electron microscopy and differential scanning calorimetry, and release was examined by carboxyfluorescein leakage. Nanoparticle heating using alternating current electromagnetic fields (EMFs) operating at radio frequencies provided selective release of the encapsulated molecule at low nanoparticle concentrations and under physiologically acceptable EMF conditions. Without radio frequency heating, spontaneous leakage from the dMLs decreased with increasing nanoparticle loading, consistent with greater bilayer stability and a decrease in the effective dML surface area due to aggregation. With radio frequency heating, the initial rate and extent of leakage increased significantly as a function of nanoparticle loading and electromagnetic field strength. The mechanism of release is attributed to a combination of bilayer permeabilization and partial dML rupture.

  16. Formulation and quality control of a topical gel product for treatment of melasmaFormulation and quality control of a topical gel product for treatment of melasma

    Directory of Open Access Journals (Sweden)

    A. Ketabi

    2017-11-01

    Full Text Available Background and objectives: Melasma is one of the most common pigmentary disorders. It has a considerable impact on quality of life. The treatment of melasma has still remained a challenge because the efficient treatment has not been proven until now and there is still a need to find new depigmenting products.Allium cepa L. and Cucumis melo L. seeds as well as tragacanth have been introduced in Iranian traditional medicine (ITM as depigmenting agents. Moreover, modern studies have shown their antioxidant and inhibitory mushroom tyrosinase effect.In this study, a topical gel containing Allium cepa L. and Cucumis melo L. seeds extract was prepared with tragacanth and quality control evaluations have been accomplished. Method: After performing quality control of plants seeds and tragacanth according to pharmacopoeia, the ethanol extract of A. cepa and hydroalcoholic extract of C. melo seeds were prepared. An appropriate gel formulation was selected on the base of suitable viscosity. The gel product was formulated using 5% of each plant extracts in tragacanth gel base. In addition, the herbal gel was evaluated using pharmaceutical behavior such as physical appearance, pH, viscosity, spreadability as well as phenolics content. Results: The herbal gel product showed acceptable pharmaceutical behavior as well as considerable phenolic content (1.43±0.01 mg/g. Conclusion: The prepared topical gel product could be a good natural formulation candidate for clinical studies in the field of hyperpigmentation. Moreover, phenolic content of the product could be considered as an indicator for its quality control.

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

    Science.gov (United States)

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

    2009-12-01

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

  18. Rheological behaviour and physical properties of controlled-release gluten-based bioplastics.

    Science.gov (United States)

    Gómez-Martínez, D; Partal, P; Martínez, I; Gallegos, C

    2009-03-01

    Bioplastics based on glycerol, water and wheat gluten have been manufactured in order to determine the effect that mechanical processing and further thermal treatments exert on different thermo-mechanical properties of the biomaterials obtained. An "active agent", KCl was incorporated in these matrices to develop controlled-release formulations. Oscillatory shear, dynamic mechanical thermal analysis (DMTA), diffusion and water absorption tests were carried out in order to study the influence of the above-mentioned treatments on the physico-chemical characteristics and rheological behaviour of these bioplastic samples. Wheat gluten protein-based bioplastics studied in this work present a high ability for thermosetting modification, due to protein denaturation, which may favour the development of a wide variety of biomaterials. Bioplastic hygroscopic properties depend on plasticizer nature and processing procedure, and may be a key factor for industrial applications where water absorption is required. On the other hand, high water absorption and slow KCl release from bioplastic samples (both of them suitable properties in agricultural applications) may be obtained by adding citric acid to a given formulation, at selected processing conditions.

  19. In vitro characterization of a formulation of butorphanol tartrate in a poloxamer 407 base intended for use as a parenterally administered slow-release analgesic agent.

    Science.gov (United States)

    Laniesse, Delphine; Smith, Dale A; Knych, Heather K; Mosley, Cornelia; Guzman, David Sanchez-Migallon; Beaufrère, Hugues

    2017-06-01

    OBJECTIVE To assess rheological properties and in vitro diffusion of poloxamer 407 (P407) and butorphanol-P407 (But-P407) hydrogels and to develop a sustained-release opioid formulation for use in birds. SAMPLE P407 powder and a commercially available injectable butorphanol tartrate formulation (10 mg/mL). PROCEDURES P407 and But-P407 gels were compounded by adding water or butorphanol to P407 powder. Effects of various concentrations of P407 (20%, 25% and 30% [{weight of P407/weight of diluent} × 100]), addition of butorphanol, and sterilization through a microfilter on rheological properties of P407 were measured by use of a rheometer. In vitro diffusion of butorphanol from But-P407 25% through a biological membrane was compared with that of a butorphanol solution. RESULTS P407 20% and 25% formulations were easily compounded, whereas it was difficult to obtain a homogenous P407 30% formulation. The P407 was a gel at avian body temperature, although its viscosity was lower than that at mammalian body temperature. The But-P407 25% formulation (butorphanol concentration, 8.3 mg/mL) was used for subsequent experiments. Addition of butorphanol to P407 as well as microfiltration did not significantly affect viscosity. Butorphanol diffused in vitro from But-P407, and its diffusion was slower than that from a butorphanol solution. CONCLUSIONS AND CLINICAL RELEVANCE But-P407 25% had in vitro characteristics that would make it a good candidate for use as a sustained-release analgesic medication. Further studies are needed to characterize the pharmacokinetic and pharmacodynamic properties of But-P407 25% in vivo before it can be recommended for use in birds.

  20. A foam formulation of an entomopathogenic fungus for control of boring beetles in avocado orchards

    Science.gov (United States)

    A foam formulation of Beauveria bassiana was adapted to control boring beetles in avocado orchards. The two geographically independent avocado growing areas in the United States are threatened by emerging diseases vectored by boring beetles. In the California growing region, Fusarium dieback is vect...

  1. 77 FR 30025 - Importer of Controlled Substances; Notice of Registration; Formulation Technologies, LLC

    Science.gov (United States)

    2012-05-21

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration Importer of Controlled Substances; Notice of Registration; Formulation Technologies, LLC By Notice dated January 26, 2012, and published in the Federal..., Austin, Texas 78758, made application by renewal to the Drug Enforcement Administration (DEA) to be...

  2. A comparison of the extended-release and standard-release formulations of tacrolimus in de novo kidney transplant recipients: a 12-month outcome study.

    Science.gov (United States)

    Fanous, Helen; Zheng, Rebecca; Campbell, Carolyn; Huang, Michael; Nash, Michelle M; Rapi, Lindita; Zaltzman, Jeffrey S; Prasad, G V Ramesh

    2013-02-01

    BACKGROUND: Limited comparative data are available on the outcomes between extended-release and standard-release tacrolimus when used de novo in kidney transplant recipients (KTRs). METHODS: We identified KTRs transplanted at our institution during 2009-10 routinely prescribed extended-release tacrolimus and compared them with those transplanted during 2008-09 prescribed standard-release tacrolimus. Graft function (eGFR by MDRD-7 equation) at 12 months post-transplant (primary outcome); new-onset diabetes and other cardiovascular risk factors, BK viremia incidence, acute rejection, and graft survival to 12 months (secondary outcomes) were compared by intent-to-treat analysis. Time-to-steady-state concentration and number of dose adjustments required to attain steady state were recorded. RESULTS: There were no important demographic differences between the extended-release (N = 106) and standard-release (N = 95) cohorts. The estimated glomerular filtration rate (eGFR) at 12 months was similar (58.8 ± 17 versus 59.2 ± 18 mL/min/1.73 m(2), P = 0.307). There was no difference in new-onset diabetes (17 versus 20%, P = 0.581), BK viremia (10 versus 7%, P = 0.450), acute rejection (7 versus 16%, P = 0.067) or graft survival (97 versus 95%, P = 0.301). Time-to-steady state was similar (9.2 ± 1.1 versus 8.1 ± 4.7 days, P = 0.490) although extended-release patients required fewer adjustments to attain steady state (1.2 ± 1.7 [0-8] versus 1.7 ± 1.5 [0-7], P = 0.030) but a similar dose (7.2 ± 2.4 [2-17] versus 7 ± 2.7 [2-16] mg/day, P = 0.697). CONCLUSION: De novo KTRs prescribed extended-release or standard-release tacrolimus demonstrate similar 12-month outcomes.

  3. Controlled release of ibuprofen by meso-macroporous silica

    Science.gov (United States)

    Santamaría, E.; Maestro, A.; Porras, M.; Gutiérrez, J. M.; González, C.

    2014-02-01

    Structured meso-macroporous silica was successfully synthesized from an O/W emulsion using decane as a dispersed phase. Sodium silicate solution, which acts as a silica source and a poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (EO19PO39EO19) denoted as P84 was used in order to stabilize the emulsion and as a mesopore template. The materials obtained were characterized through transmission electron microscopy (TEM), scanning electron microscopy (SEM), small-angle X-ray diffraction scattering (SAXS) and nitrogen adsorption-desorption isotherms. Ibuprofen (IBU) was selected as the model drug and loaded into ordered meso-macroporous materials. The effect of the materials’ properties on IBU drug loading and release was studied. The results showed that the loading of IBU increases as the macropore presence in the material is increased. The IBU adsorption process followed the Langmuir adsorption isotherm. A two-step release process, consisting of an initial fast release and then a slower release was observed. Macropores enhanced the adsorption capacity of the material; this was probably due to the fact that they allowed the drug to access internal pores. When only mesopores were present, ibuprofen was probably adsorbed on the mesopores close to the surface. Moreover, the more macropore present in the material, the slower the release behaviour observed, as the ibuprofen adsorbed in the internal pores had to diffuse along the macropore channels up to the surface of the material. The material obtained from a highly concentrated emulsion was functionalized with amino groups using two methods, the post-grafting mechanism and the co-condensation mechanism. Both routes improve IBU adsorption in the material and show good behaviour as a controlled drug delivery system.

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

    Directory of Open Access Journals (Sweden)

    Suman Jangra

    2016-09-01

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

  5. Controlled release effervescent buccal discs of buspirone hydrochloride: in vitro and in vivo evaluation studies.

    Science.gov (United States)

    Jaipal, A; Pandey, M M; Charde, S Y; Sadhu, N; Srinivas, A; Prasad, R G

    2016-01-01

    In the present study controlled release effervescent buccal discs of buspirone hydrochloride (BS) were designed using HPMC as rate controlling and bioadhesive polymer by direct compression method. Sodium bicarbonate and citric acid were used in varying amounts as effervescence forming agents. Carbon dioxide evolved due to reaction of sodium bicarbonate and citric acid was explored for its potential as buccal permeation enhancer. The designed buccal discs were evaluated for physical characteristics and in vitro drug release studies. Bioadhesive behavior of designed buccal discs was assessed using texture analyzer. In vivo animal studies were performed in rabbits to study bioavailability of BS in the designed buccal discs and to establish permeation enhancement ability of carbon dioxide. It was observed that effervescent buccal discs have faster drug release compared to non-effervescent buccal discs in vitro and effervescent buccal discs demonstrated significant increase in bioavailability of drug when compared to non-effervescent formulation. Hence, effervescent buccal discs can be used as an alternative to improve the drug permeation resulting in better bioavailability. However, the amount of acid and base used for generation of carbon dioxide should be selected with care as this may damage the integrity of bioadhesive dosage form.

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

    Science.gov (United States)

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

    2000-05-03

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

  7. Controlled release of ibuprofen by meso–macroporous silica

    Energy Technology Data Exchange (ETDEWEB)

    Santamaría, E., E-mail: esthersantamaria@ub.edu; Maestro, A.; Porras, M.; Gutiérrez, J.M.; González, C.

    2014-02-15

    Structured meso–macroporous silica was successfully synthesized from an O/W emulsion using decane as a dispersed phase. Sodium silicate solution, which acts as a silica source and a poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) (EO{sub 19}PO{sub 39}EO{sub 19}) denoted as P84 was used in order to stabilize the emulsion and as a mesopore template. The materials obtained were characterized through transmission electron microscopy (TEM), scanning electron microscopy (SEM), small-angle X-ray diffraction scattering (SAXS) and nitrogen adsorption–desorption isotherms. Ibuprofen (IBU) was selected as the model drug and loaded into ordered meso–macroporous materials. The effect of the materials’ properties on IBU drug loading and release was studied. The results showed that the loading of IBU increases as the macropore presence in the material is increased. The IBU adsorption process followed the Langmuir adsorption isotherm. A two-step release process, consisting of an initial fast release and then a slower release was observed. Macropores enhanced the adsorption capacity of the material; this was probably due to the fact that they allowed the drug to access internal pores. When only mesopores were present, ibuprofen was probably adsorbed on the mesopores close to the surface. Moreover, the more macropore present in the material, the slower the release behaviour observed, as the ibuprofen adsorbed in the internal pores had to diffuse along the macropore channels up to the surface of the material. The material obtained from a highly concentrated emulsion was functionalized with amino groups using two methods, the post-grafting mechanism and the co-condensation mechanism. Both routes improve IBU adsorption in the material and show good behaviour as a controlled drug delivery system. - Graphical abstract: Ibuprofen release profiles for the materials obtained from samples P84{sub m}eso (black diamonds), P84{sub 2}0% (white squares), P84{sub 5

  8. Controlled release of ibuprofen by meso–macroporous silica

    International Nuclear Information System (INIS)

    Santamaría, E.; Maestro, A.; Porras, M.; Gutiérrez, J.M.; González, C.

    2014-01-01

    Structured meso–macroporous silica was successfully synthesized from an O/W emulsion using decane as a dispersed phase. Sodium silicate solution, which acts as a silica source and a poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) (EO 19 PO 39 EO 19 ) denoted as P84 was used in order to stabilize the emulsion and as a mesopore template. The materials obtained were characterized through transmission electron microscopy (TEM), scanning electron microscopy (SEM), small-angle X-ray diffraction scattering (SAXS) and nitrogen adsorption–desorption isotherms. Ibuprofen (IBU) was selected as the model drug and loaded into ordered meso–macroporous materials. The effect of the materials’ properties on IBU drug loading and release was studied. The results showed that the loading of IBU increases as the macropore presence in the material is increased. The IBU adsorption process followed the Langmuir adsorption isotherm. A two-step release process, consisting of an initial fast release and then a slower release was observed. Macropores enhanced the adsorption capacity of the material; this was probably due to the fact that they allowed the drug to access internal pores. When only mesopores were present, ibuprofen was probably adsorbed on the mesopores close to the surface. Moreover, the more macropore present in the material, the slower the release behaviour observed, as the ibuprofen adsorbed in the internal pores had to diffuse along the macropore channels up to the surface of the material. The material obtained from a highly concentrated emulsion was functionalized with amino groups using two methods, the post-grafting mechanism and the co-condensation mechanism. Both routes improve IBU adsorption in the material and show good behaviour as a controlled drug delivery system. - Graphical abstract: Ibuprofen release profiles for the materials obtained from samples P84 m eso (black diamonds), P84 2 0% (white squares), P84 5 0% (black triangles), P84 7

  9. Innovation of novel 'Tab in Tab' system for release modulation of milnacipran HCl: optimization, formulation and in vitro investigations.

    Science.gov (United States)

    Parejiya, Punit B; Barot, Bhavesh S; Patel, Hetal K; Shelat, Pragna K; Shukla, Arunkumar

    2013-11-01

    The study was aimed toward development of modified release oral drug delivery system for highly water soluble drug, Milnacipran HCl (MH). Novel Tablet in Tablet system (TITs) comprising immediate and extended release dose of MH in different parts was fabricated. The outer shell was composed of admixture of MH, lactose and novel herbal disintegrant obtained from seeds of Lepidium sativum. In the inner core, MH was matrixed with blend of hydrophilic (Benecel®) and hydrophobic (Compritol®) polymers. 3² full factorial design and an artificial neuron network (ANN) were employed for correlating effect of independent variables on dependent variables. The TITs were characterized for pharmacopoeial specifications, in vitro drug release, SEM, drug release kinetics and FTIR study. The release pattern of MH from batch A10 containing 25.17% w/w Benecel® and 8.21% w/w of Compritol® exhibited drug release pattern close proximal to the ideal theoretical profile (t(50%) = 5.92 h, t(75%) = 11.9 h, t(90%) = 18.11 h). The phenomenon of drug release was further explained by concept of percolation and the role of Benecel® and Compritol® in drug release retardation was studied. The normalized error obtained from ANN was less, compared with the multiple regression analysis, and exhibits the higher accuracy in prediction. The results of short-term stability study revealed stable chataracteristics of TITs. SEM study of TITs at different dissolution time points confirmed both diffusion and erosion mechanisms to be operative during drug release from the batch A10. Novel TITs can be a succesful once a day delivery system for highly water soluble drugs.

  10. A Mathematical Formulation of the SCOLE Control Problem. Part 2: Optimal Compensator Design

    Science.gov (United States)

    Balakrishnan, A. V.

    1988-01-01

    The study initiated in Part 1 of this report is concluded and optimal feedback control (compensator) design for stability augmentation is considered, following the mathematical formulation developed in Part 1. Co-located (rate) sensors and (force and moment) actuators are assumed, and allowing for both sensor and actuator noise, stabilization is formulated as a stochastic regulator problem. Specializing the general theory developed by the author, a complete, closed form solution (believed to be new with this report) is obtained, taking advantage of the fact that the inherent structural damping is light. In particular, it is possible to solve in closed form the associated infinite-dimensional steady-state Riccati equations. The SCOLE model involves associated partial differential equations in a single space variable, but the compensator design theory developed is far more general since it is given in the abstract wave equation formulation. The results thus hold for any multibody system so long as the basic model is linear.

  11. Formulation and evaluation of gas release scenarios for the silo in Swedish Final Repository for Radioactive Waste (SFR)

    International Nuclear Information System (INIS)

    Carlsson, J.; Moreno, L.

    1992-01-01

    The Swedish Final Repository for Radioactive Waste (SFR) has been in operation since 1988 and is located in the crystalline rock, 60 m below the Baltic Sea. In the licensing procedure for the SFR the safety assessment has been complemented with a detailed scenario analysis of the performance of the repository. The scenarios include the influence on radionuclide release by gas formation and gas transport processes in the silo. The overall conclusion is that the release of most radionuclides from the silo is only marginally affected by the formation and release of gas, even for scenarios considering unexpected events. The largest effects were found for short-lived radionuclides and radionuclides that have no or low sorption ability. Except for very extreme scenarios for the silo the overall impact from repository on the environment is by far dominated by the release of radionuclides from the rock vaults. 10 refs., 6 figs

  12. DEET microencapsulation: a slow-release formulation enhancing the residual efficacy of bed nets against malaria vectors

    NARCIS (Netherlands)

    N'Guessan, R.; Knols, B.G.J.; Pennetier, C.; Rowland, M.

    2008-01-01

    Textile materials treated with synthetic repellents have the potential to provide protection against insect disease vectors but lack the residual activity necessary to achieve a prolonged effect or to be cost-effective. DEET MC is a formulation of DEET (N,N diethyl-m-toluamide) in which the

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  14. Formulation design of an HPMC-based sustained release tablet for pyridostigmine bromide as a highly hygroscopic model drug and its in vivo/in vitro dissolution properties.

    Science.gov (United States)

    Huang, Yuh-Tyng; Tsai, Tong-Rong; Cheng, Chun-Jen; Cham, Thau-Ming; Lai, Tsun-Fwu; Chuo, Wen-Ho

    2007-11-01

    Pyridostigmine bromide (PB), a highly hygroscopic drug was selected as the model drug. A sustained-release (SR) tablet prepared by direct compression of wet-extruded and spheronized core pellets with HPMC excipients and exhibited a zero-order sustained release (SR) profile. The 2(3) full factorial design was utilized to search an optimal SR tablet formulation. This optimal formulation was followed zero-order mechanism and had specific release rate at different time intervals (released % of 1, 6, and 12 hr were 15.84, 58.56, and 93.10%). The results of moisture absorption by Karl Fischer meter showed the optimum SR tablet could improve the hygroscopic defect of the pure drug (PB). In the in vivo study, the results of the bioavailability data showed the T(max) was prolonged (from 0.65 +/- 0.082 hr to 4.83 +/- 1.60 hr) and AUC(0-t) (from 734.88 +/- 230.68 ng/ml.hr to 1153.34 +/- 488.08 ng/ml.hr) and was increased respectively for optimum PB-SR tablets when compared with commercial immediate release (IR) tablets. Furthermore, the percentages of in vitro dissolution and in vivo absorption in the rabbits have good correlation. We believe that PB-SR tablets designed in our study would improve defects of PB, decrease the frequency of administration and enhance the retention period of drug efficacy in vivo for personnel exposed to contamination situations in war or terrorist attacks in the future.

  15. A double-blind comparison of slow-release and standard tablet formulations of fentiazac in the treatment of patients with tendinitis and bursitis.

    Science.gov (United States)

    Ginsberg, F; Famaey, J P

    1985-01-01

    Two double-blind studies were carried out to compare the effectiveness and tolerance of a slow-release tablet formulation of 300 mg fentiazac, given once daily, with the standard tablet formulations of 100 mg, given 4-times daily, or 200 mg, given twice daily. A total of 60 patients suffering from acute bicipital tendinitis and/or subdeltoid bursitis was studied, 15 patients on the slow-release and 15 on one of the two standard tablets in each of the two trials. Patients were assessed on entry and at Days 7 and 14 of treatment. The results in both studies showed that there was significant improvement in tenderness, pain on movement, overall pain and in the range of movement after treatment, there being no significant difference between those receiving the slow-release form or the standard tablets. Tolerance was good in all groups and only a few minor or moderate side-effects, mainly of a gastro-intestinal type, were reported.

