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Sample records for sustained release formulations

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

    African Journals Online (AJOL)

    Conclusion: Microballoons is a potential suitable delivery system for sustained release of metformin hydrochloride with improved bioavailability when compared with conventional dosage forms of the drug. Keywords: Gastroretentive drug delivery system (GDDS), Solvent evaporation and diffusion method, Higuchi, ...

  2. Formulation and evaluation of sustained release paracetamol ...

    African Journals Online (AJOL)

    From the dissolution data of the eight tablet formulations that resulted from the experimental design, a polynomial regression equation was generated from which an optimum formulation was obtained. Three different batches of granules of the \\'optimum formulation\\' were compressed into tablets at a compression force of 15 ...

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

    African Journals Online (AJOL)

    SEM images of the tablets before and after dissolution showed some morphological changes on the tablet surface while FTIR and DSC thermogram studies confirmed ... Conclusion: The results of the study demonstrate that modified karaya gum is a potential matrix material for formulating suitable sustained-release matrix ...

  4. Nanoparticle-based topical ophthalmic formulations for sustained celecoxib release.

    Science.gov (United States)

    Ibrahim, Mohammed Mostafa; Abd-Elgawad, Abd-Elgawad Helmy; Soliman, Osama Abd-Elazeem; Jablonski, Monica M

    2013-03-01

    Celecoxib-loaded NPs were prepared from biodegradable polymers such as poly-ε-caprolactone (PCL), poly(L-lactide) (PLA), and poly(D,L-lactide-co-glycolide) (PLGA) by spontaneous emulsification solvent diffusion method. Different concentrations of polymers, emulsifier, and cosurfactants were used for formulation optimization. Nanoparticles (NPs) were characterized regarding their particle size, PDI, zeta potential, shape, morphology, and drug content. Celecoxib-loaded NPs were incorporated into eye drops, in situ gelling system, and gel and characterized regarding their pH, viscosity, uniformity of drug content, in vitro release, and cytotoxicity. The results of optimized celecoxib-loaded PCL-, PLGA-, and PLA-NPs, respectively, are particle size 119 ± 4, 126.67 ± 7.08, and 135.33 ± 4.15 nm; zeta potential -22.43 ± 2.91, -25.46 ± 2.35, and -31.81 ± 2.54 mV; and encapsulation efficiency 93.44 ± 3.6%, 86.00 ± 1.67%, and 79.04 ± 2.6%. TEM analyses revealed that NPs have spherical shapes with dense core and distinct coat. Formulations possessed uniform drug content with pH and viscosity compatible with the eye. Formulations showed sustained release without any burst effect with the Higuchi non-fickian diffusion mechanism. Cytotoxicity studies revealed that all formulations are nontoxic. Our formulations provide a great deal of flexibility to formulation scientist whereby sizes and zeta potentials of our NPs can be tuned to suit the need using scalable and robust methodologies. These formulations can thus serve as a potential drug delivery system for both anterior and posterior eye diseases. Copyright © 2012 Wiley Periodicals, Inc.

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

    African Journals Online (AJOL)

    Matrix tablets of DTZ were prepared using varying ratios of unmodified karaya gum (K) and MK by direct compression. The matrix tablets were evaluated for pharmacotechnical properties and in vitro release, including release kinetics. The optimized formulation was compared with Dilzem SR which served as reference.

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

    African Journals Online (AJOL)

    HP

    2012-02-23

    Feb 23, 2012 ... appears simple, but in reality, the release pattern is a complex phenomenon. At the molecular level, it ... The drug is thus a suitable model candidate for sustained drug delivery [12]. The objective of the .... anomalous transport (non-Fickian) refers to a combination of both diffusion and erosion controlled-drug ...

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

    African Journals Online (AJOL)

    Erah

    characterized by scanning electron microscopy (SEM), Fourier transform infra-red spectroscopy (FTIR) and differential scanning calorimetry (DSC). Results: Tablets with MK showed higher mean ..... Park CR, Munday DL. Evaluation of selected polysaccharide excipients in buccoadhesive tablets for sustained release of ...

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

    African Journals Online (AJOL)

    Methods: Matrix tablets of DTZ were prepared at different ratios of drug:gum (1:1, 1:2, and 1:4) and of the gum blends (K, K/LB, K/H and K/LB/H) by direct compression. The matrix tablets were evaluated for hardness, friability, in vitro release and drug content. The formulations were also characterised by scanning electron ...

  9. Pharmacokinetics and in vivo scintigraphic monitoring of a sustained release acetylsalicylic acid formulation

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, C.G.; Hardy, J.C. (Queen' s Medical Centre, Nottingham (UK)); Parr, G.D.; Kennerley, J.W.; Taylor, M.J.; Davis, S.S. (Nottingham Univ. (UK)); Rees, J.A. (Boots Research Laboratories, Nottingham (UK))

    1984-01-01

    The in vivo dissolution and pharmacokinetics of a sustained release aspirin formulation labelled with (sup(99m)Tc)diethylenetriaminepentaacetic acid has been monitored in 5 subjects by the use of gamma scintigraphy and drug analysis undertaken of blood and urine samples. The data obtained enabled the position of the tablet in vivo to be related to the plasma and urinary salicylate levels. The study confirms the sustained release properties of the cellulose acetate phthalate formulation.

  10. 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/O1 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.

  11. 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

  12. 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

    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. In conclusion

  13. Formulation and evaluation of sustained release enteric-coated pellets of budesonide for intestinal delivery.

    Science.gov (United States)

    Raval, Mihir K; Ramani, Riddhi V; Sheth, Navin R

    2013-10-01

    The aim of present work was to develop intestinal-targeted pellets of Budesonide, a potent glucocorticoid, used for the treatment of ulcerative colitis and Crohn's disease by extrusion and spheronization method. Current available oral formulations of Budesonide have low efficacy because of the premature drug release in the upper part of the gastrointestinal tract. In this study, a pH-controlled intestinal-targeted pellet of budesonide was established using 3(2) full factorial design by giving an enteric coating with Eudragit S100. Budesonide-sustained release pellets were prepared by extruder and spheronization technique using a combination of water-soluble and permeable polymers by applying 3(2) full factorial design. The pellets were coated by spray coating technique using Eudragit S100 as an enteric polymer. The pellets were characterized for its flowability, sphericity, friability, and in vitro drug release. Release behaviour was studied in different pH media. The release profile was studied for the mechanism of drug release. The optimized formulation showed negligible drug release in the stomach followed by release for 12 h in the intestinal pH. Differential scanning calorimetry and Fourier Transform Infrared Spectroscopy studies indicated no interaction between drug and polymer. Scanning Electron Microscopy image of coated pellets suggested a uniform and smooth coat over the surface of pellets. Accelerated stability studies showed a stable nature of drug in the formulation. All evaluation parameter showed that pellets were good in spherocity and flowability. Sustained release pellets of Budesonide could be prepared by extrusion and spheronization which released the drug in intestinal pH for an intestine to treat inflammatory bowel disease. A ratio of polymer combination could be decided using a full factorial design.

  14. Compression of coated drug beads for sustained release tablet of glipizide: formulation, and dissolution.

    Science.gov (United States)

    Nguyen, Chien; Christensen, J Mark; Ayres, James W

    2014-02-01

    A promising glipizide formulation comprising compression of four-layer coated beads into tablets was prepared. The tablet offered the advantages of: a two-hour lag time before drug release, retaining sustained release characteristics and providing approximately zero-order drug release. Drug release was nearly independent of paddle speeds of 50 and 100 rpm releasing 80% over 14 h similar to the commercial glipizide osmotic pump tablet during dissolution testing while keeping the benefits of multiparticular dosage forms. The tablets contain beads with four layers: (1) the innermost layer consists of 2.5 g glipizide and 3.75 g solid ethylcellulose (Surelease®) coated onto 71.25 g of sugar beads; (2) next a hardening layer of 5 g of hypromellose; (3) the controlled release layer of 7.5 g of Surelease®:lactose at a solids ratio of 100:7 and (4) an outermost layer of 20 g of lactose:sodium starch glycolate (Explotab®) at a 2:1 ratio. Then, beads were compressed into tablets containing 11 mg of glipizide using 1500 lbs of compression pressure. The dissolution test similarity factor (f2) was above 50 for all test conditions for formulation F13 and Glucotrol® with a high of 69.9. The two Surelease® layers both aid controlling drug release, with the Surelease®-drug layer affecting drug release to a greater extent.

  15. Selection of 12-Hour Sustained-Release Acetaminophen (Paracetamol) Formulation Through Comparison of Pharmacokinetic Profiles of 4 Sustained-Release Prototype Formulations and Standard Acetaminophen Formulation: An Open-Label, Randomized, Proof-of-Principle Pharmacokinetic Study.

    Science.gov (United States)

    Yue, Yong; Liu, Dongzhou J

    2017-08-16

    Acetaminophen (APAP; paracetamol), a widely used analgesic and antipyretic, is available in modified-release and immediate-release (IR) formulations requiring 3- or 4-times-daily dosing. This phase 1 open-label crossover study compared pharmacokinetic profiles of single 2000-mg doses of 4 different sustained-release (SR) formulations of APAP (designed to allow twice-daily dosing) against two 1000-mg doses (taken 6 hours apart) of standard IR APAP in 14 healthy volunteers. The primary end point was duration of time that plasma APAP concentration exceeded a plasma concentration (TC ) of 4 μg/mL. Of the 4 SR APAP formulations studied, a single 2000-mg dose of a bilayer SR formulation had the longest mean TC>4μg/mL (8.1 hours), similar to that of 2 doses of IR APAP (8.3 hours). Mean TC>4μg/mL was 7.3 hours with a single-layer SR APAP, 7.5 hours with another single-layer SR APAP formulation using a different excipient, and 7.1 hours with an enteric-coated SR APAP coupled with a fast-dissolving IR APAP. Secondary pharmacokinetic analyses showed a similar extent of absorption and lower peak concentration for the bilayer SR formulation compared with IR APAP. Adverse events were all mild. Based on these results, the bilayer SR APAP formulation was selected for further development. © 2017, The American College of Clinical Pharmacology.

  16. Transformations of Nanoenabled Copper Formulations Govern Release, Antifungal Effectiveness, and Sustainability throughout the Wood Protection Lifecycle.

    Science.gov (United States)

    Pantano, Daniele; Neubauer, Nicole; Navratilova, Jana; Scifo, Lorette; Civardi, Chiara; Stone, Vicki; von der Kammer, Frank; Müller, Philipp; Sobrido, Marcos Sanles; Angeletti, Bernard; Rose, Jerome; Wohlleben, Wendel

    2018-02-06

    Here we compare the standard European benchmark of wood treatment by molecularly dissolved copper amine (Cu-amine), also referred to as aqueous copper amine (ACA), against two nanoenabled formulations: copper(II)oxide nanoparticles (CuO NPs) in an acrylic paint to concentrate Cu as a barrier on the wood surface, and a suspension of micronized basic copper carbonate (CuCO 3 ·Cu(OH) 2 ) for wood pressure treatment. After characterizing the properties of the (nano)materials and their formulations, we assessed their effects in vitro against three fungal species: Coniophora puteana, Gloeophyllum trabeum, and Trametes versicolor, finding them to be mediated only partially by ionic transformation. To assess the use phase, we quantify both release rate and form. Cu leaching rates for the two types of impregnated wood (conventional and nanoenabled) are not significantly different at 172 ± 6 mg/m 2 , with Cu being released predominantly in ionic form. Various simulations of outdoor aging with release sampling by runoff, during condensation, by different levels of mechanical shear, all resulted in comparable form and rate of release from the nanoenabled or the molecular impregnated woods. Because of dissolving transformations, the nanoenabled impregnation does not introduce additional concern over and above that associated with the traditional impregnation. In contrast, Cu released from wood coated with the CuO acrylate contained particles, but the rate was at least 100-fold lower. In the same ranking, the effectiveness to protect against the wood-decaying basidiomycete Coniophora puteana was significant with both impregnation technologies but remained insignificant for untreated wood and wood coated by the acrylic CuO. Accordingly, a lifecycle-based sustainability analysis indicates that the CuO acrylic coating is less sustainable than the technological alternatives, and should not be developed into a commercial product.

  17. A formulation approach for development of HPMC-based sustained release tablets for tolterodine tartrate with a low release variation

    DEFF Research Database (Denmark)

    Cao, Qing-Ri; Choi, Jae-Seung; Liu, Yan

    2013-01-01

    Objective: The purpose of this study was to develop hydroxypropylmethylcellulose (HPMC)-based sustained release (SR) tablets for tolterodine tartrate with a low drug release variation. Methods: The SR tablets were prepared by formulating a combination of different grades of HPMC as the gelling...... agents. The comparative dissolution study for the HPMC-based SR tablet as a test and Detrusitol(®) SR capsule as a reference was carried out, and the bioequivalence study of the two products was also conducted in human volunteers. Results: The amount of HPMC, the grade of HPMC and the combination ratio...... of different grades of HPMC had remarkable effects on drug release from the SR tablets. Both the test and reference products had no significant difference in terms of comparative dissolution patterns in four different media (f(2) > 50). Furthermore, the dissolution method and rotation speed showed no effects...

  18. Development and characterization of gastroretentive sustained-release formulation by combination of swelling and mucoadhesive approach: a mechanistic study.

    Science.gov (United States)

    Sankar, R; Jain, Subheet Kumar

    2013-01-01

    Acyclovir has pharmacokinetic limitations, including poor oral bioavailability of 15%-30%, high variability, and short elimination half-life of 2.3 hours. These limitations necessitate frequent administration of acyclovir, up to five times daily, leading to poor patient compliance, which in turn leads to a reduction in therapeutic efficacy and development of resistance. A gastroretentive sustained-release (GR) formulation of acyclovir, based on a combination of swelling and mucoadhesive mechanisms, has been developed. Composition has been optimized after evaluation of different polymers, carbomer, polyethylene oxide, and sodium alginate alone and/or in combination. GR formulations were characterized for in-process quality-control tests, drug release and release rate kinetics, similarity factor analysis, swelling index, and matrix erosion. A formulation containing a combination of carbomer and polyethylene oxide had the highest similarity of drug release compared with a target drug-release profile obtained by pharmacokinetic simulations. The measurement of mucoadhesive strength, carried out with a texture analyzer, showed that the mucoadhesive strength of the GR formulation was significantly higher than that of the immediate-release (IR) tablet. The optimized GR formulation was found to be retained in the upper part of the gastrointestinal tract for 480 minutes; the IR tablet was retained for only 90 minutes as measured using a gastrointestinal retention study in albino rabbits. The GR formulation was also found to maintain more sustained plasma concentrations than the IR tablet. Mean residence time of the GR formulation was 7 hours versus 3.3 hours for the IR formulation. The relative bioavailability of the GR formulation was 261% of the IR formulation. The GR formulation of acyclovir, based on swelling and mucoadhesive mechanisms, has prolonged retention in the upper gastrointestinal tract, sustained in vitro drug release, prolonged in vivo absorption, and better

  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. Formulating nanoparticles by flash nanoprecipitation for drug delivery and sustained release

    Science.gov (United States)

    Liu, Ying

    This dissertation provides a fundamental understanding of the process for generating nanoparticles with controlled size distribution and of predicting nanoparticle stability for drug delivery and sustained release. We developed and characterized a novel technology to generate organic and inorganic nanoparticles protected by biocompatible and biodegradable polymers with precisely controlled size and size distribution. Computational fluid mechanics (CFD) together with experimental results provided details of the micromixing in the mixer. The particle size dependence on Reynolds number and supersaturation was illustrated. The study of the fundamental mass transfer phenomena leading to Ostwald ripening enables quantitative prediction of the time evolution of nanoparticles with monodistribution and relatively broader multi-distribution using beta-carotene and polystyrene-b-poly(ethylene oxide) (PS-b-PEO) as a model system. Negatively charged latex particles were used to exam the attachment of the diblock copolymer, PS-b-PEO, on the surface. The stability provided by the Columbic repulsion was replaced by steric stabilization. The attachment of the block copolymers on the surface of the colloids depends on the flow field, i.e. Reynolds number, of the mixing process. The slow degradation of poly(epsilon-caprolactone) (PCL) and poly(gamma-methyl-epsilon-caprolactone) (PMCL) was demonstrated. The slow degradation ensures long-term stability and long-term blood circulation of the polymeric nanoparticles. As a practical application, we formulate the anti-tuberculosis drug, rifampicin, into nanoparticles by conjugation to other hydrophobic molecules (such as vitamin E, PCL and 2-ethylhexyl vinyl ether) by pH sensitive cleavable chemical bonds to increase the drug loading, return stability of the nanoparticle suspension, and control drug release. The in vitro release profiles were provided by using HPLC and E.coli growth inhibition on LB agar plates. The prodrug nanoparticle

  1. Psyllium: a promising polymer for sustained release formulations in combination with HPMC polymers.

    Science.gov (United States)

    Kaialy, Waseem; Emami, Parastou; Asare-Addo, Kofi; Shojaee, Saeed; Nokhodchi, Ali

    2014-05-01

    Psyllium has a mucilaginous property that makes it a good candidate to be utilized as an excipient in the preparation of controlled release systems. Various formulations were prepared using theophylline as a model drug and investigated with a view to achieve an ideal slow drug release profile. The addition of hydroxypropyl methylcellulose (HPMC) to psyllium significantly reduced the burst release; however, the percentage of drug release within a 12 h period was too slow and thereby inadequate. This was overcome by the addition of lactose as a hydrophilic filler that enabled a slow release with roughly 80% drug release in 12 h. The inclusion of HPMC within psyllium formulations changed the drug release kinetics from Fickian diffusion to anomalous transport. Granulated formulations demonstrated slower drug release than ungranulated or physical mixture and caused a change in the dissolution kinetics from Fickian diffusion to anomalous transport. Milled granules showed more efficient controlled drug release with no burst release. Milling of the granules also changed the drug release kinetics to anomalous transport. Although psyllium was proved to be a promising polymer to control the drug release, a combination of psyllium-HPMC and formulation processes should be considered in an attempt to achieve a zero-order release.

  2. Formulation Design, Optimization and Pharmacodynamic Evaluation of Sustained Release Mucoadhesive Microcapsules of Venlafaxine HCl.

    Science.gov (United States)

    Swain, S; Behera, A; Dinda, S C; Patra, C N; Jammula, Sruti; Beg, S; Rao, M E B

    2014-07-01

    The objective of present research work was to design and characterize the venlafaxine HCl-loaded sodium alginate-based mucoadhesive microcapsules by ionic gelation technique using HPMC K100M as mucoadhesive polymer. The Placket-Burman Design was applied for preliminary screening of the formulations and systematic optimization by using Box-Behnken Design. The prepared microcapsules were characterized for drug content, entrapment efficiency, micromeritic properties, particle size, swelling index, mucoadhesive strength, in vitro drug release and in vivo antidepressant activity. FTIR and differential scanning calorimetry studies showed no incompatibility. Surface morphology studies revealed spherical nature of the prepared microcapsules. In vitro drug release studies revealed sustained release by diffusion mechanism. Further, the microcapsules were effective in reducing the depression induced by forced swimming test in Sprague-Dawley rats compared to the pure drug. The microcapsules were found to be stable under accelerated stability conditions, which suggest them as better alternative delivery systems for enhanced therapeutic efficacy of antidepressant drug, venlafaxine HCl.

  3. Nanoparticle-based topical ophthalmic formulation for sustained release of stereoisomeric dipeptide prodrugs of ganciclovir.

    Science.gov (United States)

    Yang, Xiaoyan; Shah, Sujay J; Wang, Zhiying; Agrahari, Vibhuti; Pal, Dhananjay; Mitra, Ashim K

    2016-09-01

    Poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles (NP) of Val-Val dipeptide monoester prodrugs of ganciclovir (GCV) including L-Val-L-Val-GCV (LLGCV), L-Val-D-Val-GCV (LDGCV) and D-Val-L-Val-GCV (DLGCV) were formulated and dispersed in thermosensitive PLGA-PEG-PLGA polymer gel for the treatment of herpes simplex virus type 1 (HSV-1)-induced viral corneal keratitis. Nanoparticles containing prodrugs of GCV were prepared by a double-emulsion solvent evaporation technique using various PLGA polymers with different drug/polymer ratios. Nanoparticles were characterized with respect to particle size, entrapment efficiency, polydispersity, drug loading, surface morphology, zeta potential and crystallinity. Prodrugs-loaded NP were incorporated into in situ gelling system. These formulations were examined for in vitro release and cytotoxicity. The results of optimized entrapment efficiencies of LLGCV-, LDGCV- and DLGCV-loaded NP are of 38.7 ± 2.0%, 41.8 ± 1.9%, and 45.3 ± 2.2%; drug loadings 3.87 ± 0.20%, 2.79 ± 0.13% and 3.02 ± 0.15%; yield 85.2 ± 3.0%, 86.9 ± 4.6% and 76.9 ± 2.1%; particle sizes 116.6 ± 4.5, 143.0 ± 3.8 and 134.1 ± 5.2 nm; and zeta potential -15.0 ± 4.96, -13.8 ± 5.26 and -13.9 ± 5.14 mV, respectively. Cytotoxicity studies suggested that all the formulations are non-toxic. In vitro release of prodrugs from NP showed a biphasic release pattern with an initial burst phase followed by a sustained phase. Such burst effect was completely eliminated when NP were suspended in thermosensitive gels with near zero-order release kinetics. Prodrugs-loaded PLGA NP dispersed in thermosensitive gels can thus serve as a promising drug delivery system for the treatment of anterior eye diseases.

