WorldWideScience

Sample records for sustained trans-dermal release

  1. Sustained release of radioprotective agents

    International Nuclear Information System (INIS)

    Shani, J.

    1980-11-01

    New pharmaceutical formulations for the sustained release into the G.I. tract of radioprotective agents have been developed by the authors. The experimental method initially consisted in the production of methylcellulose microcapsules. This method failed apparently because of the premature ''explosion'' of the microcapsules and the consequent premature release of massive amounts of the drug. A new method has been developed which consists in drying and pulverising cysteamine and cysteine preparations, mixing them in various proportions with stearic acid and ethylcellulose as carriers. The mixture is then compressed into cylindrical tablets at several pressure values and the leaching rate of the radioprotective agents is then measured by spectrophotometry. The relation between the concentration of the active drug and its rate of release, and the effect on the release rate of the pressure applied to the tablet during its formation were also investigated. Results indicating that the release rate was linearly related to the square root of ''t'' seem to be in agreement with what is predictable, according to Higuchi's equation, save for the very initial and terminal phases. A clear correlation was also established between the stearic acid/ethylcellulose ratios and the release of 20% cysteine, namely a marked decrease in the rate of cysteine release was observed with increasing concentrations of stearic acid. Finally, it was observed that a higher formation pressure results in quicker release of the drug

  2. DEVELOPMENT OF SUSTAINED RELEASE TABLETS ...

    African Journals Online (AJOL)

    2013-12-31

    Dec 31, 2013 ... The SR dosage forms that release drugs pH independently in .... were determined; Post compression parameters such as weight variation test, hardness, ... Based on the ICH guidelines 12, the stability studies were carried out ...

  3. 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 ...

  4. Sustained-release progesterone vaginal suppositories 1--development of sustained-release granule--.

    Science.gov (United States)

    Nakayama, Ayako; Sunada, Hisakazu; Okamoto, Hirokazu; Furuhashi, Kaoru; Ohno, Yukiko; Ito, Mikio

    2009-02-01

    Progesterone (P) is an important hormone for the establishment of pregnancy, and its administration is useful for luteal insufficiency. Considering the problems of commercially available oral and injection drugs, hospital-formulated vaginal suppositories are clinically used. However, since the half-life of P suppositories is short, it is difficult to maintain its constant blood concentration. To sustain drug efficacy and prevent side-effects, we are attempting to develop sustained-release suppositories by examining the degree of sustained-release of active ingredients. In this study, we examined the combinations of granulation methods and release systems for the preparation of sustained-release granules of P, and produced 13 types of sustained-release granules. We also examined the diameter, content, and dissolution of each type of granules, and confirmed that the sustained-release of all types of granules was satisfactory. Among the sustained-release granules, we selected granules with a content and a degree of sustained-release suitable for sustained-release suppositories.

  5. Sustained Release Drug Delivery Applications of Polyurethanes

    Directory of Open Access Journals (Sweden)

    Michael B. Lowinger

    2018-05-01

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

  6. Preparation of venlafaxine hydrochloride sustained-release tablets

    Directory of Open Access Journals (Sweden)

    GUO Lingling

    2013-08-01

    Full Text Available To prepare venlafxine hydrochloride sustained-release tablets.Hydroxypropylmethyl cellulose(HPMC and methyl cellulose(MC were used as main materials to prepare sustained-release tablets of velafaxine hydrochloride and the influence of important factors on in vitro release curves of venlafaxine hydrochloride sustained-release tablets was investigated.Results:The optimal prescription included 100 mg HPMC,25 mg MC,and 2.5% glidant in one tablet prepared with 30kN.The tablets were prepared with the method of wet granulation by NO.16 mesh sieve.The tablets exhibited good sustained-release property in phosphate buffered solution (pH=6.8.The as-prepared venlafxine hydrochloride sustained-release tablets have good sustained-release property.

  7. 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 ...

  8. Based Indomethacin Sustained-Release Tablets

    African Journals Online (AJOL)

    Owing to the short biological half-life of this drug, a sustained ... tendency. This work is aimed at formulating sustained ... Chemie GmbH, Germany), Phospholipon® 90H. (Phospholipid ... weighed out in an analytical balance and dispersed in ...

  9. Development of Sustained-Release Microbeads of Nifedipine and In ...

    African Journals Online (AJOL)

    Methods: Nifedipine microbeads were prepared using sodium alginate and pectin in different ratios by ionic-gelation method. ... Oral sustained release dosage forms provide ... Stability in .... 37oC) in a USP XXII apparatus (Pharma Test,.

  10. Sustained Release of a Watermgoluble tiring from Directly ...

    African Journals Online (AJOL)

    Sustained Release of a Watermgoluble tiring from Directly Compressed Okra Gum Matrix. Tablets. Val). Mill, MA. Gilllllbll'ifl'l' AND KT. ... in near noromorder release of aspirin from the matrix tablets. The results indicate that okra gum is .... porous structure including alteration of the shape and size distribution of the pores.

  11. Preparation and Characterization of Sustained Release Matrix ...

    African Journals Online (AJOL)

    tablet formulations showed a percent drug release ranging from 92.54 ± 1.02 to 98.56 ± 1.26 % at the end of 12 h. Using the spinal injury rat model, ... very common and significant problem. Nonsteroidal anti-inflammatory drugs (NSAIDs) ... animal studies, its mechanism of action involves depressing polysynaptic reflexes ...

  12. DEVELOPMENT OF SUSTAINED RELEASE TABLETS CONTAINING SOLID DISPERSIONS OF BACLOFEN

    Directory of Open Access Journals (Sweden)

    K. H. Janardhana

    2015-07-01

    Full Text Available Sustained release tablets containing solid dispersions granules of a poorly water soluble drug were prepared to investigate the controlled release of the drug. Baclofen was chosen because of its poor water solubility and short elimination half-life. Poloxamer 188 and PEG 6000 were used as solid dispersion carrier. Free flowing solid dispersion granules were prepared by adsorbing the melt of the drug and carriers onto the surface of an adsorbent, Carbopol 934P followed by direct compression with HPMC K4M and HPMC K100 to obtain an solid dispersion loaded sustained release tablets. FTIR studies confirmed that the compatibility of drug and carriers. Differential scanning calorimetry (DSC and X-ray diffraction (XRD revealed partially amorphous structures of the drug in solid dispersion granules. The solid dispersion granules dissolved completely within 30 min, which was much faster than that of pure drug baclofen. The sustained release of baclofen from the solid dispersion containing tablet was achieved for 2 h in gastric fluid (pH 1.2 and for up to 10 h in intestinal fluid (pH 6.8. A combination of solid dispersion techniques using adsorption and sustained release concepts is a promising approach to control the release rate of poorly water-soluble drugs.

  13. DEVELOPMENT OF SUSTAINED RELEASE TABLETS CONTAINING SOLID DISPERSIONS OF BACLOFEN

    Directory of Open Access Journals (Sweden)

    K. H. Janardhana

    2013-12-01

    Full Text Available Sustained release tablets containing solid dispersions granules of a poorly water soluble drug were prepared to investigate the controlled release of the drug. Baclofen was chosen because of its poor water solubility and short elimination half-life. Poloxamer 188 and PEG 6000 were used as solid dispersion carrier. Free flowing solid dispersion granules were prepared by adsorbing the melt of the drug and carriers onto the surface of an adsorbent, Carbopol 934P followed by direct compression with HPMC K4M and HPMC K100 to obtain an solid dispersion loaded sustained release tablets. FTIR studies confirmed that the compatibility of drug and carriers. Differential scanning calorimetry (DSC and X-ray diffraction (XRD revealed partially amorphous structures of the drug in solid dispersion granules. The solid dispersion granules dissolved completely within 30 min, which was much faster than that of pure drug baclofen. The sustained release of baclofen from the solid dispersion containing tablet was achieved for 2 h in gastric fluid (pH 1.2 and for up to 10 h in intestinal fluid (pH 6.8. A combination of solid dispersion techniques using adsorption and sustained release concepts is a promising approach to control the release rate of poorly water-soluble drugs.

  14. Design and development of sustained-release glyburide-loaded

    Indian Academy of Sciences (India)

    The aim of this study was to develop sustained-release glyburide-loaded silica nanoparticles. Silica nanoparticles were synthesized by the sol–gel method using tetra-ethyl ortho-silane as a precursor. Glyburide was successfully entrapped in synthesized silica nanoparticles. To identify the effect of independent variables ...

  15. Statistical Optimization of Sustained Release Venlafaxine HCI Wax Matrix Tablet.

    Science.gov (United States)

    Bhalekar, M R; Madgulkar, A R; Sheladiya, D D; Kshirsagar, S J; Wable, N D; Desale, S S

    2008-01-01

    The purpose of this research was to prepare a sustained release drug delivery system of venlafaxine hydrochloride by using a wax matrix system. The effects of bees wax and carnauba wax on drug release profile was investigated. A 3(2) full factorial design was applied to systemically optimize the drug release profile. Amounts of carnauba wax (X(1)) and bees wax (X(2)) were selected as independent variables and release after 12 h and time required for 50% (t(50)) drug release were selected as dependent variables. A mathematical model was generated for each response parameter. Both waxes retarded release after 12 h and increases the t(50) but bees wax showed significant influence. The drug release pattern for all the formulation combinations was found to be approaching Peppas kinetic model. Suitable combination of two waxes provided fairly good regulated release profile. The response surfaces and contour plots for each response parameter are presented for further interpretation of the results. The optimum formulations were chosen and their predicted results found to be in close agreement with experimental findings.

  16. Sustained release of verapamil hydrochloride from sodium alginate microcapsules.

    Science.gov (United States)

    Farhana, S Ayesha; Shantakumar, S M; Shyale, Somashekar; Shalam, Md; Narasu, Laxmi

    2010-04-01

    The objective of the present study was to develop sustained release microcapsules of verapamil hydrochloride (VH) using biodegradable polymers. For this purpose microcapsules embedded verapamil hydrochloride were prepared using sodium alginate alone and also by incorporating some co polymers like methyl cellulose (MC), sodium carboxy methyl cellulose (SCMC) , poly vinyl pyrollidone (PVP) and xanthan gum by employing complex emulsion method of microencapsulation. Microcapsules were prepared in various core: coat ratios to know the effect of polymer and co polymers on drug release. Overall ten formulations were prepared and evaluated for flow behaviour, sieve analysis, drug entrapment efficiency, in vitro dissolution studies, stability studies, including scanning electron microscopy and DSC. The resulting microcapsules were discrete, large, spherical and also free flowing. The drug content in all the batches of microcapsules was found to be uniform. The release was depended on core: coat ratio and nature of the polymers. FTIR analysis revealed chemical integrity between Verapamil hydrochloride (VH), sodium alginate and between the copolymers. Among the four copolymers used methyl cellulose retarded the drug release more than the other three, hence the same formulation was subjected for in vivo studies. The drug release from the microcapsules was found to be following non fickian diffusion. Mechanism of drug release was diffusion controlled first order kinetics. Drug diffusion co efficient and correlation co efficient were also assessed by using various mathematical models. In vivo result analysis of pharmacokinetic parameters revealed that t max of reference and test formulations were almost same. From the study it was concluded that, sustained release Verapamil hydro chloride microcapsules could be achieved with success using sodium alginate alone and also in combination with other biodegradable polymers.

  17. Sustained release of fungicide metalaxyl by mesoporous silica nanospheres

    Energy Technology Data Exchange (ETDEWEB)

    Wanyika, Harrison, E-mail: hwanyika@gmail.com [Jomo Kenyatta University of Agriculture and Technology, Department of Chemistry (Kenya)

    2013-08-15

    The use of nanomaterials for the controlled delivery of pesticides is nascent technology that has the potential to increase the efficiency of food production and decrease pollution. In this work, the prospect of mesoporous silica nanoparticles (MSN) for storage and controlled release of metalaxyl fungicide has been investigated. Mesoporous silica nanospheres with average particle diameters of 162 nm and average pore sizes of 3.2 nm were prepared by a sol-gel process. Metalaxyl molecules were loaded into MSN pores from an aqueous solution by a rotary evaporation method. The loaded amount of metalaxyl as evaluated by thermogravimetric analysis was about 14 wt%. Release of the fungicide entrapped in the MSN matrix revealed sustained release behavior. About 76 % of the free metalaxyl was released in soil within a period of 30 days while only 11.5 and 47 % of the metalaxyl contained in the MSN carrier was released in soil and water, respectively, within the same period. The study showed that MSN can be used to successfully store metalaxyl molecules in its mesoporous framework and significantly delay their release in soil.

  18. Sustained release of fungicide metalaxyl by mesoporous silica nanospheres

    International Nuclear Information System (INIS)

    Wanyika, Harrison

    2013-01-01

    The use of nanomaterials for the controlled delivery of pesticides is nascent technology that has the potential to increase the efficiency of food production and decrease pollution. In this work, the prospect of mesoporous silica nanoparticles (MSN) for storage and controlled release of metalaxyl fungicide has been investigated. Mesoporous silica nanospheres with average particle diameters of 162 nm and average pore sizes of 3.2 nm were prepared by a sol–gel process. Metalaxyl molecules were loaded into MSN pores from an aqueous solution by a rotary evaporation method. The loaded amount of metalaxyl as evaluated by thermogravimetric analysis was about 14 wt%. Release of the fungicide entrapped in the MSN matrix revealed sustained release behavior. About 76 % of the free metalaxyl was released in soil within a period of 30 days while only 11.5 and 47 % of the metalaxyl contained in the MSN carrier was released in soil and water, respectively, within the same period. The study showed that MSN can be used to successfully store metalaxyl molecules in its mesoporous framework and significantly delay their release in soil

  19. 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.

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

    Science.gov (United States)

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

    2014-03-01

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

  1. Sustained Release of Antibacterial Agents from Doped Halloysite Nanotubes

    Directory of Open Access Journals (Sweden)

    Shraddha Patel

    2015-12-01

    Full Text Available The use of nanomaterials for improving drug delivery methods has been shown to be advantageous technically and viable economically. This study employed the use of halloysite nanotubes (HNTs as nanocontainers, as well as enhancers of structural integrity in electrospun poly-e-caprolactone (PCL scaffolds. HNTs were loaded with amoxicillin, Brilliant Green, chlorhexidine, doxycycline, gentamicin sulfate, iodine, and potassium calvulanate and release profiles assessed. Selected doped halloysite nanotubes (containing either Brilliant Green, amoxicillin and potassium calvulanate were then mixed with poly-e-caprolactone (PLC using the electrospinning method and woven into random and oriented-fibered nanocomposite mats. The rate of drug release from HNTs, HNTs/PCL nanocomposites, and their effect on inhibiting bacterial growth was investigated. Release profiles from nanocomposite mats showed a pattern of sustained release for all bacterial agents. Nanocomposites were able to inhibit bacterial growth for up to one-month with only a slight decrease in bacterial growth inhibition. We propose that halloysite doped nanotubes have the potential for use in a variety of medical applications including sutures and surgical dressings, without compromising material properties.

  2. Sustained Release of Antibacterial Agents from Doped Halloysite Nanotubes

    Science.gov (United States)

    Patel, Shraddha; Jammalamadaka, Uday; Sun, Lin; Tappa, Karthik; Mills, David K.

    2015-01-01

    The use of nanomaterials for improving drug delivery methods has been shown to be advantageous technically and viable economically. This study employed the use of halloysite nanotubes (HNTs) as nanocontainers, as well as enhancers of structural integrity in electrospun poly-e-caprolactone (PCL) scaffolds. HNTs were loaded with amoxicillin, Brilliant Green, chlorhexidine, doxycycline, gentamicin sulfate, iodine, and potassium calvulanate and release profiles assessed. Selected doped halloysite nanotubes (containing either Brilliant Green, amoxicillin and potassium calvulanate) were then mixed with poly-e-caprolactone (PLC) using the electrospinning method and woven into random and oriented-fibered nanocomposite mats. The rate of drug release from HNTs, HNTs/PCL nanocomposites, and their effect on inhibiting bacterial growth was investigated. Release profiles from nanocomposite mats showed a pattern of sustained release for all bacterial agents. Nanocomposites were able to inhibit bacterial growth for up to one-month with only a slight decrease in bacterial growth inhibition. We propose that halloysite doped nanotubes have the potential for use in a variety of medical applications including sutures and surgical dressings, without compromising material properties. PMID:28952563

  3. Optimization of sustained release aceclofenac microspheres using response surface methodology

    Energy Technology Data Exchange (ETDEWEB)

    Deshmukh, Rameshwar K.; Naik, Jitendra B., E-mail: jitunaik@gmail.com

    2015-03-01

    Polymeric microspheres containing aceclofenac were prepared by single emulsion (oil-in-water) solvent evaporation method using response surface methodology (RSM). Microspheres were prepared by changing formulation variables such as the amount of Eudragit® RS100 and the amount of polyvinyl alcohol (PVA) by statistical experimental design in order to enhance the encapsulation efficiency (E.E.) of the microspheres. The resultant microspheres were evaluated for their size, morphology, E.E., and in vitro drug release. The amount of Eudragit® RS100 and the amount of PVA were found to be significant factors respectively for determining the E.E. of the microspheres. A linear mathematical model equation fitted to the data was used to predict the E.E. in the optimal region. Optimized formulation of microspheres was prepared using optimal process variables setting in order to evaluate the optimization capability of the models generated according to IV-optimal design. The microspheres showed high E.E. (74.14 ± 0.015% to 85.34 ± 0.011%) and suitably sustained drug release (minimum; 40% to 60%; maximum) over a period of 12 h. The optimized microspheres formulation showed E.E. of 84.87 ± 0.005 with small error value (1.39). The low magnitudes of error and the significant value of R{sup 2} in the present investigation prove the high prognostic ability of the design. The absence of interactions between drug and polymers was confirmed by Fourier transform infrared (FTIR) spectroscopy. Differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRPD) revealed the dispersion of drug within microspheres formulation. The microspheres were found to be discrete, spherical with smooth surface. The results demonstrate that these microspheres could be promising delivery system to sustain the drug release and improve the E.E. thus prolong drug action and achieve the highest healing effect with minimal gastrointestinal side effects. - Highlights: • Aceclofenac microspheres

  4. [Studies on preparation and dissolution test in vitro of sustained-release dropping pills of curcumin].

    Science.gov (United States)

    Fang, Yu; Xiang, Bai; Pan, Zhen-Hua; Cao, De-Ying

    2010-01-01

    To study the prescription and technique of sustained-release dropping pills of curcumin and inspect their release property in vitro. The orthogonal test was used to screen the prescription and technique which were definited with the colligation evaluation of release and formation of dropping pills. The optimization of prescription and technique were as follows: stearic acid 70 mg, glycery monostearate 25 mg, solutol 6 mg, viscosity of cooling liquid was 100 mm2/s; the temperature of material liquid was 80 degrees C; the cooling temperature was 30 - 0 degrees C; the dropping speed was (21 +/- 2) dripping/min. The release behavior of sustained-release dropping pills of curcumin coincidented with Higuchi equation well and the character of sustained-release was transparent. The sustained-release dropping pills of curcumin have good property of sustained-release in vitro and their release behavior in vivo need to be inspected.

  5. Food interactions with sustained-release theophylline preparations. A review.

    Science.gov (United States)

    Jonkman, J H

    1989-03-01

    Currently, theophylline is being used predominantly as sustained-release capsules or tablets. In the mid-seventies the first preparations for use with a dosage interval of 12 hours (twice-daily preparations) were introduced. Since 1983, theophylline preparations that can be given with an interval of 24 hours (once-daily preparations) have become available. The release of theophylline from some of these products can be influenced (either increased or decreased) by concomitant intake of food. With some preparations the composition of the meal (especially the fat content) has an influence on the degree of effect. The consequence may be an effect on the rate of absorption or on the amount absorbed, or both simultaneously. This could result in an unexpected shift of the plasma theophylline concentration. Such a shift is therapeutically undesirable, because theophylline has a fairly narrow therapeutic range. A review is given of those food interactions with the sustained-release theophylline preparations, both twice-daily and once-daily products, that are currently on the world market. Special attention is paid to the specific (bio)pharmaceutical characteristics of the different products, and to the influence of the composition and timing of the meals. For each preparation the effect of food on the following pharmacokinetic parameters is discussed: area under the plasma concentration-time curve, peak plasma drug concentration and time to reach this peak. Where possible, the results for both adults and children are discussed. There are indications that children are more susceptible to food-effects than adults. The regulatory aspects are mentioned briefly. Clinically important effects of food have been observed with the following twice-daily products: 'Theo-Dur Sprinkle', 'Theolair SR' (= 'Nuelin SR') and 'Theograd'. Pronounced effects could have an even greater impact with once-daily preparations, as the total daily dose will be given at a single time. A particularly

  6. Pharmacokinetics of Sustained-Release Analgesics in Mice

    Science.gov (United States)

    Kendall, Lon V; Hansen, Ryan J; Dorsey, Kathryn; Kang, Sooah; Lunghofer, Paul J; Gustafson, Daniel L

    2014-01-01

    Buprenorphine and carprofen, 2 of the most commonly used analgesics in mice, must be administered every 8 to 12 h to provide sustained analgesia. Sustained-release (SR) formulations of analgesics maintain plasma levels that should be sufficient to provide sustained analgesia yet require less frequent dosing and thus less handling of and stress to the animals. The pharmacokinetics of SR formulations of buprenorphine (Bup-SR), butorphanol (Butp-SR), fentanyl (Fent-SR), carprofen (Carp-SR), and meloxicam (Melox-SR) were evaluated in mice over 72 h and compared with those of traditional, nonSR formulations. Bup-SR provided plasma drug levels greater than the therapeutic level for the first 24 to 48 h after administration, but plasma levels of Bup-HCl fell below the therapeutic level by 4 h. Fent-SR maintained plasma levels greater than reported therapeutic levels for 12 h. Therapeutic levels of the remaining drugs are unknown, but Carp-SR provided plasma drug levels similar to those of Carp for the first 24 h after administration, whereas Melox-SR had greater plasma levels than did Melox for the first 8 h. Butp-SR provided detectable plasma drug levels for the first 24 h, with a dramatic decrease over the first 4 h. These results indicate that Bup-SR provides a stable plasma drug level adequate for analgesia for 24 to 48 h after administration, whereas Carp-SR, Melox-SR, Fent-SR, and Butp-SR would require additional doses to provide analgesic plasma levels beyond 24 h in mice. PMID:25255070

  7. Naltrexone sustained-release/bupropion sustained-release for the management of obesity: review of the data to date

    Directory of Open Access Journals (Sweden)

    Caixàs A

    2014-09-01

    Full Text Available Assumpta Caixàs, Lara Albert, Ismael Capel, Mercedes Rigla Endocrinology and Nutrition Department, Parc Tauli Sabadell University Hospital, Autonomous University of Barcelona, Barcelona, Spain Abstract: Obesity is an emerging disease worldwide. Changes in living habits, especially with increased consumption of high-calorie foods and decreased levels of physical activity, lead to an energy imbalance that brings weight gain. Overweight and obesity are major risk factors for several chronic diseases (including cardiovascular diseases, diabetes, and cancer, reduce quality of life, and are associated with higher mortality. For all these reasons, it is of the utmost importance that the trend be reversed and obese people enabled to lose weight. It is known that eating a healthy diet and exercising regularly can help prevent obesity, but data show that in many cases these steps are not enough. This is the reason why, over the last few decades, several antiobesity drugs have been developed. However, the disappointing results demonstrated for the vast majority of them have not discouraged the pharmaceutical industry from continuing to look for an effective drug or combination of drugs. The systematic review presented here focuses on naltrexone sustained-release/bupropion sustained-release combination (Contrave®. We conclude from the current published reports that its effectiveness in the treatment of obesity can be estimated as a placebo-subtracted weight loss of around 4.5%. This weight reduction is moderate but similar to other antiobesity drugs. The safety profile of this combination is acceptable, despite additional data regarding cardiovascular disease being needed. Keywords: Contrave, weight loss, overweight, cardiovascular disease, diabetes, cancer

  8. Diclofenac sodium sustained release hot melt extruded lipid matrices.

    Science.gov (United States)

    Vithani, K; Cuppok, Y; Mostafa, S; Slipper, I J; Snowden, M J; Douroumis, D

    2014-08-01

    Sustained release diclofenac sodium (Df-Na) solid lipid matrices with Compritol® 888 ATO were developed in this study. The drug/lipid powders were processed via cold and hot melt extrusion at various drug loadings. The influence of the processing temperatures, drug loading and the addition of excipients on the obtained dissolution rates was investigated. The physicochemical characterization of the extruded batches showed the existence of crystalline drug in the extrudates with a small amount being solubilized in the lipid matrix. The drug content and uniformity on the tablet surface were also investigated by using energy dispersive X-ray microanalysis. The dissolution rates were found to depend on the actual Df-Na loading and the nature of the added excipients, while the effect of the processing temperatures was negligible. The dissolution mechanism of all extruded formulations followed Peppas-Korsemeyer law, based on the estimated determination coefficients and the dissolution constant rates, indicating drug diffusion from the lipid matrices.

  9. Characterization of unsaturated fatty acid sustained-release microspheres for long-term algal inhibition.

    Science.gov (United States)

    Ni, Lixiao; Jie, Xiaoting; Wang, Peifang; Li, Shiyin; Hu, Shuzhen; Li, Yiping; Li, Yong; Acharya, Kumud

    2015-02-01

    The unsaturated fatty acid (linoleic acid) sustained-release microspheres were prepared with linoleic acid (LA) using alginate-chitosan microcapsule technology. These LA sustained-release microspheres had a high encapsulation efficiency (up to 62%) tested by high performance liquid chromatography with a photo diode array. The dry microspheres were characterized by a scanning electron microscope, X-ray diffraction measurement, dynamic thermogravimetric analysis and Fourier transform infrared spectral analysis. The results of characterization showed that the microspheres had good thermal stability (decomposition temperature of 236°C), stable and temperature independent release properties (release time of more than 40 d). Compared to direct dosing of LA, LA sustained-released microspheres could inhibit Microcystis aeruginosa growth to the non-growth state. The results of this study suggested that the LA sustained-release microspheres may be a potential candidate for algal inhibition. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Abeer M. El-Kady

    2015-01-01

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

  11. Evaluation of the coat quality of sustained release pellets by individual pellet dissolution methodology.

    Science.gov (United States)

    Xu, Min; Liew, Celine Valeria; Heng, Paul Wan Sia

    2015-01-15

    This study explored the application of 400-DS dissolution apparatus 7 for individual pellet dissolution methodology by a design of experiment approach and compared its capability with that of the USP dissolution apparatus 1 and 2 for differentiating the coat quality of sustained release pellets. Drug loaded pellets were prepared by extrusion-spheronization from powder blends comprising 50%, w/w metformin, 25%, w/w microcrystalline cellulose and 25%, w/w lactose, and then coated with ethyl cellulose to produce sustained release pellets with 8% and 10%, w/w coat weight gains. Various pellet properties were investigated, including cumulative drug release behaviours of ensemble and individual pellets. When USP dissolution apparatus 1 and 2 were used for drug release study of the sustained release pellets prepared, floating and clumping of pellets were observed and confounded the release profiles of the ensemble pellets. Hence, the release profiles obtained did not characterize the actual drug release from individual pellet and the applicability of USP dissolution apparatus 1 and 2 to evaluate the coat quality of sustained release pellets was limited. The cumulative release profile of individual pellet using the 400-DS dissolution apparatus 7 was found to be more precise at distinguishing differences in the applied coat quality. The dip speed and dip interval of the reciprocating holder were critical operational parameters of 400-DS dissolution apparatus 7 that affected the drug release rate of a sustained release pellet during the individual dissolution study. The individual dissolution methodology using the 400-DS dissolution apparatus 7 is a promising technique to evaluate the individual pellet coat quality without the influence of confounding factors such as pellet floating and clumping observed during drug release test with dissolution apparatus 1 and 2, as well as to facilitate the elucidation of the actual drug release mechanism conferred by the applied sustained

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

    African Journals Online (AJOL)

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

  13. [Sustained-release progesterone vaginal suppositories 3-development and clinical feasibility testing].

    Science.gov (United States)

    Nakayama, Ayako; Yamaguchi, Naho; Ohno, Yukiko; Miyata, Chihiro; Kondo, Haruomi; Sunada, Hisakazu; Okamoto, Hirokazu

    2013-01-01

      Although progesterone vaginal suppositories (hospital-formulated) are used for the treatment of infertility, their half-life is so short that multiple doses are required. In this study, we aimed to develop sustained-release vaginal suppositories suitable for clinical use which maintain an effective blood concentration by once-a-day treatment, and prepared 7 types of suppository containing the sustained-release progesterone tablets to characterize their sustained-release performance. We selected one candidate suppository among them, taking recovery rate, reproducibility, and hardness, as well as the sustained-release performance into consideration. The shell of the selected suppository is composed of VOSCO S-55 and progesterone for rapid release. The molded progesterone tablets for sustained release were embedded inside. The distribution of the weight and content of the suppository was limited, and the release rate of progesterone was significantly slower than that of a conventional progesterone suppository prepared in our hospital. The single-dose administration of the selected suppository to five healthy volunteers led to significant extension of the blood concentration. We also confirmed the rise of the basic value by multiple administration. The simulation comparison suggested that the blood progesterone concentration is controlled by once-a-day administration of the selected suppository better than twice-a-day administration of the conventional suppository. In conclusion, the sustained-release vaginal suppository prepared in this study was considered to be useful for clinical treatment.

  14. 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.

  15. Development and evaluation of sustained release losartan potassium matrix tablet using kollidon SR as release retardant

    Directory of Open Access Journals (Sweden)

    Shahid Sarwar

    2012-12-01

    Full Text Available The present study was undertaken to develop sustained release (SR matrix tablets of losartan potassium, an angiotensin-II antagonist for the treatment of hypertension. The tablets were prepared by direct compression method, along with Kollidon SR as release retardant polymer. The amount of losartan potassium remains fixed (100 mg for all the three formulations whereas the amounts of Kollidon SR were 250 mg, 225 mg, and 200 mg for F-1, F-2, and F-3 respectively. The evaluation involves three stages: the micromeritic properties evaluation of granules, physical property studies of tablets, and in-vitro release kinetics studies. The USP apparatus type II was selected to perform the dissolution test, and the dissolution medium was 900 mL phosphate buffer pH 6.8. The test was carried out at 75 rpm, and the temperature was maintained at 37 ºC ± 0.5 ºC. The release kinetics was analyzed using several kinetics models. Higher polymeric content in the matrix decreased the release rate of drug. At lower polymeric level, the rate and extent of drug release were enhanced. All the formulations followed Higuchi release kinetics where the Regression co-efficient (R² values are 0.958, 0.944, and 0.920 for F-1, F-2, and F-3 respectively, and they exhibited diffusion dominated drug release. Statistically significant (PO presente estudo foi realizado para desenvolver (SR matriz de comprimidos de liberação sustentada de losartana, um antagonista da angiotensina II, para o tratamento da hipertensão arterial. Os comprimidos foram preparados pelo método de compressão direta com Kollidon SR como polímero de liberação lenta. A quantidade de losartana potássica permanece fixa (100 mg para todas as três formulações enquanto que as quantidades de Kollidon SR foram de 250 mg, 225 mg e 200 mg para F-1, F-2 e F-3, respectivamente. A avaliação envolve três etapas- propriedades micromeríticas dos grânulos, estudo das propriedades físicas dos comprimidos e

  16. Letter to the editor: naltrexone sustained-release/bupropion sustained-release for the management of obesity: review of the data to date

    Directory of Open Access Journals (Sweden)

    Buehler AM

    2015-01-01

    Full Text Available Anna M Buehler Hospital Alemao Oswaldo Cruz, Institute of Health Education and Sciences, Sao Paulo, BrazilI read with great interest the systematic review by Caixàs et al1 on the effect of naltrexone sustained-release/bupropion sustained-release (NB for the management of obesity. By comprehensively appraising five recent clinical trials, the authors concluded that the naltrexone/bupropion combination might represent an important new therapeutic option for the management of obesity, with a weight reduction effect that is similar to other drugs approved for the treatment of obesity.View original paper by Caixàs and colleagues.

  17. Sustainability, Biodiversity and Ethical Aspects of Deliberate Release of GMOs

    DEFF Research Database (Denmark)

    Agger, Peder Winkel

    2006-01-01

    Sustainable development is a way to organize complex political issues at a higher level where both natural scientific rationality and normative based arguments may be parts of a more coherent comprehension....

  18. Diclofenac transdermal patch versus the sustained release tablet: A ...

    African Journals Online (AJOL)

    polyvinyl pyrrolidone K30, with turpentine oil and sesame oil as penetration enhancers. ... therapeutic advantages over conventional oral tablets in terms of prolonged release and improvement of ..... is simple to adopt and cost-effective. In this ...

  19. 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.

  20. Alginate-Chitosan Particulate System for Sustained Release of ...

    African Journals Online (AJOL)

    Erah

    1School of Pharmacy and Health Sciences, International Medical University, Kuala Lumpur, Malaysia, 2Division of ... Both calcium alginate beads and the beads treated with chitosan failed to release ..... also found to fit the classical power law.

  1. Showcasing Sustainability in Your Toxics Release Inventory Report

    Science.gov (United States)

    From a June 2012 webinar, these slides contain guidance for reporting Pollution Prevention and Source Reduction data on the Toxics Release Inventory Form R and a synopsis of EPA's use of this information.

  2. Physical-chemical aspects of a coaxial sustained release device based on Poly-Eva

    NARCIS (Netherlands)

    Laarhoven, Johannes Antonius Hendrikus van

    2005-01-01

    Sustained release of dugs offers several advantages like increased efficacy, safety, compliance and convenience. As a consequence sustained drug delivery is often preferred above daily administration of drugs. Furthermore, drug delivery systems can be designed to deliver one or more drugs at a

  3. Nanosized sustained-release pyridostigmine bromide microcapsules: process optimization and evaluation of characteristics

    Science.gov (United States)

    Tan, Qunyou; Jiang, Rong; Xu, Meiling; Liu, Guodong; Li, Songlin; Zhang, Jingqing

    2013-01-01

    Background Pyridostigmine bromide (3-[[(dimethylamino)-carbonyl]oxy]-1-methylpyridinium bromide), a reversible inhibitor of cholinesterase, is given orally in tablet form, and a treatment schedule of multiple daily doses is recommended for adult patients. Nanotechnology was used in this study to develop an alternative sustained-release delivery system for pyridostigmine, a synthetic drug with high solubility and poor oral bioavailability, hence a Class III drug according to the Biopharmaceutics Classification System. Novel nanosized pyridostigmine-poly(lactic acid) microcapsules (PPNMCs) were expected to have a longer duration of action than free pyridostigmine and previously reported sustained-release formulations of pyridostigmine. Methods The PPNMCs were prepared using a double emulsion-solvent evaporation method to achieve sustained-release characteristics for pyridostigmine. The preparation process for the PPNMCs was optimized by single-factor experiments. The size distribution, zeta potential, and sustained-release behavior were evaluated in different types of release medium. Results The optimal volume ratio of inner phase to external phase, poly(lactic acid) concentration, polyvinyl alcohol concentration, and amount of pyridostigmine were 1:10, 6%, 3% and 40 mg, respectively. The negatively charged PPNMCs had an average particle size of 937.9 nm. Compared with free pyridostigmine, PPNMCs showed an initial burst release and a subsequent very slow release in vitro. The release profiles for the PPNMCs in four different types of dissolution medium were fitted to the Ritger-Peppas and Weibull models. The similarity between pairs of dissolution profiles for the PPNMCs in different types of medium was statistically significant, and the difference between the release curves for PPNMCs and free pyridostigmine was also statistically significant. Conclusion PPNMCs prepared by the optimized protocol described here were in the nanometer range and had good uniformity

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

    Science.gov (United States)

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

    2015-01-01

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

  5. The preparation and the sustained release of titanium dioxide hollow particles encapsulating L-ascorbic acid

    Science.gov (United States)

    Tominaga, Yoko; Kadota, Kazunori; Shimosaka, Atsuko; Yoshida, Mikio; Oshima, Kotaro; Shirakawa, Yoshiyuki

    2018-05-01

    The preparation of the titanium dioxide hollow particles encapsulating L-ascorbic acid via sol-gel process using inkjet nozzle has been performed, and the sustained release and the effect protecting against degradation of L-ascorbic acid in the particles were investigated. The morphology of titanium dioxide particles was evaluated by scanning electron microscopy (SEM) and energy dispersive X-ray spectrometry (EDS). The sustained release and the effect protecting against degradation of L-ascorbic acid were estimated by dialysis bag method in phosphate buffer saline (PBS) (pH = 7.4) as release media. The prepared titanium dioxide particles exhibited spherical porous structures. The particle size distribution of the titanium dioxide particles was uniform. The hollow titanium dioxide particles encapsulating L-ascorbic acid showed the sustained release. It was also found that the degradation of L-ascorbic acid could be inhibited by encapsulating L-ascorbic acid in the titanium dioxide hollow particles.

  6. 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.

  7. Preparation and Application of Sustained-Release Potassium Ferrate(VI

    Directory of Open Access Journals (Sweden)

    Xuan Xu

    2014-01-01

    Full Text Available In this study, a composite system for the sustained release of potassium ferrate(VI (sustained-release K2FeO4 was prepared and applied for water treatment. The objective of this research was to maximize the effectiveness of K2FeO4 for water treatment by enhancing its stability using diatomite. The sustained-release K2FeO4 was characterized using X-ray diffraction, scanning electron microscopy, and Fourier transform infrared spectroscopy. The results indicated that no new crystal phase was formed during the preparation and some K2FeO4 crystals entered the pores of the diatomite. From K2FeO4 release experiments, we found that the decomposition rate of K2FeO4 was obviously decreased, which greatly improved the contact rate between released K2FeO4 and pollutants. Via degradation of methyl orange, which was used as a model pollutant, the influential factor of K2FeO4 content within the complete sustained-release K2FeO4 system was studied. The optimal K2FeO4 content within the sustained-release K2FeO4 system was approximately 70%. In natural water samples, sustained-release K2FeO4 at a dosage of 0.06 g/L and with a reaction time of 20 minutes removed 36.84% of soluble microbial products and 17.03% of simple aromatic proteins, and these removal rates were better than those observed after traditional chlorine disinfection.

  8. Spray drying of silica microparticles for sustained release application with a new sol-gel precursor.

    Science.gov (United States)

    Wang, Bifeng; Friess, Wolfgang

    2017-10-30

    A new precursor, tetrakis(2-methoxyethyl) orthosilicate (TMEOS) was used to fabricate microparticles for sustained release application, specifically for biopharmaceuticals, by spray drying. The advantages of TMEOS over the currently applied precursors are its water solubility and hydrolysis at moderate pH without the need of organic solvents or catalyzers. Thus a detrimental effect on biomolecular drug is avoided. By generating spray-dried silica particles encapsulating the high molecular weight model compound FITC-dextran 150 via the nano spray dryer Büchi-90, we demonstrated how formulation parameters affect and enable control of drug release properties. The implemented strategies to regulate release included incorporating different quantities of dextrans with varying molecular weight as well as adjusting the pH of the precursor solution to modify the internal microstructures. The addition of dextran significantly altered the released amount, while the release became faster with increasing dextran molecular weight. A sustained release over 35days could be achieved with addition of 60 kD dextran. The rate of FITC-Dextran 150 release from the dextran 60 containing particles decreased with higher precursor solution pH. In conclusion, the new precursor TMEOS presents a promising alternative sol-gel technology based carrier material for sustained release application of high molecular weight biopharmaceutical drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Radiation crosslinked hydrogels as sustained release drug delivery systems

    International Nuclear Information System (INIS)

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

    1986-01-01

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

  10. Poly(lactide-co-glycolide) encapsulated hydroxyapatite microspheres for sustained release of doxycycline

    Energy Technology Data Exchange (ETDEWEB)

    Wang Xiaoyun [School of Pharmacy, Shenyang Pharmaceutical University, 103, Wenhua Road, Shenyang 110016 (China); Department of Pharmacy, Shandong Drug and Food Vocational College, Science and Technology Town, Hightech Industrial Development Zone, Weihai 264210 (China); Xu Hui; Zhao Yanqiu [School of Pharmacy, Shenyang Pharmaceutical University, 103, Wenhua Road, Shenyang 110016 (China); Wang Shaoning, E-mail: wsn-xh@126.com [School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103, Wenhua Road, Shenyang 110016 (China); Abe, Hiroya; Naito, Makio [Joining and Welding Research Institute, Osaka University, 11-1, Mihogaoka, Ibaraki, Osaka 567-0047 (Japan); Liu Yanli [School of Pharmacy, Shenyang Pharmaceutical University, 103, Wenhua Road, Shenyang 110016 (China); Wang Guoqing [School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103, Wenhua Road, Shenyang 110016 (China)

    2012-03-15

    Highlights: Black-Right-Pointing-Pointer PLGA encapsulated HAP-MSs were used for the sustained delivery of Doxycycline (Doxy, a broad spectrum tetracycline antibiotic). Black-Right-Pointing-Pointer Sustained Doxy release without obvious burst was observed. Black-Right-Pointing-Pointer Mechanism of the sustained Doxy release was illustrated. Black-Right-Pointing-Pointer Sustained Doxy release character in vivo was also obtained, the plasma Doxy levels were relatively lower and steady compared to that of the un-encapsulated HAP-MSs. - Abstract: The purpose of this study was to prepare a poly(lactide-co-glycolide) (PLGA) encapsulated hydroxyapatite microspheres (HAP-MSs) as injectable depot for sustained delivery of Doxycycline (Doxy). Doxy loaded HAP-MSs (Doxy-HAP-MSs) were encapsulated with PLGA by solid-in-oil-in-water (S/O/W) emulsion-solvent evaporation technique, the effects of the PLGA used (various intrinsic viscosity and LA/GA ratio) and ratio of PLGA/HAP-MSs on the formation of Doxy-HAP-MSs and in vitro release of Doxy were studied. The results showed that sustained drug release without obvious burst was obtained by using PLGA encapsulated HAP-MSs as the carrier, also the drug release rate could be tailored by changing the ratio of PLGA/HAP-MSs, or PLGA of various intrinsic viscosities or LA/GA ratio. Lower ratio of PLGA/HAP-MSs corresponded faster Doxy release, e.g. for the microspheres of PLGA/HAP-MSs ratio of 8 and 0.25, the in vitro Doxy release percents at the end of 7days were about 23% and 76%, respectively. Higher hydrophilicity (higher ratio of GA to LA) and lower molecular weight of PLGA corresponded to higher Doxy release rates. For in vivo release study, PLGA encapsulated HAP-MSs were subcutaneously injected to the back of mice, and the results showed good correlation between the in vivo and in vitro drug release. Meanwhile, the plasma Doxy levels after subcutaneous administration of PLGA encapsulated Doxy-HAP-MSs were relatively lower and steady

  11. Poly(lactide-co-glycolide) encapsulated hydroxyapatite microspheres for sustained release of doxycycline

    International Nuclear Information System (INIS)

    Wang Xiaoyun; Xu Hui; Zhao Yanqiu; Wang Shaoning; Abe, Hiroya; Naito, Makio; Liu Yanli; Wang Guoqing

    2012-01-01

    Highlights: ► PLGA encapsulated HAP-MSs were used for the sustained delivery of Doxycycline (Doxy, a broad spectrum tetracycline antibiotic). ► Sustained Doxy release without obvious burst was observed. ► Mechanism of the sustained Doxy release was illustrated. ► Sustained Doxy release character in vivo was also obtained, the plasma Doxy levels were relatively lower and steady compared to that of the un-encapsulated HAP-MSs. - Abstract: The purpose of this study was to prepare a poly(lactide-co-glycolide) (PLGA) encapsulated hydroxyapatite microspheres (HAP-MSs) as injectable depot for sustained delivery of Doxycycline (Doxy). Doxy loaded HAP-MSs (Doxy-HAP-MSs) were encapsulated with PLGA by solid-in-oil-in-water (S/O/W) emulsion-solvent evaporation technique, the effects of the PLGA used (various intrinsic viscosity and LA/GA ratio) and ratio of PLGA/HAP-MSs on the formation of Doxy-HAP-MSs and in vitro release of Doxy were studied. The results showed that sustained drug release without obvious burst was obtained by using PLGA encapsulated HAP-MSs as the carrier, also the drug release rate could be tailored by changing the ratio of PLGA/HAP-MSs, or PLGA of various intrinsic viscosities or LA/GA ratio. Lower ratio of PLGA/HAP-MSs corresponded faster Doxy release, e.g. for the microspheres of PLGA/HAP-MSs ratio of 8 and 0.25, the in vitro Doxy release percents at the end of 7days were about 23% and 76%, respectively. Higher hydrophilicity (higher ratio of GA to LA) and lower molecular weight of PLGA corresponded to higher Doxy release rates. For in vivo release study, PLGA encapsulated HAP-MSs were subcutaneously injected to the back of mice, and the results showed good correlation between the in vivo and in vitro drug release. Meanwhile, the plasma Doxy levels after subcutaneous administration of PLGA encapsulated Doxy-HAP-MSs were relatively lower and steady compared to that of the un-encapsulated microspheres. In conclusion, PLGA encapsulated HAP-MSs may

  12. Enteric-coated sustained-release nanoparticles by coaxial electrospray: preparation, characterization, and in vitro evaluation

    Science.gov (United States)

    Hao, Shilei; Wang, Bochu; Wang, Yazhou; Xu, Yingqian

    2014-02-01

    Enteric-coated formulations can delay the release of drugs until they have passed through the stomach. However, high concentration of drugs caused by rapidly released in the small intestine leads to the intestinal damage, and frequent administration would increase the probability of missing medication and reduce the patient compliance. To solve the above-mentioned problems, aspirin-loaded enteric-coated sustained-release nanoparticles with core-shell structure were prepared via one-step method using coaxial electrospray in this study. Eudragit L100-55 as pH-sensitive polymer and Eudragit RS as sustained-release polymer were used for the outer coating and inner core of the nanoparticles, respectively. The maximum loading capacity of nanoparticles was 23.66 % by changing the flow rate ratio of outer/inner solutions, and the entrapment efficiency was nearly 100 %. Nanoparticles with core-shell structure were observed via fluorescence microscope and transmission electron microscope. And pH-sensitive and sustained drug release profiles were observed in the media with different pH values (1.2 and 6.8). In addition, mild cytotoxicity in vitro was detected, and the nanoparticles could be taken up by Caco-2 cells within 1.0 h in cellular uptake study. These results indicate that prepared enteric-coated sustained-release nanoparticles would be a more safety and effective carrier for oral drug delivery.

  13. Storage and sustained release of volatile substances from a hollow silica matrix

    Energy Technology Data Exchange (ETDEWEB)

    Wang Jiexin [Key Lab for Nanomaterials, Ministry of Education, Beijing 100029 (China); Ding Haomin [Research Center of the Ministry of Education for High Gravity Engineering and Technology, Beijing University of Chemical Technology, Beijing 100029 (China); Tao Xia [Key Lab for Nanomaterials, Ministry of Education, Beijing 100029 (China); Chen Jianfeng [Key Lab for Nanomaterials, Ministry of Education, Beijing 100029 (China)

    2007-06-20

    Porous hollow silica nanospheres (PHSNSs) prepared by adopting a nanosized CaCO{sub 3} template were utilized for the first time as a novel carrier for the storage and sustained release of volatile substances. Two types of volatile substances, Indian pipal from perfumes and peroxyacetic acid from disinfectants, were selected and then tested by one simple adsorption process with two separate comparative carriers, i.e. activated carbon and solid porous silica. It was demonstrated that a high storage capacity (9.6 ml{sub perfume}/mg{sub carrier}) of perfume could be achieved in a PHSNS matrix, which was almost 14 times as much as that of activated carbon. The perfume release profiles showed that PHSNSs exhibited sustained multi-stage release behaviour, while the constant release of activated carbon at a low level was discerned. Further, a Higuchi model study proved that the release process of perfume in both carriers followed a Fickian diffusion mechanism. For peroxyacetic acid as a disinfectant model, PHSNSs also displayed a much better delayed-delivery process than a solid porous silica system owing to the existence of unique hollow frameworks. Therefore, the aforementioned excellent sustained-release behaviours would make PHSNSs a promising carrier for storage and sustained delivery applications of volatile substances.

  14. Sustained release nimesulide microparticles: evaluation of release modifying property of ethy

    International Nuclear Information System (INIS)

    Khan, S.A.; Ahmed, M.; Nisar-ur-Rehman; Madni, A.U.; Aamir, M.N.; Murtaza, G.

    2011-01-01

    Microencapsulated controlled-release preparations of nimesulide were formulated. Microparticles were prepared by modified phase separation (non-solvent addition) technique using different ratios of ethylcellulose. The microparticles (M/sub 1/, M/sub 2/, and M/sub 3/) were yellow, free flowing and spherical in shape with the particle size varying from 93.62 +- 14.15 to 104.19 +- 18.15 mu m. The t/sub 60%/of nimesulide release from microparticles was found to be 3 +- 0.6, 5 +- 0.6 and 8 +- 0.8 h for formulations M/sub 1/, M/sub 2/, and M/sub 3/, respectively. FT-IR, XRD, and thermal analysis were done which showed that there is no interaction between the polymer and drug. The mechanism of drug release from nimesulide microparticles was studied by using Higuchi and Korsmeyer-Peppas models. The value of coefficient of determination (R/sup 2/) for M/sub 1/, M/sub 2/, and M/sub 3/ indicates anomalous and case-II transport release mechanism. The dissolution data of designed system verified its ability to maintain plasma concentration without the need of frequent dosing. The Nimesulide microparticles prolonged drug release for 12 hours or longer. Based on the results of release studies, M/sub 3/ was opted as a suitable microparticulate formulation allowing the controlled release of nimesulide over a prolonged period of time. Moreover, its encapsulation efficiency was also comparable to the other two formulations (M/sub 1/ and M/sub 2/). In conclusion, the influence of polymer concentration should be considered during formulation development. (author)

  15. Eudragit RS PO nanoparticles for sustained release of pyridostigmine bromide

    International Nuclear Information System (INIS)

    Hoobakht, Fatemeh; Ganji, Fariba; Vasheghani-Farahani, Ebrahim; Mousavi, Seyyed Mohammad

    2013-01-01

    Pyridostigmine bromide (PB) is an inhibitor of cholinesterase, which is used in the treatment of myasthenia gravis and administered for protection against exposure to toxic nerve agents. Tests were done to investigate prolonging the half-life of PB and improving its release behavior. PB was loaded in nanoparticles (NPs) of Eudragit RS PO (Eu-RS) prepared using the technique of quasi emulsion solvent diffusion. Variables of output power of the sonicator, bath temperature and mixing time, were chosen as the optimization factors to obtain the minimum sized NPs. In addition, emulsions were tested at different ratios of drug-to-polymer by dynamic light scattering to determine size and zeta potential of NPs. UV-spectroscopy was used to determine PB content of the NPs. Drug-loaded NPs were characterized by scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectra. Results determined that mixing time had a significant impact on the size of Eu-RS NPs, but power output of sonicator and bath temperature had no significant effect. The particle size obtained at the optimum condition (power output of 70 W, bath temperature of 33 °C, and mixing time of 7 min) was less than 200 nm (optimum sizes were 138.9 and 179.5 nm for Eu-RS and PB-loaded Eu-RS NPs, respectively). The optimum PB-loaded Eu-RS NPs at the PB to Eu-RS weight ratio of 1–4 and 20 % of loaded PB released from the nanocarriers within 100 h

  16. Eudragit RS PO nanoparticles for sustained release of pyridostigmine bromide

    Energy Technology Data Exchange (ETDEWEB)

    Hoobakht, Fatemeh; Ganji, Fariba, E-mail: fganji@modares.ac.ir; Vasheghani-Farahani, Ebrahim [Tarbiat Modares University, Biomedical Engineering Group, Chemical Engineering Department (Iran, Islamic Republic of); Mousavi, Seyyed Mohammad [Tarbiat Modares University, Biotechnology Group, Chemical Engineering Department (Iran, Islamic Republic of)

    2013-09-15

    Pyridostigmine bromide (PB) is an inhibitor of cholinesterase, which is used in the treatment of myasthenia gravis and administered for protection against exposure to toxic nerve agents. Tests were done to investigate prolonging the half-life of PB and improving its release behavior. PB was loaded in nanoparticles (NPs) of Eudragit RS PO (Eu-RS) prepared using the technique of quasi emulsion solvent diffusion. Variables of output power of the sonicator, bath temperature and mixing time, were chosen as the optimization factors to obtain the minimum sized NPs. In addition, emulsions were tested at different ratios of drug-to-polymer by dynamic light scattering to determine size and zeta potential of NPs. UV-spectroscopy was used to determine PB content of the NPs. Drug-loaded NPs were characterized by scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectra. Results determined that mixing time had a significant impact on the size of Eu-RS NPs, but power output of sonicator and bath temperature had no significant effect. The particle size obtained at the optimum condition (power output of 70 W, bath temperature of 33 Degree-Sign C, and mixing time of 7 min) was less than 200 nm (optimum sizes were 138.9 and 179.5 nm for Eu-RS and PB-loaded Eu-RS NPs, respectively). The optimum PB-loaded Eu-RS NPs at the PB to Eu-RS weight ratio of 1-4 and 20 % of loaded PB released from the nanocarriers within 100 h.

  17. Design and characterization of sustained release ketoprofen entrapped carnauba wax microparticles.

    Science.gov (United States)

    Oliveira, Rodinelli B; Nascimento, Thais L; Lima, Eliana M

    2012-01-01

    Ketoprofen is a non-steroid anti-inflammatory drug (NSAID) used in the treatment of rheumatic diseases and in mild to moderate pain. Ketoprofen has a short biological half-life and the commercially available conventional release formulations require dosages to be administered at least 2-3 times a day. Due to these characteristics, ketoprofen is a good candidate for the preparation of controlled release formulations. In this work, a multiparticulate-sustained release dosage form containing ketoprofen in a carnauba wax matrix was developed. Particles were prepared by an emulsion congealing technique. System variables were optimized using fractional factorial and response surface experimental design. Characterization of the particles included size and morphology, flow rate, drug loading and in vitro drug release. Spherical particles were obtained with high drug load and sustained drug release profile. The optimized particles had an average diameter of approximately 200 µm, 50% (w/w) drug load, good flow properties and prolonged ketoprofen release for more than 24 h. Carnauba wax microspheres prepared in this work represent a new multiparticulate-sustained release system for the NSAID ketoprofen, exhibiting good potential for application in further pharmaceutical processes.

  18. [Establishment of modern multi-component sustained-release preparations of oral traditional Chinese medicines].

    Science.gov (United States)

    Xia, Hai-Jian; Zhang, Zhen-Hai; Liu, Dan; Yu, Dan-Hong; Jia, Xiao-Bin

    2013-10-01

    Traditional Chinese medicines have a long history, with a large quantity of efficient traditional Chinese medicines and prescriptions. However, the vast majority of pharmaceutical dose forms remain common preparations, with very few efficient, long-lasting and low-dose preparations. The sustain-release preparation allows sustained drug release in a longer period of time, maintains blood drug concentration, reduces the toxic effect and medication frequency, and improves medication compliance. Unlike monomer drugs, the material base of traditional Chinese medicine and compounds is multi-component, instead of single or several active monomers. Therefore, under the guidance of the Chinese medicine theories, modern multi-component sustained-release preparations were developed for oral traditional Chinese medicines, with the aim of finally improving the clinical efficacy of traditional Chinese medicines.

  19. Doc2b synchronizes secretion from chromaffin cells by stimulating fast and inhibiting sustained release

    DEFF Research Database (Denmark)

    da Silva Pinheiro, Paulo César; de Wit, Heidi; Walter, Alexander M

    2013-01-01

    Synaptotagmin-1 and -7 constitute the main calcium sensors mediating SNARE-dependent exocytosis in mouse chromaffin cells, but the role of a closely related calcium-binding protein, Doc2b, remains enigmatic. We investigated its role in chromaffin cells using Doc2b knock-out mice and high temporal...... resolution measurements of exocytosis. We found that the calcium dependence of vesicle priming and release triggering remained unchanged, ruling out an obligatory role for Doc2b in those processes. However, in the absence of Doc2b, release was shifted from the readily releasable pool to the subsequent...... sustained component. Conversely, upon overexpression of Doc2b, the sustained component was largely inhibited whereas the readily releasable pool was augmented. Electron microscopy revealed an increase in the total number of vesicles upon Doc2b overexpression, ruling out vesicle depletion as the cause...

  20. The physical and chemical stability of suspensions of sustained-release diclofenac microspheres.

    Science.gov (United States)

    Lewis, L; Boni, R L; Adeyeye, C M

    1998-01-01

    The major challenge in liquid sustained-release oral suspensions is to minimize drug diffusion into the suspending medium and to retain the original properties of the microparticles during storage. Diclofenac wax microspheres prepared by the hydrophobic congealable disperse phase method were formulated as a sustained release suspension and stored at three different temperatures (25, 37 and 45 degrees C) for 3 months, to evaluate the physical and chemical stability of the suspended microspheres. Suspensions of microspheres stored at ambient temperatures were both physically and chemically stable, but at higher temperatures, up to 45 degrees C, there was a decrease in drug release due to scaling and melting on the microsphere surface as observed by scanning electron microscopy. However, on prolonged storage, up to 90 days, especially at 45 degrees C, temperature became a dominant factor causing an increase in drug release. The suspension of diclofenac microspheres was chemically stable for 3 months, while the plain drug suspension exhibited slight degradation.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-05-15

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

  2. Pharmacokinetics of propafenone hydrochloride sustained-release capsules in male beagle dogs.

    Science.gov (United States)

    Pan, Liping; Qian, Yafang; Cheng, Minlu; Gu, Pan; He, Yanna; Xu, Xiaowen; Ding, Li

    2015-01-01

    This paper describes the development and validation of a liquid chromatography-mass spectrometric assay for propafenone and its application to a pharmacokinetic study of propafenone administered as a new propafenone hydrochloride sustained-release capsule (SR-test), as an instant-release tablet (IR-reference) and as the market leader sustained-release capsule (Rythmol, SR-reference) in male beagle dogs (n=8). In Study A comparing SR-test with IR-reference in a crossover design T max and t 1/2 of propafenone for SR-test were significantly higher than those for IR-reference while C max and AUC were lower demonstrating the sustained release properties of the new formulation. In Study B comparing SR-test with SR-reference the observed C max and AUC of propafenone for SR-test (124.5±140.0 ng/mL and 612.0±699.2 ng·h/mL, respectively) were higher than for SR-reference (78.52±72.92 ng/mL and 423.6±431.6 ng·h/mL, respectively) although the differences were not significant. Overall, the new formulation has as good if not better sustained release characteristics to the market leader formulation.

  3. Pharmacokinetics of propafenone hydrochloride sustained-release capsules in male beagle dogs

    Directory of Open Access Journals (Sweden)

    Liping Pan

    2015-01-01

    Full Text Available This paper describes the development and validation of a liquid chromatography–mass spectrometric assay for propafenone and its application to a pharmacokinetic study of propafenone administered as a new propafenone hydrochloride sustained-release capsule (SR-test, as an instant-release tablet (IR-reference and as the market leader sustained-release capsule (Rythmol, SR-reference in male beagle dogs (n=8. In Study A comparing SR-test with IR-reference in a crossover design Tmax and t1/2 of propafenone for SR-test were significantly higher than those for IR-reference while Cmax and AUC were lower demonstrating the sustained release properties of the new formulation. In Study B comparing SR-test with SR-reference the observed Cmax and AUC of propafenone for SR-test (124.5±140.0 ng/mL and 612.0±699.2 ng·h/mL, respectively were higher than for SR-reference (78.52±72.92 ng/mL and 423.6±431.6 ng·h/mL, respectively although the differences were not significant. Overall, the new formulation has as good if not better sustained release characteristics to the market leader formulation.

  4. Preparation and evaluation of tolmetin sodium conventional and sustained-release suppositories

    OpenAIRE

    B., Baloǧlu; O., Kirkaǧaçhoǧlu

    2002-01-01

    Conventional suppositories of tolmetin sodium were prepared by using two different types of Witepsol as an oily base and two different ratios of polyethylene glycol 400: polyethylene glycol 4000 as an water-soluble base. In addition, sustained- release suppositories were prepared by adding Eudragit L-100 ta the suppositories. The effects of the suppository base and the ratios of the polyethylene glycol 400: polyethylene glycols 4000 on the in vitro release characteristics were investigated. T...

  5. Development of Sustained Release Capsules Containing “Coated Matrix Granules of Metoprolol Tartrate”

    OpenAIRE

    Siddique, Sabahuddin; Khanam, Jasmina; Bigoniya, Papiya

    2010-01-01

    The objective of this investigation was to prepare sustained release capsule containing coated matrix granules of metoprolol tartrate and to study its in vitro release and in vivo absorption. The design of dosage form was performed by choosing hydrophilic hydroxypropyl methyl cellulose (HPMC K100M) and hydrophobic ethyl cellulose (EC) polymers as matrix builders and Eudragit® RL/RS as coating polymers. Granules were prepared by composing drug with HPMC K100M, EC, dicalcium phosphate by wet gr...

  6. Influence of Natural, Synthetic Polymers and Fillers on sustained release matrix tablets of Pregabalin

    OpenAIRE

    Vijaya Durga. K; Ashok Kumar. P; Suresh V Kulkarni

    2013-01-01

    The objective of the present study was to develop sustained release matrix tablets of Pregabalin for the treatment of neuropathic pain and epilepsy. The tablets were prepared by wet granulation and formulated using drug with Hydrophilic, hydrophobic, synthetic, natural polymers and 4 different fillers were used. The effect of Polymer concentration, combination and fillers on drug release rate was analyzed for the formulations F-1 to F-17. The tablets were subjected to physicochemical studies,...

  7. Preparation and Optimization of Immediate Release/Sustained Release Bilayered Tablets of Loxoprofen Using Box-Behnken Design.

    Science.gov (United States)

    Tak, Jin Wook; Gupta, Biki; Thapa, Raj Kumar; Woo, Kyu Bong; Kim, Sung Yub; Go, Toe Gyeong; Choi, Yongjoo; Choi, Ju Yeon; Jeong, Jee-Heon; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

    2017-05-01

    The aim of our current study was to characterize and optimize loxoprofen immediate release (IR)/sustained release (SR) tablet utilizing a three-factor, three-level Box-Behnken design (BBD) combined with a desirability function. The independent factors included ratio of drug in the IR layer to total drug (X 1 ), ratio of HPMC to drug in the SR layer (X 2 ), and ratio of Eudragit RL PO to drug in the SR layer (X 3 ). The dependent variables assessed were % drug released in distilled water at 30 min (Y 1 ), % drug released in pH 1.2 at 2 h (Y 2 ), and % drug released in pH 6.8 at 12 h (Y 3 ). The responses were fitted to suitable models and statistical validation was performed using analysis of variance. In addition, response surface graphs and contour plots were constructed to determine the effects of different factor level combinations on the responses. The optimized loxoprofen IR/SR tablets were successfully prepared with the determined amounts of ingredients that showed close agreement in the predicted and experimental values of tablet characterization and drug dissolution profile. Therefore, BBD can be utilized for successful optimization of loxoprofen IR/SR tablet, which can be regarded as a suitable substitute for the current marketed formulations.

  8. Oral sustained release tablets of zidovudine using binary blends of natural and synthetic polymers.

    Science.gov (United States)

    Emeje, Martins; Olaleye, Olajide; Isimi, Christiana; Fortunak, Joseph; Byrn, Stephen; Kunle, Olobayo; Ofoefule, Sabinus

    2010-01-01

    Oral sustained release matrix tablets of zidovudine (ZDV) were prepared using different types, proportions and blends of carbopol 71G (C71) and a plant gum obtained from Abelmoschus esculentus (AEG). The effect of various formulation factors like polymer proportion, polymer type and pH of the dissolution medium on the in vitro release of the drug was studied, using the half change technique, in 900 ml of dissolution medium, at 100 rpm. Release kinetics were analyzed using Zero-order, Higuchi's square-root and Ritger-Peppas' empirical equations. In vitro release performance as revealed by the time taken for 70% of the drug to be released (t70%), showed that the release rate decreased with increase in polymer proportion. Matrix tablets containing 10 and 20% AEG were found to exhibit immediate-release characteristics. Matrix tablets containing 30% AEG showed t70% value of 204 min and extended the release up to 5 h, while matrix tablets containing 30% carbopol showed t70% value of 234 min and extended the release up to 6 h. Three blends of AEG and C71 at the ratio of 1:2, 2:1 and 1:3 showed t70% values of 132, 312 and 102 min respectively and extended the release up to 8 h. Mathematical analysis of the release kinetics indicated that the nature of drug release from the matrix tablets followed Fickian and anomalous release. Drug release from matrix tablets of zidovudine containing blends of AEG and C71 demonstrates the advantage of blending a natural and synthetic polymer over single polymer use.