  16. A Glutamate Homeostat Controls the Presynaptic Inhibition of Neurotransmitter Release

    Directory of Open Access Journals (Sweden)

    Xiling Li

    2018-05-01

    Full Text Available Summary: We have interrogated the synaptic dialog that enables the bi-directional, homeostatic control of presynaptic efficacy at the glutamatergic Drosophila neuromuscular junction (NMJ. We find that homeostatic depression and potentiation use disparate genetic, induction, and expression mechanisms. Specifically, homeostatic potentiation is achieved through reduced CaMKII activity postsynaptically and increased abundance of active zone material presynaptically at one of the two neuronal subtypes innervating the NMJ, while homeostatic depression occurs without alterations in CaMKII activity and is expressed at both neuronal subtypes. Furthermore, homeostatic depression is only induced through excess presynaptic glutamate release and operates with disregard to the postsynaptic response. We propose that two independent homeostats modulate presynaptic efficacy at the Drosophila NMJ: one is an intercellular signaling system that potentiates synaptic strength following diminished postsynaptic excitability, while the other adaptively modulates presynaptic glutamate release through an autocrine mechanism without feedback from the postsynaptic compartment. : Homeostatic mechanisms stabilize synaptic strength, but the signaling systems remain enigmatic. Li et al. suggest the existence of a homeostat operating at the Drosophila neuromuscular junction that responds to excess glutamate through an autocrine mechanism to adaptively inhibit presynaptic neurotransmitter release. This system parallels forms of plasticity at central synapses. Keywords: homeostatic synaptic plasticity, glutamate homeostasis, synaptic depression, Drosophila neuromuscular junction

  17. Tunable controlled release of molecular species from Halloysite nanotubes

    Science.gov (United States)

    Elumalai, Divya Narayan

    Encouraged by potential applications in rust coatings, self-healing composites, selective delivery of drugs, and catalysis, the transport of molecular species through Halloysite nanotubes (HNTs), specifically the storage and controlled release of these molecules, has attracted strong interest in recent years. HNTs are a naturally occurring biocompatible nanomaterial that are abundantly and readily available. They are alumosilicate based tubular clay nanotubes with an inner lumen of 15 nm and a length of 600-900 nm. The size of the inner lumen of HNTs may be adjusted by etching. The lumen can be loaded with functional agents like antioxidants, anticorrosion agents, flame-retardant agents, drugs, or proteins, allowing for a sustained release of these agents for hours. The release times can be further tuned for days and months by the addition of tube end-stoppers. In this work a three-dimensional, time-quantified Monte Carlo model that efficiently describes diffusion through and from nanotubes is implemented. Controlled delivery from Halloysite Nanotubes (HNT) is modeled based on interactions between the HNT's inner wall and the nanoparticles (NP) and among NPs themselves. The model was validated using experimental data published in the literature. The validated model is then used to study the effect of multiple parameters like HNT diameter and length, particle charge, ambient temperature and the creation of smart caps at the tube ends on the release of encapsulated NPs. The results show that release profiles depend on the size distribution of the HNT batch used for the experiment, as delivery is sensitive to HNT lumen and length. The effect of the addition of end-caps to the HNTs, on the rate of release of encapsulated NPs is also studied here. The results show that the release profiles are significantly affected by the addition of end caps to the HNTs and is sensitive to the end-cap pore lumen. A very good agreement with the experiment is observed when a weight

  18. Controlled release and intracellular protein delivery from mesoporous silica nanoparticles.

    Science.gov (United States)

    Deodhar, Gauri V; Adams, Marisa L; Trewyn, Brian G

    2017-01-01

    Protein therapeutics are promising candidates for disease treatment due to their high specificity and minimal adverse side effects; however, targeted protein delivery to specific sites has proven challenging. Mesoporous silica nanoparticles (MSN) have demonstrated to be ideal candidates for this application, given their high loading capacity, biocompatibility, and ability to protect host molecules from degradation. These materials exhibit tunable pore sizes, shapes and volumes, and surfaces which can be easily functionalized. This serves to control the movement of molecules in and out of the pores, thus entrapping guest molecules until a specific stimulus triggers release. In this review, we will cover the benefits of using MSN as protein therapeutic carriers, demonstrating that there is great diversity in the ways MSN can be used to service proteins. Methods for controlling the physical dimensions of pores via synthetic conditions, applications of therapeutic protein loaded MSN materials in cancer therapies, delivering protein loaded MSN materials to plant cells using biolistic methods, and common stimuli-responsive functionalities will be discussed. New and exciting strategies for controlled release and manipulation of proteins are also covered in this review. While research in this area has advanced substantially, we conclude this review with future challenges to be tackled by the scientific community. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2011-02-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-02-25

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

  2. Evaluation of a 12-Hour Sustained-Release Acetaminophen (Paracetamol) Formulation: A Randomized, 3-Way Crossover Pharmacokinetic and Safety Study in Healthy Volunteers.

    Science.gov (United States)

    Yue, Yong; Collaku, Agron; Liu, Dongzhou J

    2018-01-01

    Acetaminophen (paracetamol) is a first-line treatment for mild and moderate pain. A twice-daily sustained-release (SR) formulation may be more convenient for chronic users than standard immediate-release (IR) acetaminophen. This randomized, 3-way crossover study evaluated pharmacokinetics and safety of single-dose 1500- and 2000-mg SR acetaminophen formulations and 2 doses of IR acetaminophen 1000 mg given 6 hours apart in healthy adults (n = 14). Primary outcome was time that plasma acetaminophen concentration was ≥4 μg/mL (T C≥4μg/mL ). Key secondary outcomes were area under the plasma concentration-time curve (AUC) from time 0 to time t, when plasma acetaminophen was detectable (AUC 0-t ), AUC from 0 to infinity (AUC 0-inf ), and maximum plasma acetaminophen concentration (C max ). T C≥4μg/mL from 2000-mg SR acetaminophen was similar to that from 2 doses of IR acetaminophen, whereas T C≥4μg/mL for 1500-mg SR acetaminophen was significantly shorter than that for IR acetaminophen (P = .004). The extent of acetaminophen absorption from 2000-mg SR and 2 doses of the IR formulation was similar and within bioequivalence limits with regard to AUC 0-12 , AUC 0-t , and AUC 0-inf . The extent of acetaminophen absorption from 1500-mg SR was significantly lower than that from IR acetaminophen. The 2000-mg SR represents a potential candidate formulation for 12-hour dosing with acetaminophen. © 2017, The American College of Clinical Pharmacology.

  3. Estudio de bioequivalencia de dos formulaciones de tabletas de carbamazepina de liberación retardada Study of bioequivalence of two carbamazepine retard-release tablet formulations

    Directory of Open Access Journals (Sweden)

    2000-03-01

    Full Text Available En 12 voluntarios sanos se efectuó un estudio de bioequivalencia de dos preparados comerciales de carbamazepina en tabletas de liberación retardada. Este estudio permitió comparar la biodisponibilidad de la formulación de referencia Tegretol® Retard de Ciba Geigy elaborado en Colombia por Novartis, y la formulación de prueba Carbamazepina MK Retard, de Tecnoquímicas. Para evaluar la bioequivalencia se determinaron las curvas de concentración plasmática vs tiempo de las dos formulaciones y se calcularon las áreas bajo la curva (AUC y las concentraciones máximas (Cmáx. Para la formulación de prueba el intervalo de confianza del 90% para el AUC estuvo entre 95.7 y 100.7% y para el C(máx entre el 88.6 y el 106.1%. Para ambas determinaciones el rango de aceptación, según normas internacionales, está entre 80 y 125% de la formulación de referencia. Esto demuestra la bioequivalencia de las dos formulaciones. A study of the bioequivalence of two comercial carbamazepine retard-release formulations was carried out in 12 healthy volunteers. Studies of bioequivalence allow to compare the bioavailability of the innovator formulation with generic, alternative or branch formulations. In order to evaluate the bioequivalence, plasma carbamazepine concentration/time curves were obtained for the Tegretol® Retard Tablets –reference formulationand for the test formulation; the area under each curve and the maximum concentration were calculated. After the calculation, statistical analysis of data for the area under the curve of the Carbamazepine Retard Tablets –test formulation, was between 95.7% and 100.7 % and the maximum concentration of the test formulation was between 88.6% and 106.1%; both parameters with the 90% confidence interval. Since the acceptance range was determined to be between 80.0% and 125.0% of the reference formulation, we concluded from this study that the two formulations are bioequivalent.

  4. Formulation and evaluation of rifampicin sustained release tablets using juice of Citrus limetta as bio-retardant.

    Science.gov (United States)

    Gaur, K Pawan; Soam, Kulwant; Gupta, S K; Dabral, Prashant

    2012-03-01

    The advantages of biopolymers over synthetic polymers are low cost, natural origin, free from side effects, biocompatible, bio-acceptable, environmental friendly processing, local availability, better patient tolerance as well as public acceptance. Sustained release tablets containing rifampicin was prepared by adding 100 mg polymer and 50 mg Drug and Granules. Same procedure was followed with 3% and 5% of polymer for preparation of sustained release tablets. Additional Tablets of 100 mg, 200 mg and 400 mg were prepared using 5% of the polymer. The results indicated that the selected biopolymer had a good release retardant property thus it can be concluded that the selected biopolymer can be utilized as low cost natural biocompatible and biodegradable agent.

  5. Formulation and evaluation of rifampicin sustained release tablets using juice of Citrus limetta as bio-retardant

    Directory of Open Access Journals (Sweden)

    K Pawan Gaur

    2012-01-01

    Full Text Available The advantages of biopolymers over synthetic polymers are low cost, natural origin, free from side effects, biocompatible, bio-acceptable, environmental friendly processing, local availability, better patient tolerance as well as public acceptance. Sustained release tablets containing rifampicin was prepared by adding 100 mg polymer and 50 mg Drug and Granules. Same procedure was followed with 3% and 5% of polymer for preparation of sustained release tablets. Additional Tablets of 100 mg, 200 mg and 400 mg were prepared using 5% of the polymer. The results indicated that the selected biopolymer had a good release retardant property thus it can be concluded that the selected biopolymer can be utilized as low cost natural biocompatible and biodegradable agent.

  6. Bioavailability of oxycodone after administration of a new prolonged-release once-daily tablet formulation in healthy subjects, in comparison to an established twice-daily tablet
.

    Science.gov (United States)

    Scheidel, Bernhard; Maritz, Martina A; Gschwind, Yves J; Steigerwald, Kerstin; Guth, Volker; Kovacs, Peter; Rey, Helene

    2017-11-01

    To evaluate and to compare the bioavailability, the influence of food intake on the bioavailability, and the safety and tolerability of a newly-developed oxycodone once-daily (OOD) prolonged-release tablet with an established oxycodone twice-daily (OTD) prolonged-release tablet after single-dose administration under fasting or fed conditions as well as after multiple-dose administration. Three single-center, open-label, randomized, balanced, two-treatment, two-period, two-sequence crossover studies were conducted. In each study, 36 healthy volunteers were randomized to receive 10 mg oxycodone daily as OOD (oxycodone HCL 10-mg PR tablets XL (Develco Pharma Schweiz AG, Pratteln, Switzerland); administration of 1 tablet in the morning) or as OTD (reference formulation: oxygesic 5-mg tablets (Mundipharma GmbH, Limburg an der Lahn, Germany); administration of 1 tablet in the morning and 1 tablet in the evening). Tablets were administered once daily or twice daily under fasting conditions (study 1) or under fed conditions (study 2) as well as after multiple-dose administration (study 3). A sufficient number of blood samples were taken for describing plasma profiles and for calculation of pharmacokinetic parameters. Plasma concentrations of oxycodone were determined by LC-MS/MS. Safety and tolerability were monitored and assessed in all three studies. Plasma profiles of OOD reveal sustained concentrations of oxycodone over the complete dosing interval of 24 hours. In comparison to the OTD reference formulation, the OOD test formulation showed a slightly slower increase of concentrations within the absorption phase and similar plasma concentrations at the maximum and at the end of the dosing interval (24 hours). Extent of bioavailability (AUC), maximum plasma concentrations (Cmax), and plasma concentrations at the end of the dosing interval (Cτ,ss,24h) of OOD could be classified as comparable to OTD considering 90% confidence intervals (CIs) and acceptance limits of 80

  7. Three-dimensional endothelial cell morphogenesis under controlled ion release from copper-doped phosphate glass.

    Science.gov (United States)

    Stähli, Christoph; James-Bhasin, Mark; Nazhat, Showan N

    2015-02-28

    Copper ions represent a promising angiogenic agent but are associated with cytotoxicity at elevated concentrations. Phosphate-based glasses (PGs) exhibit adjustable dissolution properties and allow for controlled ion release. This study examined the formation of capillary-like networks by SVEC4-10 endothelial cells (ECs) seeded in a three-dimensional (3D) type I collagen hydrogel matrix mixed with PG particles of the formulation 50P2O5-30CaO-(20-x)Na2O-xCuO (x=0 and 10 mol%). Copper and total phosphorus release decreased over time and was more sustained in the case of 10% CuO PG. Moreover, increasing the concentration of 10% CuO PG in collagen substantially delayed dissolution along with preferential release of copper. A 3D morphometric characterization method based on confocal laser scanning microscopy image stacks was developed in order to quantify EC network length, connectivity and branching. Network length was initially reduced in a concentration-dependent fashion by 10% CuO PG and, to a lesser extent, by 0% CuO PG, but reached values identical to the non-PG control by day 5 in culture. This reduction was attributed to a PG-mediated decrease in cell metabolic activity while cell proliferation as well as network connectivity and branching were independent of PG content. Gene expression of matrix metalloproteinases (MMP)-1 and -2 was up-regulated by PGs, indicating that MMPs did not play a critical role in network growth. The relationship between ion release and EC morphogenesis in 3D provided in this study is expected to contribute to an ultimately successful pro-angiogenic application of CuO-doped PGs. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Promoting fertilizer use via controlled release of a bacteria-encapsulated film bag.

    Science.gov (United States)

    Wu, Chin-San

    2010-05-26

    A phosphate-solubilizing bacterium ( Burkholderia cepacia isolate) encapsulated in maleic anhydride (MA) grafted onto poly(butylene succinate adipate) (PBSA) and then combined with starch as film bag material (PBSA-g-MA/starch) incubated in a saline solution required approximately 20 days to deplete the starch in the film bags. Thereafter, the cell concentration in the saline solution increased significantly because of the release of cells from the severely destroyed film bags and also their growth by use of depolymerized PBSA-g-MA fragments as a substrate. The incubation proceeded for 60 days, by which time the PBSA-g-MA/starch composite had suffered a >80% weight loss. For practical application, effectiveness of the above-mentioned film bags was demonstrated because it could improve the absorbability of a fertilizer for plants and promote the growth of plants. As a result, it can avoid the accumulation of the phosphate in excess fertilizer that lead to the phenomenon of poor soils. These results demonstrate that PBSA-g-MA/starch can be used to encapsulate cells of an indigenous phosphate-solubilizing bacterium ( B. cepacia isolate) to form a controlled release of bacteria-encapsulated film bag (BEFB). The B. cepacia isolate was able to degrade the film bags material, causing cell release. Biodegradability of the film bags depended upon the type of material used, because the PBSA film bags were also degraded but to a lesser degree. The addition of starch made the film bags more biodegradable. The decrease in intrinsic viscosity was also higher for the starch composite, suggesting a strong connection between the biodegradability and these characteristics. The results suggest that the release of fertilizer-promoted bacteria might be controllable via a suitable film bag material formulation. In addition, this work adopted live bacteria to promote the absorption of phosphate, which is superior to the phosphate used in the traditional way.

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

    Directory of Open Access Journals (Sweden)

    Helena Prior Filipe

    2016-06-01

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

  10. Managing severe pain and abuse potential: the potential impact of a new abuse-deterrent formulation oxycodone/naltrexone extended-release product

    Directory of Open Access Journals (Sweden)

    Pergolizzi, J

    2018-02-01

    Full Text Available Joseph V Pergolizzi, Jr,1 Robert Taylor Jr,1 Jo Ann LeQuang,1 Robert B Raffa2,3 On behalf of the NEMA Research Group 1NEMA Research Inc., Naples, FL, USA; 2University of Arizona College of Pharmacy, Tucson, AZ, USA; 3Temple University School of Pharmacy, Philadelphia, PA, USA Abstract: Proper management of severe pain represents one of the most challenging clinical dilemmas. Two equally important goals must be attained: the humanitarian/medical goal to relieve suffering and the societal/legal goal to not contribute to the drug abuse problem. This is an age-old problem, and the prevailing emphasis placed on one or the other goal has resulted in pendulum swings that have resulted in either undertreatment of pain or the current epidemic of misuse and abuse. In an effort to provide efficacious strong pain relievers (opioids that are more difficult to abuse by the most dangerous routes of administration, pharmaceutical companies are developing products in which the opioid is manufactured in a formulation that is designed to be tamper resistant. Such a product is known as an abuse-deterrent formulation (ADF. ADF opioid products are designed to deter or resist abuse by making it difficult to tamper with the product and extracting the opioid for inhalation or injection. To date, less than a dozen opioid formulations have been approved by the US Food and Drug Administration to carry specific ADF labeling, but this number will likely increase in the coming years. Most of these products are extended-release formulations. Keywords: oxycodone/naltrexone, abuse-deterrent formulation, abuse-deterrent opioid, oxycodone, abuse liability

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

    Science.gov (United States)

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

    2016-06-01

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

  12. The antianginal efficacy and tolerability of controlled-release metoprolol once daily

    DEFF Research Database (Denmark)

    Egstrup, K; Gundersen, T; Härkönen, R

    1988-01-01

    In a randomized, double-blind, cross-over study treatment with a new controlled-release (CR) preparation of metoprolol, given once daily, was compared with treatment with conventional metoprolol tablets, given twice daily, in 115 patients with stable effort angina pectoris. The patients were...... questionnaire. When all patients were analysed together there were no differences in antianginal efficacy between the two treatment regimens. However, when the group taking 200 mg daily was analysed separately better exercise tolerance was found during metoprolol CR therapy, as measured by onset of chest pain...... and ST-segment change, compared with conventional metoprolol therapy. The two formulations were well tolerated. When given once daily in a total daily dose of 100 mg, the CR preparation induced less adverse effects than the conventional tablets, 50 mg twice daily. It was concluded that the new metoprolol...

  13. Controlled swollen and drug release from urea-cross-linked polyether/siloxane hybrids

    International Nuclear Information System (INIS)

    Santilli, Celso V.; Lopes, Leandro; Pulcinelli, Sandra H.; Chiavacci, Leila A.; Oliveira, Anselmo G.

    2009-01-01

    From a simple synthesis method we produced transparent ureasil cross-linked polyether (poly(ethylene oxide), PEO, or poly (propylene oxide), PPO) networks, whose designed inter cross-linking distance and tunable swell ability was assessed by small angle X-ray scattering on the D11A-SAXS1 beamline of the LNLS, we demonstrated that the controlled drug release from swell able hydrophilic ureasil-PEO materials can be sustained during some days, while from the unswell able ureasil-PPO ones, during some weeks. This outstanding feature conjugated with the bio medically safe formulation of the ureasil cross-linked polyether/siloxane hybrid widen their scope of application to include the domain of soft and implantable drug delivery devices. (author)

  14. Controlled release of biofunctional substances by radiation-induced polymerization

    International Nuclear Information System (INIS)

    Yoshida, M.; Kumakura, M.; Kaetsu, I.

    1978-01-01

    The release behaviour of a drug from flat circular capsules obtained by radiation-induced polymerization at low temperatures and with different hydrophilic properties has been studied. The effect of various factors on release property was investigated. The release process could be divided into three parts, an initial quick release stage, stationary state release stage and a retarded release stage. Release behaviour in the stationary state was examined using Noyes-Whitney and Higuchi equations. It was shown that the hydrophilic property of polymer matrix expressed by water content was the most important effect on diffusion and release rate. Rigidity of the polymer may also affect diffusivity. The first quick release step could be attributed to rapid dissolution of drug in the matrix surface due to polymer swelling. (author)

  15. L-Cysteine conjugated poly L-lactide nanoparticles containing 5-fluorouracil: formulation, characterization, release and uptake by tissues in vivo.

    Science.gov (United States)

    Mishra, Brijeshkunvar J; Kaul, Ankur; Trivedi, Piyush

    2015-02-01

    Targeted delivery of drugs is still a therapeutic challenge and numerous methods have been reported for the same. In this study, emphasis was placed on developing nanoparticles loaded with 5-fluorouracil (FU) and modifying the surface of the nanoparticles by conjugation with amino acid, to improve the distribution of 5-FU in the lungs. An emulsion solvent evaporation technique was used to formulate nanoparticles of FU using Poly L-lactide and Pluronic F-68. The nanoparticles were conjugated with L-Cysteine using EDC as the activator of COOH group and were evaluated for product yield, particle size, surface morphology, amount of conjugation by Ellman's method and in vitro drug release study. The results indicated 60-65% yield with an average particle size of 242.7 ± 37.11 nm for the cysteine conjugated nanoparticle (CNP) formulation and more than 70% conjugation of cysteine. The cumulative percentage of drug released over a period of 24 h was found to be 58%. An increase in distribution of the delivery system in lungs (11.4% ID after 1 h) in mice was found indicating the role of L-Cysteine in the transport mechanism to the lungs. In vivo kinetic studies in rats revealed higher circulation time of CNP as compared to pure FU solution. The study helps in designing a colloidal delivery system for increased distribution of drugs to the lungs and may be helpful in delivery of drugs in conditions like non-small cell lung carcinomas.

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

    Science.gov (United States)

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

    2005-06-01

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

  17. Formulation and quality control of Prunus domestica syrup, prepared according to Iranian Traditional Medicine

    Directory of Open Access Journals (Sweden)

    M. Hamzeloo-Moghadam

    2015-05-01

    Full Text Available Background and objectives: Prunus domestica (plum has been considered as a useful remedy for several disorders in Iranian Traditional Medicine (ITM. It has cold and wet temperament and is used as syrup for hot temperament diseases such as hot headache and stomach disorders. In the present study, plum syrup has been formulated according to ITM manuscripts and quality control evaluations have been accomplished to present a suitable formulation. Methods: The fruits of Prunus domestica L. were macerated in water, then decocted. The mixture was filtered. The filtrate was concentrated to have a suitable viscosity. The extract was sweetened by adding sugar (1:2 and heated till sugar was completely dissolved. The final product was evaluated physicochemically and microbiologically according to standard protocols and total phenolics content of the syrup stability was determined. The syrup was assessed in accelerated condition (40 ºC during 6 months. Results: The prepared formulation was a viscose and brown syrup with plum flavor and fragrance. No precipitation and cap locking were observed in the syrup. Dry residue, pH, density, viscosity and total phenolics of the syrup were found 43.1%, 3.49, 1.27 g/ml, 6.5 cP and 152.3 mg/100ml, respectively. No microbial growth was observed in the formulation. In the accelerated stability tests, no remarkable changes were seen in the product. Total phenolics content was decreased 2.2% during 6 months in 40 ºC. Conclusion: The formulated Prunus domestica syrup could be introduced for further mass production after completing the final required evaluations.