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

    African Journals Online (AJOL)

    HP

    2013-07-15

    Jul 15, 2013 ... Purpose: To develop and optimise sustained release (SR) matrix tablets of diltiazem hydrochloride (DHL). Methods: ... Keywords: Diltiazem, Matrix tablet, Hydroxypropyl methylcellulose Eudragit, In vitro/in vivo correlation, Optimization. Tropical ..... Makhija S, Vavia P. Once daily sustained release tablets.

  5. Development and characterization of gastroretentive sustained-release formulation by combination of swelling and mucoadhesive approach: a mechanistic study

    Directory of Open Access Journals (Sweden)

    Sankar R

    2013-12-01

    Full Text Available R Sankar,1 Subheet Kumar Jain1,2 1Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India; 2Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, India Background: Acyclovir has pharmacokinetic limitations, including poor oral bioavailability of 15%–30%, high variability, and short elimination half-life of 2.3 hours. These limitations necessitate frequent administration of acyclovir, up to five times daily, leading to poor patient compliance, which in turn leads to a reduction in therapeutic efficacy and development of resistance. Methods: A gastroretentive sustained-release (GR formulation of acyclovir, based on a combination of swelling and mucoadhesive mechanisms, has been developed. Composition has been optimized after evaluation of different polymers, carbomer, polyethylene oxide, and sodium alginate alone and/or in combination. GR formulations were characterized for in-process quality-control tests, drug release and release rate kinetics, similarity factor analysis, swelling index, and matrix erosion. Results: A formulation containing a combination of carbomer and polyethylene oxide had the highest similarity of drug release compared with a target drug-release profile obtained by pharmacokinetic simulations. The measurement of mucoadhesive strength, carried out with a texture analyzer, showed that the mucoadhesive strength of the GR formulation was significantly higher than that of the immediate-release (IR tablet. The optimized GR formulation was found to be retained in the upper part of the gastrointestinal tract for 480 minutes; the IR tablet was retained for only 90 minutes as measured using a gastrointestinal retention study in albino rabbits. The GR formulation was also found to maintain more sustained plasma concentrations than the IR tablet. Mean residence time of the GR formulation was 7 hours versus 3.3 hours for the IR formulation. The relative

  6. Formulation and In-vitro Characterization of Sustained Release Matrix Type Ocular Timolol Maleate Mini-Tablet

    OpenAIRE

    Mortazavi, Seyed Alireza; Jafariazar, Zahra; Ghadjahani, Yasaman; Mahmoodi, Hoda; Mehtarpour, Farzaneh

    2014-01-01

    The purpose of this study was preparation and evaluation of sustained release matrix type ocular mini-tablets of timolol maleate, as a potential formulation for the treatment of glaucoma. Following the initial studies on timolol maleate powder, it was formulated into ocular mini-tablets. The polymers investigated in this study included cellulose derivatives (HEC, CMC, EC) and Carbopol 971P. Mannitol was used as the solubilizing agent and magnesium stearate as the lubricant. Mini-tablets were ...

  7. Formulation and evaluation of sustained release enteric-coated pellets of budesonide for intestinal delivery

    National Research Council Canada - National Science Library

    Raval, Mihir K; Ramani, Riddhi V; Sheth, Navin R

    2013-01-01

    ...) full factorial design by giving an enteric coating with Eudragit S100. Budesonide-sustained release pellets were prepared by extruder and spheronization technique using a combination of water-soluble and permeable polymers by applying 3(2...

  8. Use of dika fat in the formulation of sustained release theophylline ...

    African Journals Online (AJOL)

    Sustained release theophylline tablets and capsules were prepared with dika fat, a solid vegetable oil extracted from the kernels of Irvingia gabonesis var gabonesis and var excelsia. Anhydrous theophylline was incorporated into dika fat by the fusion method. The in vitro release of the theophylline was monitored by the ...

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

    African Journals Online (AJOL)

    Purpose: To develop and optimise sustained release (SR) matrix tablets of diltiazem hydrochloride (DHL). Methods: DHL tablets were prepared by direct compression and consisted of hydroxyprpoylmethyl cellulose, Kollidon SR and Eudragit RSPO. A 32 full factorial design was applied to study the effect of polymers used ...

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

    African Journals Online (AJOL)

    HP

    2013-07-15

    Jul 15, 2013 ... Purpose: To develop and optimise sustained release (SR) matrix tablets of diltiazem hydrochloride (DHL). Methods: DHL tablets were prepared by direct compression and consisted of hydroxyprpoylmethyl cellulose,. Kollidon SR and Eudragit RSPO. A 32 full factorial design was applied to study the effect of ...

  11. A sustained release formulation of novel quininib-hyaluronan microneedles inhibits angiogenesis and retinal vascular permeability in vivo.

    Science.gov (United States)

    Galvin, Orla; Srivastava, Akshay; Carroll, Oliver; Kulkarni, Rajiv; Dykes, Steve; Vickers, Steven; Dickinson, Keith; Reynolds, Alison L; Kilty, Claire; Redmond, Gareth; Jones, Rob; Cheetham, Sharon; Pandit, Abhay; Kennedy, Breandán N

    2016-07-10

    Pathologic neovascularisation and ocular permeability are hallmarks of proliferative diabetic retinopathy and age-related macular degeneration. Current pharmacologic interventions targeting VEGF are effective in only 30-60% of patients and require multiple intraocular injections associated with iatrogenic infection. Thus, our goal is to develop novel small molecule drugs that are VEGF-independent are amenable to sustained ocular-release, and which reduce retinal angiogenesis and retinal vascular permeability. Here, the anti-angiogenic drug quininib was formulated into hyaluronan (HA) microneedles whose safety and efficacy was evaluated in vivo. Quininib-HA microneedles were formulated via desolvation from quininib-HA solution and subsequent cross-linking with 4-arm-PEG-amine prior to freeze-drying. Scanning electron microscopy revealed hollow needle-shaped particle ultrastructure, with a zeta potential of -35.5mV determined by electrophoretic light scattering. The incorporation efficiency and pharmacokinetic profile of quininib released in vitro from the microneedles was quantified by HPLC. Quininib incorporation into these microneedles was 90%. In vitro, 20% quininib was released over 4months; or in the presence of increasing concentrations of hyaluronidase, 60% incorporated quininib was released over 4months. Zebrafish hyaloid vasculature assays demonstrated quininib released from these microneedles significantly (pmicroneedles allow for sustained release of quininib; are safe in vivo and quininib released from these microneedles effectively inhibits angiogenesis and RVP in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. 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.

  13. 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 Cmax 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.

  14. 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.

  15. Formulation of novel sustained release rifampicin-loaded solid lipid microparticles based on structured lipid matrices from Moringa oleifera.

    Science.gov (United States)

    Onyishi, Ikechukwu V; Chime, Salome A; Ogudiegwu, Echezona O

    2015-01-01

    To formulate sustained release rifampicin-loaded solid lipid microparticles (SLMs) using structured lipid matrices based on Moringa oil (MO) and Phospholipon 90G (P90G). Rifampicin-loaded and unloaded SLMs were formulated by melt homogenization and characterized in terms of particle morphology and size, percentage drug content (PDC), pH stability, stability in simulated gastric fluid (SGF, pH 1.2), minimum inhibitory concentration (MIC) and in vitro release. In vivo release was studied in Wistar rats. Rifampicin-loaded SLMs had particle size range of 32.50 ± 2.10 to 34.0 ± 8.40 μm, highest PDC of 87.6% and showed stable pH. SLMs had good sustained release properties with about 77.1% release at 12 h in phosphate buffer (pH 6.8) and 80.3% drug release at 12 h in simulated intestinal fluid (SIF, pH 7.4). SLMs exhibited 48.51% degradation of rifampicin in SGF at 3 h, while rifampicin pure sample had 95.5% degradation. Formulations exhibited MIC range of 0.781 to 1.562, 31.25 to 62.5 and 6.25 to 12.5 μg/ml against Salmonella typhi, Escherichia coli, and Bacillus subtilis respectively and had higher in vivo absorption than the reference rifampicin (p < 0.05). Rifampicin-loaded SLMs could be used once daily for the treatment tuberculosis.

  16. [Outcomes of an Independent Clinical Study to Compare Branded and Generic Formulations of Sustained-Release Oxycodone].

    Science.gov (United States)

    Yamamoto, Mai; Saito, Yoshiko; Onodera, Yurika; Okawa, Masayo; Shimizu, Kei; Yamamoto, Yusuke; Nawa, Takeshi; Aoyama, Yoshifumi

    2017-03-01

    To evaluate the potential for the adoption of a generic formulation of sustained-release oxycodone(Oxycodone SR Capsules), an independent clinical study was planned to accurately evaluate the efficacy and safety during a 9-day period. After a 3-day pretreatment period, the generic formulation was administered to patients with progressive cancer, who had been treated with a branded formulation(OxyContin®Tablets)of the drug for 5 days at the same dose. This was followed by a 1- day observation period. Drug administration to 3 patients with pulmonary cancer achieved the primary(dose, pain level, and adverse drug reactions)and secondary(rescue dose frequency and quality of life)endpoints, as well as safety goals. The merits of adopting a different dosage form were also noted. Independent data collection using an appropriate evaluation method consequently promoted the understanding of generic opioids in the clinical setting.

  17. Characterization and evaluation of self-nanoemulsifying sustained-release pellet formulation of ziprasidone with enhanced bioavailability and no food effect.

    Science.gov (United States)

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

    2016-09-01

    The purpose of this work was to develop self-nanomulsifying drug delivery systems (SNEDDS) in sustained-release pellets of ziprasidone to enhance the oral bioavailability and overcome the food effect of ziprasidone. Preformulation studies including screening of excipients for solubility and pseudo-ternary phase diagrams suggested the suitability of Capmul MCM as oil phase, Labrasol as surfactant, and PEG 400 as co-surfactant for preparation of self-nanoemulsifying formulations. Preliminary composition of the SNEDDS formulations were selected from the pseudo-ternary phase diagrams. The prepared ziprasidone-SNEDDS formulations were characterized for self-emulsification time, effect of pH and robustness to dilution, droplet size analysis and zeta potential. The optimized ziprasidone-SNEDDS were used to prepare ziprasidone-SNEDDS sustained-release pellets via extrusion-spheronization method. The pellets were characterized for SEM, particle size, droplet size distribution and zeta potential. In vitro drug release studies indicated the ziprsidone-SNEDDS sustained-release pellets showed sustained release profiles with 90% released within 10 h. The ziprsidone-SNEDDS sustained-release pellets were administered to fasted and fed beagle dogs and their pharmacokinetics were compared to commercial formulation of Zeldox as a control. Pharmacokinetic studies in beagle dogs showed ziprasidone with prolonged actions and enhanced bioavailability with no food effect was achieved simultaneously in ziprsidone-SNEDDS sustained-release pellets compared with Zeldox in fed state. The results indicated a sustained release with prolonged actions of schizophrenia and bipolar disorder treatment.

  18. Development of Denticap, a matrix based sustained release formulation for treatment of toothache, dental infection and other gum problem.

    Science.gov (United States)

    Mukherjee, Biswajit; Roy, Gopa; Ghosh, Soma

    2009-04-01

    Toothache is a serious problem worldwide. To give relief from this intolerable toothache, doctors prescribe painkillers along with antibiotics. Most of the painkillers, if not all, produce hyperacidity and gastric irritation upon oral administration. Oral antibiotics have slow onset of action and undergo hepatic "first-pass" effect. Moreover, available dental formulations are mostly liquid and last only few hours upon application, before being washed out by saliva. To overcome the above-mentioned problems, a soft polymeric mold containing antibiotic and analgesic drugs and having an appropriate consistency to adhere to the tooth, was developed for sustained drug release to provide better relief in dental patients. Eudragit L 100-55, carbopol 971 P, gum karaya powder and ethyl cellulose were used to prepare the mold "Denticaps" containing Lidocaine hydrochloride and Amoxicillin trihydrate individually and in combination, by mixing and solvent evaporation technique. Different physicochemical characterization studies such as mucoadhesion test, water absorption capacity and swelling index were carried out. In vitro drug release studies showed sustained release of Lidocaine hydrochloride and Amoxicillin trihydrate in simulated saliva for 24 h. Further studies are warranted to succeed with these formulations in humans. Upon success, this type of dosage form may open up new avenues towards dentistry.

  19. Formulation and pharmaceutical development of quetiapine fumarate sustained release matrix tablets using a QbD approach

    Directory of Open Access Journals (Sweden)

    Gavan Alexandru

    2017-03-01

    Full Text Available The main objective of the present study was to apply QbD methodology in the development of once-a-day sustained release quetiapine tablets. The quality target product profile (QTPP was defined after the pharmaceutical properties and kinetic release of the innovator product, Seroquel XR 200 mg. For the D-optimal experimental design, the level and ratio of matrix forming agents and the type of extragranular diluent were chosen as independent inputs, which represented critical formulation factors. The critical quality attributes (CQAs studied were the cumulative percentages of quetiapine released after certain time intervals. After the analysis of the experimental design, optimal formulas and the design space were defined. Optimal formulas demonstrated zero-order release kinetics and a dissolution profile similar to the innovator product, with f2 values of 74.53 and 83.74. It was concluded that the QbD approach allowed fast development of sustained release tablets with similar dissolution behavior as the innovator product.

  20. Original research paper. Formulation and pharmaceutical development of quetiapine fumarate sustained release matrix tablets using a QbD approach.

    Science.gov (United States)

    Gavan, Alexandru; Porfire, Alina; Marina, Cristina; Tomuta, Ioan

    2017-03-01

    The main objective of the present study was to apply QbD methodology in the development of once-a-day sustained release quetiapine tablets. The quality target product profile (QTPP) was defined after the pharmaceutical properties and kinetic release of the innovator product, Seroquel XR 200 mg. For the D-optimal experimental design, the level and ratio of matrix forming agents and the type of extragranular diluent were chosen as independent inputs, which represented critical formulation factors. The critical quality attributes (CQAs) studied were the cumulative percentages of quetiapine released after certain time intervals. After the analysis of the experimental design, optimal formulas and the design space were defined. Optimal formulas demonstrated zero-order release kinetics and a dissolution profile similar to the innovator product, with f2 values of 74.53 and 83.74. It was concluded that the QbD approach allowed fast development of sustained release tablets with similar dissolution behavior as the innovator product.

  1. Sustained-release morphine sulfate with sequestered naltrexone for moderate to severe pain: a new opioid analgesic formulation and beyond.

    Science.gov (United States)

    Ruan, Xiulu

    2011-05-01

    Opioid usage during chronic nonmalignant pain has increased substantially over the past two decades. Prescription opioids have become the second most misused drug in the USA and prescription opioid abuse has escalated into a widespread public health problem. It is hoped that abuse-deterrent opioid formulations will take an important role in reducing opioid abuse, misuse and diversion. Embeda (sustained-release morphine sulfate with sequestered naltrexone)represents a new opioid formulation with an intended abuse-deterrent feature, now available on the market. Although Embeda seems to be a successful formulation by passing the efficacy trial, safety trial, pharmacokinetic study and abuse liability study, etc., it will require some long-term prospective epidemiological studies to substantiate fully its abuse-deterrent benefit. Embeda represents a new opioid formulation, adding to our arsenal to treat moderate to severe pain and playing its potential role in discouraging opioid abuse, misuse and diversion. Faced with an overwhelmingly expanding public health burden due to prescription opioid abuse, clinicians should always keep in mind the balance of maximizing pain relief and minimizing prescription opioid abuse. © 2011 Informa UK, Ltd

  2. Constructing herbicide metribuzin sustained-release formulations based on the natural polymer poly-3-hydroxybutyrate as a degradable matrix.

    Science.gov (United States)

    Volova, Tatiana G; Zhila, Natalia O; Vinogradova, Olga N; Nikolaeva, Elena D; Kiselev, Evgeniy G; Shumilova, Anna A; Shershneva, Anna M; Shishatskaya, Ekaterina I

    2016-02-01

    Polymer poly(3-hydroxybutyrate) [P(3HB)] has been used as a matrix in slow-release formulations of the herbicide metribuzin (MET). Physical P(3HB)/MET mixtures in the form of solutions, powders, and emulsions were used to construct different metribuzin formulations (films, granules, pellets, and microparticles). SEM, X-Ray, and DSC proved the stability of these formulations incubated in sterile water in vitro for long periods of time (up to 49 days). Metribuzin release from the polymer matrix has been also studied. By varying the shape of formulations (microparticles, granules, films, and pellets), we were able to control the release time of metribuzin, increasing or decreasing it.

  3. Evaluation of formulation and effects of process parameters on drug release and mechanical properties of tramadol hydrocloride sustained release matrix tablets

    Directory of Open Access Journals (Sweden)

    Nikolić Nenad D.

    2015-01-01

    Full Text Available This study investigates using of high molecular weight polyethylene oxide (PEO WSR Coagulant for the preparation of sustained release matrix tablets containing high dose, highly water soluble drug, tramadol HCl. Proportion of PEO polymer, type of insoluble filler, proportion of tramadol HCl, amount of drug in tablet, tablet diameter and compression pressure were recognized as critical formulation and process parameters and their influence on drug release and tablet mechanical properties was evaluated. Percentages of tramadol HCl released after 30 and 240 minutes were selected for evaluation of drug release, while tensile strength was used as indicator of tablet mechanical properties. Only proportion of tramadol HCl exhibits statistically significant effect on percentages of tramadol HCl released after 30 and 240 minutes, with higher, wherein increasing of the tramadol HCl proportion increased its release rate among the evaluated variables in selected ranges. All of the investigated factors exhibit statistically significant effect on tablets tensile strength, with the largest influence of filler type. Tablets prepared with highly compressible filler (microcrystalline celullose exhibit higher tensile strength and therefore better mechanical properties to those prepared with partially pregelatinised starch (Strach 1500. [Projekat Ministarstva nauke Republike Srbije, br. TR 34007

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

    African Journals Online (AJOL)

    HP

    A fair correlation between the dissolution profile and bioavailability for the optimized formulation ... Diltiazem HCl is a water soluble calcium-channel .... bioavailability and bioequivalence studies (CDSCO, DGHS, India). [16]. The subjects enrolled in the study were presented with full details of the investigation, both verbally ...

  5. Formulation Design, Optimization and Pharmacodynamic Evaluation of Sustained Release Mucoadhesive Microcapsules of Venlafaxine HCl

    OpenAIRE

    Swain, S.; Behera, A.; Dinda, S. C.; Patra, C. N.; Jammula, Sruti; Beg, S.; Rao, M. E. B.

    2014-01-01

    The objective of present research work was to design and characterize the venlafaxine HCl-loaded sodium alginate-based mucoadhesive microcapsules by ionic gelation technique using HPMC K100M as mucoadhesive polymer. The Placket-Burman Design was applied for preliminary screening of the formulations and systematic optimization by using Box-Behnken Design. The prepared microcapsules were characterized for drug content, entrapment efficiency, micromeritic properties, particle size, swelling inde...

  6. Clinical Evaluation of Modified Release and Immediate Release Tacrolimus Formulations.

    Science.gov (United States)

    Tremblay, Simon; Alloway, Rita R

    2017-09-01

    The science of drug delivery has evolved considerably and has led to the development of multiple sustained release formulations. Each of these formulations can present particular challenges in terms of clinical evaluation and necessitate careful study to identify their optimal use in practice. Tacrolimus is an immunosuppressive agent that is widely used in organ transplant recipients. However, it is poorly soluble, has an unpredictable pharmacokinetic profile subject to important genetic polymorphisms and drug-drug interactions, and has a narrow therapeutic index. For these reasons, it represents an agent that could benefit from modified release formulations to overcome these limitations. The objective of this review is to discuss the clinical evaluation of immediate and modified release tacrolimus formulations in renal transplant recipients. Clinical trials from early development of immediate release tacrolimus to formulation-specific post-marketing trials of modified release tacrolimus formulations are reviewed with an emphasis on key elements relating to trial design end endpoint assessment. Particular elements that can be addressed with formulation alterations, such as pharmacokinetics, pharmacogenomics, and toxicity and corresponding clinical evaluations are discussed. In addition, current knowledge gaps in the clinical evaluation of immediate and modified release tacrolimus formulations are discussed to highlight potential avenues for the future development of different tacrolimus formulations with outcomes relevant to the regulators, the transplant community, and to transplant recipients. This review shows that new formulations may alter tacrolimus bioavailability, alleviate certain adverse events while potentially enhancing patient convenience.