  9. Sustained release of BMP-2 in bioprinted alginate for osteogenicity in mice and rats.

    Directory of Open Access Journals (Sweden)

    Michelle T Poldervaart

    Full Text Available The design of bioactive three-dimensional (3D scaffolds is a major focus in bone tissue engineering. Incorporation of growth factors into bioprinted scaffolds offers many new possibilities regarding both biological and architectural properties of the scaffolds. This study investigates whether the sustained release of bone morphogenetic protein 2 (BMP-2 influences osteogenicity of tissue engineered bioprinted constructs. BMP-2 loaded on gelatin microparticles (GMPs was used as a sustained release system, which was dispersed in hydrogel-based constructs and compared to direct inclusion of BMP-2 in alginate or control GMPs. The constructs were supplemented with goat multipotent stromal cells (gMSCs and biphasic calcium phosphate to study osteogenic differentiation and bone formation respectively. BMP-2 release kinetics and bioactivity showed continuous release for three weeks coinciding with osteogenicity. Osteogenic differentiation and bone formation of bioprinted GMP containing constructs were investigated after subcutaneous implantation in mice or rats. BMP-2 significantly increased bone formation, which was not influenced by the release timing. We showed that 3D printing of controlled release particles is feasible and that the released BMP-2 directs osteogenic differentiation in vitro and in vivo.

  10. 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 ...

  11. Sustained-release of caffeine from a polymeric tablet matrix: An in vitro and pharmacokinetic study

    International Nuclear Information System (INIS)

    Tan, Donna; Zhao Bin; Moochhala, Shabbir; Yang Yiyan

    2006-01-01

    Caffeine is utilized as a stimulant to impart a desired level of alertness during certain working hours. Usually, a single dose of caffeine induces 2-3 h of alertness coupled with side effects whereas a longer effect of 8-12 h is very useful for both daily life and military action. Thus, there is a need to deliver the stimulant continuously to an individual at one time to impart an increased level of alertness for the period stated after administration. This study aimed to design a polymeric microparticle system for sustained delivery of caffeine using a polymeric matrix. Poly(ethylene oxide) (PEO) was used as the erodible matrix material and the caffeine polymeric tablets were fabricated by compression using a Graseby Specac hydraulic press. In vitro release profiles as well as the pharmacokinetics studies data were obtained. Caffeine tablets fabricated using various polymers showed a high initial burst release type profile as compared to the caffeine-PEO-tablet. The PK studies showed sustained delivery of caffeine resulted in two expected phenomena: a reduction in the initial high rate of caffeine release (burst release) as well as a reduction in the change in caffeine concentration in the systemic circulation. A simple two-component system for sustained-release caffeine formulation therefore has been achieved

  12. Sustained-release of caffeine from a polymeric tablet matrix: An in vitro and pharmacokinetic study

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Donna [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117597 (Singapore); Zhao Bin [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117597 (Singapore); Moochhala, Shabbir [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117597 (Singapore)]. E-mail: mshabbir@dso.org.sg; Yang Yiyan [Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, 04-01, The Nanos, Singapore 138669 (Singapore)

    2006-07-25

    Caffeine is utilized as a stimulant to impart a desired level of alertness during certain working hours. Usually, a single dose of caffeine induces 2-3 h of alertness coupled with side effects whereas a longer effect of 8-12 h is very useful for both daily life and military action. Thus, there is a need to deliver the stimulant continuously to an individual at one time to impart an increased level of alertness for the period stated after administration. This study aimed to design a polymeric microparticle system for sustained delivery of caffeine using a polymeric matrix. Poly(ethylene oxide) (PEO) was used as the erodible matrix material and the caffeine polymeric tablets were fabricated by compression using a Graseby Specac hydraulic press. In vitro release profiles as well as the pharmacokinetics studies data were obtained. Caffeine tablets fabricated using various polymers showed a high initial burst release type profile as compared to the caffeine-PEO-tablet. The PK studies showed sustained delivery of caffeine resulted in two expected phenomena: a reduction in the initial high rate of caffeine release (burst release) as well as a reduction in the change in caffeine concentration in the systemic circulation. A simple two-component system for sustained-release caffeine formulation therefore has been achieved.

  13. Sustained Release of Protein Therapeutics from Subcutaneous Thermosensitive Biocompatible and Biodegradable Pentablock Copolymers (PTSgels

    Directory of Open Access Journals (Sweden)

    Elizabeth Schaefer

    2016-01-01

    Full Text Available Objective. To evaluate thermosensitive, biodegradable pentablock copolymers (PTSgel for sustained release and integrity of a therapeutic protein when injected subcutaneously. Materials and Methods. Five PTSgels with PEG-PCL-PLA-PCL-PEG block arrangements were synthesized. In vitro release of IgG from PTSgels and concentrations was evaluated at 37°C. Released IgG integrity was characterized by SDS-PAGE. In vitro disintegration for 10GH PTSgel in PBS was monitored at 37°C over 72 days using gravimetric loss and GPC analysis. Near-infrared IgG in PTSgel was injected subcutaneously and examined by in vivo imaging and histopathology for up to 42 days. Results. IgG release was modulated from approximately 7 days to more than 63 days in both in vitro and in vivo testing by varying polymer composition, concentration of PTSgel aqueous solution, and concentration of IgG. Released IgG in vitro maintained structural integrity by SDS-PAGE. Subcutaneous PTSgels were highly biocompatible and in vitro IgG release occurred in parallel with the disappearance of subcutaneous gel in vivo. Conclusions. Modulation of release of biologics to fit the therapeutic need can be achieved by varying the biocompatible and biodegradable PTSgel composition. Release of IgG parallels disappearance of the polymeric gel; hence, little or no PTSgel remains after drug release is complete.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  15. Development of theophylline sustained release dosage form based on Kollidon SR.

    Science.gov (United States)

    Reza, Md Selim; Quadir, Mohiuddin Abdul; Haider, Syed Shabbir

    2002-01-01

    Sustained release theophylline matrix tablets constituting Kollidon SR (Polyvinyl acetate and povidone based matrix retarding polymer) were developed in this study in an attempt to design a dosage form that manifests desirable release profile and thorough adherence to official monographs. Four matrix tablet formulations were prepared by dry blending and direct compression of Kollidon SR and HPMC-15cps (hydroxypropylmethylcellulose) in varying proportion with fixed percentage of theophylline. Tablets containing only Kollidon SR with the active ingredient demonstrated a rapid rate of drug release with an initial burst effect. Incorporation of HPMC-15cps in the matrix tablet prolonged the release of drug with subsequent minimization of burst effect as confirmed by mean dissolution time, T50 and Higuchi release rate data. Among the batches containing HPMC-15 cps, a direct relationship was obtained between release rate and the percentage of HPMC used. A suitable controlled release profile was obtained with the matrix tablets containing 20% Kollidon SR and 30% HPMC-15cps. The formulation showed close resemblance to commercial products and compliance with USP specification. The results were explored and explained by the difference of physico-chemical property and hydration characteristics of the polymers. In addition to this result, the exponential model was applied to characterize the drug release behaviour from polymeric systems. It was found that, Fickian release is predominant in tablets containing Kollidon SR alone and non-Fickian mechanism plays an important role in the release of drug from HPMC containing tablets with a trend towards zero-order or case II release. In vitro release profile of two commercial brands were also undertaken for comparison and modulation of the experimental batches.

  16. 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

  17. 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

  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. Taste masking of ofloxacin and formation of interpenetrating polymer network beads for sustained release

    Directory of Open Access Journals (Sweden)

    A. Michael Rajesh

    2017-08-01

    Full Text Available The objective of this study was to carry out taste masking of ofloxacin (Ofl by ion exchange resins (IERs followed by sustained release of Ofl by forming interpenetrating polymer network (IPN beads. Drug-resin complexes (DRCs with three different ratios of Ofl to IERs (1:1, 1:2, 1:4 were prepared by batch method and investigated for in vivo and in vitro taste masking. DRC of methacrylic acid-divinyl benzene (MD resin and Ofl prepared at a ratio of 1:4 was used to form IPN beads. IPN beads of MD 1:4 were prepared by following the ionic cross-linking method using sodium carboxymethyl xanthan gum (SCMXG and SCMXG-sodium carboxymethyl cellulose (SCMXG-SCMC. IPN beads were characterized with FT-IR and further studied on sustained release of Ofl at different pH. In vivo taste masking carried out by human volunteers showed that MD 1:4 significantly reduced the bitterness of Ofl. Characterization studies such as FT-IR, DSC, P-XRD and taste masking showed that complex formation took place between drug and resin. In vitro study at gastric pH showed complete release of drug from MD 1:4 within 30 min whereas IPN beads took 5 h at gastric pH and 10 h at salivary pH for the complete release of drug. As the crosslinking increased the release kinetics changed into non-Fickian diffusion to zero-order release mechanism. MD 1:4 showed better performance for the taste masking of Ofl and IPNs beads prepared from it were found useful for the sustained release of Ofl at both the pH, indicating a versatile drug delivery system.

  20. Development and evaluation of Ketoprofen sustained release matrix tablet using Hibiscus rosa-sinensis leaves mucilage

    Directory of Open Access Journals (Sweden)

    M. Kaleemullah

    2017-07-01

    Full Text Available Currently, the use of natural gums and mucilage is of increasing importance in pharmaceutical formulations as valuable drug excipient. Natural plant-based materials are economic, free of side effects, biocompatible and biodegradable. Therefore, Ketoprofen matrix tablets were formulated by employing Hibiscus rosa-sinensis leaves mucilage as natural polymer and HPMC (K100M as a synthetic polymer to sustain the drug release from matrix system. Direct compression method was used to develop sustained released matrix tablets. The formulated matrix tablets were evaluated in terms of physical appearance, weight variation, thickness, diameter, hardness, friability and in vitro drug release. The difference between the natural and synthetic polymers was investigated concurrently. Matrix tablets developed from each formulation passed all standard physical evaluation tests. The dissolution studies of formulated tablets revealed sustained drug release up to 24 h compared to the reference drug Apo Keto® SR tablets. The dissolution data later were fitted into kinetic models such as zero order equation, first order equation, Higuchi equation, Hixson Crowell equation and Korsmeyer-Peppas equation to study the release of drugs from each formulation. The best formulations were selected based on the similarity factor (f2 value of 50% and more. Through the research, it is found that by increasing the polymers concentration, the rate of drug release decreased for both natural and synthetic polymers. The best formulation was found to be F3 which contained 40% Hibiscus rosa-sinensis mucilage polymer and showed comparable dissolution profile to the reference drug with f2 value of 78.03%. The release kinetics of this formulation has shown to follow non-Fickian type which involved both diffusion and erosion mechanism. Additionally, the statistical results indicated that there was no significant difference (p > 0.05 between the F3 and reference drug in terms of MDT and

  1. PNIPAAM modified mesoporous hydroxyapatite for sustained osteogenic drug release and promoting cell attachment

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Tao [The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079 (China); Tan, Lei [Key Laboratory of Biomedical Polymers of Ministry of Education, College of Chemistry and Molecular Science, Wuhan University, Wuhan 430072 (China); Cheng, Ning; Yan, Qi; Zhang, Yu-Feng [The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079 (China); Liu, Chuan-Jun, E-mail: cjliu@whu.edu.cn [Key Laboratory of Biomedical Polymers of Ministry of Education, College of Chemistry and Molecular Science, Wuhan University, Wuhan 430072 (China); Shi, Bin, E-mail: shibin_dentist@126.com [The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079 (China)

    2016-05-01

    This work presented a sustained release system of simvastatin (SIM) based on the mesoporous hydroxyapatite (MHA) capped with poly(N-isopropylacrylamide) (PNIPAAM). The MHA was prepared by using cetyltrimethylammonium bromide (CTAB) as a template and the modified PNIPAAM layer on the surface of MHA was fabricated through surface-initiated atom transfer radical polymerization (SI-ATRP). The SIM loaded MHA-PNIPAAM showed a sustained release of SIM at 37 °C over 16 days. The bone marrow mesenchymal stem cell (BMSC) proliferation was assessed by cell counting kit-8 (CCK-8) assay, and the osteogenic differentiation was evaluated by alkaline phosphatase (ALP) activity and Alizarin Red staining. The release profile showed that the release of SIM from MHA-SIM-PNIPAAM lasted 16 days and the cumulative amount of released SIM was almost seven-fold than MHA-SIM. Besides, SIM loaded MHA-PNIPAAM exhibited better performance on cell proliferation, ALP activity, and calcium deposition than pure MHA due to the sustained release of SIM. The quantity of ALP in MHA-SIM-PNIPAAM group was more than two fold than pure MHA group at 7 days. Compared to pure MHA, better BMSC attachment on PNIPAAM modified MHA was observed using fluorescent microscopy, indicating the better biocompatibility of MHA-PNIPAAM. - Highlights: • PNIPAAM modified mesoporous hydroxyapatite (MHA) was fabricated by SI-ATRP. • SIM loaded MHA-PNIPAAM continually released SIM in effect concentration for 16 days. • MHA-SIM-PNIPAAM behaved well on cell proliferation, ALP activity and calcium deposition.

  2. Development and evaluation of Ketoprofen sustained release matrix tablet using Hibiscus rosa-sinensis leaves mucilage.

    Science.gov (United States)

    Kaleemullah, M; Jiyauddin, K; Thiban, E; Rasha, S; Al-Dhalli, S; Budiasih, S; Gamal, O E; Fadli, A; Eddy, Y

    2017-07-01

    Currently, the use of natural gums and mucilage is of increasing importance in pharmaceutical formulations as valuable drug excipient. Natural plant-based materials are economic, free of side effects, biocompatible and biodegradable. Therefore, Ketoprofen matrix tablets were formulated by employing Hibiscus rosa-sinensis leaves mucilage as natural polymer and HPMC (K100M) as a synthetic polymer to sustain the drug release from matrix system. Direct compression method was used to develop sustained released matrix tablets. The formulated matrix tablets were evaluated in terms of physical appearance, weight variation, thickness, diameter, hardness, friability and in vitro drug release. The difference between the natural and synthetic polymers was investigated concurrently. Matrix tablets developed from each formulation passed all standard physical evaluation tests. The dissolution studies of formulated tablets revealed sustained drug release up to 24 h compared to the reference drug Apo Keto® SR tablets. The dissolution data later were fitted into kinetic models such as zero order equation, first order equation, Higuchi equation, Hixson Crowell equation and Korsmeyer-Peppas equation to study the release of drugs from each formulation. The best formulations were selected based on the similarity factor ( f 2 ) value of 50% and more. Through the research, it is found that by increasing the polymers concentration, the rate of drug release decreased for both natural and synthetic polymers. The best formulation was found to be F3 which contained 40% Hibiscus rosa-sinensis mucilage polymer and showed comparable dissolution profile to the reference drug with f 2 value of 78.03%. The release kinetics of this formulation has shown to follow non-Fickian type which involved both diffusion and erosion mechanism. Additionally, the statistical results indicated that there was no significant difference (p > 0.05) between the F3 and reference drug in terms of MDT and T50% with p

  3. Postoperative Analgesia Due to Sustained-Release Buprenorphine, Sustained-Release Meloxicam, and Carprofen Gel in a Model of Incisional Pain in Rats (Rattus norvegicus).

    Science.gov (United States)

    Seymour, Travis L; Adams, Sean C; Felt, Stephen A; Jampachaisri, Katechan; Yeomans, David C; Pacharinsak, Cholawat

    2016-01-01

    Postoperative analgesia in laboratory rats is complicated by the frequent handling associated with common analgesic dosing requirements. Here, we evaluated sustained-release buprenorphine (Bup-SR), sustained-release meloxicam (Melox-SR), and carprofen gel (CG) as refinements for postoperative analgesia. The aim of this study was to investigate whether postoperative administration of Bup-SR, Melox-SR, or CG effectively controls behavioral mechanical and thermal hypersensitivity in a rat model of incisional pain. Rats were randomly assigned to 1 of 5 treatment groups: saline, 1 mL/kg SC BID; buprenorphine HCl (Bup HCl), 0.05 mg/kg SC BID; Bup-SR, 1.2 mg/kg SC once; Melox-SR, 4 mg/kg SC once; and CG, 2 oz PO daily. Mechanical and thermal hypersensitivity were tested daily from day-1 through 4. Bup HCl and Bup-SR attenuated mechanical and thermal hypersensitivity on days 1 through 4. Melox-SR and CG attenuated mechanical hypersensitivity-but not thermal hypersensitivity-on days 1 through 4. Plasma concentrations, measured by using UPLC with mass spectrometry, were consistent between both buprenorphine formulations. Gross pathologic examination revealed no signs of toxicity in any group. These findings suggest that postoperative administration of Bup HCl and Bup-SR-but not Melox-SR or CG-effectively attenuates mechanical and thermal hypersensitivity in a rat model of incisional pain.

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

    Directory of Open Access Journals (Sweden)

    Xiao Li

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

  5. An Injectable System for Local and Sustained Release of Antimicrobial Agents in the Periodontal Pocket.

    Science.gov (United States)

    Morelli, Laura; Cappelluti, Martino Alfredo; Ricotti, Leonardo; Lenardi, Cristina; Gerges, Irini

    2017-08-01

    Periodontitis treatments usually require local administration of antimicrobial drugs with the aim to reduce the bacterial load inside the periodontal pocket. Effective pharmaceutical treatments may require sustained local drug release for several days in the site of interest. Currently available solutions are still not able to fulfill the clinical need for high-quality treatments, mainly in terms of release profiles and patients' comfort. This work aims to fill this gap through the development of an in situ gelling system, capable to achieve controlled and sustained release of antimicrobial agents for medium-to-long-term treatments. The system is composed of micrometer-sized β-cyclodextrin-based hydrogel (bCD-Jef-MPs), featured by a strong hydrophilic character, suspended in a synthetic block-co-polymer solution (Poloxamer 407), which is capable to undergo rapid thermally induced sol-gel phase transition at body temperature. The chemical structure of bCD-Jef-MPs was confirmed by cross-correlating data from Fourier transform infrared (FTIR) spectroscopy, swelling test, and degradation kinetics. The thermally induced sol-gel phase transition is demonstrated by rheometric tests. The effectiveness of the described system to achieve sustained release of antimicrobial agents is demonstrated in vitro, using chlorhexidine digluconate as a drug model. The results achieved in this work disclose the potential of the mentioned system in effectively treating periodontitis lesions. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. 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.

  7. Sustained release of estrogens from PEGylated nanoparticles for treatment of secondary spinal cord injury

    Science.gov (United States)

    Barry, John

    Spinal Cord Injury (SCI) is a debilitating condition which causes neurological damage and can result in paralysis. SCI results in immediate mechanical damage to the spinal cord, but secondary injuries due to inflammation, oxidative damage, and activated biochemical pathways leading to apoptosis exacerbate the injury. The only currently available treatment, methylprednisolone, is controversial because there is no convincing data to support its therapeutic efficacy for SCI treatment. In the absence of an effective SCI treatment option, 17beta-estradiol has gained significant attention for its anti-oxidant, anti-inflammatory, and anti-apoptotic abilities, all events associated with secondary. Sadly, 17beta-estradiol is associated with systemic adverse effects preclude the use of free estrogen even for local administration due to short drug half-life in the body. Biodegradable nanoparticles can be used to increase half-life after local administration and to bestow sustained release. Sustained release using PEGylated biodegradable polymeric nanoparticles constructed from poly(lactic-co-glycolic acid) (PLGA) will endow a consistent, low, but effective dose to be delivered locally. This will limit systemic effects due to local administration and low dose, sustained release. PLGA was chosen because it has been used extensively for sustained release, and has a record of safety in humans. Here, we show the in vitro efficacy of PEGylated nanoparticles loaded with 17beta-estradiol for treatment of secondary SCI. We achieved a high loading efficiency and controlled release from the particles over a several day therapeutic window. The particles also show neuroprotection in two in vitro cell culture models. Both the dose and pretreatment time with nanoparticles was evaluated in an effort to translate the treatment into an animal model for further study.

  8. Development of sustained release capsules containing "coated matrix granules of metoprolol tartrate".

    Science.gov (United States)

    Siddique, Sabahuddin; Khanam, Jasmina; Bigoniya, Papiya

    2010-09-01

    The objective of this investigation was to prepare sustained release capsule containing coated matrix granules of metoprolol tartrate and to study its in vitro release and in vivo absorption. The design of dosage form was performed by choosing hydrophilic hydroxypropyl methyl cellulose (HPMC K100M) and hydrophobic ethyl cellulose (EC) polymers as matrix builders and Eudragit® RL/RS as coating polymers. Granules were prepared by composing drug with HPMC K100M, EC, dicalcium phosphate by wet granulation method with subsequent coating. Optimized formulation of metoprolol tartrate was formed by using 30% HPMC K100M, 20% EC, and ratio of Eudragit® RS/RL as 97.5:2.5 at 25% coating level. Capsules were filled with free flowing optimized granules of uniform drug content. This extended the release period upto 12 h in vitro study. Similarity factor and mean dissolution time were also reported to compare various dissolution profiles. The network formed by HPMC and EC had been coupled satisfactorily with the controlled resistance offered by Eudragit® RS. The release mechanism of capsules followed Korsemeyer-Peppas model that indicated significant contribution of erosion effect of hydrophilic polymer. Biopharmaceutical study of this optimized dosage form in rabbit model showed 10 h prolonged drug release in vivo. A close correlation (R(2) = 0.9434) was established between the in vitro release and the in vivo absorption of drug. The results suggested that wet granulation with subsequent coating by fluidized bed technique, is a suitable method to formulate sustained release capsules of metoprolol tartrate and it can perform therapeutically better than conventional immediate release dosage form.

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

    Science.gov (United States)

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

    2016-01-01

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

  10. Hydrolytic conversion of amorphous calcium phosphate into apatite accompanied by sustained calcium and orthophosphate ions release

    Energy Technology Data Exchange (ETDEWEB)

    Niu, Xufeng, E-mail: nxf@buaa.edu.cn [Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191 (China); BUAA Research Institute, Guangzhou 510530 (China); Research Institute of Beihang University in Shenzhen, Shenzhen 518057 (China); Chen, Siqian; Tian, Feng; Wang, Lizhen [Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191 (China); Feng, Qingling [State Key Laboratory of New Ceramic and Fine Processing, Tsinghua University, Beijing 100084 (China); Fan, Yubo, E-mail: yubofan@buaa.edu.cn [Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191 (China)

    2017-01-01

    The aim of this study is to investigate the calcium and orthophosphate ions release during the transformation of amorphous calcium phosphate (ACP) to hydroxyapatite (HA) in aqueous solution. The ACP is prepared by a wet chemical method and further immersed in the distilled water for various time points till 14 d. The release of calcium and orthophosphate ions is measured with calcium and phosphate colorimetric assay kits, respectively. The transition of ACP towards HA is detected by x-ray diffraction (XRD), transmission electron microscopy (TEM), and fourier transform infrared spectroscopy (FTIR). The results indicate that the morphological conversion of ACP to HA occurs within the first 9 h, whereas the calcium and orthophosphate ions releases last for over 7 d. Such sustained calcium and orthophosphate ions release is very useful for ACP as a candidate material for hard tissue regeneration. - Highlights: • ACP is prepared using a wet chemical method. • The conversion of crystal morphology and structure occurs mainly within the initial 9 h. • The calcium and orthophosphate ions release sustains over 14 d.

  11. Sustained release of antibiotics from injectable and thermally responsive polypeptide depots.

    Science.gov (United States)

    Adams, Samuel B; Shamji, Mohammed F; Nettles, Dana L; Hwang, Priscilla; Setton, Lori A

    2009-07-01

    Biodegradable polymeric scaffolds are of interest for delivering antibiotics to local sites of infection in orthopaedic applications, such as bone and diarthrodial joints. The objective of this study was to develop a biodegradable scaffold with ease of drug loading in aqueous solution, while providing for drug depot delivery via syringe injection. Elastin-like polypeptides (ELPs) were used for this application, biopolymers of repeating pentapeptide sequences that were thermally triggered to undergo in situ depot formation at body temperature. ELPs were modified to enable loading with the antibiotics, cefazolin, and vancomycin, followed by induction of the phase transition in vitro. Cefazolin and vancomycin concentrations were monitored, as well as bioactivity of the released antibiotics, to test an ability of the ELP depot to provide for prolonged release of bioactive drugs. Further tests of formulation viscosity were conducted to test suitability as an injectable drug carrier. Results demonstrate sustained release of therapeutic concentrations of bioactive antibiotics by the ELP, with first-order time constants for drug release of approximately 25 h for cefazolin and approximately 500 h for vancomycin. These findings illustrate that an injectable, in situ forming ELP depot can provide for sustained release of antibiotics with an effect that varies across antibiotic formulation. ELPs have important advantages for drug delivery, as they are known to be biocompatible, biodegradable, and elicit no known immune response. These benefits suggest distinct advantages over currently used carriers for antibiotic drug delivery in orthopedic applications. (c) 2008 Wiley Periodicals, Inc.

  12. Evaluation of rate of swelling and erosion of verapamil (VRP) sustained-release matrix tablets.

    Science.gov (United States)

    Khamanga, Sandile M; Walker, Roderick B

    2006-01-01

    Tablets manufactured in-house were compared to a marketed sustained-release product of verapamil to investigate the rate of hydration, erosion, and drug-release mechanism by measuring the wet and subsequent dry weights of the products. Swelling and erosion rates depended on the polymer and granulating fluid used, which ultimately pointed to their permeability characteristics. Erosion rate of the marketed product was highest, which suggests that the gel layer that formed around these tablets was weak as opposed to the robust and resistant layers of test products. Anomalous and near zero-order transport mechanisms were dominant in tests and commercial product, respectively.

  13. Novel Polyurethane Matrix Systems Reveal a Particular Sustained Release Behavior Studied by Imaging and Computational Modeling.

    Science.gov (United States)

    Campiñez, María Dolores; Caraballo, Isidoro; Puchkov, Maxim; Kuentz, Martin

    2017-07-01

    The aim of the present work was to better understand the drug-release mechanism from sustained release matrices prepared with two new polyurethanes, using a novel in silico formulation tool based on 3-dimensional cellular automata. For this purpose, two polymers and theophylline as model drug were used to prepare binary matrix tablets. Each formulation was simulated in silico, and its release behavior was compared to the experimental drug release profiles. Furthermore, the polymer distributions in the tablets were imaged by scanning electron microscopy (SEM) and the changes produced by the tortuosity were quantified and verified using experimental data. The obtained results showed that the polymers exhibited a surprisingly high ability for controlling drug release at low excipient concentrations (only 10% w/w of excipient controlled the release of drug during almost 8 h). The mesoscopic in silico model helped to reveal how the novel biopolymers were controlling drug release. The mechanism was found to be a special geometrical arrangement of the excipient particles, creating an almost continuous barrier surrounding the drug in a very effective way, comparable to lipid or waxy excipients but with the advantages of a much higher compactability, stability, and absence of excipient polymorphism.

  14. Effect of cross-linked biodegradable polymers on sustained release of sodium diclofenac-loaded microspheres

    Directory of Open Access Journals (Sweden)

    Avik Kumar Saha

    2013-12-01

    Full Text Available The objective of this study was to formulate an oral sustained release delivery system of sodium diclofenac(DS based on sodium alginate (SA as a hydrophilic carrier in combination with chitosan (CH and sodium carboxymethyl cellulose (SCMC as drug release modifiers to overcome the drug-related adverse effects and to improve bioavailability. Microspheres of DS were prepared using an easy method of ionotropic gelation. The prepared beads were evaluated for mean particle size, entrapment efficiency, swelling capacity, erosion and in-vitro drug release. They were also subjected to various studies such as Fourier Transform Infra-Red Spectroscopy (FTIR for drug polymer compatibility, Scanning Electron Microscopy for surface morphology, X-ray Powder Diffraction Analysis (XRD and Differential Scanning Calorimetric Analysis (DSC to determine the physical state of the drug in the beads. The addition of SCMC during the preparation of polymeric beads resulted in lower drug loading and prolonged release of the DS. The release profile of batches F5 and F6 showed a maximum drug release of 96.97 ± 0.356% after 8 h, in which drug polymer ratio was decreased. The microspheres of sodium diclofenac with the polymers were formulated successfully. Analysis of the release profiles showed that the data corresponds to the diffusion-controlled mechanism as suggested by Higuchi.

  15. Thermal and Isothermal Methods in Development of Sustained Release Dosage Forms of Ketorolac Tromethamine

    Directory of Open Access Journals (Sweden)

    Dimple Chopra

    2008-01-01

    Full Text Available Differential scanning calorimetry (DSC is a rapid and convenient and conclusive method of screening drug-polymer blend during preformulation studies as it allows polymer incompatibility to be established instantaneously. Various batches of matrix tablets of ketorolac tromethamine (KTM with a series of compatible polymers were prepared. Batches of tablets which gave desired sustained release profile were subjected to stability testing according to ICH guidelines. The analysis for drug content was done using high performance liquid chromatography (HPLC method. The results revealed that there was no statistically significant change in drug content after storage of matrix tablets at elevated temperature of 40°C and 75% relative humidity. From our study we conclude that with careful selection of different polymers and their combinations, a stable sustained release oral dosage form of ketorolac tromethamine can be achieved.

  16. 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.

  17. Sustained-release progesterone nanosuspension following intramuscular injection in ovariectomized rats

    OpenAIRE

    Kharshoum, rasha

    2010-01-01

    Heba F SalemFaculty of Pharmacy, Beni-Suef University, Beni-Suef, EgyptAbstract: The production of an intramuscular (IM) injection of natural progesterone would provide a safer solution than using semi synthetic progesterone. However, disadvantages such as low solubility and a short half life prevent the use of natural progesterone. In this study, we formulated a sustained release form of natural progesterone to be given as IM injection. A progesterone nanosuspension (PNS) was first developed...

  18. Progesterone PLGA/mPEG-PLGA Hybrid Nanoparticle Sustained-Release System by Intramuscular Injection.

    Science.gov (United States)

    Xie, Bin; Liu, Yang; Guo, Yuting; Zhang, Enbo; Pu, Chenguang; He, Haibing; Yin, Tian; Tang, Xing

    2018-02-14

    To prepare sustained-release PLGA/mPEG-PLGA hybrid nanoparticles of progesterone (PRG), and evaluate the descending required administration dosage in vivo. PRG hybrid nanoparticles (PRG H-NPs) based on PLGA/mPEG-PLGA were compared with PRG nanoparticles (PRG-NPs) of pure PLGA as the matrix and PRG-oil solutions. Nanoparticles (NPs) were formed by the method of nanoemulsion, and the pharmacokinetics of the sustained-release PRG H-NPs in male Sprague dawley (SD) rats were investigated. The rats were randomly divided into four groups, each group received: single dose of PRG H-NPs (14.58 mg/kg, i.m.) and PRG-NPs (14.58 mg/kg, i.m.), repeated dosing for 7 days of PRG-oil (2.08 mg/kg, i.m.) solution (Oil-L) and a higher dosage of PRG-oil (6.24 mg/kg, i.m.) solution (Oil-H), respectively. In the pharmacokinetic test, the PRG H-NPs exhibited a comparatively good sustained-release effect against the PRG-NPs without mPEG-PLGA and PRG-oil solution. The pharmacokinetic parameters of the PRG H-NPs, PRG-NPs, Oil-L and Oil-H were AUC 0-t (ng·h·mL -1 ) 8762.1, 1546.1, 1914.5, and 12,138.9, t 1/2 (h)52.7, 44.1, 8.4 and 44.6 respectively. Owing to the modification of PEG, PRG H-NPs can act as safe delivery platforms for sustained-release of drugs with a lower dosage required.

  19. Layer-by-layer films assembled from natural polymers for sustained release of neurotrophin

    International Nuclear Information System (INIS)

    Zhang, Zhiling; Li, Qianqi; Han, Lin; Zhong, Yinghui

    2015-01-01

    Cortical neural prostheses (CNPs) hold great promise for paralyzed patients by recording neural signals from the brain and translating them into movement commands. However, these electrodes normally fail to record neural signals weeks to months after implantation due to inflammation and neuronal loss around the implanted neural electrodes. Sustained local delivery of neurotrophins from biocompatible coatings on CNPs can potentially promote neuron survival and attract the nearby neurons to migrate toward the electrodes to increase neuron density at the electrode/brain interface, which is important for maintaining the recording quality and long-term performance of the implanted CNPs. However, sustained release of neurotrophins from biocompatible ultrathin coatings is very difficult to achieve. In this study, we investigated the potential of several biocompatible natural polyanions including heparin, dextran sulfate, and gelatin to form layer-by-layer (LbL) assembly with positively charged neurotrophin nerve growth factor (NGF) and its model protein lysozyme, and whether sustained release of NGF and lysozyme can be achieved from the nanoscale thin LbL coatings. We found that gelatin, which is less negatively charged than heparin and dextran sulfate, showed the highest efficacy in loading proteins into the LbL films because other interactions in addition to electrostatic interactions were involved in LbL assembly. Sustained release of NGF and lysozymes for approximately 2 weeks was achieved from the gelatin-based LbL coatings. Released NGF maintained the bioactivity to stimulate neurite outgrowth from PC12 cells. Gelatin is generally recognized as safe by the FDA. Thus, the biocompatible LbL coating developed in this study is highly promising to be used for implanted CNPs to improve their long-term performance in human patients. (paper)

  20. Sustained release of nucleic acids from polymeric nanoparticles using microemulsion precipitation in supercritical carbon dioxide.

    Science.gov (United States)

    Ge, Jun; Jacobson, Gunilla B; Lobovkina, Tatsiana; Holmberg, Krister; Zare, Richard N

    2010-12-21

    A general approach for producing biodegradable nanoparticles for sustained nucleic acid release is presented. The nanoparticles are produced by precipitating a water-in-oil microemulsion in supercritical CO(2). The microemulsion consists of a transfer RNA aqueous solution (water phase), dichloromethane containing poly(l-lactic acid)-poly(ethylene glycol) (oil phase), the surfactant n-octyl β-D-glucopyranoside, and the cosurfactant n-butanol.

  1. Development and evaluation of Ketoprofen sustained release matrix tablet using Hibiscus rosa-sinensis leaves mucilage

    OpenAIRE

    Kaleemullah, M.; Jiyauddin, K.; Thiban, E.; Rasha, S.; Al-Dhalli, S.; Budiasih, S.; Gamal, O.E.; Fadli, A.; Eddy, Y.

    2016-01-01

    Currently, the use of natural gums and mucilage is of increasing importance in pharmaceutical formulations as valuable drug excipient. Natural plant-based materials are economic, free of side effects, biocompatible and biodegradable. Therefore, Ketoprofen matrix tablets were formulated by employing Hibiscus rosa-sinensis leaves mucilage as natural polymer and HPMC (K100M) as a synthetic polymer to sustain the drug release from matrix system. Direct compression method was used to develop susta...

  2. Experience with sustained-release melatonin for the treatment of sleep disorders in depression

    Directory of Open Access Journals (Sweden)

    Svetlana Vladimirovna Prokhorova

    2015-01-01

    Full Text Available The data available in the literature on the role of melatonin in the regulation of circadian rhythms and sleep disorders in the population and in patients with mental diseases are analyzed. The cause of insomnia may be circadian rhythm disorders due to the age-related decline in the elaboration of the endogenous hormones that are responsible for the quality and duration of sleep, one of which is melatonin.Sustained-release melatonin is a synthetic analogue of the endogenous human pineal hormone melatonin. According to clinical findings, the main proven clinical effects of sustained-release melatonin 2 mg are a reduction in the latency of sleep, improvement of its quality, and lack of daytime sleepiness. The drug causes no dependence on its long use and rebound symptoms (increased insomnia symptoms, positively affects cognitive functions, and lowers nocturnal blood pressure in hypertensive patients.The paper describes a clinical case of a female patient with recurrent depressive disorder, in whom sustained-release melatonin 2 mg has demonstrated high efficacy and good tolerability in the combination therapy of sleep disorders in the pattern of depression.

  3. Sustained release of sphingosine 1-phosphate for therapeutic arteriogenesis and bone tissue engineering.

    Science.gov (United States)

    Sefcik, Lauren S; Petrie Aronin, Caren E; Wieghaus, Kristen A; Botchwey, Edward A

    2008-07-01

    Sphingosine 1-phosphate (S1P) is a bioactive phospholipid that impacts migration, proliferation, and survival in diverse cell types, including endothelial cells, smooth muscle cells, and osteoblast-like cells. In this study, we investigated the effects of sustained release of S1P on microvascular remodeling and associated bone defect healing in vivo. The murine dorsal skinfold window chamber model was used to evaluate the structural remodeling response of the microvasculature. Our results demonstrated that 1:400 (w/w) loading and subsequent sustained release of S1P from poly(lactic-co-glycolic acid) (PLAGA) significantly enhanced lumenal diameter expansion of arterioles and venules after 3 and 7 days. Incorporation of 5-bromo-2-deoxyuridine (BrdU) at day 7 revealed significant increases in mural cell proliferation in response to S1P delivery. Additionally, three-dimensional (3D) scaffolds loaded with S1P (1:400) were implanted into critical-size rat calvarial defects, and healing of bony defects was assessed by radiograph X-ray, microcomputed tomography (muCT), and histology. Sustained release of S1P significantly increased the formation of new bone after 2 and 6 weeks of healing and histological results suggest increased numbers of blood vessels in the defect site. Taken together, these experiments support the use of S1P delivery for promoting microvessel diameter expansion and improving the healing outcomes of tissue-engineered therapies.

  4. Therapeutic effects of 5-fluorouracil sustained-release particles in 81 malignant pericardial effusion patients

    Directory of Open Access Journals (Sweden)

    Yong-Li Ji

    2015-02-01

    Full Text Available This study aimed to investigate the clinical application value of the 5-fluorouracil (5-FU sustained-release particles implanted along the cardiac tangent direction into malignant pericardial effusion (MPCE. A total of 81 MPCE patients underwent pericardiocentesis, and were implanted with 5-FU sustained-release particles into the pericardial cavity under ultrasound guidance. The puncturing path was along the cardiac tangent direction. Ultrasound examinations were performed every week, and the efficacy was evaluated 4 weeks after treatment. The 45 patients who were treated with pericardial catheter drainage and simultaneous intracavitary chemotherapy were used as the control group. The success rate of pericardiocentesis was 100%. Ultrasound reviews performed 4 weeks after treatment showed that 71 cases achieved complete remission and eight cases achieved partial remission, while treatment was completely ineffective in two cases. The total remission rate was 97.53%, which was significantly higher than that of the control group (77.78%, p < 0.01. The implantation of 5-FU sustained-release particles along the cardiac tangent direction was safe, and demonstrated good efficacy and fewer adverse reactions. Thus, this method could be ideal for the treatment of MPCE.

  5. 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.

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

    International Nuclear Information System (INIS)

    Yue Ling; Yang Zhanshan; Yang Shuqin; Li Qinghua

    2009-01-01

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

  7. Development and evaluation of new multiple-unit levodopa sustained-release floating dosage forms.

    Science.gov (United States)

    Goole, J; Vanderbist, F; Amighi, K

    2007-04-04

    This work relates to the development and the in vitro evaluation of sustained-release minitablets (MT), prepared by melt granulation and subsequent compression, which are designed to float over an extended period of time. Levodopa was used as a model drug. The importance of the composition and manufacturing parameters of the MT on their floating and dissolution properties was then examined. The investigation showed that MT composition and MT diameter had the greatest influence on drug release, which was sustained for more than 8h. By using the same formulation, the best floating properties were obtained with 3mm MT prepared at low compression forces ranging between 50 and 100N. Their resultant-weight (RW) values were always higher than those obtained with a marketed HBS dosage form within 13h. When they were filled into gelatin capsules, no sticking was observed. By evaluating the dissolution profiles of levodopa at different pH values, it was found that dissolution profiles depend more on the prolonged-release ability of Methocel K15M than on the pH-dependent solubility of levodopa. Finally, the robustness of the floating MT was assessed by testing the drug release variability in function of the stirring conditions during dissolution tests.

  8. Design and in vitro/in vivo evaluation of sustained-release floating tablets of itopride hydrochloride.

    Science.gov (United States)

    Ahmed, Sayed M; Ahmed Ali, Adel; Ali, Ahmed Ma; Hassan, Omiya A

    2016-01-01

    The aim of the present study was to improve the bioavailability of itopride (ITO) and sustain its action by formulating as a floating dosage form. Sustained-release floating tablets of ITO hydrochloride (HCl) were prepared by direct compression using different hydrocolloid polymers such as hydroxypropyl methylcellulose and ethylcellulose and/or methacrylic acid polymers Eudragit RSPM and Carbopol 934P. The floating property was achieved using an effervescent mixture of sodium bicarbonate and anhydrous citric acid (1:1 mol/mol). Hardness, friability, content uniformity, and dissolution rate of the prepared floating tablets were evaluated. The formulation F 10 composed of 28.5% Eudragit RSPM, 3% NaHCO 3 , and 7% citric acid provided sustained drug release. In vitro results showed sustained release of F 10 where the drug release percentage was 96.51%±1.75% after 24 hours ( P =0.031). The pharmacokinetic results indicated that the area under the curve (AUC 0-∞ ) of the prepared sustained-release floating tablets at infinity achieved 93.69 µg·h/mL compared to 49.89 µg·h/mL for the reference formulation (Ganaton ® ) and the relative bioavailability of the sustained-release formulation F 10 increased to 187.80% ( P =0.022). The prepared floating tablets of ITO HCl (F 10 ) could be a promising drug delivery system with sustained-release action and enhanced drug bioavailability.

  9. 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.

  10. Nanodiamond-based injectable hydrogel for sustained growth factor release: Preparation, characterization and in vitro analysis.

    Science.gov (United States)

    Pacelli, Settimio; Acosta, Francisca; Chakravarti, Aparna R; Samanta, Saheli G; Whitlow, Jonathan; Modaresi, Saman; Ahmed, Rafeeq P H; Rajasingh, Johnson; Paul, Arghya

    2017-08-01

    Nanodiamonds (NDs) represent an emerging class of carbon nanomaterials that possess favorable physical and chemical properties to be used as multifunctional carriers for a variety of bioactive molecules. Here we report the synthesis and characterization of a new injectable ND-based nanocomposite hydrogel which facilitates a controlled release of therapeutic molecules for regenerative applications. In particular, we have formulated a thermosensitive hydrogel using gelatin, chitosan and NDs that provides a sustained release of exogenous human vascular endothelial growth factor (VEGF) for wound healing applications. Addition of NDs improved the mechanical properties of the injectable hydrogels without affecting its thermosensitive gelation properties. Biocompatibility of the generated hydrogel was verified by in vitro assessment of apoptotic gene expressions and anti-inflammatory interleukin productions. NDs were complexed with VEGF and the inclusion of this complex in the hydrogel network enabled the sustained release of the angiogenic growth factor. These results suggest for the first time that NDs can be used to formulate a biocompatible, thermosensitive and multifunctional hydrogel platform that can function both as a filling agent to modulate hydrogel properties, as well as a delivery platform for the controlled release of bioactive molecules and growth factors. One of the major drawbacks associated with the use of conventional hydrogels as carriers of growth factors is their inability to control the release kinetics of the loaded molecules. In fact, in most cases, a burst release is inevitable leading to diminished therapeutic effects and unsuccessful therapies. As a potential solution to this issue, we hereby propose a strategy of incorporating ND complexes within an injectable hydrogel matrix. The functional groups on the surface of the NDs can establish interactions with the model growth factor VEGF and promote a prolonged release from the polymer network

  11. Surface modified zeolite-based granulates for the sustained release of diclofenac sodium.

    Science.gov (United States)

    Serri, Carla; de Gennaro, Bruno; Quagliariello, Vincenzo; Iaffaioli, Rosario Vincenzo; De Rosa, Giuseppe; Catalanotti, Lilia; Biondi, Marco; Mayol, Laura

    2017-03-01

    In this study, a granulate for the oral controlled delivery of diclofenac sodium (DS), an anionic sparingly soluble nonsteroidal anti-inflammatory drug, has been realized by wet granulation, using a surface modified natural zeolite (SMNZ) as an excipient. The surface modification of the zeolite has been achieved by means of a cationic surfactant, so as to allow the loading of DS through ionic interaction and bestow a control over the drug release mechanism. The granules possessed a satisfactory dosage uniformity, a flowability suitable for an oral dosage form manufacturing, along with a sustained drug release up to 9h, driven by both ion exchange and transport kinetics. Furthermore, the obtained granulate did not elicit a significant cytotoxicity and could also induce a prolonged anti-inflammatory effect on RAW264.7 cells. Taking also into account that natural zeolites are generally abundant and economic, SMNZ can be considered as an attracting alternative excipient for the production of granules with sustained release features. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Preparation and characterization of bee venom-loaded PLGA particles for sustained release.

    Science.gov (United States)

    Park, Min-Ho; Jun, Hye-Suk; Jeon, Jong-Woon; Park, Jin-Kyu; Lee, Bong-Joo; Suh, Guk-Hyun; Park, Jeong-Sook; Cho, Cheong-Weon

    2016-12-14

    Bee venom-loaded poly(lactic-co-glycolic acid) (PLGA) particles were prepared by double emulsion-solvent evaporation, and characterized for a sustained-release system. Factors such as the type of organic solvent, the amount of bee venom and PLGA, the type of PLGA, the type of polyvinyl alcohol, and the emulsification method were considered. Physicochemical properties, including the encapsulation efficiency, drug loading, particle size, zeta-potential and surface morphology were examined by Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD). The size of the bee venom-loaded PLGA particles was 500 nm (measured using sonication). Zeta-potentials of the bee venom-loaded PLGA particles were negative owing to the PLGA. FT-IR results demonstrated that the bee venom was completely encapsulated in the PLGA particles, indicated by the disappearance of the amine and amide peaks. In addition, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis indicated that the bee venom in the bee venom-loaded PLGA particles was intact. In vitro release of the bee venom from the bee venom-loaded PLGA particles showed a sustained-release profile over 1 month. Bee venom-loaded PLGA particles can help improve patients' quality of life by reducing the number of injections required.

  13. Sustained release of a novel anti-quorum-sensing agent against oral fungal biofilms.

    Science.gov (United States)

    Feldman, Mark; Shenderovich, Julia; Al-Quntar, Abed Al Aziz; Friedman, Michael; Steinberg, Doron

    2015-04-01

    Thiazolidinedione-8 (S-8) has recently been identified as a potential anti-quorum-sensing/antibiofilm agent against bacteria and fungi. Based on these results, we investigated the possibility of incorporating S-8 in a sustained-release membrane (SRM) to increase its pharmaceutical potential against Candida albicans biofilm. We demonstrated that SRM containing S-8 inhibits fungal biofilm formation in a time-dependent manner for 72 h, due to prolonged release of S-8. Moreover, the SRM effectively delivered the agent in its active form to locations outside the membrane reservoir. In addition, eradication of mature biofilm by the SRM containing S-8 was also significant. Of note, S-8-containing SRM affected the characteristics of mature C. albicans biofilm, such as thickness, exopolysaccharide (EPS) production, and morphogenesis of fungal cells. The concept of using an antibiofilm agent with no antifungal activity incorporated into a sustained-release delivery system is new in medicine and dentistry. This concept of an SRM containing a quorum-sensing quencher with an antibiofilm effect could pave the way for combating oral fungal infectious diseases. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  14. Protein instability and immunogenicity: roadblocks to clinical application of injectable protein delivery systems for sustained release.

    Science.gov (United States)

    Jiskoot, Wim; Randolph, Theodore W; Volkin, David B; Middaugh, C Russell; Schöneich, Christian; Winter, Gerhard; Friess, Wolfgang; Crommelin, Daan J A; Carpenter, John F

    2012-03-01

    Protein instability and immunogenicity are two main roadblocks to the clinical success of novel protein drug delivery systems. In this commentary, we discuss the need for more extensive analytical characterization in relation to concerns about protein instability in injectable drug delivery systems for sustained release. We then will briefly address immunogenicity concerns and outline current best practices for using state-of-the-art analytical assays to monitor protein stability for both conventional and novel therapeutic protein dosage forms. Next, we provide a summary of the stresses on proteins arising during preparation of drug delivery systems and subsequent in vivo release. We note the challenges and difficulties in achieving the absolute requirement of quantitatively assessing the degradation of protein molecules in a drug delivery system. We describe the potential roles for academic research in further improving protein stability and developing new analytical technologies to detect protein degradation byproducts in novel drug delivery systems. Finally, we provide recommendations for the appropriate approaches to formulation design and assay development to ensure that stable, minimally immunogenic formulations of therapeutic proteins are created. These approaches should help to increase the probability that novel drug delivery systems for sustained protein release will become more readily available as effective therapeutic agents to treat and benefit patients. Copyright © 2011 Wiley Periodicals, Inc.

  15. Clinical applications of the sustained-release dexamethasone implant for treatment of macular edema

    Directory of Open Access Journals (Sweden)

    Rocío Herrero-Vanrell, Jose Augusto Cardillo

    2011-02-01

    Full Text Available Rocío Herrero-Vanrell1, Jose Augusto Cardillo2, Baruch D Kuppermann31Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Complutense University, Madrid, Spain; 2Hospital de Olhos de Araraquara, Araraquara, São Paulo, Brazil; 3Gavin Herbert Eye Institute, University of California, Irvine, CA, USAAbstract: Macular edema is one of the leading causes of vision loss among patients with retinal vein occlusion, diabetic retinopathy, and posterior chamber inflammatory disease. However, the treatment of macular edema is considerably limited by the difficulty in delivering effective doses of therapeutic agents into the vitreous cavity. In recent years, the development of a sustained-release dexamethasone intravitreal implant (Ozurdex® has enabled more controlled drug release at a stable rate over a long period of time, with a potentially lower rate of adverse events. Clinical studies indicate that this dexamethasone implant is a promising new treatment option for patients with persistent macular edema resulting from retinal vein occlusion, diabetic retinopathy, and uveitis or Irvine-Gass syndrome.Keywords: diabetic retinopathy, macular edema, Ozurdex®, posterior-segment inflammatory disease, retinal vein occlusion, sustained-release dexamethasone implant

  16. 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.

  17. 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 ...

  18. 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.

  19. 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).

  20. LC for analysis of two sustained-release mixtures containing cough cold suppressant drugs.

    Science.gov (United States)

    El-Gindy, Alaa; Sallam, Shehab; Abdel-Salam, Randa A

    2010-07-01

    A liquid chromatographic method was applied for the analysis of two sustained-release mixtures containing dextromethorphane hydrobromide, carbinoxamine maleate with either phenylephrine hydrochloride in pharmaceutical capsules (Mix 1) or phenyl-propanolamine, methylparaben, and propylparaben, which bonds as a drug base to ion exchange resin in pharmaceutical syrup (Mix 2). The method was used for their simultaneous determination using a CN column with a mobile phase consisting of acetonitrile-12 mM ammonium acetate in the ratio of 60:40 (v/v, pH 6.0) for Mix 1 and 45:55 (v/v, pH 6.0) for Mix 2.

  1. Natural gums and modified natural gums as sustained-release carriers.

    Science.gov (United States)

    Bhardwaj, T R; Kanwar, M; Lal, R; Gupta, A

    2000-10-01

    Although natural gums and their derivatives are used widely in pharmaceutical dosage forms, their use as biodegradable polymeric materials to deliver bioactive agents has been hampered by the synthetic materials. These natural polysaccharides do hold advantages over the synthetic polymers, generally because they are nontoxic, less expensive, and freely available. Natural gums can also be modified to have tailor-made materials for drug delivery systems and thus can compete with the synthetic biodegradable excipients available in the market. In this review, recent developments in the area of natural gums and their derivatives as carriers in the sustained release of drugs are explored.

  2. Nanomedicine for glaucoma: liposomes provide sustained release of latanoprost in the eye

    Directory of Open Access Journals (Sweden)

    Natarajan JV

    2012-01-01

    Full Text Available Jayaganesh V Natarajan1*, Marcus Ang2*, Anastasia Darwitan1, Sujay Chattopadhyay3, Tina T Wong2, Subbu S Venkatraman1 1Materials Science and Engineering, Nanyang Technological University, Singapore; 2Singapore Eye Research Institute, Singapore; 3Polymer Division, Indian Institute of Technology Roorkee, India*These authors contributed equally to this workPurpose: To report the development and therapeutic evaluation of a liposomal nanocarrier for sustained release of latanoprost, in the rabbit eye.Methods: We fabricated latanoprost-loaded egg-phosphatidylcholine (EggPC liposomes using the film hydration technique. The delivery vehicles were nano-sized (Z avg = 109 ± 18 nm, had a narrow poly dispersity index (PDI = 0.19 ± 0.04, and a very high loading efficiency (94% ± 5%. Based on in vitro data, we evaluated this formulation for lowering intraocular pressure (IOP in rabbit eyes. Following a single subconjunctival injection of the latanoprost loaded formulation, the eyes were clinically monitored and the IOP recorded.Results: Latanoprost-loaded EggPC liposomes demonstrated a high drug/lipid mole ratio of 0.181, remained stable for at least 6 months on storage (4°C, and at least 1 month at 25°C. A slow and sustained release of 60% of latanoprost was achieved by 14 days in the in vitro release study. The same formulation demonstrated a greater sustained IOP lowering effect compared with daily administration of topical latanoprost beyond 90 days (4.8 ± 1.5 vs 2.5 ± 0.9 mmHg; P < 0.001. No signs of inflammation were evident in the eyes from slit-lamp examination analysis.Conclusion: The loading required for a long-term sustained delivery of latanoprost for up to 90 days in the rabbit eyes was achieved with EggPC liposomes. A single injection of latanoprost-loaded EggPC liposomes can lower the IOP for up to 90 days, with a greater IOP lowering effect than daily topical administration of latanoprost.Keywords: nanomedicine, nanoliposomes, Egg

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-10-01

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

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

  5. Effect of sustained-release isosorbide dinitrate on post-prandial gastric emptying and gastroduodenal motility in healthy humans

    DEFF Research Database (Denmark)

    Madsen, J L; Rasmussen, S L; Linnet, J

    2004-01-01

    Nitric oxide (NO) is an inhibitory neurotransmitter released by non-adrenergic and non-cholinergic neurons that innervate the smooth muscles of the gastrointestinal tract. We examined whether NO, derived from a sustained-release preparation of isosorbide dinitrate, influenced gastric emptying and...

  6. Preparation and characterization of genipin-cross-linked silk fibroin/chitosan sustained-release microspheres

    Directory of Open Access Journals (Sweden)

    Zeng SG

    2015-05-01

    Full Text Available Shuguang Zeng,1,* Manwen Ye,1,2,* Junqi Qiu,1 Wei Fang,1 Mingdeng Rong,1 Zehong Guo,1 Wenfen Gao11Department of Oral and Maxillofacial Surgery, Guangdong Provincial Stomatological Hospital, Southern Medical University, 2Department of Stomatology, Guangdong Women and Children Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workAbstract: We report the effects of distinct concentrations of genipin and silk fibroin (SF:chitosan (CS ratios on the formation of SF–CS composite microspheres. We selected microspheres featuring an SF:CS ratio of 1:1, encapsulated various concentrations of bovine serum albumin (BSA, and then compared their encapsulation efficiency and sustained-release rate with those of pure CS microspheres. We determined that the following five groups of microspheres were highly spherical and featured particle sizes ranging from 70 µm to 147 µm: mass ratio of CS:SF =1:0.5, 0.1 g or 0.5 g genipin; CS:SF =1:1, 0.05 g or 1 g genipin; and CS:SF =1:2, 0.5 g genipin. The microspheres prepared using 1:1 CS:SF ratio and 0.05 g genipin in the presence of 10 mg, 20 mg, and 50 mg of BSA exhibited encapsulation efficiencies of 50.16%±4.32%, 56.58%±3.58%, and 42.19%±7.47%, respectively. Fourier-transform infrared spectroscopy (FTIR results showed that SF and CS were cross-linked and that the α-helices and random coils of SF were converted into β-sheets. BSA did not chemically react with CS or SF. Moreover, thermal gravimetric analysis (TGA results showed that the melting point of BSA did not change, which confirmed the FTIR results, and X-ray diffraction results showed that BSA was entrapped in microspheres in a noncrystalline form, which further verified the TGA and FTIR data. The sustained-release microspheres prepared in the presence of 10 mg, 20 mg, and 50 mg of BSA burst release 30.79%±3.43%, 34.41%±4.46%, and 41.75%±0.96% of the

  7. Novel bio-active lipid nanocarriers for the stabilization and sustained release of sitosterol

    International Nuclear Information System (INIS)

    Lacatusu, I; Badea, N; Stan, R; Meghea, A

    2012-01-01

    In this work, new stable and efficiently bio-active lipid nanocarriers (NLCs) with antioxidant properties have been developed for the transport of active ingredients in food. The novel NLCs loaded with β-sitosterol/β-sitosterol and green tea extract (GTE) and prepared by a combination of natural oils (grape seed oil, fish oil and squalene) and biological lipids with food grade surfactants, were physico-chemically examined by DLS, TEM, electrokinetic potential, DSC and HPLC and found to have main diameters less than 200 nm, a spherical morphology, excellent physical stability, an imperfect crystalline lattice and high entrapment efficiency. The novel loaded-NLCs have demonstrated the potential to develop a high blocking action of chain reactions, trapping up to 92% of the free-oxygen radicals, as compared to the native β-sitosterol (AA%=36.5). Another advantage of this study is associated with the quality of bio-active NLCs based on grape seed oil and squalene to manifest a better sitosterol—sustained release behaviour as compared to their related nanoemulsions. By coupling both in vitro results, i.e. the enhanced antioxidant activity and superior release properties, this study emphasizes the sustainability of novel bio-active nanocarriers to gain specific bio-food features for development of functional foods with a high applicability spectrum. (paper)

  8. Multifunctional Environmental Smart Fertilizer Based on l-Aspartic Acid for Sustained Nutrient Release.

    Science.gov (United States)

    Lü, Shaoyu; Feng, Chen; Gao, Chunmei; Wang, Xinggang; Xu, Xiubin; Bai, Xiao; Gao, Nannan; Liu, Mingzhu

    2016-06-22

    Fertilizer is one of the most important elements of modern agriculture. However, conventional fertilizer, when applied to crops, is vulnerable to losses through volatilization, leaching, nitrification, or other means. Such a loss limits crop yields and pollutes the environment. In an effort to enhance nutrient use efficiency and reduce environmental pollution, an environmental smart fertilizer was reported in the current study. Poly(aspartic acid) and a degradable macro-cross-linker based on l-aspartic acid were synthesized and introduced into the fertilizer as a superabsorbent to improve the fertilizer degradability and soil moisture-retention capacity. Sustained release behavior of the fertilizer was achieved in soil. Cumulative release of nitrogen and phosphorus was 79.8% and 64.4% after 30 days, respectively. The water-holding and water-retention capacities of soil with the superabsorbent are obviously higher than those of the control soil without superabsorbent. For the sample of 200 g of soil with 1.5 g of superabsorbent, the water-holding capacity is 81.8%, and the water-retention capacity remains 22.6% after 23 days. All of the current results in this study indicated that the as-prepared fertilizer has a promising application in sustainable modern agriculture.

  9. Novel Injectable Pentablock Copolymer Based Thermoresponsive Hydrogels for Sustained Release Vaccines.

    Science.gov (United States)

    Bobbala, Sharan; Tamboli, Viral; McDowell, Arlene; Mitra, Ashim K; Hook, Sarah

    2016-01-01

    The need for multiple vaccinations to enhance the immunogenicity of subunit vaccines may be reduced by delivering the vaccine over an extended period of time. Here, we report two novel injectable pentablock copolymer based thermoresponsive hydrogels made of polyethyleneglycol-polycaprolactone-polylactide-polycaprolactone-polyethyleneglycol (PEG-PCL-PLA-PCL-PEG) with varying ratios of polycaprolactone (PCL) and polylactide (PLA), as single shot sustained release vaccines. Pentablock copolymer hydrogels were loaded with vaccine-encapsulated poly lactic-co-glycolic acid nanoparticles (PLGA-NP) or with the soluble vaccine components. Incorporation of PLGA-NP into the thermoresponsive hydrogels increased the complex viscosity of the gels, lowered the gelation temperature, and minimized the burst release of antigen and adjuvants. The two pentablock hydrogels stimulated both cellular and humoral responses. The addition of PLGA-NP to the hydrogels sustained immune responses for up to 49 days. The polymer with a higher ratio of PCL to PLA formed a more rigid gel, induced stronger immune responses, and stimulated effective anti-tumor responses in a prophylactic melanoma tumor model.

  10. A dual strategy to improve psychotic patients’ compliance using sustained release quetiapine oral disintegrating tablets

    Directory of Open Access Journals (Sweden)

    Refaat Ahmed

    2016-12-01

    Full Text Available Quetiapine (QT is a short acting atypical antipsychotic drug effective in schizophrenia and bipolar disorder. This study aims at designing a novel dosage form of sustained release taste-masked QT orally disintegrating tablets (ODTs based on solid lipid micro-pellets (SLMPs. QT SLMPs were prepared using the hot melt extrusion technique and utilizing three lipid carriers: Compritol, Precirol and white beeswax either alone or in mixtures. They showed sustained QT release and a taste masking effect. The selected QT SLMP was further blended with an aqueous solution containing polyvinylpyrollidone (2.5 %, croscarmellose sodium (2 % and mannitol (50 %; it was then lyophilized into ODT in a mass ratio of 1:2, respectively. ODTs containing QT SLMPs showed: average wetting time (40.92 s, average oral disintegration time (21.49 s, average hardness (16.85 N and also imparted suitable viscosity to suspend pellets during the lyophilization process. In conclusion, lyophilization is a promising technique for the formulation of multiparticulate systems into ODTs.

  11. Sustained release donepezil loaded PLGA microspheres for injection: Preparation, in vitro and in vivo study

    Directory of Open Access Journals (Sweden)

    Wenjia Guo

    2015-10-01

    Full Text Available The purpose of this study was to develop a PLGA microspheres-based donepezil (DP formulation which was expected to sustain release of DP for one week with high encapsulation efficiency (EE. DP derived from donepezil hydrochloride was encapsulated in PLGA microspheres by the O/W emulsion-solvent evaporation method. The optimized formulation which avoided the crushing of microspheres during the preparation process was characterized in terms of particle size, morphology, drug loading and EE, physical state of DP in the matrix and in vitro and in vivo release behavior. DP microspheres were prepared successfully with average diameter of 30 µm, drug loading of 15.92 ± 0.31% and EE up to 78.79 ± 2.56%. Scanning electron microscope image showed it has integrated spherical shape with no drug crystal and porous on its surface. Differential scanning calorimetry and X-ray diffraction results suggested DP was in amorphous state or molecularly dispersed in microspheres. The Tg of PLGA was increased with the addition of DP. The release profile in vitro was characterized with slow but continuous release that lasted for about one week and fitted well with first-order model, which suggested the diffusion governing release mechanism. After single-dose administration of DP microspheres via subcutaneous injection in rats, the plasma concentration of DP reached peak concentration at 0.50 d, and then declined gradually, but was still detectable at 15 d. A good correlation between in vitro and in vivo data was obtained. The results suggest the potential use of DP microspheres for treatment of Alzheimer's disease over long periods.

  12. Effect of sustained-release isosorbide dinitrate on post-prandial gastric emptying and gastroduodenal motility in healthy humans

    DEFF Research Database (Denmark)

    Madsen, Jan Lysgård; Rasmussen, S L; Linnet, J

    2004-01-01

    and gastroduodenal motility after a meal. Eleven healthy volunteers participated in a double-blind, placebo-controlled, cross-over study. Each subject ingested 40 mg isosorbide dinitrate orally as a sustained-release formulation or oral placebo, in random order. Gastric emptying and gastroduodenal motility were...... consecutive 15-min periods. A 40 mg single dose of sustained-released isosorbide dinitrate does not seem to alter gastric emptying or gastroduodenal motility after a meal.......Nitric oxide (NO) is an inhibitory neurotransmitter released by non-adrenergic and non-cholinergic neurons that innervate the smooth muscles of the gastrointestinal tract. We examined whether NO, derived from a sustained-release preparation of isosorbide dinitrate, influenced gastric emptying...