  18. Halloysite Nanotubes: Controlled Access and Release by Smart Gates.

    Science.gov (United States)

    Cavallaro, Giuseppe; Danilushkina, Anna A; Evtugyn, Vladimir G; Lazzara, Giuseppe; Milioto, Stefana; Parisi, Filippo; Rozhina, Elvira V; Fakhrullin, Rawil F

    2017-07-28

    Hollow halloysite nanotubes have been used as nanocontainers for loading and for the triggered release of calcium hydroxide for paper preservation. A strategy for placing end-stoppers into the tubular nanocontainer is proposed and the sustained release from the cavity is reported. The incorporation of Ca(OH)₂ into the nanotube lumen, as demonstrated using transmission electron microscopy (TEM) imaging and Energy Dispersive X-ray (EDX) mapping, retards the carbonatation, delaying the reaction with CO₂ gas. This effect can be further controlled by placing the end-stoppers. The obtained material is tested for paper deacidification. We prove that adding halloysite filled with Ca(OH)₂ to paper can reduce the impact of acid exposure on both the mechanical performance and pH alteration. The end-stoppers have a double effect: they preserve the calcium hydroxide from carbonation, and they prevent from the formation of highly basic pH and trigger the response to acid exposure minimizing the pH drop-down. These features are promising for a composite nanoadditive in the smart protection of cellulose-based materials.

  19. Controlled drug release from a novel injectable biodegradable microsphere/scaffold composite based on poly(propylene fumarate).

    Science.gov (United States)

    Kempen, Diederik H R; Lu, Lichun; Kim, Choll; Zhu, Xun; Dhert, Wouter J A; Currier, Bradford L; Yaszemski, Michael J

    2006-04-01

    The ideal biomaterial for the repair of bone defects is expected to have good mechanical properties, be fabricated easily into a desired shape, support cell attachment, allow controlled release of bioactive factors to induce bone formation, and biodegrade into nontoxic products to permit natural bone formation and remodeling. The synthetic polymer poly(propylene fumarate) (PPF) holds great promise as such a biomaterial. In previous work we developed poly(DL-lactic-co-glycolic acid) (PLGA) and PPF microspheres for the controlled delivery of bioactive molecules. This study presents an approach to incorporate these microspheres into an injectable, porous PPF scaffold. Model drug Texas red dextran (TRD) was encapsulated into biodegradable PLGA and PPF microspheres at 2 microg/mg microsphere. Five porous composite formulations were fabricated via a gas foaming technique by combining the injectable PPF paste with the PLGA or PPF microspheres at 100 or 250 mg microsphere per composite formulation, or a control aqueous TRD solution (200 microg per composite). All scaffolds had an interconnected pore network with an average porosity of 64.8 +/- 3.6%. The presence of microspheres in the composite scaffolds was confirmed by scanning electron microscopy and confocal microscopy. The composite scaffolds exhibited a sustained release of the model drug for at least 28 days and had minimal burst release during the initial phase of release, as compared to drug release from microspheres alone. The compressive moduli of the scaffolds were between 2.4 and 26.2 MPa after fabrication, and between 14.9 and 62.8 MPa after 28 days in PBS. The scaffolds containing PPF microspheres exhibited a significantly higher initial compressive modulus than those containing PLGA microspheres. Increasing the amount of microspheres in the composites was found to significantly decrease the initial compressive modulus. The novel injectable PPF-based microsphere/scaffold composites developed in this study

  20. Controlled Pesticide Release from Porous Composite Hydrogels Based on Lignin and Polyacrylic Acid

    Directory of Open Access Journals (Sweden)

    Yajie Sun

    2016-01-01

    Full Text Available For the controlled release of pesticides, a novel composite porous hydrogel (LBPAA was prepared based on lignin and polyacrylic acid for use as the support frame of a pore structure for water delivery. The LBPAA was analyzed to determine its water-swelling and slow release properties. The controlled release properties of LBPAA were evaluated through experiments in relation to the cumulative release of pesticides, with particular emphasis on environmental effects and release models. The porous LBPAA hydrogel showed improved properties compared to polyacrylic acid, and could therefore be considered an efficient material for application in controlled release systems in agriculture.

  1. Critical review of controlled release packaging to improve food safety and quality.

    Science.gov (United States)

    Chen, Xi; Chen, Mo; Xu, Chenyi; Yam, Kit L

    2018-03-19

    Controlled release packaging (CRP) is an innovative technology that uses the package to release active compounds in a controlled manner to improve safety and quality for a wide range of food products during storage. This paper provides a critical review of the uniqueness, design considerations, and research gaps of CRP, with a focus on the kinetics and mechanism of active compounds releasing from the package. Literature data and practical examples are presented to illustrate how CRP controls what active compounds to release, when and how to release, how much and how fast to release, in order to improve food safety and quality.

  2. PEGylated lipid nanocapsules with improved drug encapsulation and controlled release properties.

    Science.gov (United States)

    Hervella, Pablo; Alonso-Sande, Maria; Ledo, Francisco; Lucero, Maria L; Alonso, Maria J; Garcia-Fuentes, Marcos

    2014-01-01

    Drugs with poor lipid and water solubility are some of the most challenging to formulate in nanocarriers, typically resulting in low encapsulation efficiencies and uncontrolled release profiles. PEGylated nanocapsules (PEG-NC) are known for their amenability to diverse modifications that allow the formation of domains with different physicochemical properties, an interesting feature to address a drug encapsulation problem. We explored this problem by encapsulating in PEG-NC the promising anticancer drug candidate F10320GD1, used herein as a model for compounds with such characteristics. The nanocarriers were prepared from Miglyol(®), lecithin and PEG-sterate through a solvent displacement technique. The resulting system was a homogeneous suspension of particles with size around 200 nm. F10320GD1 encapsulation was found to be very poor (<15%) if PEG-NC were prepared using water as continuous phase; but we were able to improve this value to 85% by fixing the pH of the continuous phase to 9. Interestingly, this modification also improved the controlled release properties and the chemical stability of the formulation during storage. These differences in pharmaceutical properties together with physicochemical data suggest that the pH of the continuous phase used for PEG-NC preparation can modify drug allocation, from the external shell towards the inner lipid core of the nanocapsules. Finally, we tested the bioactivity of the drug-loaded PEG-NC in several tumor cell lines, and also in endothelial cells. The results indicated that drug encapsulation led to an improvement on drug cytotoxicity in tumor cells, but not in non-tumor endothelial cells. Altogether, the data confirms that PEG-NC show adequate delivery properties for F10320GD1, and underlines its possible utility as an anticancer therapy.

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

    Directory of Open Access Journals (Sweden)

    Xin Hua

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

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

    Science.gov (United States)

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

    2014-01-01

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

  5. Mechanical properties and antibiotic release characteristics of poly(methyl methacrylate)-based bone cement formulated with mesoporous silica nanoparticles.

    Science.gov (United States)

    Letchmanan, Kumaran; Shen, Shou-Cang; Ng, Wai Kiong; Kingshuk, Poddar; Shi, Zhilong; Wang, Wilson; Tan, Reginald B H

    2017-08-01

    The influence of mesoporous silica nanoparticles (MSNs) loaded with antibiotics on the mechanical properties of functional poly(methyl methacrylate)-(PMMA) based bone cements is investigated. The incorporation of MSNs to the bone cements (8.15wt%) shows no detrimental effects on the biomechanical properties of the freshly solidified bone cements. Importantly, there are no significant changes in the compression strength and bending modulus up to 6 months of aging in PBS buffer solution. The preserved mechanical properties of MSN-functionalized bone cements is attributed to the unchanged microstructures of the cements, as more than 96% of MSNs remains in the bone cement matrix to support the cement structures after 6 months of aging. In addition, the MSN-functionalized bone cements are able to increase the drug release of gentamicin (GTMC) significantly as compared with commercially available antibiotic-loaded bone cements. It can be attributed to the loaded nano-sized MSNs with uniform pore channels which build up an effective nano-network path enable the diffusion and extended release of GTMC. The combination of excellent mechanical properties and sustainable drug delivery efficiency demonstrates the potential applicability of MSN-functionalized PMMA bone cements for orthopedic surgery to prevent post-surgery infection. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. High efficiency dry coating of non-subcoated pellets for sustained drug release formulations using amino methacrylate copolymers.

    Science.gov (United States)

    Klar, Fabian; Urbanetz, Nora Anne

    2017-12-12

    Dry coating utilizing a fluidized bed was evaluated in order to produce films with sustained drug release using amino methacrylate copolymers as film former. In contrast to other dry coating procedures using amino methacrylate copolymers, the described method enables an appropriate polymer adhesion by the selection of a plasticizer additive mixture in combination with the use of a three-way nozzle for simultaneous application. Well spreading fatty acid esters were found to increase the coating efficiency from 73% to approximately 86%, when they were used in conjunction with the plasticizer. Pellets were used as drug cores without previous treatment. After a curing step at 55 °C, the pellets exhibited a prolongation of the drug release over a period of about 6 h. Mainly the three parameters, coating level, composition of the polymers in the coating mixture, and the type of plasticizer, were found to exert distinct influence on the dissolution profile. Despite the differences in the coating procedure, the dissolution profiles of the coated pellets as well as the influencing parameters were similar to those known from conventional coating techniques.

  7. Controlled release of liraglutide using thermogelling polymers in treatment of diabetes

    Science.gov (United States)

    Chen, Yipei; Li, Yuzhuo; Shen, Wenjia; Li, Kun; Yu, Lin; Chen, Qinghua; Ding, Jiandong

    2016-01-01

    In treatment of diabetes, it is much desired in clinics and challenging in pharmaceutics and material science to set up a long-acting drug delivery system. This study was aimed at constructing a new delivery system using thermogelling PEG/polyester copolymers. Liraglutide, a fatty acid-modified antidiabetic polypeptide, was selected as the model drug. The thermogelling polymers were presented by poly(ε-caprolactone-co-glycolic acid)-poly(ethylene glycol)-poly(ε-caprolactone-co-glycolic acid) (PCGA-PEG-PCGA) and poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA). Both the copolymers were soluble in water, and their concentrated solutions underwent temperature-induced sol-gel transitions. The drug-loaded polymer solutions were injectable at room temperature and gelled in situ at body temperature. Particularly, the liraglutide-loaded PCGA-PEG-PCGA thermogel formulation exhibited a sustained drug release manner over one week in both in vitro and in vivo tests. This feature was attributed to the combined effects of an appropriate drug/polymer interaction and a high chain mobility of the carrier polymer, which facilitated the sustained diffusion of drug out of the thermogel. Finally, a single subcutaneous injection of this formulation showed a remarkably improved glucose tolerance of mice for one week. Hence, the present study not only developed a promising long-acting antidiabetic formulation, but also put forward a combined strategy for controlled delivery of polypeptide. PMID:27531588

  8. Factors controlling alkalisalt deposition in recovery boiler- release mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    McKeough, P.; Kylloenen, H.; Kurkela, M. [VTT Energy, Espoo (Finland). Process Technology Group

    1996-12-01

    As part of a cooperative effort to develop a model to describe the behaviour of inorganic compounds in kraft recovery boilers, an experimental investigation of the release of sulphur during black liquor pyrolysis has been undertaken. Previous to these studies, the mechanisms of sulphur release and the reasons for the observed effects of process conditions on sulphur release were very poorly understood. On the basis of the experimental results, the main reactions leading to sulphur release have been elucidated with a fair degree of certainty. Logical explanations for the variations of sulphur release with temperature and with liquor solids content have been proposed. The influence of pressure has been investigated in order to gain insights into the effects of mass transfer on the sulphur-release rate. In the near future, the research will be aimed at generating the kinetic data necessary for modelling the release of sulphur in the recovery furnace. (author)

  9. Preparation and evaluation of a timolol maleate drug-resin ophthalmic suspension as a sustained-release formulation in vitro and in vivo.

    Science.gov (United States)

    Qin, Fuhong; Zeng, Li; Zhu, Yongtao; Cao, Jingjing; Wang, Xiaohui; Liu, Wei

    2016-01-01

    The aim of this work was to assess the performance of resin as an ocular delivery system. Timolol maleate (TM) was chosen as the model drug and an ion exchange resin (IER) as the carrier. The drug-resin complex was prepared using an oscillation method and then characterized regarding particle size, zeta potential, morphology, and drug content. After in vitro drug release study and corneal permeation study were performed, in vivo studies were performed in New Zealand albino rabbits using a suspension with particles sized 4.8 ± 1.2 μm and drug loading at 43.00 ± 0.09%. The results indicate that drug released from the drug-resin ophthalmic suspension permeated the cornea and displayed a sustained-release behavior. Drug levels in the ocular tissues after administration of the drug-resin ophthalmic suspension were significantly higher than after treatment with an eye drop formulation but were lower in body tissues and in the plasma. In conclusion, resins have great potential as effective ocular drug delivery carriers to increase ocular bioavailability of timolol while simultaneously reducing systemic drug absorption.

  10. Formulation and characterization of polysaccharide beads for controlled release of plant growth regulators

    Science.gov (United States)

    Mei Li; Mandla A. Tshabalala; Gisela Buschle-Diller

    2016-01-01

    Owing to their chemical, physical, and functional characteristics, polysaccharides are considered to be the most versatile natural polymers. As a result, their properties have been exploited in various fields of research in the biomedical, pharmaceutical, cosmetic, food, and agricultural industries. A property of special interest is their ability to form systems or...

  11. Fuel formulation and mixing strategy for rate of heat release control with PCCI combustion

    NARCIS (Netherlands)

    Zegers, R.P.C.; Yu, M.; Luijten, C.C.M.; Dam, N.J.; Baert, R.S.G.; Goey, de L.P.H.

    2009-01-01

    Premixed charge compression ignition (or PCCI) is a new combustion concept that promises very low emissions of nitrogen oxides and of particulate matter by internal combustion engines. In the PCCIcombustion mode fuel, products from previous combustion events and air are mixed and compresseduntil the

  12. Weed control and persistence of two oxyfluorfen formulations in olive groves under non tillage conditions.

    Science.gov (United States)

    Martínez, M J; Farsaoui, K; de Prado, R

    2004-01-01

    To obtain profitable yields in olive groves, residual preemergence herbicides are applied in October or November before the winter rains, and before the winter annual weeds germinate. Simazine, one of the herbicides most used for weed control in olive groves, has recently been banned. Oxyfluorfen is presented as a good alternative to simazine in olive fields. Experiments were carried out in 2002 and 2003 to evaluate the behaviour of two oxyfluorfen formulations, 2XL and G4F, at 480 g a.i. ha(-1) for three different soil management systems with three replications (1. bare soil; 2. bare soil and grassed buffer strips, chemically controlled and 3. bare soil and grassed buffer strips with controlled mowing; under non tillage conditions in all three cases). The most important species that survived 2XL and G4F treatments was Sagina apetala ARD. Oxyfluorfen residues were evaluated throughout 158 days after the applications. Three soil samples from each plot were collected, mixed and air dried. The herbicide extractions were made with methanol and the residues were analyzed by HPLC. We found no differences between the two formulations, but results showed that recoveries of oxyfluorfen were higher in plots with chemically controlled buffer grassed strips than in the other soil management types.

  13. Colorimetry as Quality Control Tool for Individual Inkjet-Printed Pediatric Formulations

    DEFF Research Database (Denmark)

    Wickström, Henrika; Nyman, Johan O; Indola, Mathias

    2017-01-01

    with specific needs, such as children and the elderly, and patients facing multimorbidity. Printing of pharmaceuticals as technique generates new demands on the quality control procedures. For example, rapid quality control is needed as the printing can be done on demand and at the point of care. This study...... evaluated the potential use of a handheld colorimetry device for quality control of printed doses of vitamin Bs on edible rice and sugar substrates. The structural features of the substrates with and without ink were also compared. A multicomponent ink formulation with vitamin B1, B2, B3, and B6......*) was observed on the substrates. Liquid chromatography mass spectrometry was used as a reference method for the colorimetry measurements plotted against the number of printed layers. It was concluded that colorimetry could be used as a quality control tool for detection of different doses. However, optimization...

  14. Duddingtonia flagrans formulated in rice bran in the control of Oesophagostomum spp. intestinal parasite of swine.

    Science.gov (United States)

    Facchini Rodrigues, João Victor; Braga, Fabio Ribeiro; Campos, Artur Kanadani; de Carvalho, Lorendane Millena; Araujo, Juliana Milani; Aguiar, Anderson Rocha; Ferraz, Carolina Magri; da Silveira, Wendeo Ferreira; Valadão, Marisa Caixeta; de Oliveira, Thais; de Freitas, Samuel Galvão; de Araújo, Jackson Victor

    2018-01-01

    Three experimental assays with Duddingtonia flagrans (isolated AC001) were carried out. The growth of the genus Duddingtonia present in formulation of rice bran, its predatory capability on Oesophagostomum spp. infective larvae (L 3 ) in petri dishes (assay 1), its action in faecal cultures with eggs of that parasite (assay 2) and isolate's capability of predation after passing through gastrointestinal tract of swine (assay 3) was evaluated. At assay 3, feces were collected at time intervals of 12, 24, 36, 48, and 60 h after feed animals with the formulation. Assays 1 and 2 showed a statistical difference (p  0.05). The results demonstrate that the fungal isolate AC001 formulated in rice bran can prey on L 3 of Oesophagostomum spp., in vitro and after passing through the gastrointestinal tract, without loss of viability. This isolate may be an alternative in the control of Oesophagostomum spp. in swine. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Physically Targeted Intravenous Polyurethane Nanoparticles for Controlled Release of Atorvastatin Calcium

    Science.gov (United States)

    Eftekhari, Behnaz Sadat; Karkhaneh, Akbar; Alizadeh, Ali

    2017-01-01

    Background: Intravenous drug delivery is an advantageous choice for rapid administration, immediate drug effect, and avoidance of first-pass metabolism in oral drug delivery. In this study, the synthesis, formulation, and characterization of atorvastatin-loaded polyurethane (PU) nanoparticles were investigated for intravenous route of administration. Method: First, PU was synthesized and characterized. Second, nanoparticles were prepared in four different ratios of drug to polymer through two different techniques, including emulsion-diffusion and single-emulsion. Finally, particle size and polydispersity index, shape and surface morphology, drug entrapment efficiency (EE), drug loading, and in vitro release were evaluated by dynamics light scattering, scanning electron microscopy, and UV visible spectroscopy, respectively. Results: Within two methods, the prepared nanoparticles had a spherical shape and a smooth surface with a diversity of size ranged from 174.04 nm to 277.24 nm in emulsion-diffusion and from 306.5 nm to 393.12 in the single-emulsion method. The highest EE was 84.76%, for (1:4) sample in the emulsion-diffusion method. It has also been shown that in vitro release of nanoparticles, using the emulsion-diffusion method, was sustained up to eight days by two mechanisms: drug diffusion and polymer relaxation. Conclusion: PU nanoparticles, that were prepared by the emulsion-diffusion method, could be used as effective carriers for the controlled drug delivery of poorly water soluble drugs such as atorvastatin calcium. PMID:28532144

  16. Controlled release system for ametryn using polymer microspheres: Preparation, characterization and release kinetics in water

    International Nuclear Information System (INIS)

    Grillo, Renato; Pereira, Anderson do Espirito Santo; Ferreira Silva de Melo, Nathalie; Porto, Raquel Martins; Feitosa, Leandro Oliveira; Tonello, Paulo Sergio; Dias Filho, Newton L.; Rosa, Andre Henrique; Lima, Renata; Fraceto, Leonardo Fernandes

    2011-01-01

    The purpose of this work was to develop a modified release system for the herbicide ametryn by encapsulating the active substance in biodegradable polymer microparticles produced using the polymers poly(hydroxybutyrate) (PHB) or poly(hydroxybutyrate-valerate) (PHBV), in order to both improve the herbicidal action and reduce environmental toxicity. PHB or PHBV microparticles containing ametryn were prepared and the efficiencies of herbicide association and loading were evaluated, presenting similar values of approximately 40%. The microparticles were characterized by scanning electron microscopy (SEM), which showed that the average sizes of the PHB and PHBV microparticles were 5.92 ± 0.74 μm and 5.63 ± 0.68 μm, respectively. The ametryn release profile was modified when it was encapsulated in the microparticles, with slower and more sustained release compared to the release profile of pure ametryn. When ametryn was associated with the PHB and PHBV microparticles, the amount of herbicide released in the same period of time was significantly reduced, declining to 75% and 87%, respectively. For both types of microparticle (PHB and PHBV) the release of ametryn was by diffusion processes due to anomalous transport (governed by diffusion and relaxation of the polymer chains), which did not follow Fick's laws of diffusion. The results presented in this paper are promising, in view of the successful encapsulation of ametryn in PHB or PHBV polymer microparticles, and indications that this system may help reduce the impacts caused by the herbicide, making it an environmentally safer alternative.

  17. Cross-linked chitosan-dextran sulphate vehicle system for controlled release of ciprofloxaxin drug: An ophthalmic application

    Directory of Open Access Journals (Sweden)

    Chetan Chavan

    2017-01-01

    Full Text Available The major challenge associated with conventional eye-drop is the rapid drug loss due to precorneal defence barrier. In this context, controlled-release system of ciprofloxacin-conjugated chitosan (CS-Dextran sulphate (DS nanoparticles (NPs have been synthesized, to increase the bioavailability. The formulated drug delivery vehicle was evaluated for its therapeutic value in the simulated tear fluidat pH 7.4. Ophthalmic microbes were tested with this formulation, to confirm the drug efficacy; which showed conducive therapeutic values of both MIC and MBC. Ocular irritancy test was performed using HET-CAM test, which showed that the CS-DS system did not yield any vascular response, offering it to be a non-irritant to the ocular surface. The release studies showed monotonous controlled-release for duration of 21 h. A fine cross-linking between CS and DS has been demonstrated to form CS-DS NPs and their interaction with drug has been evaluated using conventional characterization tools.