  7. 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

  8. Pharmacokinetics of a Sustained Release Formulation of Buprenorphine After Intramuscular and Subcutaneous Administration to American Kestrels ( Falco sparverius ).

    Science.gov (United States)

    Guzman, David Sanchez-Migallon; Knych, Heather K; Olsen, Glenn H; Paul-Murphy, Joanne R

    2017-06-01

    Previous studies have validated the clinical use of opioids with μ-receptor affinities for pain management in raptors. Buprenorphine appears to have a longer duration of action and minimal adverse effects when compared to other opioids in American kestrels ( Falco sparverius ). To determine the pharmacokinetics of a sustained release formulation of buprenorphine in kestrels, we administered a commercially available product (Buprenorphine SR-LAB; Wildlife Pharmaceuticals, Windsor, CO, USA) intramuscularly and subcutaneously to adult kestrels in a partial-crossover experimental design study. A total of 12 birds (6 males and 6 females) were assigned randomly to 3 groups of 4 birds each. A single dose of Buprenorphine SR-LAB (1.8 mg/kg) was administered intramuscularly (IM), and blood samples were collected at 0.25, 3, and 24 hours (n = 4); 1, 6, and 48 hours (n = 4); and 2, 12, and 72 hours (n = 4) after drug administration. Plasma buprenorphine concentrations were measured by tandem liquid chromatography-mass spectrometry. Pharmacokinetic parameters were determined by use of least squares linear regression and noncompartmental analysis of naïve pooled data. After 1 year, the same dose of buprenorphine was administered subcutaneously (SC) to 12 birds divided into 3 groups as previously, and blood samples were collected at the same times after drug administration. Maximum plasma buprenorphine concentration was measured at 15 minutes after IM and SC administration. Mean plasma buprenorphine concentrations were >1 ng/mL for 48 hours after IM and SC administration. The elimination half-life was 13.5 and 11.1 hours for IM and SC administration, respectively. Depending on the severity and type of pain, adjunctive therapy, and the individual response, Buprenorphine SR-LAB administered at 1.8 mg/kg IM or SC to American kestrels would require administration every 12 to 72 hours to manage pain. Further pharmacodynamic and clinical evaluations are warranted in kestrels and

  9. Potential Use of Polyvinyl Acetate-Polyvinylpyrrolidone Mixture for the Development of Atenolol Sustained Release Matrix Tablets: Optimization of Formulation through in Vitro-in Vivo Assessment Study.

    Science.gov (United States)

    Owayez, Ali Saeed; Abd El-Ghany, Galal Mahmoud; Abu Hashim, Irhan Ibrahim

    2017-01-01

    The objective of this study was to develop sustained release matrix tablets of atenolol (AT) using different concentrations of polyvinyl acetate-polyvinylpyrrolidone mixture (KSR) (20, 30, or 40%) with various types of fillers such as spray dried lactose (SP.D.L), avicel pH 101 (AV), and emcompress (EMS). The physical characteristics of the prepared tablets were evaluated. Characterization of the optimized formulation was performed using Fourier transform (FT)-IR spectroscopy and differential scanning calorimetry (DSC). Moreover, the in vitro release profiles of AT formulations were investigated in different pH dissolution media. Drug release kinetics and mechanisms were also determined. The results revealed that there was no potential incompatibility of the drug with the polymer. The release profiles of AT were affected by the concentration of KSR, fillers used, and pH of the dissolution media. The drug release kinetic from most of the formulations obeyed Higuchi diffusion model. The selected formulae were investigated for their stability by storage at 30 and 40°C with atmospheric humidity and 75% relative humidity (RH), respectively. The results demonstrated that no change in the physicochemical properties of the tablets stored at 30°C/atmospheric RH in comparison with some changes at 40°C/75% RH. Finally, the in vivo study provided an evidence that the optimized AT tablet containing 40% KSR and SP.D.L exhibited prominent higher oral bioavailability and more efficient sustained-release effect than the drug alone or the commercial tablet product. It is noteworthy that KSR could be considered as a promising useful release retardant for the production of AT sustained release matrix tablets.

  10. 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.

  11. Sustained Release Formulation of Primaquine for Prevention of Relapse of Plasmodium vivax Malaria: A Randomized, Double-Blind, Comparative, Multicentric Study

    OpenAIRE

    Pareek, Anil; Chandurkar, Nitin; Gogtay, Nithya; Deshpande, Alaka; Kakrani, Arjun; Kaneria, Mala; Karmakar, Partha; Jain, Arvind; Kochar, Dhanpat; Chogle, Arun; Ray, Arnab

    2015-01-01

    Background. Primaquine is used to eradicate latent Plasmodium vivax parasite from liver, with administration of standard dose daily up to 14 days. We studied efficacy, safety, and tolerability of sustained release (SR) formulation of primaquine in comparison with conventional primaquine in preventing relapse of P. vivax malaria. Methods. Microscopically confirmed cases of P. vivax malaria received chloroquine therapy for three days. Aparasitemic and asymptomatic patients were then randomized ...

  12. Investigation of the potential application of sodium bentonite as an excipient in formulation of sustained release tablets

    Directory of Open Access Journals (Sweden)

    Jamal Alyoussef Alkrad

    2017-05-01

    Full Text Available In this study, the application of sodium bentonite (SB in formulation of tablets prepared by direct compression for oral administration was tested. Three different model drugs with different solubilities: paracetamol, diclofenac sodium and metformin HCl were tested. Each drug was mixed with SB at ratio of 50% and the mixtures were subsequently compressed. Compatibility studies were conducted using both Deferential Scanning Calorimeter (DSC and Fourier Transform Infrared Spectroscopy (FTIR. The dissolution profile for each drug was determined in USP-buffers at different time intervals. Diclofenac sodium in pH 6.8 buffer and paracetamol in both pH 6.8 and pH 4.5 buffers showed extended release. However, metformin HCl showed immediate release at the different pH values. The study showed that using SB was possible to prepare tablets with different release profiles. However, these profiles differ depending on dissolution media and drug type.

  13. Plasma concentrations of buprenorphine following a single subcutaneous administration of a sustained release formulation of buprenorphine in sheep

    OpenAIRE

    Zullian, Chiara; Lema, Pablo; Lavoie, Melissa; Dodelet-Devillers, Aurore; Beaudry, Francis; Vachon, Pascal

    2016-01-01

    The goal of the present study was to evaluate the potential use of slow release buprenorphine in sheep. Twelve adult female sheep (6 Dorset and 6 Suffolk, 12 months of age) were used for this project and were divided into 2 experimental groups (n = 6/group comprising 3 Dorset and 3 Suffolk sheep). Sustained release (SR) buprenorphine was administered subcutaneously in the scapular region at a concentration of 0.1 mg/kg body weight (BW) for group 1 and of 0.05 mg/kg BW for group 2. Following b...

  14. Solutions as solutions--synthesis and use of a liquid polyester excipient to dissolve lipophilic drugs and formulate sustained-release parenterals.

    Science.gov (United States)

    Asmus, Lutz R; Gurny, Robert; Möller, Michael

    2011-11-01

    Solid poly(lactides) and poly(lactide-co-glycolides) are widely used polymers for sustained-release parenterals. However, they have some unfavorable properties regarding manufacturing of the formulations and administration to the patient due to their solid aggregate state. In contrast, hexyl-substituted poly(lactic acid) (hexPLA, poly(2-hydroxyoctanoic acid)) is a viscous degradable polyester. To date, a two-step ring-opening polymerization was used for its synthesis. Here, we investigated a novel one-pot one-step melt polycondensation method to prepare hexPLA for biomedical applications by a simple green chemistry process. No catalyst or solely pharmaceutically acceptable catalysts and environmentally friendly purification methods without organic solvents were used. The resulting hexPLA polymers are stable under dry heat sterilization conditions. Low molecular weight hexPLAs with less than 5000 g/mol are less viscous than high molecular weight polymers. HexPLA can dissolve lipophilic active substances, with generally high incorporation capacities in low molecular weight polymers. The incorporation of solid compounds increases the viscosity and glass transition temperature, whereas the addition of small amounts of plasticizers or sparse warming significantly decreases the viscosity. Loratadine is soluble in hexPLA up to 28%. This highly concentrated Loratadine-hexPLA formulation released the active compound entirely over 14 days without initial burst in a zero order kinetic, matching the clinical requirements for such a sustained-release formulation. This demonstrates the potential of hexPLA as an excipient for injectable sustained-release formulations. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Safety and clinical effectiveness of a compounded sustained-release formulation of buprenorphine for postoperative analgesia in New Zealand White rabbits.

    Science.gov (United States)

    DiVincenti, Louis; Meirelles, Luiz A D; Westcott, Robin A

    2016-04-01

    To determine the clinical effectiveness and safety of a compounded sustained-release formulation of buprenorphine, compared with effects of regular buprenorphine, for postoperative analgesia in rabbits. Blinded randomized controlled clinical trial. 24 purpose-bred adult male New Zealand White rabbits. Rabbits received titanium implants in each tibia as part of another study. Immediately prior to surgery, each rabbit received regular buprenorphine hydrochloride (0.02 mg/kg [0.009 mg/lb], SC, q 12 h for 3 days) or 1 dose of a compounded sustained-release formulation of buprenorphine (0.12 mg/kg [0.055 mg/lb], SC) followed by an equal volume of saline (0.9% NaCl) solution (SC, q 12 h for 3 days) after surgery. For 7 days after surgery, rabbits were evaluated for signs of pain by means of rabbit grimace and activity scoring and for adverse effects. No significant differences were identified between treatment groups in grimace and activity scores at any point. No major adverse effects were detected for either drug. However, 3 rabbits that received regular buprenorphine had pain scores suggestive of moderate to severe pain by the time dose administration was due (ie, within the 12-hour administration interval). No clinically important differences were detected in intraoperative anesthetic or postoperative recovery variables. Sustained-release buprenorphine administered SC at 0.12 mg/kg was at least as effective as regular buprenorphine in providing analgesia for rabbits following orthopedic surgery without any major adverse effects. This sustained-release formulation represents an important alternative for rabbit analgesia with potential to improve rabbit welfare over existing analgesic standards.

  16. Sustained reduction of diversion and abuse after introduction of an abuse deterrent formulation of extended release oxycodone.

    Science.gov (United States)

    Severtson, Stevan Geoffrey; Ellis, Matthew S; Kurtz, Steven P; Rosenblum, Andrew; Cicero, Theodore J; Parrino, Mark W; Gilbert, Michael K; Buttram, Mance E; Dasgupta, Nabarun; BucherBartelson, Becki; Green, Jody L; Dart, Richard C

    2016-11-01

    The development of abuse deterrent formulations is one strategy for reducing prescription opioid misuse and abuse. A putative abuse deterrent formulation of oxycodone extended release (OxyContin(®)) was introduced in 2010. Early reports demonstrated reduced abuse and diversion, however, an analysis of social media found 32 feasible methods to circumvent the abuse deterrent mechanism. We measured trends of diversion, abuse and street price of OxyContin to assess the durability of the initial reduction in abuse. Data from the Poison Center Program, Drug Diversion Program, Opioid Treatment Program, Survey of Key Informant Patients Program and StreetRx program of the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS(®)) System were used. The average quarterly rates of abuse and diversion for OxyContin were compared from before reformulation to the rate in second quarter 2015. Rates were adjusted for population using US Census data and drug availability. OxyContin abuse and diversion declined significantly each quarter after reformulation and persisted for 5 years. The rate of abuse of other opioid analgesics increased initially and then decreased, but to lesser extent than OxyContin. Abuse through both oral and non-oral routes of self-administration declined following the reformulation. The geometric mean difference in the street price of reformulated OxyContin was 36% lower than the reformulated product in the year after reformulation. Despite methods to circumvent the abuse deterrent mechanism, abuse and diversion of OxyContin decreased promptly following the introduction of a crush- and solubility- resistant formulation and continued to decrease over the subsequent 5 years. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  17. Formulation development and evaluation of the anti-malaria properties of sustained release artesunate-loaded solid lipid microparticles based on phytolipids.

    Science.gov (United States)

    Chinaeke, E E; Chime, S A; Onyishi, V I; Attama, A A; Okore, V C

    2015-01-01

    CONTEXTS: Artemisinins and its derivatives are considered the basis in the treatment of Plasmodium falciparum malaria due to their high potency and rapid action. However, they have short half life, low solubility, and poor oral bioavailability, hence the need to formulate sustained release lipid particulate dosage form of these drugs. To formulate and evaluate artesunate-loaded solid lipid microparticles (SLMs) based on structured lipid matrices consisting of soybean oil and dika wax. The lipid matrices were characterized by differential scanning calorimetry (DSC), small-angle X-ray diffraction (SAXD), and wide-angle X-ray diffraction (WAXD). The SLMs were prepared by hot melt-homogenization. Time-dependent particle size analysis, time-dependent pH stability studies, encapsulation efficiency (EE%), and in vitro drug release were carried out on the SLMs. In vivo anti-malarial studies were performed using a modified Peter's 4-day suppressive protocol using Plasmodium berghei infected mice. Thermograms of the lipid matrices showed modifications in the microstructure of dika wax as a result of inclusion of soybean oil. SAXD and WAXD diffractograms showed that the lipid matrices were found to be non-lamellar. Particle size of SLM increased with time, while the pH was almost constant. The SLMs had maximum EE% of 80.6% and sustained the release of artesunate more than the reference tablet. In vivo pharmacodynamic studies showed that the SLMs had significant (p daily in the treatment of malaria.

  18. Plasma concentrations of buprenorphine following a single subcutaneous administration of a sustained release formulation of buprenorphine in sheep.

    Science.gov (United States)

    Zullian, Chiara; Lema, Pablo; Lavoie, Melissa; Dodelet-Devillers, Aurore; Beaudry, Francis; Vachon, Pascal

    2016-07-01

    The goal of the present study was to evaluate the potential use of slow release buprenorphine in sheep. Twelve adult female sheep (6 Dorset and 6 Suffolk, 12 months of age) were used for this project and were divided into 2 experimental groups (n = 6/group comprising 3 Dorset and 3 Suffolk sheep). Sustained release (SR) buprenorphine was administered subcutaneously in the scapular region at a concentration of 0.1 mg/kg body weight (BW) for group 1 and of 0.05 mg/kg BW for group 2. Following blood collections at selected time points, plasma concentrations of buprenorphine was performed by tandem liquid chromatograph-mass spectrometry. Mean buprenorphine concentration was above 0.1 ng/mL at 48 h up to 192 h post-injection for group 1 and it was above 0.1 ng/mL at 48 h up to 72 h post-injection for group 2. In conclusion, a long lasting potential analgesic plasma level of buprenorphine is attained following a single subcutaneous injection of 0.1 mg/kg BW of SR buprenorphine in sheep. However the effective analgesic plasma threshold still needs to be determined in sheep.

  19. Pregnancy success of lactating Holstein cows after a single administration of a sustained-release formulation of recombinant bovine somatotropin

    Directory of Open Access Journals (Sweden)

    Gutiérrez CG

    2008-06-01

    Full Text Available Abstract Background Results regarding the use of bovine somatotropin for enhancing fertility in dairy cattle are variable. Here, the hypothesis was tested that a single injection of a sustained-release preparation of bovine somatotropin (bST during the preovulatory period would improve pregnancy success of lactating dairy cows at first service. Results The first experiment was conducted in a temperate region of Mexico. Cows inseminated following natural estrus or timed artificial insemination were given a single injection of bST or a placebo injection at insemination (n = 100 cows per group. There was no significant difference between bST and control groups in the proportion of inseminated cows diagnosed pregnant (29 vs 31% pregnant. The second experiment was performed during heat stress in Florida. Cows were subjected to an ovulation synchronization regimen for first insemination. Cows treated with bST received a single injection at 3 days before insemination. Controls received no additional treatment. As expected, bST did not increase vaginal temperature. Treatment with bST did not significantly increase the proportion of inseminated cows diagnosed pregnant although it was numerically greater for the bST group (24.2% vs 17.8%, 124–132 cows per group. There was a tendency (p = 0.10 for a smaller percent of control cows to have high plasma progesterone concentrations (≥ 1 ng/ml at Day 7 after insemination than for bST-treated cows (72.6 vs 81.1%. When only cows that were successfully synchronized were considered, the magnitude of the absolute difference in the percentage of inseminated cows that were diagnosed pregnant between bST and control cows was reduced (24.8 vs 22.4% pregnant for bST and control. Conclusion Results failed to indicate a beneficial effect of bST treatment on fertility of lactating dairy cows.

  20. 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.

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

    African Journals Online (AJOL)

    Purpose: To formulate matrix type sustained-release (SR) tablets of tizanidine hydrochloride (TH) for prolonged drug release and improvement in motor activity after spinal injuries. Methods: Matrix tablets were prepared by the wet granulation method using four polymers (hydroxyl propyl methyl cellulose [HPMC] K 100, ethyl ...

  2. 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

  3. Pharmacokinetics of an ultralong sustained-release theophylline formulation when given twice daily in elderly patients with chronic obstructive pulmonary disease: monitoring implications.

    Science.gov (United States)

    Armijo, Juan A; Sánchez, Blanca M; Peralta, F Galo; González-Ruiz, Mario; Cuadrado, Antonio; Verdejo, Asunción; Cos, María A de; Arjona, Rafael

    2003-05-01

    The steady-state pharmacokinetics of an ultralong sustained release formulation of theophylline (Unilong) twice daily (bid) in elderly hospitalized patients suffering from chronic obstructive pulmonary disease (COPD) have been studied in order to establish guidelines for monitoring. The study was carried out in 37 patients (33 men), aged 60-87 years. Samples were collected from 0 to 12 h after the morning dose on day 9 of treatment with 250 mg bid (n=25) or 375 mg bid (n=12). Considerable variability in apparent clearance (range 0.33-1.49 ml/min per kg of ideal body weight), Css(min)/D (range 0.28-1.86), Css(max)/D (range 0.65-2.33) and (Css(max)-Css(min))/Css(avg) (range 0.18-0.80) was observed. There was no significant correlation between the patient's age and apparent clearance within this elderly population. The concentration-to-dose ratio and the relationship between the steady-state plasma concentration at different times during the dosage interval and Css(avg) are described. It is concluded that the interpatient variability in peak-trough fluctuation of this formulation was higher than that described in healthy volunteers by other investigators, and that the apparent clearance did not decrease with age within this elderly population with COPD. The importance of theophylline monitoring is emphasized and rules to estimate Css(avg) and Css(5h) from Css(0h) when only a single sample obtained before the morning dose is available are given. Copyright 2003 John Wiley & Sons, Ltd.

  4. Sustained Release Formulation of Primaquine for Prevention of Relapse of Plasmodium vivax Malaria: A Randomized, Double-Blind, Comparative, Multicentric Study

    Directory of Open Access Journals (Sweden)

    Anil Pareek

    2015-01-01

    Full Text Available Background. Primaquine is used to eradicate latent Plasmodium vivax parasite from liver, with administration of standard dose daily up to 14 days. We studied efficacy, safety, and tolerability of sustained release (SR formulation of primaquine in comparison with conventional primaquine in preventing relapse of P. vivax malaria. Methods. Microscopically confirmed cases of P. vivax malaria received chloroquine therapy for three days. Aparasitemic and asymptomatic patients were then randomized to receive either conventional primaquine 15 mg for 14 days or primaquine SR 15 mg for 14 days, or primaquine SR 30 mg for seven days. Results. Of the 360 patients, who received chloroquine therapy, 358 patients were randomized. Two-hundred eighty-eight patients completed six-month follow-up and four patients (three: conventional primaquine 15 mg (2.86%, one: primaquine SR 30 mg (0.93% showed relapse confirmed by PCR genotyping. Drug compliance was significantly better in primaquine SR 30 mg group (95.57%, p=0.039 without any serious adverse events. Conclusion. Primaquine SR 15 mg and primaquine SR 30 mg could be an effective alternative to conventional primaquine 15 mg due to their comparable cure rates and safety profile. Shorter treatment duration with primaquine SR 30 mg may increase patient compliance and may further reduce relapse rates. Clinical Trial Registration. This trial is registered with CTRI/2010/091/000245.

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

    African Journals Online (AJOL)

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

  6. [Study on sustained release preparations of Epimedium component].

    Science.gov (United States)

    Yan, Hong-mei; Ding, Dong-mei; Zhang, Zhen-hai; Sun, E; Song, Jie; Jia, Xiao-bin

    2015-04-01

    The formulation for sustained release tablet of Epinedium component was selected and the evaluation equation of in vitro release was established. The liquidity of component was improved with the help of colloidal silica aided by spray drying, which would be the main drug in the sustained release tablets. Dissolution was selected as an evaluation index to investigate skeletal material type, fillers, impact porogen, lubricants and other materials on the quality of sustained release tablet. The sustained release tablets were prepared by dry compression. Formulation of sustained release preparations was main drug 35%, HPMC K(4M) 20% and HPMC K(15M) 10% as skeleton material, MCC 31% as filler, PEG6000 2% as porogen and magnesium stearate 2% as lubricant. The sustained release tablets released up to 80% in 8 h. The zero order equation, primary equation and Higuchi equation could simulate the release characteristics of sustained release tablets in vitro, the correlation coefficients r were larger than 0.96. The primary equation was most similar in vitro release characteristics and its correlation coefficient r was 0.9950. The preparation method is simple and the results of formulation selection are reliable. It can be used to guide the production of Epimedium component sustained release preparations.