  13. Sustained Release Talazoparib Implants for Localized Treatment of BRCA1-deficient Breast Cancer.

    Science.gov (United States)

    Belz, Jodi E; Kumar, Rajiv; Baldwin, Paige; Ojo, Noelle Castilla; Leal, Ana S; Royce, Darlene B; Zhang, Di; van de Ven, Anne L; Liby, Karen T; Sridhar, Srinivas

    2017-01-01

    Talazoparib, a potent PARP inhibitor, has shown promising clinical and pre-clinical activity by inducing synthetic lethality in cancers with germline Brca1/2 mutations. Conventional oral delivery of Talazoparib is associated with significant off-target effects, therefore we sought to develop new delivery systems in the form of an implant loaded with Talazoparib for localized, slow and sustained release of the drug at the tumor site in Brca1 -deficient breast cancer. Poly(lactic-co-glycolic acid) (PLGA) implants (0.8 mm diameter) loaded with subclinical dose (25 or 50 µg) Talazoparib were fabricated and characterized. In vitro studies with Brca1 -deficient W780 and W0069 breast cancer cells were conducted to test sensitivity to PARP inhibition. The in vivo therapeutic efficacy of Talazoparib implants was assessed following a one-time intratumoral injection in Brca1 Co/Co ;MMTV-Cre;p53 +/- mice and compared to drug-free implants and oral gavage. Immunohistochemistry studies were performed on tumor sections using PCNA and γ-H2AX staining. Sustained release of Talazoparib was observed over 28 days in vitro . Mice treated with Talazoparib implants showed statistically significant tumor growth inhibition compared to those receiving drug-free implants or free Talazoparib orally. Talazoparib implants were well-tolerated at both drug doses and resulted in less weight loss than oral gavage. PARP inhibition in mice treated with Talazoparib implants significantly increased double-stranded DNA damage and decreased tumor cell proliferation as shown by PCNA and γ-H2AX staining as compared to controls. These results demonstrate that localized and sustained delivery of Talazoparib via implants has potential to provide superior treatment outcomes at sub-clinical doses with minimal toxicity in patients with BRCA1 deficient tumors.

  14. Surface modified natural zeolite as a carrier for sustained diclofenac release: A preliminary feasibility study.

    Science.gov (United States)

    de Gennaro, Bruno; Catalanotti, Lilia; Cappelletti, Piergiulio; Langella, Alessio; Mercurio, Mariano; Serri, Carla; Biondi, Marco; Mayol, Laura

    2015-06-01

    In view of zeolite potentiality as a carrier for sustained drug release, a clinoptilolite-rich rock from California (CLI_CA) was superficially modified with cetylpyridinium chloride and loaded with diclofenac sodium (DS). The obtained surface modified natural zeolites (SMNZ) were characterized by confocal scanning laser microscopy (CLSM), powder X-ray diffraction (XRPD) and laser light scattering (LS). Their flowability properties, drug adsorption and in vitro release kinetics in simulated intestinal fluid (SIF) were also investigated. CLI_CA is a Na- and K-rich clinoptilolite with a cationic exchange ability that fits well with its zeolite content (clinoptilolite=80 wt%); the external cationic exchange capacity is independent of the cationic surfactant used. LS and CLSM analyses have shown a wide distribution of volume diameters of SMNZ particles that, along with their irregular shape, make them cohesive with scarce flow properties. CLSM observation has revealed the localization of different molecules in/on SMNZ by virtue of their chemical nature. In particular, cationic and polar probes prevalently localize in SMNZ bulk, whereas anionic probes preferentially arrange themselves on SMNZ surface and the loading of a nonpolar molecule in/on SMNZ is discouraged. The adsorption rate of DS onto SMNZ was shown by different kinetic models highlighting the fact that DS adsorption is a pseudo-second order reaction and that the diffusion through the boundary layer is the rate-controlling step of the process. DS release in an ionic medium, such as SIF, can be sustained for about 5h through a mechanism prevalently governed by anionic exchange with a rapid final phase. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. The in vitro sustained release profile and antitumor effect of etoposide-layered double hydroxide nanohybrids

    Directory of Open Access Journals (Sweden)

    Qin LL

    2013-05-01

    Full Text Available Lili Qin,1 Mei Wang,2 Rongrong Zhu,3 Songhui You,1 Ping Zhou,1 Shilong Wang31Department of Physical Education, Tongji University, Shanghai, People's Republic of China; 2Department of Chemistry, Tongji University, Shanghai, People's Republic of China; 3School of Life Science and Technology, Tongji University, Shanghai, People's Republic of ChinaAbstract: Magnesium-aluminum layered double hydroxides intercalated with antitumor drug etoposide (VP16 were prepared for the first time using a two-step procedure. The X-ray powder diffraction data suggested the intercalation of VP16 into layers with the increased basal spacing from 0.84–1.18 nm was successful. Then, it was characterized by X-ray powder diffraction, Fourier transform infrared spectroscopy, thermogravimetry and differential thermal analysis, and transmission electron microscopy. The prepared nanoparticles, VP16-LDH, showed an average diameter of 62.5 nm with a zeta potential of 20.5 mV. Evaluation of the buffering effect of VP16-LDH indicated that the nanohybrids were ideal for administration of the drugs that treat human stomach irritation. The loading amount of intercalated VP16 was 21.94% and possessed a profile of sustained release. The mechanism of VP16-LDH release in the phosphate buffered saline solution at pH 7.4 is likely controlled by the diffusion of VP16 anions from inside to the surface of LDH particles. The in vitro cytotoxicity and antitumor assays indicated that VP16-LDH hybrids were less toxic to GES-1 cells while exhibiting better antitumor efficacy on MKN45 and SGC-7901 cells. These results imply that VP16-LDH is a potential antitumor drug for a broad range of gastric cancer therapeutic applications.Keywords: layered double hydroxides, etoposide, drug delivery, antitumor effect, sustained release

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

    Directory of Open Access Journals (Sweden)

    Dinesh M. Morkhade

    2017-09-01

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

  17. Heparin modified graphene oxide for pH-sensitive sustained release of doxorubicin hydrochloride

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Baomei; Yang, Xiaoye; Wang, Yang; Zhai, Guangxi, E-mail: professorgxzhai@126.com

    2017-06-01

    A novel nanocarrier of heparin (Hep) modified graphene oxide (GO) was fabricated via a linker (adipic dihydrazide) and used as a pH-sensitive drug delivery system for controlling the release of anticancer drug doxorubicin (DOX) for anti-tumor therapy. The finally obtained nanocarrier was GO-ADH-Hep with better stability, blood compatibility and biocompatibility confirmed by the hemolytic test and in vitro cytotoxicity study. Its safety issue was greatly improved via Hep modification. The amount of DOX loaded onto GO-ADH-Hep was significantly high and dependent on pH value. The release rate of DOX from GO- ADH-Hep/DOX was pH-sensitive and much-slower than that of free DOX solution suggesting the sustained drug-release capacity of this prepared nanocomplexes. In addition, the results of cytotoxicity study illustrated that this fabricated nanocomplexes displayed effective cytotoxicity to MCF-7 and HepG2 cells. What's more, the results of the in vivo pharmacokinetic study was also indicated that the GO-ADH-Hep/DOX nanocomplexes could significantly prolong the retention time of DOX in vivo and this was consistent with the in vitro drug release performance. And finally, according to the biodistribution study, DOX delivered by GO-ADH-Hep could reduce cardiotoxicity deriving from DOX solution and also decrease the pulmonary toxicity deriving from unmodified GO. Based on the in vitro and in vivo investigations, the fabricated GO-ADH-Hep could be a promising candidate as an ideal nano-carrier for drug delivery and anti-cancer therapy. - Highlights: • Firstly, a novel nanocarrier-GO-ADH-Hep was fabricated with improved stability, little cytotoxicity and little hemolysis ratio. • Secondly, GO-ADH-Hep was used to load the anticancer drug (DOX) with high drug loading and pH-sensitive sustained drug release. • Thirdly, the anti-cancer efficacy of GO-ADH-Hep/DOX was dose- and time-dependent in vitro. • Finally, according to the in vivo studies, this synthesized nano

  18. Chlorogenic acid loaded chitosan nanoparticles with sustained release property, retained antioxidant activity and enhanced bioavailability

    Directory of Open Access Journals (Sweden)

    Ilaiyaraja Nallamuthu

    2015-06-01

    Full Text Available In this study, chlorogenic acid (CGA, a phenolic compound widely distributed in fruits and vegetables, was encapsulated into chitosan nanoparticles by ionic gelation method. The particles exhibited the size and zeta potential of 210 nm and 33 mV respectively. A regular, spherical shaped distribution of nanoparticles was observed through scanning electron microscopy (SEM and the success of entrapment was confirmed by FTIR analysis. The encapsulation efficiency of CGA was at about 59% with the loading efficiency of 5.2%. In vitro ABTS assay indicated that the radical scavenging activity of CAG was retained in the nanostructure and further, the release kinetics study revealed the burst release of 69% CGA from nanoparticles at the end of 100th hours. Pharmacokinetic analysis in rats showed a lower level of Cmax, longer Tmax, longer MRT, larger AUC0–t and AUC0–∞ for the CGA nanoparticles compared to free CGA. Collectively, these results suggest that the synthesised nanoparticle with sustained release property can therefore ease the fortification of food-matrices targeted for health benefits through effective delivery of CGA in body.

  19. Reduction of radiocesium transfer to animal products using sustained release boli with ammoniumiron(3)-Hexacyanoferrate(2)

    International Nuclear Information System (INIS)

    Hove, K.; Hansen, H.S.

    1993-01-01

    A sustained release boulus with the cesium binder ammoniumiron(III) - hexacyanoferrate (AFCF) has been developed as a countermeasure for small ruminants grazing pastures contaminated by radiocesium ( 134 Cs+ 137 Cs). The boli (40-50 g) are produced by compression of a mixture of AFCF, barite and wax. The release of AFCF from boli labelled with 137Cs-iron-hexacyanoferrate complex was studied in laboratory sheep. The release rate followed first order kinetics during the 108 d of observation and decreased from 40 to 22, 110 to 35 and 280 to 25 mg d -1 in sheep treated with 1, 2 or 3 boli respectively. The efficiency of boli in reducing radiocesium transfer to meat and milk was tested in laboratory studies with goats fed 134 Cs tracer. Until 40 d after treatment the transfer of radiocesium to milk was reduced by 35%, 60% and 85% in goats given 1, 2 og 3 boli, respectively. The reduction in radiocaesium transfer persisted for 90 d but with a lower efficiency. A similar relationship was found between number of boli and the reduction in radiocesium transfer to meat with an observed maximal reduction of 60%. (au) (20 refs.)

  20. Preparation of sustained release capsules by electrostatic dry powder coating, using traditional dip coating as reference.

    Science.gov (United States)

    Yang, Yan; Shen, Lian; Yuan, Feng; Fu, Hui; Shan, Weiguang

    2018-05-30

    Lately, a great deal of attention is being paid to capsule coating, since the coat protects active pharmaceutical ingredients (APIs) from damage, as is in the case of tablet and pellet. However, moisture and heat sensitivity of gelatin shells make it challenging to coat capsules using the conventional aqueous coating techniques. In an effort to overcome this challenge, the present study aims to coat capsules using two different coating techniques: electrostatic dry powder coating (EDPC) and dip coating (DC). Both capsule coatings and free films were prepared by these two coating techniques, and the effects of coating formulations and processing conditions on the film quality were investigated. The corresponding drug in vitro release and mechanisms were characterized and compared. The results of dissolution tests demonstrated that the drug release behavior of both EDPC and DC coated capsules could be optimized to a sustained release of 24 h, following the Fick's diffusion law. The results of this study suggest that EDPC method is better than DC method for coating capsules, with respect to the higher production efficiency and better stability, indicating that this dry coating technology has promised in gelatin capsule coating applications. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. WATER HYACINTH: A POSSIBLE ALTERNATIVE RATE RETARDING NATURAL POLYMER USED IN SUSTAINED RELEASE TABLET DESIGN

    Directory of Open Access Journals (Sweden)

    Sabera eKhatun

    2014-06-01

    Full Text Available In recent years natural polymers have been widely used, because of their effectiveness and availability over synthetic polymers. In this present investigation matrix tablets of Metformin hydrochloride were formulated using Water hyacinth powder and its rate retardant activity was studied. Tablets were prepared using wet granulation method with 8% starch as granulating agent and 5%, 10%, 15%, 20%, 25% and 30% of Water hyacinth powder to the drug. In preformulation study, angle of repose, Carr’s Index and Hausner ratio were calculated. Fourier Transform Infrared Spectroscopy (FTIR, Differential Scanning Calorimetry (DSC and Scanning Electron Microscopy (SEM studies were performed and no interactions were found between drug and excipients. Weight variation, friability, hardness, thickness, diameter, and in vitro release study were performed with the prepared matrix tablets. Dissolution studies were conducted using USP type II apparatus at a speed of 100 rpm at 37oC ± 0.5 temperature, for 8 hours. All the formulations comply with both BP and USP requirements, but among all the formulations F-1 (5% of Water hyacinth was the best fitted formula. The drug release patterns were explained in different kinetic models such as Zero order, First order, Higuchi, Hixson Crowell and Korsmeyer-Peppas equations. The current investigation implies that Water hyacinth has the potential to be used as a rate-retarding agent in sustained release drug formulations.

  2. Electrospun Blank Nanocoating for Improved Sustained Release Profiles from Medicated Gliadin Nanofibers

    Directory of Open Access Journals (Sweden)

    Xinkuan Liu

    2018-03-01

    Full Text Available Nanomaterials providing sustained release profiles are highly desired for efficacious drug delivery. Advanced nanotechnologies are useful tools for creating elaborate nanostructure-based nanomaterials to achieve the designed functional performances. In this research, a modified coaxial electrospinning was explored to fabricate a novel core-sheath nanostructure (nanofibers F2, in which a sheath drug-free gliadin layer was successfully coated on the core ketoprofen (KET-gliadin nanocomposite. A monolithic nanocomposite (nanofibers F1 that was generated through traditional blending electrospinning of core fluid was utilized as a control. Scanning electron microscopy demonstrated that both nanofibers F1 and F2 were linear. Transmission electron microscopy verified that nanofibers F2 featured a clear core-sheath nanostructure with a thin sheath layer about 25 nm, whereas their cores and nanofibers F1 were homogeneous KET-gliadin nanocomposites. X-ray diffraction patterns verified that, as a result of fine compatibility, KET was dispersed in gliadin in an amorphous state. In vitro dissolution tests demonstrated that the thin blank nanocoating in nanofibers F2 significantly modified drug release kinetics from a traditional exponential equation of nanofibers F1 to a zero-order controlled release model, linearly freeing 95.7 ± 4.7% of the loaded cargoes over a time period of 16 h.

  3. Electrospun Blank Nanocoating for Improved Sustained Release Profiles from Medicated Gliadin Nanofibers.

    Science.gov (United States)

    Liu, Xinkuan; Shao, Wenyi; Luo, Mingyi; Bian, Jiayin; Yu, Deng-Guang

    2018-03-22

    Nanomaterials providing sustained release profiles are highly desired for efficacious drug delivery. Advanced nanotechnologies are useful tools for creating elaborate nanostructure-based nanomaterials to achieve the designed functional performances. In this research, a modified coaxial electrospinning was explored to fabricate a novel core-sheath nanostructure (nanofibers F2), in which a sheath drug-free gliadin layer was successfully coated on the core ketoprofen (KET)-gliadin nanocomposite. A monolithic nanocomposite (nanofibers F1) that was generated through traditional blending electrospinning of core fluid was utilized as a control. Scanning electron microscopy demonstrated that both nanofibers F1 and F2 were linear. Transmission electron microscopy verified that nanofibers F2 featured a clear core-sheath nanostructure with a thin sheath layer about 25 nm, whereas their cores and nanofibers F1 were homogeneous KET-gliadin nanocomposites. X-ray diffraction patterns verified that, as a result of fine compatibility, KET was dispersed in gliadin in an amorphous state. In vitro dissolution tests demonstrated that the thin blank nanocoating in nanofibers F2 significantly modified drug release kinetics from a traditional exponential equation of nanofibers F1 to a zero-order controlled release model, linearly freeing 95.7 ± 4.7% of the loaded cargoes over a time period of 16 h.

  4. Reduction of radiocesium transfer to animal products using sustained release boli with ammoniumiron(3)-Hexacyanoferrate(2)

    Energy Technology Data Exchange (ETDEWEB)

    Hove, K; Hansen, H S [Department of Animal Science, Agricultural University of Norway, Aas (Norway)

    1993-01-01

    A sustained release boulus with the cesium binder ammoniumiron(III) - hexacyanoferrate (AFCF) has been developed as a countermeasure for small ruminants grazing pastures contaminated by radiocesium ([sup 134]Cs+[sup 137]Cs). The boli (40-50 g) are produced by compression of a mixture of AFCF, barite and wax. The release of AFCF from boli labelled with 137Cs-iron-hexacyanoferrate complex was studied in laboratory sheep. The release rate followed first order kinetics during the 108 d of observation and decreased from 40 to 22, 110 to 35 and 280 to 25 mg d[sup -1] in sheep treated with 1, 2 or 3 boli respectively. The efficiency of boli in reducing radiocesium transfer to meat and milk was tested in laboratory studies with goats fed [sup 134]Cs tracer. Until 40 d after treatment the transfer of radiocesium to milk was reduced by 35%, 60% and 85% in goats given 1, 2 og 3 boli, respectively. The reduction in radiocaesium transfer persisted for 90 d but with a lower efficiency. A similar relationship was found between number of boli and the reduction in radiocesium transfer to meat with an observed maximal reduction of 60%. (au) (20 refs.).

  5. Water hyacinth: a possible alternative rate retarding natural polymer used in sustained release tablet design.

    Science.gov (United States)

    Khatun, Sabera; Sutradhar, Kumar B

    2014-01-01

    In recent years natural polymers have been widely used because of their effectiveness and availability over synthetic polymers. In this present investigation matrix tablets of Metformin hydrochloride were formulated using Water hyacinth powder and its rate retardant activity was studied. Tablets were prepared using wet granulation method with 8% starch as granulating agent and 5, 10, 15, 20, 25 and 30% of Water hyacinth powder to the drug. In preformulation study, angle of repose, Carr's Index and Hausner ratio were calculated. Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Scanning Electron Microscopy (SEM) studies were performed and no interactions were found between drug and excipients. Weight variation, friability, hardness, thickness, diameter, and in vitro release study were performed with the prepared matrix tablets. Dissolution studies were conducted using USP type II apparatus at a speed of 100 rpm at 37°C ± 0.5 temperature for 8 h. Though all the formulations comply with both BP and USP requirements, formulation F-1 (5% of Water hyacinth) was the best fitted formula. The drug release patterns were explained in different kinetic models such as Zero order, First order, Higuchi, Hixson Crowell, and Korsmeyer-Peppas equations. The current investigation implies that Water hyacinth has the potential to be used as a rate-retarding agent in sustained release drug formulations.

  6. Development and Evaluation of High Bioavailable Sustained-Release Nimodipine Tablets Prepared with Monolithic Osmotic Pump Technology.

    Science.gov (United States)

    Kong, Hua; Yu, Fanglin; Liu, Yan; Yang, Yang; Li, Mingyuan; Cheng, Xiaohui; Hu, Xiaoqin; Tang, Xuemei; Li, Zhiping; Mei, Xingguo

    2018-01-01

    Frequent administration caused by short half-life and low bioavailability due to poor solubility and low dissolution rate limit the further application of poorly water-soluble nimodipine, although several new indications have been developed. To overcome these shortcomings, sophisticated technologies had to be used since the dose of nimodipine was not too low and the addition of solubilizers could not resolve the problem of poor release. The purpose of this study was to obtain sustained and complete release of nimodipine with a simple and easily industrialized technology. The expandable monolithic osmotic pump tablets containing nimodipine combined with poloxamer 188 and carboxymethylcellulose sodium were prepared. The factors affecting drug release including the amount of solubilizing agent, expanding agent, retarding agent in core tablet and porogenic agent in semipermeable film were optimized. The release behavior was investigated both in vitro and in beagle dogs. It was proved that the anticipant release of nimodipine could be realized in vitro. The sustained and complete release of nimodipine was also realized in beagles because the mean residence time of nimodipine from the osmotic pump system was longer and Cmax was lower than those from the sustained-release tablets in market while there was no difference in AUC(0-t) of the monolithic osmotic pump tablets and the sustained release tablets in market. It was reasonable to believe that the sustained and complete release of poorly watersoluble nimodipine could be realized by using simple expandable monolithic osmotic pump technology combined with surfactant. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Development of Sustained Release "NanoFDC (Fixed Dose Combination" for Hypertension - An Experimental Study.

    Directory of Open Access Journals (Sweden)

    Anjuman Arora

    Full Text Available The present study was planned to formulate, characterize and evaluate the pharmacokinetics of a novel "NanoFDC" comprising three commonly prescribed anti-hypertensive drugs, hydrochlorothiazide (a diuretic, candesartan (ARB and amlodipine (a calcium channel blocker.The candidate drugs were loaded in Poly (DL-lactide-co-gycolide (PLGA by emulsion- diffusion-evaporation method. The formulations were evaluated for their size, morphology, drug loading and in vitro release individually. Single dose pharmacokinetic profiles of the nanoformulations alone and in combination, as a NanoFDC, were evaluated in Wistar rats.The candidate drugs encapsulated inside PLGA showed entrapment efficiencies ranging from 30%, 33.5% and 32% for hydrochlorothiazide, candesartan and amlodipine respectively. The nanoparticles ranged in size from 110 to 180 nm. In vitro release profile of the nanoformulation showed 100% release by day 6 in the physiological pH 7.4 set up with PBS (phosphate buffer saline and by day 4-5 in the intestinal pH 1.2 and 8.0 set up SGF (simulated gastric fluid and SIF (simulated intestinal fluid respectively. In pharmacokinetic analysis a sustained-release for 6 days and significant increase in the mean residence time (MRT, as compared to the respective free drugs was noted [MRT of amlodipine, hydrochlorothiazide and candesartan changed from 8.9 to 80.59 hours, 11 to 69.20 hours and 9 to 101.49 hours respectively].We have shown for the first time that encapsulating amlodipine, hydrochlorothiazide and candesartan into a single nanoformulation, to get the "NanoFDC (Fixed Dose Combination" is a feasible strategy which aims to decrease pill burden.

  8. Polymer based microspheres of aceclofenac as sustained release parenterals for prolonged anti-inflammatory effect

    Energy Technology Data Exchange (ETDEWEB)

    Kaur, Manpreet; Sharma, Sumit; Sinha, VR, E-mail: sinha_vr@rediffmail.com

    2017-03-01

    Poly(lactic-co-glycolic acid) (PLGA) (75:25) and polycaprolactone (PCL) microspheres were fabricated for prolonged release of aceclofenac by parenteral administration. Microspheres encapsulating aceclofenac were designed to release the drug at controlled rate for around one month. Biodegradable microspheres were prepared by solvent emulsification evaporation method in different polymer:drug ratios (1:1, 2:1 and 3:1). After drug loading, PLGA and PCL microspheres showed a controlled size distribution with an average size of 11.75 μm and 3.81 μm respectively and entrapment efficiency in the range of 90 ± 0.72% to 91.06 ± 4.01% with PLGA and 83.01 ± 2.13% to 90.4 ± 2.11% with PCL. Scanning electron microscopy has confirmed good spherical structures of microspheres. The percent yield of biodegradable polymeric microspheres ranged between 30.95 ± 10.14% to 92.84 ± 3.15% and 47.33 ± 4.72% to 80 ± 3.60% for PLGA and PCL microspheres respectively. PLGA microspheres followed Higuchi release pattern while Korsmeyer-Peppas explained the release pattern of PCL microspheres. Stability studies of microspheres were also carried out by storing the preparations at 2-8 °C for 30, 60 and 90 days and evaluating them for entrapment efficiency, residual drug content and polymer drug compatability. In-vivo studies showed significant anti-inflammatory activity of microspheres upto 48 hours using the carrageenan induced rat paw oedema model. - Highlights: • PLGA and PCL polymeric microspheres for parenteral prolonged drug delivery system were formulated. • Polymeric microspheres were characterized physically and drug excipient incompatability. • Three months accelerated stability studies were carried for drug loaded polymeric microspheres. • Pharmacodynamic studies prove the rationality of sustained therapeutic effect of designed drug delivery system.

  9. Sustained Dye Release Using Poly(urea-urethane)/Cellulose Nanocrystal Composite Microcapsules.

    Science.gov (United States)

    Yoo, Youngman; Martinez, Carlos; Youngblood, Jeffrey P

    2017-02-14

    The aim of this study is to develop methods to reinforce polymeric microspheres with cellulose nanocrystals (CNCs) to make eco-friendly microcapsules for a variety of applications such as medicines, perfumes, nutrients, pesticides, and phase change materials. Surface hydrophobization treatments for CNCs were performed by grafting poly(lactic acid) oligomers and fatty acids (FAs) to enhance the dispersion of nanoparticles in the polymeric shell. Then, a straightforward process is demonstrated to design sustained release microcapsules by the incorporation of the modified CNCs (mCNCs) in the shell structure. The combination of the mCNC dispersion with subsequent interfacial polyurea (PU) to form composite capsules as well as their morphology, composition, mechanical properties, and release rates were examined in this study. The PU microcapsules embedded with the mCNC were characterized by Fourier transform infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA). The morphologies of the microcapsules were characterized by optical microscopy (OM) and scanning electron microscope (SEM). The rupture stress and failure behavior of the microcapsules were determined through single-capsule compression tests. Oil-soluble Sudan II dye solution in mineral oil was utilized as a model hydrophobic fill, representing other latent fills with low partition coefficients, and their encapsulation efficiency was measured spectroscopically. The release rates of the encapsulated dye from the microcapsules were examined spectroscopically by both ethanol and 2-ethyl-1-hexanol medium at room temperature. The concentration of released dye was determined by using UV-vis absorption spectrometry (UV-vis). The mCNC embedded poly(urea-urethane) capsules have strong and dense walls, which function as excellent barriers against leakage due to their extended diffusion path length and ensure enough mechanical strength from rupture for handling or postprocessing.

  10. [Construction and evaluation of the tissue engineered nerve of bFGF-PLGA sustained release microspheres].

    Science.gov (United States)

    Wang, Guanglin; Lin, Wei; Gao, Weiqiang; Xiao, Yuhua; Dong, Changchao

    2008-12-01

    To study the outcomes of nerve defect repair with the tissue engineered nerve, which is composed of the complex of SCs, 30% ECM gel, bFGF-PLGA sustained release microspheres, PLGA microfilaments and permeable poly (D, L-lactic acid) (PDLLA) catheters. SCs were cultured and purified from the sciatic nerves of 1-day-old neonatal SD rats. The 1st passage cells were compounded with bFGF-PLGA sustained release microspheres and ECM gel, and then were injected into permeable PDLLA catheters with PLGA microfilaments inside. In this way, the tissue engineered nerve was constructed. Sixty SD rats were included. The model of 15-mm sciatic nerve defects was made, and then the rats were randomly divided into 5 groups, with 12 rats in each. In group A, autograft was adopted. In group B, the blank PDLLA catheters with PBS inside were used. In group C, PDLLA catheters, with PLGA microfilaments and 30% ECM gel inside, were used. In group D, PDLLA catheters, with PLGA microfilaments, SCs and 30% ECM gel inside, were used. In group E, the tissue engineered nerve was applied. After the operation, observation was made for general conditions of the rats. The sciatic function index (SFI) analysis was performed at 12, 16, 20 and 24 weeks after the operation, respectively. Electrophysiological detection and histological observation were performed at 12 and 24 weeks after the operation, respectively. All rats survived to the end of the experiment. At 12 and 16 weeks after the operation, group E was significantly different from group B in SFI (P fibers in group E were significantly differents from those in groups A, B and C (P fibers in group E were smaller than those in group A (P fibers in group E was significantly different from those in groups A, B, C (P fibers in group E were bigger than those in groups B and C (P < 0.05). The tissue engineered nerve with the complex of SCs, ECM gel, bFGF-PLGA sustained release microspheres, PLGA microfilaments and permeable PDLLA catheters promote

  11. The Stability, Sustained Release and Cellular Antioxidant Activity of Curcumin Nanoliposomes

    Directory of Open Access Journals (Sweden)

    Xing Chen

    2015-08-01

    Full Text Available Curcumin is a multifunctional and natural agent considered to be pharmacologically safe. However, its application in the food and medical industry is greatly limited by its poor water solubility, physicochemical instability and inadequate bioavailability. Nanoliposome encapsulation could significantly enhance the solubility and stability of curcumin. Curcumin nanoliposomes exhibited good physicochemical properties (entrapment efficiency = 57.1, particle size = 68.1 nm, polydispersity index = 0.246, and zeta potential = −3.16 mV. Compared with free curcumin, curcumin nanoliposomes exhibited good stability against alkaline pH and metal ions as well as good storage stability at 4 °C. Curcumin nanoliposomes also showed good sustained release properties. Compared with free curcumin, curcumin nanoliposomes presented an equal cellular antioxidant activity, which is mainly attributed to its lower cellular uptake as detected by fluorescence microscopy and flow cytometry. This study provide theoretical and practical guides for the further application of curcumin nanoliposomes.

  12. 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

  13. Hydrogel doped with nanoparticles for local sustained release of siRNA in breast cancer.

    Science.gov (United States)

    Segovia, Nathaly; Pont, Maria; Oliva, Nuria; Ramos, Victor; Borrós, Salvador; Artzi, Natalie

    2015-01-28

    Of all the much hyped and pricy cancer drugs, the benefits from the promising siRNA small molecule drugs are limited. Lack of efficient delivery vehicles that would release the drug locally, protect it from degradation, and ensure high transfection efficiency, precludes it from fulfilling its full potential. This work presents a novel platform for local and sustained delivery of siRNA with high transfection efficiencies both in vitro and in vivo in a breast cancer mice model. siRNA protection and high transfection efficiency are enabled by their encapsulation in oligopeptide-terminated poly(β-aminoester) (pBAE) nanoparticles. Sustained delivery of the siRNA is achieved by the enhanced stability of the nanoparticles when embedded in a hydrogel scaffold based on polyamidoamine (PAMAM) dendrimer cross-linked with dextran aldehyde. The combination of oligopeptide-terminated pBAE polymers and biodegradable hydrogels shows improved transfection efficiency in vivo even when compared with the most potent commercially available transfection reagents. These results highlight the advantage of using composite materials for successful delivery of these highly promising small molecules to combat cancer. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Controlled release for crop and wood protection: Recent progress toward sustainable and safe nanostructured biocidal systems.

    Science.gov (United States)

    Mattos, Bruno D; Tardy, Blaise L; Magalhães, Washington L E; Rojas, Orlando J

    2017-09-28

    We review biocide delivery systems (BDS), which are designed to deter or control harmful organisms that damage agricultural crops, forests and forest products. This is a timely topic, given the growing socio-economical concerns that have motivated major developments in sustainable BDS. Associated designs aim at improving or replacing traditional systems, which often consist of biocides with extreme behavior as far as their solubility in water. This includes those that compromise or pollute soil and water (highly soluble or volatile biocides) or those that present low bioavailability (poorly soluble biocides). Major breakthroughs are sought to mitigate or eliminate consequential environmental and health impacts in agriculture and silviculture. Here, we consider the most important BDS vehicles or carriers, their synthesis, the environmental impact of their constituents and interactions with the active components together with the factors that affect their rates of release such as environmental factors and interaction of BDS with the crops or forest products. We put in perspective the state-of-the-art nanostructured carriers for controlled release, which need to address many of the challenges that exist in the application of BDS. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Halloysite Clay Nanotubes for Loading and Sustained Release of Functional Compounds.

    Science.gov (United States)

    Lvov, Yuri; Wang, Wencai; Zhang, Liqun; Fakhrullin, Rawil

    2016-02-10

    Halloysite is an alumosilicate tubular clay with a diameter of 50 nm, an inner lumen of 15 nm and a length of 600-900 nm. It is a natural biocompatible nanomaterial available in thousands of tons at low price, which makes it a good candidate for nanoarchitectural composites. The inner lumen of halloysite may be adjusted by etching to 20-30% of the tube volume and loading with functional agents (antioxidants, anticorrosion agents, flame-retardant agents, drugs, or proteins) allowing for formulations with sustained release tuned by the tube end-stoppers for hours and days. Clogging the tube ends in polymeric composites allows further extension of the release time. Thus, antioxidant-loaded halloysite doped into rubber enhances anti-aging properties for at least 12 months. The addition of 3-5 wt% of halloysite increases the strength of polymeric materials, and the possibility of the tube's orientation promises a gradient of properties. Halloysite nanotubes are a promising mesoporous media for catalytic nanoparticles that may be seeded on the tube surface or synthesized exclusively in the lumens, providing enhanced catalytic properties, especially at high temperatures. In vitro and in vivo studies on biological cells and worms indicate the safety of halloysite, and tests for efficient adsorption of mycotoxins in animals' stomachs are also carried out. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Direct encapsulation of water-soluble drug into silica microcapsules for sustained release applications

    International Nuclear Information System (INIS)

    Wang Jiexin; Wang Zhihui; Chen Jianfeng; Yun, Jimmy

    2008-01-01

    Direct encapsulation of water-soluble drug into silica microcapsules was facilely achieved by a sol-gel process of tetraethoxysilane (TEOS) in W/O emulsion with hydrochloric acid (HCl) aqueous solution containing Tween 80 and drug as well as cyclohexane solution containing Span 80. Two water-soluble drugs of gentamicin sulphate (GS) and salbutamol sulphate (SS) were chosen as model drugs. The characterization of drug encapsulated silica microcapsules by scanning electronic microscopy (SEM), FTIR, thermogravimetry (TG) and N 2 adsorption-desorption analyses indicated that drug was successfully entrapped into silica microcapsules. The as-prepared silica microcapsules were uniform spherical particles with hollow structure, good dispersion and a size of 5-10 μm, and had a specific surface area of about 306 m 2 /g. UV-vis and thermogravimetry (TG) analyses were performed to determine the amount of drug encapsulated in the microcapsules. The BJH pore size distribution (PSD) of silica microcapsules before and after removing drug was examined. In vitro release behavior of drug in simulated body fluid (SBF) revealed that such system exhibited excellent sustained release properties

  17. Neural tissue engineering scaffold with sustained RAPA release relieves neuropathic pain in rats.

    Science.gov (United States)

    Ding, Tan; Zhu, Chao; Kou, Zhen-Zhen; Yin, Jun-Bin; Zhang, Ting; Lu, Ya-Cheng; Wang, Li-Ying; Luo, Zhuo-Jing; Li, Yun-Qing

    2014-09-01

    To investigate the effect of locally slow-released rapamycin (RAPA) from bionic peripheral nerve stent to reduce the incidence of neuropathic pain or mitigate the degree of pain after nerve injury. We constructed a neural tissue engineering scaffold with sustained release of RAPA to repair 20mm defects in rat sciatic nerves. Four presurgical and postsurgical time windows were selected to monitor the changes in the expression of pain-related dorsal root ganglion (DRG) voltage-gated sodium channels 1.3 (Nav1.3), 1.7 (Nav1.7), and 1.8 (Nav1.8) through immunohistochemistry (IHC) and Western Blot, along with the observation of postsurgical pathological pain in rats by pain-related behavior approaches. Relatively small upregulation of DRG sodium channels was observed in the experimental group (RAPA+poly(lactic-co-glycolic acid) (PLGA)+stent) after surgery, along with low degrees of neuropathic pain and anxiety, which were similar to those in the Autologous nerve graft group. Autoimmune inflammatory response plays a leading role in the occurrence of post-traumatic neuropathic pain, and that RAPA significantly inhibits the abnormal upregulation of sodium channels to reduce pain by alleviating inflammatory response. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Fabrication and evaluation of a sustained-release chitosan-based scaffold embedded with PLGA microspheres

    International Nuclear Information System (INIS)

    Song, Kedong; Liu, Yingchao; Macedo, Hugo M.; Jiang, Lili; Li, Chao; Mei, Guanyu; Liu, Tianqing

    2013-01-01

    Nutrient depletion within three-dimensional (3D) scaffolds is one of the major hurdles in the use of this technology to grow cells for applications in tissue engineering. In order to help in addressing it, we herein propose to use the controlled release of encapsulated nutrients within polymer microspheres into chitosan-based 3D scaffolds, wherein the microspheres are embedded. This method has allowed maintaining a stable concentration of nutrients within the scaffolds over the long term. The polymer microspheres were prepared using multiple emulsions (w/o/w), in which bovine serum albumin (BSA) and poly (lactic-co-glycolic) acid (PLGA) were regarded as the protein pattern and the exoperidium material, respectively. These were then mixed with a chitosan solution in order to form the scaffolds by cryo-desiccation. The release of BSA, entrapped within the embedded microspheres, was monitored with time using a BCA kit. The morphology and structure of the PLGA microspheres containing BSA before and after embedding within the scaffold were observed under a scanning electron microscope (SEM). These had a round shape with diameters in the range of 27–55 μm, whereas the chitosan-based scaffolds had a uniform porous structure with the microspheres uniformly dispersed within their 3D structure and without any morphological change. In addition, the porosity, water absorption and degradation rate at 37 °C in an aqueous environment of 1% chitosan-based scaffolds were (92.99 ± 2.51) %, (89.66 ± 0.66) % and (73.77 ± 3.21) %, respectively. The studies of BSA release from the embedded microspheres have shown a sustained and cumulative tendency with little initial burst, with (20.24 ± 0.83) % of the initial amount released after 168 h (an average rate of 0.12%/h). The protein concentration within the chitosan-based scaffolds after 168 h was found to be (11.44 ± 1.81) × 10 −2 mg/mL. This novel chitosan-based scaffold embedded with PLGA microspheres has proven to be a

  19. Fabrication and evaluation of a sustained-release chitosan-based scaffold embedded with PLGA microspheres

    Energy Technology Data Exchange (ETDEWEB)

    Song, Kedong, E-mail: kedongsong@dlut.edu.cn [Dalian R and D Center for Stem Cell and Tissue Engineering, State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024 (China); Liu, Yingchao [Dalian R and D Center for Stem Cell and Tissue Engineering, State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024 (China); Macedo, Hugo M. [Biological Systems Engineering Laboratory, Department of Chemical Engineering, Department of Chemical Engineering, South Kensington Campus, London SW7 2AZ (United Kingdom); Jiang, Lili; Li, Chao; Mei, Guanyu [Dalian R and D Center for Stem Cell and Tissue Engineering, State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024 (China); Liu, Tianqing, E-mail: liutq@dlut.edu.cn [Dalian R and D Center for Stem Cell and Tissue Engineering, State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024 (China)

    2013-04-01

    Nutrient depletion within three-dimensional (3D) scaffolds is one of the major hurdles in the use of this technology to grow cells for applications in tissue engineering. In order to help in addressing it, we herein propose to use the controlled release of encapsulated nutrients within polymer microspheres into chitosan-based 3D scaffolds, wherein the microspheres are embedded. This method has allowed maintaining a stable concentration of nutrients within the scaffolds over the long term. The polymer microspheres were prepared using multiple emulsions (w/o/w), in which bovine serum albumin (BSA) and poly (lactic-co-glycolic) acid (PLGA) were regarded as the protein pattern and the exoperidium material, respectively. These were then mixed with a chitosan solution in order to form the scaffolds by cryo-desiccation. The release of BSA, entrapped within the embedded microspheres, was monitored with time using a BCA kit. The morphology and structure of the PLGA microspheres containing BSA before and after embedding within the scaffold were observed under a scanning electron microscope (SEM). These had a round shape with diameters in the range of 27–55 μm, whereas the chitosan-based scaffolds had a uniform porous structure with the microspheres uniformly dispersed within their 3D structure and without any morphological change. In addition, the porosity, water absorption and degradation rate at 37 °C in an aqueous environment of 1% chitosan-based scaffolds were (92.99 ± 2.51) %, (89.66 ± 0.66) % and (73.77 ± 3.21) %, respectively. The studies of BSA release from the embedded microspheres have shown a sustained and cumulative tendency with little initial burst, with (20.24 ± 0.83) % of the initial amount released after 168 h (an average rate of 0.12%/h). The protein concentration within the chitosan-based scaffolds after 168 h was found to be (11.44 ± 1.81) × 10{sup −2} mg/mL. This novel chitosan-based scaffold embedded with PLGA microspheres has proven to be a

  20. Modified thermoresponsive Poloxamer 407 and chitosan sol-gels as potential sustained-release vaccine delivery systems.

    Science.gov (United States)

    Kojarunchitt, Thunjiradasiree; Baldursdottir, Stefania; Dong, Yao-Da; Boyd, Ben J; Rades, Thomas; Hook, Sarah

    2015-01-01

    Thermoresponsive, particle-loaded, Poloxamer 407 (P407)-Pluronic-R® (25R4) or chitosan-methyl cellulose (MC) formulations were developed as single-dose, sustained release vaccines. The sol-gels, loaded either with a particulate vaccine (cubosomes) or soluble antigen (ovalbumin) and adjuvants (Quil A and monophosphoryl lipid A), were free-flowing liquids at room temperature and formed stable gels at physiological temperatures. Rheological results showed that both systems meet the criteria of being thermoresponsive gels. The P407-25R4 sol-gels did not significantly sustain the release of antigen in vivo while the chitosan-MC sol-gels sustained the release of antigen up to at least 14 days after administration. The chitosan-MC sol-gels stimulated both cellular and humoral responses. The inclusion of cubosomes in the sol-gels did not provide a definitive beneficial effect. Further analysis of the formulations with small-angle X-ray scattering (SAXS) revealed that while cubosomes were stable in chitosan-MC gels they were not stable in P407-25R4 formulations. The reason for the mixed response to cubosome-loaded vehicles requires more investigation, however it appears that the cubosomes did not facilitate synchronous vaccine release and may in fact retard release, reducing efficacy in some cases. From these results, chitosan-MC sol-gels show potential as sustained release vaccine delivery systems, as compared to the P407-25R4 system that had a limited ability to sustain antigen release. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Tannate complexes of antihistaminic drug: sustained release and taste masking approaches.

    Science.gov (United States)

    Rahman, Ziyaur; Zidan, Ahmed S; Berendt, Robert T; Khan, Mansoor A

    2012-01-17

    The aim of this investigation was to evaluate the complexation potential of brompheniramine maleate (BPM) and tannic acid (TA) for sustained release and taste masking effects. The complexes (1:1-1:7 TA to BPM ratio) were prepared by the solvent evaporation method using methanol, phosphate buffer pH 6.8 or 0.1N HCl as common solvents. The complexes were characterized microscopically by scanning electron microscopy (SEM), chemically by Fourier transform infrared (FTIR) and solid-state NMR (SSNMR), thermally by differential scanning calorimetry (DSC), for crystallinity by powder X-ray powder diffraction (PXRD), for organoleptic evaluation by electronic tongue (e-tongue), and for solubility in 0.1N HCl and phosphate buffer pH 6.8. The dissolution studies were carried out using the USP II method at 50 rpm in 500 ml of dissolution media (0.1N HCl or phosphate buffer pH 6.8). SEM images revealed that the morphology of complexes were completely different from the individual components, and all complexes had the same morphological characteristics, irrespective of the solvent used for their preparation, pH or ratio of BPM and TA. The FTIR spectra showed the presence of chemical interactions between the TA and BPM. DSC, PXRD and SSNMR indicated that the drug lost its crystalline nature by formation of the complex. Complexation has significantly reduced the solubility of BPM and sustained the drug release up to 24h in phosphate buffer pH 6.8 media. The bitter taste of the BPM was completely masked which was indicated by Euclidean distance values which was far from the drug but near to its placebo in the complexes in all ratios studied. The taste masked complexes can be potentially developed as suitable dosage forms for pediatric use. In summary, complexation of BPM and TA effectively sustained the dissolution and masked the bitter taste of drug for the development of suitable dosage forms for pediatric use. Published by Elsevier B.V.

  2. Sustained-release progesterone nanosuspension following intramuscular injection in ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Heba F Salem

    2010-11-01

    Full Text Available Heba F SalemFaculty of Pharmacy, Beni-Suef University, Beni-Suef, EgyptAbstract: The production of an intramuscular (IM injection of natural progesterone would provide a safer solution than using semi synthetic progesterone. However, disadvantages such as low solubility and a short half life prevent the use of natural progesterone. In this study, we formulated a sustained release form of natural progesterone to be given as IM injection. A progesterone nanosuspension (PNS was first developed and then dispersed in a thermosensitive gel matrix. The selected nanoparticles showed an average particle size of 267 nm and a zeta potential approaching-41 mV. The in vitro release profile of PNS from the F127 plus methyl cellulose gel followed zero order kinetics and correlated linearly with the weight percentage of gel dissolved, demonstrating that the overall rate of release of PNS is controlled by dissolution of the pluronic F127/methyl cellulose (MC gel (r2 > 0.99. The pharmacokinetic parameters of the PNS (6 mg/mL in pluronic F127/MC gel were evaluated in comparison with the control progesterone suspension. After the administration of PNS in F127/MC gel into the rats, a maximum serum concentration of 22.1 ± 1.9 ng/mL was reached at a Tmax of 4.05 ± 0.1 h. The terminal half life was 12.7 ± 0.8 h. The area under the curve AUC0-∞ of the injected formula was 452.75 ± 42.8 ng•h/mL and the total mean residence time was 18.57 ± 1.44 h. The PNS in gel was significantly different from the control in rate and extent at P < 0.001. The natural progesterone which was nanosized and formulated in a thermosensitive gel significantly sustained the action of natural progesterone so that it could be injected every 36 h instead of every day. Moreover, this formula is expected to provide a much safer choice than the use of semi-synthetic progesterone.Keywords: progesterone, nanosuspension, thermosensitive gel, ovariectomized female rats

  3. Sustained-release progesterone nanosuspension following intramuscular injection in ovariectomized rats.

    Science.gov (United States)

    Salem, Heba F

    2010-11-10

    The production of an intramuscular (IM) injection of natural progesterone would provide a safer solution than using semi synthetic progesterone. However, disadvantages such as low solubility and a short half life prevent the use of natural progesterone. In this study, we formulated a sustained release form of natural progesterone to be given as IM injection. A progesterone nanosuspension (PNS) was first developed and then dispersed in a thermosensitive gel matrix. The selected nanoparticles showed an average particle size of 267 nm and a zeta potential approaching-41 mV. The in vitro release profile of PNS from the F127 plus methyl cellulose gel followed zero order kinetics and correlated linearly with the weight percentage of gel dissolved, demonstrating that the overall rate of release of PNS is controlled by dissolution of the pluronic F127/methyl cellulose (MC) gel (r² > 0.99). The pharmacokinetic parameters of the PNS (6 mg/mL) in pluronic F127/MC gel were evaluated in comparison with the control progesterone suspension. After the administration of PNS in F127/MC gel into the rats, a maximum serum concentration of 22.1 ± 1.9 ng/mL was reached at a T(max) of 4.05 ± 0.1 h. The terminal half life was 12.7 ± 0.8 h. The area under the curve AUC₀₋∞ of the injected formula was 452.75 ± 42.8 ng·h/mL and the total mean residence time was 18.57 ± 1.44 h. The PNS in gel was significantly different from the control in rate and extent at P < 0.001. The natural progesterone which was nanosized and formulated in a thermosensitive gel significantly sustained the action of natural progesterone so that it could be injected every 36 h instead of every day. Moreover, this formula is expected to provide a much safer choice than the use of semi-synthetic progesterone.

  4. Diclofenac sodium ion exchange resin complex loaded melt cast films for sustained release ocular delivery.

    Science.gov (United States)

    Adelli, Goutham R; Balguri, Sai Prachetan; Bhagav, Prakash; Raman, Vijayasankar; Majumdar, Soumyajit

    2017-11-01

    The goal of the present study is to develop polymeric matrix films loaded with a combination of free diclofenac sodium (DFS free ) and DFS:Ion exchange resin complexes (DFS:IR) for immediate and sustained release profiles, respectively. Effect of ratio of DFS and IR on the DFS:IR complexation efficiency was studied using batch processing. DFS:IR complex, DFS free , or a combination of DFS free  +   DFS:IR loaded matrix films were prepared by melt-cast technology. DFS content was 20% w/w in these matrix films. In vitro transcorneal permeability from the film formulations were compared against DFS solution, using a side-by-side diffusion apparatus, over a 6 h period. Ocular disposition of DFS from the solution, films and corresponding suspensions were evaluated in conscious New Zealand albino rabbits, 4 h and 8 h post-topical administration. All in vivo studies were carried out as per the University of Mississippi IACUC approved protocol. Complexation efficiency of DFS:IR was found to be 99% with a 1:1 ratio of DFS:IR. DFS release from DFS:IR suspension and the film were best-fit to a Higuchi model. In vitro transcorneal flux with the DFS free  +   DFS:IR (1:1) (1 + 1) was twice that of only DFS:IR (1:1) film. In vivo, DFS solution and DFS:IR (1:1) suspension formulations were not able to maintain therapeutic DFS levels in the aqueous humor (AH). Both DFS free and DFS free  +   DFS:IR (1:1) (3 + 1) loaded matrix films were able to achieve and maintain high DFS concentrations in the AH, but elimination of DFS from the ocular tissues was much faster with the DFS free formulation. DFS free  +   DFS:IR combination loaded matrix films were able to deliver and maintain therapeutic DFS concentrations in the anterior ocular chamber for up to 8 h. Thus, free drug/IR complex loaded matrix films could be a potential topical ocular delivery platform for achieving immediate and sustained release characteristics.

  5. Taste masking of ciprofloxacin by ion-exchange resin and sustain release at gastric-intestinal through interpenetrating polymer network

    Directory of Open Access Journals (Sweden)

    A. Michael Rajesh

    2015-07-01

    Full Text Available The aim of the study was to taste mask ciprofloxacin (CP by using ion-exchange resins (IERs followed by sustain release of CP by forming interpenetrating polymer network (IPN. IERs based on the copolymerization of acrylic acid with different cross linking agents were synthesised. Drug-resin complexes (DRCs with three different ratios of drug to IERs (1:1, 1:2, 1:4 were prepared & evaluated for taste masking by following in vivo and in vitro methods. Human volunteers graded ADC 1:4, acrylic acid-divinyl benzene (ADC-3 resin as tasteless. Characterization studies such as FTIR, SEM, DSC, P-XRD differentiated ADC 1:4, from physical mixture (PM 1:4 and confirmed the formation of complex. In vitro drug release of ADC 1:4 showed complete release of CP within 60 min at simulated gastric fluid (SGF i.e. pH 1.2. IPN beads were prepared with ADC 1:4 by using sodium alginate (AL and sodium alginate-chitosan (AL-CS for sustain release of CP at SGF pH and followed by simulated intestinal fluid (SIF i.e. pH 7.4. FTIR spectra confirmed the formation of IPN beads. The release of CP was sustain at SGF pH (75%. The kinetic model of IPN beads showed the release of CP was non-Fickian diffusion type.

  6. Fabrication and evaluation of a sustained-release chitosan-based scaffold embedded with PLGA microspheres.

    Science.gov (United States)

    Song, Kedong; Liu, Yingchao; Macedo, Hugo M; Jiang, Lili; Li, Chao; Mei, Guanyu; Liu, Tianqing

    2013-04-01

    Nutrient depletion within three-dimensional (3D) scaffolds is one of the major hurdles in the use of this technology to grow cells for applications in tissue engineering. In order to help in addressing it, we herein propose to use the controlled release of encapsulated nutrients within polymer microspheres into chitosan-based 3D scaffolds, wherein the microspheres are embedded. This method has allowed maintaining a stable concentration of nutrients within the scaffolds over the long term. The polymer microspheres were prepared using multiple emulsions (w/o/w), in which bovine serum albumin (BSA) and poly (lactic-co-glycolic) acid (PLGA) were regarded as the protein pattern and the exoperidium material, respectively. These were then mixed with a chitosan solution in order to form the scaffolds by cryo-desiccation. The release of BSA, entrapped within the embedded microspheres, was monitored with time using a BCA kit. The morphology and structure of the PLGA microspheres containing BSA before and after embedding within the scaffold were observed under a scanning electron microscope (SEM). These had a round shape with diameters in the range of 27-55 μm, whereas the chitosan-based scaffolds had a uniform porous structure with the microspheres uniformly dispersed within their 3D structure and without any morphological change. In addition, the porosity, water absorption and degradation rate at 37 °C in an aqueous environment of 1% chitosan-based scaffolds were (92.99±2.51) %, (89.66±0.66) % and (73.77±3.21) %, respectively. The studies of BSA release from the embedded microspheres have shown a sustained and cumulative tendency with little initial burst, with (20.24±0.83) % of the initial amount released after 168 h (an average rate of 0.12%/h). The protein concentration within the chitosan-based scaffolds after 168 h was found to be (11.44±1.81)×10(-2) mg/mL. This novel chitosan-based scaffold embedded with PLGA microspheres has proven to be a promising technique

  7. Sustained drug release and electrochemical performance of ethyl cellulose-magnesium hydrogen phosphate composite

    Energy Technology Data Exchange (ETDEWEB)

    Mohammad, Faruq, E-mail: fmohammad@ksu.edu.sa [Surfactant Research chair, Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451 (Saudi Arabia); Arfin, Tanvir, E-mail: t_arfin@neeri.res.in [Environmental Materials Division, CSIR-National Environmental Engineering Research Institute (CSIR-NEERI), Nehru Marg, Nagpur 440020 (India); Al-Lohedan, Hamad A. [Surfactant Research chair, Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451 (Saudi Arabia)

    2017-02-01

    In this, a sol-gel method was applied to prepare ethyl cellulose-magnesium hydrogen phosphate (EC-MgHPO{sub 4}) composite that can have potential applications in the sensory, pharmaceutical, and biomedical sectors. The formed composite was thoroughly characterized by making use of the instrumental analysis such as UV–Vis, FT-IR, HRTEM, EDAX, SEM and XRD. For the composite, the other parameters determined includes the water uptake, porosity, thickness, bulk and tapped densities, angle of repose, Carr's index and Hausner ratio. From the results, the material found to exhibit good flowing properties with a Carr's index of 11.11%, Hausner ratio of 1.125, and angle of response of 33°. The EDAX spectrum and HRTEM analysis confirmed for the composite formation and the particles size is investigated to be around 52 nm. The surface porosity due to the EC matrices was confirmed by the SEM analysis, which further used for the loading of drug, Proguanil. In addition, the material's conductivity was studied by taking uni-univalent electrolyte solution (KCl and NaCl) indicated that the conductivity follows the order of KCl > NaCl, while the activation energy obtained from Arrhenius method resembled that the conductivity is strongly influenced by the electrolyte type used. We found from the analysis that, with a decrease in the size of hydrated radii of ions, the conductivity of EC-MgHPO{sub 4} material also observed to be decreased in the order K{sup +} > Na{sup +} and the material proved to be mechanically stable and can be operated over a range of pHs, temperatures, and electrolyte solutions. Further, the drug loading and efficiency studies indicated that the material can trap up to 80% of Proguanil (antimalarial drug) applied for its loading. The Proguanil drug release profiles confirmed for the controlled and sustained release from the EC-MgHPO{sub 4} matrix, as the material can release up to 87% of its total loaded drug over a 90 min period. Finally, the

  8. Sustained drug release and electrochemical performance of ethyl cellulose-magnesium hydrogen phosphate composite

    International Nuclear Information System (INIS)

    Mohammad, Faruq; Arfin, Tanvir; Al-Lohedan, Hamad A.

    2017-01-01

    In this, a sol-gel method was applied to prepare ethyl cellulose-magnesium hydrogen phosphate (EC-MgHPO 4 ) composite that can have potential applications in the sensory, pharmaceutical, and biomedical sectors. The formed composite was thoroughly characterized by making use of the instrumental analysis such as UV–Vis, FT-IR, HRTEM, EDAX, SEM and XRD. For the composite, the other parameters determined includes the water uptake, porosity, thickness, bulk and tapped densities, angle of repose, Carr's index and Hausner ratio. From the results, the material found to exhibit good flowing properties with a Carr's index of 11.11%, Hausner ratio of 1.125, and angle of response of 33°. The EDAX spectrum and HRTEM analysis confirmed for the composite formation and the particles size is investigated to be around 52 nm. The surface porosity due to the EC matrices was confirmed by the SEM analysis, which further used for the loading of drug, Proguanil. In addition, the material's conductivity was studied by taking uni-univalent electrolyte solution (KCl and NaCl) indicated that the conductivity follows the order of KCl > NaCl, while the activation energy obtained from Arrhenius method resembled that the conductivity is strongly influenced by the electrolyte type used. We found from the analysis that, with a decrease in the size of hydrated radii of ions, the conductivity of EC-MgHPO 4 material also observed to be decreased in the order K + > Na + and the material proved to be mechanically stable and can be operated over a range of pHs, temperatures, and electrolyte solutions. Further, the drug loading and efficiency studies indicated that the material can trap up to 80% of Proguanil (antimalarial drug) applied for its loading. The Proguanil drug release profiles confirmed for the controlled and sustained release from the EC-MgHPO 4 matrix, as the material can release up to 87% of its total loaded drug over a 90 min period. Finally, the cell viability and

  9. Synthesis of thiolated arabinoxylan and its application as sustained release mucoadhesive film former.

    Science.gov (United States)

    Zaman, Muhammad; Hanif, Muhammad; Sultana, Kishwar; Atta-Ur-Rehman

    2018-02-08

    The present work aimed to synthesize thiolated arabinoxylan (TAX), and to evaluate its mucoadhesive potential. Synthesis of TAX was accomplished by esterification of arabinoxylan (AX) with thioglycolic acid (TGA). The appearance of a characteristic peak at 2516 cm -1 in the FTIR spectrum of TAX, and presence of 6.01 ± 1.03 m moles of thiol per gram of the polymer confirmed successful thiolation of AX. The incorporation of the thiol group considerably promoted mucoadhesive strength of the polymer-viz. 3.99-fold. Moreover, in vivo safety analysis in albino rats revealed TAX to be safe in the concentration range of 750-1000 mg kg -1 body weight. Synthesized TAX was utilized to prepare Tizanidine HCl (TZN HCl) loaded sustained release (SR) mucoadhesive buccal films using a solvent casting technique. Results proved that the prepared films were of uniform thickness, good mechanical strength (with folding endurance >300), acceptable moisture contents (5%-7%) and surface pH (6.23 ± 0.81 to 6.43 ± 0.49) compatible to that of the buccal cavity. Presence of greater that 90% of drug contents indicated the excellent drug loading ability of the prepared films. Results of in vitro dissolution studies and ex vivo permeation studies conducted respectively by USP dissolution apparatus II and Franz diffusion cell indicated that sustained effect of TAX was achieved for 8 h. These results have conclusively proven that TAX has the potential to improve the bioavailability of TZN HCl due to enhanced mucoadhesion in buccal cavity, hence signifying its suitability as a mucoadhesive buccal film former.

  10. Decreased absorption as a possible cause for the lower bioavailability of a sustained-release propranolol.

    Science.gov (United States)

    Takahashi, H; Ogata, H; Warabioka, R; Kashiwada, K; Ohira, M; Someya, K

    1990-03-01

    The influence of sustained absorption on the oral availability of propranolol (P) and the metabolic disposition of P were investigated by obtaining the partial metabolic clearances (CLm) following long-acting P (LA) dosing in comparison with the conventional propranolol tablet (CP). Ten healthy volunteers were given a single oral dose of an LA capsule (60 mg) and CP (20 mg x 3) using a crossover design. Blood and urine samples were collected over 24- and 48-h postdose periods, respectively. Concentrations of P, propranolol glucuronide (PG), 4-hydroxypropranolol (4P), 4-hydroxypropranolol glucuronide (4PG), 4-hydroxypropranolol sulfate (4PS), and naphthoxylactic acid (NLA) were determined by HPLC with fluorescence and UV detection. Significant differences were observed between LA and CP in the area under the plasma concentration-time curves (AUCs) for P, PG, and NLA and in the amounts excreted into urine (Ae) for all measured metabolites (i.e., PG, 4P, 4PG, 4PS, and NLA). The parallel decrease of the AUC for P and the excreted amounts of all measured metabolites following LA dosing resulted in partial metabolic clearances (CLm) and renal clearances (CL) for P and its metabolites that were similar to those observed for CP. Therefore, the hepatic metabolism of P would not be affected by the slower absorption at a single oral dose of 60 mg. These results indicate that the poor absorption of P from the gastrointestinal tract might be one of the factors causing the low bioavailability of P observed after administration of the sustained-release formulation.

  11. Preparation of rifampicin/poly(d,l-lactice) nanoparticles for sustained release by supercritical assisted atomization technique

    CSIR Research Space (South Africa)

    Labuschagne, Philip W

    2014-11-01

    Full Text Available In this work supercritical assisted atomization (SAA) process was used for the co-precipitation of poly(d,l-lactide) (PDLLA) and rifampicin (RIF) as nanoparticles for sustained release applications. The effect of the variation of PDLLA/RIF ratio...

  12. Managing cancer pain and symptoms of outpatients by rotation to sustained-release hydromorphone: a prospective clinical trial

    NARCIS (Netherlands)

    Wirz, Stefan; Wartenberg, Hans Christian; Elsen, Christian; Wittmann, Maria; Diederichs, Marta; Nadstawek, Joachim

    2006-01-01

    PURPOSE: In this prospective clinical trial we examined the technique of opioid rotation to oral sustained-release hydromorphone for controlling pain and symptoms in outpatients with cancer pain. METHODS: Before and after rotation, 50 patients were assessed by Numerical Analog Scales [Numerical

  13. Adverse Events With Sustained-Release Donepezil in Alzheimer Disease: Relation to Body Mass Index.

    Science.gov (United States)

    Lee, Chunsoo; Lee, Kyungsang; Yu, Hyewon; Ryu, Seung-Ho; Moon, Seok Woo; Han, Changsu; Lee, Jun-Young; Lee, Young Min; Kim, Shin-Gyeom; Kim, Ki Woong; Lee, Dong Woo; Kim, Seong Yoon; Lee, Sang-Yeol; Bae, Jae Nam; Jung, Young-Eun; Kim, Jeong Lan; Kim, Byung-Soo; Shin, Il-Seon; Kim, Young Hoon; Kim, Bong Jo; Kang, Hyo Shin; Myung, Woojae; Carroll, Bernard J; Kim, Doh Kwan

    2017-08-01

    Sustained-release, high-dose (23 mg/d) donepezil has been approved for treatment of moderate to severe Alzheimer disease (AD). Based on a previous clinical trial, body weight of less than 55 kg is a risk factor for adverse events with donepezil 23 mg/d treatment in global population. To clarify whether this finding is consistent across ethnic groups that vary in absolute body mass, we recruited Korean patients aged 45 to 90 years with moderate to severe AD who had been receiving standard donepezil immediate release 10 mg/d for at least 3 months. After screening, we analyzed a final cohort of 166 patients who received donepezil 23 mg/d for 24 weeks to compare the occurrence of treatment-emergent adverse events (TEAEs) between patients with high versus low body mass index (BMI) based on the World Health Organization overweight criteria for Asian populations (23 kg/m). Treatment-emergent adverse events were reported by 79.45% of patients in the lower BMI group and 58.06% of patients in the higher BMI group (odds ratio, 2.79; 95% confidence interval, 1.39-5.63; χ = 7.58, P = 0.006). In a multivariable survival analysis, the group with lower BMI showed a higher occurrence of TEAEs (hazard ratio, 1.83; 95% confidence interval, 1.25-2.68; P = 0.002). In Korean patients with moderate to severe AD receiving high-dose donepezil over 24 weeks, TEAEs were significantly more common in those with lower BMI (not clinically overweight), especially nausea. This finding may inform clinical practice for Asian patients.