  18. Spray-dried powders improve the controlled release of antifungal tioconazole-loaded polymeric nanocapsules compared to with lyophilized products

    International Nuclear Information System (INIS)

    Ribeiro, Roseane Fagundes; Motta, Mariana Heldt; Härter, Andréia Pisching Garcia; Flores, Fernanda Cramer; Beck, Ruy Carlos Ruver; Schaffazick, Scheila Rezende

    2016-01-01

    This work aimed to obtain solid formulations from polymeric nanocapsules and nanoemulsions containing tioconazole, a broad spectrum antifungal drug. Two dehydration methods were used: spray-drying and freeze-drying, using lactose as adjuvant (10%, w/v). The liquid formulations had a mean particle size around 206 nm and 182 nm for nanocapsules and nanoemulsions, respectively, and an adequate polydispersity index. Tioconazole content was close to the theoretical amount (1.0 mg/mL). After drying, the content ranged between 98 and 102% with a mean nanometric size of the dried products after redispersion. Scanning electron microscopy showed that the particles are rounded, sphere-shaped for the dried products obtained by spray-drying, and shapeless and irregular shapes for those obtained by freeze-drying. In the microbiological evaluation, all dried products remained active against the yeast Candida albicans when compared to the original systems. The dried products obtained by spray-drying from nanocapsules presented better control of the tioconazole release when compared to the freeze-drying products. - Highlights: • Polymeric nanocapsule suspensions containing tioconazole were submitted to spray-drying and freeze-drying. • Dried products from nanocapsule suspensions were stable for 30 days. • Release studies showed that the dried products presented greater control of drug release compared to the original suspension.

  19. Spray-dried powders improve the controlled release of antifungal tioconazole-loaded polymeric nanocapsules compared to with lyophilized products

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Roseane Fagundes [Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Av. Roraima, 1000, Santa Maria, RS, 97105-900 (Brazil); Motta, Mariana Heldt [Curso de Farmácia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Av. Roraima, 1000, Santa Maria, RS, 97105-900 (Brazil); Härter, Andréia Pisching Garcia; Flores, Fernanda Cramer [Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Av. Roraima, 1000, Santa Maria, RS, 97105-900 (Brazil); Beck, Ruy Carlos Ruver [Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre, RS, 90610-000 (Brazil); Schaffazick, Scheila Rezende [Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Av. Roraima, 1000, Santa Maria, RS, 97105-900 (Brazil); and others

    2016-02-01

    This work aimed to obtain solid formulations from polymeric nanocapsules and nanoemulsions containing tioconazole, a broad spectrum antifungal drug. Two dehydration methods were used: spray-drying and freeze-drying, using lactose as adjuvant (10%, w/v). The liquid formulations had a mean particle size around 206 nm and 182 nm for nanocapsules and nanoemulsions, respectively, and an adequate polydispersity index. Tioconazole content was close to the theoretical amount (1.0 mg/mL). After drying, the content ranged between 98 and 102% with a mean nanometric size of the dried products after redispersion. Scanning electron microscopy showed that the particles are rounded, sphere-shaped for the dried products obtained by spray-drying, and shapeless and irregular shapes for those obtained by freeze-drying. In the microbiological evaluation, all dried products remained active against the yeast Candida albicans when compared to the original systems. The dried products obtained by spray-drying from nanocapsules presented better control of the tioconazole release when compared to the freeze-drying products. - Highlights: • Polymeric nanocapsule suspensions containing tioconazole were submitted to spray-drying and freeze-drying. • Dried products from nanocapsule suspensions were stable for 30 days. • Release studies showed that the dried products presented greater control of drug release compared to the original suspension.

  20. Colon cancer risk and different HRT formulations: a case-control study

    Directory of Open Access Journals (Sweden)

    Thai Do

    2007-05-01

    Full Text Available Abstract Background Most studies have found no increased risk of colon cancer associated with hormone replacement therapy (HRT, or even a decreased risk. But information about the effects of different HRT preparations is lacking. Methods A case-control study was performed within Germany in collaboration with regional cancer registries and tumor centers. Up to 5 controls were matched to each case of colon cancer. Conditional logistic regression analysis was applied to estimate crude and adjusted odds ratios (OR and 95% confidence intervals (95% CI. Stratified analyses were performed to get an impression of the risk associated with different estrogens and progestins. Results A total of 354 cases of colon cancer were compared with 1422 matched controls. The adjusted overall risk estimate for colon cancer (ColC associated with ever-use of HRT was 0.97 (0.71 – 1.32. No clinically relevant trends for ColC risk were observed with increasing duration of HRT use, or increasing time since first or last HRT use in aggregate. Whereas the overall risk estimates were stable, the numbers in many of the sub-analyses of HRT preparation groups (estrogens and progestins were too small for conclusions. Nevertheless, if the ColC risk estimates are taken at face value, most seemed to be reduced compared with never-use of HRT, but did not vary much across HRT formulation subgroups. In particular, no substantial difference in ColC risk was observed between HRT-containing conjugated equine estrogens (CEE or medroxyprogesterone acetate (MPA and other formulations more common in Europe. Conclusion Ever-use of HRT was not associated with an increased risk of colon cancer. In contrary, most risk estimates pointed non-significantly toward a lower ColC risk in HRT ever user. They did not vary markedly among different HRT formulations (estrogens, progestins. However, the small numbers and the overlapping nature of the subgroups suggest cautious interpretation.

  1. WE-AB-BRA-03: Non-Invasive Controlled Release from Implantable Hydrogel Scaffolds Using Ultrasound

    Energy Technology Data Exchange (ETDEWEB)

    Moncion, A; Kripfgans, O.D; Putnam, A.J; Frances chi, R.T; Fabiilli, M.L [University of Michigan, Ann Arbor, MI (United States)

    2016-06-15

    Purpose: To control release of a model payload in acoustically responsive scaffolds (ARSs) using focused ultrasound (FUS). Methods: Fluorescently-labeled dextran (10 kDa) was encapsulated in sonosensitive perfluorocarbon (C{sub 6}F{sub 14} or C{sub 5}F{sub 12}) double emulsions (mean diameter: 2.9±0.1 µm). For in vitro release studies, 0.5 mL ARSs (10 mg/mL fibrin, 1% (v/v) emulsion) were polymerized in 24 well plates and covered with 0.5 mL medium. Starting one day after polymerization, ARSs were exposed to FUS (2.5 MHz, Pr = 8 MPa, 13 cycles, 100 Hz PRF) for 2 min daily. The amount of dextran released into the media was quantified. For in vivo studies, 0.25 mL ARSs were prepared as described previously and injected subcutaneously in the lower back of BALB/c mice. After polymerization, a subset of the implanted ARSs were exposed to FUS (as previously described). Animals were imaged longitudinally using a fluorescence imaging system to quantify the amount of dextran released from the ARSs. Results: In vitro: Over 6 days, +FUS displayed an 8.2-fold increase in dextran release compared to −FUS (−FUS: 2.7±0.6%; +FUS: 22.2±3.0%) for C{sub 6}F{sub 14} ARSs, and a 6.7-fold increase (−FUS: 5.0±0.8%; +FUS: 38.5±1.6%) for C{sub 5}F{sub 12}:C{sub 6}F{sub 14} ARSs. In vivo: +FUS displayed statistically greater dextran release compared to −FUS one day after implantation for C{sub 5}F{sub 12}:C{sub 6}F{sub 14} ARSs (−FUS: 55.1±1.5%; +FUS: 74.1±2.2%) and three days after implantation for C{sub 6}F{sub 14} ARSs (−FUS: 1.4±6.5%; +FUS: 30.4±5.4%). Conclusion: FUS enables non-invasive control of payload release from an ARS, which could benefit growth factor delivery for tissue regeneration. ARS are versatile due to their tunability (i.e. stiffness, emulsion composition, FUS pressure, FUS frequency, etc.) and can be modified to for optimal payload release. Future work will optimize ARS formulations for in vivo use to minimize payload release in the absence of

  2. A simple and rapid approach to evaluate the in vitro in vivo role of release controlling agent ethyl cellulose ether derivative polymer.

    Science.gov (United States)

    Akhlaq, Muhammad; Khan, Gul Majid; Jan, Syed Umer; Wahab, Abdul; Hussain, Abid; Nawaz, Asif; Abdelkader, Hamdy

    2014-11-01

    Diclofenac sodium (DCL-Na) conventional oral tablets exhibit serious side effects when given for a longer period leading to noncompliance. Controlled release matrix tablets of diclofenac sodium were formulated using simple blending (F-1), solvent evaporation (F-2) and co-precipitation techniques (F-3). Ethocel® Standard 7 FP Premium Polymer (15%) was used as a release controlling agent. Drug release study was conducted in 7.4 pH phosphate buffer solutions as dissolution medium in vitro. Pharmacokinetic parameters were evaluated using albino rabbits. Solvent evaporation technique was found to be the best release controlling technique thereby prolonging the release rate up to 24 hours. Accelerated stability studies of the optimized test formulation (F-2) did not show any significant change (prelease rate when stored for six months. A simple and rapid method was developed for DCL-Na active moiety using HPLC-UV at 276nm. The optimized test tablets (F-2) significantly (prelease. The study showed that once-daily controlled release matrix tablets of DCL-Na were successfully developed using Ethocel® Standard 7 FP Premium.

  3. A new LP formulation of the admission control problem modelled as an MDP under average reward criterion

    Science.gov (United States)

    Pietrabissa, Antonio

    2011-12-01

    The admission control problem can be modelled as a Markov decision process (MDP) under the average cost criterion and formulated as a linear programming (LP) problem. The LP formulation is attractive in the present and future communication networks, which support an increasing number of classes of service, since it can be used to explicitly control class-level requirements, such as class blocking probabilities. On the other hand, the LP formulation suffers from scalability problems as the number C of classes increases. This article proposes a new LP formulation, which, even if it does not introduce any approximation, is much more scalable: the problem size reduction with respect to the standard LP formulation is O((C + 1)2/2 C ). Theoretical and numerical simulation results prove the effectiveness of the proposed approach.

  4. Development and Characterization of Sodium Hyaluronate Microparticle-Based Sustained Release Formulation of Recombinant Human Growth Hormone Prepared by Spray-Drying.

    Science.gov (United States)

    Kim, Sun J; Kim, Chan W

    2016-02-01

    The purpose of this study was to develop and characterize a sodium hyaluronate microparticle-based sustained release formulation of recombinant human growth hormone (SR-rhGH) prepared by spray-drying. Compared to freeze-drying, spray-dried SR-rhGH showed not only prolonged release profiles but also better particle property and injectability. The results of size-exclusion high-performance liquid chromatography showed that no aggregate was detected, and dimer was just about 2% and also did not increase with increase of inlet temperature up to 150 °C. Meanwhile, the results of reversed-phase high-performance liquid chromatography revealed that related proteins increased slightly from 4.6% at 100 °C to 6.3% at 150 °C. Thermal mapping test proved that product temperature did not become high to cause protein degradation during spray-drying because thermal energy was used for the evaporation of surface moisture of droplets. The structural characterization by peptide mapping, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and circular dichroism revealed that the primary, secondary, and tertiary structures of rhGH in SR-rhGH were highly comparable to those of reference somatropin materials. The biological characterization by rat weight gain and cell proliferation assays provided that bioactivity of SR-rhGH was equivalent to that of native hGH. These data establish that spray-dried SR-rhGH is highly stable by preserving intact rhGH and hyaluronate microparticle-based formulation by spray-drying can be an alternative delivery system for proteins. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  5. Inclusion of Whole Flour from Latin-American Crops into Bread Formulations as Substitute of Wheat Delays Glucose Release and Uptake.

    Science.gov (United States)

    Laparra, José Moisés; Haros, Monika

    2018-03-01

    Bakery formulations limiting glucose availability for uptake without compromising product quality are required. Herein, bread formulations containing whole flour from Amaranthus hypochondriacus (AB), Chenopodium quinoa (QB), Salvia hispanica L (ChB) or wheat (WWB) were compared to white bread (WB) for glycaemic index (GI) in fasted animals. The hepatic expression (mRNA) of PPAR-γ receptor as key regulator in substrate fractionation towards energy expenditure was monitored. GIs were associated to fluxes of glucose release (F Gluc ) and metabolic response (MTT assay) of HepG2 cells. ChB (19.7%) and AB (13.5%) decreased GI to a higher extent than QB (2.7%), but all increased expression of PPARγ in relation to WB. F Gluc (AB> > ChB, WWB, WB > QB) showed a reciprocal relationship with the area under curve (AUC) in vivo, and decreased MTT conversion values (WB > WWB, ChB, AB, QB) by HepG2 cells. Thus, inclusion of latin-american crops (LAcs) reducing GI, without compromising bread quality, could help preventing metabolic diseases.

  6. Nano-suspension coating as a technique to modulate the drug release from controlled porosity osmotic pumps for a soluble agent.

    Science.gov (United States)

    Bahari, Leila Azharshekoufeh; Javadzadeh, Yousef; Jalali, Mohammad Barzegar; Johari, Peyvand; Nokhodchi, Ali; Shokri, Javad

    2017-05-01

    In controlled porosity osmotic pumps (CPOP), usually finding a single solvent with a capability to dissolve both film former (hydrophobic) and pore former (hydrophilic) is extremely challenging. Therefore, the aim of the present investigation was to tackle the issue associated with controlled porosity osmotic pump (CPOP) system using nano-suspension coating method. In the present study 4-Amino pyridine was used as a highly water soluble drug. In this method, a hydrophilic pore former (sucrose or mannitol) in nano range was suspended in polymeric coating solution using ball-mill. The performance of the prepared formulations was assessed in terms of D 12h (cumulative release percent after 12h), Dev zero (mean percent deviation of drug release from zero order kinetic), t L (lag time of the drug release) and RSQ zero . The results revealed that gelling agent amount (HPMC E 15LV ) in core and pore former concentration in SPM had crucial effect on SPM integrity. All the optimised formulations showed a burst drug release due to fast dissolving nature of the pore formers. Results obtained from scanning electron microscopy demonstrated the formation of nanopores in the membrane where the drug release takes place via these nanopores. Nano suspension coating method can be introduced as novel method in formulation of CPOPs. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Radiation curing of intelligent coating for controlled release and permeation

    International Nuclear Information System (INIS)

    Nakayama, Hiroshi; Kaetsu, Isao; Uchida, Kumao; Sakata, Shoei; Tougou, Kazuhide; Hara, Takamichi; Matsubara, Yoshio

    2002-01-01

    Intelligent membranes for pH and temperature-responsive drug releases were developed by coating and curing of polymer-drug composite film with electrolyte or N-isopropyl acrylamide curable mixture. It was proved that those intelligent membranes showed the stimule-sensitive and responsive release functions and could be produced efficiently by radiation curing processing with a conveyer system

  8. Controlled release of free-falling test models

    Science.gov (United States)

    Fife, W. J.; Holway, H. P.

    1970-01-01

    Releasing device, powered by a drill motor through an adjustable speed reducer, has a spinning release head with three retractable spring-loaded fingers. The fingers are retracted by manual triggering of a cable at the motor end of the unit.

  9. PH-triggered micellar membrane for controlled release microchips

    KAUST Repository

    Yang, Xiaoqiang

    2011-01-01

    A pH-responsive membrane based on polystyrene-b-poly(4-vinylpyridine) (PS-b-P4VP) block copolymer was developed on a model glass microchip as a promising controlled polymer delivery system. The PS-b-P4VP copolymer assembles into spherical and/or worm-like micelles with styrene block cores and pyridine coronas in selective solvents. The self-assembled worm-like morphology exhibited pH-responsive behaviour due to the protonation of the P4VP block at low pH and it\\'s deprotonation at high pH and thus constituting a switchable "off/on" system. Doxorubicin (Dox) was used as cargo to test the PS-b-P4VP membrane. Luminescence experiments indicated that the membrane was able to store Dox molecules within its micellar structure at neutral pH and then release them as soon as the pH was raised to 8.0. The performance of the cast membrane was predictable and most importantly reproducible. The physiochemical and biological properties were also investigated carefully in terms of morphology, cell viability and cell uptake. This journal is © The Royal Society of Chemistry.

  10. Application of a Compact Magnetic Resonance Imaging System with 1.5 T Permanent Magnets to Visualize Release from and the Disintegration of Capsule Formulations in Vitro and in Vivo.

    Science.gov (United States)

    Takeshita, Keizo; Okazaki, Shoko; Shinada, Kyosuke; Shibamoto, Yuma

    2017-01-01

    Although magnetic resonance imaging (MRI) has potential in assessments of formulations, few studies have been conducted because of the size and expense of the instrument. In the present study, the processes of in vitro and in vivo release in a gelatin capsule formulation model were visualized using a compact MRI system with 1.5 T permanent magnets, which is more convenient than the superconducting MRI systems typically used for clinical and experimental purposes. A Gd-chelate of diethylenetriamine-N,N,N',N″,N″-pentaacetic acid, a contrast agent that markedly enhances proton signals via close contact with water, was incorporated into capsule formulations as a marker compound. In vitro experiments could clearly demonstrate the preparation-dependent differences in the release/disintegration of the formulations. In some preparations, the penetration of water into the formulation and generation of bubbles in the capsule were also observed prior to the disintegration of the formulation. When capsule formulations were orally administered to rats, the release of the marker into the stomach and its transit to the duodenum were visualized. These results strongly indicate that the compact MRI system is a powerful tool for pharmaceutical studies.

  11. Utilization of wheat straw for the preparation of coated controlled-release fertilizer with the function of water retention.

    Science.gov (United States)

    Xie, Lihua; Liu, Mingzhu; Ni, Boli; Wang, Yanfang

    2012-07-18

    With the aim of improving fertilizer use efficiency and minimizing the negative impact on the environment, a new coated controlled-release fertilizer with the function of water retention was prepared. A novel low water solubility macromolecular fertilizer, poly(dimethylourea phosphate) (PDUP), was "designed" and formulated from N,N'-dimethylolurea (DMU) and potassium dihydrogen phosphate. Simultaneously, an eco-friendly superabsorbent composite based on wheat straw (WS), acrylic acid (AA), 2-acryloylamino-2-methyl-1-propanesulfonic acid (AMPS), and N-hydroxymethyl acrylamide (NHMAAm) was synthesized and used as the coating to control the release of nutrient. The nitrogen release profile and water retention capacity of the product were also investigated. The degradation of the coating material in soil solution was studied. Meanwhile, the impact of the content of N-hydroxymethyl acrylamide on the degradation extent was examined. The experimental data showed that the product with good water retention and controlled-release capacities, being economical and eco-friendly, could be promising for applications in agriculture and horticulture.

  12. Thiolation of arabinoxylan and its application in the fabrication of controlled release mucoadhesive oral films.

    Science.gov (United States)

    Hanif, Muhammad; Zaman, Muhammad

    2017-03-20

    Mucoadhesion is an important property that helps oral drug delivery system to remain attached with buccal mucosa and hence to improve the delivery of the drug. The current study was designed to achieve the thiol modification of Arabinoxylan (ARX) and to develop a mucoadhesive oral film for the improved delivery of tizanidine hydrochloride (TZN HCl). Synthesis of thiolated arabinoxylan (TARX) was accomplished by esterification of ARX with thioglycolic acid (TGA). TARX was further used for the development of mucoadhesive oral films which were prepared by using a solvent casting technique. Formulation of the films was designed and optimized by using central composite design (CCRD), selecting TARX (X 1 ) and glycerol (X 2 ) as variables. Prepared film formulations were evaluated for mechanical strength, ex-vivo mucoadhesion, in-vitro drug release, ex-vivo drug permeation, surface morphology and drug contents. Thiolation of ARX was confirmed by fourier transform infra-red spectroscopy (FTIR) as a peak related to thiol group appeared at 2516 cm -1 . The claim of successful thiolation of ARX was strengthened by the presence of 2809.003 ± 1.03 μmoles of thiol contents per gram of the polymer, which was determined by Ellman's reagent method. From the results, it was observed that the films were of satisfactory mechanical strength and mucoadhesiveness with folding endurance greater than 300 and mucoadhesive strength 11.53 ± 0.17 N, respectively. Reasonable drug retention was observed during in-vitro dissolution (85.03% cumulative drug release) and ex-vivo permeation (78.90% cumulative amount of permeated drug) studies conducted for 8 h. Effects of varying concentrations of both polymer and plasticizer on prepared mucoadhesive oral films were evaluated by ANOVA and it was observed that glycerol can enhanced the dissolution as well as permeation of the drug while TARX has opposite impact on these parameters. In nutshell, TARX in combination with glycerolwas found

  13. Role of resting metabolic rate and energy expenditure in hunger and appetite control: a new formulation.

    Science.gov (United States)

    Blundell, John E; Caudwell, Phillipa; Gibbons, Catherine; Hopkins, Mark; Naslund, Erik; King, Neil; Finlayson, Graham

    2012-09-01

    A long-running issue in appetite research concerns the influence of energy expenditure on energy intake. More than 50 years ago, Otto G. Edholm proposed that "the differences between the intakes of food [of individuals] must originate in differences in the expenditure of energy". However, a relationship between energy expenditure and energy intake within any one day could not be found, although there was a correlation over 2 weeks. This issue was never resolved before interest in integrative biology was replaced by molecular biochemistry. Using a psychobiological approach, we have studied appetite control in an energy balance framework using a multi-level experimental system on a single cohort of overweight and obese human subjects. This has disclosed relationships between variables in the domains of body composition [fat-free mass (FFM), fat mass (FM)], metabolism, gastrointestinal hormones, hunger and energy intake. In this Commentary, we review our own and other data, and discuss a new formulation whereby appetite control and energy intake are regulated by energy expenditure. Specifically, we propose that FFM (the largest contributor to resting metabolic rate), but not body mass index or FM, is closely associated with self-determined meal size and daily energy intake. This formulation has implications for understanding weight regulation and the management of obesity.