  7. [Sustained-release Opioids: Morphine, Oxycodone and Tapentadol].

    Science.gov (United States)

    Takahashi, Yoshika; Iseki, Masako

    2015-11-01

    Opioid analgesics are widely used for managing moderate to severe pain. In cancer pain management sustained-release opioids are used for continuous pain as well as immediate-release opioids for breakthrough pain. Sustained-release drugs have the advantage of stabilizing the blood concentration, although it takes some time to exert their effects. In Japan, the currently available oral sustained-release opioids include six types of sustained-release morphine (three are once-a-day formulations, while the rest are twice-a-day), one type of oxycodone and tapentadol. In this article, we will discuss the pharmacokinetic properties of MS Contin, Morphes, Kadian, P guard and Pacif as sustained-release morphine, Oxycontin as sustained-release oxycodone and Tapenta as sustained-release tapentadol.

  8. Bioavailability and pharmacokinetic properties of 2 sustained-release formulations of diclofenac sodium, Voltaren vs inflaban: effect of food on inflaban bioavailability.

    Science.gov (United States)

    Zmeili, S; Hasan, M; Najib, N; Sallam, E; Deleq, S; Shubair, M

    1996-12-01

    In this study, in vitro characterization, bioavailability and pharmacokinetics of 2 different sustained-release diclofenac sodium dosage forms were compared, Voltaren (100 mg tablets), manufactured by Ciba-Geigy and Inflaban (100 mg enteric-coated tablets), manufactured by the Arab Pharmaceutical Manufacturing Company. The in vitro results demonstrated a faster rate of dissolution for Inflaban as compared to Voltaren, but both products exhibited a sustained-release pattern. The bioavailability study was conducted on 20 healthy male subjects who received a single oral dose (100 mg) of each product according to a randomized 2-way crossover design. Blood samples were obtained over a 26-hour period, and drug concentrations were determined by an HPLC method. Concentration time profiles revealed a sustained-release pattern for both products. The Tlag for Voltaren was 0.8 +/- 0.2 h, significantly shorter than for Inflaban (1.7 +/- 0.2 h) indicating a faster rate of absorption from the upper gastrointestinal tract. The Cmax obtained with Voltaren was significantly higher than that obtained with Inflaban (1,161 +/- 102 and 799 +/- 83, respectively). With respect to Tmax and AUC0-26h parameters, both products were not found to be statistically different. Tmax for Voltaren and Inflaban was 4.2 +/- 0.5 and 4.5 +/- 0.4 h, respectively, whereas AUC0-26h values for both products were 5,423 +/- 562 and 5,237 +/- 520 ng x h/ml, respectively. It is believed that the observed differences between Voltaren and Inflaban are mainly due to the fact that Inflaban is designed as an enteric-coated tablet form, with a core tablet having different sustained-release behavior. In addition, the effect of food on the bioavailability of Inflaban was evaluated in randomly selected 6 male volunteers. Our results revealed that, following light and heavy meals, the AUC0-30 and Cmax were minimally affected by food whereas a significant increase in Tmax and Tlag as compared to fasting conditions was

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

    African Journals Online (AJOL)

    Various granulations of paracetamol were prepared with TCG at the concentrations of 0.5 – 4% w/w. Similar formulations were prepared using sodium carboxymethyl cellulose, SCMC and acacia gums as standards. In each case the release properties of the drug were studied in both 0.1 N HCl and 0.1 N NaOH. Generally ...

  10. Formulation Optimization of Sustained-Release Ammonio Methacrylate Copolymer Microspheres. Effects of Log P and Concentration of Polar Cosolvents, and Role of the Drug/Copolymer Ratio

    Directory of Open Access Journals (Sweden)

    Piroska Szabó-Révész

    2011-11-01

    Full Text Available The objectives of this work were the formulation optimization of the preparation process parameters and to evaluate spray-dried sustained-release microspheres using ammonio methacrylate copolymer (AMC as a polymer matrix. The effects of log P and the concentrations of the cosolvents (acetone, methyl ethyl ketone and n-butyl acetate and different drug/copolymer ratios as independent variables on the physicochemical parameters (the W1/O emulsion viscosity, the microsphere production yield, the average particle size, the encapsulation efficiency and the cumulative in vitro drug release as dependent variables were studied. The optimization was carried out on the basis of the 33 factorial design study. The optimization process results showed that addition of polar cosolvents proved effective, linear relationships were observed between the independent and the dependent variables. The best conditions were achieved by microspheres prepared by using a low/medium cosolvent log P, cosolvent concentration of 25–50% v/v and a drug/copolymer ratio of 1:16. The microspheres ensured sustained release with Nernst and Baker-Lonsdale release profiles.

  11. Controlled Release Formulations of Auxinic Herbicides

    Science.gov (United States)

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

    2013-04-01

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

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

    African Journals Online (AJOL)

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

  13. Preparation and characterization of slow release formulations of ...

    African Journals Online (AJOL)

    *

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

  14. Lyophilized Oral Sustained Release Polymeric Nanoparticles of Nateglinide

    OpenAIRE

    Kaleemuddin, Mohammad; Srinivas, Prathima

    2012-01-01

    The objective of this study is to formulate lyophilized oral sustained release polymeric nanoparticles of nateglinide in order to decrease dosing frequency, minimize side effects, and increase bioavailability. Nateglinide-loaded poly Ɛ-caprolactone nanoparticles were prepared by emulsion solvent evaporation with ultrasonication technique and subjected to various studies for characterization including scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, photon correlati...

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

    African Journals Online (AJOL)

    Purpose: To formulate and evaluate sustained-release microbeads of nifedipine for prolonged delivery. Methods: Nifedipine microbeads were prepared using sodium alginate and pectin in different ratios by ionic-gelation method. The microbeads were evaluated for surface morphology and shape by scanning electron ...

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

    African Journals Online (AJOL)

    dosage forms in the stomach [1-3] in order to increase gastric residence ... temperature. The resulting solution was poured into 250 ml of distilled water containing 0.01 %v/v Tween 80, maintained at different temperatures (i.e., 10, 20, 30 and. 40 0C), and then ... diluted (10 times) with 0.1M HCl (pH1.2) and filtered to remove ...

  17. 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,

  18. FORMULATION AND EVALUATION OF PRAVASTATIN SODIUM IMMEDIATE RELEASE TABLETS

    OpenAIRE

    Devanand Pinate; Ravikumar; Mahesh Kumar S; Senthil A; Raut Rahul; Narayanaswamy V B

    2012-01-01

    The aim of present investigation is to develop immediate release formulation of Pravastatin sodium for oral drug delivery by using suitable concentration of superdisintegrants. Croscarmellose sodium (AC-DI-SOL), povidone, MCC, Magnesium oxide, magnesium stearate were used to formulate the Immediate release tablet. Croscarmellose sodium was used as superdisintegrant and povidone was used as a binder to control the release of drug. Optimization of superdisintegrant concentration that can contro...

  19. Preparation and Dissolution Characteristics of Sustained Release ...

    African Journals Online (AJOL)

    In the present study, the applicability of Eudragit to produce matrix tablet by a wet granulation technique was evaluated. The effect of various formulation variables on the release of drug from these tablets was examined. Release profiles of diltiazem hydrochloride were investigated using the rotating basket method ...

  20. Modifying sorbents in controlled release formulations to prevent herbicides pollution

    Energy Technology Data Exchange (ETDEWEB)

    Cespedes, F.F.; Sanchez, M.V.; Garcia, S.P.; Perez, M.F. [University of Almeria, Almeria (Spain). Dept. of Inorganic Chemistry

    2007-10-15

    The herbicides chloridazon and metribuzin, identified as groundwater pollutants, were incorporated in alginate-based granules to obtain controlled release properties. In this research the effect of incorporation of sorbents such as bentonite, anthracite and activated carbon in alginate basic formulation were not only studied on encapsulation efficiency but also on the release rate of herbicides which was studied using water release kinetic tests. In addition, sorption studies of herbicides with bentonite, anthracite and activated carbon were made. The kinetic experiments of chloridazon and metribuzin release in water have shown that the release rate is higher in metribuzin systems than in those prepared with chloridazon, which has lower water solubility. Besides, it can be deduced that the use of sorbents reduces the release rate of the chloridazon and metribuzin in comparison to the technical product and to the alginate formulation without sorbents. The highest decrease in release rate corresponds to the formulations prepared with activated carbon as a sorbent. The water uptake, permeability, and time taken for 50% of the active ingredient to be released into water, were calculated to compare the formulations. On the basis of a parameter of an empirical equation used to fit the herbicide release data, the release of chloridazon and metribuzin from the various formulations into water is controlled by a diffusion mechanism.

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

    African Journals Online (AJOL)

    Particle size analysis indicated that the particles were irregular in shape with size ranging from 5.10 ± 0.10 to 13.40 ±. 2.20 µm. Yield decreased with increase in drug concentrations in the SLMs formulations. EE data showed that the microparticles containing 1 % w/w of AZT had the highest entrapment efficiency of 74.0.

  2. Lyophilized oral sustained release polymeric nanoparticles of nateglinide.

    Science.gov (United States)

    Kaleemuddin, Mohammad; Srinivas, Prathima

    2013-03-01

    The objective of this study is to formulate lyophilized oral sustained release polymeric nanoparticles of nateglinide in order to decrease dosing frequency, minimize side effects, and increase bioavailability. Nateglinide-loaded poly Ɛ-caprolactone nanoparticles were prepared by emulsion solvent evaporation with ultrasonication technique and subjected to various studies for characterization including scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, photon correlation spectroscopy and evaluated for in vitro drug release and pharmacodynamic studies. The influence of increase in polymer concentration, ultrasonication time, and solvent evaporation rate on nanoparticle properties was investigated. The formulations were optimized based on the above characterization, and the formulation using 5% polymer, 3-min sonication time, and rota-evaporated was found to have the best drug entrapment efficiency of 64.09±4.27% and size of 310.40±11.42 nm. Based on SEM, nanoparticles were found to be spherical with a smooth surface. In vitro drug release data showed that nanoparticles sustained the nateglinide release for over 12 h compared to conventional tablets (Glinate 60 mg), and drug release was found to follow Fickian mechanism. In vivo studies showed that nanoparticles prolonged the antidiabetic activity of nateglinide in rats significantly (p≤0.05) compared to the conventional tablets (Glinate 60 mg) over a period of 12 h. Accelerated stability data indicated that there was minimal to no change in drug entrapment efficiency.

  3. Cetirizine release from cyclodextrin formulated compressed chewing gum

    DEFF Research Database (Denmark)

    Stojanov, Mladen; Larsen, Kim Lambertsen

    2012-01-01

    Beside the efficient effect on masking cetirizine bitter taste, the cyclodextrins (CDs) as well could have influence on the release from the formulation. In vitro release profiles of cetirizine from compressed chewing gums containing α-, β- and γ-CD were investigated using a three cell chewing...... instead the complexes with respect to release yield. Thus unnecessary expenses for the complex preformulation may be avoided. Keywords: Cetirizine, chewing gum, cyclodextrin, complex, drug release...

  4. Development of sustained release tablets containing solid ...

    African Journals Online (AJOL)

    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.

  5. Development of extended-release formulation of domperidone using ...

    African Journals Online (AJOL)

    Purpose: To develop an extended-release formulation of domperidone using a blend of Raphia hookeri gum and hydroxypropyl methylcellulose as tablet matrix. Methods: Tablets (400 mg) containing 30 mg domperidone (DPD) were formulated using binary mixtures of hydroxypropyl methylcellulose (HPMC) and Raphia ...

  6. 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.

  7. Mechanistic model and analysis of doxorubicin release from liposomal formulations.

    Science.gov (United States)

    Fugit, Kyle D; Xiang, Tian-Xiang; Choi, Du H; Kangarlou, Sogol; Csuhai, Eva; Bummer, Paul M; Anderson, Bradley D

    2015-11-10

    Reliable and predictive models of drug release kinetics in vitro and in vivo are still lacking for liposomal formulations. Developing robust, predictive release models requires systematic, quantitative characterization of these complex drug delivery systems with respect to the physicochemical properties governing the driving force for release. These models must also incorporate changes in release due to the dissolution media and methods employed to monitor release. This paper demonstrates the successful development and application of a mathematical mechanistic model capable of predicting doxorubicin (DXR) release kinetics from liposomal formulations resembling the FDA-approved nanoformulation DOXIL® using dynamic dialysis. The model accounts for DXR equilibria (e.g. self-association, precipitation, ionization), the change in intravesicular pH due to ammonia release, and dialysis membrane transport of DXR. The model was tested using a Box-Behnken experimental design in which release conditions including extravesicular pH, ammonia concentration in the release medium, and the dilution of the formulation (i.e. suspension concentration) were varied. Mechanistic model predictions agreed with observed DXR release up to 19h. The predictions were similar to a computer fit of the release data using an empirical model often employed for analyzing data generated from this type of experimental design. Unlike the empirical model, the mechanistic model was also able to provide reasonable predictions of release outside the tested design space. These results illustrate the usefulness of mechanistic modeling to predict drug release from liposomal formulations in vitro and its potential for future development of in vitro - in vivo correlations for complex nanoformulations. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    African Journals Online (AJOL)

    In vitro release kinetics and mechanism of release were assessed sequentially in simulated gastric fluid (SGF, pH 1.2)and simulated intestinal fluid (SIF, pH 7.2). Results: The ratio 1: 1 formulation was the most stable in terms of physical observation.. Particle size analysis indicated that the particles were irregular in shape ...

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

    African Journals Online (AJOL)

    Investigation of the effects of certain formulation factors on release properties of paracetamol tablets using 23 factorial design. ... The release properties of the tablets- measured by the disintegration and the dissolution times were used as assessment parameters. Results: Changing the concentration of factor A from” low” to ...

  10. Controlled release formulations of metribuzin: release kinetics in water and soil.

    Science.gov (United States)

    Kumar, Jitendra; Nisar, Keyath; Shakil, N A; Walia, Suresh; Parsad, Rajender

    2010-05-01

    Controlled release (CR) formulations of metribuzin in Polyvinyl chloride [(PVC) (emulsion)], carboxy methyl cellulose (CMC), and carboxy methyl cellulose-kaolinite composite (CMC-KAO), are reported. Kinetics of its release in water and soil was studied in comparison with the commercial formulation (75 DF). Metribuzin from the commercial formulation became non-detectable after 35 days whereas it attained maxima between 35-49 days and became non-detectable after 63 days in the developed products. Amongst the CR formulations, the release in both water and soil was the fastest in CMC and slowest in PVC. The CMC-KAO composite reduced the rate of release as compared to CMC alone. The diffusion exponent (n value) of metribuzin in water and soil ranged from 0.515 to 0.745 and 0.662 to 1.296, respectively in the various formulations. The release was diffusion controlled with half release time (t(1/2)) from different controlled release matrices of 12.98 to 47.63 days in water and 16.90 to 51.79 days in soil. It was 3.25 and 4.66 days, respectively in the commercial formulation. The period of optimum availability of metribuzin in water and soil from controlled released formulations ranged from 15.09 to 31.68 and 17.99 to 34.72 days as against 5.03 and 8.80 days in the commercial formulation.

  11. Formulation and In vitro Dissolution Characteristics of Sustained ...

    African Journals Online (AJOL)

    ... gain occurred. Conclusion: Suitable sustained-release tablets of tizanidine hydrochloride have been successfully prepared using direct compression Drug release is sustained by increasing the content of the matrix polymers used. Keywords: Tizanidine, HPMC, EC, Koppcha, Hixson-Crowell, Stokes-Einstein's equation ...

  12. IPX066: a new intermediate-and extended-release carbidopa–levodopa formulation

    OpenAIRE

    Yacoubian, Talene A.

    2013-01-01

    Carbidopa–levodopa (CD–LD) is the mainstay of treatment for Parkinson’s disease (PD), yet most patients with advanced PD develop motor fluctuations with time when treated with CD–LD. Development of longer-acting CD–LD formulations is a major goal for reducing motor fluctuations in advanced PD. IPX066 is a new formulation of CD–LD that contains both an immediate-release and a sustained-release levodopa component, which is currently under review by the US FDA. Recent clinical trials have demons...

  13. Formulation development and evaluation of lamivudine controlled release tablets using cross-linked sago starch.

    Science.gov (United States)

    Singh, Akhilesh Vikram; Nath, Lila Kanta

    2013-02-01

    Modified starches based polymeric substances find utmost applicability in pharmaceutical formulation development. Cross-linked starches showed very promising results in drug delivery application. The present investigation concerns with the development of controlled release tablets of lamivudine using cross-linked sago starch. The cross-linked derivative was synthesized with phosphorous oxychloride and native sago starch in basic pH medium. The cross-linked sago starch was tested for acute toxicity and drug-excipient compatibility study. The formulated tablets were evaluated for various physical characteristics, in vitro dissolution release study and in vivo pharmacokinetic study in rabbit model. In vitro release study showed that the optimized formulation exhibited highest correlation (R) in case of zero order kinetic model and the release mechanism followed a combination of diffusion and erosion process. There was a significant difference in the pharmacokinetic parameters (T(max), C(max), AUC, V(d), T(1/2), and MDT) of the optimized formulation as compared to the marketed conventional tablet Lamivir®. The cross-linked starch showed promising results in terms of controlling the release behavior of the active drug from the matrix. The hydrophilic matrix synthesized by cross-linking could be used with a variety of active pharmaceutical ingredients for making their controlled/sustained release formulations.

  14. Effect of different polymers and their combinations on the release of metoclopramide HCl from sustained-release hydrophilic matrix tablets.

    Science.gov (United States)

    Savaşer, Ayhan; Taş, Çetin; Bayrak, Ziya; Özkan, Cansel Köse; Özkan, Yalçın

    2013-01-01

    Metoclopramide HCl (MTC) is commonly used for the management of gastrointestinal disorders. It has a short biological half-life and is usually administered four times daily to maintain effective concentrations throughout the day. The aim of this study is to develop sustained-release hydrophilic matrix tablet formulations of drug to achieve reproducible and predictable release rates, extended duration of activity, decreased toxicity, reduction of required dose, optimized therapy, and improved patient compliance. Hydroxypropylmethyl cellulose (HPMC), carboxymethylcellulose sodium (NaCMC), chitosan and Carbopol 981 were incorporated in the matrix system separately or in combinations as release controlling factor by direct compression technique. Compatibility among the formulation components was assessed by DSC and FTIR analysis. MTC release from matrix was evaluated by using the US Pharmacopeia dissolution apparatus II. All formulations met the criteria of pharmacopeial requirements. Dissolution studies show that polymer type and concentration are important parameters on drug release. Chitosan, carbopol and NaCMC formulations exhibited pH-dependent drug release profile whereas HPMC did not. All the formulations containing 1:1 ratio of HPMC and chitosan exhibited desired drug release showing that all active substance releases progressively in a period of whole dissolution time and therefore it can be regarded as worthy of consideration for the manufacture of sustained-release MTC product.

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

    African Journals Online (AJOL)

    Erah

    2010-12-27

    Dec 27, 2010 ... toothpaste and dental floss, and as a health- food/dietary supplement in various dosage forms - tablets, capsules, ampoules and syrups [3]. The United ..... by diffusion and that erosion contributes negligibly. F13 formulation showed an optimal drug release properties as it closely approximated zero order.

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

    Directory of Open Access Journals (Sweden)

    Munira eMomin

    2015-07-01

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

  17. Formulation and characterization of antibacterial fluoride-releasing sealants.

    Science.gov (United States)

    Fan, Yuwei; Townsend, Janice; Wang, Yapin; Lee, Eun Chee; Evans, Katie; Hender, Erica; Hagan, Joseph L; Xu, Xiaoming

    2013-01-01

    The purpose of this study was to formulate and characterize experimental antibacterial fluoride-releasing sealants and compare them with commercial sealants for fluoride release, recharge, adhesion, and microleakage. Two experimental sealants (Exp-1, Exp-2) containing a synthesized antibacterial fluoride-releasing monomer and fluoride-releasing filler were formulated. Exp-2 also contained NovaMin nanoparticles. Commercial sealants Clinpro (CL) FluroShield (FS), and SeLECT Defense (E34) were also included. Fluoride release from disk samples in deionized water was measured daily using an ion-selective electrode for 14 days, and after recharging with Neutra-Foam (2.0% sodium fluoride), fluoride was measured for 5 days. Microtensile bonding strengths (MTBS) to enamel were tested after 24-hour storage in water at 37°C or thermocycling 5-55°C for 1,000 cycles. A microleakage test was conducted on extracted teeth using a dye-penetration method. The data were analyzed using analysis of variance with the Tukey's honestly significant difference test and Kruskal-Wallis test. Exp-1 and Exp-2 had significantly higher fluoride release and recharge capabilities than CL and FL (Psealants had similar MTBS before and after thermocycling. Exp-2 and Exp-1 had significantly lower microleakage scores (Psealants had higher fluoride release and recharge capabilities and similar or better retention than commercial sealants.