  14. Plant Extract Synthesized PLA Nanoparticles for Controlled and Sustained Release of Quercetin: A Green Approach

    Science.gov (United States)

    Yadav, Sudesh Kumar

    2012-01-01

    Background Green synthesis of metallic nanoparticles (NPs) has been extensively carried out by using plant extracts (PEs) which have property of stabilizers/ emulsifiers. To our knowledge, there is no comprehensive study on applying a green approach using PEs for fabrication of biodegradable PLA NPs. Conventional methods rely on molecules like polyvinyl alcohol, polyethylene glycol, D-alpha-tocopheryl poly(ethylene glycol 1000) succinate as stabilizers/emulsifiers for the synthesis of such biodegradable NPs which are known to be toxic. So, there is urgent need to look for stabilizers which are biogenic and non-toxic. The present study investigated use of PEs as stabilizers/emulsifiers for the fabrication of stable PLA NPs. Synthesized PLA NPs through this green process were explored for controlled release of the well known antioxidant molecule quercetin. Methodology/Principal Findings Stable PLA NPs were synthesized using leaf extracts of medicinally important plants like Syzygium cumini (1), Bauhinia variegata (2), Cedrus deodara (3), Lonicera japonica (4) and Eleaocarpus sphaericus (5). Small and uniformly distributed NPs in the size range 70±30 nm to 143±36 nm were formed with these PEs. To explore such NPs for drugs/ small molecules delivery, we have successfully encapsulated quercetin a lipophilic molecule on a most uniformly distributed PLA-4 NPs synthesized using Lonicera japonica leaf extract. Quercetin loaded PLA-4 NPs were observed for slow and sustained release of quercetin molecule. Conclusions This green approach based on PEs mediated synthesis of stable PLA NPs pave the way for encapsulating drug/small molecules, nutraceuticals and other bioactive ingredients for safer cellular uptake, biodistribution and targeted delivery. Hence, such PEs synthesized PLA NPs would be useful to enhance the therapeutic efficacy of encapsulated small molecules/drugs. Furthermore, different types of plants can be explored for the synthesis of PLA as well as other

  15. Design and in vitro/in vivo evaluation of sustained-release floating tablets of itopride hydrochloride

    Directory of Open Access Journals (Sweden)

    Ahmed SM

    2016-12-01

    Full Text Available Sayed M Ahmed,1 Adel Ahmed Ali,2 Ahmed MA Ali,2,3 Omiya A Hassan2,4 1Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, 2Department of Pharmaceutics, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt; 3Department of Pharmaceutics, Faculty of Pharmacy, Taif University, Taif, Kingdom of Saudi Arabia; 4Department of Pharmaceutics, Faculty of Pharmacy, Deraya University, El-Minia Gadida, Egypt Purpose: The aim of the present study was to improve the bioavailability of itopride (ITO and sustain its action by formulating as a floating dosage form. Materials and methods: Sustained-release floating tablets of ITO hydrochloride (HCl were prepared by direct compression using different hydrocolloid polymers such as hydroxypropyl methylcellulose and ethylcellulose and/or methacrylic acid polymers Eudragit RSPM and Carbopol 934P. The floating property was achieved using an effervescent mixture of sodium bicarbonate and anhydrous citric acid (1:1 mol/mol. Hardness, friability, content uniformity, and dissolution rate of the prepared floating tablets were evaluated. The formulation F10 composed of 28.5% Eudragit RSPM, 3% NaHCO3, and 7% citric acid provided sustained drug release. Results: In vitro results showed sustained release of F10 where the drug release percentage was 96.51%±1.75% after 24 hours (P=0.031.The pharmacokinetic results indicated that the area under the curve (AUC0–∞ of the prepared sustained-release floating tablets at infinity achieved 93.69 µg·h/mL compared to 49.89 µg·h/mL for the reference formulation (Ganaton® and the relative bioavailability of the sustained-release formulation F10 increased to 187.80% (P=0.022. Conclusion: The prepared floating tablets of ITO HCl (F10 could be a promising drug delivery system with sustained-release action and enhanced drug bioavailability. Keywords: itopride HCl, oral drug delivery, stability study, bioavailability

  16. Preparation and stability investigation of tamsulosin hydrochloride sustained release pellets containing acrylic resin polymers with two different techniques

    Directory of Open Access Journals (Sweden)

    Rui Fan

    2017-03-01

    Full Text Available The objective of this study was to prepare tamsulosin hydrochloride-sustained release (TSH-SR pellets which showed good release stability with frame-controlled method. TSH was added to Eudragit®NE30D and Eudragit®L30D-55 polymers to form drug-loaded inner core. Afterwards, enteric Eudragit®L30D-55 polymer was modified on the surface of it to the final product. Dissolution studies showed that TSH-SR pellets were more stable during the coating process, different curing temperatures and storage conditions compared with TSH pellets produced by film-controlled technique. Appearances and glass transition temperatures (Tgs of free films and surface morphologies observed by scanning electron microscopy (SEM of blank sustained release pellets prepared by different ratios of Eudragit®NE30D and Eudragit®L30D-55 further indicated that temperature and relative humidity (RH were the key factors when Eudragit®NE30D blended with Eudragit®L30D-55 were applied to sustained/controlled release preparations. In addition, SEM identified the surface morphologies of TSH-SR pellets before and after dissolution, which showed intact surface structure and great correlation with release curve respectively.

  17. 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.

  18. 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.

  19. Sustainability.

    Science.gov (United States)

    Chang, Chein-Chi; DiGiovanni, Kimberly; Mei, Ying; Wei, Li

    2016-10-01

    This review on Sustainability covers selected 2015 publications on the focus of Sustainability. It is divided into the following sections : • Sustainable water and wastewater utilities • Sustainable water resources management • Stormwater and green infrastructure • Sustainability in wastewater treatment • Life cycle assessment (LCA) applications • Sustainability and energy in wastewater industry, • Sustainability and asset management.

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

    Science.gov (United States)

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

    2011-05-01

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

  1. A bioequivalence study of two tamsulosin sustained-release tablets in Indonesian healthy volunteers.

    Science.gov (United States)

    Prasaja, Budi; Harahap, Yahdiana; Lusthom, Windy; Setiawan, Evy C; Ginting, Mena B; Hardiyanti; Lipin

    2011-06-01

    The bioavailability of two 0.4 mg tamsulosin sustained-release film-coated tablet formulations was compared; using generic tablets (Prostam(®)) as test formulation and the originator product as reference formulation. Twenty-four subjects were included in this single-dose, open-label, randomized two-way crossover design following an overnight fasting. A one-week wash-out period was applied. Blood samples were drawn up to 72 h following drug administration. Plasma concentration of tamsulosin was determined by liquid chromatography-tandem mass spectrometry method with TurboIonSpray mode. Pharmacokinetic parameters AUC(0-t,) AUC(0-∞), C (max) and t (½) were determined and used for bioequivalence evaluation after log-transformation, whereas t (max) ratios were evaluated non-parametrically. The estimated point and 90% confidence intervals (CI) for AUC(0-t,) AUC(0-∞), C (max) and t (½) were 109.55% (96.41-124.49%), 109.94% (96.85-124.81%), 105.87% (92.88-120.67%) and 100.00% (90.56-110.43%), respectively. These results indicated that the two formulations of tamsulosin were bioequivalent; therefore they may be prescribed interchangeably.

  2. Treatment of Gastrin-Secreting Tumor With Sustained-Release Octreotide Acetate in a Dog.

    Science.gov (United States)

    Kim, Sangho; Hosoya, Kenji; Takagi, Satoshi; Okumura, Masahiro

    2015-01-01

    An 8 yr old, intact male Shiba Inu was presented with loose stool, polydipsia, hematuria, vomiting, and anorexia. On abdominal ultrasonography, numerous nodules were detected in the hepatic parenchyma distributed diffusely throughout all lobes. Excisional biopsy of one of the nodules was performed via exploratory laparotomy. A histopathological diagnosis of the lesion was carcinoid, and the tumor cells stained positive to chromogranin A and gastrin. The serum gastrin level of the dog was 45,613 pg/mL (reference range: 160-284). In addition to medical treatment with omeprazole(c) and famotidine(e), suppression of gastrin secretion was attempted with octreotide acetate. A test dose of octreotide acetate significantly decreased the serum gastrin level to approximately one third of the baseline in 2 hr and the effect lasted approximately for 6 hr. On day 21, treatment with sustained-release formulation of octreotide acetate(a) (5 mg intramuscular, q 4 wk) was initiated. The serum gastrin concentration gradually decreased over 32 days and then progressively increased in parallel with the progression of the hepatic nodules. The dog gradually developed recurrence of initial clinical signs, and was lost to follow-up on day 510.

  3. Laboratory and Field Evaluation of Biodegradable Polyesters for Sustained Release of Isometamidium and Ethidium

    Directory of Open Access Journals (Sweden)

    S Geerts

    1999-03-01

    Full Text Available An overview is presented of the results obtained with biodegradable sustained release devices (SRDs containing a mixture of polymers and either isometamidium (ISMM or ethidium. Under controlled laboratory conditions (monthly challenge with tsetse flies infected with Trypanosoma congolense the protection period in SRD treated cattle could be extended by a factor 2.8 (for ethidium up to 4.2 (for ISMM as compared to animals treated intramuscularly with the same drugs. Using a competitive drug ELISA ISMM concentrations were detected up to 330 days after the implantation of the SRDs, whereas after i.m. injection the drug was no longer present three to four months post treatment. Two field trials carried out in Mali under heavy tsetse challenge showed that the cumulative infection rate was significantly lower in the ISMM-SRD implanted cattle than in those which received ISMM intramuscularly. Using ethidium SRD, however, contradictory results were obtained in field trials in Zambia and in Mali. The potential advantages and inconvenients of the use of SRDs are discussed and suggestions are made in order to further improve the currently available devices.

  4. Advances in Hybrid Polymer-Based Materials for Sustained Drug Release

    Directory of Open Access Journals (Sweden)

    Lígia N. M. Ribeiro

    2017-01-01

    Full Text Available The use of biomaterials composed of organic pristine components has been successfully described in several purposes, such as tissue engineering and drug delivery. Drug delivery systems (DDS have shown several advantages over traditional drug therapy, such as greater therapeutic efficacy, prolonged delivery profile, and reduced drug toxicity, as evidenced by in vitro and in vivo studies as well as clinical trials. Despite that, there is no perfect delivery carrier, and issues such as undesirable viscosity and physicochemical stability or inability to efficiently encapsulate hydrophilic/hydrophobic molecules still persist, limiting DDS applications. To overcome that, biohybrid systems, originating from the synergistic assembly of polymers and other organic materials such as proteins and lipids, have recently been described, yielding molecularly planned biohybrid systems that are able to optimize structures to easily interact with the targets. This work revised the biohybrid DDS clarifying their advantages, limitations, and future perspectives in an attempt to contribute to further research of innovative and safe biohybrid polymer-based system as biomaterials for the sustained release of active molecules.

  5. A sustained release system using porous cellulose spheres modified by grafting as matrices

    International Nuclear Information System (INIS)

    Hosoi, Fumio; Makuuchi, Keizo; Saito, Kenji; Koishi, Masumi.

    1987-01-01

    Polymer-coated spheres, obtained by the graft polymerization of methyl methacrylate (MMA) onto porous spheres based on cellulose by the pre-irradiation method, were used as matrices for the drug sustained release system for salicylic acid. The adsorption of salicylic acid was carried out by dipping the grafted spheres in a 50% aqueous ethanol solution containing salicylic acid. The amount of salicylic acid adsorbed (Q) increased proportionately with the percent graft of MMA (G) to the power of 2.9. Adsorption mechanism of salicylic acid could be expressed in term of Langmuir's adsorption isotherm. The ratio of constants for adsorption and desorption (k) and the saturated amount of salicylic acid adsorbed (Q 0 ) were expressed as k = k 1 G and Q 0 = k 2 G 2.4 , respectively. These results indicate that the number of adsorption sites increased proportionately with the nth power of G as a results of the interaction of grafted poly (methyl methacrylate)(PMMA) and cellulose. Similar results were obtained with grafting of MMA, MMA-styrene (St), and MMA-methacrylic acid (MAc) in the presence of salicylic acid. (author)

  6. Development and validation of dissolution study of sustained release dextromethorphan hydrobromide tablets.

    Science.gov (United States)

    Rajan, Sekar; Colaco, Socorrina; Ramesh, N; Meyyanathan, Subramania Nainar; Elango, K

    2014-02-01

    This study describes the development and validation of dissolution tests for sustained release Dextromethorphan hydrobromide tablets using an HPLC method. Chromatographic separation was achieved on a C18 column utilizing 0.5% triethylamine (pH 7.5) and acetonitrile in the ratio of 50:50. The detection wavelength was 280 nm. The method was validated and response was found to be linear in the drug concentration range of 10-80 microg mL(-1). The suitable conditions were clearly decided after testing sink conditions, dissolution medium and agitation intensity. The most excellent dissolution conditions tested, for the Dextromethorphan hydrobromide was applied to appraise the dissolution profiles. The method was validated and response was found to be linear in the drug concentration range of 10-80 microg mL(-1). The method was established to have sufficient intermediate precision as similar separation was achieved on another instrument handled by different operators. Mean Recovery was 101.82%. Intra precisions for three different concentrations were 1.23, 1.10 0.72 and 1.57, 1.69, 0.95 and inter run precisions were % RSD 0.83, 1.36 and 1.57%, respectively. The method was successfully applied for dissolution study of the developed Dextromethorphan hydrobromide tablets.

  7. Co-extrusion as a processing technique to manufacture a dual sustained release fixed-dose combination product.

    Science.gov (United States)

    Vynckier, An-Katrien; Voorspoels, Jody; Remon, Jean Paul; Vervaet, Chris

    2016-05-01

    This study aimed to design a fixed-dose combination dosage form which provides a sustained release profile for both the freely water-soluble metformin HCl and the poorly soluble gliclazide, two antidiabetic compounds used to treat diabetes mellitus. Hot-melt co-extrusion was used as an innovative manufacturing technique for a pharmaceutical fixed-dose combination product. In this way, a matrix formulation that sustained metformin release could be developed, despite the high drug load in the formulation and the freely soluble nature of the drug. It was clear that co-extrusion was perfectly suited to produce a fixed-dose combination product with adequate properties for each of the incorporated APIs. A coat layer, containing at least 30% CAPA(®) 6506 as a hydrophobic polymer, was necessary to adequately sustain the release of the highly dosed freely soluble drug from the 70% metformin HCl-loaded CAPA(®) 6506 core of the co-extrudate. To obtain a complete gliclazide release over 24-h solubilization in Kollidon(®) VA, added as a second polymer to the CAPA(®) 6506 in the coat, was needed. Both active pharmaceutical ingredients (APIs), which have different physicochemical characteristics, were formulated in a single dosage form, using co-extrusion. © 2016 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology.

  8. 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.

  9. [Fabrication of a new composite scaffold material for delivering rifampicin and its sustained drug release in rats].

    Science.gov (United States)

    Ma, Xue-Ming; Lin, Zhen; Zhang, Jia-Wei; Sang, Chao-Hui; Qu, Dong-Bin; Jiang, Jian-Ming

    2016-03-01

    To fabricate a new composite scaffold material as an implant for sustained delivery of rifampicin and evaluate its performance of sustained drug release and biocompatibility. The composite scaffold material was prepared by loading poly(lactic-co-glycolic) acid (PLGA) microspheres that encapsulated rifampicin in a biphasic calcium composite material with a negative surface charge. The in vitro drug release characteristics of the microspheres and the composite scaffold material were evaluated; the in vivo drug release profile of the composite scaffold material implanted in a rat muscle pouch was evaluated using high-performance liquid chromatography. The biochemical parameters of the serum and liver histopathologies of the rats receiving the transplantation were observed to assess the biocompatibility of the composite scaffold material. The encapsulation efficiency and drug loading efficiency of microspheres were (56.05±5.33)% and (29.80±2.88)%, respectively. The cumulative drug release rate of the microspheres in vitro was (94.19±5.4)% at 28 days, as compared with the rate of (82.23±6.28)% of composite scaffold material. The drug-loaded composite scaffold material showed a good performance of in vivo drug release in rats, and the local drug concentration still reached 16.18±0.35 µg/g at 28 days after implantation. Implantation of the composite scaffold material resulted in transient and reversible liver injury, which was fully reparred at 28 days after the implantation. The composite scaffold material possesses a good sustained drug release capacity and a good biocompatibility, and can serve as an alternative approach to conventional antituberculous chemotherapy.

  10. Preparation of sustained-release coated particles by novel microencapsulation method using three-fluid nozzle spray drying technique.

    Science.gov (United States)

    Kondo, Keita; Niwa, Toshiyuki; Danjo, Kazumi

    2014-01-23

    We prepared sustained-release microcapsules using a three-fluid nozzle (3N) spray drying technique. The 3N has a unique, three-layered concentric structure composed of inner and outer liquid nozzles, and an outermost gas nozzle. Composite particles were prepared by spraying a drug suspension and an ethylcellulose solution via the inner and outer nozzles, respectively, and mixed at the nozzle tip (3N-PostMix). 3N-PostMix particles exhibited a corrugated surface and similar contact angles as ethylcellulose bulk, thus suggesting encapsulation with ethylcellulose, resulting in the achievement of sustained release. To investigate the microencapsulation process via this approach and its usability, methods through which the suspension and solution were sprayed separately via two of the four-fluid nozzle (4N) (4N-PostMix) and a mixture of the suspension and solution was sprayed via 3N (3N-PreMix) were used as references. It was found that 3N can obtain smaller particles than 4N. The results for contact angle and drug release corresponded, thus suggesting that 3N-PostMix particles are more effectively coated by ethylcellulose, and can achieve higher-level controlled release than 4N-PostMix particles, while 3N-PreMix particles are not encapsulated with pure ethylcellulose, leading to rapid release. This study demonstrated that the 3N spray drying technique is useful as a novel microencapsulation method. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Design of sustained-release nitrendipine microspheres having solid dispersion structure by quasi-emulsion solvent diffusion method

    DEFF Research Database (Denmark)

    Cui, Fude; Yang, Mingshi; Jiang, Yanyan

    2003-01-01

    crystallization technique, i.e. quasi-emulsion solvent diffusion method. The factors of effect on micromeritic properties and release profiles of the resultant microspheres were investigated. And the bioavailability of nitrendipine microspheres was evaluated in six healthy dogs. The results showed...... that the particle size of microspheres was determined mainly by the agitation speed. The dissolution rate of nitrendipine from microspheres was enhanced significantly with increasing the amount of dispersing agents, and sustained by adding retarding agents. The release rate of microspheres could be controlled...

  12. Butyrate-Loaded Chitosan/Hyaluronan Nanoparticles: A Suitable Tool for Sustained Inhibition of ROS Release by Activated Neutrophils

    DEFF Research Database (Denmark)

    Sacco, Pasquale; Decleva, Eva; Tentor, Fabio

    2017-01-01

    that butyrate inhibits neutrophil ROS release in a dose and time-dependent fashion. Given the short half-life of butyrate, chitosan/hyaluronan nanoparticles are next designed and developed as controlled release carriers able to provide cells with a long-lasting supply of this SCFA. Notably, while the inhibition...... of neutrophil ROS production by free butyrate declines over time, that of butyrate-loaded chitosan/hyaluronan nanoparticles (B-NPs) is sustained. Additional valuable features of these nanoparticles are inherent ROS scavenger activity, resistance to cell internalization, and mucoadhesiveness. B-NPs appear...

  13. Design of sustained release pellets of ferrous fumarate using cow ghee as hot-melt coating agent.

    Science.gov (United States)

    Sakarkar, Dinesh M; Dorle, Avinash K; Mahajan, Nilesh Manoharrao; Sudke, Suresh Gendappa

    2013-07-01

    The objective of the present study was to design ferrous fumarate (FF) sustained release (SR) pellets using of cow ghee (CG) as an important hot-melt coating (HMC) agent. The pellets were coated by HMC technique using CG and ethyl cellulose composition by conventional coating pan without the use of spray system. FF formulated as pellets and characterized with regard to the drug content and physico-chemical properties. Stability studies were carried out on the optimized formulation for a period of 6 months at 40 ± 2°C and 75 ± 5% relative humidity. Pellets with good surface morphology and smooth texture confirmed by stereo micrographs. HMC is easy, efficient, rapid and simple method since virtually no agglomeration seen during coating. In-vitro release from pellets at a given level of coating and for present pellet size was dependent upon the physico-chemical property of the drug and mostly aqueous solubility of the drug. The selection of optimized FF formulation was confirmed by comparing percent cumulative drug release with theoretical release profile. Formulation F2 had difference factor (f 1) and similarity factor (f 2) values was found to be 5 and 66 respectively. F2 showed SR of drug for 8 h with cumulative per cent release of 98.03 ± 4.49%. Release kinetics indicates approximately zero order release pattern. HMC pellets were stable during the course of stability study. By means of HMC using CG and ethyl cellulose, SR pellets containing FF were successfully prepared.

  14. 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...

  15. Comparative study of sustained-release lipid microparticles and solid dispersions containing ibuprofen

    Directory of Open Access Journals (Sweden)

    Hugo Almeida

    2012-09-01

    Full Text Available Ibuprofen is one of the most important non-steroidal anti-inflammatory drugs used in the treatment of inflammatory diseases. In its pure state, ibuprofen presents poor physical and mechanical characteristics and its use in solid dosage forms needs the addition of excipients that improve these properties. The selection of the best excipients and the most suitable pharmaceutical dosage form to carry ibuprofen is very important for the industrial success of this drug. Given these factors, lipid microparticles and solid dispersions of ibuprofen with cetyl alcohol, stearic acid, and hydrogenated castor oil were prepared. These formulations were intended to improve the physical and mechanical characteristics and to sustain the release of this drug. Physical mixtures were also prepared with the same ingredients in similar proportions. The solid dispersions of ibuprofen/stearic acid and ibuprofen/hydrogenated castor oil showed the best flow characteristics compared with pure ibuprofen. Further, gelatin capsules filled with lipid microparticles and solid dispersions were submitted to dissolution tests in order to study the influence of the prepared systems in the release profiles of ibuprofen. Prolonged release of ibuprofen was achieved with the lipid microparticles and solid dispersions prepared with the different types of excipients.O ibuprofeno é um dos antiinflamatórios não esteróides mais utilizados no tratamento de patologias associadas a processos inflamatórios. Este fármaco, quando no seu estado puro, apresenta características físicas e mecânicas pouco satisfatórias e a sua utilização em formas sólidas só é possível se forem adicionados excipientes que permitam melhorar estas propriedades. A seleção dos excipientes ideais e da forma farmacêutica mais adequada para veicular o ibuprofeno é fundamental para o sucesso industrial deste fármaco. Tendo em conta estes fatores, prepararam-se micropartículas lipídicas e dispersões s

  16. Preparation and in-vitro in-vivo evaluation of sustained release matrix diclofenac sodium tablets using PVP-K90 and natural gums.

    Science.gov (United States)

    Iqbal, Zafar; Khan, Raza; Nasir, Fazli; Khan, Jamshaid Ali; Rashid, Abdur; Khan, Abbas; Khan, Abad

    2011-10-01

    Conventional dosage form is nowadays mostly replaced by sustained release formulation in order to increase drug efficacy and patient compliance. The sustained release properties of the PVP K90 alone and in combination with guar gum, xanthan gum and gum tragacanth were evaluated using diclofenac sodium (100 mg/tablet) as a model drug. Tablets were processed using wet granulation method and evaluated for sustained drug release properties. The drug release from the formulations was studied in relationship with Commercially available Diclofenac Sodium SR, used as a reference tablets and results were expressed as similarity (f1) and differential factor (f2). The tablets prepared using PVP K90 160 mg/tablet sustained the release of diclofenac sodium for 12 hours. Formulations where the PVP K90 was partially replaced with different gums also sustained the release of drug for 12 hours. The release of the drug from these formulations mainly followed Higuchi model and super case-II and Non-Fickian diffusion. The in-vivo drug release was studied in healthy human volunteers using non-blinded cross over, two period design using Diclofenac Sodium SR Tablets as a reference drug. The relative bioavailability of the formulation containing PVP K90 and gum tragacanth was 0.91. The studies showed that the use of the PVP K90 in combination with gum tragacanth both in-vitro and in-vivo sustained the release of the drug.

  17. Sustained-release indomethacin in the management of the acute painful shoulder from bursitis and/or tendinitis.

    Science.gov (United States)

    Calabro, J J; Londino, A V; Eyvazzadeh, C

    1985-10-25

    Of all the forms of nonarticular rheumatism, by far the most common are bursitis and tendinitis. Yet, the bursae and neighboring tendon sheaths are the most neglected anatomic structures of the body. Moreover, like the joints, they are lined by synovial membrane, secrete synovial fluid, and are common sites of rheumatic problems. The vast majority of painful shoulder problems are caused by acute subacromial (subdeltoid) bursitis and bicipital tendinitis. In the management of these periarticular disorders, the ultimate goal is to preserve shoulder motion. Although this is accomplished by daily range-of-motion exercises, it is clearly facilitated by suppression of periarticular inflammation and discomfort through the use of nonsteroidal anti-inflammatory drugs. Of these, sustained-release indomethacin provides the anti-inflammatory efficacy of indomethacin and by virtue of its sustained-release formulation, may promote patient compliance since it need be given only once or twice daily.

  18. Modified thermoresponsive Poloxamer 407 and chitosan sol-gels as potential sustained-release vaccine delivery systems

    DEFF Research Database (Denmark)

    Kojarunchitt, Thunjiradasiree; Baldursdottir, Stefania; Dong, Yao-Da

    2015-01-01

    Thermoresponsive, particle-loaded, Poloxamer 407 (P407)-Pluronic-R® (25R4) or chitosan-methyl cellulose (MC) formulations were developed as single-dose, sustained release vaccines. The sol-gels, loaded either with a particulate vaccine (cubosomes) or soluble antigen (ovalbumin) and adjuvants (Quil...... the chitosan-MC sol-gels sustained the release of antigen up to at least 14 days after administration. The chitosan-MC sol-gels stimulated both cellular and humoral responses. The inclusion of cubosomes in the sol-gels did not provide a definitive beneficial effect. Further analysis of the formulations...... with small-angle X-ray scattering (SAXS) revealed that while cubosomes were stable in chitosan-MC gels they were not stable in P407-25R4 formulations. The reason for the mixed response to cubosome-loaded vehicles requires more investigation, however it appears that the cubosomes did not facilitate...

  19. Sustained release of simvastatin from hollow carbonated hydroxyapatite microspheres prepared by aspartic acid and sodium dodecyl sulfate.

    Science.gov (United States)

    Wang, Ke; Wang, Yinjing; Zhao, Xu; Li, Yi; Yang, Tao; Zhang, Xue; Wu, Xiaoguang

    2017-06-01

    Hollow carbonated hydroxyapatite (HCHAp) microspheres as simvastatin (SV) sustained-release vehicles were fabricated through a novel and simple one-step biomimetic strategy. Firstly, hollow CaCO 3 microspheres were precipitated through the reaction of CaCl 2 with Na 2 CO 3 in the presence of aspartic acid and sodium dodecyl sulfate. Then, the as-prepared hollow CaCO 3 microspheres were transformed into HCHAp microspheres with a controlled anion-exchange method. The HCHAp microspheres were 3-5μm with a shell thickness of 0.5-1μm and were constructed of short needle nanoparticles. The HCHAp microspheres were then loaded with SV, exhibiting excellent drug-loading capacity and sustained release properties. These results present a new material synthesis strategy for HCHAp microspheres and suggest that the as-prepared HCHAp microspheres are promising for applications in drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Sustained Dorzolamide Release Prevents Axonal and Retinal Ganglion Cell Loss in a Rat Model of IOP-Glaucoma.

    Science.gov (United States)

    Pitha, Ian; Kimball, Elizabeth C; Oglesby, Ericka N; Pease, Mary Ellen; Fu, Jie; Schaub, Julie; Kim, Yoo-Chun; Hu, Qi; Hanes, Justin; Quigley, Harry A

    2018-04-01

    To determine if one injection of a sustained release formulation of dorzolamide in biodegradable microparticles (DPP) reduces retinal ganglion cell (RGC) loss in a rat model of glaucoma. We injected either DPP or control microparticles intravitreally in rats. Two days later, unilateral ocular hypertension was induced by translimbal, diode laser treatment by a surgeon masked to treatment group. IOP and clinical exams were performed until sacrifice 6 weeks after laser treatment. RGC loss was measured by masked observers in both optic nerve cross-sections and RGC layer counts from retinal whole mounts. Cumulative IOP exposure was significantly reduced by DPP injection (49 ± 48 mm Hg × days in treated versus 227 ± 191 mm Hg × days in control microparticle eyes; P = 0.012, t -test). While control-injected eyes increased in axial length by 2.4 ± 1.7%, DPP eyes did not significantly enlarge (0.3 ± 2.2%, difference from control, P = 0.03, t -test). RGC loss was significantly less in DPP eyes compared with control microparticle injection alone (RGC axon count reduction: 21% vs. 52%; RGC body reduction: 25% vs. 50% [beta tubulin labeling]; P = 0.02, t -test). A single injection of sustained release DPP protected against RGC loss and axial elongation in a rat model of IOP glaucoma. Sustained release IOP-lowering medications have the potential to stop glaucoma progression.

  1. The effect of food on gastrointestinal (GI) transit of sustained-release ibuprofen tablets as evaluated by gamma scintigraphy

    International Nuclear Information System (INIS)

    Borin, M.T.; Khare, S.; Beihn, R.M.; Jay, M.

    1990-01-01

    The GI transit of radiolabeled sustained-release ibuprofen 800-mg tablets in eight healthy, fed volunteers was monitored using external gamma scintigraphy. Ibuprofen serum concentrations were determined from blood samples drawn over 36 hr following dosing. Sustained-release ibuprofen tablets containing 0.18% of 170Er2O3 (greater than 96% 170Er) in the bulk formulation were manufactured under pilot-scale conditions and were radiolabeled utilizing a neutron activation procedure which converted stable 170Er to radioactive 171Er (t1/2 = 7.5 hr). At the time of dosing, each tablet contained 50 mu Ci of 171Er. Dosage form position were reported at various time intervals. In five subjects the sustained-release tablet remained in the stomach and eroded slowly over 7-12 hr, resulting in gradual increases in small bowel radioactivity. In the remaining three subjects, the intact tablet was ejected from the stomach and a gastric residence time of approximately 4 hr was measured. This is in marked contrast to a previous study conducted in fasted volunteers in which gastric retention time ranged from 10 to 60 min. Differences in GI transit between fed and fasted volunteers had little effect on ibuprofen bioavailability. AUC and Tmax were unaltered and Cmax was increased by 24%, which is in agreement with results from a previous, crossover-design food effect study

  2. Preparation and In-Vitro Evaluation of Sustained Release Matrix Diclofenac Sodium Tablets Using HPMC KM 100 and Gums

    Directory of Open Access Journals (Sweden)

    Zafar Iqbal, Raza Khan, Fazli Nasir, Jamshaid Ali Khan, Lateef Ahmad, Abad Khan, Yaser Shah

    2010-12-01

    Full Text Available Objectives: The impact of hydroxypropylmethyl cellulose(HPMC K 100M alone and in combination with the guar gum,xanthan gum and gum tragacanth on the release of the diclofenac sodium matrix tablets were evaluated.Materials and Methods: The granules were prepared using wet granulation method and compressed into tablets using different ratio of drug and gum ratio. The physical properties of the tablets were within acceptable pharmacopeial limits.The release profiles of the matrix tablets were evaluated in vitro,using USP dissolution apparatus II (paddle method.Results: The formulations containing HPMC K 100M drug ratio1:1.3 and 1:1.6 and formulations containing HPMC, gum and drug with different ratio also sustained the release of diclofenac sodium for 12 hours. The mechanism of drug release from the matrix tablets was studied using Zero order, First order, Higuchi and Korsmeyer’s models using regression coefficient method. The stability of the selected formulations was evaluated at 40˚C and 70% RH for 6 months.Conclusions: HPMC K100M alone and in combination with natural gums as the retarding material retarded the release upto 12 hours and showed little deviation from the theoretical release pattern.

  3. Effect of Misoprostol on the Pharmacokinetics of Sustained Release Diclofenac in Myanmar Healthy Male Volunteers

    Directory of Open Access Journals (Sweden)

    Htet Htet Aung

    2017-03-01

    Full Text Available Background: Sustained release diclofenac (diclofenac SR is the commonly used non-steroidal anti-inflammatory drug for chronic inflammatory conditions such as rheumatoid arthritis. Misoprostol, prostaglandin analogue, is the agent that enhances gastrointestinal mucosal defense. Concomitant administration of misoprostol with diclofenac SR can prevent the gastrointestinal side effects of diclofenac SR. Objective: The purpose of the study was to explore the effect of misoprostol on the pharmacokinetics of diclofenac SR in healthy volunteers. Methods: Crossover study was evaluated in 14 male volunteers. Single oral dose of 100 mg diclofenac SR was concomitantly administered with 200 μg misoprostol with one-week wash out period. Plasma concentrations at 0, 0.5, 1, 1.5, 2, 3, 6 and 10 hrs were determined by high performance liquid chromatography (HPLC. Pharmacokinetic parameters such as area under concentration-time curve (AUC0-α, peak plasma concentration (Cmax, time to achieve peak plasma concentration (Tmax, absorption half-life (T½(ab, elimination half-life (T1/2(el, absorption rate constant (Kab, and elimination rate constant (Kel were determined. Results: With misoprostol, the mean AUC0-α of diclofenac SR was significantly reduced from 12.11±5.25μg/ mL×hr to 4.17±2.72μg/mL×hr (p0.05. The mean T½(ab was decreased from 0.56±0.23hr to 0.54±0.19hr (p>0.05. The mean Kab were almost the same 1.43±0.54hr-1 and 1.43±0.48hr-1. The mean T1/2(el was decreased from 3.68±1.64hr to 3.03±1.08hr (p>0.05. The mean Kel was increased from 0.21±0.09hr-1 to 0.25±0.09hr-1 (p>0.05. Conclusion: There was a significant reduction in the extent of absorption of diclofenac SR when concomitantly administered with misoprostol. Therefore, the dose of diclofenac SR may need to be increased to avoid therapeutic failure of diclofenac SR or concurrent use with misoprostol may need to be changed to other gastroprotective agents.

  4. The Influence of Polyethylene Glycol Solution on the Dissolution Rate of Sustained Release Morphine.

    Science.gov (United States)

    Hodgman, Michael; Holland, Michael G; Englich, Ulrich; Wojcik, Susan M; Grant, William D; Leitner, Erich

    2016-12-01

    Whole bowel irrigation (WBI) is a management option for overdose of medications poorly adsorbed to activated charcoal, with modified release properties, or for body packers. Polyethylene glycol (PEG) is a mixture of ethylene oxide polymers of varying molecular weight. PEG with an average molecular weight of 3350 g/mol is used for WBI. PEG electrolyte lavage solution has been shown in vitro to hasten the dissolution of acetaminophen. The impact of PEG on the pharmacokinetics of extended release pharmaceuticals is unknown. Lower average molecular weight PEG mixtures are used as solvents and excipients. We sought to investigate the impact of PEG on the release of morphine from several extended release morphine formulations. An in vitro gastric model was developed. To test the validity of our model, we first investigated the previously described interaction of ethanol and Avinza®. Once demonstrated, we then investigated the effect of PEG with several extended release morphine formulations. In the validation portion of our study, we confirmed an ethanol Avinza® interaction. Subsequently, we did not observe accelerated release of morphine from Avinza® or generic extended release morphine in the presence of PEG. The use of PEG for gastric decontamination following ingestion of these extended release morphine formulations is unlikely to accelerate morphine release and aggravate intoxication.

  5. Sustained-release bupropion versus naltrexone in the treatment of pathological gambling: a preliminary blind-rater study.

    Science.gov (United States)

    Dannon, Pinhas N; Lowengrub, Katherine; Musin, Ernest; Gonopolski, Yehudit; Kotler, Moshe

    2005-12-01

    Pathological gambling (PG) is a relatively common and highly disabling impulse control disorder. A range of psychotherapeutic agents, including selective serotonin reuptake inhibitors, mood stabilizers, and opioid antagonists, has been shown to be effective in the treatment of PG. The use of selective serotonin reuptake inhibitors and opioid antagonists for PG is consistent with the observation that PG shares features of both the obsessive-compulsive spectrum disorders and addictive disorders. The aim of the study is to compare the effectiveness of sustained-release bupropion versus naltrexone in the treatment of PG. Thirty-six male pathological gamblers were enrolled in our study. A comprehensive psychiatric diagnostic evaluation was performed at baseline on all patients, and patients were screened for symptoms of gambling, depression, and anxiety using the South Oaks Gambling Screen, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Clinical Global Impression-Severity Scale. In addition, the patients completed self-report questionnaires about their demographic status. Patients were randomized in 2 groups and received either naltrexone (n = 19) or sustained-release bupropion (n = 17) for 12 weeks in a parallel fashion. Treatment response was monitored using the Clinical Global Impression-Improvement Scale which was performed at weeks 2, 4, 8, and 12. Patients were also assessed for the presence of gambling behavior via an unstructured interview, which was also performed at weeks 2, 4, 6, 8, and 12. Raters were blind to the study treatment. The majority of patients responded well to the drug treatment. Twelve of 17 patients in the sustained-release bupropion group completed the 12-week study, and 13 of 19 naltrexone patients completed the study. Nine (75%) of the 12 completers were rated as full responders in the sustained-release bupropion group versus 10 (76%) of 12 in the naltrexone group. Three (25%) of 12 completers in the

  6. Pore size is a critical parameter for obtaining sustained protein release from electrochemically synthesized mesoporous silicon microparticles

    Directory of Open Access Journals (Sweden)

    Ester L. Pastor

    2015-10-01

    Full Text Available Mesoporous silicon has become a material of high interest for drug delivery due to its outstanding internal surface area and inherent biodegradability. We have previously reported the preparation of mesoporous silicon microparticles (MS-MPs synthesized by an advantageous electrochemical method, and showed that due to their inner structure they can adsorb proteins in amounts exceeding the mass of the carrier itself. Protein release from these MS-MPs showed low burst effect and fast delivery kinetics with complete release in a few hours. In this work, we explored if tailoring the size of the inner pores of the particles would retard the protein release process. To address this hypothesis, three new MS-MPs prototypes were prepared by electrochemical synthesis, and the resulting carriers were characterized for morphology, particle size, and pore structure. All MS-MP prototypes had 90 µm mean particle size, but depending on the current density applied for synthesis, pore size changed between 5 and 13 nm. The model protein α-chymotrypsinogen was loaded into MS-MPs by adsorption and solvent evaporation. In the subsequent release experiments, no burst release of the protein was detected for any prototype. However, prototypes with larger pores (>10 nm reached 100% release in 24–48 h, whereas prototypes with small mesopores (<6 nm still retained most of their cargo after 96 h. MS-MPs with ∼6 nm pores were loaded with the osteogenic factor BMP7, and sustained release of this protein for up to two weeks was achieved. In conclusion, our results confirm that tailoring pore size can modify protein release from MS-MPs, and that prototypes with potential therapeutic utility for regional delivery of osteogenic factors can be prepared by convenient techniques.

  7. Improvement in autologous human fat transplant survival with SVF plus VEGF-PLA nano-sustained release microspheres.

    Science.gov (United States)

    Li, Liqun; Pan, Shengsheng; Ni, Binting; Lin, Yuanshao

    2014-08-01

    Early neovascularization is important for autologous fat transplant survival. SVF cells are ideal seed cells. Both vascular endothelial growth factor (VEGF) and SVF cells can promote neovascularization. However, the half-life (about 50 min) of VEGF is too short to sustain an adequate local concentration. We have investigated whether VEGF-polylactic acid (PLA) nano-sustained release microspheres plus SVF cells can improve neovascularization and survival of transplanted fat tissues. SVF cells were harvested and constructed VEGF-PLA nano-sustained release microspheres in vitro. Human fat tissues was mixed with SVF cells plus VEGF-PLA, SVF cells alone or Dulbecco's modified Eagle's medium as the control. These three mixtures were injected into random sites in 18 nude mice. Two months later, the transplants were weighed and examined histologically; and capillaries were counted to quantify neovascularization. Hematoxylin-eosin (HE) and anti-VEGF stains were applied to reveal cell infiltration. The mean wet weight of fat in the SVF plus VEGF-PLA, SVF alone, and control transplants were 0.18 ± 0.013 g, 0.16 ± 0.015 g, and 0.071 ± 0.12 g, respectively; the differences between groups were statistically significant. More vessels were present in the SVF plus VEGF-PLA transplants than in the other two types. Transplants mixed with SVF cells also had an acceptable density of capillaries. Histological analysis revealed that both the SVF plus VEGF-PLA and SVF alone transplants, but not the control transplants, were composed of adipose tissue, and had less fat necrosis and less fibrosis than control specimens. SVF plus VEGF-PLA transplants had significantly greater capillary density and VEGF expression than the other two transplant groups. Thus transplanted fat tissue survival and quality can be enhanced by the addition of VEGF-PLA nano-sustained release microspheres plus SVF cells. © 2014 International Federation for Cell Biology.

  8. Bimatoprost-loaded ocular inserts as sustained release drug delivery systems for glaucoma treatment: in vitro and in vivo evaluation.

    Directory of Open Access Journals (Sweden)

    Juçara Ribeiro Franca

    Full Text Available The purpose of the present study was to develop and assess a novel sustained-release drug delivery system of Bimatoprost (BIM. Chitosan polymeric inserts were prepared using the solvent casting method and characterized by swelling studies, infrared spectroscopy, differential scanning calorimetry, drug content, scanning electron microscopy and in vitro drug release. Biodistribution of 99mTc-BIM eye drops and 99mTc-BIM-loaded inserts, after ocular administration in Wistar rats, was accessed by ex vivo radiation counting. The inserts were evaluated for their therapeutic efficacy in glaucomatous Wistar rats. Glaucoma was induced by weekly intracameral injection of hyaluronic acid. BIM-loaded inserts (equivalent to 9.0 µg BIM were administered once into conjunctival sac, after ocular hypertension confirmation. BIM eye drop was topically instilled in a second group of glaucomatous rats for 15 days days, while placebo inserts were administered once in a third group. An untreated glaucomatous group was used as control. Intraocular pressure (IOP was monitored for four consecutive weeks after treatment began. At the end of the experiment, retinal ganglion cells and optic nerve head cupping were evaluated in the histological eye sections. Characterization results revealed that the drug physically interacted, but did not chemically react with the polymeric matrix. Inserts sustainedly released BIM in vitro during 8 hours. Biodistribution studies showed that the amount of 99mTc-BIM that remained in the eye was significantly lower after eye drop instillation than after chitosan insert implantation. BIM-loaded inserts lowered IOP for 4 weeks, after one application, while IOP values remained significantly high for the placebo and untreated groups. Eye drops were only effective during the daily treatment period. IOP results were reflected in RGC counting and optic nerve head cupping damage. BIM-loaded inserts provided sustained release of BIM and seem to be a

  9. Sustained release of piroxicam from solid lipid nanoparticle as an effective anti-inflammatory therapeutics in vivo.

    Science.gov (United States)

    Peng, Li-Hua; Wei, Wei; Shan, Ying-Hui; Chong, Yee-Song; Yu, Lian; Gao, Jian-Qing

    2017-01-01

    This study aims to investigate the solid lipid nanoparticle (SLN) as a novel vehicle for the sustained release and transdermal delivery of piroxicam, as well as to determine the anti-inflammation effect of piroxicam-loaded SLN. SLN formulation was optimized and the particle size, polydispersity index, zeta potential (ZP), encapsulation efficiency, drug release, and morphological properties were characterized. The transdermal efficiency and mechanism of the piroxicam-loaded SLNs were investigated in vitro. With the inflammation induced edema model in rat, the anti-inflammatory efficiency of piroxicam-enriched SLNs (Pir-SLNs) was evaluated. The SLN formulation was optimized as: lecithin 100 mg, glycerin monostearate 200 mg, and Tween (1%, w/w). The particle size is around 102 ± 5.2 nm with a PDI of 0.262. The ZP is 30.21 ± 2.05 mV. The prepared SLNs showed high entrapment efficiency of 87.5% for piroxicam. There is no interaction between piroxicam and the vehicle components. The presence of polymorphic form of lipid with higher drug content in the optimized Pir-SLNs enables the Pir-SLNs to release the drug with a sustained manner. Pir-SLNs with oleic acid as enhancer can radically diffuse into both the stratum corneum and dermal layer, as well as penetrate through the hair follicles and sebaceous glands with significantly higher density than the other control groups. Pir-SLNs promptly inhibited the inflammation since the 3rd hour after the treatment by decreasing the PGE 2 level. SLN was demonstrated to be a promising carrier for encapsulation and sustained release of piroxicam. Pir-SLN is a novel topical preparation with great potential for anti-inflammation application.

  10. Preparation and evaluation of tamsulosin hydrochloride sustained-release pellets modified by two-layered membrane techniques

    Directory of Open Access Journals (Sweden)

    Jingmin Wang

    2015-02-01

    Full Text Available The aim of the present study was to develop tamsulosin hydrochloride sustained-release pellets using two-layered membrane techniques. Centrifugal granulator and fluidized-bed coater were employed to prepare drug-loaded pellets and to employ two-layered membrane coating respectively. The prepared pellets were evaluated for physicochemical characterization, subjected to differential scanning calorimetry (DSC and in vitro release of different pH. Different release models and scanning electron microscopy (SEM were utilized to analyze the release mechanism of Harnual® and home-made pellets. By comparing the dissolution profiles, the ratio and coating weight gain of Eudragit® NE30D and Eudragit® L30D55 which constitute the inside membrane were identified as 18:1 and 10%–11%. The coating amount of outside membrane containing Eudragit® L30D55 was determined to be 0.8%. The similarity factors (f2 of home-made capsule and commercially available product (Harnual® were above 50 in different dissolution media. DSC studies confirmed that drug and excipients had good compatibility and SEM photographs showed the similarities and differences of coating surface between Harnual® and self-made pellets before and after dissolution. According to Ritger-Peppas model, the two dosage form had different release mechanism.

  11. Metal ion-assisted self-assembly of complexes for controlled and sustained release of minocycline for biomedical applications

    International Nuclear Information System (INIS)

    Zhang, Zhiling; Wang, Zhicheng; Nong, Jia; Nix, Camilla A; Zhong, Yinghui; Ji, Hai-Feng

    2015-01-01

    This study reports the development of novel drug delivery complexes self-assembled by divalent metal ion-assisted coacervation for controlled and sustained release of a hydrophilic small drug molecule minocycline hydrochloride (MH). MH is a multifaceted agent that has demonstrated therapeutic effects in infection, inflammation, tumor, as well as cardiovascular, renal, and neurological disorders due to its anti-microbial, anti-inflammatory, and cytoprotective properties. However, the inability to translate the high doses used in experimental animals to tolerable doses in human patients limits its clinical application. Localized delivery can potentially expose the diseased tissue to high concentrations of MH that systemic delivery cannot achieve, while minimizing the side effects from systemic exposure. The strong metal ion binding-assisted interaction enabled high drug entrapment and loading efficiency, and stable long term release for more than 71 d. Released MH demonstrated potent anti-biofilm, anti-inflammatory, and neuroprotective activities. Furthermore, MH release from the complexes is pH-sensitive as the chelation between minocycline and metal ions decreases with pH, allowing ‘smart’ drug release in response to the severity of pathology-induced tissue acidosis. This novel metal ion binding-mediated drug delivery mechanism can potentially be applied to other drugs that have high binding affinity for metal ions and may lead to the development of new delivery systems for a variety of drugs. (paper)

  12. A poly({epsilon}-caprolactone) device for sustained release of an anti-glaucoma drug

    Energy Technology Data Exchange (ETDEWEB)

    Natu, Madalina V; De Sousa, HermInio C; Gil, M H [Department of Chemical Engineering, University of Coimbra, Polo II, Pinhal de Marrocos, 3030-290, Coimbra (Portugal); Gaspar, Manuel N; Fontes Ribeiro, Carlos A [Institute of Pharmacology and Experimental Therapeutics, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-354, Coimbra (Portugal); Correia, IlIdio J; Silva, Daniela, E-mail: hgil@eq.uc.pt [Centro de Investigacao em Ciencias da Saude, Faculdade de Ciencias da Saude, Universidade da Beira Interior, Covilha (Portugal)

    2011-04-15

    Implantable dorzolamide-loaded discs were prepared by blending poly({epsilon}-caprolactone), PCL, with poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide), Lu. By blending, crystallinity, water uptake and mass loss were modified relative to the pure polymers. Burst was diminished by coating the discs with a PCL shell. All samples presented burst release except PCL-coated samples that showed controlled release during 18 days. For PCL-coated samples, barrier control of diffusion coupled with partition control from the core slowed down the release, while for 50/50 Lu/PCL-coated samples, the enhancement in the porosity of the core diminished partition control of drug release. Nonlinear regression analysis suggested that a degradation model fully describes the release curve considering a triphasic release mechanism: the instantaneous diffusion (burst), diffusion and polymer degradation stages. The MTT test indicated that the materials are not cytotoxic for corneal endothelial cells. A good in vitro-in vivo correlation was obtained, with similar amounts of drug released in vitro and in vivo. The discs decreased intraocular pressure (IOP) in normotensive rabbit eyes by 13.0% during 10 days for PCL-coated and by 13.0% during 4 days for 50/50 Lu/PCL-coated samples. The percentages of IOP decrease are similar to those obtained by dorzolamide eyedrop instillation (11.0%).

  13. [Discussion on releasing price of Chinese patent medicine to market economy to achieve sustainable development].

    Science.gov (United States)

    Long, Xingchao; Huang, Luqi; Jiang, Erguo; Zhou, Yonghong; Xu, Yanfeng; Zheng, Shuhua; Ning, Xiaoling; Liu, Hongwei; Chen, Lin

    2012-02-01

    To analyze costs of the traditional Chinese medicine industry focusing on production costs. Data of 50 planted Chinese herbal medicines and 50 wild Chinese herbal medicines were summarized and analyzed to see the changes of price of Chinese herbal medicines. The derivative problems of limited price were analyzed by crude drug, quality of Chinese medicine and sustainable utilization of resource. The price of Chinese medicine shall be adapted to sustainable development of market economy.

  14. Sustained release of antibiotic complexed by multivalent ion: in vitro and in vivo study for the treatment of peritonitis.

    Science.gov (United States)

    Na, Seung Yeon; Oh, Se Heang; Kim, Tae Ho; Yoon, Jin A; Lee, In Soo; Lee, Jin Ho

    2014-12-10

    The main aims of this study are (i) the development of an antibiotic complexed with multivalent ion, which can allow sustained release of the antibiotic without any additional matrix or difficult process and (ii) the feasibility study of the ion-complexed antibiotic as a therapeutic technique for peritonitis treatment. An ion-complexed antibiotic is prepared by simple mixing of two aqueous solutions containing an ionized (water-soluble) drug (tetracycline) and a multivalent counter ionic compound. The ion-complexed antibiotic shows a continuous release of the antibiotic up to 21 days, and thus prolonged anti-bacterial effect by gradual ionic exchange between the multivalent ions in the complex and same-charged monovalent ions in surrounding medium. From the in vivo animal study using a cecum perforated peritonitis mouse model, the ion-complexed antibiotic group shows sufficient anti-bacterial effect and thus effectively treat the peritonitis because of the extermination of the contaminated enteric bacteria in the peritoneum during wound healing of injury cecum (by the sustained release of antibiotic from the ion complex). These results suggest that the ion-complexed antibiotic system may be promising for the effective treatment of the peritonitis caused by frequent gastrointestinal defect in clinical fields. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. High-amylose sodium carboxymethyl starch matrices: development and characterization of tramadol hydrochloride sustained-release tablets for oral administration.

    Science.gov (United States)

    Nabais, Teresa; Leclair, Grégoire

    2014-01-01

    Substituted amylose (SA) polymers were produced from high-amylose corn starch by etherification of its hydroxyl groups with chloroacetate. Amorphous high-amylose sodium carboxymethyl starch (HASCA), the resulting SA polymer, was spray-dried to obtain an excipient (SD HASCA) with optimal binding and sustained-release (SR) properties. Tablets containing different percentages of SD HASCA and tramadol hydrochloride were produced by direct compression and evaluated for dissolution. Once-daily and twice-daily SD HASCA tablets containing two common dosages of tramadol hydrochloride (100 mg and 200 mg), a freely water-soluble drug, were successfully developed. These SR formulations presented high crushing forces, which facilitate further tablet processing and handling. When exposed to both a pH gradient simulating the pH variations through the gastrointestinal tract and a 40% ethanol medium, a very rigid gel formed progressively at the surface of the tablets providing controlled drug-release properties. These properties indicated that SD HASCA was a promising and robust excipient for oral, sustained drug-release, which may possibly minimize the likelihood of dose dumping and consequent adverse effects, even in the case of coadministration with alcohol.

  16. Dual-drug delivery by porous silicon nanoparticles for improved cellular uptake, sustained release, and combination therapy.

    Science.gov (United States)

    Wang, Chang-Fang; Mäkilä, Ermei M; Kaasalainen, Martti H; Hagström, Marja V; Salonen, Jarno J; Hirvonen, Jouni T; Santos, Hélder A

    2015-04-01

    Dual-drug delivery of antiangiogenic and chemotherapeutic drugs can enhance the therapeutic effect for cancer therapy. Conjugation of methotrexate (MTX) to porous silicon (PSi) nanoparticles (MTX-PSi) with positively charged surface can improve the cellular uptake of MTX and inhibit the proliferation of cancer cells. Herein, MTX-PSi conjugates sustained the release of MTX up to 96 h, and the released fragments including MTX were confirmed by mass spectrometry. The intracellular distribution of the MTX-PSi nanoparticles was confirmed by transmission electron microscopy. Compared to pure MTX, the MTX-PSi achieved similar inhibition of cell proliferation in folate receptor (FR) over-expressing U87 MG cancer cells, and a higher effect in low FR-expressing EA.hy926 cells. Nuclear fragmentation analysis demonstrated programmed cell apoptosis of MTX-PSi in the high/low FR-expressing cancer cells, whereas PSi alone at the same dose had a minor effect on cell apoptosis. Finally, the porous structure of MTX-PSi enabled a successful concomitant loading of another anti-angiogenic hydrophobic drug, sorafenib, and considerably enhanced the dissolution rate of sorafenib. Overall, the MTX-PSi nanoparticles can be used as a platform for combination chemotherapy by simultaneously enhancing the dissolution rate of a hydrophobic drug and sustaining the release of a conjugated chemotherapeutic drug. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  17. 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.

  18. Iron released from ilmenite mineral sustains a phytoplankton community in microcosms

    Digital Repository Service at National Institute of Oceanography (India)

    Fernandes, C.E.G.; Velip, D.; Mourya, B.S.; Shaikh, S.; Das, A.; LokaBharathi, P.A.

    Natural biotic communities from Kalbadevi Bay were monitored in microcosms (1-l glass flasks) to test the hypothesis that iron released from ilmenite through microbial action contributes to proliferation of phytoplankton. Microcosms containing...

  19. Sustained transdermal release of diltiazem hydrochloride through electron beam irradiated different PVA hydrogel membranes

    Energy Technology Data Exchange (ETDEWEB)

    Bhunia, Tridib [Department of Polymer Science and Technology, University of Calcutta, 92 A.P.C. Road, Calcutta 700009 (India); Goswami, Luna [KIIT School of Biotechnology, KIIT University Campus XI, Patia, Bhubaneswar 751024, Orissa (India); Chattopadhyay, Dipankar [Department of Polymer Science and Technology, University of Calcutta, 92 A.P.C. Road, Calcutta 700009 (India); Bandyopadhyay, Abhijit, E-mail: abpoly@caluniv.ac.in [Department of Polymer Science and Technology, University of Calcutta, 92 A.P.C. Road, Calcutta 700009 (India)

    2011-08-15

    Extremely fast release of diltiazem hydrochloride (water soluble, anti anginal drug used to treat chest pain) together with its faster erosion has been the primary problem in conventional oral therapy. It has been addressed in this paper by encapsulating the drug in electron beam irradiated various poly (vinyl alcohol) hydrogel membranes and delivering it through transdermal route. Results show excellent control over the release of diltiazem hydrochloride through these membranes subject to their physico-mechanicals.

  20. Sustained transdermal release of diltiazem hydrochloride through electron beam irradiated different PVA hydrogel membranes

    Science.gov (United States)

    Bhunia, Tridib; Goswami, Luna; Chattopadhyay, Dipankar; Bandyopadhyay, Abhijit

    2011-08-01

    Extremely fast release of diltiazem hydrochloride (water soluble, anti anginal drug used to treat chest pain) together with its faster erosion has been the primary problem in conventional oral therapy. It has been addressed in this paper by encapsulating the drug in electron beam irradiated various poly (vinyl alcohol) hydrogel membranes and delivering it through transdermal route. Results show excellent control over the release of diltiazem hydrochloride through these membranes subject to their physico-mechanicals.

  1. Sustained transdermal release of diltiazem hydrochloride through electron beam irradiated different PVA hydrogel membranes

    International Nuclear Information System (INIS)

    Bhunia, Tridib; Goswami, Luna; Chattopadhyay, Dipankar; Bandyopadhyay, Abhijit

    2011-01-01

    Extremely fast release of diltiazem hydrochloride (water soluble, anti anginal drug used to treat chest pain) together with its faster erosion has been the primary problem in conventional oral therapy. It has been addressed in this paper by encapsulating the drug in electron beam irradiated various poly (vinyl alcohol) hydrogel membranes and delivering it through transdermal route. Results show excellent control over the release of diltiazem hydrochloride through these membranes subject to their physico-mechanicals.

  2. Local sustained-release delivery systems of the antibiofilm agent thiazolidinedione-8 for prevention of catheter-associated urinary tract infections.

    Science.gov (United States)

    Shenderovich, Julia; Feldman, Mark; Kirmayer, David; Al-Quntar, Abed; Steinberg, Doron; Lavy, Eran; Friedman, Michael

    2015-05-15

    Thiazolidinedione-8 (TZD-8) is an anti-quorum-sensing molecule that has the potential to effectively prevent catheter-associated urinary tract infections, a major healthcare challenge. Sustained-release drug-delivery systems can enhance drugs' therapeutic potential, by maintaining their therapeutic level and reducing their side effects. Varnishes for sustained release of TZD-8 based on ethylcellulose or ammonio methacrylate copolymer type A (Eudragit(®) RL) were developed. The main factors affecting release rate were found to be film thickness and presence of a hydrophilic or swellable polymer in the matrix. The release mechanism of ethylcellulose-based systems matched the Higuchi model. Selected varnishes were retained on catheters for at least 8 days. Sustained-release delivery systems of TZD-8 were active against Candida albicans biofilms. The present study demonstrates promising results en route to developing applications for the prevention of catheter-associated infections. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. 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.

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

    International Nuclear Information System (INIS)

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

    2008-01-01

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

  5. Absorption kinetics and steady-state plasma concentrations of theophylline following therapeutic doses of two sustained-release preparations

    DEFF Research Database (Denmark)

    Andersen, O; Nielsen, M K; Eriksen, P B

    1983-01-01

    Ten healthy volunteers received two sustained-release preparations as a single and multiple dose regimen in an open crossover study. Plasma theophylline concentrations were measured by an enzyme immunoassay. The limited fluctuation of the theophylline levels at steady state, with twice daily...... formulation, whereas this was not the case for the other (r = 0.27 and 0.49). The daily dose necessary to keep the plasma concentration within the therapeutic range of 55-110 mumole/liter varied from 7.9 to 22.9 mg/kg. Only mild side effects were recorded, but they were not correlated to the plasma...... theophylline concentration....

  6. Application of Metal-Organic Framework Nano-MIL-100(Fe) for Sustainable Release of Doxycycline and Tetracycline.

    Science.gov (United States)

    Taherzade, Seyed Dariush; Soleimannejad, Janet; Tarlani, Aliakbar

    2017-08-06

    Nanostructures of MIL-100 were synthesized and used as a drug delivery platform for two members of the Tetracycline family. Doxycycline monohydrate (DOX) and Tetracycline hydrochloride (TC) were loaded separately on nano-MIL-100 (nanoparticles of drug@carrier were abbreviated as DOX@MIL-100 and TC@MIL-100). Characterizations were carried out using FT-IR, XRD, BET, DLS, and SEM. The FT-IR spectra revealed that the drugs were loaded into the framework of the carrier. The XRD patterns of DOX@MIL-100 and TC@MIL-100 indicated that no free DOX or TC were present. It could be concluded that the drugs are well dispersed into the pores of nano-MIL-100. The microporosity of the carrier was confirmed by BJH data. BET analysis showed a reduction in the free surface for both DOX@MIL-100 and TC@MIL-100. The release of TC and DOX was investigated, and it was revealed that MIL-100 mediated the drug solubility in water, which in turn resulted in a decrease in the release rate of TC (accelerating in DOX case) without lowering the total amount of released drug. After 48 h, 96 percent of the TC was sustain released, which is an unprecedented amount in comparison with other methods.

  7. High loading efficiency and sustained release of siRNA encapsulated in PLGA nanoparticles: quality by design optimization and characterization.

    Science.gov (United States)

    Cun, Dongmei; Jensen, Ditte Krohn; Maltesen, Morten Jonas; Bunker, Matthew; Whiteside, Paul; Scurr, David; Foged, Camilla; Nielsen, Hanne Mørck

    2011-01-01

    Poly(DL-lactide-co-glycolide acid) (PLGA) is an attractive polymer for delivery of biopharmaceuticals owing to its biocompatibility, biodegradability and outstanding controlled release characteristics. The purpose of this study was to understand and define optimal parameters for preparation of small interfering RNA (siRNA)-loaded PLGA nanoparticles by the double emulsion solvent evaporation method and characterize their properties. The experiments were performed according to a 2(5-1) fractional factorial design based on five independent variables: The volume ratio between the inner water phase and the oil phase, the PLGA concentration, the sonication time, the siRNA load and the amount of acetylated bovine serum albumin (Ac-BSA) in the inner water phase added to stabilize the primary emulsion. The effects on the siRNA encapsulation efficiency and the particle size were investigated. The most important factors for obtaining an encapsulation efficiency as high as 70% were the PLGA concentration and the volume ratio whereas the size was mainly affected by the PLGA concentration. The viscosity of the oil phase was increased at high PLGA concentration, which explains the improved encapsulation by stabilization of the primary emulsion and reduction of siRNA leakage to the outer water phase. Addition of Ac-BSA increased the encapsulation efficiency at low PLGA concentrations. The PLGA matrix protected siRNA against nuclease degradation, provided a burst release of surface-localized siRNA followed by a triphasic sustained release for two months. These results enable careful understanding and definition of optimal process parameters for preparation of PLGA nanoparticles encapsulating high amounts of siRNA with immediate and long-term sustained release properties. Copyright © 2010 Elsevier B.V. All rights reserved.

  8. Therapeutic effect of an injectable sustained-release sinomenine hydrochloride and sodium hyaluronate compound in a rabbit model of osteoarthritis.

    Science.gov (United States)

    Liu, Wen-Guang; Ling, Pei-Xue; Lin, Xiu-Kun; Chen, Jian-Ying; Wang, Shao-Jin; Li, Peng; Wu, Xiao-Juan; Zhao, Dong-Mei; Liu, Sheng-Hou

    2012-07-01

    While intra-articular injection of sinomenine hydrochloride has a therapeutic effect on osteoarthritis, it has a short half-life, and is thermolabile and photolabile. The aim of this research was to evaluate the sustained-release of sinomenine hydrochloride from an injectable sinomenine hydrochloride and sodium hyaluronate compound (CSSSI) and its therapeutic effect in a rabbit model of osteoarthritis following intra-articular injection. An injectable compound consisting of 1% sodium hyaluronate and 2.5% sinomenine hydrochloride was prepared and kept as the experiment group, and 2.5% sinomenine hydrochloride was prepared and kept as the control group. The cumulative mass release was measured at different time points in each group in vitro. Sixty-five male Zelanian rabbits were randomly divided into five groups: 15 (30 knees) each for the control, sodium hyaluronate, sinomenine hydrochloride, and CSSSI groups respectively, and five (10 knees) for the modeling group. Papain was injected into both knees of each rabbit for model establishment. Subsequently, 0.2 ml of the corresponding drugs was injected into the articular cavities of the remaining experiment groups, while the control group was treated with 0.2 ml normal saline. All groups were treated once a week for 4 weeks. Seven days after the last treatment, knees were anatomized to perform pathological observations and Mankin's evaluation of the synovium. Four groups were compared using the SPSS 13.0 software package. In the in vitro sustained-release experiments, 90% of the drug was released in the experiment group 360 minutes following the injection. Comparison of the Mankin's evaluations of the four groups illustrated statistical discrepancies (P sodium hyaluronate/sinomenine hydrochloride groups, statistical significance was uniformly obtained. Moreover, sodium hyaluronate and sinomenine hydrochloride treatments showed significant improvement over the modeling control (P sodium hyaluronate vs. sinomenine

  9. Sustained release donepezil loaded PLGA microspheres for injection: Preparation, in vitro and in vivo study

    DEFF Research Database (Denmark)

    Guo, Wenjia; Quan, Peng; Fang, Liang

    2015-01-01

    -solvent evaporation method. The optimized formulation which avoided the crushing of microspheres during the preparation process was characterized in terms of particle size, morphology, drug loading and EE, physical state of DP in the matrix and in vitro and in vivo release behavior. DP microspheres were prepared...... release mechanism. After single-dose administration of DP microspheres via subcutaneous injection in rats, the plasma concentration of DP reached peak concentration at 0.50 d, and then declined gradually, but was still detectable at 15 d. A good correlation between in vitro and in vivo data was obtained...