  14. Role of resting metabolic rate and energy expenditure in hunger and appetite control: a new formulation

    Directory of Open Access Journals (Sweden)

    John E. Blundell

    2012-09-01

    Full Text Available A long-running issue in appetite research concerns the influence of energy expenditure on energy intake. More than 50 years ago, Otto G. Edholm proposed that “the differences between the intakes of food [of individuals] must originate in differences in the expenditure of energy”. However, a relationship between energy expenditure and energy intake within any one day could not be found, although there was a correlation over 2 weeks. This issue was never resolved before interest in integrative biology was replaced by molecular biochemistry. Using a psychobiological approach, we have studied appetite control in an energy balance framework using a multi-level experimental system on a single cohort of overweight and obese human subjects. This has disclosed relationships between variables in the domains of body composition [fat-free mass (FFM, fat mass (FM], metabolism, gastrointestinal hormones, hunger and energy intake. In this Commentary, we review our own and other data, and discuss a new formulation whereby appetite control and energy intake are regulated by energy expenditure. Specifically, we propose that FFM (the largest contributor to resting metabolic rate, but not body mass index or FM, is closely associated with self-determined meal size and daily energy intake. This formulation has implications for understanding weight regulation and the management of obesity.

  15. Formulation and quality control of amla oil (Phyllantus emblica based on Iranian traditional medicine

    Directory of Open Access Journals (Sweden)

    N. Nikmanesh

    2017-11-01

    Full Text Available Background and objectives: Amla is native to India and is exported to Iran. Although amla has been mentioned in Iranian traditional medicine (ITM manuscripts, no pharmaceuticals have been prepared from this medicinal plant in Iran; thus, in the present study amla oil has been designed and formulated according to ITM. Methods: Phyllantus emblica and Myrtus communis were purchased from herbal market of Tehran and their scientific names were confirmed. Quality control tests were performed on the herbs. For preparing amla oil, the aqueous extract of Myrtus communis leaves was prepared by using maceration method for 24 h. Then, the mixture was filtered and amla was added to the extract and shaked for 48 h. After filtering the mixture, sesame oil was added to the filtrate (in equal volume and heated until all water was evaporated and the oil remained. Quality control examinations including determination of viscosity, density, acid value, saponification value and microbial tests were performed on the oil. Results: Amla oil was dark yellowin color with sesame odor. The density was found to be 0.966 mg/mL and the viscosity was 108.2 centipoise. Acid value was 3.03 mg KH/g oil and saponification value was zero. No fungal or bacterial growth was observed. Conclusion: The formulated amla oil demonstrated acceptable physicochemical charactristics and could be introduced for further mass production after completing the final required evaluations.

  16. Dose proportionality and pharmacokinetics of carvedilol sustained-release formulation: a single dose-ascending 10-sequence incomplete block study

    Directory of Open Access Journals (Sweden)

    Kim YH

    2015-06-01

    Full Text Available Yo Han Kim,1 Hee Youn Choi,1 Yook-Hwan Noh,1 Shi Hyang Lee,1 Hyeong-Seok Lim,1 Chin Kim,2 Kyun-Seop Bae11Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, 2Chong Kun Dang Clinical Research and Clinical Epidemiology and Medical Information, CKD Pharmaceuticals, Seoul, Republic of KoreaBackground: Carvedilol is a third-generation β-blocker indicated for congestive heart failure and high blood pressure. The aim of this study was to investigate the dose proportionality of the carvedilol sustained-release (SR formulation in healthy male subjects.Methods: An open-label, single dose-ascending, 10-sequence, 3-period balanced incomplete block study was performed using healthy male subjects. In varying sequences, each subject received three of five carvedilol SR formulations (8, 16, 32, 64, or 128 mg once. The treatment periods were separated by a washout period of 7 days. Serial blood samples were collected up to 48 h after dosing. The plasma concentrations of carvedilol were determined by using validated liquid chromatography–tandem mass spectrometry. Pharmacokinetic parameters including the area under the plasma concentration–time curve (AUC from time 0 to the last measurable time (AUClast, AUC extrapolated to infinity (AUCinf, and the measured peak plasma concentration (Cmax were obtained by noncompartmental analysis. Dose proportionality was evaluated if the ln–ln plots of AUClast, AUCinf, and Cmax versus dose were linear and the 90% confidence intervals (CIs of the slopes were within 0.9195 and 1.0805. Tolerability was assessed by vital signs, electrocardiogram, clinical laboratory tests, and monitoring of adverse events (AEs throughout the study.Results: A total of 31 subjects were enrolled, and 30 completed the study. The assessment of dose proportionality meets the statistical criteria; the point estimates of slope were 1.0104 (90% CI: 0.9849–1.0359 for AUClast, 1

  17. In vitro solubility, dissolution and permeability studies combined with semi-mechanistic modeling to investigate the intestinal absorption of desvenlafaxine from an immediate- and extended release formulation.

    Science.gov (United States)

    Franek, F; Jarlfors, A; Larsen, F; Holm, P; Steffansen, B

    2015-09-18

    Desvenlafaxine is a biopharmaceutics classification system (BCS) class 1 (high solubility, high permeability) and biopharmaceutical drug disposition classification system (BDDCS) class 3, (high solubility, poor metabolism; implying low permeability) compound. Thus the rate-limiting step for desvenlafaxine absorption (i.e. intestinal dissolution or permeation) is not fully clarified. The aim of this study was to investigate whether dissolution and/or intestinal permeability rate-limit desvenlafaxine absorption from an immediate-release formulation (IRF) and Pristiq(®), an extended release formulation (ERF). Semi-mechanistic models of desvenlafaxine were built (using SimCyp(®)) by combining in vitro data on dissolution and permeation (mechanistic part of model) with clinical data (obtained from literature) on distribution and clearance (non-mechanistic part of model). The model predictions of desvenlafaxine pharmacokinetics after IRF and ERF administration were compared with published clinical data from 14 trials. Desvenlafaxine in vivo dissolution from the IRF and ERF was predicted from in vitro solubility studies and biorelevant dissolution studies (using the USP3 dissolution apparatus), respectively. Desvenlafaxine apparent permeability (Papp) at varying apical pH was investigated using the Caco-2 cell line and extrapolated to effective intestinal permeability (Peff) in human duodenum, jejunum, ileum and colon. Desvenlafaxine pKa-values and octanol-water partition coefficients (Do:w) were determined experimentally. Due to predicted rapid dissolution after IRF administration, desvenlafaxine was predicted to be available for permeation in the duodenum. Desvenlafaxine Do:w and Papp increased approximately 13-fold when increasing apical pH from 5.5 to 7.4. Desvenlafaxine Peff thus increased with pH down the small intestine. Consequently, desvenlafaxine absorption from an IRF appears rate-limited by low Peff in the upper small intestine, which "delays" the predicted

  18. Evaluation of Plantago major L. seed mucilage as a rate controlling matrix for sustained release of propranolol hydrochloride.

    Science.gov (United States)

    Saeedi, Majid; Morteza-Semnani, Katayoun; Sagheb-Doust, Mehdi

    2013-03-01

    Polysaccharide mucilage derived from the seeds of Plantago major L. (family Plantaginaceae) was investigated for use in matrix formulations containing propranolol hydrochloride. HPMC K4M and tragacanth were used as standards for comparison. The hardness, tensile strength, and friability of tablets increased as the concentration of mucilage increased, indicating good compactibility of mucilage powders. The rate of release of propranolol hydrochloride from P. major mucilage matrices was mainly controlled by the drug/mucilage ratio. Formulations containing P. major mucilage were found to exhibit a release rate comparable to HPMC containing matrices at a lower drug/polymer ratio (drug/HPMC 2:1). These results demonstrated that P. major mucilage is a better release retardant compared to tragacanth at an equivalent content. The results of kinetic analysis showed that in F3 (containing 1:2 drug/mucilage) the highest correlation coefficient was achieved with the zero order model. The swelling and erosion studies revealed that as the proportion of mucilage in tablets was increased, there was a corresponding increase in percent swelling and a decrease in percent erosion of tablets. The DSC and FT-IR studies showed that no formation of complex between the drug and mucilage or changes in crystallinity of the drug had occurred.

  19. Lecithin-based microemulsions for targeted delivery of ceramide AP into the stratum corneum: formulation, characterizations, and in vitro release and penetration studies.

    Science.gov (United States)

    Sahle, Fitsum F; Metz, Hendrik; Wohlrab, Johannes; Neubert, Reinhard H H

    2013-02-01

    To improve the solubility and penetration of Ceramide AP (CER [AP]) into the stratum corneum that potentially restores the barrier function of aged and affected skin. CER [AP] microemulsions (MEs) were formulated using lecithin, Miglyol® 812 (miglyol) and water-1,2 pentandiol (PeG) mixture as amphiphilic, oily and hydrophilic components, respectively. The nanostructure of the MEs was revealed using electrical conductivity, differential scanning calorimeter (DSC) and electron paramagnetic resonance (EPR) techniques. Photon correlation spectroscopy (PCS) was used to measure the sizes and shape of ME droplets. The release and penetration of the CER into the stratum corneum was investigated in vitro using a multi-layer membrane model. The MEs exhibited excellent thermodynamic stability (>2 years) and loading capacity (0.5% CER [AP]). The pseudo-ternary phase diagrams of the MEs were obtained and PCS results showed that the droplets are spherical in shape and bigger in size. In vitro investigations showed that the MEs exhibited excellent rate and extent of release and penetration. Stable lecithin-based CER [AP] MEs that significantly enhance the solubility and penetration of CER [AP] into the stratum corneum were developed. The MEs also have better properties than the previously reported polyglycerol fatty acid surfactant-based CER [AP] MEs.

  20. Controlled Release of Damascone from Poly(styrene-co-maleic anhydride-based Bioconjugates in Functional Perfumery

    Directory of Open Access Journals (Sweden)

    Andreas Herrmann

    2013-02-01

    Full Text Available Poly(styrene-co-maleic anhydrides were modified with poly(propylene oxide (PO-co-ethylene oxide (EO side chains (Jeffamine® with different EO/PO molar ratios, varying between 0.11 and 3.60. These copolymers were then further functionalized with a β-mercapto ketone of δ-damascone. The obtained poly(maleic acid monoamide-based β-mercapto ketones were then studied as delivery systems for the controlled release of δ-damascone by retro 1,4-addition. The release of δ-damascone, a volatile, bioactive molecule of the family of rose ketones, was studied by dynamic headspace analysis above a cotton surface after deposition of a cationic surfactant containing fabric softening formulation, as a function of the ethylene oxide (EO/propylene oxide (PO molar ratio of the grafted copolymer side chains. The polarity of the EO/PO side chain influenced the release efficiency of the damascone in a typical fabric softening application. PO-rich copolymers and the corresponding poly(styrene-co-maleic anhydride without Jeffamine® side chains were found to be less efficient for the desired fragrance release than the corresponding bioconjugate with a EO/PO ratio of 3.60 in the side chain. This copolymer conjugate seemed to represent a suitable balance between hydrophilicity and hydrophobicity to favor the release of the δ-damascone and to improve the deposition of the conjugate from an aqueous environment onto a cotton surface.

  1. Pharmacokinetics of hydrocodone extended-release tablets formulated with different levels of coating to achieve abuse deterrence compared with a hydrocodone immediate-release/acetaminophen tablet in healthy subjects.

    Science.gov (United States)

    Darwish, Mona; Bond, Mary; Tracewell, William; Robertson, Philmore; Yang, Ronghua

    2015-01-01

    A hydrocodone extended-release (ER) formulation employing the CIMA(®) Abuse-Deterrence Technology platform was developed to provide resistance against rapid release of hydrocodone when tablets are comminuted or taken with alcohol. This study evaluated the pharmacokinetics of three hydrocodone ER tablet prototypes with varying levels of polymer coating to identify the prototype expected to have the greatest abuse deterrence potential based on pharmacokinetic characteristics that maintain systemic exposure to hydrocodone comparable to that of a commercially available hydrocodone immediate-release (IR) product. In this four-period crossover study, healthy subjects aged 18-45 years were randomized to receive a single intact, oral 45-mg tablet of one of three hydrocodone ER prototypes (low-, intermediate-, or high-level coating) or an intact, oral tablet of hydrocodone IR/acetaminophen (APAP) 10/325 mg every 6 h until four tablets were administered, with each of the four treatments administered once over the four study periods. Dosing periods were separated by a minimum 5-day washout. Naltrexone 50 mg was administered to block opioid receptors. Blood samples for pharmacokinetic assessments were collected predose and through 72 h postdose. Parameters assessed included maximum observed plasma hydrocodone concentration (C(max)), time to C(max) (t(max)), and area under the concentration-time curve from time 0 to infinity (AUC(0-∞)). Mean C(max) values were 49.2, 32.6, and 28.4 ng/mL for the low-, intermediate-, and high-level coating hydrocodone ER tablet prototypes, respectively, and 37.3 ng/mL for the hydrocodone IR/APAP tablet; respective median t(max) values were 5.9, 8.0, 8.0, and 1.0 h. Total systemic exposure to hydrocodone (AUC(0-∞)) was comparable between hydrocodone ER tablet prototypes (640, 600, and 578 ng·h/mL, respectively) and hydrocodone IR/APAP (581 ng·h/mL). No serious adverse events or deaths were reported. The most common adverse events included

  2. Control of anoplophora glabripennis by releasing sterile insects

    International Nuclear Information System (INIS)

    Liu Xiaohui; Li Yongjun; Zhang Shuyong; Wang Endong; Lu Daguang

    2003-01-01

    An experiment to evaluate the effect of released sterile insects on reproduction of natural A. glabripennis population was conducted at a 30-hectare poplar tree forest in Ying County of Shanxi Province from July 10 to August 29, 2001. Though the releasing ratio was only about 2-5, results from different methods showed that the reproduction of natural A. glabripennis population was suppressed effectively by releasing sterile insects, and that hatch ratio of eggs laid by parent generation was about 20% and survival ratio of F1 progeny about 27%. (authors)

  3. Formulation of a strategy for monitoring control integrity in critical digital control systems

    Science.gov (United States)

    Belcastro, Celeste M.; Fischl, Robert; Kam, Moshe

    1991-01-01

    Advanced aircraft will require flight critical computer systems for stability augmentation as well as guidance and control that must perform reliably in adverse, as well as nominal, operating environments. Digital system upset is a functional error mode that can occur in electromagnetically harsh environments, involves no component damage, can occur simultaneously in all channels of a redundant control computer, and is software dependent. A strategy is presented for dynamic upset detection to be used in the evaluation of critical digital controllers during the design and/or validation phases of development. Critical controllers must be able to be used in adverse environments that result from disturbances caused by an electromagnetic source such as lightning, high intensity radiated field (HIRF), and nuclear electromagnetic pulses (NEMP). The upset detection strategy presented provides dynamic monitoring of a given control computer for degraded functional integrity that can result from redundancy management errors and control command calculation error that could occur in an electromagnetically harsh operating environment. The use is discussed of Kalman filtering, data fusion, and decision theory in monitoring a given digital controller for control calculation errors, redundancy management errors, and control effectiveness.

  4. Formulation of polylactide-co-glycolic acid nanospheres for encapsulation and sustained release of poly(ethylene imine-poly(ethylene glycol copolymers complexed to oligonucleotides

    Directory of Open Access Journals (Sweden)

    Wheatley Margaret A

    2009-04-01

    Full Text Available Abstract Antisense oligonucleotides (AOs have been shown to induce dystrophin expression in muscles cells of patients with Duchenne Muscular Dystrophy (DMD and in the mdx mouse, the murine model of DMD. However, ineffective delivery of AOs limits their therapeutic potential. Copolymers of cationic poly(ethylene imine (PEI and non-ionic poly(ethylene glycol (PEG form stable nanoparticles when complexed with AOs, but the positive surface charge on the resultant PEG-PEI-AO nanoparticles limits their biodistribution. We adapted a modified double emulsion procedure for encapsulating PEG-PEI-AO polyplexes into degradable polylactide-co-glycolic acid (PLGA nanospheres. Formulation parameters were varied including PLGA molecular weight, ester end-capping, and sonication energy/volume. Our results showed successful encapsulation of PEG-PEI-AO within PLGA nanospheres with average diameters ranging from 215 to 240 nm. Encapsulation efficiency ranged from 60 to 100%, and zeta potential measurements confirmed shielding of the PEG-PEI-AO cationic charge. Kinetic measurements of 17 kDa PLGA showed a rapid burst release of about 20% of the PEG-PEI-AO, followed by sustained release of up to 65% over three weeks. To evaluate functionality, PEG-PEI-AO polyplexes were loaded into PLGA nanospheres using an AO that is known to induce dystrophin expression in dystrophic mdx mice. Intramuscular injections of this compound into mdx mice resulted in over 300 dystrophin-positive muscle fibers distributed throughout the muscle cross-sections, approximately 3.4 times greater than for injections of AO alone. We conclude that PLGA nanospheres are effective compounds for the sustained release of PEG-PEI-AO polyplexes in skeletal muscle and concomitant expression of dystrophin, and may have translational potential in treating DMD.

  5. Predictive property models for use in design of controlled release of pesticides

    DEFF Research Database (Denmark)

    Suné, Nuria Muro; Gani, Rafiqul; Bell, G.

    2005-01-01

    A model capable of predicting the release of an Active Ingredient (AI) from a specific device would be very useful in the field of pesticide controlled release technology for design purposes. For the release of an AI from a microcapsule a mathematical model is briefly presented here, as an introd...

  6. CONTROLLED-RELEASE OF PARACETAMOL FROM AMYLODEXTRIN TABLETS - IN-VITRO AND IN-VIVO RESULTS

    NARCIS (Netherlands)

    VANDERVEEN, J; EISSENS, AC; LERK, CF

    Amylodextrin is a suitable excipient for the design of solid controlled-release systems. The release of paracetamol from tablets containing 30% drug and 70% amylodextrin was studied in vitro and in vivo. In vitro dissolution profiles showed almost-constant drug release rates during 8 hr, when

  7. Materials for Pharmaceutical Dosage Forms: Molecular Pharmaceutics and Controlled Release Drug Delivery Aspects

    Directory of Open Access Journals (Sweden)

    Patrick P. DeLuca

    2010-09-01

    Full Text Available Controlled release delivery is available for many routes of administration and offers many advantages (as microparticles and nanoparticles over immediate release delivery. These advantages include reduced dosing frequency, better therapeutic control, fewer side effects, and, consequently, these dosage forms are well accepted by patients. Advances in polymer material science, particle engineering design, manufacture, and nanotechnology have led the way to the introduction of several marketed controlled release products and several more are in pre-clinical and clinical development.

  8. Preparation and characterization of novel functionalized prochloraz microcapsules using silica-alginate-elements as controlled release carrier materials.

    Science.gov (United States)

    Zhang, Wenbing; He, Shun; Liu, Yao; Geng, Qianqian; Ding, Guanglong; Guo, Mingcheng; Deng, Yufang; Zhu, Juanli; Li, Jianqiang; Cao, Yongsong

    2014-07-23

    Controlled release formulation of pesticides is an effective approach to achieve the desirable purpose of increasing the utilization of pesticides and reducing the environmental residuals. In this work, a novel functionalized microcapsule using silica cross-linked with alginate, and some beneficial elements to crops, was prepared. The microcapsules were structurally characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis, and X-ray photoelectron spectroscopy. The results showed that the microcapsules had a high loading efficiency of prochloraz (about 30% w/w) and could effectively protect prochloraz against degradation under UV irradiation and alkaline conditions, showed sustainable release for at least 60 days, and also likely increased disease resistance due to the element on the surface. Given the advantages of the microcapsules, this delivery system may be extended to other photosensitive or pH-sensitive pesticides in the future.

  9. Identification and control of unspecified impurity in trimetazidine dihydrochloride tablet formulation

    Science.gov (United States)

    Jefri; Puspitasari, A. D.; Talpaneni, J. S. R.; Tjandrawinata, R. R.

    2018-04-01

    Trimetazidine dihydrochloride is an anti-ischemic metabolic agent which is used as drug for angina pectoris treatment. The drug substance monograph is available in European Pharmacopoeia and British Pharmacopoeia, while the drug product monograph is not available in any of the pharmacopoeias. During development of trimetazidine dihydrochloride tablet formulation, we found increase of an unspecified impurity during preliminary stability study. The unspecified impurity was identified by high performance liquid chromatography coupled with mass spectrometry (LC-MS) and the molecular weight obtained was matching with the molecular weight of N-formyl trimetazidine (m/z 295). Further experiments were performed to confirm the suspected result by injecting the impurity standard and spiking formic acid into the drug substance. The retention time of N-formyl trimetazidine was similar to the unspecified impurity in drug product. Even spiking of formic acid into drug substance showed that the suspected impurity increased with increasing concentration of formic acid. The proposed mechanism of impurity formation is via amidation of piperazine moiety of trimetazidine by formic acid which present as residual solvent in tablet binder used in the formulation. Subsequently, the impurity in our product was controlled by choosing the primary packaging which could minimize the formation of impurity.

  10. FUEL FORMULATION EFFECTS ON DIESEL FUEL INJECTION, COMBUSTION, EMISSIONS AND EMISSION CONTROL

    Energy Technology Data Exchange (ETDEWEB)

    Boehman, A; Alam, M; Song, J; Acharya, R; Szybist, J; Zello, V; Miller, K

    2003-08-24

    This paper describes work under a U.S. DOE sponsored Ultra Clean Fuels project entitled ''Ultra Clean Fuels from Natural Gas,'' Cooperative Agreement No. DE-FC26-01NT41098. In this study we have examined the incremental benefits of moving from low sulfur diesel fuel and ultra low sulfur diesel fuel to an ultra clean fuel, Fischer-Tropsch diesel fuel produced from natural gas. Blending with biodiesel, B100, was also considered. The impact of fuel formulation on fuel injection timing, bulk modulus of compressibility, in-cylinder combustion processes, gaseous and particulate emissions, DPF regeneration temperature and urea-SCR NOx control has been examined. The primary test engine is a 5.9L Cummins ISB, which has been instrumented for in-cylinder combustion analysis and in-cylinder visualization with an engine videoscope. A single-cylinder engine has also been used to examine in detail the impacts of fuel formulation on injection timing in a pump-line-nozzle fueling system, to assist in the interpretation of results from the ISB engine.

  11. Formulation and Characterization of Matrix and Triple-Layer matrix tablets for Controlled Delivery of Metoprolol tartrate

    OpenAIRE

    Izhar Ahmed Syed; Lakshmi Narsu Mangamoori; Yamsani Madhusudan Rao

    2011-01-01

    In the present study matrix and triple layer matrix tablets of metoprolol tartrate were formulated by using xanthan gum as the matrix forming agent and Sodium Carboxy Methyl Cellulose (Na CMC) as barrier layers. The prepared tablets were analysed for their hardness, friability, drug content and in-vitro drug release studies. Marked differences in dissolution characteristics of (M3) and (M3L3) were observed and showed a significant difference statistically. Mean dissolution time (MDT) for M3 a...