  18. Formulation and Characterization of Antibacterial Fluoride-releasing Sealants

    Science.gov (United States)

    Fan, Yuwei; Townsend, Janice; Wang, Yapin; Lee, Eun Chee; Evans, Katie; Hender, Erica; Hagan, Joseph L.; Xu, Xiaoming

    2013-01-01

    Purpose The purpose of this study was to formulate and characterize experimental antibacterial fluoride-releasing sealants and compare them with commercial sealants for fluoride release, recharge, adhesion, and microleakage. Methods Two experimental sealants (Exp-1, Exp-2) containing a synthesized antibacterial fluoride-releasing monomer and fluoride-releasing filler were formulated. Exp-2 also contained NovaMin nanoparticles. Commercial sealants Clinpro (CL) FluoroShield (FS), and SeLECT Defense (E34) were also included. Fluoride release from disk samples in deionized water was measured daily using an ion-selective electrode for 14 days, and after recharging with Neutra-Foam (2.0% sodium fluoride), fluoride was measured for 5 days. Microtensile bonding strengths (MTBS) to enamel were tested after 24-hour storage in water at 37°C or thermocycling 5-55°C for 1,000 cycles. A microleakage test was conducted on extracted teeth using a dye-penetration method. The data were analyzed using analysis of variance with the Tukey’s honestly significant difference test and Kruskal-Wallis test. Results Exp-1 and Exp-2 had significantly higher fluoride release and recharge capabilities than CL and FL (P<.05). All tested sealants had similar MTBS before and after thermocycling. Exp-2 and Exp-1 had significantly lower microleakage scores (P<.05) than other groups. Conclusion The experimental sealants had higher fluoride release and recharge capabilities and similar or better retention than commercial sealants. PMID:23635887

  19. Formulation optimization study for an immediate-release tablet.

    Science.gov (United States)

    Kyriacos, Soula; Dimassi, Hani

    2009-01-01

    A simple method based on statistical analysis was used to optimize an immediate-release tablet formulation that includes a water soluble drug. The objective of this study was to optimize different factors to develop a tablet formulation that has good tablet characteristics (hardness of 85 to 90 Newtons), disintegration time between 3 to 6 minutes, and friability of less than 1%. The critical formulation/process factors were the type and concentration of microcrystalline cellulose, the ratio of lactose to microcrystalline cellulose, the concentration of croscarmellose, and the the compression force. A two-step approach was implemented. First an optimization study was performed to determine the type of microcrystalline cellulose and its ratio to lactose. Subsequently, a final optimization formulation study was performed based on the results obtained in the preliminary study. Data were analyzed using the SPSS 15 (Statistical Software for Social Sciences). The differences in means between the formulation and the targeted product were tested using the independent t-test. The optimization study gave the following results: croscarmellose 1%, anhydrous lactose: Avicel PH-302 at a ratio of 3 to 1, magnesium stearate 0.25% compressed into tablets at a pressure of 2.5 tons. A high P value reflected no statistical difference with the reference product. A final formulation was scaled up to 52 tablets and product quality was confirmed. The new formulation was successfully developed using a simple two-step approach. The results of the study in terms of disintegration, hardness, and friability showed no statistically significant defference between the new and the targeted formulation. Statistical analysis provides a systemic approach and allows a rapid and effective way to compound an immediate-release tablet for a water-soluble drug.

  20. [Application of an artificial neural network in the design of sustained-release dosage forms].

    Science.gov (United States)

    Wei, X H; Wu, J J; Liang, W Q

    2001-09-01

    To use the artificial neural network (ANN) in Matlab 5.1 tool-boxes to predict the formulations of sustained-release tablets. The solubilities of nine drugs and various ratios of HPMC: Dextrin for 63 tablet formulations were used as the ANN model input, and in vitro accumulation released at 6 sampling times were used as output. The ANN model was constructed by selecting the optimal number of iterations (25) and model structure in which there are one hidden layer and five hidden layer nodes. The optimized ANN model was used for prediction of formulation based on desired target in vitro dissolution-time profiles. ANN predicted profiles based on ANN predicted formulations were closely similar to the target profiles. The ANN could be used for predicting the dissolution profiles of sustained release dosage form and for the design of optimal formulation.

  1. Individual Oral Therapy with Immediate Release and Effervescent Formulations Delivered by the Solid Dosage Pen

    Science.gov (United States)

    Wening, Klaus; Laukamp, Eva Julia; Thommes, Markus; Breitkreutz, Jörg

    2012-01-01

    New devices enabling freely selectable dosing of solid oral medications are urgently needed for personalized medicine. One approach is the use of the recently published Solid Dosage Pen, allowing flexible dosing of tablet-like sustained release slices from drug loaded extruded strands. Slices were suitable for oral single dosed application. The aim of the present study was the development of immediate release dosage forms for applications of the device, especially for young children. Using two model drugs, two different concepts were investigated and evaluated. Effervescent formulations were manufactured by an organic wet-extrusion process and immediate release formulations by a melt-extrusion process. Dissolution experiments were performed for both formulations to ensure the immediate release behavior. Extruded strands were individually dosed by the Solid Dosage Pen. Various doses of the two formulations were analyzed regarding uniformity of mass and content according to pharmacopoeial specifications. Proof of concept was demonstrated in both approaches as results comply with the regulatory requirements. Furthermore, storing stress tests were performed and drug formulations were characterized after storing. The results show that suitable packaging material has been selected and storage stability is probable. PMID:25562361

  2. Slow- Release Fertilizer Formulation Using Acrylic and Chitosan Coating

    Directory of Open Access Journals (Sweden)

    Lili Handayani

    2015-01-01

    Full Text Available The low-efficiency problem in fertilizer application can be overcome by controlling fertilizer solubility, i.e. by rendering the fertilizer to be released gradually; such material is also known as slow-release fertilizer (SRF. This research was aimed to formulate SRF by coating technique using acrylic and chitosan as the coating material, and to evaluate fertilizer resistance to too fast disintegration, and rate of nutrient release method. The results demonstrated that fertilizer formulation containing N, P, K, Fe, Cu, and Zn with granulation technique yielded 74% of granules with 2-5 mm in diameter. The SRFs (formulated fertilizer with acrylic or chitosan coating were more resistant to water pounding than non-SRF. Furthermore, shaking test with distilled water or 2% citric acid, or by percolation test with distilled water showed that the SRFs had lower nutrient solubility than the non-SRFs. The results of shaking test also specifically indicated that coating with acrylic made the fertilizer more resistant to the citric acid,suggesting that this coating material would be more suitable in acidic soils. The SRFs formulated with the addition of chitosan during blending of micronutrients prior to mixing with macronutrients, granulation, and final coating exhibited lower nutrient solubility than the SRFs without the pre-coating chitosan addition.

  3. Controlled release tablet formulation containing natural Δ(9)-tetrahydrocannabinol.

    Science.gov (United States)

    Punyamurthula, Nagendra S; Hingorani, Tushar; Adelli, Goutham; Gul, Waseem; ElSohly, Mahmoud A; Repka, Michael A; Majumdar, Soumyajit

    2016-01-01

    Cannabinoids are increasingly being used in the treatment of chemotherapy-induced nausea and vomiting (CINV) because of their action on the cannabinoid receptors, CB1 and CB2. The currently marketed capsule formulations (sesame oil based and crystalline powder) are required to be administered frequently to maintain therapeutic levels, which leads to non-compliance. In the present study, oral controlled release tablet formulations of Δ(9)-tetrahydrocannabinol (THC) were prepared using the lipids Precirol® and Compritol®. Release profiles using THC-lipid matrices and/or with the lipids in the external phase (blend) were evaluated. The effect of directly compressible diluents lactose mixture (Ludipress®), dicalcium phosphate anhydrous (Emcompress®) and microcrystalline cellulose (Avicel® 102) on tablet characteristics and in vitro drug release was also investigated. Further, in vitro THC release in the presence of a lipase inhibitor, Pluronic® F68, was also studied. A 24 h zero-order THC release profile was obtained with a combination of Precirol® and Compritol® in the compression blend. Addition of Pluronic® F68 did not alter THC release in vitro. These optimized tablets were chemically and physically stable for 3 months, the last time point tested, at 25 °C/60% RH. The overall results demonstrate the feasibility of preparing oral THC tablets for once a day administration which can improve CINV management.

  4. Sustained Release of a Water~§oiuble itrng i'rom Directly ...

    African Journals Online (AJOL)

    desirable properties have encouraged a more extensive assessment of the gum as a hydrophilic controlled release delivery system. The aim of this study was to evaluate the gum extracted from the pods of Hibiscus esculentus. (commonly known as okra) in in vitro sustained release formulations containing the water-.

  5. [Clinical data of the prolonged-release formulation of ropinirole].

    Science.gov (United States)

    Jost, W H; Bergmann, L

    2010-03-01

    Ropinirole is a non-ergoline dopamine agonist with medium elimination half time, which has been licensed for the therapy of idiopathic Parkinson syndrome in mono- and add-on therapy for more than 10 years. Since 2008 a prolonged-release formulation has been available in Germany, which can be taken once daily. This formulation results in less plasma level fluctuations compared to the thrice-daily immediate-release formulation enabling smoother dopaminergic therapy with symptomatic efficacy day and night. Ropinirole PR has shown good efficacy and tolerability in controlled trials in monotherapy in early patients as well as in add-on studies in advanced patients. In a head-to-head comparison of both formulations as add-on therapy in advanced patients higher doses were achieved with ropinirole PR accompanied by a higher mean decrease of L-Dopa dose. Under these conditions significantly higher efficacy was observed. The titration regime of ropinirole PR is faster with significant efficacy versus placebo as early as in week 2. Especially in patients with pre-existing Parkinson-related poor sleep quality positive effects on sleep and nocturnal symptoms were shown.

  6. Development of enteric coated sustained release minitablets containing mesalamine

    National Research Council Canada - National Science Library

    Souza, Dayse Fernanda de; Goebel, Karin; Andreazza, Itamar Francisco

    2013-01-01

    The aim of this study was to develop and evaluate a multiparticulate modified release system, composed of minitablets with a sustained release matrix system coated with a pH-dependent release polymer...

  7. 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

  8. Formulation and in vitro evaluation of theophylline-Eudragit® sustained-release tablets Desenvolvimento e avaliação in vitro de comprimidos de liberação prolongada de teofilina preparados com Eudragit®

    Directory of Open Access Journals (Sweden)

    Evelyn Ojoe

    2005-09-01

    Full Text Available Tablets containing theophylline (66.67% based on a Eudragit® RS 30D and NE 30D matrices containing 10% to 30% of either of the polymer were produced by compression method. The influence of the different proportions of methacrylic esters, the use of lactose and tribasic calcium phosphate as diluents and also the effects of the addition of magnesium stearate as a hydrophobic agent lubricant on the theophylline release, were studied. Physicochemical analyses and drug content was evaluated. In vitro drug release studies were carried out in simulated gastric fluid without pepsin (pH1.2 and simulated intestinal fluid without pancreatin (pH7.5. A relatively prolonged release of theophylline from the polymer matrices for a 7 hr-release period was detected. Magnesium stearate at 0.5% and Eudragit® NE 30D at 10% was considered a better sustained-release matrix compressed theophylline tablets comparing with Eudragit® RS 30D in the same conditions (USP. Results from physicochemical analyses were in accordance with specifications. The release patterns were analyzed from the viewpoint of square-root of time and as a first-order, zero-order kinetics, and Higuchi. Additionally, half-life of release (Td50% and dissolution rates (kd were calculated. Higuchi was the model that better fitted theophylline kinetic, and diffusion controlled was involved.Comprimidos contendo teofilina (66.67% e polímeros de Eudragit® NE 30D e RS 30D entre 10 e 30% foram produzidos por compressão. A influência das diferentes proporções de ésteres do ácido metacrílico, uso da lactose e fosfato de cálcio tribásico como diluente, bem como os efeitos da adição de estearato de magnésio como agente lubrificante hidrofóbico na liberação da teofilina foram estudados. Análises físico-químicas e teor de fármaco foram avaliados. Estudos da liberação do fármaco in vitro foram conduzidos em fluido gástrico simulado (pH 1,2 e fluido intestinal simulado sem pancreatina (p

  9. Gastrointestinal release behaviour of modified-release drug products: dynamic dissolution testing of mesalazine formulations.

    Science.gov (United States)

    Goyanes, Alvaro; Hatton, Grace B; Merchant, Hamid A; Basit, Abdul W

    2015-04-30

    The aminosalicylate mesalazine (mesalamine) forms the mainstay of treatment in ulcerative colitis (UC), a disease for which many commercial modified-release products have been developed with the aim of providing targeted gastrointestinal release. The release profiles of five of these commercial formulations were evaluated in bicarbonate buffer using a novel dissolution model that mimics the dynamic conditions of the gastrointestinal tract. Monolithic and multi-particulate mesalazine formulations with pH-dependent and/or independent release mechanisms were evaluated (Asacol(®) 800, Octasa(®), Mezavant(®) XL, Salofalk(®), Pentasa(®)), and each of the products displayed a distinctive dissolution profile. The dissolution results for Mezavant(®) XL (Lialda(®)) (lag time 290 min) demonstrated good correlation with previously reported in vivo disintegration times assessed by gamma-scintigraphy in humans. Octasa(®) showed a similar lag time to Mezavant(®) XL. Drug release from Asacol(®) 800 (Asacol(®) HD) showed a wide standard deviation, reflecting the great variability in vivo. Salofalk(®) displayed both delayed release and extended release characteristics. Pentasa(®) released more than 50% of its drug load in the stomach compartment of the model, which is attributed to the absence of a gastro-resistant coating in this product. The new dissolution method provided a realistic and discriminative in vitro assessment of mesalazine release from different formulations. These results demonstrate that this strategy can be used to predict intestinal release behaviour, and potentially aid the rational design of products developed to target different sites of the gut. Copyright © 2015. Published by Elsevier B.V.

  10. Effects of artemisinin sustained-release granules on mixed alga growth and microcystins production and release.

    Science.gov (United States)

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

    2015-12-01

    To safely and effectively apply artemisinin sustained-release granules to control and prevent algal water-blooms, the effects of artemisinin and its sustained-release granules on freshwater alga (Scenedesmus obliquus (S. obliquus) and Microcystis aeruginosa (M. aeruginosa)), as well as the production and release of microcystins (MCs) were studied. The results showed that artemisinin sustained-release granules inhibited the growth of M. aeruginosa (above 95% IR) and S. obliquus (about 90% IR), with M. aeruginosa more sensitive. The artemisinin sustained-release granules had a longer inhibition effect on growth of pure algae and algal coexistence than direct artemisinin dosing. The artemisinin sustained-release granules could decrease the production and release of algal toxins due to the continued stress of artemisinin released from artemisinin sustained-release granules. There was no increase in the total amount of MC-LR in the algal cell culture medium.

  11. Encapsulated Urea-Kaolinite Nanocomposite for Controlled Release Fertilizer Formulations

    Directory of Open Access Journals (Sweden)

    Siafu Ibahati Sempeho

    2015-01-01

    Full Text Available Urea controlled release fertilizer (CRF was prepared via kaolinite intercalation followed by gum arabic encapsulation in an attempt to reduce its severe losses associated with dissolution, hydrolysis, and diffusion. Following the beneficiation, the nonkaolinite fraction decreased from 39.58% to 0.36% whereas the kaolinite fraction increased from 60.42% to 99.64%. The X-ray diffractions showed that kaolinite was a major phase with FCC Bravais crystal lattice with particle sizes ranging between 14.6 nm and 92.5 nm. The particle size varied with intercalation ratios with methanol intercalated kaolinite > DMSO-kaolinite > urea-kaolinite (KPDMU. Following intercalation, SEM analysis revealed a change of order from thick compact overlapping euhedral pseudohexagonal platelets to irregular booklets which later transformed to vermiform morphology and dispersed euhedral pseudohexagonal platelets. Besides, dispersed euhedral pseudohexagonal platelets were seen to coexist with blocky-vermicular booklets. In addition, a unique brain-form agglomeration which transformed into roundish particles mart was observed after encapsulation. The nanocomposites decomposed between 48 and 600°C. Release profiles showed that 100% of urea was released in 97 hours from KPDMU while 87% was released in 150 hours from the encapsulated nanocomposite. The findings established that it is possible to use Pugu kaolinite and gum arabic biopolymer to prepare urea CRF formulations.

  12. Tailor-Made Pentablock Copolymer Based Formulation for Sustained Ocular Delivery of Protein Therapeutics

    Directory of Open Access Journals (Sweden)

    Sulabh P. Patel

    2014-01-01

    Full Text Available The objective of this research article is to report the synthesis and evaluation of novel pentablock copolymers for controlled delivery of macromolecules in the treatment of posterior segment diseases. Novel biodegradable PB copolymers were synthesized by sequential ring-opening polymerization. Various ratios and molecular weights of each block (polyglycolic acid, polyethylene glycol, polylactic acid, and polycaprolactone were selected for synthesis and to optimize release profile of FITC-BSA, IgG, and bevacizumab from nanoparticles (NPs and thermosensitive gel. NPs were characterized for particle size, polydispersity, entrapment efficiency, and drug loading. In vitro release study of proteins from NPs alone and composite formulation (NPs suspended in thermosensitive gel was performed. Composite formulations demonstrated no or negligible burst release with continuous near zero-order release in contrast to NPs alone. Hydrodynamic diameter of protein therapeutics and hydrophobicity of PB copolymer exhibited significant effect on entrapment efficiency and in vitro release profile. CD spectroscopy confirmed retention of structural conformation of released protein. Biological activity of released bevacizumab was confirmed by in vitro cell proliferation and cell migration assays. It can be concluded that novel PB polymers can serve a platform for sustained delivery of therapeutic proteins.

  13. Process Analytical Quality Control of Tailored Drug Release Formulation Prepared via Hot-Melt Extrusion Technology.

    Science.gov (United States)

    Park, Jun-Bom; Lee, Beom-Jin; Kang, Chin-Yang; Repka, Michael A

    2017-04-01

    The objective of the present study was to compare the influence of Eudragit® RS PO and RL PO blends on the release of water-soluble and insoluble drugs from hot-melt extruded formulations. In addition, we aimed to evaluate drug content uniformity and distribution by Fourier transform-infrared (FT-IR) chemical imaging. Theophylline (TP) and carbamazepine (CBZ) were selected as the water-soluble and insoluble model drugs, respectively. Eudragit® RS PO and RL PO were selected as the polymeric matrices. FT-IR chemical imaging clearly demonstrated the content uniformity and distribution for both drugs in the extrudates, which was confirmed by HPLC. Increasing the ratio of Eudragit® RL PO led to an increase in the in vitro drug release, whereas an increase in the ratio of Eudragit® RS PO sustained the drug release for up to 12 h. The hot-melt extrusion of TP and CBZ with varying ratios of Eudragit® RS PO and RL PO can be employed to tailor the drug release profiles. In this study, we demonstrated, for the first time, the use of FT-IR chemical imaging as a process analytical technique to determine the drug content uniformity and distribution. Our data correlated well with the results of HPLC analysis in the study of tailored drug release from the prepared hot-melt extruded formulation.

  14. Continuous direct compression as manufacturing platform for sustained release tablets.

    Science.gov (United States)

    Van Snick, B; Holman, J; Cunningham, C; Kumar, A; Vercruysse, J; De Beer, T; Remon, J P; Vervaet, C

    2017-03-15

    This study presents a framework for process and product development on a continuous direct compression manufacturing platform. A challenging sustained release formulation with high content of a poorly flowing low density drug was selected. Two HPMC grades were evaluated as matrix former: standard Methocel CR and directly compressible Methocel DC2. The feeding behavior of each formulation component was investigated by deriving feed factor profiles. The maximum feed factor was used to estimate the drive command and depended strongly upon the density of the material. Furthermore, the shape of the feed factor profile allowed definition of a customized refill regime for each material. Inline NIRs was used to estimate the residence time distribution (RTD) in the mixer and monitor blend uniformity. Tablet content and weight variability were determined as additional measures of mixing performance. For Methocel CR, the best axial mixing (i.e. feeder fluctuation dampening) was achieved when an impeller with high number of radial mixing blades operated at low speed. However, the variability in tablet weight and content uniformity deteriorated under this condition. One can therefore conclude that balancing axial mixing with tablet quality is critical for Methocel CR. However, reformulating with the direct compressible Methocel DC2 as matrix former improved tablet quality vastly. Furthermore, both process and product were significantly more robust to changes in process and design variables. This observation underpins the importance of flowability during continuous blending and die-filling. At the compaction stage, blends with Methocel CR showed better tabletability driven by a higher compressibility as the smaller CR particles have a higher bonding area. However, tablets of similar strength were achieved using Methocel DC2 by targeting equal porosity. Compaction pressure impacted tablet properties and dissolution. Hence controlling thickness during continuous manufacturing of

  15. 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 F10 composed of 28.5% Eudragit RSPM, 3% NaHCO3, and 7% citric acid provided sustained drug release. 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). The prepared floating tablets of ITO HCl (F10) could be a promising drug delivery system with sustained-release action and enhanced drug bioavailability.