  10. The Sustainable Release of Vancomycin and Its Degradation Products From Nanostructured Collagen/Hydroxyapatite Composite Layers

    Czech Academy of Sciences Publication Activity Database

    Suchý, Tomáš; Šupová, Monika; Klapková, E.; Horný, L.; Rýglová, Šárka; Žaloudková, Margit; Braun, Martin; Sucharda, Zbyněk; Ballay, R.; Veselý, J.; Chlup, H.; Denk, František

    2016-01-01

    Roč. 105, č. 3 (2016), 1288-1294 ISSN 0022-3549 R&D Projects: GA TA ČR(CZ) TA04010330 Institutional support: RVO:67985891 Keywords : anti-infectives * HPLC * coating * controlled release * degradation products * drug delivery systems * nanoparticles * pharmacokinetics * polymeric drug delivery systems Subject RIV: JI - Composite Materials Impact factor: 2.713, year: 2016

  11. 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 ...

  12. 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.

  13. A Meta-Analysis of the Efficacy of Bupropion Sustained-Release for Smoking Cessation in Heavy Smokers

    Directory of Open Access Journals (Sweden)

    Adrian Paszek

    2017-09-01

    Full Text Available Cigarette smoking damages just about every organ in the body and reduces overall health. Even with the prevalence of accessible nicotine replacement therapies and behavioral counseling, there remains a need for alternative therapies to improve the odds of successfully abstaining from smoking in the long term. Bupropion sustained-release (SR is a pharmacological, prescription-only intervention that is approved as a first-line treatment for smoking cessation. This meta-analysis examines the effectiveness of bupropion sustained-release for smoking cessation amongst heavy smokers, defined as those who consistently smoke at least fifteen or more cigarettes per day. Across five qualifying studies, bupropion SR increased odds of cessation over placebo treatment at six and twelve months. Bupropion SR is a well-tolerated, non-nicotinic therapy for smoking cessation. Treatment with bupropion SR reduces initial cravings and withdrawal effects but does not appear to address the multi-faceted problem of cigarette addiction, resulting in decreased abstinence rates over time. An integrated approach incorporating bupropion SR with other interventions, such as nicotine replacement therapies and psychotherapy, may provide the necessary means to achieve lasting cessation and promote well-being.

  14. The effect of sustained release boli with ammoniumiron(III)-hexacyanoferrate(II) on radiocesium accumulation in sheep grazing contaminated pasture

    International Nuclear Information System (INIS)

    Hansen, H.S.; Hove, K.; Barvik, K.

    1996-01-01

    Sustained release boli with the cesium binder ammoniumiron(III)-hexacyanoferrate(II) (AFCF) were tested under practical conditions for sheep grazing on pastures contaminated with radiocesium ( 134 Cs+ 137 Cs) from the Chernobyl fallout. Two types of AFCF boli were developed: boli without a protective surface coating intended to last 4-8 wk; and boli coated by a wax-mixture with an extended duration of 10-12 wk. From 1989 to 1993 we measured the effect of wax-coated and uncoated boli administered at various times during the grazing season to a total of 3,248 animals. Reductions in radiocesium levels in meat of sheep were measured by in vivo monitoring. Administration of AFCF boli without a wax-coating reduced the mean radiocesium levels in lambs by 42-75% over a 408 wk period, and administration of the wax-coated AFCF boli reduced the mean radiocesium levels by 48-65% over a 9-11 wk period. The coefficients of variation in meat radiocesium levels were similar in treated and control groups at the end of the observation period, showing that the reduction of meat radiocesium values was homogeneous throughout the treated groups. The boli giving sustained release of AFCF is a labor-saving and cost effective counter-measure for sheep grazing radiocesium contaminated pastures. 16 refs., 4 figs., 4 tabs

  15. Sustained release of melatonin from TiO2 nanotubes for modulating osteogenic differentiation of mesenchymal stem cells in vitro.

    Science.gov (United States)

    Lai, Min; Jin, Ziyang; Tang, Qiang; Lu, Min

    2017-10-01

    To control the sustained release of melatonin and modulate the osteogenic differentiation of mesenchymal stem cells (MSCs), melatonin was firstly loaded onto TiO 2 nanotubes by direct dropping method, and then a multilayered film was coated by a spin-assisted layer-by-layer technique, which was composed of chitosan (Chi) and gelatin (Gel). Successful fabrication was characterized by field emission scanning electron microscopy, atomic force microscope, X-ray photoelectron spectroscopy and contact angle measurement, respectively. The efficient sustained release of melatonin was measured by UV-visible-spectrophotometer. After 2 days of culture, well-spread morphology was observed in MSCs grown on the Chi/Gel multilayer-coated melatonin-loaded TiO 2 nanotube substrates as compared to different groups. After 4, 7, 14 and 21 days of culture, the multilayered-coated melatonin-loaded TiO 2 nanotube substrates increased cell proliferation, increased alkaline phosphatase (ALP) and mineralization, increased expression of mRNA levels for runt-related transcription factor 2 (Runx2), ALP, osteopontin (OPN) and osteocalcin (OC), indicative of osteoblastic differentiation. These results demonstrated that Chi/Gel multilayer-coated melatonin-loaded TiO 2 nanotube substrates promoted cell adhesion, spreading, proliferation and differentiation and could provide an alternative fabrication method for titanium-based implants to enhance the osteointegration between bone tissues and implant surfaces.

  16. Sorption/Desorption Behavior and Mechanism of NH4(+) by Biochar as a Nitrogen Fertilizer Sustained-Release Material.

    Science.gov (United States)

    Cai, Yanxue; Qi, Hejinyan; Liu, Yujia; He, Xiaowei

    2016-06-22

    Biochar, the pyrolysis product of biomass material with limited oxygen, has the potential to increase crop production and sustained-release fertilizer, but the understanding of the reason for improving soil fertility is insufficient, especially the behavior and mechanism of ammonium sulfate. In this study, the sorption/desorption effect of NH4(+) by biochar deriving from common agricultural wastes under different preparation temperatures from 200 to 500 °C was studied and its mechanism was discussed. The results showed that biochar displayed excellent retention ability in holding NH4(+) above 90% after 21 days under 200 °C preparation temperature, and it can be deduced that the oxygen functional groups, such as carboxyl and keto group, played the primary role in adsorbing NH4(+) due to hydrogen bonding and electrostatic interaction. The sorption/desorption effect and mechanism were studied for providing an optional way to dispose of agricultural residues into biochar as a nitrogen fertilizer sustained-release material under suitable preparation temperature.

  17. Correlation of ibuprofen bioavailability with gastrointestinal transit by scintigraphic monitoring of 171Er-labeled sustained-release tablets

    International Nuclear Information System (INIS)

    Parr, A.F.; Beihn, R.M.; Franz, R.M.; Szpunar, G.J.; Jay, M.

    1987-01-01

    External gamma scintigraphy was used to monitor the gastrointestinal (GI) transit of radiolabeled sustained-release tablets containing 800 mg ibuprofen in eight fasted healthy volunteers. Ibuprofen serum concentrations were determined from blood samples drawn sequentially over a 24-hr period. Serum concentrations and related parameters were correlated to the position of the dosage form in the GI tract from the scintiphotos. The sustained-release tablets were radiolabeled intact utilizing a neutron activation procedure, by incorporating 0.18% of 170 Er2O3 (enriched to greater than 96% 170 Er) into the bulk formulation. After manufacture of the final dosage forms, the tablets were irradiated in a neutron flux (4.4 x 10(13) n/cm2.sec) for 2 min, converting the stable 170 Er to radioactive 171 Er (t1/2 = 7.5 hr). Each tablet contained 50 microCi of 171 Er at the time of administration. The scintigraphy studies suggested that the greatest proportion of ibuprofen was absorbed from this dosage form while the tablet was in the large bowel. The dosage forms eroded slowly in the small bowel and appeared to lose their integrity in the large bowel. In vitro studies showed only minimal effects of the neutron irradiation procedure on the dosage form performance

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

    Science.gov (United States)

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

    2011-12-01

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

  19. Carboxylic acid functionalization of halloysite nanotubes for sustained release of diphenhydramine hydrochloride

    Energy Technology Data Exchange (ETDEWEB)

    Zargarian, S. Sh.; Haddadi-Asl, V., E-mail: haddadi@aut.ac.ir; Hematpour, H. [Amirkabir University of Technology, Department of Polymer Engineering and Color Technology (Iran, Islamic Republic of)

    2015-05-15

    Halloysite nanotubes (HNT) (cylindrical shape with external diameter and length in the range of 30–80 nm and 0.2–1 µm, respectively) were functionalized with 3-aminopropyltriethoxysilane (APTES) from hydroxyl groups by a coupling reaction. Subsequently, maleic anhydride was attached to the APTES moieties to yield carboxylic acid-functionalized HNT. Loading and subsequent release of a model drug molecule diphenhydramine hydrochloride (DPH) on modified and unmodified nanotubes were investigated. Morphology of HNT was studied by electron microscopy. Successful attachment of APTES and carboxylic acid groups to halloysite and drug loading were evaluated by Fourier transform infrared spectroscopy. The amount of surface modification and drug adsorption capacity were calculated via thermogravimetric analysis. The ordered crystal structure of loaded drug was evaluated by X-ray diffraction. UV–Visible spectrophotometer was used to study drug release from modified and unmodified samples. Carboxylated halloysite exhibits higher loading capacity and prolonged release of DPH as compared to that of the natural halloysite.

  20. Carboxylic acid functionalization of halloysite nanotubes for sustained release of diphenhydramine hydrochloride

    International Nuclear Information System (INIS)

    Zargarian, S. Sh.; Haddadi-Asl, V.; Hematpour, H.

    2015-01-01

    Halloysite nanotubes (HNT) (cylindrical shape with external diameter and length in the range of 30–80 nm and 0.2–1 µm, respectively) were functionalized with 3-aminopropyltriethoxysilane (APTES) from hydroxyl groups by a coupling reaction. Subsequently, maleic anhydride was attached to the APTES moieties to yield carboxylic acid-functionalized HNT. Loading and subsequent release of a model drug molecule diphenhydramine hydrochloride (DPH) on modified and unmodified nanotubes were investigated. Morphology of HNT was studied by electron microscopy. Successful attachment of APTES and carboxylic acid groups to halloysite and drug loading were evaluated by Fourier transform infrared spectroscopy. The amount of surface modification and drug adsorption capacity were calculated via thermogravimetric analysis. The ordered crystal structure of loaded drug was evaluated by X-ray diffraction. UV–Visible spectrophotometer was used to study drug release from modified and unmodified samples. Carboxylated halloysite exhibits higher loading capacity and prolonged release of DPH as compared to that of the natural halloysite

  1. Polymeric and Solid Lipid Nanoparticles for Sustained Release of Carbendazim and Tebuconazole in Agricultural Applications

    Science.gov (United States)

    Campos, Estefânia Vangelie Ramos; Oliveira, Jhones Luiz De; da Silva, Camila Morais Gonçalves; Pascoli, Mônica; Pasquoto, Tatiane; Lima, Renata; Abhilash, P. C.; Fernandes Fraceto, Leonardo

    2015-09-01

    Carbendazim (MBC) (methyl-2-benzimidazole carbamate) and tebuconazole (TBZ) ((RS)-1-(4-chlorophenyl)-4,4-dimethyl-3-(1H-1,2,4-triazol-1-ylmethyl)pentan-3-ol) are widely used in agriculture for the prevention and control of fungal diseases. Solid lipid nanoparticles and polymeric nanocapsules are carrier systems that offer advantages including changes in the release profiles of bioactive compounds and their transfer to the site of action, reduced losses due to leaching or degradation, and decreased toxicity in the environment and humans. The objective of this study was to prepare these two types of nanoparticle as carrier systems for a combination of TBZ and MBC, and then investigate the release profiles of the fungicides as well as the stabilities and cytotoxicities of the formulations. Both nanoparticle systems presented high association efficiency (>99%), indicating good interaction between the fungicides and the nanoparticles. The release profiles of MBC and TBZ were modified when the compounds were loaded in the nanoparticles, and cytotoxicity assays showed that encapsulation of the fungicides decreased their toxicity. These fungicide systems offer new options for the treatment and prevention of fungal diseases in plants.

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

    Directory of Open Access Journals (Sweden)

    Julia M. Tan

    2014-01-01

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

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

    Science.gov (United States)

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

    2018-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Ashlesha Pravin Pandit

    2010-09-01

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

  5. In-vitro evaluation of ion-exchange microspheres for the sustained release of liposomal-adenoviral conjugates.

    Science.gov (United States)

    Steel, Jason C; Cavanagh, Heather M A; Burton, Mark A; Dingwall, Daniel; Kalle, Wouter H J

    2004-03-24

    This study looks at the development of a novel combination vector consisting of adenovirus conjugated to liposomes (AL complexes) bound to cation-exchanging microspheres (MAL complexes). With adenovirus having a net negative charge and the liposomes a net positive charge it was possible to modify the net charge of the AL complexes by varying the concentrations of adenovirus to liposomes. The modification of the net charge resulted in altered binding and release characteristics. Of the complexes tested, the 5:1 and 2:1 ratio AL complexes were able to be efficiently bound by the microspheres and exhibited sustained release over 24 h. The 1:1 and 1:2 AL complexes, however, bound poorly to the microspheres and were rapidly released. In addition the MAL complexes also were able to reduce the toxicity of the AL complexes, which was seen with the 10:1 ratio. The AL complexes showed considerably more toxicity alone than in combination with microspheres, highlighting a potential benefit of this vector.

  6. Anhydrous polymer-based coating with sustainable controlled release functionality for facile, efficacious impregnation, and delivery of antimicrobial peptides.

    Science.gov (United States)

    Lim, Kaiyang; Saravanan, Rathi; Chong, Kelvin K L; Goh, Sharon H M; Chua, Ray R Y; Tambyah, Paul A; Chang, Matthew W; Kline, Kimberly A; Leong, Susanna S J

    2018-04-17

    Anhydrous polymers are actively explored as alternative materials to overcome limitations of conventional hydrogel-based antibacterial coating. However, the requirement for strong organic solvent in polymerization reactions often necessitates extra protection steps for encapsulation of target biomolecules, lowering encapsulation efficiency, and increasing process complexity. This study reports a novel coating strategy that allows direct solvation and encapsulation of antimicrobial peptides (HHC36) into anhydrous polycaprolactone (PCL) polymer-based dual layer coating. A thin 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) film is layered onto the peptide-impregnated PCL as a diffusion barrier, to modulate and enhance release kinetics. The impregnated peptides are eventually released in a controlled fashion. The use of 2,2,2-trifluoroethanol (TFE), as polymerization and solvation medium, induces the impregnated peptides to adopt highly stable turned conformation, conserving peptide integrity, and functionality during both encapsulation and subsequent release processes. The dual layer coating showed sustained antibacterial functionality, lasting for 14 days. In vivo assessment using an experimental mouse wounding model demonstrated good biocompatibility and significant antimicrobial efficacy of the coating under physiological conditions. The coating was translated onto silicone urinary catheters and showed promising antibacterial efficacy, even outperforming commercial silver-based Dover cather. This anhydrous polymer-based platform holds immense potential as an effective antibacterial coating to prevent clinical device-associated infections. The simplicity of the coating process enhances its industrial viability. © 2018 Wiley Periodicals, Inc.

  7. Cross-Linked Dependency of Boronic Acid-Conjugated Chitosan Nanoparticles by Diols for Sustained Insulin Release

    Directory of Open Access Journals (Sweden)

    Nabil A. Siddiqui

    2016-10-01

    Full Text Available Boronic acids have been widely investigated for their potential use as glucose sensors in glucose responsive polymeric insulin delivery systems. Interactions between cyclic diols and boronic acids, anchored to polymeric delivery systems, may result in swelling of the delivery system, releasing the drug. In this study, 4-formylphenylboronic acid conjugated chitosan was formulated into insulin containing nanoparticles via polyelectrolyte complexation. The nanoparticles had an average diameter of 140 ± 12.8 nm, polydispersity index of 0.17 ± 0.1, zeta potential of +19.1 ± 0.69 mV, encapsulation efficiency of 81% ± 1.2%, and an insulin loading capacity of 46% ± 1.8% w/w. Changes in size of the nanoparticles and release of insulin were type of sugar- and concentration-dependent. High concentration of diols resulted in a sustained release of insulin due to crosslink formation with boronic acid moieties within the nanoparticles. The formulation has potential to be developed into a self-regulated insulin delivery system for the treatment of diabetes.

  8. Real-time Monitoring of Sustained Drug Release using the Optical Properties of Porous Silicon Photonic Crystal Particles

    Science.gov (United States)

    Wu, E.C.; Andrew, J.S.; Cheng, L; Freeman, W.R.; Pearson, L; Sailor, M.J.

    2011-01-01

    A controlled and observable drug delivery system that enables long-term local drug administration is reported. Biodegradable and biocompatible drug-loaded porous Si microparticles were prepared from silicon wafers, resulting in a porous 1-dimensional photonic crystal (rugate filter) approx. 12 micrometers thick and 35 micrometers across. An organic linker, 1-undecylenic acid, was attached to the Si-H terminated inner surface of the particles by hydrosilylation and the anthracycline drug daunorubicin was bound to the carboxy terminus of the linker. Degradation of the porous Si matrix in vitro was found to release the drug in a linear and sustained fashion for 30 d. The bioactivity of the released daunorubicin was verified on retinal pigment epithelial (RPE) cells. The degradation/drug delivery process was monitored in situ by digital imaging or spectroscopic measurement of the photonic resonance reflected from the nanostructured particles, and a simple linear correlation between observed wavelength and drug release was observed. Changes in the optical reflectance spectrum were sufficiently large to be visible as a distinctive red to green color change. PMID:21122914

  9. The Research and Application of Sustainable Long-release Carbon Material with Agricultural Waste

    Science.gov (United States)

    Wen, Z.

    2017-12-01

    (1) The element analysis shown that ten kinds of agricultural wastes containing a certain amount of C, N, H elements, the highest content of C element, and t value ranges from 36.02% 36.02%, and the variation of C, N, H elements content in difference materials was not significant. The TOC concentration of sugar cane was up to 38.66 mg·g-1, and quality ratio was 39‰, significantly lower than C elements content. The released TOC quality of the rest materials were 2.36 2.36 mg·g-1, and the order from high to low were the soybean straw, rice straw, corn straw, rice husk, poplar branches, wheat straw, reeds, corn cob and wood chips respectively. The long-term leaching experiment of selected Optimized agricultural waste showed that the TOC content in leaching solution rise rapidly to peak value and was stable afterwards, with the concentration of 4.59 19.46 mg·g-1. The TOC releasing amount order was same with the short-term leaching experiment. (2) The releasing of nitrate nitrogen in ten kinds of agricultural waste was low (corn straw was up to 0.12mg·g-1, and the rest were all below 0.04mg·g-1 without accumulation. Most of the ammonia nitrogen concentration in leachate was lower than 0.3mg·g-1. The kjeldahl nitrogen in the corn straw, soybean straw, rice straw, reed, rice husk, and sugar cane leachate (0.81 1.65mg·g-1) were higher than that of poplar branches, corn cob and wood chips (corn straw, rice husk and wheat straw leachate. Above all, it can be concluded that the sugar cane, corn straw, rice husk, wheat straw, corn cob, wood were ideal carbon source material in ten kinds of agricultural.

  10. Sustained release of neurotrophin-3 via calcium phosphate-coated sutures promotes axonal regeneration after spinal cord injury.

    Science.gov (United States)

    Hanna, Amgad; Thompson, Daniel L; Hellenbrand, Daniel J; Lee, Jae-Sung; Madura, Casey J; Wesley, Meredith G; Dillon, Natalie J; Sharma, Tapan; Enright, Connor J; Murphy, William L

    2016-07-01

    Because of the dynamics of spinal cord injury (SCI), the optimal treatment will almost certainly be a combination approach to control the environment and promote axonal growth. This study uses peripheral nerve grafts (PNGs) as scaffolds for axonal growth while delivering neurotrophin-3 (NT-3) via calcium phosphate (CaP) coatings on surgical sutures. CaP coating was grown on sutures, and NT-3 binding and release were characterized in vitro. Then, the NT-3-loaded sutures were tested in a complete SCI model. Rats were analyzed for functional improvement and axonal growth into the grafts. The CaP-coated sutures exhibited a burst release of NT-3, followed by a sustained release for at least 20 days. Functionally, the rats with PNGs + NT-3-loaded sutures and the rats treated with PNGs scored significantly higher than controls on day 56 postoperatively. However, functional scores in rats treated with PNGs + NT-3-loaded suture were not significantly different from those of rats treated with PNGs alone. Cholera toxin subunit B (CTB) labeling rostral to the graft was not observed in any controls, but CTB labeling rostral to the graft was observed in almost all rats that had had a PNG. Neurofilament labeling on transverse sections of the graft revealed that the rats treated with the NT-3-loaded sutures had significantly more axons per graft than rats treated with an NT-3 injection and rats without NT-3. These data demonstrate that PNGs serve as scaffolds for axonal growth after SCI and that CaP-coated sutures can efficiently release NT-3 to increase axonal regeneration. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Sustained Na+/H+ exchanger activation promotes gliotransmitter release from reactive hippocampal astrocytes following oxygen-glucose deprivation.

    Directory of Open Access Journals (Sweden)

    Pelin Cengiz

    Full Text Available Hypoxia ischemia (HI-related brain injury is the major cause of long-term morbidity in neonates. One characteristic hallmark of neonatal HI is the development of reactive astrogliosis in the hippocampus. However, the impact of reactive astrogliosis in hippocampal damage after neonatal HI is not fully understood. In the current study, we investigated the role of Na(+/H(+ exchanger isoform 1 (NHE1 protein in mouse reactive hippocampal astrocyte function in an in vitro ischemia model (oxygen/glucose deprivation and reoxygenation, OGD/REOX. 2 h OGD significantly increased NHE1 protein expression and NHE1-mediated H(+ efflux in hippocampal astrocytes. NHE1 activity remained stimulated during 1-5 h REOX and returned to the basal level at 24 h REOX. NHE1 activation in hippocampal astrocytes resulted in intracellular Na(+ and Ca(2+ overload. The latter was mediated by reversal of Na(+/Ca(2+ exchange. Hippocampal astrocytes also exhibited a robust release of gliotransmitters (glutamate and pro-inflammatory cytokines IL-6 and TNFα during 1-24 h REOX. Interestingly, inhibition of NHE1 activity with its potent inhibitor HOE 642 not only reduced Na(+ overload but also gliotransmitter release from hippocampal astrocytes. The noncompetitive excitatory amino acid transporter inhibitor TBOA showed a similar effect on blocking the glutamate release. Taken together, we concluded that NHE1 plays an essential role in maintaining H(+ homeostasis in hippocampal astrocytes. Over-stimulation of NHE1 activity following in vitro ischemia disrupts Na(+ and Ca(2+ homeostasis, which reduces Na(+-dependent glutamate uptake and promotes release of glutamate and cytokines from reactive astrocytes. Therefore, blocking sustained NHE1 activation in reactive astrocytes may provide neuroprotection following HI.

  12. Coaxial Electrospray of Curcumin-Loaded Microparticles for Sustained Drug Release.

    Directory of Open Access Journals (Sweden)

    Shuai Yuan

    Full Text Available Curcumin exhibits superior anti-inflammatory, antiseptic and analgesic activities without significant side effects. However, clinical dissemination of this natural medicine is limited by its low solubility and poor bio-availability. To overcome this limitation, we propose to encapsulate curcumin in poly(lactic-co-glycolic acid (PLGA microparticles (MPs by an improved coaxial electrospray (CES process. This process is able to generate a stable cone-jet mode in a wide range of operation parameters in order to produce curcumin-loaded PLGA MPs with a clear core-shell structure and a designated size of several micrometers. In order to optimize the process outcome, the effects of primary operation parameters such as the applied electric voltages and the liquid flow rates are studied systemically. In vitro drug release experiments are also carried out for the CES-produced MPs in comparison with those by a single axial electrospray process. Our experimental results show that the CES process can be effectively controlled to encapsulate drugs of low aqueous solubility for high encapsulation efficiency and optimal drug release profiles.

  13. 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.

  14. 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.

  15. Evaluation of sustained release polylactate electron donors for removal of hexavalent chromium from contaminated groundwater

    Energy Technology Data Exchange (ETDEWEB)

    Brodie, E.L.; Joyner, D. C.; Faybishenko, B.; Conrad, M. E.; Rios-Velazquez, C.; Mork, B.; Willet, A.; Koenigsberg, S.; Herman, D.; Firestone, M. K.; Hazen, T. C.; Malave, Josue; Martinez, Ramon

    2011-02-15

    To evaluate the efficacy of bioimmobilization of Cr(VI) in groundwater at the Department of Energy Hanford site, we conducted a series of microcosm experiments using a range of commercial electron donors with varying degrees of lactate polymerization (polylactate). These experiments were conducted using Hanford Formation sediments (coarse sand and gravel) immersed in Hanford groundwater, which were amended with Cr(VI) and several types of lactate-based electron donors (Hydrogen Release Compound, HRC; primer-HRC, pHRC; extended release HRC) and the polylactate-cysteine form (Metal Remediation Compound, MRC). The results showed that polylactate compounds stimulated an increase in bacterial biomass and activity to a greater extent than sodium lactate when applied at equivalent carbon concentrations. At the same time, concentrations of headspace hydrogen and methane increased and correlated with changes in the microbial community structure. Enrichment of Pseudomonas spp. occurred with all lactate additions, and enrichment of sulfate-reducing Desulfosporosinus spp. occurred with almost complete sulfate reduction. The results of these experiments demonstrate that amendment with the pHRC and MRC forms result in effective removal of Cr(VI) from solution most likely by both direct (enzymatic) and indirect (microbially generated reductant) mechanisms.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  17. Sustained release of doxorubicin from zeolite-magnetite nanocomposites prepared by mechanical activation

    International Nuclear Information System (INIS)

    Arruebo, Manuel; Fernandez-Pacheco, Rodrigo; Irusta, Silvia; Arbiol, Jordi; Ibarra, M Ricardo; SantamarIa, Jesus

    2006-01-01

    Nanocomposites consisting of magnetite and FAU zeolite with a high surface area and adsorption capacity have been prepared by mechanical activation using high-energy milling at room temperature. FTIR results, as well as HRTEM, EFTEM, and XPS measurements, show that the resulting magnetic nanoparticles are covered by a thin aluminosilicate coating. A saturation magnetization as high as 16 emu g -1 and 94.2 Oe of coercivity were observed for the obtained composites. The main advantages of this synthesis procedure are (i) simplicity of the preparation procedure (ii) prevention of agglomeration of the magnetite nanoparticles to a large extent, and (iii) absence of free magnetite outside the zeolitic matrix. In addition, in vitro experiments revealed that the nanoparticles prepared were able to store and release substantial amounts of doxorubicin. In view of these advantages, these magnetic nanoparticles can be considered as potential candidates for drug-delivery applications

  18. [The enantioselective pharmacokinetic study of desvenlafaxine sustained release tablet in Chinese healthy male volunteers after oral administration].

    Science.gov (United States)

    Chen, Yin-xia; Du, Jiang-bo; Zhang, Yi-fan; Chen, Xiao-yan; Zhong, Da-fang

    2015-04-01

    A chiral LC-MS/MS method for the simultaneous analysis of desvenlafaxine (DVS) enantiomers in human plasma was developed and applied to a pharmacokinetic study on 12 Chinese healthy volunteers. d6-Desvenlafaxine was used as internal standard (IS). Chromatographic separation was performed on the Astec Chirobiotic V chiral column (150 mm x 4.6 mm, 5 μm). The assay was linear over the concentration range of 0.500-150 ng x mL(-1) for both enantiomers (r2 > 0.99). The method was successfully applied to a stereoselective pharmacokinetic study of 100 mg desvenlafaxine sustained release tablets on 12 Chinese healthy volunteers under fasting conditions. The results showed that the pharmacokinetic parameters were similar to both enantiomers in Chinese healthy volunteers. The AUC(0-t), and C(max) of the two enantiomers were about 1.5 times higher than those of blacks and whites reported in the literature.

  19. The effects of sustained release metofluthrin on the biting, movement, and mortality of Aedes aegypti in a domestic setting.

    Science.gov (United States)

    Rapley, Luke P; Russell, Richard C; Montgomery, Brian L; Ritchie, Scott A

    2009-07-01

    The impact of a sustained release metofluthrin emanator and an allethrin-based mosquito coil on biting, movement and mortality of female Aedes aegypti was assessed in an apartment. In the room in which the metofluthrin emanator was activated, mosquito biting counts were reduced to zero. Metofluthrin also had a spillover effect, significantly (P metofluthrin. Indeed, a significantly (P = 0.023) greater proportion of mosquitoes were found in the treated room after exposure to metofluthrin when compared with either the coil or control treatment. Furthermore, in the room treated with metofluthrin the majority of mosquitoes died and a spillover effect into the neighboring room caused greater than one-third mortality of the mosquitoes. Metofluthrin could be used to prevent dengue transmission within a household.

  20. Sustained release vancomycin-coated titanium alloy using a novel electrostatic dry powder coating technique may be a potential strategy to reduce implant-related infection.

    Science.gov (United States)

    Han, Jing; Yang, Yi; Lu, Junren; Wang, Chenzhong; Xie, Youtao; Zheng, Xuebin; Yao, Zhenjun; Zhang, Chi

    2017-07-24

    In order to tackle the implant-related infection, a novel way was developed in this study to coat vancomycin particles mixed with controlled release coating materials onto the surface of titanium alloy by using an electrostatic dry powder coating technique. To characterize this sustained release antibacterial coating, surface morphology, in vitro and in vivo drug release were sequentially evaluated. In vitro cytotoxicity was tested by Cell Counting Kit-8 (CCK-8) assay and cytological changes were observed by inverted microscope. The antibacterial properties against MRSA, including a bacterial growth inhibition assay and a colony-counting test by spread plate method were performed. Results indicated that the vancomycin-coated sample was biocompatible for Human osteoblast cell line MG-63 and displayed effective antibacterial ability against MRSA. The coating film was revealed uniform by scanning electron microscopy. Both the in vitro and in vivo drug release kinetics showed an initially high release rate, followed by an extended period of sustained drug release over 7 days. These results suggest that with good biocompatibility and antibacterial ability, the sustained release antibacterial coating of titanium alloy using our novel electrostatic dry powder coating process may provide a promising candidate for the treatment of orthopedic implant-related infection.

  1. Antifouling coating with controllable and sustained silver release for long-term inhibition of infection and encrustation in urinary catheters.

    Science.gov (United States)

    Wang, Rong; Neoh, Koon Gee; Kang, En-Tang; Tambyah, Paul Anantharajah; Chiong, Edmund

    2015-04-01

    Urinary tract infections constitute a large proportion of nosocomial infections, and the urinary catheter is the most important predisposing factor. Encrustation induced by urease-producing uropathogens like Proteus mirabilis causes further complications. In the present work, a strategy for controllable and sustained release of silver over several weeks has been developed for combating bacterial infection and encrustation in urinary devices. Silver nanoparticles (AgNPs) were first immobilized on polydopamine (PDA) pre-treated silicone catheter surface and this was followed by another PDA coating. The number of AgNP-PDA bilayers could be manipulated to control the amount of silver loaded and its subsequent release. Poly(sulfobetaine methacrylate-co-acrylamide) was then grafted to provide an antifouling outer layer, and to ensure free diffusion of Ag from the surface. The micron-scale combination of an antifouling coating with AgNP-PDA bilayers reduced colonization of the urinary catheter by uropathogens by approximately two orders of magnitude. With one and two AgNP-PDA bilayers, the coated catheter could resist encrustation for 12 and 45 days, respectively, compared with approximately 6 days with the Dover™ silver-coated catheter. Such anti-infective and anti-encrustation catheters can potentially have a large impact on reducing patient morbidity and healthcare expenditure. © 2014 Wiley Periodicals, Inc.

  2. 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.

  3. Development of a Sustainable Release System for a Ranibizumab Biosimilar Using Poly(lactic-co-glycolic acid) Biodegradable Polymer-Based Microparticles as a Platform.

    Science.gov (United States)

    Tanetsugu, Yusuke; Tagami, Tatsuaki; Terukina, Takayuki; Ogawa, Takaya; Ohta, Masato; Ozeki, Tetsuya

    2017-01-01

    Ranibizumab is a humanized monoclonal antibody fragment against vascular endothelial growth factor (VEGF)-A and is widely used to treat age-related macular degeneration (AMD) caused by angiogenesis. Ranibizumab has a short half-life in the eye due to its low molecular weight and susceptibility to proteolysis. Monthly intravitreal injection of a large amount of ranibizumab formulation is a burden for both patients and medical staff. We therefore sought to develop a sustainable release system for treating the eye with ranibizumab using a drug carrier. A ranibizumab biosimilar (RB) was incorporated into microparticles of poly(lactic-co-glycolic acid) (PLGA) biodegradable polymer. Ranibizumab was sustainably released from PLGA microparticles (80+% after 3 weeks). Assay of tube formation by endothelial cells indicated that RB released from PLGA microparticles inhibited VEGF-induced tube formation and this tendency was confirmed by a cell proliferation assay. These results indicate that RB-loaded PLGA microparticles are useful for sustainable RB release and suggest the utility of intraocular sustainable release systems for delivering RB site-specifically to AMD patients.

  4. [Sustained release of recombinant human bone morphogenetic protein-2 combined with stromal vascular fraction cells in promoting posterolateral spinal fusion in rat model].

    Science.gov (United States)

    Yuan, Wei; Zheng, Jun; Qian, Jinyu; Zhou, Xiaoxiao; Wang, Minghui; Wang, Xiuhui

    2017-07-01

    To observe the effect of stromal vascular fraction cells (SVFs) from rat fat tissue combined with sustained release of recombinant human bone morphogenetic protein-2 (rhBMP-2) in promoting the lumbar fusion in rat model. SVFs were harvested from subcutaneous fat of bilateral inguinal region of 4-month-old rat through the collagenase I digestion. The sustained release carrier was prepared via covalent bond of the rhBMP-2 and β-tricalcium phosphate (β-TCP) by the biominetic apatite coating process. The sustained release effect was measured by BCA method. Thirty-two rats were selected to establish the posterolateral lumbar fusion model and were divided into 4 groups, 8 rats each group. The decalcified bone matrix (DBX) scaffold+PBS, DBX scaffold+rhBMP-2/β-TCP sustained release carrier, DBX scaffold+SVFs, and DBX scaffold+rhBMP-2/β-TCP sustained release carrier+SVFs were implanted in groups A, B, C, and D respectively. X-ray films, manual spine palpation, and high-resolution micro-CT were used to evaluate spinal fusion at 8 weeks after operation; bone mineral density (BMD) and bone volume fraction were analyzed; the new bone formation was evaluated by HE staining and Masson's trichrome staining, osteocalcin (OCN) was detected by immunohistochemical staining. The cumulative release amount of rhBMP-2 was about 40% at 2 weeks, indicating sustained release effect of rhBMP-2; while the control group was almost released within 2 weeks. At 8 weeks, the combination of manual spine palpation, X-ray, and micro-CT evaluation showed that group D had the strongest bone formation (100%, 8/8), followed by group B (75%, 6/8), group C (37.5%, 3/8), and group A (12.5%, 1/8). Micro-CT analysis showed BMD and bone volume fraction were significantly higher in group D than groups A, B, and C ( P cells with bone matrix deposition, and an active osteogenic process similar to the mineralization of long bones in group D. The bone formation of group B was weaker than that of group D, and

  5. Sustained release of milrinone delivered via microparticles in a rodent model of myocardial infarction.

    Science.gov (United States)

    Al Kindi, Hamood; Paul, Arghya; You, Zhipeng; Nepotchatykh, Oleg; Schwertani, Adel; Prakash, Satya; Shum-Tim, Dominique

    2014-11-01

    The aim of the present study was to construct a new drug delivery system for milrinone using microparticles. This novel technology enhances drug bioavailability and decreases toxicity, with future implications for the treatment of end-stage heart failure. Polylactic-co-glycolic acid microparticles (PLGA-MPs) loaded with milrinone were prepared using a double emulsion-solvent evaporation technique. In vitro release kinetics was evaluated at physiologic conditions. A total of 24 female Lewis rats underwent left coronary artery ligation. One week after ligation, all rats were randomized to 1 of 3 groups (n=8 per group). Group I received an intravenous injection of PLGA-MPs alone; group II, a bolus intravenous injection of milrinone; and group III an intravenous injection of milrinone-PLGA-MPs. All injections were administrated slowly by way of the tail vein over 10 minutes. Transthoracic echocardiography, noninvasive heart rate monitoring, and blood pressure measurements were performed at different predetermined intervals before and for 24 hours after the injection. All rats survived for 24 hours and were then killed by euthanasia. Serum plasma was taken for cytokine assays and determination of milrinone levels using high-performance liquid chromatography. Group III had a significantly greater left ventricular ejection fraction at 90 minutes and 3, 6, and 12 hours after treatment compared with the other groups. The milrinone plasma level was significantly greater in group III than in the other groups (group I, 0 ng/mL; group II, 1.7±2.4 ng/mL; group III, 9.1±2.2 ng/mL; Pmilrinone. We propose a new strategy for future drug delivery in patients with end-stage heart failure. Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  6. Application of 5-Fluorouracil-Polycaprolactone Sustained-Release Film in Ahmed Glaucoma Valve Implantation Inhibits Postoperative Bleb Scarring in Rabbit Eyes.

    Science.gov (United States)

    Bi, Xiu-Zeng; Pan, Wei-Hua; Yu, Xin-Ping; Song, Zong-Ming; Ren, Zeng-Jin; Sun, Min; Li, Cong-Hui; Nan, Kai-Hui

    2015-01-01

    This study was designed to investigate whether 5-fluorouracil (5-Fu)-polycaprolactone sustained-release film in Ahmed glaucoma valve implantation inhibits postoperative bleb scarring in rabbit eyes. Eighteen New Zealand white rabbits were randomly divided into three groups (A, B and C; n = 6 per group). Group A received combined 5-Fu-polycaprolactone sustained-release film application and Ahmed glaucoma valve implantation, group B received local infiltration of 5-Fu and Ahmed glaucoma valve implantation, and group C received Ahmed glaucoma valve implantation. Postoperative observations were made of the anterior segment, intraocular pressure, central anterior chamber depth, blebs, drainage tube, and accompanying ciliary body detachment. The pathology of the blebs and surrounding tissues were observed at month 3 postoperatively. We revealed that the 5-Fu-polycaprolactone sustained-release film maintained a release concentration range of 13.7 ± 0.12 to 37.41 ± 0.47 μg/ml over three months in vitro. Postoperatively, diffuse blebs with ridges were found in all eyes in group A, two blebs were observed in group B, and no bleb formation was present in group C. The postoperative central anterior chamber depth in group A was significantly less than that of the other two groups. The postoperative intraocular pressure of group A stabilized at 6.33-8.67 mmHg, whereas that of group C gradually remained at 7.55-10.02 mmHg. The histopathology showed that the fibrous tissue thickness of the blebs in group A was significantly thinner than that of the other groups. We conclude that the 5-Fu-polycaprolactone sustained-release film had a sustained drug release effect, which promoted the inhibition of bleb scarring after Ahmed glaucoma valve implantation.

  7. Carnauba wax as a promising excipient in melt granulation targeting the preparation of mini-tablets for sustained release of highly soluble drugs.

    Science.gov (United States)

    Nart, Viviane; Beringhs, André O'Reilly; França, Maria Terezinha; de Espíndola, Brenda; Pezzini, Bianca Ramos; Stulzer, Hellen Karine

    2017-01-01

    Mini-tablets are a new tendency in solid dosage form design for overcoming therapeutic obstacles such as impaired swallowing and polypharmacy therapy. Among their advantages, these systems offer therapeutic benefits such as dose flexibility and combined drug release patterns. The use of lipids in the formulation has also drawn considerable interest as means to modify the drug release from the dosage form. Therefore, this paper aimed at developing sustained release mini-tablets containing the highly soluble drugs captopril and metformin hydrochloride. Carnauba wax was used as a lipid component in melt granulation, targeting the improvement of the drugs poor flowability and tabletability, as well as to sustain the drug release profiles in association with other excipients. To assist sustaining the drug release, Ethocel™ (EC) and Kollicoat® SR 30D associated with Opadry® II were employed as matrix-forming and reservoir-forming materials, respectively. The neat drugs, granules and the bulk formulations were evaluated for their angle of repose, compressibility index, Hausner ratio and tabletability. Mini-tablets were evaluated for their weight variation, hardness, friability, drug content and in-vitro drug release. The results indicated that melt granulation with carnauba wax improved the flow and the tabletability of the drugs, allowing the preparation of mini-tablets with adequate tensile strength under reduced compaction pressures. All mini-tablet formulations showed acceptable hardness (within the range of 1.16 to 3.93Kp) and friability (carnauba wax proved to be a promising excipient in melt granulation targeting the preparation of mini-tablets for sustained release of soluble drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Development and Characterization of Chitosan Cross-Linked With Tripolyphosphate as a Sustained Release Agent in Tablets, Part I: Design of Experiments and Optimization.

    Science.gov (United States)

    Pinto, Colin A; Saripella, Kalyan K; Loka, Nikhil C; Neau, Steven H

    2018-04-01

    Certain issues with the use of particles of chitosan (Ch) cross-linked with tripolyphosphate (TPP) in sustained release formulations include inefficient drug loading, burst drug release, and incomplete drug release. Acetaminophen was added to Ch:TPP particles to test for advantages of drug addition extragranularly over drug addition made during cross-linking. The influences of Ch concentration, Ch:TPP ratio, temperature, ionic strength, and pH were assessed. Design of experiments allowed identification of factors and 2-factor interactions that have significant effects on average particle size and size distribution, yield, zeta potential, and true density of the particles, as well as drug release from the directly compressed tablets. Statistical model equations directed production of a control batch that minimized span, maximized yield, and targeted a t 50 of 90 min (sample A); sample B that differed by targeting a t 50 of 240-300 min to provide sustained release; and sample C that differed from sample B by maximizing span. Sample B maximized yield and provided its targeted t 50 and the smallest average particle size, with the higher zeta potential and the lower span of samples B and C. Extragranular addition of a drug to Ch:TPP particles achieved 100% drug loading, eliminated a burst drug release, and can accomplish complete drug release. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  9. Sustained intra-articular release of celecoxib from in situ forming gels made of acetyl-capped PCLA-PEG-PCLA triblock copolymers in horses

    NARCIS (Netherlands)

    Petit, Audrey|info:eu-repo/dai/nl/371748461; Redout, Everaldo M; van de Lest, Chris H|info:eu-repo/dai/nl/146063570; de Grauw, Janny C|info:eu-repo/dai/nl/304822469; Müller, Benno; Meyboom, Ronald; van Midwoud, Paul; Vermonden, Tina|info:eu-repo/dai/nl/275124517; Hennink, Wim E|info:eu-repo/dai/nl/070880409; van Weeren, René|info:eu-repo/dai/nl/074628550

    In this study, the intra-articular tolerability and suitability for local and sustained release of an in situ forming gel composed of an acetyl-capped poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-lactide) (PCLA-PEG-PCLA) copolymer loaded with celecoxib was

  10. A multicenter, randomized, double-blind, placebo-controlled, 6-month trial of bupropion hydrochloride sustained-release tablets as an aid to smoking cessation in hospital employees

    DEFF Research Database (Denmark)

    Dalsgareth, Oli Jacob; Hansen, Niels-Christian Gerner; Søes-Petersen, Ulrik

    2004-01-01

    Despite changes in smoking behavior, one-third of the Danish population continues to smoke. Many of these smokers are hospital employees. This 6-month, multicenter, parallel group, randomized, double-blind, placebo-controlled study evaluated treatment with bupropion hydrochloride sustained release...

  11. Three-dimensional Printed Scaffolds with Gelatin and Platelets Enhance In vitro Preosteoblast Growth Behavior and the Sustained-release Effect of Growth Factors

    Directory of Open Access Journals (Sweden)

    Wei Zhu

    2016-01-01

    Conclusions: Our experiments confirmed that the 3D printed scaffolds we had designed could provide a sustained-release effect for growth factors and improve the proliferation of preosteoblasts with little cytotoxicity in vitro. They may hold promise as bone graft substitute materials in the future.

  12. Improvement of cellular uptake, in vitro antitumor activity and sustained release profile with increased bioavailability from a nanoemulsion platform.

    Science.gov (United States)

    Choudhury, Hira; Gorain, Bapi; Karmakar, Sanmoy; Biswas, Easha; Dey, Goutam; Barik, Rajib; Mandal, Mahitosh; Pal, Tapan Kumar

    2014-01-02

    Paclitaxel, a potential anticancer agent against solid tumors has been restricted from its oral use due to poor water solubility as well as Pgp efflux property. The present study was aimed to improve the oral bioavailability of paclitaxel through development of (o/w) nanoemulsion consisting of Capryol 90 as internal phase with Tween 20 as emulsifier with water as an external phase. Formulations were selected from the nanoemulsion region of pseudo-ternary phase diagrams, formulated by aqueous titration method. The developed nanoemulsion has been characterized by its thermodynamic stability, morphology, droplet size, zeta potential, viscosity where in vitro release was evaluated through dialysis. Paclitaxel nanoemulsion exhibited thermodynamical stability with low viscosity, nano-sized oil droplets in water with low poly-dispersity index. The shelf life of the paclitaxel nanoemulsion was found to be approximately 2.38 years. Increased permeability through the Caco-2 cell monolayer and decreased efflux is great advantageous for nanoemulsion formulation. The effects of paclitaxel nanoemulsion on breast cancer cell proliferation, morphology and DNA fragmentation were analyzed in vitro which showed significant anti-proliferation and decreased IC50 values in nanoemulsion group which may be due to enhanced uptake of paclitaxel through the oil core. Moreover, the absolute oral bioavailability and sustained release profile of the paclitaxel nanoemulsion evaluated in mouse model was found to improve up to 55.9%. The concentration of paclitaxel in mice plasma was determined by our validated LC-MS/MS method. By reviewing the significant outcome of the present investigation based on stability study, Caco-2 permeability, cell proliferative assay and pharmacokinetic profile it may be concluded that the oral nanoemulsion has got encouraging advantages over the presently available formulations of this injectable chemotherapeutic drug. Copyright © 2013 Elsevier B.V. All rights

  13. Sustained release of anticancer agent phytic acid from its chitosan-coated magnetic nanoparticles for drug-delivery system.

    Science.gov (United States)

    Barahuie, Farahnaz; Dorniani, Dena; Saifullah, Bullo; Gothai, Sivapragasam; Hussein, Mohd Zobir; Pandurangan, Ashok Kumar; Arulselvan, Palanisamy; Norhaizan, Mohd Esa

    2017-01-01

    Chitosan (CS) iron oxide magnetic nanoparticles (MNPs) were coated with phytic acid (PTA) to form phytic acid-chitosan-iron oxide nanocomposite (PTA-CS-MNP). The obtained nanocomposite and nanocarrier were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, vibrating sample magnetometry, transmission electron microscopy, and thermogravimetric and differential thermogravimetric analyses. Fourier transform infrared spectra and thermal analysis of MNPs and PTA-CS-MNP nanocomposite confirmed the binding of CS on the surface of MNPs and the loading of PTA in the PTA-CS-MNP nanocomposite. The coating process enhanced the thermal stability of the anticancer nanocomposite obtained. X-ray diffraction results showed that the MNPs and PTA-CS-MNP nanocomposite are pure magnetite. Drug loading was estimated using ultraviolet-visible spectroscopy and showing a 12.9% in the designed nanocomposite. Magnetization curves demonstrated that the synthesized MNPs and nanocomposite were superparamagnetic with saturation magnetizations of 53.25 emu/g and 42.15 emu/g, respectively. The release study showed that around 86% and 93% of PTA from PTA-CS-MNP nanocomposite could be released within 127 and 56 hours by a phosphate buffer solution at pH 7.4 and 4.8, respectively, in a sustained manner and governed by pseudo-second order kinetic model. The cytotoxicity of the compounds on HT-29 colon cancer cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The HT-29 cell line was more sensitive against PTA-CS-MNP nanocomposite than PTA alone. No cytotoxic effect was observed on normal cells (3T3 fibroblast cells). This result indicates that PTA-CS-MNP nanocomposite can inhibit the proliferation of colon cancer cells without causing any harm to normal cell.

  14. Angiogenic properties of sustained release platelet-rich plasma: characterization in-vitro and in the ischemic hind limb of the mouse.

    Science.gov (United States)

    Bir, Shyamal Chandra; Esaki, Jiro; Marui, Akira; Yamahara, Kenichi; Tsubota, Hideki; Ikeda, Tadashi; Sakata, Ryuzo

    2009-10-01

    While single growth factor has limitation to induce optimal neovascularization, platelet-rich plasma (PRP) is an autologous reserver of various growth factors. However, little is known about the mechanism of PRP-related neovascularization.The objective of this investigation was to characterize the angiogenic and growth factor content of PRP and to determine, in vitro, its effect on endothelial cell proliferation. Additionally, this experiment sought to determine the effectiveness of different compositions of PRP (solution versus sustained release) on perfusion and neovascularization in a murine model of hind limb ischemia. Different growth factors were measured by enzyme-linked immunosorbent assay (ELISA). In vivo study, we used gelatin hydrogel as a sustained release carrier for growth factors in PRP. We induced hind limb ischemia by excising right femoral artery in wild type C57BL6 mice. After surgery, mice were randomly assigned to four experimental groups; control (C), 100 muL of sustained release form of platelet-poor plasma (PPP), 100 muL of solution form of PRP (PRP-sol), 100 muL of sustained release form of PRP (PRP-sr); each formulation was administered via an intramuscular injection to the ischemic hind limb. Endpoint evaluations were blood perfusion by laser Doppler perfusion image, vascular density by anti Von Willebrand factor (vWF), and mature vessel density by anti smooth muscle actin (SMA) antibody. Green fluorescent protein (GFP+) transgenic mice were generated by transplantation of bone marrow derived mononuclear cells to wild type C57BL6 mice, and finally CD34+ cell in the ischemic site of transgenic mice was detected by staining with anti-CD34 antibody. In vitro study showed that PRP containing different growth factors induces endothelial cell proliferation and capillary tube formation. In vivo study demonstrated that sustained release of PRP increased perfusion of ischemic tissue as measured by laser Doppler perfusion imaging (LDPI) (57 +/- 12

  15. Sustained release of growth hormone and sodium nitrite from biomimetic collagen coating immobilized on silicone tubes improves endothelialization.

    Science.gov (United States)

    Salehi-Nik, Nasim; Malaie-Balasi, Zahra; Amoabediny, Ghassem; Banikarimi, Seyedeh Parnian; Zandieh-Doulabi, Behrouz; Klein-Nulend, Jenneke

    2017-08-01

    Biocompatibility of biomedical devices can be improved by endothelialization of blood-contacting parts mimicking the vascular endothelium's function. Improved endothelialization might be obtained by using biomimetic coatings that allow local sustained release of biologically active molecules, e.g. anti-thrombotic and growth-inducing agents, from nanoliposomes. We aimed to test whether incorporation of growth-inducing nanoliposomal growth hormone (nGH) and anti-thrombotic nanoliposomal sodium nitrite (nNitrite) into collagen coating of silicone tubes enhances endothelialization by stimulating endothelial cell proliferation and inhibiting platelet adhesion. Collagen coating stably immobilized on acrylic acid-grafted silicone tubes decreased the water contact angle from 102° to 56°. Incorporation of 50 or 500nmol/ml nNitrite and 100 or 1000ng/ml nGH into collagen coating decreased the water contact angle further to 48°. After 120h incubation, 58% nitrite and 22% GH of the initial amount of sodium nitrite and GH in nanoliposomes were gradually released from the nNitrite-nGH-collagen coating. Endothelial cell number was increased after surface coating of silicone tubes with collagen by 1.6-fold, and with nNitrite-nGH-collagen conjugate by 1.8-3.9-fold after 2days. After 6days, endothelial cell confluency in the absence of surface coating was 22%, with collagen coating 74%, and with nNitrite-nGH-collagen conjugate coating 83-119%. In the absence of endothelial cells, platelet adhesion was stimulated after collagen coating by 1.3-fold, but inhibited after nNitrite-nGH-collagen conjugate coating by 1.6-3.7-fold. The release of anti-thrombotic prostaglandin I 2 from endothelial cells was stimulated after nNitrite-nGH-collagen conjugate coating by 1.7-2.2-fold compared with collagen coating. Our data shows improved endothelialization and blood compatibility using nNitrite-nGH-collagen conjugate coating on silicone tubes suggesting that these coatings are highly suitable

  16. Single-Dose pharmacokinetics of sustained-release fampridine (Fampridine-SR) in healthy volunteers and adults with renal impairment.

    Science.gov (United States)

    Smith, William; Swan, Suzanne; Marbury, Thomas; Henney, Herbert

    2010-02-01

    Fampridine-SR is a sustained-release formulation of fampridine (4-aminopyridine), a potassium channel blocker demonstrated to improve walking ability in patients with multiple sclerosis. This study evaluated the pharmacokinetics of fampridine and its metabolites after administration of fampridine-SR 10 mg in healthy volunteers and in subjects with mild, moderate, or severe renal impairment (5 per group). Analysis of variance was used to calculate 90% confidence intervals (CIs) for the ratios (impaired/healthy) of least squares mean in maximum plasma concentration (C(max)) and area under the plasma concentration-time curve (AUC). Clearance was primarily through urinary excretion. In renally impaired subjects, fampridine plasma concentrations were consistently higher than in healthy individuals: ratios for C(max) ranged from 166.5% to 199.9% for mild and severe renal impairment, respectively. AUC(0-infinity) ratios ranged from 175.3% to 398.7%, respectively, for mild and severe renal impairment. Mean terminal disposition half-life was 6.4 hours in healthy individuals, compared with 7.4, 8.1, and 14.3 hours in patients with mild, moderate, and severe renal impairment, respectively. Regression analysis confirmed the significant relationship between creatinine clearance and extent of exposure as quantified by AUC for fampridine and its metabolites, suggesting cautious use in patients with mild renal impairment and avoidance in cases of moderate or severe renal impairment.

  17. Developments in human growth hormone preparations: sustained-release, prolonged half-life, novel injection devices, and alternative delivery routes

    Directory of Open Access Journals (Sweden)

    Cai Y

    2014-07-01

    Full Text Available Yunpeng Cai,1,2 Mingxin Xu,2 Minglu Yuan,2 Zhenguo Liu,1 Weien Yuan2 1Department of Neurology, Xinhua Hospital, School of Medicine, 2School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People’s Republic of China Abstract: Since the availability of recombinant human growth hormone (rhGH enabled the application of human growth hormone both in clinical and research use in the 1980s, millions of patients were prescribed a daily injection of rhGH, but noncompliance rates were high. To address the problem of noncompliance, numerous studies have been carried out, involving: sustained-release preparations, prolonged half-life derivatives, new injectors that cause less pain, and other noninvasive delivery methods such as intranasal, pulmonary and transdermal deliveries. Some accomplishments have been made and launched already, such as the Nutropin Depot® microsphere and injectors (Zomajet®, Serojet®, and NordiFlex®. Here, we provide a review of the different technologies and illustrate the key points of these studies to achieve an improved rhGH product. Keywords: intranasal, pulmonary, transdermal, microsphere, microneedle, hydrogel

  18. 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.

  19. 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

  20. Preparation and characterization of cross-linked excipient of coprocessed xanthan gum-acacia gum as matrix for sustained release tablets

    Science.gov (United States)

    Surini, Silvia; Wati, Dina Risma; Syahdi, Rezi Riadhi

    2018-02-01

    Sustained release tablet is solid dosage form which is designed to release drugs slowly in the body. This research was intended to prepare and characterize the cross-linked excipients of co-processed xanthan gum-acacia gum (CL-Co-XGGA) as matrices for sustained release tablets with gliclazide as a model drug. CL-Co-XGGA excipients were cross-linked materials of co-processed excipients of xanthan gum-acacia gum (Co-XGGA) using sodium trimetaphosphate. Co-processed excipients of xanthan gum-acacia gum were prepared in the ratio of each excipient 1:2, 1:1 and 2:1. Co-XGGA and CL-Co-XGGA excipients were characterized physically, chemically and functionally. Then, the sustained release (SR) tablets were formulated by wet granulation method using CL-Co-XGGA excipients as matrices. Also, the dissolution study of the gliclazide SR tablets was carried out in phosphate buffer medium pH 7,4 containing sodium lauryl sulphate 0.2% for 12 hours. The results showed that the degree of substitution (DS) of CL-Co-XGGA 1:2, 1:1, 2:1 excipients were respectively 0.067, 0.082 and 0.08. Besides that, the excipients gel strengths were 14.03, 17.27 and 20,70 gF, respectively. The cross-linked excipients had improved flow properties and swelling capability compared to the Co-XGGA excipients. The results of the gliclazide SR tablets evaluations showed that all tablets were passed all tablet requirements. Moreover, the gliclazide release from SR tablets F1 - F6 revealed the sustained release profile, which was following zero order kinetics (F1, F2, F3, F6) and Higuchi kinetics (F4 and F5). It could be concluded that the obtained CL-Co-XGGA excipients might be used as matrices for sustained release tablets and could retard drug release up to 8 until 32 hours.

  1. Improvement of survival in C6 rat glioma model by a sustained drug release from localized PLGA microspheres in a thermoreversible hydrogel.

    Science.gov (United States)

    Ozeki, Tetsuya; Kaneko, Daiki; Hashizawa, Kosuke; Imai, Yoshihiro; Tagami, Tatsuaki; Okada, Hiroaki

    2012-05-10

    A local drug delivery system based on sustained drug release is an attractive approach to treat brain tumors. We have developed a novel device using drug-incorporated poly(lactic-co-glycolic acid) (PLGA) microspheres embedded in thermoreversible gelation polymer (TGP) formulation (drug/PLGA/TGP formulation). TGP forms a gel at body temperature but sol at room temperature. Therefore, when this formulation is injected into the brain tumor, the PLGA microspheres in TGP gel are localized at the injection site and do not diffuse throughout the brain tissue; eventually, sustained drug release from PLGA microspheres is achieved at the target site. In this study, two chemotherapeutic drugs (camptothecin (CPT) or vincristine (VCR)) were incorporated into PLGA microspheres to prepare drug/PLGA/TGP formulations. VCR/PLGA microspheres exhibited the higher encapsulation efficiency than CPT/PLGA microspheres (70.1% versus 30.1%). In addition, VCR/PLGA microspheres showed a higher sustained release profile than CPT/PLGA microspheres (54.5% versus 72.5% release, at 28 days). Therapeutic effect (mean survival) was evaluated in the C6 rat glioma model (control group, 18 days; CPT/PLGA/TGP treatment group, 24 days; VCR/PLGA/TGP treatment group, 33 days). In particular, the VCR/PLGA/TGP formulation produced long-term survivors (>60 days). Therefore, this formulation can be therapeutically effective formulation for the glioma therapy. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. 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.

  3. Pharmacokinetics and Paw Withdrawal Pressure in Female Guinea Pigs (Cavia porcellus) Treated with Sustained-Release Buprenorphine and Buprenorphine Hydrochloride.

    Science.gov (United States)

    Smith, Brian J; Wegenast, Daniel J; Hansen, Ryan J; Hess, Ann M; Kendall, Lon V

    2016-11-01

    Providing appropriate analgesia is essential in minimizing pain and maintaining optimal animal care and welfare in laboratory animals. Guinea pigs are common animal models in biomedical research, often requiring analgesic support. Here we evaluated the pharmacokinetics and efficacy of a sustained-release formulation of buprenorphine (Bup-SR) in this species. Guinea pigs (n = 7 each group) received either Bup-HCl (0.05 mg/kg BID for 3 d) or Bup-SR (0.3 mg/kg once). Plasma collection and measurement of paw-withdrawal pressure (PWP) was conducted at 0, 1, 3, 6, 12, 26, 48, and 72 h after treatment. Plasma levels of Bup-HCl peaked at 2331 pg/mL at 1 h after administration and declined to 165 pg/mL by 12 h. Plasma concentrations of Bup-SR peaked at 1344 pg/mL at 26 h after administration and declined to 429 pg/mL by 48 h. The PWP of the Bup-HCltreated guinea pigs peaked at 674 g at 1 h and declined to 402 g at 6 h, whereas that of Bup-SRtreated guinea pigs at 1 h was 361 g, 555 g at 6 h (significantly higher than that after Bup-HCl), and peaked at 680 g at 12 h. The PWP of both treatments was similar from 24 to 72 h and ranged from 348 to 450 g. The plasma concentration and PWP showed good correlation. These results suggest that Bup-SR provides consistent analgesia equivalent to that of Bup-HCl for a prolonged period of time and that Bup-SR is an alternative method of analgesia in guinea pigs.

  4. Attitude and perception of patients and health care practitioners toward oral sustained release dosage forms in Palestine.

    Science.gov (United States)

    Zaid, Abdel Naser

    2010-10-01

    To evaluate the knowledge of health professionals in Palestine regarding the advantages of sustained release dosage forms (SRDFs) over conventional therapy. Data were gathered from a questionnaire that was handed out to community pharmacists, physicians and patients. Pharmaceutical industry decision makers were enrolled in this study. Data were analyzed using the SPSS. Pharmacists (92.9%) and 89.2% of physicians thought that SRDFs improve patient compliance. 81.5% of pharmacists and 77% of physicians were in agreement regarding the capacity of SRDFs to maintain therapeutic activity during night. In this study, 81.5% of pharmacists and 81% of physicians believed that SRDFs provide further advantage with psychiatric patients who forget to take their medications. Pharmacists (63.1%) and only 63.5% of physicians believed that SRDFs yield a time saving for nurses who use SRDFs in hospital. Only 45.3% of physicians and 43.4% of pharmacists thought that SRDFs result in cost saving due to better disease management. Pharmacists (95.2%) and 95.9% of physicians agreed that SRDFs could be the right choice for faith patient's who must take their medication during the month of Ramadan. Pharmacists (66.7%) and 50.7% of physicians recognize that SRDFs may be unsafe if they are improperly formulated. Bad swallowing was also recognized as inconveniences of SRDFs by 67.9% of pharmacists and 57.3% of physicians. Given the above advantages, 75% of patients showed economical problems regarding the cost of the single course therapy of SRDFs and 100% of interviewed patients were enthusiastic about the advantage of SRDFs during Ramadan. The advantages of SRDFs are not completely understood by Palestinian health professionals. Pharmaceutical industries should pay more attention to the development and advertising of SRDFs due to the valuable advantages of these dosage forms.