  12. Factors controlling alkali salt deposition in recovery boilers. Release mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    McKeough, P; Kurkela, M; Kylloenen, H; Tapola, E [VTT Energy, Espoo (Finland). Process Technology Group

    1997-10-01

    The research was part of an ongoing cooperative research effort aimed at developing a model to describe the behaviour of inorganic compounds in kraft recovery boilers. During 1996 experimental investigations of sulphur release were continued. Experiments at elevated pressures and employing larger particle sizes were performed in order to gain information about mass transfer effects. The first experiments yielding data on the rates of the sulphur-release reactions were performed. This data will be used as the basis of a drop model for sulphur release being developed in cooperation with another research group. The other part of the work during 1996 explored the possibility of using chemical equilibrium calculations to predict the release of sodium, potassium and chlorine in the recovery furnace. The approach is essentially different from that employed in earlier studies in that the effects of fume formation are taken into account. So far, the predictions of the chemical equilibrium release model have, in no way, conflicted with field measurements. (orig.)

  13. ROLE OF NATURAL POLYMER IN SUSTAINED AND CONTROLLED RELEASE

    OpenAIRE

    Vaishali S. Kadam, G. R. Shendarkar

    2017-01-01

    Now a day there has been an important development in different dosage forms for existing and newly designed drugs and natural products, and synthetic as well as semi-synthetic excipients always need to be used for a variety of purposes. Gums and mucilages are widely used as natural materials for conventional and novel dosage forms. With the increasing interest in polymers of natural origin, the pharmaceutical world has compliance to use most of them in their formulations. Moreover, the tremen...

  14. Application of Electrostatic Extrusion – Flavour Encapsulation and Controlled Release

    OpenAIRE

    Manojlovic, Verica; Rajic, Nevenka; Djonlagic, Jasna; Obradovic, Bojana; Nedovic, Viktor; Bugarski, Branko

    2008-01-01

    The subject of this study was the development of flavour alginate formulations aimed for thermally processed foods. Ethyl vanilline was used as the model flavour compound. Electrostatic extrusion was applied for the encapsulation of ethyl vanilline in alginate gel microbeads. The obtained microbeads with approx. 10 % w/w of ethyl vanilline encapsulated in about 2 % w/w alginate were uniformly sized spheres of about 450 ?m. Chemical characterization by H-NMR spectroscopy revealed that the algi...

  15. Gastrin release: Antrum microdialysis reveals a complex neural control

    DEFF Research Database (Denmark)

    Ericsson, P; Håkanson, R; Rehfeld, Jens F.

    2010-01-01

    in both serum and microdialysate. Food intake induced a 2- to 3-fold increase in serum gastrin, while gastrin in antral microdialysate increased 10- to 15-fold. In unilaterally vagotomized rats (fasted, 3 days post-op.), food evoked a prompt peak gastrin release followed by a gradual decline on the intact......We used microdialysis to monitor local gastrin release in response to food, acid blockade and acute vagal excitation. For the first time, gastrin release has been monitored continuously in intact conscious rats in a physiologically relevant experimental setting in a fashion that minimizes...... in serum regardless of the prandial state. The rats were conscious during microdialysis except when subjected to electrical vagal stimulation. Acid blockade (omeprazole treatment of freely fed rats for 4 days), or bilateral sectioning of the abdominal vagal trunks (fasted, 3 days post-op.), raised...

  16. Improved design and characterization of PLGA/PLA-coated Chitosan based micro-implants for controlled release of hydrophilic drugs.

    Science.gov (United States)

    Manna, Soumyarwit; Donnell, Anna M; Kaval, Necati; Al-Rjoub, Marwan F; Augsburger, James J; Banerjee, Rupak K

    2018-05-29

    Repetitive intravitreal injections of Methotrexate (MTX), a hydrophilic chemotherapeutic drug, are currently used to treat selected vitreoretinal (VR) diseases, such as intraocular lymphoma. To avoid complications associated with the rapid release of MTX from the injections, a Polylactic acid (PLA) and Chitosan (CS)-based MTX micro-implant prototype was fabricated in an earlier study, which showed a sustained therapeutic release rate of 0.2-2.0 µg/day of MTX for a period ∼1 month in vitro and in vivo. In the current study, different combinations of Poly(lactic-co-glycolic) acid (PLGA)/PLA coatings were used for lipophilic surface modification of the CS-MTX micro-implant, such as PLGA 5050, PLGA 6535 and PLGA 7525 (PLA: PGA - 50:50, 65:35, 75:25, respectively; M.W: 54,400 - 103,000) and different PLA, such as PLA 100 and PLA 250 (MW: 102,000 and 257,000, respectively). This improved the duration of total MTX release from the coated CS-MTX micro-implants to ∼3-5 months. With an increase in PLA content in PLGA and molecular weight of PLA, a) the initial burst of MTX and the mean release rate of MTX can be reduced; and b) the swelling and biodegradation of the micro-implants can be delayed. The controlled drug release mechanism is caused by a combination of diffusion process and hydrolysis of the polymer coating, which can be modulated by a) PLA content in PLGA and b) molecular weight of PLA, as inferred from Korsmeyer Peppas model, Zero order, First order and Higuchi model fits. This improved micro-implant formulation has the potential to serve as a platform for controlled release of hydrophilic drugs to treat selected VR diseases. Copyright © 2018. Published by Elsevier B.V.

  17. Controlled release fertilizers using superabsorbent hydrogel prepared by gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Elbarbary, Ahmed M.; Ghobashy, Mohamed Mohamady [Atomic Energy Authority, Nasr City (Egypt). National Center for Radiation Research and Technology (NCRTT)

    2017-07-01

    Superabsorbent hydrogels (PVP/CMC) based on polyvinylpyrrolidone (PVP)/carboxylmethyl cellulose (CMC) of different copolymer compositions were prepared by gamma radiation. Factors affecting the gel content (%) and the swelling ratio (g/g) of hydrogel such as irradiation dose as well as copolymer composition were investigated. With increasing the CMC content in PVP/CMC hydrogels, increases the swelling and improves the water retention capability. The high swelling ratio was observed at copolymer composition of PVP/CMC (60/40). Fast swelling of the hydrogels was obtained after 20 min. The effect of different fertilizers and buffers of different pH's on equilibrium swelling of hydrogels was investigated. Fertilizers such as urea, monopotassium-phosphate (MPK), and nitrogen-phosphate-potassium (NPK) were loaded onto the hydrogel to supply nitrogen, potassium and phosphorous nutrients. PVP/CMC hydrogels retained 28-36% after 72 h and slow retention was noticed up to 9 days. The swelling of hydrogel in fertilizer solutions is lower than that in water. The hydrogels showed adsorption desorption of fertilizers which governs by slow release property. The release rate of urea is much higher 10 times than that of phosphate. After 3 days, urea released 60%, while phosphate released 10-12%. The applicability of PVP/CMC hydrogels in the agricultural fields shows greater growth effect on zea maize plants. The growth of zea maize plant in soil mixed with PVP/CMC hydrogels loaded fertilizers is greater than untreated soil. The slow release fertilize, the high swelling and the slow water retention behaviors of PVP/CMC hydrogels encourage their use as safer release systems for fertilizers and as soil conditioner in agricultural applications.

  18. Controlled release fertilizers using superabsorbent hydrogel prepared by gamma radiation

    International Nuclear Information System (INIS)

    Elbarbary, Ahmed M.; Ghobashy, Mohamed Mohamady

    2017-01-01

    Superabsorbent hydrogels (PVP/CMC) based on polyvinylpyrrolidone (PVP)/carboxylmethyl cellulose (CMC) of different copolymer compositions were prepared by gamma radiation. Factors affecting the gel content (%) and the swelling ratio (g/g) of hydrogel such as irradiation dose as well as copolymer composition were investigated. With increasing the CMC content in PVP/CMC hydrogels, increases the swelling and improves the water retention capability. The high swelling ratio was observed at copolymer composition of PVP/CMC (60/40). Fast swelling of the hydrogels was obtained after 20 min. The effect of different fertilizers and buffers of different pH's on equilibrium swelling of hydrogels was investigated. Fertilizers such as urea, monopotassium-phosphate (MPK), and nitrogen-phosphate-potassium (NPK) were loaded onto the hydrogel to supply nitrogen, potassium and phosphorous nutrients. PVP/CMC hydrogels retained 28-36% after 72 h and slow retention was noticed up to 9 days. The swelling of hydrogel in fertilizer solutions is lower than that in water. The hydrogels showed adsorption desorption of fertilizers which governs by slow release property. The release rate of urea is much higher 10 times than that of phosphate. After 3 days, urea released 60%, while phosphate released 10-12%. The applicability of PVP/CMC hydrogels in the agricultural fields shows greater growth effect on zea maize plants. The growth of zea maize plant in soil mixed with PVP/CMC hydrogels loaded fertilizers is greater than untreated soil. The slow release fertilize, the high swelling and the slow water retention behaviors of PVP/CMC hydrogels encourage their use as safer release systems for fertilizers and as soil conditioner in agricultural applications.

  19. Model-based computer-aided design for controlled release of pesticides

    DEFF Research Database (Denmark)

    Muro Sunè, Nuria; Gani, Rafiqul; Bell, G.

    2005-01-01

    In the field of controlled release technology for pesticides or active ingredients (AI), models that can predict its delivery during application are important for purposes of design and marketing of the pesticide product. Appropriate models for the controlled release of pesticides, if available, ...... extended models have been developed and implemented into a computer-aided system. The total model consisting of the property models embedded into the release models are then employed to study the release of different combinations of AIs and polymer-based microcapsules.......In the field of controlled release technology for pesticides or active ingredients (AI), models that can predict its delivery during application are important for purposes of design and marketing of the pesticide product. Appropriate models for the controlled release of pesticides, if available...

  20. Optimization of chlorphenesin emulgel formulation.

    Science.gov (United States)

    Mohamed, Magdy I

    2004-10-11

    This study was conducted to develop an emulgel formulation of chlorphenesin (CHL) using 2 types of gelling agents: hydroxypropylmethyl cellulose (HPMC) and Carbopol 934. The influence of the type of the gelling agent and the concentration of both the oil phase and emulsifying agent on the drug release from the prepared emulgels was investigated using a 2(3) factorial design. The prepared emulgels were evaluated for their physical appearance, rheological behavior, drug release, antifungal activity, and stability. Commercially available CHL topical powder was used for comparison. All the prepared emulgels showed acceptable physical properties concerning color, homogeneity, consistency, spreadability, and pH value. They also exhibited higher drug release and antifungal activity than the CHL powder. It was found that the emulsifying agent concentration had the most pronounced effect on the drug release from the emulgels followed by the oil phase concentration and finally the type of the gelling agent. The drug release from all the emulgels was found to follow diffusion-controlled mechanism. Rheological studies revealed that the CHL emulgels exhibited a shear-thinning behavior with thixotropy. Stability studies showed that the physical appearance, rheological properties, drug release, and antifungal activity in all the prepared emulgels remained unchanged upon storage for 3 months. As a general conclusion, it was suggested that the CHL emulgel formulation prepared with HPMC with the oil phase concentration in its low level and emulsifying agent concentration in its high level was the formula of choice since it showed the highest drug release and antifungal activity.

  1. Control of Black Rot Disease in Tomato Fruits by Using Formulated Ginger Essential oil Treated by Gamma Radiation

    International Nuclear Information System (INIS)

    Helal, I.M.; Abdeldaiem, M.H.

    2008-01-01

    Ginger essential oil (Zingiber officinale) treated by gamma radiation at dose of 10 kGy was selected as an active ingredient for formulation of the biocide. Liquid formulations (emulsifiable concentrates) were prepared using different emulsifiers (Emulgator B.L.M. and tween 80 or tween 20) and additive oil (soybean oil). Physicochemical properties of the formulated oil (spontaneous emulsification, emulsion stability; cold stability and heat stability, viscosity, surface tension and ph) were measured. The formulated oil was tested in vivo to investigate its efficiency for controlling the growth of Alternaria alternata inoculated into tomato fruits. The results indicated that soaking inoculated tomato fruits in the formulated oil (ginger essential oil + soybean oil + emulgator B.L.M. + tween 80) treatment at concentration of 300 ppm for a period of 12 minute was the most effective for controlling the growth of the tested fungus. In addition, the formulated oil had efficiency for controlling the rot development on tomato fruits when applied as therapeutic and protective agents

  2. Development of antiproliferative nanohybrid compound with controlled release property using ellagic acid as the active agent

    Directory of Open Access Journals (Sweden)

    Hussein MZ

    2011-07-01

    Full Text Available Mohd Zobir Hussein1,2, Samer Hasan Al Ali2, Zulkarnain Zainal2, Muhammad Nazrul Hakim31Advanced Materials and Nanotechnology Laboratory, Institute of Advanced Technology (ITMA, 2Department of Chemistry, Faculty of Science, 3Department of Biomedical Science, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Selangor, MalaysiaAbstract: An ellagic acid (EA–zinc layered hydroxide (ZLH nanohybrid (EAN was synthesized under a nonaqueous environment using EA and zinc oxide (ZnO as the precursors. Powder X-ray diffraction showed that the basal spacing of the nanohybrid was 10.4 Å, resulting in the spatial orientation of EA molecules between the interlayers of 22.5° from z-axis with two negative charges at 8,8′ position of the molecules pointed toward the ZLH interlayers. FTIR study showed that the intercalated EA spectral feature is generally similar to that of EA, but with bands slightly shifted. This indicates that some chemical bonding of EA presence between the nanohybrid interlayers was slightly changed, due to the formation of host–guest interaction. The nanohybrid is of mesopores type with 58.8% drug loading and enhanced thermal stability. The release of the drug active, EA from the nanohybrid was found to be sustained and therefore has good potential to be used as a drug controlled-release formulation. In vitro bioassay study showed that the EAN has a mild effect on the hepatocytes cells, similar to its counterpart, free EA.Keywords: ellagic acid, nonaqueous solution, ZnO, zinc-layered hydroxide, viability test

  3. Controlling benthic release of phosphorus in different Baltic Sea scales

    DEFF Research Database (Denmark)

    Pitkänen, Heikki; Bendtsen, Jørgen; Hansen, Jørgen L. S.

    The general aim of the PROPPEN project was to study whether it is possible to counteract near-bottom anoxia and excess benthic nutrient release ("internal loading") in the Baltic Sea by artificial oxygenation in cost-efficient and socio-economically beneficial ways. Two pilot sites were selected ...

  4. Biodegradable hollow fibres for the controlled release of drugs

    NARCIS (Netherlands)

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

    1988-01-01

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

  5. Radioimmunoassay for 6-D-tryptophan analog of luteinizing hormone-releasing hormone: measurement of serum levels after administration of long-acting microcapsule formulations

    International Nuclear Information System (INIS)

    Mason-Garcia, M.; Vigh, S.; Comaru-Schally, A.M.; Redding, T.W.; Somogyvari-Vigh, A.; Horvath, J.; Schally, A.V.

    1985-01-01

    A sensitive and specific radioimmunoassay for [6-D-tryptophan]luteinizing hormone-releasing hormone ([D-Trp 6 ]LH-RH) was developed and used for following the rate of liberation of [D-Trp 6 ]LH-RH from a long-acting delivery systems based on a microcapsule formulation. Rabbit antibodies were generated against [D-Trp 6 ]LH-RH conjugated to bovine serum albumin with glutaraldehyde. Crossreactivity with LH-RH was less than 1%; there was no significant cross-reactivity with other peptides. The minimal detectable dose of [D-Trp 6 ]LH-RH was 2 pg per tube. In tra- and interassay coefficients of variation were 8% and 10%, respectively. The radioimmunoassay was suitable for direct determination of [D-Trp 6 ]LH-RH in serum, permitting the study of blood levels of the analog after single injections into normal men and after one-a-month administration of microcapsules to rats. In men, 90 min after subcutaneous injection of 250 μg of the peptide, serum [D-Trp 6 ]LH-RH rose to 6-12 ng/ml. Luteinizing hormone was increased 90 min and 24 hr after the administration of the analog. Several batches of microcapsules were tested in rats and the rate of release of [D-Trp 6 ]LH-RH was followed. The improved batch of microcapsules of [D-Trp 6 ]LH-RH increased serum concentrations of the analog for 30 days or longer after intramuscular injection

  6. Supervisory control of mobile sensor networks: math formulation, simulation, and implementation.

    Science.gov (United States)

    Giordano, Vincenzo; Ballal, Prasanna; Lewis, Frank; Turchiano, Biagio; Zhang, Jing Bing

    2006-08-01

    This paper uses a novel discrete-event controller (DEC) for the coordination of cooperating heterogeneous wireless sensor networks (WSNs) containing both unattended ground sensors (UGSs) and mobile sensor robots. The DEC sequences the most suitable tasks for each agent and assigns sensor resources according to the current perception of the environment. A matrix formulation makes this DEC particularly useful for WSN, where missions change and sensor agents may be added or may fail. WSN have peculiarities that complicate their supervisory control. Therefore, this paper introduces several new tools for DEC design and operation, including methods for generating the required supervisory matrices based on mission planning, methods for modifying the matrices in the event of failed nodes, or nodes entering the network, and a novel dynamic priority assignment weighting approach for selecting the most appropriate and useful sensors for a given mission task. The resulting DEC represents a complete dynamical description of the WSN system, which allows a fast programming of deployable WSN, a computer simulation analysis, and an efficient implementation. The DEC is actually implemented on an experimental wireless-sensor-network prototyping system. Both simulation and experimental results are presented to show the effectiveness and versatility of the developed control architecture.

  7. Dexamethasone-loaded poly(3-hydroxybutyrate-co-3-hydroxyvalerate) microparticles for controlled release

    International Nuclear Information System (INIS)

    Riekes, Manoela Klueppel; Paula, Josiane Padilha de; Farago, Paulo Vitor; Zawadzki, Sonia Faria

    2009-01-01

    Dexamethasone (DEX) has been widely used for the treatment of ulcerative colitis. The aim of the present study was to obtain DEX-loaded poly(3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV) microparticles prepared by simple emulsion/solvent evaporation method. The drug loading and the encapsulation efficiency were determined by a previously validated UV method at 233 nm. Morphological, spectroscopical and dissolution analyses were also performed. The microparticles (formulation F no. 0, F no. 1 and F no. 2) were successfully obtained as off-white powders. A drug loading of 92.27 mg.g -1 and 218.54 mg.g -1 and an encapsulation efficiency of 93.96 % and 87.43 % were respectively observed for F no. 1 and F no. 2. Particles showed spherical and rough aspect by SEM. X-ray diffraction analysis demonstrated that the encapsulation reduced the drug crystallinity. FTIR spectra showed that no chemical bonding occurred between PHBV and DEX. Drug-loaded microparticles revealed controlled release profiles compared to pure DEX. (author)

  8. Application of tumbling melt granulation (TMG) method to prepare controlled-release fine granules.

    Science.gov (United States)

    Maejima, T; Kubo, M; Osawa, T; Nakajima, K; Kobayashi, M

    1998-03-01

    The tumbling melt granulation (TMG) method was applied to prepare controlled-release fine granules of diltiazem hydrochloride (DH). The entire process, from the preparation of the cores by the adherence of DH to the sucrose crystal to the subsequent coating of the controlled-release layer, was performed without using any solvent. A mixture of meltable material, talc, and ethylcellulose was used for the controlled-release layer and controlled-release fine granules approximately 400 microns in diameter were obtained with excellent producibility. The dissolution rate of DH from these fine granules was similar to that of a once-a-day dosage form obtained in the market; further, the dependency of the dissolution profile on pH of the media was less. Thus, it was concluded that this TMG method was very useful for preparing not only controlled-release beads of granule size (usually 500 to 1400 microns) but also fine granules.

  9. Acoustically Triggered Disassembly of Multilayered Polyelectrolyte Thin Films through Gigahertz Resonators for Controlled Drug Release Applications

    Directory of Open Access Journals (Sweden)

    Zhixin Zhang

    2016-11-01

    Full Text Available Controlled drug release has a high priority for the development of modern medicine and biochemistry. To develop a versatile method for controlled release, a miniaturized acoustic gigahertz (GHz resonator is designed and fabricated which can transfer electric supply to mechanical vibrations. By contacting with liquid, the GHz resonator directly excites streaming flows and induces physical shear stress to tear the multilayered polyelectrolyte (PET thin films. Due to the ultra-high working frequency, the shear stress is greatly intensified, which results in a controlled disassembling of the PET thin films. This technique is demonstrated as an effective method to trigger and control the drug release. Both theory analysis and controlled release experiments prove the thin film destruction and the drug release.

  10. Gastrin release: Antrum microdialysis reveals a complex neural control

    DEFF Research Database (Denmark)

    Ericsson, P; Håkanson, R; Rehfeld, Jens F.

    2010-01-01

    We used microdialysis to monitor local gastrin release in response to food, acid blockade and acute vagal excitation. For the first time, gastrin release has been monitored continuously in intact conscious rats in a physiologically relevant experimental setting in a fashion that minimizes...... in serum regardless of the prandial state. The rats were conscious during microdialysis except when subjected to electrical vagal stimulation. Acid blockade (omeprazole treatment of freely fed rats for 4 days), or bilateral sectioning of the abdominal vagal trunks (fasted, 3 days post-op.), raised...... the gastrin concentration in blood as well as microdialysate. The high gastrin concentration following omeprazole treatment was not affected by vagotomy. Vagal excitation stimulated the G cells: electrical vagal stimulation and pylorus ligation (fasted rats) raised the gastrin concentration transiently...

  11. Clearance and release from control - An international perspective

    International Nuclear Information System (INIS)

    Thierfeldt, S.