  16. Controlled Release System for Localized and Sustained Drug Delivery Applications

    Science.gov (United States)

    Rodriguez, Lidia Betsabe

    Current controlled release formulations has many drawbacks such as excess of initial burst release, low drug efficiency, non-degradability of the system and low reproducibility. The present project aims to offer an alternative by developing a technique to prepare uniform, biodegradable particles ( ˜19 mum ) that can sustainably release a drug for a specific period of time. Chitosan is a natural polysaccharide that has many characteristics to be used for biomedical applications. In the last two decades, there have been a considerable number of studies affirming that chitosan could be used for pharmaceutical applications. However, chitosan suffers from inherent weaknesses such as low mechanical stability and dissolution of the system in acidic media. In the present study, chitosan microparticles were prepared by emulsification process. The model drug chosen was acetylsalicylic acid as it is a small and challenging molecule. The maximum loading capacity obtained for the microparticles was approximately 96%. The parameters for the preparation of uniform particles with a narrow size distribution were identified in a triangular phase diagram. Moreover, chitosan particles were successfully coated with thin layers of poly lactic-coglycolic acid (PLGA) and poly lactic acid (PLA). The performance of different layerswas tested for in vitro drug release and degradation studies. Additionally, the degradability of the system was evaluated by measuring the weight loss of the system when exposed to enzyme and without enzyme. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM) and inductively coupled plasma optical emission spectrometry (ICP-OES) were used to characterize the controlled release system. Additionally, the in vitro drug release was monitored by ultraviolet-visible spectrophotometry (UV-Vis) and liquid chromatography mass spectrometry (LC-MS). The results obtained from this project showed that it is

  17. The control of phosphate ion release from ion permeable microcapsules formulated into rosin varnish and resin glaze.

    Science.gov (United States)

    Falbo, Michelle M; Elassal, Phillip; Greving, Theresa A; McHale, William A; Latta, Mark A; Gross, Stephen M

    2013-07-01

    The occurrence of recurrent caries at the interface of dental materials and the enamel surface is an important performance issue. The objective of this study was to investigate the most effective way to control the release rate of bioavailable phosphate ions contained in aqueous solutions within ion permeable microcapsules formulated into rosin based varnishes and resin based sealants, in order to promote remineralization. Microcapsules that contained aqueous solutions of K2HPO4 with concentrations from 0.8 to 7.4M were prepared. 3-50w/w% of microcapsules were loaded into both rosin and resin based dental formulations. The effect of initial salt solution concentration inside the microcapsules and weight percent loading of the microcapsules on release rate were contrasted. The effect of microcapsule loading was found to be highly dependent on the continuous phase. In rosin, 3-15w/w% loading resulted in rapid release of ions. Higher weight percent loadings were initially slower but resulted in sustained release of ions. In resin, 3-15w/w% formulations slowly released ions for at least 300 days, while higher loading formulations released an initial burst of ions. Initial salt solution concentration contained inside the microcapsule affected ion release rate. Initial rate of ion release was greatest at a concentration that was less than the maximum concentration studied in both continuous phases. Phosphate ion release can be controlled from resin or rosin based dental material by adjusting initial salt solution concentration in microcapsules or percent loading of microcapsules. The potential for burst release from a varnish or slow, sustained release from a sealant has been demonstrated. Copyright © 2013 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  18. 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.

  19. Preparation in high-shear mixer of sustained-release pellets by melt pelletisation.

    Science.gov (United States)

    Voinovich, D; Moneghini, M; Perissutti, B; Filipovic-Grcic, J; Grabnar, I

    2000-08-10

    The preparation of sustained-release pellets by melt pelletisation was investigated in a 10-l high shear mixer and ternary mixtures containing stearic acid as a melting binder, anhydrous lactose as a filler and theophylline as a model drug. A translated Doehlert matrix was applied for the optimisation of process variables and quality control of pellets characteristics. After determination of size distribution, the pellets were characterised with scanning electron microscopy, X-ray photoelectron spectroscopy and porosimetric analysis. Finally, the in vitro release from every single size fraction was evaluated and the release mechanism was analysed. Since the drug release rate decreased when enhancing the pellet size fraction, the 2000-microm fraction, exhibiting a substantially zero-order release, was selected for further in vivo biovailability studies. These data demonstrated that pellets based on the combination of stearic acid and lactose can be used to formulate sustained release pellets for theophylline.

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

    Indian Academy of Sciences (India)

    Home; Journals; Bulletin of Materials Science; Volume 40; Issue 2. Design and development of sustained-release ... Keywords. Silica nanoparticles; glyburide; sustained release; sol–gel method. ... Silica nanoparticles were synthesized by the sol–gel method using tetra-ethyl ortho-silane as a precursor. Glyburide was ...

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

    Directory of Open Access Journals (Sweden)

    Zbyněk Sklenář

    2012-01-01

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

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

    African Journals Online (AJOL)

    Conclusion: Transdermal films of diclofenac, formulated with permeation enhancers, may have greater therapeutic advantages over conventional oral tablets in terms of prolonged release and improvement of patient compliance in rheumatoid arthritis. Keywords: Analgesic activity, Diclofenac, Permeation enhancer, ...

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

    NARCIS (Netherlands)

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

    2005-01-01

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

  4. Sustained Release of Amoxicillin from Ethyl Cellulose-Coated Amoxicillin/Chitosan–Cyclodextrin-Based Tablets

    OpenAIRE

    Songsurang, Kultida; Pakdeebumrung, Jatuporn; Praphairaksit, Narong; Muangsin, Nongnuj

    2010-01-01

    Sustained release mucoadhesive amoxicillin tablets with tolerance to acid degradation in the stomach were studied. The sustained-release tablets of amoxicillin were prepared from amoxicillin coated with ethyl cellulose (EC) and then formulated into tablets using chitosan (CS) or a mixture of CS and beta-cyclodextrin (CD) as the retard polymer. The effects of various (w/w) ratios of EC/amoxicillin, the particle sized of EC coated amoxicillin and the different (w/w) ratios of CS/CD for the reta...

  5. Sustained protein release from hydrogel microparticles using layer-by-layer (LbL) technology.

    Science.gov (United States)

    Sakr, Omar S; Jordan, Olivier; Borchard, Gerrit

    2016-10-01

    Since most of developed therapeutic proteins are intended to treat chronic diseases, patients are prescribed multiple injections for long time periods, and therefore, sustained release formulations are much needed. However, challenges facing these formulations are quite significant. In this context, a model protein, lysozyme (Lys), was loaded on hydrogel microparticles (beads) and the ability of layer-by-layer (LbL) coating to control Lys release and maintain its activity over a one-month period was investigated. LbL coating was composed of chondroitin sulfate as a negatively charged polyelectrolyte and a biocompatible, hydrolytically degradable poly β-aminoester as a positively charged polyelectrolyte. Loading distribution was monitored by fluorescence imaging, and followed by depositing a series of LbL coatings of different thicknesses. Release of Lys from these formulations was studied and activity of released fraction was determined. Lys was loaded effectively on hydrogel beads achieving about 9 mg protein/100 mg wet spheres. LbL coating was proven successful by monitoring the zeta potential of the beads, which was reversed after the addition of each layer. In vitro release studies showed sustained release profiles that depend on the thickness of the deposited coat, with t50 extended from 4.9 to 143.9 h. More importantly, released Lys possessed a high degree of biological activity during the course of release maintaining at least 72% of initial activity. Successful loading of Lys and extension of its release while maintaining a considerable degree of activity might make this formulation suitable for use with other active therapeutic proteins.

  6. The impact of the injection mold temperature upon polymer crystallization and resulting drug release from immediate and sustained release tablets.

    Science.gov (United States)

    Van Renterghem, Jeroen; Dhondt, Heleen; Verstraete, Glenn; De Bruyne, Michiel; Vervaet, Chris; De Beer, Thomas

    2018-01-31

    It was the aim of this study to elucidate the impact of the injection mold temperature upon the polymer crystallinity, its microstructure and the resulting drug release from immediate and sustained release tablets containing semi-crystalline polymers. The immediate release formulation contained 20% (w/w) ketoprofen (KETO) in poly (ethylene oxide) (PEO) and the sustained release formulation contained 20 - 40% (w/w) metoprolol tartrate (MPT) in polycaprolactone (PCL). Physical mixtures of drug-polymer were characterized via isothermal crystallization experiments using DSC and rheological measurements to elucidate the impact of the drug solid-state upon the crystallization kinetics. Tablets were prepared using various thermal histories (extrusion barrel temperature and injection mold temperatures). Polymer crystallinity and microstructure in the tablets was characterized via DSC and polarized optical microscopy. The polymer microstructure was altered by the various applied thermal histories. The differences in PEO crystallinity induced by the various mold temperatures did not affect the KETO dissolution from the tablets. On the other hand, MPT (20 - 40% w/w) dissolution from the PCL matrix when extruded at 80 °C and injection molded at 25 and 35 °C was significantly different due to the changes in the polymer microstructure. More perfect polymer crystals are obtained with higher mold temperatures, decreasing the drug diffusion rate through the PCL matrix. The results presented in this study imply that the injection mold temperature should be carefully controlled for sustained release formulations containing hydrophobic semi-crystalline polymers. Copyright © 2018. Published by Elsevier B.V.

  7. Development of lipid micromatrices based sustained release tablets of glipizide: suitability of stearic acid as release retardant

    Directory of Open Access Journals (Sweden)

    Deepak Singh

    2016-06-01

    Full Text Available The objective of research was to explore the suitability of lipids like compritol 888 ATO and stearic acid as release retardant to develop sustained release (SR tablets. The SR micromatrices of lipid (s and glipizide were prepared (LM1- LM6 as intermediate product by fusion method and assessed for various pharmacotechnical properties. Micromatrices were formulated as SR tablets (F1-F6 by direct compression method and subjected to Pharmacopoeial and Non Pharmacopoeial tests.  In vitro drug release behavior of SR tablets demonstrated incomplete release of drug from compitrol based formulations whereas stearic acid based formulations (F4-F6 released more than 90% drug in 12 h with F5 displaying  maximum %CDR of  95.70 ± 0.78%. A t50% of 3 h exhibited by F5 was significantly lower (2.7 h than of marketed formulation (Glytop SR® (t50% = 5.7 h. Similarity and dissimilarity factor for F5, with reference to Glytop SR® was 21.65% and 26.34% respectively, suggesting F5 has potential to exercise better control on drug release. Scanning Electron Microscopy (SEM revealed drug particles embedded in stearic acid micromatrices that were confirmed by The X-ray powder diffraction (XRPD and simultaneously Diffuse Reflectance Infrared Fourier Transform (DRIFT confirmed the stability of F5. Conclusively, stearic acid explored as a suitable lipidic release retardant for development of SR tablet of glipizide that were stable for the test period of 6 months.

  8. Dual delivery nanosystem for biomolecules. Formulation, characterization, and in vitro release.

    Science.gov (United States)

    Ortega-Oller, Inmaculada; Del Castillo-Santaella, Teresa; Padial-Molina, Miguel; Galindo-Moreno, Pablo; Jódar-Reyes, Ana Belén; Peula-García, José Manuel

    2017-11-01

    Because of the biocompatible and biodegradable properties of poly (lactic-co-glycolic acid) (PLGA), nanoparticles (NPs) based on this polymer have been widely studied for drug/biomolecule delivery and long-term sustained-release. In this work, two different formulation methods for lysozyme-loaded PLGA NPs have been developed and optimized based on the double-emulsion (water/oil/water, W/O/W) solvent evaporation technique. They differ mainly in the phase in which the surfactant (Pluronic® F68) is added: water (W-F68) and oil (O-F68). The colloidal properties of these systems (morphology by SEM and STEM, hydrodynamic size by DLS and NTA, electrophoretic mobility, temporal stability in different media, protein encapsulation, release, and bioactivity) have been analyzed. The interaction surfactant-protein depending on the formulation procedure has been characterized by surface tension and dilatational rheology. Finally, cellular uptake by human mesenchymal stromal cells and cytotoxicity for both systems have been analyzed. Spherical hard NPs are made by the two methods However, in one case, they are monodisperse with diameters of around 120nm (O-F68), and in the other case, a polydisperse system of NPs with diameters between 100 and 500nm is found (W-F68). Protein encapsulation efficiency, release and bioactivity are maintained better by the W-F68 formulation method. This multimodal system is found to be a promising "dual delivery" system for encapsulating hydrophilic proteins with strong biological activity at the cell-surface and cytoplasmic levels. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. In-vivo/in-vitro correlation of four extended release formulations of pseudoephedrine sulfate.

    Science.gov (United States)

    Mojaverian, P; Rosen, J; Vadino, W A; Liebowitz, S; Radwanski, E

    1997-01-01

    An in-vivo/in-vitro correlation was established for four formulations of pseudoephedrine sulfate modified release tablets exhibiting different in-vivo and in-vitro release rate and absorption characteristics. In-vitro release rate data were obtained for 12 individual tablets of each formulation using the USP Apparatus 2 paddle stirrer at 50 rev min-1 in 1000 ml 0.1 N hydrochloric acid for the first hour followed by 0.1 M phosphate buffer at pH 7.5 for hours 2-16. Inspection of the individual and mean release rate data indicated that the in-vitro release rate of pseudoephedrine sulfate was consistent with the intended design of the four extended release formulations. The in-vivo bioavailability and pharmacokinetics of these formulations were evaluated in 20 healthy volunteers under fasted conditions. Wagner-Nelson analyses of the in-vivo data revealed extended release absorption profiles for all four formulations. Linear regression analyses of the mean percentage of dose absorbed versus the mean in-vitro release resulted in statistically significant correlations (r2 > 0.99, p < 0.0001) for each formulation. Qualitative rank order correlations were observed among all combinations of in-vivo and in-vitro parameters. These data support a Level A correlation between in-vivo absorption profiles and in-vitro release rates of four pseudoephedrine sulfate extended release formulations determined in fasted healthy volunteers.

  10. Development of sustained-release matrix tablets of BKP-01-041 (tilorone derivative) containing Hypromellose.

    Science.gov (United States)

    Chen, Liangmei; Wang, Fei

    2013-10-01

    The objective of this research was to develop and evaluate sustained-release matrix tablets of BKP-01-041 (tilorone derivative) based on Hypromellose (hydroxypropyl methylcellulose, HPMC) as the matrix forming polymer. The sustained-release tablets were prepared by the wet granulation method. The influence of HPMC viscosity and ratios on drug release was investigated in vitro. Dissolution of the tablets developed with 26% HPMC K4 M/K100 M (1:2) (w/w) content showed a better drug release profile than the other batches tested in 12 h. Drug release from the optimal formulation was analyzed using release kinetics equations. The release kinetics parameters were determined and the value of the exponent (n) representing the apparent drug release mechanism determined from the Peppas equation was about 0.726. These results suggest that the drug release mechanism was non-Fickian (0.45 < n < 0.89), and drug release was dependent on both drug diffusion and polymer erosion.

  11. Preparation and Evaluation of Sustained Release Matrix Tablets of ...

    African Journals Online (AJOL)

    Erah

    Purpose: To prepare oral sustained release matrix tablets of a highly water soluble drug, tramadol hydrochloride, and to evaluate the effect of .... (IRAffinity-1, Shimadzu). Their spectra were obtained over the wave number range of ... square root kinetic model describes a time- dependent release process. The value of n.

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

    African Journals Online (AJOL)

    Methods: Various metformin hydrochloride formulations containing a hydrophobic carrier (stearic acid) and a hydrophilic polymer (polyethylene oxide) were prepared using a 32 factorial design. Two types of formulation techniques – melt granulation and direct compression – were evaluated. The influence of the carrier, ...

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

    African Journals Online (AJOL)

    Erah

    hydrochloride using a combination of a hydrophobic carrier and a hydrophilic polymer, and two types of formulation techniques. Methods: Various metformin hydrochloride formulations containing a hydrophobic carrier (stearic acid) and a hydrophilic polymer ..... be attributed to the dissolution of drug from the tablet surface.

  14. Formulation Development and Release Studies of Indomethacin Suppositories

    OpenAIRE

    Sah, M. L.; Saini, T. R.

    2008-01-01

    Indomethacin suppositories were prepared by using water-soluble and oil soluble suppository bases, and evaluated for in vitro release by USP I and modified continuous flow through bead bed apparatus. Effect of the Tween 80 (1% and 5%) was further studied on in vitro release of the medicament. Release rate was good in water-soluble suppositories bases in comparison to oil soluble suppositories bases. Release was found to be greater in modified continuous flow through bead bed...

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

    African Journals Online (AJOL)

    (F10) extended the drug release up to 24 h with initial burst effect. Upon modification, using ethyl cellulose as granulating agent (F11) extended drug release up to 24 h that followed zero order release kinetics (r2 = 0.9872). Model independent parameters such as t25%, t50%, t90%, DE720 and mean dissolution time (MDT) ...

  16. 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.

  17. Impact of formulation and process variables on solid-state stability of theophylline in controlled release formulations.

    Science.gov (United States)

    Korang-Yeboah, Maxwell; Rahman, Ziyaur; Shah, Dhaval; Mohammad, Adil; Wu, Suyang; Siddiqui, Akhtar; Khan, Mansoor A

    2016-02-29

    Understanding the impact of pharmaceutical processing, formulation excipients and their interactions on the solid-state transitions of pharmaceutical solids during use and in storage is critical in ensuring consistent product performance. This study reports the effect of polymer viscosity, diluent type, granulation and granulating fluid (water and isopropanol) on the pseudopolymorphic transition of theophylline anhydrous (THA) in controlled release formulations as well as the implications of this transition on critical quality attributes of the tablets. Accordingly, 12 formulations were prepared using a full factorial screening design and monitored over a 3 month period at 40 °C and 75%. Physicochemical characterization revealed a drastic drop in tablet hardness accompanied by a very significant increase in moisture content and swelling of all formulations. Spectroscopic analysis (ssNMR, Raman, NIR and PXRD) indicated conversion of THA to theophylline monohydrate (TMO) in all formulations prepared by aqueous wet granulation in as early as two weeks. Although all freshly prepared formulations contained THA, the hydration-dehydration process induced during aqueous wet granulation hastened the pseudopolymorphic conversion of theophylline during storage through a cascade of events. On the other hand, no solid state transformation was observed in directly compressed formulations and formulations in which isopropanol was employed as a granulating fluid even after the twelve weeks study period. The transition of THA to TMO resulted in a decrease in dissolution while an increase in dissolution was observed in directly compressed and IPA granulated formulation. Consequently, the impact of pseudopolymorphic transition of theophylline on dissolution in controlled release formulations may be the net result of two opposing factors: swelling and softening of the tablets which tend to favor an increase in drug dissolution and hydration of theophylline which decreases the drug

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

    African Journals Online (AJOL)

    Erah

    2011-07-30

    Jul 30, 2011 ... liquid chromatography (HPLC) and determination of the values of fat and fixed oils. ... the formulations was evaluated by USP dissolution (rotating basket) method I and the ..... likely to be compatible with human body than.

  19. Evaluation of dibutyrylchitin as new excipient for sustained drug release.

    Science.gov (United States)

    Casettari, Luca; Cespi, Marco; Castagnino, Enzo

    2012-08-01

    Dibutyrylchitin (DBC), a lipophilic chitin diester, has been synthesized from chitin and butyric anhydride with methanesulfonic acid as catalyst. Exhaustive esterification of free alcoholic groups of chitin was assessed by FT-IR and (1)H-NMR spectroscopy. High degree of alkyl substitution allowed DBC to acquire an almost completely lipophilic character. Tablets of paracetamol and metformin employing DBC as major excipient, in comparison with starch, microcrystalline cellulose, lactose and polyvinylpyrrolidone, were prepared and rates of drug release were checked by dissolution test assays. DBC released drug at a lower rate than that of the other tested materials. A comparison study of rate release of metformin from DBC tablets and from metformin-hydroxypropyl methylcellulose prolonged release oral formulation available on the market has been also curried out. Under the same conditions and in the presence of the same amount of loaded drug, DBC released 64% of metformin whereas hypromellose-based tablets released 87%.