  5. Bypassing the EPR effect with a nanomedicine harboring a sustained-release function allows better tumor control.

    Science.gov (United States)

    Shen, Yao An; Shyu, Ing Luen; Lu, Maggie; He, Chun Lin; Hsu, Yen Mei; Liang, Hsiang Fa; Liu, Chih Peng; Liu, Ren Shyan; Shen, Biing Jiun; Wei, Yau Huei; Chuang, Chi Mu

    2015-01-01

    The current enhanced permeability and retention (EPR)-based approved nanomedicines have had little impact in terms of prolongation of overall survival in patients with cancer. For example, the two Phase III trials comparing Doxil(®), the first nanomedicine approved by the US Food and Drug Administration, with free doxorubicin did not find an actual translation of the EPR effect into a statistically significant increase in overall survival but did show less cardiotoxicity. In the current work, we used a two-factor factorial experimental design with intraperitoneal versus intravenous delivery and nanomedicine versus free drug as factors to test our hypothesis that regional (intraperitoneal) delivery of nanomedicine may better increase survival when compared with systemic delivery. In this study, we demonstrate that bypassing, rather than exploiting, the EPR effect via intraperitoneal delivery of nanomedicine harboring a sustained-release function demonstrates dual pharmacokinetic advantages, producing more efficient tumor control and suppressing the expression of stemness markers, epithelial-mesenchymal transition, angiogenesis signals, and multidrug resistance in the tumor microenvironment. Metastases to vital organs (eg, lung, liver, and lymphatic system) are also better controlled by intraperitoneal delivery of nanomedicine than by standard systemic delivery of the corresponding free drug. Moreover, the intraperitoneal delivery of nanomedicine has the potential to replace hyperthermic intraperitoneal chemotherapy because it shows equal efficacy and lower toxicity. In terms of efficacy, exploiting the EPR effect may not be the best approach for developing a nanomedicine. Because intraperitoneal chemotherapy is a type of regional chemotherapy, the pharmaceutical industry might consider the regional delivery of nanomedicine as a valid alternative pathway to develop their nanomedicine(s) with the goal of better tumor control in the future.

  6. Use of ibuprofen sustained release for treating osteoarthritic pain: findings from 15 general medical practices in Egypt

    Directory of Open Access Journals (Sweden)

    Khalifa N

    2014-05-01

    Full Text Available Nabil Khalifa,1 Timour El-Husseini,1 Ahmed Morrah,2 Elshenawy Mostafa,3 Hesham Hamoud41Department of Orthopedic Surgery, Ain Shams University, Cairo, Egypt; 2Department of Orthopedic Surgery, Cairo University, Cairo, Egypt; 3Department of Orthopedic Surgery, Mansoura University, Mansoura, Egypt; 4Department of Rheumatology, Azhar University, Cairo, EgyptPurpose: Ibuprofen sustained release (SR has been shown to provide effective symptomatic pain relief in chronic arthritic conditions such as osteoarthritis in European and US patient populations. Few studies have been conducted in other patient populations. A 4-week prospective multicenter open-label observational study was designed to explore and describe the combined effect of ibuprofen SR and standard medical care in patients suffering from osteoarthritis in 15 general medical practices in Egypt.Patients and methods: In total, 519 patients were prescribed ibuprofen SR 2 ×800 mg once daily for 4 weeks.Results: Ibuprofen SR combined with standard medical care significantly improved day and night pain, with 99.4% of the patients reporting improvement. The treatment reduced the symptom severity of joint tenderness/stiffness and the duration of morning stiffness, and allowed more patients to carry out normal activities. Overall compliance with the prescribed ibuprofen SR regimen was 98.6%. Ibuprofen SR was generally well tolerated with no serious adverse events reported during the study. There was no increase in blood pressure or heart rate.Conclusion: The combined treatment provided effective relief of pain in patients with osteoarthritis in a large real-life general medical practice setting in Egypt. Owing to its convenient once-daily dosing regimen, ibuprofen SR may enhance patient compliance.Keywords: chronic arthritis, compliance, pain score, real-life

  7. Extracellular Matrix (ECM) Multilayer Membrane as a Sustained Releasing Growth Factor Delivery System for rhTGF-β3 in Articular Cartilage Repair

    Science.gov (United States)

    Park, Sang-Hyug; Kim, Moon Suk; Kim, Young Jick; Choi, Byung Hyune; Lee, Chun Tek; Park, So Ra; Min, Byoung-Hyun

    2016-01-01

    Recombinant human transforming growth factor beta-3 (rhTGF-β3) is a key regulator of chondrogenesis in stem cells and cartilage formation. We have developed a novel drug delivery system that continuously releases rhTGF-β3 using a multilayered extracellular matrix (ECM) membrane. We hypothesize that the sustained release of rhTGF-β3 could activate stem cells and result in enhanced repair of cartilage defects. The properties and efficacy of the ECM multilayer-based delivery system (EMLDS) are investigated using rhTGF-β3 as a candidate drug. The bioactivity of the released rhTGF-ß3 was evaluated through chondrogenic differentiation of mesenchymal stem cells (MSCs) using western blot and circular dichroism (CD) analyses in vitro. The cartilage reparability was evaluated through implanting EMLDS with endogenous and exogenous MSC in both in vivo and ex vivo models, respectively. In the results, the sustained release of rhTGF-ß3 was clearly observed over a prolonged period of time in vitro and the released rhTGF-β3 maintained its structural stability and biological activity. Successful cartilage repair was also demonstrated when rabbit MSCs were treated with rhTGF-β3-loaded EMLDS ((+) rhTGF-β3 EMLDS) in an in vivo model and when rabbit chondrocytes and MSCs were treated in ex vivo models. Therefore, the multilayer ECM membrane could be a useful drug delivery system for cartilage repair. PMID:27258120

  8. Extracellular Matrix (ECM Multilayer Membrane as a Sustained Releasing Growth Factor Delivery System for rhTGF-β3 in Articular Cartilage Repair.

    Directory of Open Access Journals (Sweden)

    Soon Sim Yang

    Full Text Available Recombinant human transforming growth factor beta-3 (rhTGF-β3 is a key regulator of chondrogenesis in stem cells and cartilage formation. We have developed a novel drug delivery system that continuously releases rhTGF-β3 using a multilayered extracellular matrix (ECM membrane. We hypothesize that the sustained release of rhTGF-β3 could activate stem cells and result in enhanced repair of cartilage defects. The properties and efficacy of the ECM multilayer-based delivery system (EMLDS are investigated using rhTGF-β3 as a candidate drug. The bioactivity of the released rhTGF-ß3 was evaluated through chondrogenic differentiation of mesenchymal stem cells (MSCs using western blot and circular dichroism (CD analyses in vitro. The cartilage reparability was evaluated through implanting EMLDS with endogenous and exogenous MSC in both in vivo and ex vivo models, respectively. In the results, the sustained release of rhTGF-ß3 was clearly observed over a prolonged period of time in vitro and the released rhTGF-β3 maintained its structural stability and biological activity. Successful cartilage repair was also demonstrated when rabbit MSCs were treated with rhTGF-β3-loaded EMLDS ((+ rhTGF-β3 EMLDS in an in vivo model and when rabbit chondrocytes and MSCs were treated in ex vivo models. Therefore, the multilayer ECM membrane could be a useful drug delivery system for cartilage repair.

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

    Science.gov (United States)

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

    2015-04-01

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

  10. Novel Fabrication of Biodegradable Superabsorbent Microspheres with Diffusion Barrier through Thermo-Chemical Modification and Their Potential Agriculture Applications for Water Holding and Sustained Release of Fertilizer.

    Science.gov (United States)

    Feng, Diejing; Bai, Bo; Wang, Honglun; Suo, Yourui

    2017-07-26

    Synergistic utilization of water and fertilizer has vital contribution to the modern production of agriculture. This work reports on a simple and facile strategy to prepare biodegradable yeast/sodium alginate/poly(vinyl alcohol) superabsorbent microspheres with a diffusion barrier merit by thermo-chemical modification route. The integrated performances, including water absorbency, water retention, water evaporation ratio, leaching loss control, sustained-release behaviors, and degradation in soil, were systematically investigated. The results revealed that the modified microspheres were a triumphant water and fertilizer manager to effectively hold water and control the unexpected leakage of fertilizer for sustained release. Therefore, this work provides a promising approach to ameliorate the utilization efficiency of water and fertilizer in potential agriculture applications.

  11. In situ depot comprising phase-change materials that can sustainably release a gasotransmitter H2S to treat diabetic wounds.

    Science.gov (United States)

    Lin, Wei-Chih; Huang, Chieh-Cheng; Lin, Shu-Jyuan; Li, Meng-Ju; Chang, Yen; Lin, Yu-Jung; Wan, Wei-Lin; Shih, Po-Chien; Sung, Hsing-Wen

    2017-11-01

    Patients with diabetes mellitus are prone to develop refractory wounds. They exhibit reduced synthesis and levels of circulating hydrogen sulfide (H 2 S), which is an ephemeral gaseous molecule. Physiologically, H 2 S is an endogenous gasotransmitter with multiple biological functions. An emulsion method is utilized to prepare a microparticle system that comprises phase-change materials with a nearly constant temperature of phase transitions to encapsulate sodium hydrosulfide (NaHS), a highly water-labile H 2 S donor. An emulsion technique that can minimize the loss of water-labile active compounds during emulsification must be developed. The as-prepared microparticles (NaHS@MPs) provide an in situ depot for the sustained release of exogenous H 2 S under physiological conditions. The sustained release of H 2 S promotes several cell behaviors, including epidermal/endothelial cell proliferation and migration, as well as angiogenesis, by extending the activation of cellular ERK1/2 and p38, accelerating the healing of full-thickness wounds in diabetic mice. These experimental results reveal the strong potential of NaHS@MPs for the sustained release of H 2 S for the treatment of diabetic wounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Hydrophobic ion pairing of a minocycline/Ca(2+)/AOT complex for preparation of drug-loaded PLGA nanoparticles with improved sustained release.

    Science.gov (United States)

    Holmkvist, Alexander Dontsios; Friberg, Annika; Nilsson, Ulf J; Schouenborg, Jens

    2016-02-29

    Polymeric nanoparticles is an established and efficient means to achieve controlled release of drugs. Incorporation of minocycline, an antibiotic with anti-inflammatory and neuroprotective properties, into biodegradable nanoparticles may therefore provide an efficient means to combat foreign body reactions to implanted electrodes in the brain. However, minocycline is commonly associated with poor encapsulation efficiencies and/or fast release rates due to its high solubility in water. Moreover, minocycline is unstable under conditions of low and high pH, heat and exposure to light, which exacerbate the challenges of encapsulation. In this work drug loaded PLGA nanoparticles were prepared by a modified emulsification-solvent-diffusion technique and characterized for size, drug encapsulation and in vitro drug release. A novel hydrophobic ion pair complex of minocycline, Ca(2+) ions and the anionic surfactant AOT was developed to protect minocycline from degradation and prolong its release. The optimized formulation resulted in particle sizes around 220 nm with an entrapment efficiency of 43% and showed drug release over 30 days in artificial cerebrospinal fluid. The present results constitute a substantial increase in release time compared to what has hitherto been achieved for minocycline and indicate that such particles might provide useful for sustained drug delivery in the CNS. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Pharmacokinetics and Adverse Effects of 3 Sustained-release Buprenorphine Dosages in Healthy Guinea Pigs (Cavia porcellus).

    Science.gov (United States)

    Zanetti, Andrea S; Putta, Sumanth K; Casebolt, Donald B; Louie, Stan G

    2017-11-01

    In guinea pigs, studies addressing the efficacy, safety, and pharmacokinetic profiles of different sustained-release buprenorphine (SRB) formulations are still in their infancy. Here we assessed the pharmacokinetic profiles of 3 SRB dosages (SR-LAB, ZooPharm; SRBLow, 0.15 mg/kg; SRBMedium, 0.3 mg/kg; and SRBHigh, 0.6 mg/kg) for 72 h after a single subcutaneous administration to 8 (4 male and 4 female) healthy guinea pigs. Body weight, fecal output, and cortisol levels were also monitored and the results compared with those of the sham group. Within the first h after administration, the maximal plasma concentration (Cmax) of the drug was 64.3 ± 9.2 ng/mL (males) and 71.3 ± 3.7 ng/mL (females) in the SRBHigh group; 11.5 ± 3.2 ng/mL (males) and 6.9 ± 0.9 ng/mL (females) in the SRBMedium group; and 2.3 ± 0.8 ng/mL (males) and 2.0 ± 0.5 ng/mL (females) in the SRBLow group. After 72 h, therapeutic levels of the drug (>1 ng/mL) were observed only in guinea pigs treated with SRBHigh (both sexes) and males treated with SRBMediu cm. Fecal output (quantity and distribution) and body weight were significantly lower in the SRB groups as compared with the sham group, and with the SRBHigh group showing larger reductions. Baseline levels of serum cortisol in healthy females (1440 ± 106 ng/mL) were significantly greater than in males (550 ± 66 ng/mL). But, independent of the sex, SRB administration significantly reduced those levels. In conclusion, the data indicate that all 3 SRB dosages can be safely used in guinea pigs. However, therapeutic levels of the drug were observed for at least 48 h only guinea pigs treated with SRBHigh and SRBMedium. Further investigation is needed to determine if these dosages can alleviate pain in guinea pigs.

  14. Potential sustainable slow release fertilizers obtained by mechanochemical activation of layered double hydroxides and K{sub 2}HPO{sub 4}

    Energy Technology Data Exchange (ETDEWEB)

    Borges, Roger; Wypych, Fernando, E-mail: 1roger.borges@gmail.com [Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil); Prevot, Vanessa; Forano, Claude [Universite Blaise Pascal, Clermont-Ferrand (France)

    2016-07-01

    Full text: This study describes the preliminary results on the development of potential sustainable slow-release fertilizer (SSRF), obtained by mechanochemical activation of mixtures of calcined layered double hydroxides (LDH) Mg{sub 2}Al-CO{sub 3} and Mg{sub 2}Fe-CO{sub 3} and K{sub 2}HPO{sub 4}. The effect of LDH temperature of calcination, milling time (using a high-energy balls mill) and LDH:K{sub 2}HPO{sub 4} molar were investigated. The samples were characterized by XRD and FTIR. Phosphate release essays shown that its solubility is reduced, while the solubility of amorphous structures from LDH can be increased, which characterize the expected slow release behavior of a SSRF. (author)

  15. Preparation and in vitro-in vivo evaluation of none gastric resident dipyridamole (DIP) sustained-release pellets with enhanced bioavailability.

    Science.gov (United States)

    Xu, Lishuang; Luo, Yanfei; Feng, Jia; Xu, Ming; Tao, Xiaoguang; He, Haibing; Tang, Xing

    2012-01-17

    The objective of this study was to develop none gastric resident sustained-release pellets loaded with dipyridamole with a high bioavailability. Two different kinds of core pellets, one containing citric acid as a pH-modifier (CAP) and, the other without pH-modifier (NCAP) were prepared by extrusion-spheronization and then coated with mixtures of enteric soluble and insoluble polymers (referred to as CAP(1) and NCAP(1)) or insoluble polymer alone (referred to as CAP(2) and NCAP(2)). The relative bioavailability of the sustained-release pellets was studied in fasted beagle dogs after oral administration using a commercially available immediate release tablet (IRT) as a reference. The in vitro release, in vivo absorption and in vitro-in vivo correlation were also evaluated. Results revealed that the plasma drug concentrations after administration of CAP(2), NCAP(1) and NCAP(2) were undetectable, indicating that the drug release was almost zero from the preparations throughout the gastro-intestinal tract. The C(max), T(max) and AUC((0→24)) of CAP(1) were 0.78 ± 0.23 (μg/ml), 3.80 ± 0.30 (h), and 6.74 ± 0.47 (μg/mlh), respectively. While the corresponding values were 2.23 ± 0.32 (μg/ml), 3.00 ± 0.44 (h) and 9.42 ± 0.69 (μg/mlh) for IRT. The relative bioavailability of CAP(1) was 71.55% compared with IRT. By combined incorporation of a pH-modifier into the core of pellets to modify the inner micro-environment and employing mixtures of enteric soluble and insoluble polymers as a retarding layer, drugs with high solubility in stomach and limited solubility in small intestine, such as DIP, could be successfully formulated as sustained release preparations with no pH-dependence in drug release and enhanced bioavailability. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Engineered collagen hydrogels for the sustained release of biomolecules and imaging agents: promoting the growth of human gingival cells.

    Science.gov (United States)

    Choi, Jonghoon; Park, Hoyoung; Kim, Taeho; Jeong, Yoon; Oh, Myoung Hwan; Hyeon, Taeghwan; Gilad, Assaf A; Lee, Kwan Hyi

    2014-01-01

    We present here the in vitro release profiles of either fluorescently labeled biomolecules or computed tomography contrast nanoagents from engineered collagen hydrogels under physiological conditions. The collagen constructs were designed as potential biocompatible inserts into wounded human gingiva. The collagen hydrogels were fabricated under a variety of conditions in order to optimize the release profile of biomolecules and nanoparticles for the desired duration and amount. The collagen constructs containing biomolecules/nanoconstructs were incubated under physiological conditions (ie, 37°C and 5% CO2) for 24 hours, and the release profile was tuned from 20% to 70% of initially loaded materials by varying the gelation conditions of the collagen constructs. The amounts of released biomolecules and nanoparticles were quantified respectively by measuring the intensity of fluorescence and X-ray scattering. The collagen hydrogel we fabricated may serve as an efficient platform for the controlled release of biomolecules and imaging agents in human gingiva to facilitate the regeneration of oral tissues.

  17. In Vivo Imaging of the Stability and Sustained Cargo Release of an Injectable Amphipathic Peptide-Based Hydrogel.

    Science.gov (United States)

    Oyen, Edith; Martin, Charlotte; Caveliers, Vicky; Madder, Annemieke; Van Mele, Bruno; Hoogenboom, Richard; Hernot, Sophie; Ballet, Steven

    2017-03-13

    Hydrogels are promising materials for biomedical applications such as tissue engineering and controlled drug release. In the past two decades, the peptide hydrogel subclass has attracted an increasing level of interest from the scientific community because of its numerous advantages, such as biocompatibility, biodegradability, and, most importantly, injectability. Here, we report on a hydrogel consisting of the amphipathic hexapeptide H-FEFQFK-NH 2 , which has previously shown promising in vivo properties in terms of releasing morphine. In this study, the release of a small molecule, a peptide, and a protein cargo as representatives of the three major drug classes is directly visualized by in vivo fluorescence and nuclear imaging. In addition, the in vivo stability of the peptide hydrogel system is investigated through the use of a radiolabeled hydrogelator sequence. Although it is shown that the hydrogel remains present for several days, the largest decrease in volume takes place within the first 12 h of subcutaneous injection, which is also the time frame wherein the cargos are released. Compared to the situation in which the cargos are injected in solution, a prolonged release profile is observed up to 12 h, showing the potential of our hydrogel system as a scaffold for controlled drug delivery. Importantly, this study elucidates the release mechanism of the peptide hydrogel system that seems to be based on erosion of the hydrogel providing a generally applicable controlled release platform for small molecule, peptide, and protein drugs.

  18. 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.

  19. Design of sustained release fine particles using two-step mechanical powder processing: particle shape modification of drug crystals and dry particle coating with polymer nanoparticle agglomerate.

    Science.gov (United States)

    Kondo, Keita; Ito, Natsuki; Niwa, Toshiyuki; Danjo, Kazumi

    2013-09-10

    We attempted to prepare sustained release fine particles using a two-step mechanical powder processing method; particle-shape modification and dry particle coating. First, particle shape of bulk drug was modified by mechanical treatment to yield drug crystals suitable for the coating process. Drug crystals became more rounded with increasing rotation speed, which demonstrates that powerful mechanical stress yields spherical drug crystals with narrow size distribution. This process is the result of destruction, granulation and refinement of drug crystals. Second, the modified drug particles and polymer coating powder were mechanically treated to prepare composite particles. Polymer nanoparticle agglomerate obtained by drying poly(meth)acrylate aqueous dispersion was used as a coating powder. The porous nanoparticle agglomerate has superior coating performance, because it is completely deagglomerated under mechanical stress to form fine fragments that act as guest particles. As a result, spherical drug crystals treated with porous agglomerate were effectively coated by poly(meth)acrylate powder, showing sustained release after curing. From these findings, particle-shape modification of drug crystals and dry particle coating with nanoparticle agglomerate using a mechanical powder processor is expected as an innovative technique for preparing controlled-release coated particles having high drug content and size smaller than 100 μm. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Preparation of a Sustained-Release Nebulized Aerosol of R-terbutaline Hydrochloride Liposome and Evaluation of Its Anti-asthmatic Effects via Pulmonary Delivery in Guinea Pigs.

    Science.gov (United States)

    Li, Qingrui; Zhan, Shuyao; Liu, Qing; Su, Hao; Dai, Xi; Wang, Hai; Beng, Huimin; Tan, Wen

    2018-01-01

    An aerosolized liposome formulation for the pulmonary delivery of an anti-asthmatic medication was developed. Asthma treatment usually requires frequent administration of medication for a sustained bronchodilator response. Liposomes are known for their sustained drug release capability and thus would be a suitable delivery system for prolonging the therapeutic effect of anti-asthmatic medication. Liposomes prepared by thin film hydration were loaded with a model drug, R-terbutaline hydrochloride(R-TBH), using an ammonium sulfate-induced transmembrane electrochemical gradient. This technique provided an encapsulation efficiency of up to 71.35% and yielded R-TBH liposomes with a particle size of approximately 145 ± 20 nm. According to stability studies, these R-TBH liposomes should be stored at 4°C before usage. Compared to R-TBH solution, which showed 90.84% release within 8 h, liposomal R-TBH had a cumulative release of 73.53% at 37°C over 192 h. A next generation impactor (NGI) was used to analyze the particle size distribution in the lungs of R-TBH liposome aerosol in vitro at 5°C. The therapeutic efficacy of the nebulized aerosol of the R-TBH liposomes was assessed via pulmonary delivery in guinea pigs. The results showed that, compared to the R-TBH solution group, the R-TBH liposome group had a prolonged anti-asthma effect.

  1. Self-assembled nanoparticles of modified-chitosan conjugates for the sustained release of dl-α-tocopherol

    DEFF Research Database (Denmark)

    Quinones, Javier Perez; Gothelf, Kurt Vesterager; Kjems, Jørgen

    2013-01-01

    Synthetic O6-succinylated chitosan and commercial glycol chitosan were covalently linked to dl-α-tocopheryl monoesters for controlled release of vitamin E. These conjugates formed self-assembled nanoparticles in aqueous solution with 254–496 nm mean diameters and dl-α-tocopherol contents between 27...... and 39% (w/w). The particles appeared as 40–75 nm almost spherical nanoparticles when studied by scanning and transmission electron microscopy upon drying. Drug linking to chitosan matrix was confirmed by FTIR spectroscopy and proton NMR. Conjugates were also characterized by differential scanning...... calorimetry and wide-angle X-ray diffraction. In vitro tocopherol release studies performed in water at acid pH indicated a drug release dependence on drug content, hydrated particle sizes and employed chitosan derivative. Almost constant release rates were observed the first 7 h. The obtained nanoparticles...

  2. 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.

  3. Depressive symptoms as a side effect of the sustained release form of methylphenidate in a 7-year-old boy with attention-deficit hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Lakić Aneta

    2012-01-01

    Full Text Available Introduction. Hyperkinetic disorder or attention-deficit hyperactivity disorder (ADHD is a clinical entity consisting of a cluster of symptoms including hyperactivity, attention disorder and impulse control disorder group. In the context of ADHD etiology we may say that genetic, clinical and imaging studies point out a disruption of the brain dopamine system, which is corroborated by the clinical effectiveness of stimulant drugs, which increase extracellular dopamine in the brain. Basically, it is a biological and not psychological disorder, which is important both for the comprehension and therapeutical approach to this problem. Today, the best recommended approach regarding children with ADHD is a combination of two therapeutic modalities: pharmacotherapy and behavioral treatment. The first-choice drugs for this disorder belong to the group of sympathomimetics - psychostimulants and atomoxetine (more recently. As the firstchoice therapy, methylphenydate in sustained release form has numerous advantages. Like all drugs, methylphenidate has its unwanted side effects. Most common are: loss of appetite, weight loss, sleeping disorders, irritability, headache. These side effects are well-known and documented in the literature. By analysing the available literature we have found cases of psychiatric side effects such as: psychosis, mania, visual hallucinations, agitation, suicidal ideas. We have not found examples of ADHD in children who use increased dosage of sustained release of methylphenidate leading to depressive symptomatology. On the other side, methylphenidate may be prescribed for off-label use in treatmentresistant cases of depression. Case report. The case of a 7- year-old boy diagnosed with ADHD was on a minimal dose of sustained release form of methylphenidate. After initial titration of the drug, i.e. after raising the dose to the next level the boy developed clinical signs of depression. The treatment was ceased and depressive

  4. Sustained-release diclofenac potassium-loaded solid lipid microparticle based on solidified reverse micellar solution: in vitro and in vivo evaluation.

    Science.gov (United States)

    Chime, Salome Amarachi; Attama, Anthony Amaechi; Builders, Philip F; Onunkwo, Godswill C

    2013-01-01

    To formulate sustained-release diclofenac potassium-loaded solid lipid microparticles (SLMs) based on solidified reverse micellar solution (SRMS) and to evaluate the in vitro and in vivo properties. SRMS consisting of mixtures of Phospholipon® 90H and Softisan® 154 were used to formulate diclofenac potassium-loaded SLMs. Characterization based on the particle size and morphology, stability and encapsulation efficiency (EE%) were carried out on the SLMs. In vitro release was carried out in simulated intestinal fluid (pH 7.5). Anti-inflammatory and ulcerogenic properties were studied using rats. Maximum EE% of 95%, 94% and 93% were obtained for SLMs formulated with SRMS 1:1, 2:1 and 1:2, respectively. In vitro release showed about 85-90% drug release at 13 h. Diclofenac potassium-loaded SLMs showed good anti-inflammatory and gastro-protective properties. Diclofenac potassium-loaded SLMs based on SRMS could be used orally or parenterally under controlled conditions, for once daily administration.

  5. A biodegradable, sustained-released, prednisolone acetate microfilm drug delivery system effectively prolongs corneal allograft survival in the rat keratoplasty model.

    Directory of Open Access Journals (Sweden)

    Yu-Chi Liu

    Full Text Available Frequent and long-term use of topical corticosteroids after corneal transplantation is necessary to prevent graft rejection. However, it relies heavily on patient compliance, and sustained therapeutic drug levels are often not achieved with administration of topical eye drops. A biodegradable drug delivery system with a controlled and sustained drug release may circumvent these limitations. In this study, we investigated the efficacy of a prednisolone acetate (PA-loaded poly (d,l-lactide-co-ε-caprolactone (PLC microfilm drug delivery system on promoting the survival of allogeneic grafts after penetrating keratoplasty (PK using a rat model. The drug release profiles of the microfilms were characterized (group 1. Subsequently, forty-eight PK were performed in four experimental groups: syngeneic control grafts (group 2, allogeneic control grafts (group 3, allogeneic grafts with subconjunctivally-implanted PA microfilm (group 4, and allogeneic grafts with PA eye drops (group 5; n = 12 in each. PA-loaded microfilm achieved a sustained and steady release at a rate of 0.006-0.009 mg/day, with a consistent aqueous drug concentration of 207-209 ng/ml. The mean survival days was >28 days in group 2, 9.9±0.8 days in group 3, 26.8±2.7 days in group 4, and 26.4±3.4 days in group 5 (P = 0.023 and P = 0.027 compared with group 3. Statistically significant decrease in CD4+, CD163+, CD 25+, and CD54+ cell infiltration was observed in group 4 and group 5 compared with group 3 (P<0.001. There was no significant difference in the mean survival and immunohistochemical analysis between group 4 and group 5. These results showed that sustained PA-loaded microfilm effectively prolongs corneal allograft survival. It is as effective as conventional PA eye drops, providing a promising clinically applicable alternative for patients undergoing corneal transplantation.

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

    Directory of Open Access Journals (Sweden)

    Hsu YH

    2014-09-01

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

  7. Sustained release of vancomycin from novel biodegradable nanofiber-loaded vascular prosthetic grafts: in vitro and in vivo study

    OpenAIRE

    Liu, Kuo-Sheng; Lee, Cheng-Hung; Wang, Yi-Chuan; Liu, Shih-Jung

    2015-01-01

    Kuo-Sheng Liu,1 Cheng-Hung Lee,2 Yi-Chuan Wang,3 Shih-Jung Liu3 1Department of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan; 2Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan; 3Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan Abstract: This study describes novel biodegradable, drug-eluting nanofiber-loaded vascular prosthetic grafts that provide local and sustained...

  8. The sustained-release behavior and in vitro and in vivo transfection of pEGFP-loaded core-shell-structured chitosan-based composite particles

    Science.gov (United States)

    Wang, Yun; Lin, Fu-xing; Zhao, Yu; Wang, Mo-zhen; Ge, Xue-wu; Gong, Zheng-xing; Bao, Dan-dan; Gu, Yu-fang

    2014-01-01

    Novel submicron core-shell-structured chitosan-based composite particles encapsulated with enhanced green fluorescent protein plasmids (pEGFP) were prepared by complex coacervation method. The core was pEGFP-loaded thiolated N-alkylated chitosan (TACS) and the shell was pH- and temperature-responsive hydroxybutyl chitosan (HBC). pEGFP-loaded TACS-HBC composite particles were spherical, and had a mean diameter of approximately 120 nm, as measured by transmission electron microscopy and particle size analyzer. pEGFP showed sustained release in vitro for >15 days. Furthermore, in vitro transfection in human embryonic kidney 293T and human cervix epithelial cells, and in vivo transfection in mice skeletal muscle of loaded pEGFP, were investigated. Results showed that the expression of loaded pEGFP, both in vitro and in vivo, was slow but could be sustained over a long period. pEGFP expression in mice skeletal muscle was sustained for >60 days. This work indicates that these submicron core-shell-structured chitosan-based composite particles could potentially be used as a gene vector for in vivo controlled gene transfection. PMID:25364253

  9. 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.

  10. 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.

  11. Lipid-coated hollow mesoporous silica nanospheres for co-delivery of doxorubicin and paclitaxel: Preparation, sustained release, cellular uptake and pharmacokinetics

    International Nuclear Information System (INIS)

    Qiu, Yang; Wu, Chao; Jiang, Jie; Hao, Yanna; Zhao, Ying; Xu, Jie; Yu, Tong; Ji, Peng

    2017-01-01

    A carrier consisting of lipid-coated hollow mesoporous silica nanospheres (L-HMSN) was produced for the combination of the water-insoluble drug (paclitaxel, PTX) and the water-soluble drug (doxorubicin, DOX). DOX was adsorbed into the nanoscale hollow structure of the hollow mesoporous silica nanospheres (HMSN) by adsorption and PTX was wrapped in the phospholipid layer of the HMSN surface by lipid film hydration method. The characterization results showed that DOX and PTX were present in the nanopheres in an amorphous state. The loaded L-HMSN (DOX/PTX@L-HMSN) in vitro drug release showed a sustained release in phosphate buffered solution (PBS) at pH 6.8 and 0.001%SDS. The cellular uptake experiment indicated that L-HMSN was successfully taken up by A549 cells. In addition, the combination of DOX and PTX in L-HMSN exhibited a marked synergistic effect in inhibiting the proliferation of A549 cells. The pharmacokinetic study demonstrated that L-HMSN could significantly improve the relative bioavailability of DOX and PTX. These results confirm that L-HMSN is a promising carrier for successful drug combination. - Highlights: • L-HMSN as a platform is used for combination of DOX and PTX • The drug delivery system demonstrates synergy effect in inhibiting A549 cell proliferation • The drug delivery system slowly releases the drugs and improves drug absorption

  12. Lipid-coated hollow mesoporous silica nanospheres for co-delivery of doxorubicin and paclitaxel: Preparation, sustained release, cellular uptake and pharmacokinetics

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, Yang; Wu, Chao, E-mail: wuchao27@126.com; Jiang, Jie; Hao, Yanna; Zhao, Ying; Xu, Jie; Yu, Tong; Ji, Peng

    2017-02-01

    A carrier consisting of lipid-coated hollow mesoporous silica nanospheres (L-HMSN) was produced for the combination of the water-insoluble drug (paclitaxel, PTX) and the water-soluble drug (doxorubicin, DOX). DOX was adsorbed into the nanoscale hollow structure of the hollow mesoporous silica nanospheres (HMSN) by adsorption and PTX was wrapped in the phospholipid layer of the HMSN surface by lipid film hydration method. The characterization results showed that DOX and PTX were present in the nanopheres in an amorphous state. The loaded L-HMSN (DOX/PTX@L-HMSN) in vitro drug release showed a sustained release in phosphate buffered solution (PBS) at pH 6.8 and 0.001%SDS. The cellular uptake experiment indicated that L-HMSN was successfully taken up by A549 cells. In addition, the combination of DOX and PTX in L-HMSN exhibited a marked synergistic effect in inhibiting the proliferation of A549 cells. The pharmacokinetic study demonstrated that L-HMSN could significantly improve the relative bioavailability of DOX and PTX. These results confirm that L-HMSN is a promising carrier for successful drug combination. - Highlights: • L-HMSN as a platform is used for combination of DOX and PTX • The drug delivery system demonstrates synergy effect in inhibiting A549 cell proliferation • The drug delivery system slowly releases the drugs and improves drug absorption.

  13. 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.

  14. Sustained release of stem cell factor in a double network hydrogel for ex vivo culture of cord blood-derived CD34+ cells.

    Science.gov (United States)

    Zhang, Yuanhao; Pan, Xiuwei; Shi, Zhen; Cai, Haibo; Gao, Yun; Zhang, Weian

    2018-04-01

    Stem cell factor (SCF) is considered as a commonly indispensable cytokine for proliferation of haematopoietic stem cells (HSCs), which is used in large dosages during ex vivo culture. The work presented here aimed to reduce the consumption of SCF by sustained release but still support cells proliferation and maintain the multipotency of HSCs. Stem cell factor was physically encapsulated within a hyaluronic acid/gelatin double network (HGDN) hydrogel to achieve a slow release rate. CD34 + cells were cultured within the SCF-loaded HGDN hydrogel for 14 days. The cell number, phenotype and functional capacity were investigated after culture. The HGDN hydrogels had desirable properties and encapsulated SCF kept being released for more than 6 days. SCF remained the native bioactivity, and the proliferation of HSCs within the SCF-loaded HGDN hydrogel was not affected, although the consumption of SCF was only a quarter in comparison with the conventional culture. Moreover, CD34 + cells harvested from the SCF-loaded HGDN hydrogels generated more multipotent colony-forming units (CFU-GEMM). The data suggested that the SCF-loaded HGDN hydrogel could support ex vivo culture of HSCs, thus providing a cost-effective culture protocol for HSCs. © 2017 John Wiley & Sons Ltd.

  15. [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

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

    Directory of Open Access Journals (Sweden)

    Zheng-mou DONG

    2011-01-01

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

  17. Evaluating the patient experience after implantation of a 0.4 mg sustained release dexamethasone intracanalicular insert (DextenzaTM: results of a qualitative survey

    Directory of Open Access Journals (Sweden)

    Gira JP

    2017-03-01

    Full Text Available Joseph P Gira,1 Reginald Sampson,2 Steven M Silverstein,3 Thomas R Walters,4 Jamie Lynne Metzinger,5 Jonathan H Talamo5 1Ophthalmology Consultants, St Louis, MO, 2Montebello Medical Center, Inc., Montebello, CA, 3Silverstein Eye Centers, Kansas City, MO, 4Texan Eye, Austin, TX, 5Ocular Therapeutix, Inc., Bedford, MA, USA Purpose: The purpose of this study is to evaluate the patient experience of sustained release dexamethasone intracanalicular insert (Dextenza™ following cataract surgery as part of a Phase III clinical trial program. Methods: This cross-sectional, qualitative evaluation involved individual interviews lasting approximately 45 minutes. Patients from four US investigational study sites who had previously received an insert were enrolled. There were no predesignated end points; this was a qualitative survey seeking a deeper understanding of patient experience. Results: Twenty-five patients were interviewed. Most patients (92% reported the highest level of satisfaction grade with regard to overall product satisfaction. All patients described the insert as comfortable. Most patients (96% described their overall experience with the insert as very convenient or extremely convenient. Twenty-two of 23 (96% participants rated their experience with the insert as “very” or “extremely convenient”, compared to previous topical therapy, and 88% of patients stated that if they were to undergo cataract surgery again, they would request the insert. When asked if they would recommend the insert to family members or friends, 92% stated they would. The survey found that 84% of participants would be willing to pay more for the insert than for eye drop therapy. Conclusion: The dexamethasone insert was found by patients to be highly favorable with regard to overall satisfaction, convenience, and comfort. The insert was well received and largely preferred over topical therapy alternatives following surgery. More extensive evaluation of the

  18. Solvent-free biodegradable scleral plugs providing sustained release of vancomycin, amikacin, and dexamethasone--an in vivo study.

    Science.gov (United States)

    Peng, Yi-Jie; Kau, Yi-Chuan; Wen, Chin-Wei; Liu, Kuo-Sheng; Liu, Shih-Jung

    2010-08-01

    Delivering effective drugs at sufficiently high concentrations to the area of infection is a standard treatment for infectious disease, such as endophthalmitis. This is currently done by empirical trans pars plana intravitreal injection of both antibiotics directed against gram-positive and gram-negative microorganisms and steroids. However, injections by needles repeatedly may increase the risks of intraocular infection and hemorrhage, as well as retinal detachment. This article explores the alternative of using biodegradable polymers as scleral plugs for a long-term drug release in vivo. To manufacture plugs, poly(lactide-glycolide) copolymers were first mixed with vancomycin, amikacin, and dexamethasone. The mixture was compressed and sintered at 55 degrees C to form scleral plugs 1.4 mm in diameter. Biodegradable scleral plugs released high concentrations of antibiotics (well above the minimum inhibitory concentrations, MIC) and steroids in vivo for the period of time needed to treat intraocular infection. In addition, no major complications such as infectious or sterile endophthalmitis, retinal detachment, ocular phthisis, or uvea protrusion at sclerotomy site were observed throughout the experiment. The sclerotomy wound healed after total degradation of the scleral implants without leakage or local necrosis. Antibiotic/steroid-impregnated biodegradable scleral plugs may have a potential role in the treatment of various intraocular infections. (c) 2010 Wiley Periodicals, Inc.

  19. Electrospinning of calcium phosphate-poly(D,L-lactic acid nanofibers for sustained release of water-soluble drug and fast mineralization

    Directory of Open Access Journals (Sweden)

    Fu QW

    2016-10-01

    Full Text Available Qi-Wei Fu,1,* Yun-Peng Zi,1,* Wei Xu,1 Rong Zhou,1 Zhu-Yun Cai,1 Wei-Jie Zheng,1 Feng Chen,2 Qi-Rong Qian1 1Department of Orthopedics, Changzheng Hospital, Second Military Medical University, 2State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Calcium phosphate-based biomaterials have been well studied in biomedical fields due to their outstanding chemical and biological properties which are similar to the inorganic constituents in bone tissue. In this study, amorphous calcium phosphate (ACP nanoparticles were prepared by a precipitation method, and used for preparation of ACP-poly(D,L-lactic acid (ACP-PLA nanofibers and water-soluble drug-containing ACP-PLA nanofibers by electrospinning. Promoting the encapsulation efficiency of water-soluble drugs in electrospun hydrophobic polymer nanofibers is a common problem due to the incompatibility between the water-soluble drug molecules and hydrophobic polymers solution. Herein, we used a native biomolecule of lecithin as a biocompatible surfactant to overcome this problem, and successfully prepared water-soluble drug-containing ACP-PLA nanofibers. The lecithin and ACP nanoparticles played important roles in stabilizing water-soluble drug in the electrospinning composite solution. The electrospun drug-containing ACP-PLA nanofibers exhibited fast mineralization in simulated body fluid. The ACP nanoparticles played the key role of seeds in the process of mineralization. Furthermore, the drug-containing ACP-PLA nanofibers exhibited sustained drug release which simultaneously occurred with the in situ mineralization in simulated body fluid. The osteoblast-like (MG63 cells with spreading filopodia were well observed on the as-prepared nanofibrous mats after culturing for 24 hours, indicating a high cytocompatibility. Due

  20. Preparation and Sustained-Release Property of Triblock Copolymer/Calcium Phosphate Nanocomposite as Nanocarrier for Hydrophobic Drug

    Directory of Open Access Journals (Sweden)

    Cao Shao-Wen

    2010-01-01

    Full Text Available Abstract The P123/ACP nanocomposite with sizes less than 100 nm consisting of triblock copolymer P123 and amorphous calcium phosphate (ACP has been prepared by using an aqueous solution containing CaCl2, (NH43PO4, and P123 at room temperature. The P123/ACP nanocomposite is used as the nanocarrier for hydrophobic drug ibuprofen, based on the combined advantages of both amphiphilic block copolymer and calcium phosphate delivery system. The P123/ACP nanocomposite has a much higher ibuprofen loading capacity (148 mg/g than the single-phase calcium phosphate nanostructures. The drug release percentage of the P123/ACP nanocomposite in simulated body fluid reaches about 100% in a period of 156 h, which is much slower than that of single-phase calcium phosphate nanostructures. It is expected that the P123/ACP nanocomposite is promising for the application in the controlled delivery of hydrophobic drugs.

  1. Sustained, Controlled and Stimuli-Responsive Drug Release Systems Based on Nanoporous Anodic Alumina with Layer-by-Layer Polyelectrolyte

    Science.gov (United States)

    Porta-i-Batalla, Maria; Eckstein, Chris; Xifré-Pérez, Elisabet; Formentín, Pilar; Ferré-Borrull, J.; Marsal, Lluis F.

    2016-08-01

    Controlled drug delivery systems are an encouraging solution to some drug disadvantages such as reduced solubility, deprived biodistribution, tissue damage, fast breakdown of the drug, cytotoxicity, or side effects. Self-ordered nanoporous anodic alumina is an auspicious material for drug delivery due to its biocompatibility, stability, and controllable pore geometry. Its use in drug delivery applications has been explored in several fields, including therapeutic devices for bone and dental tissue engineering, coronary stent implants, and carriers for transplanted cells. In this work, we have created and analyzed a stimuli-responsive drug delivery system based on layer-by-layer pH-responsive polyelectrolyte and nanoporous anodic alumina. The results demonstrate that it is possible to control the drug release using a polyelectrolyte multilayer coating that will act as a gate.

  2. A multicenter, randomized, double-blind, placebo-controlled, 6-month trial of bupropion hydrochloride sustained-release tablets as an aid to smoking cessation in hospital employees

    DEFF Research Database (Denmark)

    Dalsgareth, O.J.; Gerner Hansen, Niels-Christian; Soes-Petersen, U.

    2004-01-01

    (Zyban) compared with placebo as an aid to smoking cessation in health care workers. A total of 336 hospital employees who smoked at least 10 cigarettes daily were randomized (2:1) to 7 weeks of treatment with bupropion (n=222) or placebo (n=114). All participants were motivated to quit smoking......Despite changes in smoking behavior, one-third of the Danish population continues to smoke. Many of these smokers are hospital employees. This 6-month, multicenter, parallel group, randomized, double-blind, placebo-controlled study evaluated treatment with bupropion hydrochloride sustained release...... more frequently in the bupropion group than in the placebo group. Bupropion was effective as an aid to smoking cessation in a broad group of hospital employees in Denmark....

  3. The antimicrobial efficacy of sustained release silver–carbene complex-loaded l-tyrosine polyphosphate nanoparticles: Characterization, in vitro and in vivo studies

    Science.gov (United States)

    Hindi, Khadijah M.; Ditto, Andrew J.; Panzner, Matthew J.; Medvetz, Douglas A.; Han, Daniel S.; Hovis, Christine E.; Hilliard, Julia K.; Taylor, Jane B.; Yun, Yang H.; Cannon, Carolyn L.; Youngs, Wiley J.

    2009-01-01

    The pressing need to treat multi-drug resistant bacteria in the chronically infected lungs of cystic fibrosis (CF) patients has given rise to novel nebulized antimicrobials. We have synthesized a silver–carbene complex (SCC10) active against a variety of bacterial strains associated with CF and chronic lung infections. Our studies have demonstrated that SCC10-loaded into l-tyrosine polyphosphate nanoparticles (LTP NPs) exhibits excellent antimicrobial activity in vitro and in vivo against the CF relevant bacteria Pseudomonas aeruginosa. Encapsulation of SCC10 in LTP NPs provides sustained release of the antimicrobial over the course of several days translating into efficacious results in vivo with only two administered doses over a 72 h period. PMID:19395021

  4. Evaluating the patient experience after implantation of a 0.4 mg sustained release dexamethasone intracanalicular insert (Dextenza™): results of a qualitative survey.

    Science.gov (United States)

    Gira, Joseph P; Sampson, Reginald; Silverstein, Steven M; Walters, Thomas R; Metzinger, Jamie Lynne; Talamo, Jonathan H

    2017-01-01

    The purpose of this study is to evaluate the patient experience of sustained release dexamethasone intracanalicular insert (Dextenza™) following cataract surgery as part of a Phase III clinical trial program. This cross-sectional, qualitative evaluation involved individual interviews lasting approximately 45 minutes. Patients from four US investigational study sites who had previously received an insert were enrolled. There were no predesignated end points; this was a qualitative survey seeking a deeper understanding of patient experience. Twenty-five patients were interviewed. Most patients (92%) reported the highest level of satisfaction grade with regard to overall product satisfaction. All patients described the insert as comfortable. Most patients (96%) described their overall experience with the insert as very convenient or extremely convenient. Twenty-two of 23 (96%) participants rated their experience with the insert as "very" or "extremely convenient", compared to previous topical therapy, and 88% of patients stated that if they were to undergo cataract surgery again, they would request the insert. When asked if they would recommend the insert to family members or friends, 92% stated they would. The survey found that 84% of participants would be willing to pay more for the insert than for eye drop therapy. The dexamethasone insert was found by patients to be highly favorable with regard to overall satisfaction, convenience, and comfort. The insert was well received and largely preferred over topical therapy alternatives following surgery. More extensive evaluation of the patient experience is warranted, and future studies should help inform design of the next generation of sustained release drug delivery systems.

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  6. Slow and sustained nitric oxide releasing compounds inhibit multipotent vascular stem cell proliferation and differentiation without causing cell death

    Energy Technology Data Exchange (ETDEWEB)

    Curtis, Brandon M.; Leix, Kyle Alexander [Department of Chemistry, Central Michigan University, Mount Pleasant, MI 48859 (United States); Ji, Yajing [Department of Biomedical Science and Medicine, Michigan State University, East Lansing, MI 48824 (United States); Glaves, Richard Samuel Elliot [Department of Biology, Central Michigan University, Mount Pleasant, MI 48859 (United States); Ash, David E. [Department of Chemistry, Central Michigan University, Mount Pleasant, MI 48859 (United States); Mohanty, Dillip K., E-mail: Mohan1dk@cmich.edu [Department of Chemistry, Central Michigan University, Mount Pleasant, MI 48859 (United States)

    2014-07-18

    Highlights: • Multipotent vascular stem cells (MVSCs) proliferate and differentiate. • Nitric oxide inhibits proliferation of MVSCs. • Nitric oxide inhibits MVSC differentiation to mesenchymal-like stem cells (MSCs). • Smooth muscle cells (SMCs) neither de-differentiate nor proliferate. - Abstract: Atherosclerosis is the leading cause of cerebral and myocardial infarction. It is believed that neointimal growth common in the later stages of atherosclerosis is a result of vascular smooth muscle cell (SMC) de-differentiation in response to endothelial injury. However, the claims of the SMC de-differentiation theory have not been substantiated by monitoring the fate of mature SMCs in response to such injuries. A recent study suggests that atherosclerosis is a consequence of multipotent vascular stem cell (MVSC) differentiation. Nitric oxide (NO) is a well-known mediator against atherosclerosis, in part because of its inhibitory effect on SMC proliferation. Using three different NO-donors, we have investigated the effects of NO on MVSC proliferation. Results indicate that NO inhibits MVSC proliferation in a concentration dependent manner. A slow and sustained delivery of NO proved to inhibit proliferation without causing cell death. On the other hand, larger, single-burst NO concentrations, inhibits proliferation, with concurrent significant cell death. Furthermore, our results indicate that endogenously produced NO inhibits MVSC differentiation to mesenchymal-like stem cells (MSCs) and subsequently to SMC as well.

  7. Slow and sustained nitric oxide releasing compounds inhibit multipotent vascular stem cell proliferation and differentiation without causing cell death

    International Nuclear Information System (INIS)

    Curtis, Brandon M.; Leix, Kyle Alexander; Ji, Yajing; Glaves, Richard Samuel Elliot; Ash, David E.; Mohanty, Dillip K.

    2014-01-01

    Highlights: • Multipotent vascular stem cells (MVSCs) proliferate and differentiate. • Nitric oxide inhibits proliferation of MVSCs. • Nitric oxide inhibits MVSC differentiation to mesenchymal-like stem cells (MSCs). • Smooth muscle cells (SMCs) neither de-differentiate nor proliferate. - Abstract: Atherosclerosis is the leading cause of cerebral and myocardial infarction. It is believed that neointimal growth common in the later stages of atherosclerosis is a result of vascular smooth muscle cell (SMC) de-differentiation in response to endothelial injury. However, the claims of the SMC de-differentiation theory have not been substantiated by monitoring the fate of mature SMCs in response to such injuries. A recent study suggests that atherosclerosis is a consequence of multipotent vascular stem cell (MVSC) differentiation. Nitric oxide (NO) is a well-known mediator against atherosclerosis, in part because of its inhibitory effect on SMC proliferation. Using three different NO-donors, we have investigated the effects of NO on MVSC proliferation. Results indicate that NO inhibits MVSC proliferation in a concentration dependent manner. A slow and sustained delivery of NO proved to inhibit proliferation without causing cell death. On the other hand, larger, single-burst NO concentrations, inhibits proliferation, with concurrent significant cell death. Furthermore, our results indicate that endogenously produced NO inhibits MVSC differentiation to mesenchymal-like stem cells (MSCs) and subsequently to SMC as well

  8. The sustained-release behavior and in vitro and in vivo transfection of pEGFP-loaded core-shell-structured chitosan-based composite particles

    Directory of Open Access Journals (Sweden)

    Wang Y

    2014-10-01

    Full Text Available Yun Wang,1 Fu-xing Lin,2 Yu Zhao,1 Mo-zhen Wang,2 Xue-wu Ge,2 Zheng-xing Gong,1 Dan-dan Bao,1 Yu-fang Gu1 1Department of Plastic Surgery, First Affiliated Hospital of Anhui Medical University, 2CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China Abstract: Novel submicron core-shell-structured chitosan-based composite particles ­encapsulated with enhanced green fluorescent protein plasmids (pEGFP were prepared by complex coacervation method. The core was pEGFP-loaded thiolated N-alkylated chitosan (TACS and the shell was pH- and temperature-responsive hydroxybutyl chitosan (HBC. pEGFP-loaded TACS-HBC composite particles were spherical, and had a mean diameter of approximately 120 nm, as measured by transmission electron microscopy and particle size analyzer. pEGFP showed sustained release in vitro for >15 days. Furthermore, in vitro transfection in human embryonic kidney 293T and human cervix epithelial cells, and in vivo transfection in mice skeletal muscle of loaded pEGFP, were investigated. Results showed that the expression of loaded pEGFP, both in vitro and in vivo, was slow but could be sustained over a long period. pEGFP expression in mice skeletal muscle was sustained for >60 days. This work indicates that these submicron core-shell-structured chitosan-based composite particles could potentially be used as a gene vector for in vivo controlled gene transfection. Keywords: gene therapy, gene transfection, hydroxybutyl chitosan, thiolated N-alkylated chitosan, pEGFP, complex coacervation

  9. Solventless dry powder coating for sustained drug release using mechanochemical treatment based on the tri-component system of acetaminophen, carnauba wax and glidant.

    Science.gov (United States)

    Hoashi, Yohei; Tozuka, Yuichi; Takeuchi, Hirofumi

    2013-02-01

    Solventless dry powder coating methods have many advantages compared to solvent-based methods: they are more economical, simpler, safer, more environmentally friendly and easier to scale up. The purpose of this study was to investigate a highly effective dry powder coating method using the mechanofusion system, a mechanochemical treatment equipped with high compressive and shearing force. Acetaminophen (AAP) and carnauba wax (CW) were selected as core particles of the model drug and coating material, respectively. Mixtures of AAP and CW with and without talc were processed using the mechanofusion system. Sustained AAP release was observed by selecting appropriate processing conditions for the rotation speed and the slit size. The dissolution rate of AAP processed with CW substantially decreased with an increase in talc content up to 40% of the amount of CW loaded. Increasing the coating amount by two-step addition of CW led to more effective coating and extended drug release. Scanning electron micrographs indicated that CW adhered and showed satisfactory coverage of the surface of AAP particles. Effective CW coating onto the AAP surface was successfully achieved by strictly controlling the processing conditions and the composition of core particles, coating material and glidant. Our mechanochemical dry powder coating method using the mechanofusion system is a simple and promising means of solventless pharmaceutical coating.

  10. Coaxial Electrospinning with Mixed Solvents: From Flat to Round Eudragit L100 Nanofibers for Better Colon-Targeted Sustained Drug Release Profiles

    Directory of Open Access Journals (Sweden)

    Deng-Guang Yu

    2014-01-01

    Full Text Available A modified coaxial electrospinning process was developed for creating drug-loaded composite nanofibers. Using a mixed solvent of ethanol and N,N-dimethylacetamide as a sheath fluid, the electrospinning of a codissolving solution of diclofenac sodium (DS and Eudragit L100 (EL100 could run smoothly and continuously without any clogging. A series of analyses were undertaken to characterize the resultant nanofibers from both the modified coaxial process and a one-fluid electrospinning in terms of their morphology, physical form of the components, and their functional performance. Compared with those from the one-fluid electrospinning, the DS-loaded EL100 fibers from the modified coaxial process were rounder and smoother and possessed higher quality in terms of diameter and distribution with the DS existing in the EL100 matrix in an amorphous state; they also provided a better colon-targeted sustained drug release profile with a longer release time period. The modified coaxial process not only can smooth the electrospinning process to prevent clogging of spinneret, but also is a useful tool to tailor the shape of electrospun nanofibers and thus endow them improved functions.

  11. Nanocomposite hydrogels stabilized by self-assembled multivalent bisphosphonate-magnesium nanoparticles mediate sustained release of magnesium ion and promote in-situ bone regeneration.

    Science.gov (United States)

    Zhang, Kunyu; Lin, Sien; Feng, Qian; Dong, Chaoqun; Yang, Yanhua; Li, Gang; Bian, Liming

    2017-12-01

    Hydrogels are appealing biomaterials for applications in regenerative medicine due to their tunable physical and bioactive properties. Meanwhile, therapeutic metal ions, such as magnesium ion (Mg 2+ ), not only regulate the cellular behaviors but also stimulate local bone formation and healing. However, the effective delivery and tailored release of Mg 2+ remains a challenge, with few reports on hydrogels being used for Mg 2+ delivery. Bisphosphonate exhibits a variety of specific bioactivities and excellent binding affinity to multivalent cations such as Mg 2+ . Herein, we describe a nanocomposite hydrogel based on hyaluronic acid and self-assembled bisphosphonate-magnesium (BP-Mg) nanoparticles. These nanoparticles bearing acrylate groups on the surface not only function as effective multivalent crosslinkers to strengthen the hydrogel network structure, but also promote the mineralization of hydrogels and mediate sustained release of Mg 2+ . The released Mg 2+ ions facilitate stem cell adhesion and spreading on the hydrogel substrates in the absence of cell adhesion ligands, and promote osteogenesis of the seeded hMSCs in vitro. Furthermore, the acellular porous hydrogels alone can support in situ bone regeneration without using exogenous cells and inductive agents, thereby greatly simplifying the approaches of bone regeneration therapy. In this study, we developed a novel bioactive nanocomposite hydrogel based on hyaluronic acid and self-assembled bisphosphonate-magnesium (BP-Mg) nanoparticles. Such hydrogels are stabilized by the multivalent crosslinking domains formed by the aggregation of Ac-BP-Mg NPs, and therefore show enhanced mechanical properties, improved capacity for mineralization, and controlled release kinetics of Mg 2+ . Moreover, the released Mg 2+ can enhance cell adhesion and spreading, and further promote the osteogenic differentiation of hMSCs. Owing to these unique properties, these acellular hydrogels alone can well facilitate the in vivo

  12. Trehalose maintains bioactivity and promotes sustained release of BMP-2 from lyophilized CDHA scaffolds for enhanced osteogenesis in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Jun Zhao

    Full Text Available Calcium phosphate (Ca-P scaffolds have been widely employed as a supportive matrix and delivery system for bone tissue engineering. Previous studies using osteoinductive growth factors loaded Ca-P scaffolds via passive adsorption often experience issues associated with easy inactivation and uncontrolled release. In present study, a new delivery system was fabricated using bone morphogenetic protein-2 (BMP-2 loaded calcium-deficient hydroxyapatite (CDHA scaffold by lyophilization with addition of trehalose. The in vitro osteogenesis effects of this formulation were compared with lyophilized BMP-2/CDHA construct without trehalose and absorbed BMP-2/CDHA constructs with or without trehalose. The release characteristics and alkaline phosphatase (ALP activity analyses showed that addition of trehalose could sufficiently protect BMP-2 bioactivity during lyophilization and achieve sustained BMP-2 release from lyophilized CDHA construct in vitro and in vivo. However, absorbed BMP-2/CDHA constructs with or without trehalose showed similar BMP-2 bioactivity and presented a burst release. Quantitative real-time PCR (RT-qPCR and enzyme-linked immunosorbent assay (ELISA demonstrated that lyophilized BMP-2/CDHA construct with trehalose (lyo-tre-BMP-2 promoted osteogenic differentiation of bone marrow stromal cells (bMSCs significantly and this formulation could preserve over 70% protein bioactivity after 5 weeks storage at 25°C. Micro-computed tomography, histological and fluorescent labeling analyses further demonstrated that lyo-tre-BMP-2 formulation combined with bMSCs led to the most percentage of new bone volume (38.79% ± 5.32% and area (40.71% ± 7.14% as well as the most percentage of fluorochrome stained bone area (alizarin red S: 2.64% ± 0.44%, calcein: 6.08% ± 1.37% and mineral apposition rate (4.13 ± 0.62 µm/day in critical-sized rat cranial defects healing. Biomechanical tests also indicated the maximum stiffness (118.17 ± 15.02 Mpa and

  13. Low Molecular Weight Glucosamine/L-lactide Copolymers as Potential Carriers for the Development of a Sustained Rifampicin Release System: Mycobacterium Smegmatis as a Tuberculosis Model

    Science.gov (United States)

    Ragusa, Jorge Alejandro

    suggest that these drug carrier materials are potentially very attractive candidates for the development of high-payload, sustained-release antibiotic/resorbable polymer particle systems for treating bacterial lung infections.

  14. Mussel-inspired fabrication of konjac glucomannan/microcrystalline cellulose intelligent hydrogel with pH-responsive sustained release behavior.

    Science.gov (United States)

    Wang, Lin; Du, Yu; Yuan, Yi; Mu, Ruo-Jun; Gong, Jingni; Ni, Yongsheng; Pang, Jie; Wu, Chunhua

    2018-07-01

    Intelligent hydrogels are attractive biomaterials for various applications, however, fabricating a hydrogel with both adequate self-healing ability and mechanical properties remains a challenge. Herein, a series of novel intelligent konjac glucomannan (KGM)/microcrystalline cellulose (MCC) hydrogels were prepared vis the mussel-inspired chemistry. MCC was firstly functionalized by the oxidative polymerization of dopamine, and the intelligent hydrogels were obtained by mixing aqueous solutions of KGM and functionalized MCC (PDMCC). By introducing PDMCC, a more compact interconnected porous structure formed for the resulting hydrogels. The self-healing ability and mechanical properties of intelligent hydrogels were dependence on the PDMCC content. Compared with KGM hydrogels, KGM/PDMCC hydrogels exhibited a more distinct pH sensitivity and a lower initial burst release, which was attributed to the compact structure and strong intermolecular hydrogen bond interaction between PDMCC and KGM. These results suggest that the KGM/PDMCC intelligent hydrogels may be promising carriers for controlled drug delivery. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Octadecylamine-Mediated Versatile Coating of CoFe2O4 NPs for the Sustained Release of Anti-Inflammatory Drug Naproxen and in Vivo Target Selectivity.

    Science.gov (United States)

    Georgiadou, Violetta; Makris, George; Papagiannopoulou, Dionysia; Vourlias, Georgios; Dendrinou-Samara, Catherine

    2016-04-13

    Magnetic nanoparticles (MNPs) can play a distinct role in magnetic drug delivery via their distribution to the targeted area. The preparation of such MNPs is a challenging multiplex task that requires the optimization of size, magnetic, and surface properties for the achievement of desirable target selectivity, along with the sustained drug release as a prerequisite. In that context, CoFe2O4 MNPs with a small size of ∼7 nm and moderate saturation magnetization of ∼60 emu g(-1) were solvothermally synthesized in the presence of octadecylamine (ODA) with a view to investigate the functionalization route effect on the drug release. Synthetic regulations allowed us to prepare MNPs with aminated (AmMNPs) and amine-free (FAmMNPs) surface. The addition of the nonsteroidal anti-inflammatory drug with a carboxylate donor, Naproxen (NAP), was achieved by direct coupling with the NH2 groups, rendered by ODA, through the formation of an amide bond in the case of AmMNPs. In the case of FAmMNPs, indirect coupling of NAP was performed through an intermediate linker (polyethylenimine) and on PEG-ylated MNPs. FT-IR, (1)H NMR, (13)C NMR, and UV-vis data confirmed the addition of NAP, whereas diverse drug-release behavior was observed for the different functionalization approaches. The biological behavior of the MNPs@NAP was evaluated in vitro in rat serum and in vivo in mice, after radiolabeling with a γ-emitting radionuclide, (99m)Tc. The in vivo fate of MNPs@NAP carriers was in straightforward relation with the direct or indirect coupling of NAP. Furthermore, an inflammation was induced intramuscularly, where the directly coupled (99m)Tc-MNPs@NAP carriers showed increased accumulation at the inflammation site.

  16. Vincristine sulfate loaded dextran microspheres amalgamated with thermosensitive gel offered sustained release and enhanced cytotoxicity in THP-1, human leukemia cells: In vitro and in vivo study.

    Science.gov (United States)

    Thakur, Vivek; Kush, Preeti; Pandey, Ravi Shankar; Jain, Upendra Kumar; Chandra, Ramesh; Madan, Jitender

    2016-04-01

    Vincristine sulfate (VCS) is a drug of choice for the treatment of childhood and adult acute lymphocytic leukemia, Hodgkin's, non-Hodgkin's lymphoma as well as solid tumors including sarcomas. However, poor biopharmaceutical and pharmacokinetic traits of VCS like short serum half-life (12 min), high dosing frequency (1.4 mg/m(2) per week for 4 weeks) and extensive protein binding (75%) limit the clinical potential of VCS in cancer therapy. In present investigation, injectable vincristine sulfate loaded dextran microspheres (VCS-Dextran-MSs) were prepared and amalgamated with chitosan-β-glycerophosphate gel (VCS-Dextran-MSs-Gel) to surmount the biopharmaceutical and pharmacokinetic limitations of VCS that consequently induced synergistic sustained release pattern of the drug. Particle size and zeta-potential of VCS-Dextran-MSs were measured to be 6.8 ± 2.4 μm and -18.3 ± 0.11 mV along with the encapsulation efficiency of about 60.4 ± 4.5%. Furthermore, VCS-Dextran-MSs and VCS-Dextran-MSs-Gel exhibited slow release pattern and 94.7% and 95.8% of the drug was released in 72 h and 720 h, respectively. Results from cell viability assay and pharmacokinetic as well as histopathological analysis in mice indicated that VCS-Dextran-MSs-Gel offers superior therapeutic potential and higher AUClast than VCS-Dextran-MSs and drug solution. In conclusion, VCS-Dextran-MSs-Gel warrants further preclinical tumor growth study to scale up the technology. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Inhibition of growth of experimental prostate cancer with sustained delivery systems (microcapsules and microgranules) of the luteinizing hormone-releasing hormone antagonist SB-75.