    2005-01-01

    This paper tries to give an overview of the clearance, or release from regulatory control, on an international scale, including some of those countries where clearance has become or is about to become vital for D and D. The emphasis lies on the impact of clearance, and in particular of differences between clearance levels of various countries, on D and D. Relevance of clearance for D and D of nuclear installations Clearance is an essential part of waste management (or more general, material management) in nuclear installations, and in particular during the decommissioning phase where waste streams continues to arise. Of course, the relevance of clearance in a particular country depends on a number of factors, like: availability of a final repository and its price; prevailing decommissioning strategy; number of nuclear installations reaching decommissioning phase. This small selection of reasons why clearance may be of varying importance for different countries may already suffice to illustrate why up to now clearance has been developed and implemented in quite different ways. If one thinks of additional reasons that may influence clearance, like politics, the public opinion, availability of funds etc., the situation becomes even more complex. It is, however safe to draw the conclusion that countries with a certain number of nuclear installations which have been or will soon be shut down or which are already in the decommissioning phase will need to implement provisions for clearance. This has indeed been the case with countries like the UK, Germany, the USA, Sweden, and a number of others. It is not essential for clearance levels to be exactly equal between various countries. They may differ as long as the difference is not too large, e.g. the values fall into the same order of magnitude. This is the reason why for example Germany has no problems with clearance levels which differ from the EU recommendation RP 122 partially adopted in a number of EU countries

  12. Coupling 3D printing with hot-melt extrusion to produce controlled-release tablets.

    Science.gov (United States)

    Zhang, Jiaxiang; Feng, Xin; Patil, Hemlata; Tiwari, Roshan V; Repka, Michael A

    2017-03-15

    The main objective of this work was to explore the potential of coupling fused deposition modeling in three-dimensional (3D) printing with hot-melt extrusion (HME) technology to facilitate additive manufacturing, in order to fabricate tablets with enhanced extended release properties. Acetaminophen was used as the model drug and different grades and ratios of polymers were used to formulate tablets. Three-point bending and hardness tests were performed to determine the mechanical properties of the filaments and tablets. 3D-printed tablets, directly compressed mill-extruded tablets, and tablets prepared from a physical mixture were evaluated for drug release rates using a USP-II dissolution apparatus. The surface and cross-sectional morphology of the 3D-printed tablets were assessed by scanning electron microscopy. Differential scanning calorimetry and thermogravimetric analysis were used to characterize the crystal states and thermal properties of materials, respectively. The 3D-printed tablets had smooth surfaces and tight structures; therefore, they showed better extended drug release rates than the directly compressed tablets did. Further, this study clearly demonstrated the feasibility of coupling HME with 3D printing technology, which allows for the formulation of drug delivery systems using different grades and ratios of pharmaceutical polymers. In addition, formulations can be made based on the personal needs of patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Polyoxometalate coordination induced controllable release of quinolone in hybrid film

    Science.gov (United States)

    Yang, Fan; Li, Yang; Lv, Yu-Guang; Zhou, Shu-Jing; Li, Si; Gao, Guang-Gang; Liu, Hong

    2018-05-01

    Due to some side effects of quinolones in vivo, it is an urgent issue to extend their new applications in vitro. In this paper, structure-determined vanadium-quinolone functionalized polymolybdates of (NH4)2 [(γ-Mo8O26){VO(CF)2}2] (1) and (NH4)2 [(γ-Mo8O26){VO(NF)2}2] (2) (CF = ciprofloxacin; NF = norfloxacin) have been designed and synthesized. Complex 1 or 2 features a γ-type [Mo8O26]4- polyanion functionalized by two monocapped vanadium-quinolone complexes. Different H-bonds and π···π interactions allow 1 or 2 to form a 2D layered structure at solid state. When complex 1 or 2 is transferred into polyvinyl alcohol (PVA) film, its release rate in solution is lower than that of CF- or NF-PVA film and thus forming a novel quinolone delivery system. This is the first time that slow release effect of quinolone is achieved by polyoxometalate coordination effect. The slow release of 1 or 2 in PVA film is mainly ascribed to the coordination of quinolone with polyoxometalate anions.

  14. Phenobarbital loaded microemulsion: development, kinetic release and quality control

    Directory of Open Access Journals (Sweden)

    Kayo Alves Figueiredo

    Full Text Available ABSTRACT This study aimed to obtain and characterize a microemulsion (ME containing phenobarbital (PB. The PB was incorporated in the proportion of 5% and 10% in a microemulsion system containing Labrasol(r, ethanol, isopropyl myristate and purified water. The physicochemical characterization was performed and the primary stability of the ME was evaluated. An analytical method was developed using spectrophotometry in UV = 242 nm. The kinetics of the in vitro release (Franz model of the ME and the emulsion (EM containing PB was evaluated. The incorporation of PB into ME at concentrations of 5 and 10% did not change pH and resistance to centrifugation. There was an increase in particle size, a decrease of conductivity and a change in the refractive index in relation to placebo ME. The ME remained stable in preliminary stability tests. The analytical method proved to be specific, linear, precise, accurate and robust. Regarding the kinetics of the in vitro release, ME obtained an in vitro release profile greater than the EM containing PB. Thus, the obtained ME has a potential for future transdermal application, being able to compose a drug delivery system for the treatment of epilepsy.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-10-15

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

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  17. Controlled release of ibuprofen using Mg Al LDH nano carrier

    Science.gov (United States)

    Dasgupta, Sudip

    2017-08-01

    In the present study, NSAID (non-steroidal anti-inflammatory drugs) such as ibuprofen in anionic form has been intercalated in-situ into the interlayer space of Mg Al LDH nanoparticle during co-precipitation of hydroxides. LDH nanohybrids are characterized by XRD, FTIR and UV spectroscopy. Mg1-xAlx(NO3)x(OH)2.nH2O nanoparticles were synthesized using co-precipitation method from an aqueous solution of Mg(NO3)2.6H2O and Al(NO3)3.9H2O. Ibuprofen was intercalated in inter layer space of Mg-Al LDH during coprecipitation of drug LDH conjugate in nitrogen atmosphere. The nanopowders synthesised were in the size range between 25 to 90 nm with an average particle size of 55 nm. XRD analysis proved that there is an increase in d003 spacing from 7.89 Å for pristine LDH to 14.71 Å for ibuprofen intercalated LDH due to the intercalation of bigger ibuprofen molecule in the interlayer space of LDH. FTIR analysis showed hydroxyl and carbonyl stretching of ibuprofen in LDH-IBU sample confirming the intercalation of ibuprofen in the interlayer structure of LDH. The drug release study in phosphate buffer solution at pH 7.4 using UV-Vis spectroscopy demonstrated that 50 % drug molecules were released in 15 hours and more than 85 % release was achieved after 36 hours.

  18. Colorimetry as Quality Control Tool for Individual Inkjet-Printed Pediatric Formulations.

    Science.gov (United States)

    Wickström, Henrika; Nyman, Johan O; Indola, Mathias; Sundelin, Heidi; Kronberg, Leif; Preis, Maren; Rantanen, Jukka; Sandler, Niklas

    2017-02-01

    Printing technologies were recently introduced to the pharmaceutical field for manufacturing of drug delivery systems. Printing allows on demand manufacturing of flexible pharmaceutical doses in a personalized manner, which is critical for a successful and safe treatment of patient populations with specific needs, such as children and the elderly, and patients facing multimorbidity. Printing of pharmaceuticals as technique generates new demands on the quality control procedures. For example, rapid quality control is needed as the printing can be done on demand and at the point of care. This study evaluated the potential use of a handheld colorimetry device for quality control of printed doses of vitamin Bs on edible rice and sugar substrates. The structural features of the substrates with and without ink were also compared. A multicomponent ink formulation with vitamin B 1 , B 2 , B 3 , and B 6 was developed. Doses (4 cm 2 ) were prepared by applying 1-10 layers of yellow ink onto the white substrates using thermal inkjet technology. The colorimetric method was seen to be viable in detecting doses up to the 5th and 6th printed layers until color saturation of the yellow color parameter (b*) was observed on the substrates. Liquid chromatography mass spectrometry was used as a reference method for the colorimetry measurements plotted against the number of printed layers. It was concluded that colorimetry could be used as a quality control tool for detection of different doses. However, optimization of the color addition needs to be done to avoid color saturation within the planned dose interval.

  19. A novel and alternative approach to controlled release drug delivery system based on solid dispersion technique

    Directory of Open Access Journals (Sweden)

    Tapan Kumar Giri

    2012-12-01

    Full Text Available The solid dispersion method was originally used to improve the dissolution properties and the bioavailability of poorly water soluble drugs by dispersing them into water soluble carriers. In addition to the above, dissolution retardation through solid dispersion technique using water insoluble and water swellable polymer for the development of controlled release dosage forms has become a field of interest in recent years. Development of controlled release solid dispersion has a great advantage for bypassing the risk of a burst release of drug; since the structure of the solid dispersion is monolithic where drug molecules homogeneously disperse. Despite the remarkable potential and extensive research being conducted on controlled release solid dispersion system, commercialization and large scale production are limited. The author expects that recent technological advances may overcome the existing limitations and facilitate the commercial utilization of the techniques for manufacture of controlled release solid dispersions. This article begins with an overview of the different carriers being used for the preparation of controlled release solid dispersion and also different techniques being used for the purpose. Kinetics of drug release from these controlled release solid dispersions and the relevant mathematical modeling have also been reviewed in this manuscript.

  20. Controlled Release Kinetics in Hydroxy Double Salts: Effect of Host Anion Structure

    Directory of Open Access Journals (Sweden)

    Stephen Majoni

    2014-01-01

    Full Text Available Nanodimensional layered metal hydroxides such as layered double hydroxides (LDHs and hydroxy double salts (HDSs can undergo anion exchange reactions releasing intercalated anions. Because of this, these metal hydroxides have found applications in controlled release delivery of bioactive species such as drugs and pesticides. In this work, isomers of hydroxycinnamate were used as model compounds to systematically explore the effects of anion structure on the rate and extent of anion release in HDSs. Following intercalation and subsequent release of the isomers, it has been demonstrated that the nature and position of substituent groups on intercalated anions have profound effects on the rate and extent of release. The extent of release was correlated with the magnitude of dipole moments while the rate of reaction showed strong dependence on the extent of hydrogen bonding within the layers. The orthoisomer showed a more sustained and complete release as compared to the other isomers.

  1. Metal cation controls phosphate release in the myosin ATPase.

    Science.gov (United States)

    Ge, Jinghua; Huang, Furong; Nesmelov, Yuri E

    2017-11-01

    Myosin is an enzyme that utilizes ATP to produce a conformational change generating a force. The kinetics of the myosin reverse recovery stroke depends on the metal cation complexed with ATP. The reverse recovery stroke is slow for MgATP and fast for MnATP. The metal ion coordinates the γ phosphate of ATP in the myosin active site. It is accepted that the reverse recovery stroke is correlated with the phosphate release; therefore, magnesium "holds" phosphate tighter than manganese. Magnesium and manganese are similar ions in terms of their chemical properties and the shell complexation; hence, we propose to use these ions to study the mechanism of the phosphate release. Analysis of octahedral complexes of magnesium and manganese show that the partial charge of magnesium is higher than that of manganese and the slightly larger size of manganese ion makes its ionic potential smaller. We hypothesize that electrostatics play a role in keeping and releasing the abstracted γ phosphate in the active site, and the stronger electric charge of magnesium ion holds γ phosphate tighter. We used stable myosin-nucleotide analog complex and Raman spectroscopy to examine the effect of the metal cation on the relative position of γ phosphate analog in the active site. We found that in the manganese complex, the γ phosphate analog is 0.01 nm further away from ADP than in the magnesium complex. We conclude that the ionic potential of the metal cation plays a role in the retention of the abstracted phosphate. © 2017 The Protein Society.

  2. Operational control of material release and discharges from nuclear power plant

    International Nuclear Information System (INIS)

    Szabo, I. C.; Ranga, T.; Daroczi, L.; Deme, S.; Kerekes, A.

    2003-01-01

    The operational control of radioactive materials during atmospheric release and aquatic discharge from nuclear power plant is a licensing criterion for NPPs. Originally at the Paks NPP the release control was based on activity limits for four groups of elements. These groups were noble gases, long living radio-aerosols, radioiodine and radiostrontium for atmospheric release and specified activity limit for beta emitters, strontium and tritium for aquatic discharge into Danube. These groups were controlled with proper sampling and/or measuring instrumentation. The limit for atmospheric release was given as a 30-day moving average, for liquid discharges the annual limit was stipulated. The new release and discharge limitation system is based on the environmental dose limitation. The dose constraint for Paks NPP is 90 Sv/year of the critical group for all release pathways and the investigation dose limit is equal to 27 Sv/year. The regulation did not subdivide the dose limit for atmospheric and liquid components but for operational control subdivision of dose limits for atmospheric release and aquatic discharge and shorter time period (one day-one month) seems to be useful. The subdivision can be based on past release data and/or previous activity limits. To satisfy dose below the investigation dose limit there should be a proper operation control level for each separately measured component and pathway belonging to reasonable time interval significantly shorter than one year. The main task of the NPP staff is elaboration of reasonable control levels and reference time intervals for different radionuclide and element groups to be used in operational control. Operational control levels are based on measured daily or monthly release rates. In case of noble gases, aerosols and iodine the daily release rates have several sharp peaks per year. Operational control levels give opportunity to detect these peaks for internal investigation purposes. Investigation release limits

  3. Application of controlled release technology to uranium mill tailings stabilization

    International Nuclear Information System (INIS)

    Burton, F.G.; Cataldo, D.A.; Cline, J.F.; Skiens, W.E.

    1981-01-01

    A trifluralin (herbicide) releasing device was developed with a theoretical effective lifetime in excess of 100 years. When placed in a layer in soil, the PCD system will prevent root penetration through that layer without harming the overlying vegetation. Equilibrium concentrations of trifluralin in soil can be adjusted (along with the theoretical life of the device) to suit specific needs. The present system was designed specifically to protect the asphalt layer or clay/aggregate barriers on uranium mill tailings piles; PCD devices composed of pellets could also be implanted over burial sites for radioactive and/or toxic materials, preventing translocation of those materials to plant shoots, and thence into the biosphere

  4. Budget impact of switching from an immediate-release to a prolonged-release formulation of tacrolimus in renal transplant recipients in the UK based on differences in adherence

    Directory of Open Access Journals (Sweden)

    Muduma G

    2014-03-01

    Full Text Available Gorden Muduma,1 Isaac Odeyemi,1 Jayne Smith-Palmer,2 Richard F Pollock21Astellas Pharma Europe, Chertsey, UK; 2Ossian Health Economics and Communications, Basel, SwitzerlandBackground and aims: Advagraf is a once-daily prolonged-release formulation of tacrolimus with proven noninferiority to Prograf, a twice-daily immediate-release formulation of tacrolimus, in biopsy-proven acute rejection, graft survival and patient survival in renal transplant recipients. Advagraf is associated with improved adherence compared with Prograf, which may ultimately improve long-term outcomes. The present study assessed the budget impact of switching patients from Prograf to Advagraf in the UK.Materials and methods: A budget-impact model was constructed based on published data on acute rejection, graft failure, and mortality in the UK setting. Patients were assumed to convert from Prograf to Advagraf on a 1:1 milligram:milligram basis. In a study comparing the adherence rates between once-daily versus twice-daily formulations of tacrolimus, the proportion of patients taking the prescribed number of daily doses was 88.2% in Advagraf patients and 78.8% in Prograf patients. The model applied a relative risk of graft failure of 3.47 to nonadherent patients based on data from a 2004 meta-analysis (based on graft-failure rates of 1.3%–40.0% in adherent patients, compared with 6.1%–100% in nonadherent patients. Cost data were taken from the March 2013 British National Formulary and 2012–2013 National Health Service tariff information. The analysis was performed over a 5-year time horizon and future costs were not discounted, in line with International Society for Pharmacoeconomics and Outcomes Research guidelines.Results: Over a 5-year time horizon, the mean cost per patient (including tacrolimus, concomitant immunosuppressive medications, dialysis after graft failure, and treatment for acute rejection was £29,328 (standard deviation [SD] £2,844 for Advagraf

  5. Application of Electrostatic Extrusion - Flavour Encapsulation and Controlled Release.

    Science.gov (United States)

    Manojlovic, Verica; Rajic, Nevenka; Djonlagic, Jasna; Obradovic, Bojana; Nedovic, Viktor; Bugarski, Branko

    2008-03-03

    The subject of this study was the development of flavour alginate formulationsaimed for thermally processed foods. Ethyl vanilline was used as the model flavourcompound. Electrostatic extrusion was applied for the encapsulation of ethyl vanilline inalginate gel microbeads. The obtained microbeads with approx. 10 % w/w of ethylvanilline encapsulated in about 2 % w/w alginate were uniformly sized spheres of about450 μm. Chemical characterization by H-NMR spectroscopy revealed that the alginateused in this study had a high content (67 %) of guluronic residues and was rich in GG diadblocks (FGG = 55%) and thus presented a high-quality immobilisation matrix. The thermalbehaviour of alginate beads encapsulating ethyl vanilline was investigated bythermogravimetric (TG) and differential scanning calorimetry measurements (TG-DSC)under heating conditions which mimicked usual food processing to provide informationabout thermal decomposition of alginate matrix and kinetics of aroma release. Two wellresolved weight losses were observed. The first one was in the 50-150 °C temperaturerange with the maximum at approx. 112 °C, corresponding to the dehydration of thepolymer network. The second loss in the 220-325 °C temperature range, with a maximumat ~ 247 °C corresponded to the release of vanilline. The obtained results indicate that up to230 °C most of the vanilline remained intacta, while prolonged heating at elevatedtemperatures led to the entire loss of the aroma compound.

  6. Use of fibrin sealants for the localized, controlled release of cefazolin

    Science.gov (United States)

    Tredwell, Stephen; Jackson, John K.; Hamilton, Donald; Lee, Vivian; Burt, Helen M.

    2006-01-01

    Background Fibrin sealants are used increasingly in surgery to reduce bleeding and improve wound healing. They have great potential as biocompatible, biodegradable drug delivery systems, because the sealant may adhere to the target tissue and allow controlled release of the drug over an extended period. We investigated the encapsulation, stability and controlled release of erythromycin and cefazolin from Beriplast fibrin sealants (Aventis Behring Canada). Methods Drug-loaded clots were cast in glass vials and allowed to set. We observed the clots for drug precipitation and aggregation, and we assessed the effect of drug encapsulation on clot strength. Drug stability and release from the clots in phosphate buffered saline (PBS) was quantified by ultraviolet and visible violet absorbance spectroscopy and high-performance liquid chromatography. Results Erythromycin was found to release slowly from the fibrin clots over the first 2 hours but then degrade rapidly. Cefazolin was found to be very stable in clots in PBS (97% stable at 2 d and 93% stable at 5 d). The drug released in a controlled manner over 2 days, with most being released during the first day. The dose of drug released could be varied by changing the amount placed in the thrombin solution. Clot thickness had no effect on the rate of cefazolin release. Conclusion Overall, the 2-day release profile and the excellent stability of the drug suggest that cefazolin-loaded fibrin sealants may offer an effective route of postoperative antibiotic delivery. PMID:17152573

  7. Control of chemical usage in drilling fluid formulations to minimize discharge to the environment

    International Nuclear Information System (INIS)

    Geehan, T.; Forbes, D.M.; Moore, D.J.

    1991-01-01

    A reduction in the environmental footprint from drilling operations can best be addressed by minimizing the sources of that footprint. One of the principal sources of possible environmental damage is drilling fluid and drill solid discharge. The toxicity as measured by acute and/or sub-chronic testing regimes depends on the composition of the drilling fluid/drill solids slurry. The trend within the drilling fluids industry has been to direct its attention to finding drilling fluid products which alone and in combination are considered to be non-toxic as determined by required testing procedures. This paper goes on to describe a parallel approach in which the total volume of chemicals discharged (whether considered toxic or benign) is reduced. Both approaches can be considered complimentary. The reduction in volume/mass of discharge is achieved by increased monitoring of both drilling fluid properties, composition and solids control operational efficiency. Additionally the increased monitoring allows less complicated formulations to be used to produce the desired drilling fluid properties; as specified by the mud programme. The need for more complete rigsite monitoring packages, will become more important as oilbased muds are replaced by waterbased mud for difficult drilling situations with stricter environmental regulations on discharge of drilling waste. The paper also outlines how the optimization of the drilling fluid operation was linked to a reduction in drilling fluid costs at the same time maintaining drilling efficiency

  8. Limited mobility of target pests crucially lowers controllability when sterile insect releases are spatiotemporally biased.

    Science.gov (United States)

    Ikegawa, Yusuke; Himuro, Chihiro

    2017-05-21

    The sterile insect technique (SIT) is a genetic pest control method wherein mass-reared sterile insects are periodically released into the wild, thereby impeding the successful reproduction of fertile pests. In Okinawa Prefecture, Japan, the SIT has been implemented to eradicate the West Indian sweet potato weevil Euscepes postfasciatus (Fairmaire), which is a flightless agricultural pest of sweet potatoes. It is known that E. postfasciatus is much less mobile than other insects to which the SIT has been applied. However, previous theoretical studies have rarely examined effects of low mobility of target pests and variation in the spatiotemporal evenness of sterile insect releases. To theoretically examine the effects of spatiotemporal evenness on the regional eradication of less mobile pests, we constructed a simple two-patch population model comprised of a pest and sterile insect moving between two habitats, and numerically simulated different release strategies (varying the number of released sterile insects and release intervals). We found that spatially biased releases allowed the pest to spatially escape from the sterile insect, and thus intensively lowered its controllability. However, we showed that the temporally counterbalancing spatially biased releases by swapping the number of released insects in the two habitats at every release (called temporal balancing) could greatly mitigate this negative effect and promote the controllability. We also showed that the negative effect of spatiotemporally biased releases was a result of the limited mobility of the target insect. Although directed dispersal of the insects in response to habitats of differing quality could lower the controllability in the more productive habitat, the temporal balancing could promote and eventually maximize the controllability as released insects increased. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Analgesic and anti-inflammatory controlled-released injectable microemulsion: Pseudo-ternary phase diagrams, in vitro, ex vivo and in vivo evaluation.