  20. Constructing Slow-Release Formulations of Ammonium Nitrate Fertilizer Based on Degradable Poly(3-hydroxybutyrate).

    Science.gov (United States)

    Boyandin, Anatoly Nikolayevich; Kazantseva, Eugenia Andreevna; Varygina, Daria Eugenievna; Volova, Tatiana Grigorievna

    2017-08-16

    The present study describes construction and investigation of experimental formulations of ammonium nitrate embedded in a matrix of degradable natural polymer poly-3-hydroxybutyrate [P(3HB)] and P(3HB) blended with wood flour shaped as tablets, some of them coated with P(3HB). Kinetics of ammonium release into soil as dependent on the composition of the polymer matrix was investigated in laboratory experiments. The rates of fertilizer release from formulations coated with a biopolymer layer were considerably (two months or longer) slower than the rates of fertilizer release from uncoated formulations, while release from polymer and composite (polymer/wood flour) formulations occurred with comparable rates. The use of the experimental formulations in laboratory ecosystems with wheat (Triticum aestivum L.) was more effective than application of free ammonium nitrate. The advantage of the slow-release fertilizer formulations is that they are buried in soil together with the seeds, and the fertilizer remains effective over the first three months of plant growth. The use of such slow-release formulations will reduce the amounts of chemicals released into the environment, which will curb their accumulation in food chains of ecosystems and mitigate their adverse effects on the biosphere.

  1. 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.

  2. Development of extended-release formulation of domperidone using ...

    African Journals Online (AJOL)

    R (%) = x 100% ……………. (3) where R is cumulative percent drug released, A is the absorbance of solution of drug released at the specified time, V is the volume of dissolution medium, S is the slope of the calibration curve of absorbance and D is the amount of drug per tablet. Statistical analysis. Data are expressed as ...

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

    African Journals Online (AJOL)

    The granules possessed better flow properties than the powder mixtures for direct compression. Paracetamol tablets prepared by wet granulation were harder than those prepared by direct compression as shown by the CS. The evaluation of the release properties showed that the amount of paracetamol released at any ...

  4. Continuous melt granulation to develop high drug loaded sustained release tablet of Metformin HCl

    Directory of Open Access Journals (Sweden)

    Pradnya Vaingankar

    2017-01-01

    The developed matrix tablet (75% drug loading resulted in 670 mg of weight for 500 mg dose strength and showed sustained drug release over 10 h. When compared, with conventional granulation techniques, it was observed that, under identical compression force, the tablet prepared by MG exhibited superior compactibility along with tablet hardness and optimal drug release profile. FTIR suggested nonexistence of chemical interaction between the drug and the other excipients while XRD and DSC analysis revealed the crystalline state of the drug. Furthermore, the results obtained from Raman spectroscopy proved the uniform distribution of the Metformin HCl and polymer in the final dosage form. This technology leads to the manufacture of sustained release matrix formulation with reduced tablet size of a high dose, highly water soluble drug otherwise difficult to process using standard batch-granulation.

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

    African Journals Online (AJOL)

    Erah

    Locust bean gum (LB) and karaya gum (K) were purchased from Sigma. Aldrich,. Steinheim,. Germany while magnesium stearate, hydrochloric acid, sodium hydroxide, and potassium phosphate monobasic were all obtained from Merck,. Mumbai, India. All chemicals were either of pharmaceutical or analytical grade. The.

  6. Oral controlled release formulation of diclofenac sodium by microencapsulation with ethyl cellulose.

    Science.gov (United States)

    Sajeev, C; Vinay, G; Archna, R; Saha, R N

    2002-01-01

    The aim of this study was to formulate and evaluate microencapsulated controlled release preparations of diclofenac sodium (DFS) using different proportions of ethyl cellulose (EC) as the retardant material to extend the release. The formulated microcapsules were then compressed into tablets to obtain controlled release oral formulations. Phase separation-coacervation technique was employed to prepare microcapsules of DFS using different proportions of EC in cyclohexane. Physical characteristics of microcapsules and their tablets, in vitro release pattern of the designed microcapsules and their tablets prepared from them were studied using USP dissolution apparatus (USP 2000) type 2 (paddle method) in triple distilled water. The prepared microcapsules were white, free flowing and spherical in shape, with the particle size varying from 49.94-52.72 microm. The duration of DFS release from microcapsules was found to be directly proportional to the proportion of EC and, thus, coat thickness. All tablets were of good quality with respect to appearance, drug content uniformity, hardness, weight variation, friability and thickness uniformity. In vitro release study of the tabletted microcapsules in triple distilled water showed a zero order release kinetics and extended release beyond 24 h. A good correlation was obtained between drug release (t(60)) and proportion of EC in the microcapsules. In the case of tabletted microcapsules, very good correlation could be established between t(60), proportion of EC, weight of the tablets and between release rate constant (K) and proportion of EC. All the formulations were highly stable and possessed reproducible release kinetics across the batches.

  7. In Vitro – In Vivo Evaluation of SustainedRelease Lithium Carbonate Matrix Tablets: Influence of Hydrophilic Matrix Materials

    Directory of Open Access Journals (Sweden)

    J Emami

    2004-04-01

    Full Text Available Background: Conventional Lithium carbonate (LC tablets produce rapid and relatively high peak blood levels resulting in adverse effects. These drawbacks can be overcome by designing a suitable sustained or controlled-release LC preparation. Methods: Sustained-release matrix tablets were therefore developed using different types and ratios of polymers including carbomer (CP, Na carboxymethylcellulose (Na CMC and hydroxypropylmethylcellulose (HPMC, to assess the release profiles and in vivo performance of the formulations. The tablets were prepared by either direct compression (DC or wet granulation (WG. In the DC method, 69% (450 mg LC, 5, 10 or 15% CP or Na CMC (of total tablet weight, lactose and /or Avicel (to maintain constant tablet weight were mixed and directly compressed. In the WG method, 450 mg LC and 10, 20, or 30% HPMC were granulated with Eudragit S100 solution, dried, and then compressed to formulate the tablets. In vitro and in vivo, newly formulated sustained-release LC tablets were compared with sustained-release commercial tablets (Eskalith and Priadel. In vivo studies were conducted in nine healthy subjects in a cross-over design, with a 3x3 Latin square sequence, and pharmacokinetic parameters were estimated using classical methods. Results: The matrix tablets containing 15% CP exhibited suitable release kinetics and uniform absorption characteristics comparable to that of Eskalith. In vivo, this formulation produced a smooth and extended absorption phase very much similar to that of Eskalith with the identical elimination half-life and extent of absorption. Conclusion: The matrix tablets containing 15% CP reduces the incidence of side effects often associated with high serum concentration of Lithium and blood level variations. Direct correlation between the dissolution profiles and the relative bioavailability of the formulations could be observed. Keywords: Lithium carbonate, Matrix tablets, Sustained-release, In vitro

  8. Naproxen release from sustained release matrix system and effect of cellulose derivatives.

    Science.gov (United States)

    Sarfraz, Muhammad Khan; Rehman, Nisar Ur; Mohsin, Sabeeh

    2006-07-01

    The present study was conducted to investigate the low viscosity grades of hydroxypropylmethyl cellulose (HPMC) and ethyl cellulose (EC) in sustaining the release of water insoluble drug, naproxen from the matrix tablets. Both HPMC and EC were incorporated in the matrix system separately or in combinations by wet granulation technique. In vitro dissolution studies indicated that EC significantly reduced the rate of drug release compared to HPMC in 12 hour testing time. But, no significant difference was observed in the release profiles of matrix tablets made by higher percentages of EC. The tablets prepared with various combinations of HPMC and EC also failed to produce produce the desired release profiles. However, comparatively linear and desirable sustained release was obtained from EC-based matrix tablets prepared by slightly modifying the granulation method. Moreover, two different compression forces used in tableting had no remarkable effect on the release profile of naproxen.

  9. Encapsulated Urea-Kaolinite Nanocomposite for Controlled Release Fertilizer Formulations

    National Research Council Canada - National Science Library

    Sempeho, Siafu Ibahati; Kim, Hee Taik; Mubofu, Egid; Pogrebnoi, Alexander; Shao, Godlisten; Hilonga, Askwar

    2015-01-01

    Urea controlled release fertilizer (CRF) was prepared via kaolinite intercalation followed by gum arabic encapsulation in an attempt to reduce its severe losses associated with dissolution, hydrolysis, and diffusion...

  10. Molecularly imprinted polymer nanocarriers for sustained release of erythromycin.

    Science.gov (United States)

    Kempe, Henrik; Parareda Pujolràs, Anna; Kempe, Maria

    2015-02-01

    To develop and evaluate molecularly imprinted nanocarriers for sustained release of erythromycin in physiological buffer media. Erythromycin-imprinted poly(methacrylic acid-co-trimethylolpropane trimethacrylate) nanocarriers and corresponding control nanocarriers were prepared by free-radical precipitation polymerization. The nanocarriers were characterized by transmission electron microscopy, dynamic light scattering, and nitrogen sorption analysis. Binding studies were carried out with erythromycin and five structurally unrelated drugs. Molecular descriptors of the drugs were computed and correlated to measured binding data by multivariate data analysis. Loading with erythromycin and in vitro release studies were carried out in physiological buffer media. Kinetic models were fitted to drug release data. The template affected the size and morphology of the nanocarriers. Binding isotherms showed that erythromycin-imprinted nanocarriers had a higher erythromycin binding capacity than corresponding control nanocarriers. Multivariate data analysis, correlating binding to molecular descriptors of the drugs, indicated a molecular imprinting effect. Erythromycin loading capacity was 76 mg/g with a loading efficiency of 87%. Release studies in physiological buffer showed an initial burst release of a quarter of loaded erythromycin during the first day and an 82% release after a week. The release was best described by the Korsmeyer-Peppas model. Sustained release of erythromycin in physiological buffer was demonstrated.

  11. Sustained release from a metal - Analgesics entrapped within biocidal silver.

    Science.gov (United States)

    Menagen, Barak; Pedahzur, Rami; Avnir, David

    2017-06-23

    Matrices for sustained release of drugs have been based on polymers, biomaterials and oxides. The use of the major family of metals as matrices for sustained release is, to the best of our knowledge, unknown. In this context we describe a new family of bio-composites for sustained release of drugs, namely analgesic drugs entrapped within metallic silver. Synthetic methodologies were developed for the preparation of ibuprofen@Ag, naproxen@Ag, tramadol@Ag and bupivacaine@Ag composites. Detailed kinetic analysis of the release of the drugs from within the metal, is provided, demonstrating that metals can indeed serve as reservoirs for drug release. The metal in our case acts not only as a drug releasing source, but also as an antibacterial agent and this property of the composites was studied. Unexpectedly, it was found that the entrapment of the analgesics within silver, dramatically enhances the growth inhibition activity of wild type Pseudomonas aeruginosa, exceeding by far the inhibition activity of the separate components. A mechanism for this interesting observation is provided. The strong antimicrobial activity combined with the analgesic activity open the road for future applications of these materials as dual-purpose components in wound treatment.

  12. Formulation optimization of hydrodynamically balanced oral controlled release bioadhesive tablets of tramadol hydrochloride.

    Science.gov (United States)

    Singh, Bhupinder; Rani, Ashu; Babita; Ahuja, Naveen; Kapil, Rishi

    2010-01-01

    The directly compressible floating-bioadhesive tablets of tramadol were formulated using varying amounts Carbopol 971P (CP) and hydroxy-propylmethyl cellulose (HPMC), along with other requisite excipients. In vitro drug release profile, floatational characteristics and ex vivo bioadhesive strength using texture analyzer were determined, and systematically optimized using a 3(2) central composite design (CCD). The studies indicated successful formulation of gastroretentive compressed matrices with excellent controlled release, mucoadhesion and hydrodynamic balance. Comparison of the dissolution profiles of the optimized formulation, with optimal composition of CP:HPMC :: 80.0:125.0, with that of the marketed controlled release formulation other indicated analogy of drug release performance with each other. Validation of optimization study using eight confirmatory experimental runs indicated very high degree of prognostic ability of CCD with mean  SEM of â0.06%  0.37. Further, the study successfully unravels the effect of the polymers on the selected response variables.

  13. Dexamethasone-releasing cochlear implant coatings: application of artificial neural networks for modelling of formulation parameters and drug release profile.

    Science.gov (United States)

    Nemati, Pedram; Imani, Mohammad; Farahmandghavi, Farhid; Mirzadeh, Hamid; Marzban-Rad, Ehsan; Nasrabadi, Ali Motie

    2013-08-01

    Over the past few decades, mathematical modelling and simulation of drug delivery systems has been steadily gained interest as a focus for academic and industrial attention. Here, simulation of dexamethasone (DEX, a corticosteroid anti-inflammatory agent) release profile from drug-eluting cochlear implant coatings is reported using artificial neural networks. The devices were fabricated as monolithic dispersions of the pharmaceutically active ingredient in a silicone rubber matrix. A two-phase exponential model was fitted on the experimentally obtained DEX release profiles. An artificial neural network (ANN) was trained to determine formulation parameters (i.e. DEX loading percentage, the devices surface area and their geometry) for a specific experimentally obtained drug release profile. In a reverse strategy, an ANN was trained for determining expected drug release profiles for the same set of formulation parameters. An algorithm was developed by combining the two previously developed ANNs in a serial manner, and this was successfully used for simulating the developed drug-eluting cochlear implant coatings. The models were validated by a leave-one-out method and performing new experiments. The developed ANN algorithms were capable to bilaterally predict drug release profile for a known set of formulation parameters or find out the levels for input formulation parameters to obtain a desired DEX release profile. © 2013 Royal Pharmaceutical Society.

  14. Sustained-release effervescent floating matrix tablets of baclofen: development, optimization and in vitro-in vivo evaluation in healthy human volunteers.

    Science.gov (United States)

    Gande, S; Rao, Ym

    2011-01-01

    Baclofen, a centrally acting skeletal muscle relaxant, is indicated in the long-term treatment of spasticity. It is difficult to formulate baclofen sustained release dosage forms because its absorption on arrival to colon (or even before) is low or nonexistent. In the present investigation efforts were made to improve the bioavailability of baclofen by increasing the residence time of the drug through sustained-release matrix tablet formulation via gastroretentive mechanism. Tablets were prepared by wet granulation technique. The influence of gas generating and gel forming agents, amount of baclofen and total weight of tablet on physical properties, in vitro buoyancy, floating lag time, drug release, DSC, X-ray studies were investigated. The release mechanisms were explored and explained by applying zero order, first order, Higuchi and Korsmeyer equations. The selected formulations were subjected to stability study for the period of three months. For all formulations, kinetics of drug release from tablet followed Higuchi's square root of time kinetic treatment heralding diffusion as predominant mechanism of drug release. Formulations containing 20 mg and 40 mg (F-1 and F-7) showed similar release profiles. There was no significant change in the selected formulations, when subjected to accelerated stability conditions over a period of three months. X-ray imaging in six healthy human volunteers revealed a mean gastric retention period of 5.50±0.7 hrs for the selected formulation. Stable, sustained release effervescent floating matrix tablets of baclofen could be prepared by wet granulation technique.

  15. Evaluation of selected polysaccharide excipients in buccoadhesive tablets for sustained release of nicotine.

    Science.gov (United States)

    Park, Calum R; Munday, Dale L

    2004-07-01

    Some naturally occurring biocompatible materials were evaluated as mucoadhesive controlled release excipients for buccal drug delivery. A range of tablets were prepared containing 0-50% w/w xanthan gum, karaya gum, guar gum, and glycol chitosan and were tested for swelling, drug release, and mucoadhesion. Guar gum was a poor mucoadhesive and lacked sufficient physical integrity for buccal delivery. Karaya gum demonstrated superior adhesion to guar gum and was able to provide zero-order drug release, but concentrations greater than 50% w/w may be required to provide suitable sustained release. Xanthan gum showed strong adhesion to the mucosal membrane and the 50% w/w formulation produced zero-order drug release over 4 hours, about the normal time interval between daily meals. Glycol chitosan produced the strongest adhesion, but concentrations greater than 50% w/w are required to produce a nonerodible matrix that can control drug release for over 4 hours. Swelling properties of the tablets were found to be a valuable indicator of the ability of the material to produce sustained release. Swelling studies also gave an indication of the adhesion values of the gum material where adhesion was solely dependent upon penetration of the polymer chains into the mucus layer.

  16. Preparation of Coated Valproic Acid and Sodium Valproate Sustained-release Matrix Tablets.

    Science.gov (United States)

    Phaechamud, T; Mueannoom, W; Tuntarawongsa, S; Chitrattha, S

    2010-03-01

    The aim of this research was to investigate the technique for preparation of coated valproic acid and sodium valproate sustained-release matrix tablets. Different diluents were tested and selected as the effective absorbent for oily valproic acid. Effect of the amount of absorbent and hydroxypropylmethylcellulose on drug release from valproic acid-sodium valproate matrix tablets prepared with wet granulation technique was evaluated in pH change system. Colloidal silicon dioxide effectively adsorbed liquid valproic acid during wet granulation and granule preparation. The amounts of colloidal silicon dioxide and hydroxypropylmethylcellulose employed in tablet formulations affected drug release from the tablets. The drug release was prominently sustained for over 12 h using hydroxypropylmethylcellulose-based hydrophilic matrix system. The mechanism of drug release through the matrix polymer was a diffusion control. The drug release profile of the developed matrix tablet was similar to Depakine Chrono(®), providing the values of similarity factor (f2) and difference factor (f1) of 85.56 and 2.37, respectively. Eudragit(®) L 30 D-55 was used as effective subcoating material for core matrix tablets before over coating with hydroxypropylmethylcellulose film with organic base solvent. Drug release profile of coated matrix tablet was almost similar to that of Depakine Chrono(®).

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

    Science.gov (United States)

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

    2011-11-01

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

  18. 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

    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...

  19. Sustained release nitrite therapy results in myocardial protection in a porcine model of metabolic syndrome with peripheral vascular disease

    OpenAIRE

    Bradley, Jessica M.; Islam, Kazi N.; Polhemus, David J.; Donnarumma, Erminia; Brewster, Luke P.; Tao, Ya-Xiong; Goodchild, Traci T.; Lefer, David J.

    2015-01-01

    In a clinically relevant porcine model of metabolic syndrome and peripheral vascular disease, treatment with a novel sustained-release nitrite formulation restored cardiac endothelial nitric oxide synthase, enhancing myocardial nitrite levels, reduced oxidative stress, and improved ex vivo coronary vascular function via endothelium-independent vasodilation mechanism in obese Ossabaw swine.

  20. Formulation of Fast-Release Gastroretentive Solid Dispersion of ...

    African Journals Online (AJOL)

    transform infrared spectroscopy FTIR, bouyancy as well as by in vitro release and in vivo studies. Further aging studies were carried out for the samples. Results: PXRD showed that ..... Lee JW, Park JH, Robinson JP, Bioadhesive based dosage forms, the next generation, J. Pharm. Sci. 2000; 89: 850-866. 3. Bardonnet PL ...

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

    African Journals Online (AJOL)

    Controlled-Release Oxybutynin Tablets in Dogs. Joonho Bae1 and Jin Woo Park2*. 1Amorepacific Corporation R&D Center, 314-1, Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-do, 446-729, 2College of. Pharmacy and Natural Medicine Research Institute, Mokpo National University, 1666 Youngsan-ro, Muan-gun, ...

  2. daily, sustained-release theophylline on sleep in nocturnal asthmatics

    African Journals Online (AJOL)

    To examine the effects of once-daily, sustained- release theophylline on sleep patterns in nocturnal asthmatics. Design. Double-blind, randomised, cross-over, placebo- controlled trial ... 22-day trial, 3 patients having withdrawn due to adverse events. During the initial 7 days of the stUdy, serum was obtained at 07hOO and ...

  3. daily, sustained-release theophylline on sleep in nocturnal asthmatics

    African Journals Online (AJOL)

    during the early hours of the morning and nocturnal asthma attacks are therefore not always prevented.2 However, improved control of nocturnal asthma has been reported with the use of once-daily, sustained-release, evening- administered theophylline.1. The influence of theophylline on sleep is not clear and.

  4. 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.

  5. An epichlorohydrin-crosslinked semi-interpenetrating GG-PEO network as a xerogel matrix for sustained release of sulpiride.

    Science.gov (United States)

    Hoosain, Famida G; Choonara, Yahya E; Kumar, Pradeep; Tomar, Lomas K; Tyagi, Charu; du Toit, Lisa C; Pillay, Viness

    2014-10-01

    The current study involved the development of a novel sustained release crosslinked semi-IPN xerogel matrix tablet prepared by chemical crosslinking of poly(ethylene) oxide (PEO) and gellan gum (GG) employing epichlorohydrin (EPI) as crosslinker. A Box-Behnken design was employed for the statistical optimization of the matrix system to ascertain the ideal combination of native polymeric and crosslinking agents. Characterization studies were performed by employing standard polymer characterization techniques such as Fourier transform infrared spectrometry, differential scanning calorimetry, and scanning electron microscopy. Formulated matrix tablets displayed zero-order release kinetics, extending over 24 h. The mechanism of drug release was primarily by swelling and surface erosion. Crosslinked semi-IPN xerogel matrix tablets were compared to non-crosslinked polymer blends; results from the study conducted showed that the physiochemical properties of the PEO and GG were sufficiently modified to allow for sustained release of sulpiride with a 100% drug release at 24 h in a controlled manner as compared to non-crosslinked formulations which displayed further release beyond the test period. Crosslinked formulations displayed water uptake between 450 and 500% indicating a controlled rate of swelling and erosion allowing for sustained release. Surface morphology of the crosslinked system depicted a porous structure formed by interpenetrating networks of polymers, allowing for a greater degree of controlled penetration into the system affording it the ability to sustain drug release. Therefore, conclusively, based on the study performed, crosslinked PEO-GG allows for the sustained release of sulpiride from a hydrophilic semi-IPN xerogel matrix system.