    Science.gov (United States)

    Korkut, E; Bokser, L; Comaru-Schally, A M; Groot, K; Schally, A V

    1991-02-01

    Inhibitory effects of the sustained delivery systems (microcapsules and microgranules) of a potent antagonist of luteinizing hormone-releasing hormone N-Ac-[3-(2-naphthyl)-D-alanine1, 4-chloro-D-phenylalanine2, 3-(3-pyridyl)-D-alanine3, D-citrulline6, D-alanine10]LH-RH (SB-75) on the growth of experimental prostate cancers were investigated. In the first experiment, three doses of a microcapsule preparation releasing 23.8, 47.6, and 71.4 micrograms of antagonist SB-75 per day were compared with microcapsules of agonist [D-Trp6]LH-RH liberating 25 micrograms/day in rats bearing Dunning R3327H transplantable prostate carcinoma. During 8 weeks of treatment, tumor growth was decreased by [D-Trp6]LH-RH and all three doses of SB-75 as compared to untreated controls. The highest dose of SB-75 (71.4 micrograms/day) caused a greater inhibition of prostate cancer growth than [D-Trp6]LH-RH as based on measurement of tumor volume and percentage change in tumor volume. Doses of 23.8 and 47.6 micrograms of SB-75 per day induced a partial and submaximal decrease, respectively, in tumor weight and volume. Tumor doubling time was the longest (50 days) with the high dose of SB-75 vs. 15 days for controls. The body weights were unchanged. The weights of testes, seminal vesicles, and ventral prostate were greatly reduced in all three groups that received SB-75, and testosterone levels were decreased to nondetectable values in the case of the two higher doses of SB-75. LH levels were also diminished. Similar results were obtained in the second experiment, in which the animals were treated for a period of 8 weeks with microgranules of SB-75. Therapy with microgranules of SB-75 significantly decreased tumor growth as measured by the final tumor volume, the percentage change from the initial tumor volume, and the reduction in tumor weight. The results indicate that antagonist SB-75, released from sustained delivery systems, can produce a state of chemical castration and effectively

  18. Sustained-release liquisolid compact tablets containing artemether-lumefantrine as alternate-day regimen for malaria treatment to improve patient compliance

    Directory of Open Access Journals (Sweden)

    Nnamani PO

    2016-11-01

    yield and encapsulation efficiency were ~92% and 93% for Precirol® ATO 5/Transcutol® HP batch, then 81% and 95% for tallow fat/Transcutol® HP batch while LUM was amorphous in NLC matrix. In vitro AL release from liquisolid compacts revealed initial burst release and subsequent sustained release. Liquisolid tablet compacts formulated with Precirol® ATO 5/Transcutol® HP-AL4 achieved higher LUM release in simulated intestinal fluid (84.32% than tallow fat/Transcutol® HP-BL3 (77.9%. Non-Fickian (anomalous diffusion and super case II transport were the predominant mechanisms of drug release. Equal parasitemia reduction was observed for both batches of tablet compacts (~92%, superior to the reduction obtained with commercial antimalarial formulations: Coartem® tablets (86% and chloroquine phosphate tablets (66%. No significant difference (P<0.05 in parasite reduction between double (4/24 mg/kg and single (2/12 mg/kg strength doses of AL compacts was observed. Our result highlights that AL could be formulated in much lower doses (4/24 mg/kg, for once-in-two days oral administration to improve patient compliance, which is currently not obtainable with conventional AL dosage forms. Keywords: malaria, artemisinin-based combination therapy, antiplasmodial activity, liquisolid compacts, nanostructured lipid carriers

  19. Sustained-release of FGF-2 from a hybrid hydrogel of heparin-poloxamer and decellular matrix promotes the neuroprotective effects of proteins after spinal injury

    Directory of Open Access Journals (Sweden)

    Xu HL

    2018-02-01

    Full Text Available  He-Lin Xu,1,* Fu-Rong Tian,1,* Jian Xiao,1,* Pian-Pian Chen,1 Jie Xu,1 Zi-Liang Fan,1 Jing-Jing Yang,1 Cui-Tao Lu,1 Ying-Zheng Zhao1,2 1Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 2Hainan Medical College, Haikou, China *These authors contributed equally to this work Introduction: The short lifetime of protein-based therapies has largely limited their therapeutic efficacy in injured nervous post-spinal cord injury (post-SCI. Methods: In this study, an affinity-based hydrogel delivery system provided sustained-release of proteins, thereby extending the efficacy of such therapies. The affinity-based hydrogel was constructed using a novel polymer, heparin-poloxamer (HP, as a temperature-sensitive bulk matrix and decellular spinal cord extracellular matrix (dscECM as an affinity depot of drug. By tuning the concentration of HP in formulation, the cold ternary fibroblast growth factor-2 (FGF2-dscECM-HP solution could rapidly gelatinize into a hydrogel at body temperature. Due to the strong affinity for FGF2, hybrid FGF2-dscECM-HP hydrogel enabled sustained-release of encapsulated FGF2 over an extended period in vitro. Results: Compared to free FGF2, it was observed that both neuron functions and tissue morphology after SCI were clearly recovered in rats treated with FGF2-dscECM-HP hydrogel. Moreover, the expression of neurofilament protein and the density of axons were increased after treatment with hybrid FGF2-dscECM-HP. In addition, the neuroprotective effects of FGF2-dscECM-HP were related to inhibition of chronic endoplasmic reticulum stress-induced apoptosis.Conclusion: The results revealed that a hybrid hydrogel system may be a potential carrier to deliver macromolecular proteins to the injured site and enhance the therapeutic effects of proteins.Keywords: spinal cord injury, decellularized extracellular matrix, thermosensitive hydrogel, adsorption, basic fibroblast growth factor

  20. 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

  1. Sustained Local Release of Methylprednisolone From a Thiol-Acrylate Poly(Ethylene Glycol) Hydrogel for Treating Chronic Compressive Radicular Pain.

    Science.gov (United States)

    Slotkin, Jonathan R; Ness, Jennifer K; Snyder, Kristin M; Skiles, Amanda A; Woodard, Eric J; OʼShea, Timothy; Layer, Rick T; Aimetti, Alex A; Toms, Steven A; Langer, Robert; Tapinos, Nikos

    2016-04-01

    A preclinical animal model of chronic ligation of the sciatic nerve was used to compare the effectiveness of a slow-release hydrogel carrying methylprednisolone to methylprednisolone injection alone, which simulates the current standard of care for chronic compressive radiculopathy (CR). To extend the short-term benefits of steroid injections by using a nonswelling, biodegradable hydrogel as carrier to locally release methylprednisolone in a regulated and sustained way at the site of nerve compression. CR affects millions worldwide annually, and is a cause of costly disability with significant societal impact. Currently, a leading nonsurgical therapy involves epidural injection of steroids to temporarily alleviate the pain associated with CR. However, an effective way to extend the short-term effect of steroid treatment to address the chronic component of CR does not exist. We induced chronic compression injury of the sciatic nerves of rats by permanent ligation. Forty-eight hours later we injected our methylprednisolone infused hydrogel and assessed the effectiveness of our treatment for 4 weeks. We quantified mechanical hyperalgesia using a Dynamic Plantar Aesthesiometer (Ugo Basile, Stoelting Co., IL, USA), whereas gait analysis was conducted using the Catwalk automated gait analysis platform (Noldus, Leesburg, VA, USA). Macrophage staining was performed with immunohistochemistry and quantification of monocyte chemoattractant protein-1 in sciatic nerve lysates was performed with multiplex immunoassay using a SECTOR Imager 2400A (Meso Scale Discovery, Rockville, MA, USA). We demonstrate that using the hydrogel to deliver methylprednisolone results in significant (P pain in an animal model of chronic CR. Our steroid-infused hydrogel could be an effective extender of the short-term benefits of epidural steroid injections for patients with chronic compression-induced radicular pain. N/A.

  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. 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.

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

    Science.gov (United States)

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

    2014-01-01

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

  5. Recovery of oxidative stress-induced damage in Cisd2-deficient cardiomyocytes by sustained release of ferulic acid from injectable hydrogel.

    Science.gov (United States)

    Cheng, Yung-Hsin; Lin, Feng-Huei; Wang, Chien-Ying; Hsiao, Chen-Yuan; Chen, Hung-Ching; Kuo, Hsin-Yu; Tsai, Ting-Fen; Chiou, Shih-Hwa

    2016-10-01

    Aging-related oxidative stress is considered a major risk factor of cardiovascular diseases (CVD) and could be associated with mitochondrial dysfunction and reactive oxygen species (ROS) overproduction. Cisd2 is an outer mitochondrial membrane protein and plays an important role in controlling the lifespan of mammals. Ferulic acid (FA), a natural antioxidant, is able to improve cardiovascular functions and inhibit the pathogenetic CVD process. However, directly administering therapeutics with antioxidant molecules is challenging because of stability and bioavailability issues. In the present study, thermosensitive chitosan-gelatin-based hydrogel containing FA was used to treat Cisd2-deficient (Cisd2(-/-)) cardiomyocytes (CM) derived from induced pluripotent stem cells of Cisd2(-/-) murine under oxidative stress. The results revealed that the developed hydrogel could provide a sustained release of FA and increase the cell viability. Post-treatment of FA-loaded hydrogel effectively decreased the oxidative stress-induced damage in Cisd2(-/-) CM via increasing catalase activity and decreasing endogenous reactive oxygen species (ROS) production. The in vivo biocompatibility of FA-loaded hydrogel was confirmed in subcutaneously injected rabbits and intramyocardially injected Cisd2(-/-) mice. These results suggest that the thermosensitive FA-loaded hydrogel could rescue Cisd2(-/-) CM from oxidative stress-induced damage and may have potential applications in the future treatment of CVD. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Dena Dorniani

    2014-01-01

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

  7. Design and in vitro evaluation of self-assembled indometacin prodrug nanoparticles for sustained/controlled release and reduced normal cell toxicity

    Science.gov (United States)

    Lin, Jinyan; Pan, Zhou; Song, Liang; Zhang, Yanmei; Li, Yang; Hou, Zhenqing; Lin, Changjian

    2017-12-01

    Despite the great efficacy of indomethacin (IND) as an anti-inflammatory agent, its clinical translation has been obstructed by the water insolubility, severe side effects, and exceedingly low bioavailability. Indomethacin prodrug-based nanoparticles (NPs) combining the strengths of both nanotechnology and prodrugs that might overcome this crucial problem are presented. Here, using the carbodiimide-mediated couple reaction, IND was conjugated to clinically approved poly(ethylene glycol) (PEG) polymer via peptide linkage that was cleavaged in the presence of cathepsin B, which was significantly induced after inflammatory. The synthesized IND-PEG-IND conjugate was characterized by UV-vis, FTIR, 1H NMR, XRD, and MALDI-TOF-MS analyses. For its intrinsic amphiphilic property, the IND prodrug self-assembled into NPs in aqueous solution and served two roles-as an anti-inflammatory prodrug and a drug carrier. The constructed IND-PEG-IND NPs had naoscaled particle size of approximately 80 nm, negative surface, spherical shape, good water-dispersity, and high and fixed drug-loading content of 20.1 wt%. In addition, IND-PEG-IND NPs demonstrated sustained and cathepsin B-controlled drug release behavior. More importantly, IND-PEG-IND NPs significantly reduced the acute totoxicity agaist normal osteoblast cells and displayed the more potent anti-inflammatory effect against macrophage cells compared to the free IND. Taken together, the nanoprodrug might exhibit increased potency for nanomedicine-prospective therapeutic use in clinical treatement of implant inflammatory diseases.

  8. Bupropion sustained release treatment decreases craving for video games and cue-induced brain activity in patients with Internet video game addiction.

    Science.gov (United States)

    Han, Doug Hyun; Hwang, Jun Won; Renshaw, Perry F

    2010-08-01

    Bupropion has been used in the treatment of patients with substance dependence based on its weak inhibition of dopamine and norepinephrine reuptake. We hypothesized that 6 weeks of bupropion sustained release (SR) treatment would decrease craving for Internet game play as well as video game cue-induced brain activity in patients with Internet video game addiction (IAG). Eleven subjects who met criteria for IAG, playing StarCraft (>30 hr/week), and eight healthy comparison subjects (HC) who had experience playing StarCraft (game, and the severity of Internet addiction were evaluated by Beck Depression Inventory, self-report of craving on a 7-point visual analogue scale, and Young's Internet Addiction Scale, respectively. In response to game cues, IAG showed higher brain activation in left occipital lobe cuneus, left dorsolateral prefrontal cortex, and left parahippocampal gyrus than HC. After a 6 week period of bupropion SR, craving for Internet video game play, total game play time, and cue-induced brain activity in dorsolateral prefrontal cortex were decreased in the IAG. We suggest that bupropion SR may change craving and brain activity in ways that are similar to those observed in individuals with substance abuse or dependence. PsycINFO Database Record 2010 APA, all rights reserved.

  9. Diffusion profile of macromolecules within and between human skin layers for (trans)dermal drug delivery

    NARCIS (Netherlands)

    Römgens, A.M.; Bader, D.L.; Bouwstra, J.A.; Baaijens, F.P.T.; Oomens, C.W.J.

    2015-01-01

    Delivering a drug into and through the skin is of interest as the skin can act as an alternative drug administration route for oral delivery. The development of new delivery methods, such as microneedles, makes it possible to not only deliver small molecules into the skin, which are able to pass the

  10. A fixed-dose combination tablet of gemigliptin and metformin sustained release has comparable pharmacodynamic, pharmacokinetic, and tolerability profiles to separate tablets in healthy subjects.

    Science.gov (United States)

    Park, Sang-In; Lee, Howard; Oh, Jaeseong; Lim, Kyoung Soo; Jang, In-Jin; Kim, Jeong-Ae; Jung, Jong Hyuk; Yu, Kyung-Sang

    2015-01-01

    sustained release can be a convenient therapeutic option in patients with type 2 diabetes mellitus requiring a combination approach.

  11. Reduction of exit-site infections of tunnelled intravascular catheters among neutropenic patients by sustained-release chlorhexidine dressings: results from a prospective randomized controlled trial.

    Science.gov (United States)

    Chambers, S T; Sanders, J; Patton, W N; Ganly, P; Birch, M; Crump, J A; Spearing, R L

    2005-09-01

    Exit-site and tunnel infections of tunnelled central intravascular catheters are a frequent source of morbidity among neutropenic patients and may necessitate catheter removal. They require antimicrobial therapy that increases healthcare costs and is associated with adverse drug reactions. A prospective randomized clinical trial was conducted among adult patients undergoing chemotherapy in a haematology unit. Tunnelled intravascular catheters were randomized to receive the control of a standard dressing regimen as recommended by the British Committee for Standards in Haematology, or to receive the intervention of a sustained-release chlorhexidine dressing. Follow-up data were available in 112 of 114 tunnelled intravascular catheters which were randomized. Exit-site or combined exit-site/tunnel infections occurred in 23 (43%) of 54 catheters in the control group, and five (9%) of 58 catheters in the intervention group [odds ratio (OR) for intervention group compared with control group =0.13, 95% confidence intervals (CI) 0.04-0.37, P<0.001]. More tunnelled intravascular catheters were prematurely removed from the control group than the intervention group for documented infections [20/54 (37%) vs 6/58 (10%), OR=0.20, 95%CI 0.53-0.07]. However, there was no difference in the numbers of tunnelled intravascular catheters removed for all proven and suspected intravascular catheter-related infections [21/54 (39%) vs 19/58 (33%)], or in the time to removal of catheters for any reason other than death or end of treatment for underlying disease. Thus chlorhexidine dressings reduced the incidence of exit-site/tunnel infections of indwelling tunnelled intravascular catheters without prolonging catheter survival in neutropenic patients, and could be considered as part of the routine management of indwelling tunnelled intravascular catheters among neutropenic patients.

  12. Effect of Metformin-sustained Release Therapy on Low-density Lipoprotein Size and Adiponectin in the South Indian Women with Polycystic Ovary Syndrome.

    Science.gov (United States)

    Kumar, D Rama Nagendra; Seshadri, Krishna G; Pandurangi, Monna

    2017-01-01

    The aim of the study is to compare surrogate markers of cardiovascular disease (CVD) risk, such as adiponectin (APN) levels and low-density lipoprotein (LDL) size, before and after sustained release metformin (Met-SR) therapy in women with polycystic ovarian syndrome (PCOS). Sixty women with PCOS and sixty age-matched controls in the age group 18-45 years were recruited after obtaining informed consent. Women with PCOS were initiated on Met-SR 1 g orally, which was increased to 1.5 g after 2 weeks and continued up to 24 weeks. Demographic data along with family history of type 2 diabetes mellitus, PCOS, and CVD were collected. Lipid profile plasma APN levels and LDL size were measured before and after therapy in the PCOS group. Data analysis was performed using the GraphPad Prism-5 software. Women with PCOS had greater dyslipidemia, lower APN level and LDL size, and increased lipid accumulating product index as compared to controls. After 6 months of Met-SR therapy, women with PCOS demonstrated significant increase in plasma APN levels and LDL size and significant decrease in weight, waist-hip ratio (WHR), waist circumference (WC), and blood pressure (BP). A significant decrease was observed in body mass index (BMI) in the overweight and obese PCOS subgroups. Met-SR increases LDL size, APN concentration and decreases weight, WC, WHR, and BP in patients with PCOS. Met-SR may have salutary effects on LDL particle size through effects on APN levels in women with PCOS.

  13. A fixed-dose combination tablet of gemigliptin and metformin sustained release has comparable pharmacodynamic, pharmacokinetic, and tolerability profiles to separate tablets in healthy subjects

    Directory of Open Access Journals (Sweden)

    Park SI

    2015-02-01

    time curves of the FDC and the separate tablets almost overlapped, leading to a GMR (90% CI of the FDC to separate tablets for the plasma DPP-4 activity and its maximum inhibition of 1.00 (0.97–1.04 and 0.92 (0.82–1.05, respectively. Likewise, all of the GMRs (90% CIs of FDC to separate tablets for the area under the plasma concentration–time curve and maximum plasma concentration of gemigliptin and metformin fell entirely within the conventional bioequivalence range of 0.80–1.25. Both the FDC and separate tablets were well tolerated.Conclusion: The PD, PK, and tolerability profiles of gemigliptin and metformin XR in FDC and separate tablets were found to be comparable. The FDC tablet of gemigliptin and metformin sustained release can be a convenient therapeutic option in patients with type 2 diabetes mellitus requiring a combination approach. Keywords: dipeptidyl peptidase 4, DPP-4 inhibitor, type 2 diabetes mellitus, T2DM

  14. Preparation of sustained release matrix pellets by melt agglomeration in the fluidized bed: influence of formulation variables and modelling of agglomerate growth.

    Science.gov (United States)

    Pauli-Bruns, Anette; Knop, Klaus; Lippold, Bernhard C

    2010-03-01

    The one-step preparation of sustained release matrix pellets, using a melting procedure in a fluidized bed apparatus, was tested in a 2(3) full factorial design of experiments, using microcrystalline wax as lipophilic binder, theophylline as model drug and talc as additional matrix forming agent. The three influence parameters were (A) size of binder particles, (B) fraction of theophylline in solid particles and (C) fraction of microcrystalline wax in formulation. The response variables were agglomerate size and size distribution, dissolution time, agglomerate crush resistance, sphericity, yield and porosity. Nearly spherical pellets comprising a smooth, closed surface could be obtained with the used method, exhibiting the hollow core typical for the immersion and layering mechanism. The reproducibility was very good concerning all responses. The size of agglomerates is proportional to the size of the binder particles, which serve as cores for pellet formation in the molten state in the fluidized bed. Additionally, the agglomerate size is influenced by the volume of the solid particles in relation to the binder particles, with more solid particles leading to larger agglomerates and vice versa. Dissolution times vary in a very wide range, resulting from the interplay between amount of drug in relation to the meltable matrix substance microcrystalline wax and the non-meltable matrix substance talc. The change of binder particle size does not lead to a structural change of the matrix; both dissolution times and porosity are not significantly altered. Agglomerate crush resistance is low due to the hollow core of the pellets. However, it is significantly increased if the volume fraction of microcrystalline wax in the matrix is high, which means that the matrix is mechanically better stabilized. A theoretical model has been established to quantitatively explain agglomerate growth and very good accordance of the full particle size distributions between predicted and

  15. Compensation for nitrogen and phosphorous release from Baltic mariculture by Nodularia spumigena harvet during summer blooms - a possible path towards sustainable aquaculture

    DEFF Research Database (Denmark)

    Buchmann, Kurt

    2016-01-01

    An alternative technology for removal of nutrients released from mariculture ishere suggested. Harvest of cyanobacteria Nodularia spumigena during summerblooms may compensate for release of N and P from mariculture or other sources.Not only content of N in the cyanobacteria but also prevention of N...

  16. Sustainability Annual Report 2013

    OpenAIRE

    2013-01-01

    Every year, Virginia Tech releases a sustainability annual report to show the university’s progress in meeting the sustainability goals. The key sustainability metrics these reports cover include: greenhouse gas (GHG) emissions, energy use intensity, alternative transportation use, recycling, and water consumption.

  17. Sustainability Annual Report 2014

    OpenAIRE

    2014-01-01

    Every year, Virginia Tech releases a sustainability annual report to show the university’s progress in meeting the sustainability goals. The key sustainability metrics these reports cover include: greenhouse gas (GHG) emissions, energy use intensity, alternative transportation use, recycling, and water consumption.

  18. Sustainability Annual Report 2017

    OpenAIRE

    2017-01-01

    Every year, Virginia Tech releases a sustainability annual report to show the university’s progress in meeting the sustainability goals. The key sustainability metrics these reports cover include: greenhouse gas (GHG) emissions, energy use intensity, alternative transportation use, recycling, and water consumption.

  19. Sustainability Annual Report 2011

    OpenAIRE

    2011-01-01

    Every year, Virginia Tech releases a sustainability annual report to show the university’s progress in meeting the sustainability goals. The key sustainability metrics these reports cover include: greenhouse gas (GHG) emissions, energy use intensity, alternative transportation use, recycling, and water consumption.

  20. Sustainability Annual Report 2012

    OpenAIRE

    2012-01-01

    Every year, Virginia Tech releases a sustainability annual report to show the university’s progress in meeting the sustainability goals. The key sustainability metrics these reports cover include: greenhouse gas (GHG) emissions, energy use intensity, alternative transportation use, recycling, and water consumption.

  1. Sustainability Annual Report 2015

    OpenAIRE

    2015-01-01

    Every year, Virginia Tech releases a sustainability annual report to show the university’s progress in meeting the sustainability goals. The key sustainability metrics these reports cover include: greenhouse gas (GHG) emissions, energy use intensity, alternative transportation use, recycling, and water consumption.

  2. Sustainability Annual Report 2016

    OpenAIRE

    2016-01-01

    Every year, Virginia Tech releases a sustainability annual report to show the university’s progress in meeting the sustainability goals. The key sustainability metrics these reports cover include: greenhouse gas (GHG) emissions, energy use intensity, alternative transportation use, recycling, and water consumption.

  3. Efficacy and tolerability of bilateral sustained-release dexamethasone intravitreal implants for the treatment of noninfectious posterior uveitis and macular edema secondary to retinal vein occlusion

    Directory of Open Access Journals (Sweden)

    Ryder SJ

    2015-06-01

    Full Text Available Steven J Ryder,1 Danilo Iannetta,1 Swetangi D Bhaleeya,2 Szilárd Kiss1 1Department of Ophthalmology, Weill Cornell Medical College, New York, NY, USA; 2Department of Ophthalmology, University of South Florida, Tampa, FL, USA Purpose: To report our experience with bilateral placement of dexamethasone 0.7 mg (DEX sustained-release intravitreal implant in the management of noninfectious posterior uveitis or macular edema secondary to retinal vein occlusion.Methods: A retrospective chart review of patients with bilateral noninfectious posterior uveitis and macular edema secondary to retinal vein occlusion who were treated with DEX intravitreal implant was performed. Ocular side effects such as intraocular pressure (IOP, cataract, and tolerability of bilateral injections was reviewed.Results: Twenty-two eyes of eleven patients treated with a total of 32 DEX implants were included. Ten of eleven patients received bilateral implants due to active noninfectious uveitis while the other demonstrated macular edema in both eyes following separate central retinal vein occlusions. Among the patients with bilateral uveitis, the mean interval between DEX implant in the initial eye and the subsequent DEX in the fellow eye was 15.6 days (range 2–71 days. Seven of the ten patients received the second implant in the fellow eye within 8 days of the initial implantation. None of the patients had bilateral implantations on the same day. Seven eyes required reimplantation for recurrence of inflammation (mean interval between first and repeat implantation was 6.00±2.39 months. Following single or, in the case of the aforementioned seven eyes, repeat DEX implantation, all 20 uveitic eyes demonstrated clinical and/or angiographic evidence of decreased inflammation in the form of reduction in vitreous cells on slit lamp ophthalmoscopy, macular edema on ophthalmoscopy, or optical coherence tomography and/or disc and vascular leakage on fluorescein angiography. The mean

  4. Kinetic and theoretical studies of novel biodegradable thermo-sensitive xerogels based on PEG/PVP/silica for sustained release of enrofloxacin

    Science.gov (United States)

    Ebadi, Azra; Rafati, Amir Abbas; Bavafa, Sadeghali; Mohammadi, Masoumah

    2017-12-01

    This study involves the synthesis of a new silica-based colloidal hybrid system. In this new hybrid system, poly (ethylene glycol) (PEG) and thermo-sensitive amphiphilic biocompatible poly (vinyl pyrrolidone) (PVP) were used to create suitable storage for hydrophobic drugs. The possibility of using variable PVP/PEG molar ratios to modulate drug release rate from silica nanoparticles was a primary goal of the current research. In addition, an investigation of the drug release kinetic was conducted. To achieve this, silica nanoparticles were synthesized in poly (ethylene glycol) (PEG) and poly (vinyl pyrrolidone) (PVP) solution incorporated with enrofloxacin (EFX) (as a model hydrophobic drug), using a simple synthetic strategy of hybrid materials which avoided waste and multi-step processes. The impacts of PVP/PEG molar ratios, temperature, and pH of the release medium on release kinetic were investigated. The physicochemical properties of the drug-loaded composites were studied by Fourier transform infrared (FT-IR) spectra, scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). In vitro drug release studies demonstrated that the drug release rate, which was evaluated by analyzing the experimental data with seven kinetic models in a primarily non-Fickian diffusion-controlled process, aligned well with both Ritger-Peppas and Sahlin-Peppas equations.

  5. Effectiveness and Safety of Transdermal Buprenorphine Versus Sustained-release Tramadol in Patients With Moderate to Severe Musculoskeletal Pain: An 8-Week, Randomized, Double-Blind, Double-Dummy, Multicenter, Active-controlled, Noninferiority Study.

    Science.gov (United States)

    Leng, Xiaomei; Li, Zhanguo; Lv, Houshan; Zheng, Yi; Liu, Yi; Dai, Kerong; Yao, Chen; Yan, Xiaoyan; Zeng, Xiaofeng

    2015-07-01

    The aim of this noninferiority study was to investigate clinical effectiveness and safety of buprenorphine transdermal system (BTDS) in patients with moderate to severe musculoskeletal pain inadequately controlled with nonsteroidal anti-inflammatory drugs, compared with sustained-release tramadol tablets. Eligible patients were randomized (1:1) to receive low-dose 7-day BTDS (5, 10, and 20 μg/h, maximum dosage of 20 μg/h) or sustained-release tramadol tablets (100 mg, maximum dosage of 400 mg/d) over an 8-week double-blind treatment period (3-week titration, 5-week maintenance). The primary endpoint was the difference in the visual analogue scale (VAS) pain scores from baseline to treatment completion. Noninferiority was assumed if the treatment difference on the VAS scale was within ±1.5 cm, this threshold indicating a clinically meaningful result. ClinicalTrials.gov identifier: NCT01476774. Two hundred eighty patients were randomized to BTDS (n=141) or to tramadol (n=139). Both treatments were associated with a significant reduction in pain by the end of the treatment. The least squares mean difference of the change from baseline in VAS scores between the BTDS and tramadol groups were 0.45 (95% confidence interval, -0.02 to 0.91), which was within the ±1.5 cm predefined threshold, indicating that the effectiveness of BTDS was not inferior to the effectiveness of sustained-release tramadol tablets. The incidence of adverse events was comparable between the 2 treatment groups. Our results suggest that BTDS is a good therapeutic option for patients experiencing chronic musculoskeletal pain of moderate to severe intensity that is insufficiently controlled by nonsteroidal anti-inflammatory drugs.

  6. Sustained Release of Lidocaine from Solvent-Free Biodegradable Poly[(d,l)-Lactide-co-Glycolide] (PLGA): In Vitro and In Vivo Study.

    Science.gov (United States)

    Kau, Yi-Chuan; Liao, Chia-Chih; Chen, Ying-Chi; Liu, Shih-Jung

    2014-09-16

    Local anesthetics are commonly used for pain relief by regional nerve blocking. In this study, we fabricated solvent-free biodegradable pellets to extend the duration of lidocaine release without any significant local or systemic toxicity levels. To manufacture the pellets, poly[(d,l)-lactide-co-glycolide] (PLGA) was first pre-mixed with lidocaine powder into different ratios. The powder mixture was then compressed with a mold (diameter of 1, 5, 8 or 10 mm) and sintered at 65 °C to form pellets. The in vitro release study showed that the lidocaine/PLGA pellets exhibited a tri-phase release behavior (a burst, a diffusion-controlled release and a degradation-dominated release) and reached completion around day 28. Scanning electron microscope (SEM) photos show that small channels could be found on the surfaces of the pellets on day 2. Furthermore, the polymer matrix swelled and fell apart on day 7, while the pellets became viscous after 10 days of in vitro elution. Perineural administration of the lidocaine/PLGA pellets produced anti-hypersensitivity effects lasting for at least 24 h in rats, significant when compared to the control group (a pure PLGA was pellet administered). In addition, no inflammation was detected within the nerve and in the neighboring muscle by histopathology.

  7. Sustained Release of Lidocaine from Solvent-Free Biodegradable Poly[(d,l-Lactide-co-Glycolide] (PLGA: In Vitro and In Vivo Study

    Directory of Open Access Journals (Sweden)

    Yi-Chuan Kau

    2014-09-01

    Full Text Available Local anesthetics are commonly used for pain relief by regional nerve blocking. In this study, we fabricated solvent-free biodegradable pellets to extend the duration of lidocaine release without any significant local or systemic toxicity levels. To manufacture the pellets, poly[(d,l-lactide-co-glycolide] (PLGA was first pre-mixed with lidocaine powder into different ratios. The powder mixture was then compressed with a mold (diameter of 1, 5, 8 or 10 mm and sintered at 65 °C to form pellets. The in vitro release study showed that the lidocaine/PLGA pellets exhibited a tri-phase release behavior (a burst, a diffusion-controlled release and a degradation-dominated release and reached completion around day 28. Scanning electron microscope (SEM photos show that small channels could be found on the surfaces of the pellets on day 2. Furthermore, the polymer matrix swelled and fell apart on day 7, while the pellets became viscous after 10 days of in vitro elution. Perineural administration of the lidocaine/PLGA pellets produced anti-hypersensitivity effects lasting for at least 24 h in rats, significant when compared to the control group (a pure PLGA was pellet administered. In addition, no inflammation was detected within the nerve and in the neighboring muscle by histopathology.

  8. Sustained release of bactericidal concentrations of penicillin in the pleural space via an antibiotic-eluting pigtail catheter coated with electrospun nanofibers: results from in vivo and in vitro studies.

    Science.gov (United States)

    Chao, Yin-Kai; Lee, Cheng-Hung; Liu, Kuo-Sheng; Wang, Yi-Chuan; Wang, Chih-Wei; Liu, Shih-Jung

    2015-01-01

    Inadequate intrapleural drug concentrations caused by poor penetration of systemic antibiotics into the pleural cavity is a major cause of treatment failure in empyema. Herein, we describe a novel antibiotic-eluting pigtail catheter coated with electrospun nanofibers used for the sustained release of bactericidal concentrations of penicillin in the pleural space. Electrospun nanofibers prepared using polylactide-polyglycolide copolymer and penicillin G sodium dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol were used to coat the surface of an Fr6 pigtail catheter. The in vitro patterns of drug release were tested by placing the catheter in phosphate-buffered saline. In vivo studies were performed using rabbits treated with penicillin either intrapleurally (Group 1, 20 mg delivered through the catheter) or systemically (Group 2, intramuscular injection, 10 mg/kg). Penicillin concentrations in the serum and pleural fluid were then measured and compared. In vitro studies revealed a burst release of penicillin (10% of the total dose) occurring in the first 24 hours, followed by a sustained release in the subsequent 30 days. Intrapleural drug levels were significantly higher in Group 1 than in Group 2 (Ppenicillin concentrations remained above the minimum inhibitory concentration breakpoint throughout the entire study period. In contrast, serum penicillin levels were significantly higher in Group 2 than in Group 1 (P<0.001). Notably, all Group 2 rabbits showed signs of systemic toxicity (paralytic ileus and weight loss). We conclude that our antibiotic-eluting catheter may serve as a novel therapeutic option to treat empyema.

  9. Temperature and magnetism bi-responsive molecularly imprinted polymers: Preparation, adsorption mechanism and properties as drug delivery system for sustained release of 5-fluorouracil.

    Science.gov (United States)

    Li, Longfei; Chen, Lin; Zhang, Huan; Yang, Yongzhen; Liu, Xuguang; Chen, Yongkang

    2016-04-01

    Temperature and magnetism bi-responsive molecularly imprinted polymers (TMMIPs) based on Fe3O4-encapsulating carbon nanospheres were prepared by free radical polymerization, and applied to selective adsorption and controlled release of 5-fluorouracil (5-FU) from an aqueous solution. Characterization results show that the as-synthesized TMMIPs have an average diameter of about 150 nm with a typical core-shell structure, and the thickness of the coating layer is approximately 50 nm. TMMIPs also displayed obvious magnetic properties and thermo-sensitivity. The adsorption results show that the prepared TMMIPs exhibit good adsorption capacity (up to 96.53 mg/g at 25 °C) and recognition towards 5-FU. The studies on 5-FU loading and release in vitro suggest that the release rate increases with increasing temperature. Meanwhile, adsorption mechanisms were explored by using a computational analysis to simulate the imprinted site towards 5-FU. The interaction energy between the imprinted site and 5-FU is -112.24 kJ/mol, originating from a hydrogen bond, Van der Waals forces and a hydrophobic interaction between functional groups located on 5-FU and a NIPAM monomer. The electrostatic potential charges and population analysis results suggest that the imprinted site of 5-FU can be introduced on the surface of TMMIPs, confirming their selective adsorption behavior for 5-FU. Copyright © 2015. Published by Elsevier B.V.

  10. Biodegradable chitosan and polylactic acid-based intraocular micro-implant for sustained release of methotrexate into vitreous: analysis of pharmacokinetics and toxicity in rabbit eyes.

    Science.gov (United States)

    Manna, Soumyarwit; Banerjee, Rupak K; Augsburger, James J; Al-Rjoub, Marwan F; Donnell, Anna; Correa, Zelia M

    2015-08-01

    The purpose of this study was to evaluate the pharmacokinetics and toxicity of a chitosan (CS) and polylactic acid (PLA) based methotrexate (MTX) intravitreal micro-implant in an animal model using rabbit eyes. CS- and PLA-based micro-implants containing 400 μg of MTX were fabricated using lyophilization and dip-coating techniques. The micro-implants were surgically implanted in the vitreous of eight New Zealand rabbits employing minimally invasive technique. The PLA-coated CS-MTX micro-implant was inserted in the right eye and the placebo micro-implant in the left eye of each rabbit. Two rabbits were euthanized at each pre-determined time point post-implantation (days 5, 12, 19, and 33) for pharmacokinetics and histopathology evaluation. A therapeutic concentration of MTX (0.1-1.0 μM) in the vitreous was detected in the rabbit eyes studied for 33 days. The MTX release from the coated micro-implants followed a first order kinetics (R (2) ~ 0.88), implying that MTX release depends on the concentration of MTX in the micro-implant. Histopathological analysis of the enucleated eyes failed to show any signs of infection or tissue toxicity in any of the specimens. The PLA-coated CS-MTX micro-implants were able to deliver therapeutic release of MTX for a period of more than 1 month without detectable toxicity in a rabbit model. The micro-implants can be further investigated as a prospective alternative to current treatment protocols of repeated intravitreal MTX injections in intraocular disorders such as primary intraocular lymphoma, and selected cases of non-microbial intraocular inflammation.

  11. Development of a novel resin-based dental material with dual biocidal modes and sustained release of Ag+ ions based on photocurable core-shell AgBr/cationic polymer nanocomposites.

    Science.gov (United States)

    Cao, Weiwei; Zhang, Yu; Wang, Xi; Chen, Yinyan; Li, Qiang; Xing, Xiaodong; Xiao, Yuhong; Peng, Xuefeng; Ye, Zhiwen

    2017-07-01

    Research on the incorporation of cutting-edge nano-antibacterial agent for designing dental materials with potent and long-lasting antibacterial property is demanding and provoking work. In this study, a novel resin-based dental material containing photocurable core-shell AgBr/cationic polymer nanocomposite (AgBr/BHPVP) was designed and developed. The shell of polymerizable cationic polymer not only provided non-releasing antibacterial capability for dental resins, but also had the potential to polymerize with other methacrylate monomers and prevented nanoparticles from aggregating in the resin matrix. As a result, incorporation of AgBr/BHPVP nanocomposites did not adversely affect the flexural strength and modulus but greatly increased the Vicker's hardness of resin disks. By continuing to release Ag + ions without the impact of anaerobic environment, resins containing AgBr/BHPVP nanoparticles are particularly suitable to combat anaerobic cariogenic bacteria. By reason of the combined bactericidal effect of the contact-killing cationic polymers and the releasing-killing Ag + ions, AgBr/BHPVP-containing resin disks had potent bactericidal activity against S. mutans. The long-lasting antibacterial activity was also achieved through the sustained release of Ag + ions due to the core-shell structure of the nanocomposites. The results of macrophage cytotoxicity showed that the cell viability of dental resins loading less than 1.0 wt% AgBr/BHPVP was close to that of neat resins. The AgBr/BHPVP-containing dental resin with dual bactericidal capability and long term antimicrobial effect is a promising material aimed at preventing second caries and prolonging the longevity of resin composite restorations.

  12. Synthesis, characterization of thiolated karaya gum and evaluation of effect of pH on its mucoadhesive and sustained release properties.

    Science.gov (United States)

    Bahulkar, Swati S; Munot, Neha M; Surwase, Sachin S

    2015-10-05

    Present study aims at synthesis and characterization of thiolated gum karaya by reacting karaya gum with 80% thioglycolic acid resulting in esterification and immobilization of thiol groups on polymeric backbone. Immobilized thiol groups were found to be 5.026 mM/g determined by Ellman's method. It was characterized by FTIR, DSC and XRD. Directly compressible tablets prepared using thiolated gum displayed more disintegration time, swelling and mucoadhesion with increase in pH of medium simulating gastric and intestinal environment than plain gum. Controlled drug release for more than 24h by Fickian diffusion following Korsemeyer-Peppas model was observed with Metoprolol Succinate as a model drug as compared to plain gum which released more than 90% of the drug within 2h. Synthesized thiomer showed no cytotoxicity determined using HepG2 cell line. According to these results, thiolated gum karaya seems to be promising excipient for the development of mucoadhesive drug delivery systems. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Tamoxifen-loaded nanoparticles based on a novel mixture of biodegradable polyesters: characterization and in vitro evaluation as sustained release systems.

    Science.gov (United States)

    Pérez, Elena; Benito, Marta; Teijón, César; Olmo, Rosa; Teijón, José M; Blanco, M Dolores

    2012-01-01

    Nanoparticles (NP) from mixtures of two poly(D,L-lactide-co-caprolactone) (PLC) copolymers, PLC 40/60 and PLC 86/14, with poly(D,L-lactide) (PDLLA) and PCL were prepared: PLC 40/60-PCL (25:75), PLC 86/14-PCL (75:25) and PLC 86/14-PLA (75:25). Tamoxifen was loaded with encapsulation efficiency between 65% and 75% (29.9-36.3 µg TMX/ mg NP). All selected systems showed spherical shape and nano-scale size. TMX-loaded NPs were in the range of 293-352 nm. TMX release from NP took place with different profiles depending on polymeric composition of the particles. After 60 days, 59.81% and 82.65% of the loaded drug was released. The cytotoxicity of unloaded NP in MCF7 and HeLa cells was very low. Cell uptake of NP took place in both cell types by unspecific internalization in a time dependent process. The administration of 6 and 10 µm TMX by TMX-loaded NP was effective on both cellular types, mainly in MCF7 cells.

  14. Implantable porous gelatin microspheres sustained release of bFGF and improved its neuroprotective effect on rats after spinal cord injury.

    Directory of Open Access Journals (Sweden)

    Li Lan

    Full Text Available In this study, porous gelatin microspheres (GMSs were constructed to improve the neuroprotective effect of basic fibroblast growth factor (bFGF on spinal cord injury. GMSs were prepared by a W/O emulsion template, followed by cross-linking, washing and drying. The particle sizes and surface porosity of the blank GMSs were carefully characterized by scan electronic microscopy. The blank GMSs have a mean particle size of 35μm and theirs surface was coarse and porous. bFGF was easily encapsulated inside the bulk GMSs through diffusion along the porous channel. 200μg of bFGF was completely encapsulated in 100mg of GMSs. The bFGF-loaded GMSs displayed a continuous drug release pattern without an obvious burst release over two weeks in vitro. Moreover, the therapeutic effects of bFGF-loaded GMSs were also evaluated in spinal cord injury rat model. After implantation of bFGF-loaded GMSs, the recovery of the motor function of SCI rats were evaluated by behavioral score and foot print experiment. The motor function of SCI rats treated with bFGF-loaded GMSs was more obvious than that treated with free bFGF solution (P<0.05. At the 28th days after treatment, rats were sacrificed and the injured spinal were removed for histopathological and apoptosis examination. Compared with treatment with free bFGF solution, treatment with bFGF-loaded GMSs resulted in a less necrosis, less infiltration of leukocytes, and a reduced the cavity ratio and less apoptotic cells in injured spinal(P<0.01, indicating its better therapeutic effect. Implantable porous GMSs may be a potential carrier to deliver bFGF for therapy of spinal cord injury.

  15. Rationale and Safety Assessment of a Novel Intravaginal Drug-Delivery System with Sustained DL-Lactic Acid Release, Intended for Long-Term Protection of the Vaginal Microbiome.

    Science.gov (United States)

    Verstraelen, Hans; Vervaet, Chris; Remon, Jean-Paul

    2016-01-01

    Bacterial vaginosis is a prevalent state of dysbiosis of the vaginal microbiota with wide-ranging impact on human reproductive health. Based on recent insights in community ecology of the vaginal microbiome, we hypothesize that sustained vaginal DL-lactic acid enrichment will enhance the recruitment of lactobacilli, while counteracting bacterial vaginosis-associated bacteria. We therefore aimed to develop an intravaginal device that would be easy to insert and remove, while providing sustained DL-lactic acid release into the vaginal lumen. The final prototype selected is a vaginal ring matrix system consisting of a mixture of ethylene vinyl acetate and methacrylic acid-methyl methacrylate copolymer loaded with 150 mg DL-lactic acid with an L/D-lactic acid ratio of 1:1. Preclinical safety assessment was performed by use of the Slug Mucosal Irritation test, a non-vertebrate assay to evaluate vaginal mucosal irritation, which revealed no irritation. Clinical safety was evaluated in a phase I trial with six healthy nulliparous premenopausal volunteering women, with the investigational drug left in place for 7 days. Colposcopic monitoring according to the WHO/CONRAD guidelines for the evaluation of vaginal products, revealed no visible cervicovaginal mucosal changes. No adverse events related to the investigational product occurred. Total release from the intravaginal ring over 7 days was estimated through high performance liquid chromatography at 37.1 (standard deviation 0.9) mg DL-lactic acid. Semisolid lactic acid formulations have been studied to a limited extent in the past and typically consist of a large volume of excipients and very high doses of lactic acid, which is of major concern to mucosal safety. We have documented the feasability of enriching the vaginal environment with pure DL-lactic acid with a prototype intravaginal ring. Though the efficacy of this platform remains to be established possibly requiring further development, this approach may offer a

  16. Effectiveness, pharmacokinetics, and safety of a new sustained-release leuprolide acetate 3.75-mg depot formulation for testosterone suppression in patients with prostate cancer: a Phase III, open-label, international multicenter study.

    Science.gov (United States)

    Marberger, Michael; Kaisary, Amir V; Shore, Neal D; Karlin, Gary S; Savulsky, Claudio; Mis, Ricard; Leuratti, Chiara; Germa, Josep R

    2010-04-01

    A microencapsulated, sustained-release formulation of leuprolide acetate 3.75 mg has been developed. This study investigated the effectiveness, pharmacokinetics, and safety profile of a 1-month leuprolide acetate 3.75-mg depot formulation for suppressing testosterone concentrations in patients with prostate cancer. This was a Phase III, open-label, international multicenter clinical trial. Patients with prostate cancer who, in the judgment of the investigators, could benefit from androgen deprivation therapy received 6 monthly intramuscular injections of leuprolide acetate 3.75-mg depot. Plasma testosterone concentrations were determined at specific times throughout the study. The primary end point was the proportion of successful patients over the total number of evaluable patients (ie, patients with evaluable testosterone concentrations at all monthly assessments and no missing values due to treatment-related adverse events). Treatment success was defined as testosterone suppression below the clinical castration level (ie, n = 12), showed sustained release of leuprolide from the formulation. Values for AUC(0-t) calculated from day 0 to day 28, days 28 to 56, and days 56 to 84 were 25,976.5 (7892.0), 30,685.5 (9348.4), and 31,030.9 (10,745.0) pg/mL per day, respectively. The most common treatment-related adverse event was hot flashes (45.0% [72/160]). Fatigue, hyperhidrosis, night sweats, and headache each occurred in

  17. Sustained Release of Prostaglandin E2 in Fibroblasts Expressing Ectopically Cyclooxygenase 2 Impairs P2Y-Dependent Ca2+-Mobilization

    Directory of Open Access Journals (Sweden)

    María Pimentel-Santillana

    2014-01-01

    Full Text Available The nucleotide uridine trisphosphate (UTP released to the extracellular milieu acts as a signaling molecule via activation of specific pyrimidine receptors (P2Y. P2Y receptors are G protein-coupled receptors expressed in many cell types. These receptors mediate several cell responses and they are involved in intracellular calcium mobilization. We investigated the role of the prostanoid PGE2 in P2Y signaling in mouse embryonic fibroblasts (MEFs, since these cells are involved in different ontogenic and physiopathological processes, among them is tissue repair following proinflammatory activation. Interestingly, Ca2+-mobilization induced by UTP-dependent P2Y activation was reduced by PGE2 when this prostanoid was produced by MEFs transfected with COX-2 or when PGE2 was added exogenously to the culture medium. This Ca2+-mobilization was important for the activation of different metabolic pathways in fibroblasts. Moreover, inhibition of COX-2 with selective coxibs prevented UTP-dependent P2Y activation in these cells. The inhibition of P2Y responses by PGE2 involves the activation of PKCs and PKD, a response that can be suppressed after pharmacological inhibition of these protein kinases. In addition to this, PGE2 reduces the fibroblast migration induced by P2Y-agonists such as UTP. Taken together, these data demonstrate that PGE2 is involved in the regulation of P2Y signaling in these cells.

  18. Increased Loading, Efficacy and Sustained Release of Silibinin, a Poorly Soluble Drug Using Hydrophobically-Modified Chitosan Nanoparticles for Enhanced Delivery of Anticancer Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Cha Yee Kuen

    2017-11-01

    Full Text Available Conventional delivery of anticancer drugs is less effective due to pharmacological drawbacks such as lack of aqueous solubility and poor cellular accumulation. This study reports the increased drug loading, therapeutic delivery, and cellular accumulation of silibinin (SLB, a poorly water-soluble phenolic compound using a hydrophobically-modified chitosan nanoparticle (pCNP system. In this study, chitosan nanoparticles were hydrophobically-modified to confer a palmitoyl group as confirmed by 2,4,6-Trinitrobenzenesulfonic acid (TNBS assay. Physicochemical features of the nanoparticles were studied using the TNBS assay, and Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR analyses. The FTIR profile and electron microscopy correlated the successful formation of pCNP and pCNP-SLB as nano-sized particles, while Dynamic Light Scattering (DLS and Field Emission-Scanning Electron Microscopy (FESEM results exhibited an expansion in size between pCNP and pCNP-SLB to accommodate the drug within its particle core. To evaluate the cytotoxicity of the nanoparticles, a Methylthiazolyldiphenyl-tetrazolium bromide (MTT cytotoxicity assay was subsequently performed using the A549 lung cancer cell line. Cytotoxicity assays exhibited an enhanced efficacy of SLB when delivered by CNP and pCNP. Interestingly, controlled release delivery of SLB was achieved using the pCNP-SLB system, conferring higher cytotoxic effects and lower IC50 values in 72-h treatments compared to CNP-SLB, which was attributed to the hydrophobic modification of the CNP system.

  19. Assay of 6-gingerol in CO2 supercritical fluid extracts of ginger and evaluation of its sustained release from a transdermal delivery system across rat skin.

    Science.gov (United States)

    Chen, Yan; Zhang, Cuiping; Zhang, Mei; Fu, Xiaobing

    2014-07-01

    Ginger has been widely used as healthy food condiment as well as traditional Chinese medicine since antiquity. Multiple potentials of ginger for treatment of various ailments have been revealed. However, the biological half-life of 6-gingerol (a principal pungent ingredient of ginger) is only 7.23 minutes while taken orally. Delivery of ginger compositions by routes other than oral have scarcely been reported. Therefore, we studied a noninvasive transdermal drug delivery system (TDDS) of ginger to bypass hepatic first pass metabolism, avoid gastrointestinal degradation and achieve long persistent release of effective compositions. After establishment of a HPLC analysis method of 6-gingerol, assays of 6-gingerol were performed to compare two kinds of ginger extracts. Then, the characteristics of transdermal delivery of 6-gingerol in TDDS were exhibited. The results showed that the contents of 6-gingerol in two kinds of ginger extracts were significantly different. The maximal delivery percentage of 6-gingerol across rat skin at 20 h was more than 40% in different TDDS formulations. TDDS may provide long-lasting delivery of ginger compounds.

  20. Bioequivalence and Safety of Twice-Daily Sustained-Release Paracetamol (Acetaminophen) Compared With 3- and 4-Times-Daily Paracetamol: A Repeat-Dose, Crossover Pharmacokinetic Study in Healthy Volunteers.

    Science.gov (United States)

    Liu, Dongzhou J; Collaku, Agron

    2018-01-01

    Twice-daily sustained-release (SR) paracetamol (acetaminophen) offers convenient administration to chronic users. This study investigated at steady state (during the last 24 hours of a 3-day dosing period) the pharmacokinetics, bioequivalence, and safety of twice-daily SR paracetamol compared with extended-release (ER) and immediate-release (IR) paracetamol. In this open-label, randomized, multidose, 3-way crossover study, 28 healthy subjects received paracetamol SR (2 × 1000 mg twice daily), ER (2 × 665 mg 3 times daily), and IR (2 × 500 mg 4 times daily). At steady state, twice-daily SR paracetamol was bioequivalent to ER and IR paracetamol. The 90% confidence intervals for the ratios of geometric means were within the acceptance interval for SR/ER paracetamol (AUC 0-t , 0.973-1.033; AUC 0-24 , 0.974-1.034; AUC 0-∞ , 0.948-1.011; C max , 1.082-1.212; C av , 1.011-1.106) and SR/IR paracetamol (AUC 0-t , 0.969-1.029; AUC 0-24 , 0.968-1.027; AUC 0-∞ , 0.963-1.026; C max , 0.902-1.010; C av , 1.004-1.098). Given twice daily, the SR formulation demonstrated SR properties as expected. Mean time at or above a 4 μg/mL plasma concentration of paracetamol from 2 daily doses of the SR formulation was significantly longer than that from 4 daily doses of IR paracetamol. SR formulation also had a greater T max , a longer half-life, and lower C min compared with ER and IR paracetamol. All formulations were well tolerated. © 2017, The American College of Clinical Pharmacology.

  1. A randomized, placebo controlled, trial of preoperative sustained release Betamethasone plus non-controlled intraoperative Ketorolac or Fentanyl on pain after diagnostic laparoscopy or laparoscopic tubal ligation [ISRCTN52633712

    Directory of Open Access Journals (Sweden)

    Piller Marsha D

    2003-08-01

    Full Text Available Abstract Background Gynecological laparoscopic surgery procedures are often complicated by postoperative pain resulting in an unpleasant experience for the patient, delayed discharge, and increased cost. Glucocorticosteroids have been suggested to reduce the severity and incidence of postoperative pain. Methods This study examines the efficacy of a sustained release betamethasone preparation to reduce postoperative pain and the requirement for pain relief drugs after either diagnostic laparoscopy or tubal ligation. Patients were recruited, as presenting, after obtaining informed consent. Prior to surgery, patients were randomly selected by a computer generated table to receive either pharmacy-coded betamethasone (12 mg IM Celestone™ or an optically identical placebo injection of Intralipid™ and isotonic saline mixture. The effect of non-controlled prophylactic intraoperative treatment with either fentanyl or ketorolac per surgeon's orders was also noted in this study. Blood samples taken at recovery and at discharge times were extracted and analyzed for circulating betamethasone. Visual analog scale data on pain was gathered at six post-recovery time points in a triple blind fashion and statistically compared. The postoperative requirement for pain relief drugs was also examined. Results Although the injection achieved a sustained therapeutic concentration, no beneficial effect of IM betamethasone on postoperative pain or reduction in pain relief drugs was observed during the postoperative period. Indeed, the mean combined pain scores during the 2 hour postoperative period, adjusted for postoperative opioids as the major confounding factor, were higher approaching statistical significance (P = 0.056 in the treatment group. Higher pain scores were also observed for the tubal ligation patients relative to diagnostic laparoscopy. Intraoperative fentanyl treatment did not significantly lower the average pain score during the 2 hour postoperative

  2. Orally Administered Bioadherent Sustained Release Microencapsulated Vaccines

    Science.gov (United States)

    1996-09-01

    microspheres consist of bovine serum albumin (BSA) and recombinant vitelline protein B (vpB) from the liver fluke Fasciola hepatica which is a known...from the liver fluke Fasciola hepatica." Biochemistry 26, 7819-7825. 10. Waite, J.H., Rice-Ficht, A.C. (1992) "Eggshell precursor proteins of Fasciola ...precursor proteins of Fasciola hepatica: I. Structure and expression of vitelline protein B." Mol. Bioch. Parasitol. 54, 127-143. 12. Yapel, A.F. (1985

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

    African Journals Online (AJOL)

    Various approaches have been used to retain ... with distilled water and dried. ... gold film (200 nm) under reduced pressure ... size and wall thickness of microballoons ... microscopy (SEM) revealed pores on the ... Table 1: Effect of various processing parameters on the particle size, drug loading, incorporation efficiency.

  4. Grassland Sustainability

    Science.gov (United States)

    Deborah U. Potter; Paulette L. Ford

    2004-01-01

    In this chapter we discuss grassland sustainability in the Southwest, grassland management for sustainability, national and local criteria and indicators of sustainable grassland ecosystems, and monitoring for sustainability at various scales. Ecological sustainability is defined as: [T]he maintenance or restoration of the composition, structure, and processes of...

  5. Effects of food on the pharmacokinetics of gemigliptin/metformin sustained-release 50/1,000 mg (25/500 mg x 2 tablets) fixeddose combination tablet in healthy male volunteers.

    Science.gov (United States)

    Choi, Hee Youn; Noh, Yook-Hwan; Kim, Yo Han; Kim, Mi Jo; Lee, Shi Hyang; Kim, Jeong-Ae; Kim, Bogyeong; Lim, Hyeong-Seok; Bae, Kyun-Seop

    2014-05-01

    For patient convenience, a gemigliptin/metformin sustainedrelease fixed-dose combination (FDC) tablet was developed. This study was conducted to investigate the effects of food on the pharmacokinetic (PK) profile of the FDC tablets. This was an open-label, randomized, single dose, 2-period, 2-sequence crossover study in 24 healthy male volunteers. The FDC tablets (25/500 mg × 2 tablets) were administered in high-fat fed and fasted states on separate occasions, and each subject was randomly allocated to each sequence with a 7-day washout period. PK blood samplings were conducted from predose to 48 hours after dosing. Tolerability assessments were performed throughout the study. Nine adverse events (AEs) of mild intensity were reported from 8 subjects after study drug administration, and the AE frequency was similar between treatments. No serious AEs were reported. The PK parameters of gemigliptin and metformin were compared between fasting and fed states. For gemigliptin, the geometric mean ratios (GMRs) (fed : fasted state) of the Cmax and AUClast were 0.886 (90% confidence interval (CI) 0.781 - 1.006) and 1.021 (90% CI 0.949 - 1.099), respectively. For metformin, the GMRs of the Cmax and AUClast were 0.811 (90% CI 0.712 - 0.923) and 1.144 (90% CI 1.013 - 1.291), respectively. A prolonged tmax for metformin was observed. These results are similar to the effects of food on each component. The FDC tablet may have a similar PK profile as that of individual drugs and is generally tolerable when administered with food. These results indicate that the FDC tablet can be administered in the same dosing regimen as each component, especially that of metformin sustained-release.

  6. Microbiological and clinical effects of enamel matrix derivative and sustained-release micro-spherical minocycline application as an adjunct to non-surgical therapy in peri-implant mucosal inflammation.

    Science.gov (United States)

    Faramarzi, Masumeh; Goharfar, Zahra; Pourabbas, Reza; Kashefimehr, Atabak; Shirmohmmadi, Adileh

    2015-08-01

    The purpose of this study was to compare the microbial and clinical effects of mechanical debridement (MD) alone or in combination with the application of enamel matrix derivative (EMD) and sustained-release micro-spherical minocycline (MSM) for treatment of peri-implant mucosal infl ammation (PIMI). Subjects with at least one implant with PIMI were included and divided into control and two different test groups. In all three groups, MD was performed. In the MSM group, following MD, MSM was placed subgingivally around the implants. In the EMD group, after MD, EMD was placed in the sulcus around the implants. Sampling of peri-implant crevicular fl uid for microbial analysis with real-time polymerase chain reaction and recording of probing depth (PD) and bleeding on probing (BOP) were performed prior to as well as two weeks and three months after treatment. Median values and interquartile range were estimated for each variable during the various assessment intervals of the study. In all groups, at two weeks and three months, the counts of Porphyromonas gingivalis decreased significantly compared to baseline. Levels of P. gingivalis were significantly reduced in MSM (P<0.001) and EMD (P=0.026) groups compared to the control group. Also, clinical parameters improved significantly at two weeks and three months. Reduction of PD was significant in MSM (P<0.001) and EMD (P<0.001) groups. The decrease in BOP in the MSM, EMD, and control groups was 60%, 50%, and 20%, respectively. The use of MSM and EMD can be an adjunctive treatment for management of PIMI and improves clinical parameters and reduces P. gingivalis burden three months after treatment.

  7. Sustainable Food & Sustainable Economics

    OpenAIRE

    Alvarez, Mavis Dora

    2012-01-01

    Cuba today is immersed in a very intense process of perfecting its agricultural production structures with the goal of making them more efficient and sustainable in their economic administration and in their social and environmental management. Agricultural cooperatives in Cuba have the responsibility of producing on 73% of the country's farmland. Their contributions are decisive to developing agricultural production and to ensuring more and better food for the population, in addition to redu...

  8. Receptors for luteinizing hormone-releasing hormone (LHRH) in Dunning R3327 prostate cancers and rat anterior pituitaries after treatment with a sustained delivery system of LHRH antagonist SB-75.

    Science.gov (United States)

    Srkalovic, G; Bokser, L; Radulovic, S; Korkut, E; Schally, A V

    1990-12-01

    Membrane receptors for LHRH were evaluated in Dunning R3327 prostate cancers and rat anterior pituitaries. The receptors were characterized both in untreated animals and after in vivo treatment with microcapsules of the agonist D-Trp6-LHRH and a sustained delivery system releasing different doses (23.8, 47.6, 71.4 micrograms/day) of LHRH antagonist [Ac-D-Nal(2)1-D-Phe(4Cl)2-D-Pal(3)3,D-Cit6, D-Ala10]-LHRH (SB-75). The therapy, which lasted 8 weeks, strongly inhibited tumor growth. A group of normal Sprague-Dawley male rats was also treated for 6 weeks with microcapsules of SB-75 releasing 25 micrograms/day. In the Dunning tumors from the control group, ligand [125I, D-Trp6]-LHRH was bound to two classes of binding sites [dissociation constant, class a (Kda) = 1.01 +/- 0.30 x 10(-9) M; Kdb = 1.71 +/- 0.41 x 10(-6) M; maximal binding capacity of receptors, class a (Bmaxa) = 48.66 +/- 22.13 fmol/mg of protein; Bmaxb = 92.10 +/- 29.40 pmol/mg of protein] in both kinetic and equilibrium studies. Treatment with D-Trp6-LHRH produced down-regulation of membrane receptors for LHRH in Dunning tumors. Microcapsules of SB-75 resulted in dose-dependent up-regulation of binding sites for LHRH in Dunning tumors. Analysis of the binding data showed that interaction of labeled D-Trp6-LHRH with binding sites in anterior pituitaries was consistent with the presence of a single class of noncooperative receptors (Kd = 43.75 x 10(-9) M; Bmax = 5.25 pmol/mg membrane proteins). Prolonged treatment with microcapsules of D-Trp6-LHRH reduced both Bmax and Kd. Lower doses of SB-75 (23.8 and 47.6 micrograms/day) produced up-regulation, whereas the highest dose (71.4 micrograms/day) resulted in down-regulation of binding sites for LHRH in rat pituitaries. In normal Sprague-Dawley rats, treatment with microcapsules of SB-75 (25 micrograms/day) for 6 weeks produced a slight increase in the number of available binding sites (Bmax = 2.35 +/- 0.82 pmol/mg membrane protein) and a moderate decrease in

  9. 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

  10. Two-step irradiance schedule versus single-dose tramadol sustained-release tablets for pain control during topical 5-aminolevulinic acid-photodynamic therapy of condyloma acuminatum in Chinese patients: a randomized comparative study.

    Science.gov (United States)

    Mchepange, Uwesu O; Huang, Chun-Yan; Sun, Yi; Tu, Ya-Ting; Tao, Juan

    2014-07-01

    Photodynamic therapy with 5-aminolevulinic acid (ALA-PDT) offers promising results for the treatment of condyloma acuminatum. However, patients have to dwell with pain to benefit from this otherwise effective and safe "off-label" treatment modality. Several techniques have been explored to control ALA-PDT-induced pain, but the desperate search for a universally accepted method is still ongoing. This study compares the two-step irradiance approach with single-dose administration of 100 mg tramadol sustained-release tablets for pain induced by ALA-PDT of condyloma acuminatum in Chinese patients. Adult Chinese patients with condyloma acuminatum were enrolled in a randomized comparative study. Pain levels were compared using the Numeric Rating Scale (NRS) at pre-defined assessment points during and after irradiation. The pain was dominated by characteristics such as burning and pricking and was almost always local and superficial. The median pain scores were lower in the two-step irradiance group at 1 minute (U = 621.5, P = 0.002) but higher at 20 minutes (U = 585.5, P = 0.002). The median pain scores between the two groups did not differ significantly at other assessment points. The pain was moderate in both groups and peaked earlier in the analgesics group (median: 5 minutes) but later in the two-step irradiance group (median: 15 minutes). The pain was generally mild. The median pain scores were equal at each assessment point, except at 3 hours where the median was lower in the analgesics group (1.0) as compared with the two-step irradiance group (2.0) (U = 725.0, P = 0.056). Pain in the two-step irradiance protocol is irradiance-dependent. The two-step irradiance approach produces significant benefits over analgesics during the initial stages of therapy but analgesics offer significant benefits thereafter. There are potential benefits of combining the two approaches in minimizing ALA-PDT-induced pain. © 2014 Wiley Periodicals

  11. 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,

  12. Sustainable Marketing

    NARCIS (Netherlands)

    Dam, van Y.K.