    Science.gov (United States)

    Pineros, Isabel; Slowing, Karla; Serrano, Dolores R; de Pablo, Esther; Ballesteros, Maria Paloma

    2017-04-01

    Development of analgesic and anti-inflammatory controlled-released injectable microemulsions utilising lysine clonixinate (LC) as model drug and generally regarded as safe (GRAS) excipients. Different microemulsions were optimised through pseudo-ternary phase diagrams and characterised measuring droplet size, viscosity, ex vivo haemolytic activity and in vitro drug release. The anti-inflammatory and analgesic activity was tested in mice (Hot plate test) and rats (Carrageenan-induced paw edema test) respectively and their activity was compared to an aqueous solution of LC salt. The aqueous solution showed a faster and shorter response whereas the optimised microemulsion increased significantly (p<0.01) the potency and duration of the analgesic and anti-inflammatory activity after deep intramuscular injection. The droplet size and the viscosity were key factors to control the drug release from the systems and enhance the effect of the formulations. The microemulsion consisting of Labrafil®/Lauroglycol®/Polysorbate 80/water with LC (56.25/18.75/15/10, w/w) could be a promising formulation after buccal surgery due to its ability to control the drug release and significantly achieve greater analgesic and anti-inflammatory effect over 24h. Copyright © 2016. Published by Elsevier B.V.

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

    Directory of Open Access Journals (Sweden)

    Rukiye Yavaşer

    2016-08-01

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

  11. A nonlinear model predictive control formulation for obstacle avoidance in high-speed autonomous ground vehicles in unstructured environments

    Science.gov (United States)

    Liu, Jiechao; Jayakumar, Paramsothy; Stein, Jeffrey L.; Ersal, Tulga

    2018-06-01

    This paper presents a nonlinear model predictive control (MPC) formulation for obstacle avoidance in high-speed, large-size autono-mous ground vehicles (AGVs) with high centre of gravity (CoG) that operate in unstructured environments, such as military vehicles. The term 'unstructured' in this context denotes that there are no lanes or traffic rules to follow. Existing MPC formulations for passenger vehicles in structured environments do not readily apply to this context. Thus, a new nonlinear MPC formulation is developed to navigate an AGV from its initial position to a target position at high-speed safely. First, a new cost function formulation is used that aims to find the shortest path to the target position, since no reference trajectory exists in unstructured environments. Second, a region partitioning approach is used in conjunction with a multi-phase optimal control formulation to accommodate the complicated forms the obstacle-free region can assume due to the presence of multiple obstacles in the prediction horizon in an unstructured environment. Third, the no-wheel-lift-off condition, which is the major dynamical safety concern for high-speed, high-CoG AGVs, is ensured by limiting the steering angle within a range obtained offline using a 14 degrees-of-freedom vehicle dynamics model. Thus, a safe, high-speed navigation is enabled in an unstructured environment. Simulations of an AGV approaching multiple obstacles are provided to demonstrate the effectiveness of the algorithm.

  12. Releases of natural enemies in Hawaii since 1980 for classical biological control of weeds

    Science.gov (United States)

    P. Conant; J. N. Garcia; M. T. Johnson; W. T. Nagamine; C. K. Hirayama; G. P. Markin; R. L. Hill

    2013-01-01

    A comprehensive review of biological control of weeds in Hawaii was last published in 1992, covering 74 natural enemy species released from 1902 through 1980. The present review summarizes releases of 21 natural enemies targeting seven invasive weeds from 1981 to 2010. These projects were carried out by Hawaii Department of Agriculture (HDOA), USDA Forest Service (USFS...

  13. Using polymer-coated controlled-release fertilizers in the nursery and after outplanting

    Science.gov (United States)

    Thomas D. Landis; R. Kasten Dumroese

    2009-01-01

    Controlled-release fertilizers (CRF) are the newest and most technically advanced way of supplying mineral nutrients to nursery crops. Compared to conventional fertilizers, their gradual pattern of nutrient release better meets plant needs, minimizes leaching, and therefore improves fertilizer use efficiency. In our review of the literature, we found many terms used...

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

    Science.gov (United States)

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

    2003-07-01

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

  15. A double-blind placebo-controlled study of controlled release fluvoxamine for the treatment of generalized social anxiety disorder.

    Science.gov (United States)

    Westenberg, Herman G M; Stein, Dan J; Yang, Haichen; Li, David; Barbato, Luigi M

    2004-02-01

    This was a randomized double-blind placebo-controlled multicenter study to assess the efficacy, safety, and tolerability of fluvoxamine in a controlled release (CR) formulation for treatment of generalized social anxiety disorder (GSAD). A total of 300 subjects with GSAD were randomly assigned to receive either fluvoxamine CR (N = 149) or placebo (N = 151) for 12 weeks. Mean changes from baseline to end point in Liebowitz Social Anxiety Scale (LSAS), Clinical Global Impression Severity of Illness Scale (CGI-S), Sheehan Disability Scale (SDS), as well as the mean end point scores in Clinical Global Impression Improvement Scale (CGI-I) and Patient Global Impression of Improvement Scale (PGI) were compared between the fluvoxamine CR and placebo treatment groups. Arizona Sexual Experience Scale (ASEX), adverse event, and other safety parameters were also assessed. The results demonstrated that fluvoxamine CR was significantly superior to placebo in decreasing LSAS total score (primary measure) starting at week 4. At end point, there was a mean change from baseline of -36.1 +/- 2.7 (37% reduction) in the LSAS total score in the fluvoxamine CR group compared with -27.3 +/- 2.4 (28% reduction) in the placebo group (P = 0.020 for mean change). Fluvoxamine CR was also significantly superior to placebo in SDS, CGI-S, CGI-I at end point (secondary measures). When compared with placebo, fluvoxamine CR did not cause any significant weight gain or clinically significant sexual dysfunction as measured by ASEX. In summary, fluvoxamine CR is an efficacious, safe, and well-tolerated treatment of generalized social anxiety disorder.

  16. Soil application of formulated Metarhizium brunneum F52 (Hypocreales: Clavicipitaceae) containing microsclerotia controls eggs of Aedes aegypti (Diptera: Culicidae)

    Science.gov (United States)

    We evaluated the potential of a granular formulation of Metarhizium brunneum F52 containing microsclerotia (MbMSc granules) for control of Aedes aegypti (L.) by targeting eggs. MbMSc granules produced infective conidia within 14 days after application to moist potting soil, producing 5.9 × 10**5, 2....

  17. Control Room Habitability for Accidental Sulfuric Acid Release

    International Nuclear Information System (INIS)

    Cho, Sungmin; Lee, Heedo; Song, Dongsoo

    2006-01-01

    The 10 CFR 50 Appendix A Criterion 19, 'Control Room', requires that a control room be provided from which actions can be taken to operate the nuclear power unit safely under normal conditions and to maintain it in a safe condition under accident conditions. For compliance with the requirement, the control room of a nuclear power plant should be appropriately protected from hazardous chemicals that may be discharged as a result of equipment failures, operator errors, or events and conditions outside the control of the nuclear power plant. We have excluded sulfuric acid from a target of estimation for control room habitability merely because its boiling point is too high; qualitative analysis in this paper shows that we can exclude sulfuric acid from the target of habitability estimation

  18. Munc13 controls the location and efficiency of dense-core vesicle release in neurons.

    Science.gov (United States)

    van de Bospoort, Rhea; Farina, Margherita; Schmitz, Sabine K; de Jong, Arthur; de Wit, Heidi; Verhage, Matthijs; Toonen, Ruud F

    2012-12-10

    Neuronal dense-core vesicles (DCVs) contain diverse cargo crucial for brain development and function, but the mechanisms that control their release are largely unknown. We quantified activity-dependent DCV release in hippocampal neurons at single vesicle resolution. DCVs fused preferentially at synaptic terminals. DCVs also fused at extrasynaptic sites but only after prolonged stimulation. In munc13-1/2-null mutant neurons, synaptic DCV release was reduced but not abolished, and synaptic preference was lost. The remaining fusion required prolonged stimulation, similar to extrasynaptic fusion in wild-type neurons. Conversely, Munc13-1 overexpression (M13OE) promoted extrasynaptic DCV release, also without prolonged stimulation. Thus, Munc13-1/2 facilitate DCV fusion but, unlike for synaptic vesicles, are not essential for DCV release, and M13OE is sufficient to produce efficient DCV release extrasynaptically.

  19. Chitosan-based nanocomplexes for simultaneous loading, burst reduction and controlled release of doxorubicin and 5-fluorouracil.

    Science.gov (United States)

    Di Martino, Antonio; Kucharczyk, Pavel; Capakova, Zdenka; Humpolicek, Petr; Sedlarik, Vladimir

    2017-09-01

    In this work, nanocomplexes based on chitosan grafted by carboxy-modified polylactic acid (SPLA) were prepared with the aim of loading simultaneously two anticancer drugs - doxorubicin and 5-fluorouracil, as well as to control their release, reduce the initial burst and boost cytotoxicity. The SPLA was prepared by a polycondensation reaction, using pentetic acid as the core molecule, and linked to the chitosan backbone through a coupling reaction. Nanocomplexes loaded with both drugs were formulated by the polyelectrolyte complexation method. The structure of the SPLA was characterized by 1 H NMR, while the product CS-SPLA was analyzed by FTIR-ATR to prove the occurrence of the reaction. Results showed that the diameters and ζ-potential of the nanocomplexes fall in the range 120-200nm and 20-37mV, respectively. SEM and TEM analysis confirmed the spherical shape and dimensions of the nanocomplexes. The presence of hydrophobic side chain SPLA did not influence the encapsulation efficiency of the drugs but strongly reduced the initial burst and prolonged release over time compared to unmodified chitosan. MS analysis showed that no degradation or interactions between the drugs and carrier were exhibited after loading or 24h of release had taken place, confirming the protective role of the nanocomplexes. In vitro tests demonstrated an increase in the cytotoxicity of the drugs when loaded in the prepared carriers. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-06-01

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

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  2. Effectiveness of the association of 2 probiotic strains formulated in a slow release vaginal product, in women affected by vulvovaginal candidiasis: a pilot study.

    Science.gov (United States)

    Vicariotto, Franco; Del Piano, Mario; Mogna, Luca; Mogna, Giovanni

    2012-10-01

    vaginal tablets (ActiCand 30 product). The main endpoint was the assessment of the establishment and maintenance of a barrier effect against Candida yeasts in women suffering from VVC. Thirty female subjects who were diagnosed with VVC by both microscopic examination and yeast culture were enrolled in the study and directed to apply a vaginal tablet once a day for 7 consecutive nights, followed by 1 tablet every 3 nights for a further 3-week application (acute phase) and, finally, 1 tablet per week to maintain a long-term vaginal colonization against possible recurrences. A medical examination of each patient was performed at enrollment (d₀), at the end of the first 4 weeks of treatment (d₂₈), and at the end of the second month of relapse prevention (d₅₆). The visual and microscopic examination was always accompanied by microbiological analyses of vaginal swabs to assess the presence of Candida. A statistical comparison was made between d₂₈, or d₅₆, and d0, and between d₅₆ and d₂₈ to quantify the efficacy against possible recurrences. The administration of the product ActiCand 30 was able to significantly solve Candida yeast symptoms after 28 days in 26 patients out of 30 (corresponding to 86.6%, Pvaginal microbiota and adhesion of the mucosa to the epithelial cells. The special formulation of ActiCand 30, consisting of slow release effervescent vaginal tablets, is able to mediate 2 types of barrier effects, the first represented by the formation of an anaerobic environment due to the release of CO₂ and the second guaranteed by the colonization and adhesion to the vaginal epithelium of the 2 probiotics L. fermentum LF10 and L. acidophilus LA02.

  3. EMERGENCY RESPONSE PROCEDURES FOR CONTROL OF HAZARDOUS SUBSTANCE RELEASES

    Science.gov (United States)

    Information is provided for selecting the best spill stabilization controls for hazardous substances regulated by the Comprehensive Enviromental Response, Compensation and Liability Act of 1980 (CERCLA). Information is also provided on the onsite assessment of spill severity, app...

  4. Controlled release and angiotensin-converting enzyme inhibition properties of an antihypertensive drug based on a perindopril erbumine-layered double hydroxide nanocomposite

    Directory of Open Access Journals (Sweden)

    Hussein Al Ali SH

    2012-04-01

    Full Text Available Samer Hasan Hussein Al Ali1, Mothanna Al-Qubaisi2, Mohd Zobir Hussein1,3, Maznah Ismail2,4, Zulkarnain Zainal1, Muhammad Nazrul Hakim51Department of Chemistry, Faculty of Science, 2Laboratory of Molecular Biomedicine, Institute of Bioscience, 3Advanced Materials and Nanotechnology Laboratory, Institute of Advanced Technology, 4Department of Nutrition and Dietetics, Faculty of Medicine and Health Science, 5Department of Biomedical Science, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Serdang, Selangor, MalaysiaBackground: The intercalation of perindopril erbumine into Zn/Al-NO3-layered double hydroxide resulted in the formation of a host-guest type of material. By virtue of the ion-exchange properties of layered double hydroxide, perindopril erbumine was released in a sustained manner. Therefore, this intercalated material can be used as a controlled-release formulation.Results: Perindopril was intercalated into the interlayers and formed a well ordered, layered organic-inorganic nanocomposite. The basal spacing of the products was expanded to 21.7 Å and 19.9 Å by the ion-exchange and coprecipitation methods, respectively, in a bilayer and a monolayer arrangement, respectively. The release of perindopril from the nanocomposite synthesized by the coprecipitation method was slower than that of its counterpart synthesized by the ion-exchange method. The rate of release was governed by pseudo-second order kinetics. An in vitro antihypertensive assay showed that the intercalation process results in effectiveness similar to that of the antihypertensive properties of perindopril.Conclusion: Intercalated perindopril showed better thermal stability than its free counterpart. The resulting material showed sustained-release properties and can therefore be used as a controlled-release formulation.Keywords: perindopril erbumine, layered double hydroxides, ion-exchange, coprecipitation, sustained release, angiotensin-converting enzyme

  5. Order release strategies to control outsourced operations in a supply chain

    NARCIS (Netherlands)

    Boulaksil, Y.; Fransoo, J.C.

    2007-01-01

    In this paper, we propose and compare three different order release strategies to plan and control outsourced operations in a supply chian where the contract manfacturer is producing different variants of a certain product.

  6. Organosilane functionalization of halloysite nanotubes for enhanced loading and controlled release

    International Nuclear Information System (INIS)

    Yuan Peng; Southon, Peter D; Kepert, Cameron J; Liu Zongwen

    2012-01-01

    The surfaces of naturally occurring halloysite nanotubes were functionalized with γ-aminopropyltriethoxysilane (APTES), which was found to have a substantial effect on the loading and subsequent release of a model dye molecule. APTES was mostly anchored at the internal lumen surface of halloysite through covalent grafting, forming a functionalized surface covered by aminopropyl groups. The dye loading of the functionalized halloysite was 32% greater than that of the unmodified sample, and the release from the functionalized halloysite was dramatically prolonged as compared to that from the unmodified one. Dye release was prolonged at low pH and the release at pH 3.5 was approximately three times slower than that at pH 10.0. These results demonstrate that organosilane functionalization makes pH an external trigger for controlling the loading of guest on halloysite and the subsequent controlled release. (paper)

  7. Organosilane functionalization of halloysite nanotubes for enhanced loading and controlled release.

    Science.gov (United States)

    Yuan, Peng; Southon, Peter D; Liu, Zongwen; Kepert, Cameron J

    2012-09-21

    The surfaces of naturally occurring halloysite nanotubes were functionalized with γ-aminopropyltriethoxysilane (APTES), which was found to have a substantial effect on the loading and subsequent release of a model dye molecule. APTES was mostly anchored at the internal lumen surface of halloysite through covalent grafting, forming a functionalized surface covered by aminopropyl groups. The dye loading of the functionalized halloysite was 32% greater than that of the unmodified sample, and the release from the functionalized halloysite was dramatically prolonged as compared to that from the unmodified one. Dye release was prolonged at low pH and the release at pH 3.5 was approximately three times slower than that at pH 10.0. These results demonstrate that organosilane functionalization makes pH an external trigger for controlling the loading of guest on halloysite and the subsequent controlled release.

  8. Pharmacokinetic comparison of sustained- and immediate-release oral formulations of cilostazol in healthy Korean subjects: a randomized, open-label, 3-part, sequential, 2-period, crossover, single-dose, food-effect, and multiple-dose study.

    Science.gov (United States)

    Lee, Donghwan; Lim, Lay Ahyoung; Jang, Seong Bok; Lee, Yoon Jung; Chung, Jae Yong; Choi, Jong Rak; Kim, Kiyoon; Park, Jin Woo; Yoon, Hosang; Lee, Jaeyong; Park, Min Soo; Park, Kyungsoo

    2011-12-01

    A sustained-release (SR) formulation of cilostazol was recently developed in Korea and was expected to yield a lower C(max) and a similar AUC to the immediate-release (IR) formulation. The goal of the present study was to compare the pharmacokinetic profiles of a newly developed SR formulation and an IR formulation of cilostazol after single- and multiple-dose administration and to evaluate the influence of food in healthy Korean subjects. This study was developed as part of a product development project at the request of the Korean regulatory agency. This was a randomized, 3-part, sequential, open-label, 2-period crossover study. Each part consisted of different subjects between the ages of 19 and 55 years. In part 1, each subject received a single dose of SR (200 mg × 1 tablet, once daily) and IR (100 mg × 2 tablets, BID) formulations of cilostazol orally 7 days apart in a fasted state. In part 2, each subject received a single dose of the SR (200 mg × 1 tablet, once daily) formulation of cilostazol 7 days apart in a fasted and a fed state. In part 3, each subject received multiple doses of the 2 formulations for 8 consecutive days 21 days apart. Blood samples were taken for 72 hours after the dose. Cilostazol pharmacokinetics were determined for both the parent drug and its metabolites (OPC-13015 and OPC-13213). Adverse events were evaluated through interviews and physical examinations. Among the 92 enrolled subjects (66 men, 26 women; part 1, n = 26; part 2, n = 26; part 3, n = 40), 87 completed the study. In part 1, all the primary pharmacokinetic parameters satisfied the criterion for assumed bioequivalence both in cilostazol and its metabolites, yielding 90% CI ratios of 0.9624 to 1.2323, 0.8873 to 1.1208, and 0.8919 to 1.1283 for C(max) and 0.8370 to 1.0134, 0.8204 to 0.9807, and 0.8134 to 0.9699 for AUC(0-last) of cilostazol, OPC-13015, and OPC-13213, respectively. In part 2, food intake increased C(max) and AUC significantly (P food and 23 with a high

  9. Metal-organic framework tethering PNIPAM for ON-OFF controlled release in solution.

    Science.gov (United States)

    Nagata, Shunjiro; Kokado, Kenta; Sada, Kazuki

    2015-05-21

    A smart metal-organic framework (MOF) exhibiting controlled release was achieved by modification with a thermoresponsive polymer (PNIPAM) via a surface-selective post-synthetic modification technique. Simple temperature variation readily switches "open" (lower temperature) and "closed" (higher temperature) states of the polymer-modified MOF through conformational change of PNIPAM grafted onto the MOF, resulting in controlled release of the included guest molecules such as resorufin, caffeine, and procainamide.

  10. Laser-activated nano-biomaterials for tissue repair and controlled drug release

    International Nuclear Information System (INIS)

    Matteini, P; Ratto, F; Rossi, F; Pini, R

    2014-01-01

    We present recent achievements of minimally invasive welding of biological tissue and controlled drug release based on laser-activated nano-biomaterials. In particular, we consider new advancements in the biomedical application of near-IR absorbing gold nano-chromophores as an original solution for the photothermal repair of surgical incisions and as nanotriggers of controlled drug release from hybrid biopolymer scaffolds. (laser biophotonics)

  11. Releasable Kinetic Energy-Based Inertial Control of a DFIG Wind Power Plant

    DEFF Research Database (Denmark)

    Lee, Jinsik; Muljadi, Eduard; Sørensen, Poul Ejnar

    2016-01-01

    Wind turbine generators (WTGs) in a wind power plant (WPP) contain different levels of releasable kinetic energy (KE) because of the wake effects. This paper proposes a releasable KE-based inertial control scheme for a doubly fed induction generator (DFIG) WPP that differentiates the contributions....... The proposed scheme adjusts the two loop gains in a DFIG controller depending on its rotor speed so that a DFIG operating at a higher rotor speed releases more KE. The performance of the proposed scheme was investigated under various wind conditions. The results clearly indicate that the proposed scheme...

  12. Controlled-release approaches towards the chemotherapy of tuberculosis

    Directory of Open Access Journals (Sweden)

    Saifullah B

    2012-10-01

    Full Text Available Bullo Saifullah,1 Mohd Zobir B Hussein,1,2 Samer Hasan Hussein Al Ali11Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 2Advanced Materials and Nanotechnology Laboratory, Institute of Advanced Technology, Universiti Putra Malaysia, Serdang, Selangor, MalaysiaAbstract: Tuberculosis (TB, caused by the bacteria Mycobacterium tuberculosis, is notorious for its lethality to humans. Despite technological advances, the tubercle bacillus continues to threaten humans. According to the World Health Organization's 2011 global report on TB, 8.8 million cases of TB were reported in 2010, with a loss of 1.7 million human lives. As drug-susceptible TB requires long-term treatment of between 6 and 9 months, patient noncompliance remains the most important reason for treatment failure. For multidrug-resistant TB, patients must take second-line anti-TB drugs for 18–24 months and many adverse effects are associated with these drugs. Drug-delivery systems (DDSs seem to be the most promising option for advancement in the treatment of TB. DDSs reduce the adverse effects of drugs and their dosing frequency as well as shorten the treatment period, and hence improve patient compliance. Further advantages of these systems are that they target the disease area, release the drugs in a sustained manner, and are biocompatible. In addition, targeted delivery systems may be useful in dealing with extensively drug-resistant TB because many side effects are associated with the drugs used to cure the disease. In this paper, we discuss the DDSs developed for the targeted and slow delivery of anti-TB drugs and their possible advantages and disadvantages.Keywords: Mycobacterium tuberculosis, drug-delivery system, targeted delivery, anti-TB drug, TB, patient compliance

  13. PH-triggered micellar membrane for controlled release microchips

    KAUST Repository

    Yang, Xiaoqiang; Moosa, Basem; Deng, Lin; Zhao, Lan; Khashab, Niveen M.

    2011-01-01

    A pH-responsive membrane based on polystyrene-b-poly(4-vinylpyridine) (PS-b-P4VP) block copolymer was developed on a model glass microchip as a promising controlled polymer delivery system. The PS-b-P4VP copolymer assembles into spherical and

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

    International Nuclear Information System (INIS)

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