    2017-01-01

    In this article, three different conceptions of sustainable marketing are discussed and compared. These different conceptions are referred to as social, green, and critical sustainable marketing. Social sustainable marketing follows the logic of demand-driven marketing management and places the

  13. Biofuels and sustainability.

    Science.gov (United States)

    Solomon, Barry D

    2010-01-01

    Interest in liquid biofuels production and use has increased worldwide as part of government policies to address the growing scarcity and riskiness of petroleum use, and, at least in theory, to help mitigate adverse global climate change. The existing biofuels markets are dominated by U.S. ethanol production based on cornstarch, Brazilian ethanol production based on sugarcane, and European biodiesel production based on rapeseed oil. Other promising efforts have included programs to shift toward the production and use of biofuels based on residues and waste materials from the agricultural and forestry sectors, and perennial grasses, such as switchgrass and miscanthus--so-called cellulosic ethanol. This article reviews these efforts and the recent literature in the context of ecological economics and sustainability science. Several common dimensions for sustainable biofuels are discussed: scale (resource assessment, land availability, and land use practices); efficiency (economic and energy); equity (geographic distribution of resources and the "food versus fuel" debate); socio-economic issues; and environmental effects and emissions. Recent proposals have been made for the development of sustainable biofuels criteria, culminating in standards released in Sweden in 2008 and a draft report from the international Roundtable on Sustainable Biofuels. These criteria hold promise for accelerating a shift away from unsustainable biofuels based on grain, such as corn, and toward possible sustainable feedstock and production practices that may be able to meet a variety of social, economic, and environmental sustainability criteria.

  14. Sustainability at BPA 2013

    Energy Technology Data Exchange (ETDEWEB)

    None

    2013-12-01

    THIS IS THE THIRD YEAR BPA has reported on sustainability program accomplishments. The report provides an opportunity to review progress made on sustainability initiatives, evaluate how far we have come and how much we can improve. The program has demonstrated maturation as the concepts of sustainability and resource conservation are communicated and understood. The sustainability program started as an employee-driven “grass roots” effort in 2010. Sustainability is becoming a consideration in how work is performed. The establishment of several policies supporting sustainability efforts proves the positive progress being made. In 2009, BPA became a founder and member of The Climate Registry, a nonprofit collaboration that sets standards to calculate, verify and report greenhouse gas emissions. This year, BPA completed and published our Greenhouse Gas inventory for the years of 2009, 2010 and 2011. The 2012 inventory is currently in the process of third-party verification and scheduled for public release in January 2014. These inventories provide a concrete measure of the progress we are making.

  15. Methane release

    International Nuclear Information System (INIS)

    Seifert, M.

    1999-01-01

    The Swiss Gas Industry has carried out a systematic, technical estimate of methane release from the complete supply chain from production to consumption for the years 1992/1993. The result of this survey provided a conservative value, amounting to 0.9% of the Swiss domestic output. A continuation of the study taking into account new findings with regard to emission factors and the effect of the climate is now available, which provides a value of 0.8% for the target year of 1996. These results show that the renovation of the network has brought about lower losses in the local gas supplies, particularly for the grey cast iron pipelines. (author)

  16. Sustainable Disruptions

    DEFF Research Database (Denmark)

    Friis, Silje Alberthe Kamille; Kjær, Lykke Bloch

    2016-01-01

    Since 2012 the Sustainable Disruptions (SD) project at the Laboratory for Sustainability at Design School Kolding (DK) has developed and tested a set of design thinking tools, specifically targeting the barriers to economically, socially, and environmentally sustainable business development....... The tools have been applied in practice in collaboration with 11 small and medium sized companies (SMEs). The study investigates these approaches to further understand how design thinking can contribute to sustainable transition in a business context. The study and the findings are relevant to organizations...... invested in the issue of sustainable business development, in particular the leaders and employees of SMEs, but also to design education seeking new ways to consciously handle and teach the complexity inherent in sustainable transformation. Findings indicate that the SD design thinking approach contributes...

  17. Computational sustainability

    CERN Document Server

    Kersting, Kristian; Morik, Katharina

    2016-01-01

    The book at hand gives an overview of the state of the art research in Computational Sustainability as well as case studies of different application scenarios. This covers topics such as renewable energy supply, energy storage and e-mobility, efficiency in data centers and networks, sustainable food and water supply, sustainable health, industrial production and quality, etc. The book describes computational methods and possible application scenarios.

  18. Sustainable Universities

    DEFF Research Database (Denmark)

    Grindsted, Thomas Skou

    2011-01-01

    Declarations on Sustainability in Higher Education (SHE) can be viewed as a piece of international regulation. Over the past 30 years research at universities has produced convincing data to warn about deterioration of the environment, resource scarcity and the need for sustainability. This in turn....... Declarations tend to have impact on three trends. Firstly, there is emerging international consensus on the university’s role and function in relation to sustainable development; secondly, the emergence of national legislation, and thirdly, an emerging international competition to be leader in sustainable...

  19. Sustainable Transition

    DEFF Research Database (Denmark)

    Hansen, Ole Erik; Søndergård, Bent

    2014-01-01

    of agendas/vision, technologies, actors and institutions in the emergent design of an urban mobility system based on an electric car sharing system. Why. Designing for sustainability is a fundamental challenge for future design practices; designers have to obtain an ability to contribute to sustainable...

  20. Sustainable transformation

    DEFF Research Database (Denmark)

    Andersen, Nicolai Bo

    This paper is about sustainable transformation with a particular focus on listed buildings. It is based on the notion that sustainability is not just a question of energy conditions, but also about the building being robust. Robust architecture means that the building can be maintained and rebuil...

  1. Sustainability Labeling

    NARCIS (Netherlands)

    Dam, van Y.K.

    2017-01-01

    Sustainability labeling originated from a need to protect the identity of alternative systems of food production and to increase market transparency. From the 1980s onwards sustainability labeling has changed into a policy instrument replacing direct government regulation of the food market, and a

  2. Making the Sustainable Development Goals Consistent with Sustainability

    Directory of Open Access Journals (Sweden)

    Mathis Wackernagel

    2017-07-01

    Full Text Available The UN’s Sustainable development Goals (SDGs are the most significant global effort so far to advance global sustainable development. Bertelsmann Stiftung and the sustainable development solutions network released an SDG index to assess countries’ average performance on SDGs. Ranking high on the SDG index strongly correlates with high per person demand on nature (or “Footprints”, and low ranking with low Footprints, making evident that the SDGs as expressed today vastly underperform on sustainability. Such underperformance is anti-poor because lowest-income people exposed to resource insecurity will lack the financial means to shield themselves from the consequences. Given the significance of the SDGs for guiding development, rigorous accounting is essential for making them consistent with the goals of sustainable development: thriving within the means of planet Earth.

  3. Making the Sustainable Development Goals Consistent with Sustainability

    Energy Technology Data Exchange (ETDEWEB)

    Wackernagel, Mathis, E-mail: mathis.wackernagel@footprintnetwork.org; Hanscom, Laurel; Lin, David [Global Footprint Network, Oakland, CA (United States)

    2017-07-11

    The UN’s Sustainable development Goals (SDGs) are the most significant global effort so far to advance global sustainable development. Bertelsmann Stiftung and the sustainable development solutions network released an SDG index to assess countries’ average performance on SDGs. Ranking high on the SDG index strongly correlates with high per person demand on nature (or “Footprints”), and low ranking with low Footprints, making evident that the SDGs as expressed today vastly underperform on sustainability. Such underperformance is anti-poor because lowest-income people exposed to resource insecurity will lack the financial means to shield themselves from the consequences. Given the significance of the SDGs for guiding development, rigorous accounting is essential for making them consistent with the goals of sustainable development: thriving within the means of planet Earth.

  4. Making the Sustainable Development Goals Consistent with Sustainability

    International Nuclear Information System (INIS)

    Wackernagel, Mathis; Hanscom, Laurel; Lin, David

    2017-01-01

    The UN’s Sustainable development Goals (SDGs) are the most significant global effort so far to advance global sustainable development. Bertelsmann Stiftung and the sustainable development solutions network released an SDG index to assess countries’ average performance on SDGs. Ranking high on the SDG index strongly correlates with high per person demand on nature (or “Footprints”), and low ranking with low Footprints, making evident that the SDGs as expressed today vastly underperform on sustainability. Such underperformance is anti-poor because lowest-income people exposed to resource insecurity will lack the financial means to shield themselves from the consequences. Given the significance of the SDGs for guiding development, rigorous accounting is essential for making them consistent with the goals of sustainable development: thriving within the means of planet Earth.

  5. Afterschool Sustainability

    Directory of Open Access Journals (Sweden)

    Hilary D. Joyce

    2014-12-01

    Full Text Available Youth participation in quality extended learning opportunities (ELOs results in positive academic, physical, mental health, and social/emotional outcomes. Funding is essential to implementing and sustaining quality ELOs; however multiple funding barriers and challenges exist. Understanding the types of funds available for ELOs and the factors that influence sustainability is critical. Through surveys and telephone interviews of ELO providers, this descriptive study identified and examined ELO funding streams, the ways ELO providers use these funding streams, and the barriers and challenges to sustainability. ELO programs often relied on one major funding stream coupled with nutrition supports as well as in-kind resources. Barriers to sustainability included year-to-year funding, transportation costs, reducing community partnerships, and difficulty in diversifying funds. Recommendations to enhance ELO sustainability are offered, particularly in relation to overcoming the challenges to diversification of funding resources and establishing mutually supportive partnerships and collaboration.

  6. Sustainable Cities

    DEFF Research Database (Denmark)

    Georg, Susse; Garza de Linde, Gabriela Lucía

    Judging from the number of communities and cities striving or claiming to be sustainable and how often eco-development is invoked as the means for urban regeneration, it appears that sustainable and eco-development have become “the leading paradigm within urban development” (Whitehead 2003....../assessment tool. The context for our study is urban regeneration in one Danish city, which had been suffering from industrial decline and which is currently investing in establishing a “sustainable city”. Based on this case study we explore how the insights and inspiration evoked in working with the tool...

  7. Sustainable Transportation

    DEFF Research Database (Denmark)

    Hall, Ralph P.; Gudmundsson, Henrik; Marsden, Greg

    2014-01-01

    The transportation system is the backbone of economic and social progress and the means by which humans access goods and services and connect with one another. Yet, as the scale of transportation activities has grown worldwide, so too have the negative environmental, social, and economic impacts...... that relate to the construction and maintenance of transportation infrastructure and the operation or use of the different transportation modes. The concept of sustainable transportation emerged in response to these concerns as part of the broader notion of sustainable development. Given the transportation...... sector’s significant contribution to global challenges such as climate change, it is often said that sustainable development cannot be achieved without sustainable transportation....

  8. Agriculture: Sustainability

    Science.gov (United States)

    Sustainability creates and maintains the conditions under which humans and nature can exist in productive harmony, that permit fulfilling the food, feed, and fiber needs of our country and the social, economic and other requirements.

  9. Sustainable consumption

    DEFF Research Database (Denmark)

    Prothero, Andrea; Dobscha, Susan; Freund, Jim

    2011-01-01

    This essay explores sustainable consumption and considers possible roles for marketing and consumer researchers and public policy makers in addressing the many sustainability challenges that pervade our planet. Future research approaches to this interdisciplinary topic need to be comprehensive...... and systematic and will benefit from a variety of different perspectives. There are a number of opportunities for future research, and three areas are explored in detail. First, the essay considers the inconsistency between the attitudes and behaviors of consumers with respect to sustainability; next, the agenda...... is broadened to explore the role of individual citizens in society; and finally, a macro institutional approach to fostering sustainability is explored. Each of these areas is examined in detail and possible research avenues and public policy initiatives are considered within each of these separate...

  10. Sustainable Futures

    Science.gov (United States)

    Sustainable Futures is a voluntary program that encourages industry to use predictive models to screen new chemicals early in the development process and offers incentives to companies subject to TSCA section 5.

  11. Sustainability reporting

    NARCIS (Netherlands)

    Kolk, A.

    2005-01-01

    This article gives an overview of developments in sustainability (also sometimes labelled corporate social responsibility) reporting. The article will first briefly indicate how accountability on social and environmental issues started, already in the 1970s when social reports were published.

  12. Sustainable transformation

    DEFF Research Database (Denmark)

    Andersen, Nicolai Bo

    This paper is about sustainable transformation with a particular focus on listed buildings. It is based on the notion that sustainability is not just a question of energy conditions, but also about the building being robust. Robust architecture means that the building can be maintained and rebuilt......, that it can be adapted to changing functional needs, and that it has an architectural and cultural value. A specific proposal for a transformation that enhances the architectural qualities and building heritage values of an existing building forms the empirical material, which is discussed using different...... theoretical lenses. It is proposed that three parameters concerning the ꞌtransformabilityꞌ of the building can contribute to a more nuanced understanding of sustainable transformation: technical aspects, programmatic requirements and narrative value. It is proposed that the concept of ꞌsustainable...

  13. Sustainable Consumption

    DEFF Research Database (Denmark)

    Røpke, Inge

    2015-01-01

    The intention of this chapter is to explore the role of consumption and consumers in relation to sustainability transition processes and wider systemic transformations. In contrast to the individualistic focus in much research on sustainable consumption, the embeddedness of consumption activities...... in wider social, economic and technological frameworks is emphasised. In particular, the chapter is inspired by practice theory and transition theory. First, various trends in consumption are outlined to highlight some of the challenges for sustainability transitions. Then, it is discussed how consumption...... patterns are shaped over time and what should be considered in sustainability strategies. While discussions on consumption often take their point of departure in the perspective of the individual and then zoom to the wider context, the present approach is the opposite. The outline starts with the basic...

  14. Stabilizing Sustainability

    DEFF Research Database (Denmark)

    Reitan Andersen, Kirsti

    The publication of the Brundtland Report in 1987 put the topic of sustainable development on the political and corporate agenda. Defining sustainable development as “a development that meets the needs of the future without compromising the ability of future generations to meet their own needs......” (WCED, 1987, p. 43), the Report also put a positive spin on the issue of sustainability by upholding capitalist beliefs in the possibility of infinite growth in a world of finite resources. While growth has delivered benefits, however, it has done so unequally and unsustainably. This thesis focuses...... on the textile and fashion industry, one of the world’s most polluting industries and an industry to some degree notorious for leading the ‘race to the bottom’ in global labour standards. Despite being faced with increasing demands to practise sustainability, most textile and fashion companies continue to fail...

  15. Seeking Sustainability

    OpenAIRE

    Clive L. Spash

    2014-01-01

    What does sustainability research do to help the environment? One might well wonder when observing the annual conference season with various academics and professors in sustainability science, ecological economics or environmental ethics driving to the airport to fly off to international meetings to discuss how bad things are getting, what should been done about it, and how time is running out for action. In fact, singling out a few academic groups is highly unfair because the link between pr...

  16. Local Sustainability

    International Nuclear Information System (INIS)

    Carrizosa Umana, Julio

    1998-01-01

    The current polemic about the possibilities of sustainable development has led to a renovated interest for the topic of the sustainability of the communities and the local sustainability. In front of the global sustainability whose conditions have been exposed by systemic ecologists and for macro economists, the sustainability of specific places arises in the planet whose conditions are object of study of the ecology of landscapes, of the ecological economy, of the cultural anthropology, of the environmental sociology and naturally, of the integral environmentalism. In this discussion the Colombian case charges unusual interest to be one of the few countries of Latin America, where a very dense net of municipalities exists, each one with its urban helmet and with a position and some functions defined by the political constitution of the nation. This net of municipalities and of urban helmets it also constitutes net of alternative to the current macro-cephalic situation. As well as Bogota grew, in a hundred years, of less than a hundred thousand inhabitants to six million inhabitants, each one of these municipalities contains a potential of growth that depends on the characteristics of its ecological, social, economic and politic sustainability

  17. Sustainable markets for sustainable energy

    Energy Technology Data Exchange (ETDEWEB)

    Millan, J.; Smyser, C.

    1997-12-01

    The author discusses how the Inter-American Development Bank (IDB) is involved in sustainable energy development. It presently has 50 loans and grants for non conventional renewable energy projects and ten grants for efficiency programs for $600 and $17 million respectively, representing 100 MW of power. The IDB is concerned with how to create a sustainable market for sustainable energy projects. The IDB is trying to work with government, private sector, NGOs, trading allies, credit sources, and regulators to find proper roles for such projects. He discusses how the IDB is working to expand its vision and objectives in renewable energy projects in Central and South America.

  18. Roundtabling Sustainability

    DEFF Research Database (Denmark)

    Ponte, Stefano

    2014-01-01

    councils’ and ‘sustainability roundtables’ and have been designed around a set of institutional features seeking to establish legitimacy, fend off possible criticism, and ‘sell’ certifications to potential users. The concept of ‘roundtabling’ emphasizes the fitting a variety of commodity...... and procedures to meet ‘good practice’ in standard setting and management. This is opening space for competing initiatives that are less democratic, quicker, and more aligned with industry interests to establish substantial presence in the market for sustainability certifications. These tend to more easily...

  19. Sustainable finance

    NARCIS (Netherlands)

    Boersma-de Jong, Margreet F.

    2012-01-01

    Presentation for Springschool of Strategy, University of Groningen, 10 October 2012. The role of CSR is to stimulate ethical behaviour, and as a result, mutual trust in society. Advantage of CSR for the company and the evolution of CSR. From CSR to Sustainable Finance: how does CSR influence

  20. Sustainable Procurement

    DEFF Research Database (Denmark)

    Telles, Pedro; Ølykke, Grith Skovgaard

    2017-01-01

    and within it how sustainable requirements have increased the level of compliance required, particularly regulatory compliance. Compliance was already present in previous EU public procurement frameworks, but its extent on Directive 2014/24/EU leads the authors to consider the current legal framework...

  1. Exergy sustainability.

    Energy Technology Data Exchange (ETDEWEB)

    Robinett, Rush D. III (.; ); Wilson, David Gerald; Reed, Alfred W.

    2006-05-01

    Exergy is the elixir of life. Exergy is that portion of energy available to do work. Elixir is defined as a substance held capable of prolonging life indefinitely, which implies sustainability of life. In terms of mathematics and engineering, exergy sustainability is defined as the continuous compensation of irreversible entropy production in an open system with an impedance and capacity-matched persistent exergy source. Irreversible and nonequilibrium thermodynamic concepts are combined with self-organizing systems theories as well as nonlinear control and stability analyses to explain this definition. In particular, this paper provides a missing link in the analysis of self-organizing systems: a tie between irreversible thermodynamics and Hamiltonian systems. As a result of this work, the concept of ''on the edge of chaos'' is formulated as a set of necessary and sufficient conditions for stability and performance of sustainable systems. This interplay between exergy rate and irreversible entropy production rate can be described as Yin and Yang control: the dialectic synthesis of opposing power flows. In addition, exergy is shown to be a fundamental driver and necessary input for sustainable systems, since exergy input in the form of power is a single point of failure for self-organizing, adaptable systems.

  2. Sustainable Buildings

    DEFF Research Database (Denmark)

    Tommerup, Henrik M.; Elle, Morten

    The scientific community agrees that: all countries must drastically and rapidly reduce their CO2 emissions and that energy efficient houses play a decisive role in this. The general attitude at the workshop on Sustainable Buildings was that we face large and serious climate change problems...

  3. Sustainable Entrepreneurship

    DEFF Research Database (Denmark)

    Schaltegger, Stefan; Beckmann, Markus; Hockerts, Kai

    2018-01-01

    . We also explore the transformation path of the case company, which starts with simple use and then moves to the feedback to core business pattern. By drawing on insights from lead user theory in innovation management and sustainable entrepreneurship, we ground the new concept in extant literature...

  4. Sustainable machining

    CERN Document Server

    2017-01-01

    This book provides an overview on current sustainable machining. Its chapters cover the concept in economic, social and environmental dimensions. It provides the reader with proper ways to handle several pollutants produced during the machining process. The book is useful on both undergraduate and postgraduate levels and it is of interest to all those working with manufacturing and machining technology.

  5. Sustainable processing

    DEFF Research Database (Denmark)

    Kristensen, Niels Heine

    2004-01-01

    Kristensen_NH and_Beck A: Sustainable processing. In Otto Schmid, Alexander Beck and Ursula Kretzschmar (Editors) (2004): Underlying Principles in Organic and "Low-Input Food" Processing - Literature Survey. Research Institute of Organic Agriculture FiBL, CH-5070 Frick, Switzerland. ISBN 3-906081-58-3...

  6. Architecture Sustainability

    NARCIS (Netherlands)

    Avgeriou, Paris; Stal, Michael; Hilliard, Rich

    2013-01-01

    Software architecture is the foundation of software system development, encompassing a system's architects' and stakeholders' strategic decisions. A special issue of IEEE Software is intended to raise awareness of architecture sustainability issues and increase interest and work in the area. The

  7. Sustainable development

    International Nuclear Information System (INIS)

    Boiteux, M.

    2004-01-01

    Marcel Boiteux evokes the results of the work on the sustainable development by the Academie des Sciences Morales et Politiques. This is a vast political programme with the goal of allowing all humanity to live well in growing unity while protecting the environment and favouring economic growth. (author)

  8. Sustainable Development

    African Journals Online (AJOL)

    Tsegai Berhane Ghebretekle

    Ethiopia is selected as a case study in light of its pace in economic growth ... Interrogating the Economy-First Paradigm in 'Sustainable Development' … 65 .... agreement, since such effective global cooperation on climate change ultimately ..... and foster innovation; reduce inequality within and among countries; make cities.

  9. Sustainable Soesterkwartier

    NARCIS (Netherlands)

    Abrahams, H.; Goosen, H.; Jong, de F.; Sickmann, J.; Prins, D.

    2010-01-01

    The municipality of Amersfoort wants to construct an endurable and sustainable eco-town in the Soesterkwartier neighbourhood, by taking future climate change into account. The impact of climate change at the location of the proposed eco-town was studied by a literature review.

  10. Synthetic sustained gene delivery systems.

    Science.gov (United States)

    Agarwal, Ankit; Mallapragada, Surya K

    2008-01-01

    Gene therapy today is hampered by the need of a safe and efficient gene delivery system that can provide a sustained therapeutic effect without cytotoxicity or unwanted immune responses. Bolus gene delivery in solution results in the loss of delivered factors via lymphatic system and may cause undesired effects by the escape of bioactive molecules to distant sites. Controlled gene delivery systems, acting as localized depot of genes, provide an extended sustained release of genes, giving prolonged maintenance of the therapeutic level of encoded proteins. They also limit the DNA degradation in the nuclease rich extra-cellular environment. While attempts have been made to adapt existing controlled drug delivery technologies, more novel approaches are being investigated for controlled gene delivery. DNA encapsulated in nano/micro spheres of polymers have been administered systemically/orally to be taken up by the targeted tissues and provide sustained release once internalized. Alternatively, DNA entrapped in hydrogels or scaffolds have been injected/implanted in tissues/cavities as platforms for gene delivery. The present review examines these different modalities for sustained delivery of viral and non-viral gene-delivery vectors. Design parameters and release mechanisms of different systems made with synthetic or natural polymers are presented along with their prospective applications and opportunities for continuous development.

  11. The road to sustainability

    Energy Technology Data Exchange (ETDEWEB)

    Sarrao, John L [Los Alamos National Laboratory; Crabtree, George [ANL

    2009-01-01

    Sustainability is the hottest topic in energy research today, but what does it actually mean? George Crabtree and John Sarrao describe what makes a technology sustainable, and outline the materials-science challenges standing between us and clean, long-lasting energy. Although most people agree that more-sustainable energy technologies are desirable, they often find it harder to agree on exactly how sustainable these technologies need to be, and even precisely what is meant by sustainability. To clarify the debate, we suggest three criteria for sustainability, each of which captures a different feature of the problem. While we do not have the lUxury of achieving full sustainability for all of our next-generation energy technologies, we can use these definitions to select our strategic sustainability targets and track our progress toward achieving them. As will become clear, the most sustainable energy technologies require the most challenging fundamental science breakthroughs. The first criterion for sustainability is 'lasts a long time'. This quality has been a feature of many energy sources we have used historically, including wood in ancient times and oil throughout most of the 20th century. The definition of 'long time' is, of course, relative: the world's demand for energy long ago outpaced the ability of wood to supply it, and the production of oil is likely to peak sometime within the next few decades. Substantial reductions in the rate of oil consumption through higher-efficiency processes can significantly impact on how long non-renewable resources last. In applying the 'long time' criterion, we need to distinguish between energy sources that are effectively limitless and those that are finite but, for the moment, adequate. The second criterion for sustainability is 'does no harm'. Burning fossil fuels releases pollutants such as sulphur and mercury that endanger human health, as well as greenhouse gases like

  12. Sustainable Sizing.

    Science.gov (United States)

    Robinette, Kathleen M; Veitch, Daisy

    2016-08-01

    To provide a review of sustainable sizing practices that reduce waste, increase sales, and simultaneously produce safer, better fitting, accommodating products. Sustainable sizing involves a set of methods good for both the environment (sustainable environment) and business (sustainable business). Sustainable sizing methods reduce (1) materials used, (2) the number of sizes or adjustments, and (3) the amount of product unsold or marked down for sale. This reduces waste and cost. The methods can also increase sales by fitting more people in the target market and produce happier, loyal customers with better fitting products. This is a mini-review of methods that result in more sustainable sizing practices. It also reviews and contrasts current statistical and modeling practices that lead to poor fit and sizing. Fit-mapping and the use of cases are two excellent methods suited for creating sustainable sizing, when real people (vs. virtual people) are used. These methods are described and reviewed. Evidence presented supports the view that virtual fitting with simulated people and products is not yet effective. Fit-mapping and cases with real people and actual products result in good design and products that are fit for person, fit for purpose, with good accommodation and comfortable, optimized sizing. While virtual models have been shown to be ineffective for predicting or representing fit, there is an opportunity to improve them by adding fit-mapping data to the models. This will require saving fit data, product data, anthropometry, and demographics in a standardized manner. For this success to extend to the wider design community, the development of a standardized method of data collection for fit-mapping with a globally shared fit-map database is needed. It will enable the world community to build knowledge of fit and accommodation and generate effective virtual fitting for the future. A standardized method of data collection that tests products' fit methodically

  13. News/Press Releases

    Data.gov (United States)

    Office of Personnel Management — A press release, news release, media release, press statement is written communication directed at members of the news media for the purpose of announcing programs...

  14. Novel Non-Intrusive Trans-Dermal Remote Wireless Micro-Fluidic Monitoring System Applied to Continuous Glucose and Lactate Assays for Casualty Care and Combat Readiness Assessment

    Science.gov (United States)

    2004-09-01

    identification of the lettered features. 2.2 BFIT Sampling Chip The BFIT sampling chip is a flexible patch-like chip with a multilayer polymeric metal...PPy) and glucose oxidase (GOD). The BFIT fabrication process uses SU8 as a principal structural material consisting of five steps (Figure 2). This...process is a subset of an earlier technology developed for the polymer material PDMS.11,12,13,14,15 The first step was the deposition of a Teflon

  15. Adjustments for drink size and ethanol content: New results from a self-report diary and trans-dermal sensor validation study

    Science.gov (United States)

    Bond, J. C.; Greenfield, T. K.; Patterson, D.; Kerr, W.C.

    2014-01-01

    Background Prior studies adjusting self-reported measures of alcohol intake for drink size and ethanol content have relied on single-point assessments. Methods A prospective 28-day diary study investigated magnitudes of drink ethanol adjustments and factors associated with these adjustments. Transdermal alcohol sensor (TAS) readings and prediction of alcohol-related problems by number of drinks versus ethanol-adjusted intake were used to validate drink ethanol adjustments. Self-completed event diaries listed up to 4 beverage types and 4 drinking events/day. Eligible volunteers had ≥ weekly drinking and ≥ 3+ drinks per occasion with ≥ 26 reported days and pre- and post-summary measures (n = 220). Event reports included drink types, sizes, brands or spirits contents, venues, drinks consumed and drinking duration. Results Wine drinks averaged 1.19, beer, 1.09 and spirits 1.54 US standard drinks (14g ethanol). Mean adjusted alcohol intake was 22% larger using drink size and strength (brand/ethanol concentration) data. Adjusted drink levels were larger than “raw” drinks in all quantity ranges. Individual-level drink ethanol adjustment ratios (ethanol adjusted/unadjusted amounts) averaged across all days drinking ranged from 0.73-3.33 (mean 1.22). Adjustment ratio was only marginally (and not significantly) positively related to usual quantity, frequency and heavy drinking (all psalcohol dependence symptoms (p<.01) and number of consequences (p<.05). In 30 respondents with sufficiently high quality TAS readings, higher correlations (p=.04) were found between the adjusted vs. the raw drinks/event and TAS areas under the curve. Conclusions Absent drink size and strength data, intake assessments are downward biased by at least 20%. Between-subject variation in typical drink content and pour sizes should be addressed in treatment and epidemiological research. PMID:25581661

  16. 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.

  17. Building sustainability

    CSIR Research Space (South Africa)

    Mass Media

    2007-11-01

    Full Text Available particu- lar social environment also being awarded. If a building can be used by the community after hours, it should be awarded extra points.” School sports facilities or meeting halls in corporate buildings, are some example. Multi-purpose use..., architect and senior researcher for the CSIR’s Built Environment Unit, the integra- tion of sustainability in building design cannot begin soon enough before it is too late. He says: “Unfortunately nothing is in place in South Africa. For a start...

  18. 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.

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

    African Journals Online (AJOL)

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

  20. Interdependences between sustainable development and sustainable economy

    OpenAIRE

    Emilia Mioara CÂMPEANU; Carmen Valentina RĂDULESCU

    2014-01-01

    Sustainable development and sustainable economy are mostly used concepts. Understanding clearly their meaning allows their use in an appropriate context and, therefore, their boundaries in terms of theoretical and practical approaches on which occasion it can be given their interdependencies. The paper aim is to analyze the interdependences between sustainable development and sustainable economy.

  1. Virtual Sustainability

    Directory of Open Access Journals (Sweden)

    William Sims Bainbridge

    2010-09-01

    Full Text Available In four ways, massively multiplayer online role-playing games may serve as tools for advancing sustainability goals, and as laboratories for developing alternatives to current social arrangements that have implications for the natural environment. First, by moving conspicuous consumption and other usually costly status competitions into virtual environments, these virtual worlds might reduce the need for physical resources. Second, they provide training that could prepare individuals to be teleworkers, and develop or demonstrate methods for using information technology to replace much transportation technology, notably in commuting. Third, virtual worlds and online games build international cooperation, even blending national cultures, thereby inching us toward not only the world consciousness needed for international agreements about the environment, but also toward non-spatial government that cuts across archaic nationalisms. Finally, realizing the potential social benefits of this new technology may urge us to reconsider a number of traditional societal institutions.

  2. Sustainability; Sustentabilidade

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-10-15

    This chapter analyses the production chain of ethanol, considering the impacts on the quality of the air, water supplies, soil occupation and biodiversity, and the efforts for the soil preservation. It is pointed out the activities of the production cycle and use of bio ethanol due to great uncertainties as far the environmental impacts is concerning and that will deserve more attention in future evaluations. At same time, the chapter highlights another activities where the present acknowledge is sufficient to assure the control and/or prediction of consequences of the desired intervention on the environment media to accommodate the sugar and ethanol production expansion. The consideration is not conservative but to promote the sustainable development.

  3. Sustainability Science Needs Sustainable Data!

    Science.gov (United States)

    Downs, R. R.; Chen, R. S.

    2013-12-01

    Sustainability science (SS) is an 'emerging field of research dealing with the interactions between natural and social systems, and with how those interactions affect the challenge of sustainability: meeting the needs of present and future generations while substantially reducing poverty and conserving the planet's life support systems' (Kates, 2011; Clark, 2007). Bettencourt & Kaur (2011) identified more than 20,000 scientific papers published on SS topics since the 1980s with more than 35,000 distinct authors. They estimated that the field is currently growing exponentially, with the number of authors doubling approximately every 8 years. These scholars are undoubtedly using and generating a vast quantity and variety of data and information for both SS research and applications. Unfortunately we know little about what data the SS community is actually using, and whether or not the data that SS scholars generate are being preserved for future use. Moreover, since much SS research is conducted by cross-disciplinary, multi-institutional teams, often scattered around the world, there could well be increased risks of data loss, reduced data quality, inadequate documentation, and poor long-term access and usability. Capabilities and processes therefore need to be established today to support continual, reliable, and efficient preservation of and access to SS data in the future, especially so that they can be reused in conjunction with future data and for new studies not conceived in the original data collection activities. Today's long-term data stewardship challenges include establishing sustainable data governance to facilitate continuing management, selecting data to ensure that limited resources are focused on high priority SS data holdings, securing sufficient rights to allow unforeseen uses, and preparing data to enable use by future communities whose specific research and information needs are not yet known. Adopting sustainable models for archival

  4. Toxics Release Inventory (TRI)

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Toxics Release Inventory (TRI) is a dataset compiled by the U.S. Environmental Protection Agency (EPA). It contains information on the release and waste...

  5. Is light water reactor technology sustainable?

    International Nuclear Information System (INIS)

    Rothwell, G.; Van der Zwaan, B.

    2001-01-01

    This paper proposes criteria for determining ''intermediate sustainability'' over a 500-year horizon. We apply these criteria to Light Water Reactor (LWR) technology and the LWR industry. We conclude that LWR technology does not violate intermediate sustainability criteria for (1) environmental externalities, (2) worker and public health and safety, or (3) accidental radioactive release. However, it does not meet criteria to (1) efficiently use depleted uranium and (2) avoid uranium enrichment technologies that can lead to nuclear weapons proliferation. Finally, current and future global demand for LWR technology might be below the minimum needed to sustain the current global LWR industry. (author)

  6. Is light water reactor technology sustainable?

    Energy Technology Data Exchange (ETDEWEB)

    Rothwell, G. [Stanford Univ., Dept. of Economics, CA (United States); Van der Zwaan, B. [Vrije Univ., Amsterdam, Inst. for Environmental Studies (Netherlands)

    2001-07-01

    This paper proposes criteria for determining ''intermediate sustainability'' over a 500-year horizon. We apply these criteria to Light Water Reactor (LWR) technology and the LWR industry. We conclude that LWR technology does not violate intermediate sustainability criteria for (1) environmental externalities, (2) worker and public health and safety, or (3) accidental radioactive release. However, it does not meet criteria to (1) efficiently use depleted uranium and (2) avoid uranium enrichment technologies that can lead to nuclear weapons proliferation. Finally, current and future global demand for LWR technology might be below the minimum needed to sustain the current global LWR industry. (author)

  7. Advancing Sustainable Materials Management: Facts and Figures Report

    Science.gov (United States)

    Each year EPA releases the Advancing Sustainable Materials Management: Facts and Figures report, formerly called Municipal Solid Waste in the United States: Facts and Figures. It includes information on Municipal Solid Waste generation, recycling, an

  8. Sustainable NREL - Site Sustainability Plan FY 2015

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2015-01-01

    NREL's Site Sustainability Plan FY 2015 reports on sustainability plans for the lab for the year 2015 based on Executive Order Goals and provides the status on planned actions cited in the FY 2014 report.

  9. Preparation of venlafaxine hydrochloride sustained-release tablets

    Directory of Open Access Journals (Sweden)

    ZHANG Yang

    2013-02-01

    Full Text Available A novel non-enzymatic glucose sensor was developed by electrodepositing copper film onto the graphene(GR substrate.The morphologies and structures of the nanocomposites were characterized by field emission scanning electron microscope (FESEM.The electrochemical performances of the Cu/GR nanocomposite film were investigated.The Cu/GR nanocomposite film showed good electrocatalytic activity towards glucose oxidation in alkaline solution.The Cu/GR nanocomposite film-based sensor displayed a linear concentration range from 8×10-6 to 9.4×10-4 mol/L with the sensitivity of 0.225 A·L·mol-1 and the detection limit (S/N=3 of 2.5 μmol/L for the detection of glucose.With an enhanced electrocatalytic property,high sensitivity and good stability.The as-prepared sensor is promising for the future development of nonenzymatic sensors.

  10. Application of mathematical modeling in sustained release delivery systems.

    Science.gov (United States)

    Grassi, Mario; Grassi, Gabriele

    2014-08-01

    This review, presenting as starting point the concept of the mathematical modeling, is aimed at the physical and mathematical description of the most important mechanisms regulating drug delivery from matrix systems. The precise knowledge of the delivery mechanisms allows us to set up powerful mathematical models which, in turn, are essential for the design and optimization of appropriate drug delivery systems. The fundamental mechanisms for drug delivery from matrices are represented by drug diffusion, matrix swelling, matrix erosion, drug dissolution with possible recrystallization (e.g., as in the case of amorphous and nanocrystalline drugs), initial drug distribution inside the matrix, matrix geometry, matrix size distribution (in the case of spherical matrices of different diameter) and osmotic pressure. Depending on matrix characteristics, the above-reported variables may play a different role in drug delivery; thus the mathematical model needs to be built solely on the most relevant mechanisms of the particular matrix considered. Despite the somewhat diffident behavior of the industrial world, in the light of the most recent findings, we believe that mathematical modeling may have a tremendous potential impact in the pharmaceutical field. We do believe that mathematical modeling will be more and more important in the future especially in the light of the rapid advent of personalized medicine, a novel therapeutic approach intended to treat each single patient instead of the 'average' patient.

  11. 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.

  12. Preparation and pre-clinical characterization of sustained- release ...

    African Journals Online (AJOL)

    This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and .... with the help of screw gauge (n = 3). Hardness .... performed by ANOVA using GraphPad Prism©. 4.0. Values of p ...

  13. Biodegradable Bioadherent Microcapsules for Orally Administered Sustained Release Vaccines

    Science.gov (United States)

    1997-05-01

    Fasciola hepatica which is a known bioadhesive’’. The encapsulation method is the classical, well described water in oil technique for the preparation of...immunization, Vaccine 12 (1994) 387-340. 6. Waite, J.H., Rice-Ficht, A.C., Presclerotized eggshell protein from the liver fluke Fasciola hepatica...Biochemistry 26 (1987) 7819-7825. 7. Waite, J.H., Rice-Ficht, A.C., Eggshell precursor proteins of Fasciola hepatica: II. Microheterogeneity in vitelline

  14. Environmentally Sustainable Construction Products and Materials – Assessment of release

    DEFF Research Database (Denmark)

    Wahlström, Margareta; Laine-Yliijoki, Jutta; Järnström, helena

    The construction sector consumes yearly about half of all natural resourcesextracted in Europe and their transformation into building products has huge energy demands. Therefore the focus of today’s environmental policy is on the building end-of-life scenarios and material efficiency. Here waste...... hardly any construction product is designed keeping recycling/reuse in mind, the “Design for theEnvironment” -concept is one of the key steps towards increased recycling and reuse and thereby towards minimal environmental impacts. This project has been carried out by VTT with cooperation with the Danish...

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

    African Journals Online (AJOL)

    Erah

    phenomenon. At the molecular level, it involves .... mark with simulated gastric fluid (SGF, pH. 1.2). ... erosion of the polymeric chain while anomalous .... appeared at 186.7oC disappeared while a ... substances and excipients on gel dynamics.

  16. 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...

  17. Design and development of sustained-release glyburide-loaded ...

    Indian Academy of Sciences (India)

    delivery of cancer imaging, i.e., diagnosis. ... hyperglycemic agent of class sulphonylurea having half-life. ∗ ... patients with chronic kidney disease [10] and active ischemic ..... [24] Montgomery D C 2008 Introduction to statistical quality.

  18. 21 CFR 520.1920 - Prochlorperazine, isopropamide sustained release capsules.

    Science.gov (United States)

    2010-04-01

    ... HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS... dogs in which gastrointestinal disturbances are associated with emotional stress. (2)(i) Capsules...

  19. Sustained Release Oral Nanoformulated Green Tea for Prostate Cancer Prevention

    Science.gov (United States)

    2013-05-01

    epigallocatechin-3-gallate. Cancer Res. 2009;69:1712-6. 2. Adhami VM, Siddiqui IA, Syed DN, Lall RK, Mukhtar H. Oral infusion of pomegranate fruit ...and fungi , and is also known for its non-toxic, non-immunogenic properties (23). It has already been used as a pharmaceutical excipient, a weight loss...component EGCG and perceived toxicity associated with its long-term use affect its clinical outcome (36,37). This study suggests a different

  20. Sustainability : Politics and governance

    NARCIS (Netherlands)

    Heinrichs, Harald; Biermann, Frank

    2016-01-01

    he article gives an overview of global sustainability policy and politics. It is shown how international policy making on sustainable development has progressed from environmental policy toward recent approaches of Earth system governance. Key challenges of international sustainability politics are

  1. Sustainability in Transport Planning

    DEFF Research Database (Denmark)

    Gudmundsson, Henrik; Greve, Carsten

    Contribution to session J: Joint University Sustainability Initiatives. This session will provide an inspiring overview of interdisciplinary research and teaching activities on sustainability bridging DTU, KU, and CBS, and introduce the joint collaboration Copenhagen Sustainability Initiative (COSI...

  2. Textiles and clothing sustainability sustainable technologies

    CERN Document Server

    2017-01-01

    This is the first book to deal with the innovative technologies in the field of textiles and clothing sustainability. It details a number of sustainable and innovative technologies and highlights their implications in the clothing sector. There are currently various measures to achieve sustainability in the textiles and the clothing industry, including innovations in the manufacturing stage, which is the crux of this book.

  3. Sustainable diets within sustainable food systems.

    Science.gov (United States)

    Meybeck, Alexandre; Gitz, Vincent

    2017-02-01

    Sustainable diets and sustainable food systems are increasingly explored by diverse scientific disciplines. They are also recognised by the international community and called upon to orient action towards the eradication of hunger and malnutrition and the fulfilment of sustainable development goals. The aim of the present paper is to briefly consider some of the links between these two notions in order to facilitate the operationalisation of the concept of sustainable diet. The concept of sustainable diet was defined in 2010 combining two totally different perspectives: a nutrition perspective, focused on individuals, and a global sustainability perspective, in all its dimensions: environmental, economic and social. The nutrition perspective can be easily related to health outcomes. The global sustainability perspective is more difficult to analyse directly. We propose that it be measured as the contribution of a diet to the sustainability of food systems. Such an approach, covering the three dimensions of sustainability, enables identification of interactions and interrelations between food systems and diets. It provides opportunities to find levers of change towards sustainability. Diets are both the results and the drivers of food systems. The drivers of change for those variously involved, consumers and private individuals, are different, and can be triggered by different dimensions (heath, environment, social and cultural). Combining different dimensions and reasons for change can help facilitate the transition to sustainable diets, recognising the food system's specificities. The adoption of sustainable diets can be facilitated and enabled by food systems, and by appropriate policies and incentives.

  4. Assessing sustainable remediation frameworks using sustainability principles.

    Science.gov (United States)

    Ridsdale, D Reanne; Noble, Bram F

    2016-12-15

    The remediation industry has grown exponentially in recent decades. International organizations of practitioners and remediation experts have developed several frameworks for integrating sustainability into remediation projects; however, there has been limited attention to how sustainability is approached and operationalized in sustainable remediation frameworks and practices - or whether sustainability plays any meaningful role at all in sustainable remediation. This paper examines how sustainability is represented in remediation frameworks and the guidance provided for practical application. Seven broad sustainability principles and review criteria are proposed and applied to a sample of six international remediation frameworks. Not all review criteria were equally satisfied and none of the frameworks fully met all criteria; however, the best performing frameworks were those identified as sustainability remediation frameworks. Intra-generational equity was addressed by all frameworks. Integrating social, economic and biophysical components beyond triple-bottom-line indicators was explicitly addressed only by the sustainable remediation frameworks. No frameworks provided principle- or rule-based guidance for dealing with trade-offs in sustainability decisions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Large scientific releases

    International Nuclear Information System (INIS)

    Pongratz, M.B.

    1981-01-01

    The motivation for active experiments in space is considered, taking into account the use of active techniques to obtain a better understanding of the natural space environment, the utilization of the advantages of space as a laboratory to study fundamental plasma physics, and the employment of active techniques to determine the magnitude, degree, and consequences of artificial modification of the space environment. It is pointed out that mass-injection experiments in space plasmas began about twenty years ago with the Project Firefly releases. Attention is given to mass-release techniques and diagnostics, operational aspects of mass release active experiments, the active observation of mass release experiments, active perturbation mass release experiments, simulating an artificial modification of the space environment, and active experiments to study fundamental plasma physics

  6. Technology and sustainability

    NARCIS (Netherlands)

    Kroeze, C.; Boersema, J.J.; Tellegen, E.; Cremers, A.

    2011-01-01

    In ten essays, this book addresses a broad range of issues related to the interplay of sustainability and technology. How do population growth and technology relate to sustainable development? Can globalization be reconciled with sustainable development? Is sustainability a subjective or an

  7. Sustainable consumption and marketing

    NARCIS (Netherlands)

    Dam, van Y.K.

    2016-01-01

    Sustainable development in global food markets is hindered by the discrepancy between positive consumer attitudes towards sustainable development or sustainability and the lack of corresponding sustainable consumption by a majority of consumers. Apparently for many (light user) consumers the

  8. Externality or sustainability economics?

    International Nuclear Information System (INIS)

    Bergh, Jeroen C.J.M. van den

    2010-01-01

    In an effort to develop 'sustainability economics' Baumgaertner and Quaas (2010) neglect the central concept of environmental economics-'environmental externality'. This note proposes a possible connection between the concepts of environmental externality and sustainability. In addition, attention is asked for other aspects of 'sustainability economics', namely the distinction weak/strong sustainability, spatial sustainability and sustainable trade, distinctive sustainability policy, and the ideas of early 'sustainability economists'. I argue that both sustainability and externalities reflect a systems perspective and propose that effective sustainability solutions require that more attention is given to system feedbacks, notably other-regarding preferences and social interactions, and energy and environmental rebound. The case of climate change and policy is used to illustrate particular statements. As a conclusion, a list of 20 insights and suggestions for research is offered. (author)

  9. Kennedy Space Center Five Year Sustainability Plan

    Science.gov (United States)

    Williams, Ann T.

    2016-01-01

    The Federal Government is committed to following sustainable principles. At its heart, sustainability integrates environmental, societal and economic solutions for present needs without compromising the ability of future generations to meet their needs. Building upon its pledge towards environmental stewardship, the Administration generated a vision of sustainability spanning ten goals mandated within Executive Order (EO) 13693, Planning for Federal Sustainability in the Next Decade. In November 2015, the National Aeronautics and Space Administration (NASA) responded to this EO by incorporating it into a new release of the NASA Strategic Sustainability Performance Plan (SSPP). The SSPP recognizes the importance of aligning environmental practices in a manner that preserves, enhances and strengthens NASA's ability to perform its mission indefinitely. The Kennedy Space Center (KSC) is following suit with KSC's Sustainability Plan (SP) by promoting, maintaining and pioneering green practices in all aspects of our mission. KSC's SP recognizes that the best sustainable solutions use an interdisciplinary, collaborative approach spanning civil servant and contractor personnel from across the Center. This approach relies on the participation of all employees to develop and implement sustainability endeavors connected with the following ten goals: Reduce greenhouse gas (GHG) emissions. Design, build and maintain sustainable buildings, facilities and infrastructure. Leverage clean and renewable energy. Increase water conservation. Improve fleet and vehicle efficiency and management. Purchase sustainable products and services. Minimize waste and prevent pollution. Implement performance contracts for Federal buildings. Manage electronic equipment and data centers responsibly. Pursue climate change resilience. The KSC SP details the strategies and actions that address the following objectives: Reduce Center costs. center dot Increase energy and water efficiencies. Promote smart

  10. Engineering Sustainability: A Technical Approach to Sustainability

    OpenAIRE

    Rosen, Marc A.

    2012-01-01

    Sustainability is a critically important goal for human activity and development. Sustainability in the area of engineering is of great importance to any plans for overall sustainability given 1) the pervasiveness of engineering activities in societies, 2) their importance in economic development and living standards, and 3) the significant impacts that engineering processes and systems have had, and continue to have, on the environment. Many factors that need to be considered and appropriate...

  11. 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.

  12. Inclusion of cefalexin in SBA-15 mesoporus material and release property

    International Nuclear Information System (INIS)

    Zhai, Qing-Zhou

    2012-01-01

    SBA-15 (Santa Barbara Amorphous-15) is a high ordered mesoporous material. It has the advantages of a non-toxic property, good hydrothermal stability and thermal stability, etc. Inside inner surface a lot of silanols exist. Pore diameter size is uniform and pore size distribution is narrow. This structural feature makes SBA-15 have a higher loading drug amount and be able to effectively extend the drug release cycle. In this paper, polyethylene glycol-block-polypropylene glycol-block-polyethylene glycol was used as template and tetraethyl orthosilicate was used as silica source to prepare SBA-15 by hydrothermal synthesis method. Cefalexin was included in SBA-15 and the included cefalexin drug content was 158.72 mg/g. The composite materials were characterized by using chemical analysis, powder X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), infrared (IR) spectroscopy, and low temperature nitrogen adsorption–desorption. The results showed that cefalexin had been successfully included in host SBA-15 pore channels. Rational analyses of the release processes of cefalexin drug from the pores of SBA-15 to the simulated body fluid, simulated gastric juice and simulated intestinal fluid were made and sustained-release effects of the drug in complex system were studied. The results showed that in simulated body fluid within 1–5 h cefalexin was fast released and the cumulative release reached 50.00% at 5 h. In 15–20 h, the sustained release speed of cefalexin drug in the composite material decreased and the sustained-release cumulative amount reached 99.87% at 20 h. The release of cefalexin was basically complete. In simulated gastric fluid, composite material sustained-release ended at 4 h, the cumulative sustained release ratio reaching 26.10%. In simulated gastric fluid, the sustained-release was complete at 7 h, the cumulative sustained release ratio reaching 32.46%. The composite material of SBA-15 and cefalexin

  13. Sustainability in Business

    DEFF Research Database (Denmark)

    Tollin, Karin; Vej, Jesper

    2012-01-01

    How do companies integrate sustainability into their strategy and practices, and what factors explain their approach? In this paper a typology of sustainability strategies is presented as well as a conceptual framework relating sustainability at the company level to the functional level of market...... managers' mindsets, a framework addressing sustainability from four organisational learning schools was designed and followed......How do companies integrate sustainability into their strategy and practices, and what factors explain their approach? In this paper a typology of sustainability strategies is presented as well as a conceptual framework relating sustainability at the company level to the functional level...... of marketing. The central contribution of the typology is a strategic and managerial view on sustainability. Furthermore, the typology shows that sustainability in business is enacted from different areas of competences and fields in the literature (e.g. supply chain management, corporate branding, value...

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

    Science.gov (United States)

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

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

  15. The 2017 Release Cloudy

    Science.gov (United States)

    Ferland, G. J.; Chatzikos, M.; Guzmán, F.; Lykins, M. L.; van Hoof, P. A. M.; Williams, R. J. R.; Abel, N. P.; Badnell, N. R.; Keenan, F. P.; Porter, R. L.; Stancil, P. C.

    2017-10-01

    We describe the 2017 release of the spectral synthesis code Cloudy, summarizing the many improvements to the scope and accuracy of the physics which have been made since the previous release. Exporting the atomic data into external data files has enabled many new large datasets to be incorporated into the code. The use of the complete datasets is not realistic for most calculations, so we describe the limited subset of data used by default, which predicts significantly more lines than the previous release of Cloudy. This version is nevertheless faster than the previous release, as a result of code optimizations. We give examples of the accuracy limits using small models, and the performance requirements of large complete models. We summarize several advances in the H- and He-like iso-electronic sequences and use our complete collisional-radiative models to establish the densities where the coronal and local thermodynamic equilibrium approximations work.

  16. EIA new releases

    International Nuclear Information System (INIS)

    1994-09-01

    This report is a compliation of news releases from the Energy Information Administration. The september-october report includes articles on energy conservation, energy consumption in commercial buildings, and a short term energy model for a personal computer

  17. Sellafield (release of radioactivity)

    Energy Technology Data Exchange (ETDEWEB)

    Cunningham, J; Goodlad, A; Morris, M

    1986-02-06

    A government statement is reported, about the release of plutonium nitrate at the Sellafield site of British Nuclear Fuels plc on 5 February 1986. Matters raised included: details of accident; personnel monitoring; whether radioactive material was released from the site; need for public acceptance of BNFL activities; whether plant should be closed; need to reduce level of radioactive effluent; number of incidents at the plant.

  18. Sustainable Table | Welcome to Sustainable Table

    Science.gov (United States)

    Sustainable Seafood Industrial Agriculture Industrial Livestock Production Antibiotics Hormones rBGH Animal , safeguarding animal welfare and supporting local communities. Questions to Ask Asking questions is the best way Livestock Husbandry Sustainable Crop Production Innovative Agriculture New Farmers Organic Agriculture Local

  19. Education for sustainable development

    DEFF Research Database (Denmark)

    Breiting, Søren

    2009-01-01

     An introduction to the idea of sustainable development (SD) and education for sustainable development (ESD) with reference to the international Decade for Education for Sustainable Development . The chapter includes a focus on conflicting interests between present and future generations related ...... to the use of natural resources and other matters, and how that kind of issues can be dealt with in education as ESD....... An introduction to the idea of sustainable development (SD) and education for sustainable development (ESD) with reference to the international Decade for Education for Sustainable Development . The chapter includes a focus on conflicting interests between present and future generations related...

  20. Smart Sustainable Islands VS Smart Sustainable Cities

    Science.gov (United States)

    Pantazis, D. N.; Moussas, V. C.; Murgante, B.; Daverona, A. C.; Stratakis, P.; Vlissidis, N.; Kavadias, A.; Economou, D.; Santimpantakis, K.; Karathanasis, B.; Kyriakopoulou, V.; Gadolou, E.

    2017-09-01

    This paper has several aims: a) the presentation of a critical analysis of the terms "smart sustainable cities" and "smart sustainable islands" b) the presentation of a number of principles towards to the development methodological framework of concepts and actions, in a form of a manual and actions guide, for the smartification and sustainability of islands. This kind of master plan is divided in thematic sectors (key factors) which concern the insular municipalities c) the creation of an island's smartification and sustainability index d) the first steps towards the creation of a portal for the presentation of our smartification actions manual, together with relative resources, smart applications examples, and, in the near future the first results of our index application in a number of Greek islands and e) the presentation of some proposals of possible actions towards their sustainable development and smartification for the municipalities - islands of Paros and Antiparos in Greece, as case studies.

  1. Conceptualising sustainability assessment

    International Nuclear Information System (INIS)

    Pope, Jenny; Annandale, David; Morrison-Saunders, Angus

    2004-01-01

    Sustainability assessment is being increasingly viewed as an important tool to aid in the shift towards sustainability. However, this is a new and evolving concept and there remain very few examples of effective sustainability assessment processes implemented anywhere in the world. Sustainability assessment is often described as a process by which the implications of an initiative on sustainability are evaluated, where the initiative can be a proposed or existing policy, plan, programme, project, piece of legislation, or a current practice or activity. However, this generic definition covers a broad range of different processes, many of which have been described in the literature as 'sustainability assessment'. This article seeks to provide some clarification by reflecting on the different approaches described in the literature as being forms of sustainability assessment, and evaluating them in terms of their potential contributions to sustainability. Many of these are actually examples of 'integrated assessment', derived from environmental impact assessment (EIA) and strategic environmental assessment (SEA), but which have been extended to incorporate social and economic considerations as well as environmental ones, reflecting a 'triple bottom line' (TBL) approach to sustainability. These integrated assessment processes typically either seek to minimise 'unsustainability', or to achieve TBL objectives. Both aims may, or may not, result in sustainable practice. We present an alternative conception of sustainability assessment, with the more ambitious aim of seeking to determine whether or not an initiative is actually sustainable. We term such processes 'assessment for sustainability'. 'Assessment for sustainability' firstly requires that the concept of sustainability be well-defined. The article compares TBL approaches and principles-based approaches to developing such sustainability criteria, concluding that the latter are more appropriate, since they avoid many

  2. Fabrication and characterization of a rapid prototyped tissue engineering scaffold with embedded multicomponent matrix for controlled drug release

    DEFF Research Database (Denmark)

    Chen, Muwan; Le, Dang Q S; Hein, San

    2012-01-01

    Bone tissue engineering implants with sustained local drug delivery provide an opportunity for better postoperative care for bone tumor patients because these implants offer sustained drug release at the tumor site and reduce systemic side effects. A rapid prototyped macroporous polycaprolactone......, this scaffold can fulfill the requirements for both bone tissue engineering and local sustained release of an anticancer drug in vitro. These results suggest that the scaffold can be used clinically in reconstructive surgery after bone tumor resection. Moreover, by changing the composition and amount...... of individual components, the scaffold can find application in other tissue engineering areas that need local sustained release of drug....

  3. Handbook of sustainable engineering

    CERN Document Server

    Lee, Kun-Mo

    2013-01-01

    "The efficient utilization of energy, sustainable use of natural resources, and large-scale adoption of sustainable technologies is the key to a sustainable future. The Handbook of Sustainable Engineering provides tools that will help us achieve these goals". Nobel Prize Winner Dr. R.K. Pauchauri, Chairman, UN Intergovernmental Panel on Climate Change As global society confronts the challenges of diminishing resources, ecological degradation, and climate change, engineers play a crucial role designing and building technologies and products that fulfil our needs for utility and sustainability. The Handbook of Sustainable Engineering equips readers with the context and the best practices derived from both academic research and practical examples of successful implementations of sustainable technical solutions. The handbook’s content revolves around the two themes, new ways of thinking and new business models, including sustainable production, products, service systems and consumption while addressing key asse...

  4. Sustainable Water Infrastructure

    Science.gov (United States)

    Resources for state and local environmental and public health officials, and water, infrastructure and utility professionals to learn about sustainable water infrastructure, sustainable water and energy practices, and their role.

  5. Sustainable development. First part

    International Nuclear Information System (INIS)

    Colombo, U.; Lanzavecchia, G.; Berrini, M; Zambrini, M.; Bologna, G.; Carraro, C.; Hinterberger, F.; Mastino, G.; Federico, A.; Gaudioso, D.; Luise, A.; Mauro, F.; Padovani, L.; Federico, A.

    1998-01-01

    This paper summarizes a collective effort and represents the second edition of: Environment, energy, economy: a sustainable future. In this work are reported various interventions on sustainable development problem [it

  6. Sustainable Public Bids

    Directory of Open Access Journals (Sweden)

    Gil César Costa de Paula

    2016-06-01

    Full Text Available In this article we will discuss the issue of sustainability in public procurement, given that the government in Brazil is constituted as a great promoter of economic development and needs to adapt its acquisitions worldwide sustainability agenda.

  7. Neighbourhood facilities for sustainability

    CSIR Research Space (South Africa)

    Gibberd, Jeremy T

    2013-01-01

    Full Text Available . In this paper these are referred to as ‘Neighbourhood Facilities for Sustainability’. Neighbourhood Facilities for Sustainability (NFS) are initiatives undertaken by individuals and communities to build local sustainable systems which not only improve...

  8. FORUM: Is Ecotourism Sustainable?

    Science.gov (United States)

    Wall

    1997-07-01

    / It is legitimate to ask whether and in what form tourism might contribute to sustainable development. This is not the same as sustainable tourism which, as a single-sector approach to development, may overlook important linkages with other sectors. If tourism is to contribute to sustainable development, then it must be economically viable, ecologically sensitive and culturally appropriate. Ecotourism is often advocated as being a sustainable form of tourism but imprecision in terminology clouds basic issues and there are strong economic, ecological, and cultural reasons for believing that, even in its purest forms, ecotourism is likely to present substantial challenges to destination areas, particularly if it competes for scarce resources and displaces existing uses and users. Sustainable tourism and ecotourism are not synonyms, many forms of ecotourism may not be sustainable, and if ecotourism is to contribute to sustainable development, then careful planning and management will be required.KEY WORDS: Ecotourism; Sustainable development; Development; Tourism

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

    Science.gov (United States)

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

    2011-01-01

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

  10. 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.

  11. ATP Release Channels

    Directory of Open Access Journals (Sweden)

    Akiyuki Taruno

    2018-03-01

    Full Text Available Adenosine triphosphate (ATP has been well established as an important extracellular ligand of autocrine signaling, intercellular communication, and neurotransmission with numerous physiological and pathophysiological roles. In addition to the classical exocytosis, non-vesicular mechanisms of cellular ATP release have been demonstrated in many cell types. Although large and negatively charged ATP molecules cannot diffuse across the lipid bilayer of the plasma membrane, conductive ATP release from the cytosol into the extracellular space is possible through ATP-permeable channels. Such channels must possess two minimum qualifications for ATP permeation: anion permeability and a large ion-conducting pore. Currently, five groups of channels are acknowledged as ATP-release channels: connexin hemichannels, pannexin 1, calcium homeostasis modulator 1 (CALHM1, volume-regulated anion channels (VRACs, also known as volume-sensitive outwardly rectifying (VSOR anion channels, and maxi-anion channels (MACs. Recently, major breakthroughs have been made in the field by molecular identification of CALHM1 as the action potential-dependent ATP-release channel in taste bud cells, LRRC8s as components of VRACs, and SLCO2A1 as a core subunit of MACs. Here, the function and physiological roles of these five groups of ATP-release channels are summarized, along with a discussion on the future implications of understanding these channels.

  12. Sustainability Statement and Policy

    Science.gov (United States)

    Journal of Education for Sustainable Development, 2009

    2009-01-01

    This article presents nine resources that focus on environmental education and sustainability. These include: (1) "Sustainability Statement and Policy," Dalhousie University, Nova Scotia, Canada, 2009, which is available at http://office.sustainability.dal.ca/Governance; (2) "Climate Literacy: The Essential Principles of Climate…

  13. The sustainable development

    International Nuclear Information System (INIS)

    2004-01-01

    In the framework of the sustainable development week (june 2003), Actu Environnement published a complete document on the sustainable development to inform the public, recall the main steps of this notion (Rio conference and the following conferences) and the possible employments. It presents also the main organizations acting in the sustainable development domain. (A.L.B.)

  14. Toward sustainable logistics

    NARCIS (Netherlands)

    Soysal, Mehmet; Bloemhof-Ruwaard, Jacqueline M.

    2017-01-01

    The fast evolution of sustainability leads to the development of a new fast-growing concept called sustainable logistics management. This research addresses recent business trends and challenges in logistics and their implications for sustainable logistics management. Additionally, we discuss policy

  15. ORNL Annual Sustainability Report

    Energy Technology Data Exchange (ETDEWEB)

    Lapsa, Melissa Voss [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Nichols, Teresa A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2014-02-01

    As described in this report, we have made substantial progress across the 25 roadmaps of the Sustainable Campus Initiative. The report also outlines our plans to continue integrating sustainable practices into the planning, execution, and evaluation of all ORNL activities. We appreciate your interest in our journey to sustainability, and we welcome your comments, questions, and suggestions.

  16. Toward sustainable logistics

    NARCIS (Netherlands)

    Soysal, Mehmet; Bloemhof-Ruwaard, Jacqueline M.

    2018-01-01

    The fast evolution of sustainability leads to the development of a new fast-growing concept called sustainable logistics management. This research addresses recent business trends and challenges in logistics and their implications for sustainable logistics management. Additionally, we discuss policy

  17. Sustainable Learning Organizations

    Science.gov (United States)

    Velazquez, Luis E.; Esquer, Javier; Munguia, Nora E.; Moure-Eraso, Rafael

    2011-01-01

    Purpose: The purpose of this paper is to debate how companies may better become a sustainable learning organization by offering the most used and insightful concepts of sustainability. Design/methodology/approach: Through literature review, learning organization and sustainability perspectives are explored and compared. Findings: Learning…

  18. RAVEN Beta Release

    International Nuclear Information System (INIS)

    Rabiti, Cristian; Alfonsi, Andrea; Cogliati, Joshua Joseph; Mandelli, Diego; Kinoshita, Robert Arthur; Wang, Congjian; Maljovec, Daniel Patrick; Talbot, Paul William

    2016-01-01

    This documents the release of the Risk Analysis Virtual Environment (RAVEN) code. A description of the RAVEN code is provided, and discussion of the release process for the M2LW-16IN0704045 milestone. The RAVEN code is a generic software framework to perform parametric and probabilistic analysis based on the response of complex system codes. RAVEN is capable of investigating the system response as well as the input space using Monte Carlo, Grid, or Latin Hyper Cube sampling schemes, but its strength is focused toward system feature discovery, such as limit surfaces, separating regions of the input space leading to system failure, using dynamic supervised learning techniques. RAVEN has now increased in maturity enough for the Beta 1.0 release.

  19. RAVEN Beta Release

    Energy Technology Data Exchange (ETDEWEB)

    Rabiti, Cristian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Alfonsi, Andrea [Idaho National Lab. (INL), Idaho Falls, ID (United States); Cogliati, Joshua Joseph [Idaho National Lab. (INL), Idaho Falls, ID (United States); Mandelli, Diego [Idaho National Lab. (INL), Idaho Falls, ID (United States); Kinoshita, Robert Arthur [Idaho National Lab. (INL), Idaho Falls, ID (United States); W