  6. 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.

  7. 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.

  8. Chlorhexidine sustained-release varnishes for catheter coating - Dissolution kinetics and antibiofilm properties.

    Science.gov (United States)

    Gefter Shenderovich, Julia; Zaks, Batya; Kirmayer, David; Lavy, Eran; Steinberg, Doron; Friedman, Michael

    2018-01-15

    Catheter-associated urinary tract infections are difficult to eradicate or prevent, due to their biofilm-related nature. Chlorhexidine, a widely used antiseptic, was previously found to be effective against catheter-related biofilms. For the present study, we developed sustained-release chlorhexidine varnishes for catheter coating and evaluated their antibiofilm properties and chlorhexidine-dissolution kinetics under various conditions. The varnishes were based on ethylcellulose or ammonio methacrylate copolymer type A (Eudragit® RL). Chlorhexidine was released by diffusion from a heterogeneous matrix in the case of the ethylcellulose-based formulation, and from a homogeneous matrix in the case of Eudragit® RL. This dictated the release pattern of chlorhexidine under testing conditions: from film specimens, and from coated catheters in a static or flow-through system. Momentary saturation was observed with the flow-through system in Eudragit® RL-based coatings, an effect that might be present in vivo with other formulations as well. The coatings were retained on the catheters for at least 2weeks, and showed prolonged activity in a biological medium, including an antibiofilm effect against Pseudomonas aeruginosa. The current study demonstrates the potential of catheter coatings with sustained release of chlorhexidine in the prevention of catheter-associated urinary tract infections. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Natural gums as sustained release carriers: development of gastroretentive drug delivery system of ziprasidone HCl

    Directory of Open Access Journals (Sweden)

    AJ Rajamma

    2012-10-01

    Full Text Available Abstract Background Objective of this study is to show the potential use of natural gums in the development of drug delivery systems. Therefore in this work gastro retentive tablet formulations of ziprasidone HCl were developed using simplex lattice design considering concentration of okra gum, locust bean gum and HPMC K4M as independent variables. A response surface plot and multiple regression equations were used to evaluate the effect of independent variables on hardness, flag time, floating time and drug release for 1 h, 2 h, and 8 h and for 24 h. A checkpoint batch was also prepared by considering the constraints and desirability of optimized formulation to improve its in vitro performance. Significance of result was analyzed using ANOVA and p was considered statistically significant. Results Formulation chiefly contains locust bean gum found to be favorable for hardness and floatability but combined effect of three variables was responsible for the sustained release of drug. The in vitro drug release data of check point batch (F8 was found to be sustained well compared to the most satisfactory formulation (F7 of 7 runs. The ‘n’ value was found to be between 0.5 and 1 suggesting that release of drug follows anomalous (non-fickian diffusion mechanism indicating both diffusion and erosion mechanism from these natural gums. Predicted results were almost similar to the observed experimental values indicating the accuracy of the design. In vivo floatability test indicated non adherence to the gastric mucosa and tablets remain buoyant for more than 24 h. Conclusions Study showed these eco-friendly natural gums can be considered as promising SR polymers.

  10. Encapsulated Urea-Kaolinite Nanocomposite for Controlled Release Fertilizer Formulations

    OpenAIRE

    Siafu Ibahati Sempeho; Hee Taik Kim; Egid Mubofu; Alexander Pogrebnoi; Godlisten Shao; Askwar Hilonga

    2015-01-01

    Urea controlled release fertilizer (CRF) was prepared via kaolinite intercalation followed by gum arabic encapsulation in an attempt to reduce its severe losses associated with dissolution, hydrolysis, and diffusion. Following the beneficiation, the nonkaolinite fraction decreased from 39.58% to 0.36% whereas the kaolinite fraction increased from 60.42% to 99.64%. The X-ray diffractions showed that kaolinite was a major phase with FCC Bravais crystal lattice with particle sizes ranging betwee...

  11. Hydrophilic thermoplastic polyurethanes for the manufacturing of highly dosed oral sustained release matrices via hot melt extrusion and injection molding.

    Science.gov (United States)

    Verstraete, G; Van Renterghem, J; Van Bockstal, P J; Kasmi, S; De Geest, B G; De Beer, T; Remon, J P; Vervaet, C

    2016-06-15

    Hydrophilic aliphatic thermoplastic polyurethane (Tecophilic™ grades) matrices for high drug loaded oral sustained release dosage forms were formulated via hot melt extrusion/injection molding (HME/IM). Drugs with different aqueous solubility (diprophylline, theophylline and acetaminophen) were processed and their influence on the release kinetics was investigated. Moreover, the effect of Tecophilic™ grade, HME/IM process temperature, extrusion speed, drug load, injection pressure and post-injection pressure on in vitro release kinetics was evaluated for all model drugs. (1)H NMR spectroscopy indicated that all grades have different soft segment/hard segment ratios, allowing different water uptake capacities and thus different release kinetics. Processing temperature of the different Tecophilic™ grades was successfully predicted by using SEC and rheology. Tecophilic™ grades SP60D60, SP93A100 and TG2000 had a lower processing temperature than other grades and were further evaluated for the production of IM tablets. During HME/IM drug loads up to 70% (w/w) were achieved. In addition, Raman mapping and (M)DSC results confirmed the homogenous distribution of mainly crystalline API in all polymer matrices. Besides, hydrophilic TPU based formulations allowed complete and sustained release kinetics without using release modifiers. As release kinetics were mainly affected by drug load and the length of the PEO soft segment, this polymer platform offers a versatile formulation strategy to adjust the release rate of drugs with different aqueous solubility. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. [Preparation and release behaviour of mesoporous silica/ethylcellulose sustained-release mini-matrix].

    Science.gov (United States)

    Wu, Qiao-li; Quan, Gui-lan; Hong, Yu; Wu, Lin-na; Zeng, You-mei; Li, Ge; Pan, Xin; Wu, Chuan-bin

    2015-04-01

    Hot-melt extrusion was applied to prepare mesoporous silica/ethylcellulose mini-matrix for sustained release, and fenofibrate was used as a model drug, ethylcellulose and xanthan gum were chosen as sustained-release agent and releasing moderator, respectively. This novel matrix obtained the controlled release ability by combining mesoporous silica drug delivery system and hot-melt extrusion technology. And mesoporous silica particle (SBA-15) was chosen as drug carrier to increase the dissolution rate of fenofibrate in this martix. Scanning electron microscope, transmission electron microscope, small angle X-ray powder diffraction and N2 adsorption-desorption were introduced to determine the particle morphology, particle size and pore structure of the synthesized SBA-15. The results showed that SBA-15 had a very high Brunauer-Emmett-Teller specific surface area, a narrow pore size distribution, large pore volume and a ordered two-dimensional hexagonal structure of p6mm symmetry. Differential scanning calorimetry and X-ray powder diffraction results demonstrated that fenofibrate dispersed in an amorphous state inside the pores of the mesoporous silica which contributed to the improvement in the dissolution rate. The drug release of mini-matrices was influenced by ethylcellulose viscosity grades and xanthan gum concentration, which increased with the increasing of xanthan gum concentration and decreasing of ethylcellulose viscosity. Mini-matrix containing 22% xanthan gum exhibited a good sustained release performance, and the drug release behavior followed the first-order kinetics.

  13. Sustained tobramycin release from polyphosphate double network hydrogels.

    Science.gov (United States)

    Lane, Dwight D; Fessler, Amber K; Goo, Seungah; Williams, Dustin L; Stewart, Russell J

    2017-03-01

    Sustained local delivery of antibiotics from a drug reservoir to treat or prevent bacterial infections can avoid many of the drawbacks of systemic administration of antibiotics. Prolonged local release of high concentrations of antibiotics may also be more effective at treating bacteria in established biofilm populations that are resistant to systemic antibiotics. A double network hydrogel comprising an organic polyphosphate pre-polymer network polymerized within a polyacrylamide network de-swelled to about 50% of its initial volume when the polyphosphate network was crosslinked with polycationic tobramycin, an aminoglycoside antibiotic. The antibiotic-loaded hydrogels contained approximately 200mg/ml of tobramycin. The hydrogels continuously released daily amounts of tobramycin above the Pseudomonas aeruginosa minimal bactericidal concentration for greater than 50days, over the pH range 6.0-8.0, and completely eradicated established P. aeruginosa biofilms within 72h in a flow cell bioreactor. The presence of physiological concentrations of Mg2+ and Ca2+ ions doubled the cumulative release over 60days. The polyphosphate hydrogels show promise as materials for sustained localized tobramycin delivery to prevent post-operative P. aeruginosa infections including infections established in biofilms. Polyphosphate hydrogels were loaded with high concentrations of tobramycin. The hydrogels provided sustained release of bactericidal concentrations of tobramycin for 50days, and were capable of completely eradicating P. aeruginosa in established biofilms. The hydrogels have potential for localized prevention or treatment of P. aeruginosa infections. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  14. Drug Release Characteristics and Tissue Distribution of Rifapentine Polylactic Acid Sustained-Release Microspheres in Rabbits after Paravertebral Implantation.

    Science.gov (United States)

    Zhang, Zheng; Wu, Linbo; Li, Haijian; Long, Zhicheng; Song, Xinghua

    2016-11-01

    Rates of drug-resistant tuberculosis (TB) and TB associated with human immunodeficiency virus (HIV) infection have increased dramatically, intensifying challenges in TB control. New formulations of TB treatment drugs that control drug release and increase local drug concentrations will have a significant impact on mitigating the toxic side effects and increasing the clinical efficacy of anti-TB drugs. The aim was to observe the sustained release characteristics of rifapentine polylactic acid sustained-release microspheres in vivo and the accumulation of rifapentine in other tissues following paravertebral implantation. This study is a basic animal experimental study that began on July 17, 2014 in the Fifth Affiliated hospital of Xinjiang Medical University. One hundred and eight New Zealand white rabbits (weighing 2.8 - 3.0 kg, male and female, China) were randomly divided into three groups of 36 rabbits each. Blood and tissue samples from the liver, lungs, kidneys, vertebrae, and paravertebral muscle were collected at different time points post-surgery. High performance liquid chromatography (HPLC) analysis with a biological internal standard was used to determine the drug concentrations in samples. In group A, no significant differences in rifapentine concentrations in the liver were detected between any two time points (P > 0.05). However, the differences in rifapentine concentrations between day 10 and day 21 were statistically significant (P 0.05). In group B, the differences in rifapentine concentration between days 3 and 10 in vertebral bone and in paravertebral muscles were statistically significant (P polylactic acid sustained-release microspheres, the concentration of rifapentine in local vertebral bone tissues was maintained above the TB minimum inhibitory concentration for up to 60 days with no apparent accumulation of the drug in other tissues.

  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. Formulation and In vitro Dissolution Characteristics of Sustained ...

    African Journals Online (AJOL)

    2013; 22(2): 177-183. 4. Khan SA, Ahmad M, Murtaza G, Muhammad NA, Nisar. UR, Rozina K, Fatima R, Mohammad A. Formulation of nimesulide floating microparticles using low viscosity hydroxypropyl mehylcellulose. Trop. J. Pharm. Res. 2010; 9(2): 293-299. 5. Murtaza G. Ethylcellulose microparticles: A review. Acta.

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

    Science.gov (United States)

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

    2017-09-01

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

  18. 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.

  19. Towards a methodology to formulate sustainable diets for livestock: accounting for environmental impact in diet formulation.

    Science.gov (United States)

    Mackenzie, S G; Leinonen, I; Ferguson, N; Kyriazakis, I

    2016-05-28

    The objective of this study was to develop a novel methodology that enables pig diets to be formulated explicitly for environmental impact objectives using a Life Cycle Assessment (LCA) approach. To achieve this, the following methodological issues had to be addressed: (1) account for environmental impacts caused by both ingredient choice and nutrient excretion, (2) formulate diets for multiple environmental impact objectives and (3) allow flexibility to identify the optimal nutritional composition for each environmental impact objective. An LCA model based on Canadian pig farms was integrated into a diet formulation tool to compare the use of different ingredients in Eastern and Western Canada. By allowing the feed energy content to vary, it was possible to identify the optimum energy density for different environmental impact objectives, while accounting for the expected effect of energy density on feed intake. A least-cost diet was compared with diets formulated to minimise the following objectives: non-renewable resource use, acidification potential, eutrophication potential, global warming potential and a combined environmental impact score (using these four categories). The resulting environmental impacts were compared using parallel Monte Carlo simulations to account for shared uncertainty. When optimising diets to minimise a single environmental impact category, reductions in the said category were observed in all cases. However, this was at the expense of increasing the impact in other categories and higher dietary costs. The methodology can identify nutritional strategies to minimise environmental impacts, such as increasing the nutritional density of the diets, compared with the least-cost formulation.

  20. Taste masking of azithromycin by resin complex and sustained release through interpenetrating polymer network with functionalized biopolymers.

    Science.gov (United States)

    Rajesh, A Michael; Popat, Kiritkumar Mangaldas

    2017-05-01

    The objective was to evaluate taste masking of azithromycin (AZI) by ion exchange resins (IERs) and the formation of covalent semi interpenetrating polymer network (IPN) beads using chitosan (CS) and sodium carboxylated agarose (SCAG) for sustained release of drug. Methacrylic acid (MAA)-based IERs were prepared by suspension polymerization method. Drug release complexes (DRCs) were prepared by different drug:resin ratios i.e. 1:1, 1:2 and 1:4. The resultant DRCs were characterized using DSC, FTIR, PXRD, in vivo and in vitro taste masking, and in vitro drug release at gastric pH. IPN beads were prepared by entrapping DRCs with bio polymers and cross linked with trisodium citrate (NaCIT), and further cross-linked with glutaraldehyde (GA) for sustained release of AZI. In vitro and in vivo taste masking studies showed that MD1:4 DRC formulation was optimal. The release of AZI from DRC was found to be very fast at gastric pH i.e. 97.37 ± 1.02% within 45 min. The formation of IPN beads was confirmed by FTIR. The release of drug from IPN beads at gastric and intestinal pH was found to be "taste masking and newly formulated IPN beads demonstrated sustained release of AZI.

  1. 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

    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...

  2. Alginate-gelatin formulation to modify lovastatin release profile from red yeast rice for hypercholesterolemia therapy.

    Science.gov (United States)

    Leone, Gemma; Consumi, Marco; Pepi, Simone; Lamponi, Stefania; Bonechi, Claudia; Tamasi, Gabriella; Donati, Alessandro; Rossi, Claudio; Magnani, Agnese

    2017-10-01

    The preparation of a delivery system able to guarantee a delayed release of lovastatin from red yeast rice (RYR) is mandatory to counteract cholesterol biosynthesis effectively. Polymeric formulations were prepared mixing alginate and gelatin, in different ratios, with RYR. The effect of different composition on stiffness, viscosity, swelling behavior and mesostructure of matrices was analyzed. Formulations obtained combining polymers in comparable amount (i.e., 60/40 and 50/50) guaranteed a delayed release of lovastatin from RYR, a prolonged inhibitory activity toward 3-hydroxy-3-methylglutaryl-coenzyme A reductase and a decreased cholesterol synthesis. The formulation obtained combining 60% gelatin and 40% of alginate showed physicochemical properties suitable to lead a lovastatin release profile compatible with cholesterol biosynthesis.

  3. 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.

  4. Sustained release nitric oxide from long-lived circulating nanoparticles.

    Science.gov (United States)

    Cabrales, Pedro; Han, George; Roche, Camille; Nacharaju, Parimala; Friedman, Adam J; Friedman, Joel M

    2010-08-15

    The current limitations of nitric oxide (NO) delivery systems have stimulated an extraordinary interest in the development of compounds that generate NO in a controlled and sustained manner with a heavy emphasis on the treatment of cardiovascular disease states. This work describes the positive physiological response to the infusion of NO-releasing nanoparticles prepared using a new platform based on hydrogel/glass hybrid nanoparticles. When exposed to moisture, these nanoparticles slowly release therapeutic levels of NO, previously generated through thermal reduction of nitrite to NO trapped within the dry particles. The controlled and sustained release of NO observed from these nanoparticles (NO-np) is regulated by its hydration over extended periods of time. In a dose-dependent manner, circulating NO-np both decreased mean arterial blood pressure and increased exhaled concentrations of NO over a period of several hours. Circulating NO-np induced vasodilatation and increased microvascular perfusion during their several hour circulation lifetime. Control nanoparticles (control-np; without nitrite) did not induce changes in arterial pressure, although a decrease in the number of capillaries perfused and an increase in leukocyte rolling and immobilization in the microcirculation were observed. The NO released by the NO-np prevents the inflammatory response observed after infusion of control-np. These data suggest that NO release from NO-np is advantageous relative to other NO-releasing compounds, because it does not depend on chemical decomposition or enzymatic catalysis; it is only determined by the rate of hydration. Based on the observed physiological properties, NO-np has clear potential as a therapeutic agent and as a research tool to increase our understanding of NO signaling mechanisms within the vasculature. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  5. Constructing Slow-Release Formulations of Metribuzin Based on Degradable Poly(3-hydroxybutyrate).

    Science.gov (United States)

    Boyandin, Anatoly Nikolayevich; Zhila, Natalia Olegovna; Kiselev, Evgeniy Gennadievich; Volova, Tatiana Grigorievna

    2016-07-20

    Experimental formulations of herbicide metribuzin embedded in matrices of degradable natural polymer poly(3-hydroxybutyrate) (P3HB) and its composites with poly(ethylene glycol) (PEG), poly-ε-caprolactone (PCL), and wood powder have been prepared in the form of pressed pellets containing 75% polymeric basis (pure P3HB or its composite with a second component at a ratio of 7:3) and 25% metribuzin. Incubation of formulations in soil laboratory systems led to the degradation of the matrix and herbicide release. The most active release of metribuzin (about 60% of the embedded herbicide over 35 days) was detected for the P3HB/PEG carrier compared to the P3HB, P3HB/wood, and P3HB/PCL forms (30-40%). Thus, the study shows that herbicide release can be controlled by the matrix formulation. Metribuzin formulations exerted a significant herbicidal effect on the plant Agrostis stolonifera, used as a weed plant model. Application of these long-term formulations will make it possible to reduce environmental release of chemicals, which will restrict the rate of their accumulation in trophic chains of ecosystems and abate their adverse effects on the biosphere.

  6. Comparison of in vitro release rates of acyclovir from cream formulations using vertical diffusion cells.

    Science.gov (United States)

    Nallagundla, Sumalatha; Patnala, Srinivas; Kanfer, Isadore

    2014-08-01

    Acyclovir, indicated in the treatment of herpes labialis ("cold sores"), is formulated as semisolid topical dosage forms and marketed in numerous countries. Since the formulations of the various acyclovir products may differ from country to country, this study was undertaken to compare the in vitro release of acyclovir from various generic cream products available on the South African and Indian markets using the respective brand/innovator product as the reference product. The in vitro studies were carried out using vertical diffusion cells with a diffusional surface area of 1.767 cm(2) and various commercially available membranes. Normal saline was used as receptor fluid and the temperature maintained at 32 ± 0.5°C. The in vitro release comparisons were based on the recommendations described in the US Food and Drug Administration Draft Guidance for acyclovir ointment and the SUPAC-SS Guidance for non-sterile semisolid dosage forms. The release rates (slope) of the test (T) and the relevant reference product (R) were monitored and compared. The comparative release of acyclovir from the various generic formulations compared with the reference product was found to be within the limits of 75-133.33% with a 90% confidence interval. These experiments indicate that the generic acyclovir cream formulations exhibited release rates that were comparable to the innovator product and could be considered to be bioequivalent.

  7. Release of rosmarinic acid from semisolid formulations and its penetration through human skin ex vivo

    Directory of Open Access Journals (Sweden)

    Stelmakienė Ada

    2015-06-01

    Full Text Available The aim of this study was to evaluate the release of rosmarinic acid (RA from the experimental topical formulations with the Melissa officinalis L. extract and to evaluate its penetration through undamaged human skin ex vivo. The results of the in vitro release study showed that higher amounts of RA were released from the emulsion vehicle when lemon balm extract was added in its dry form. An inverse correlation was detected between the released amount of RA and the consistency index of the formulation. Different penetration of RA into the skin may be influenced by the characteristics of the vehicle as well as by the form of the extract. The results of penetration assessment showed that the intensity of RA penetration was influenced by its lipophilic properties: RA was accumulating in the epidermis, while the dermis served as a barrier, impeding its deeper penetration.

  8. 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.

  9. Evaluation of Gum of Moringa oleifera as a Binder and Release Retardant in Tablet Formulation

    OpenAIRE

    Panda, D. S.; Choudhury, N. S. K.; Yedukondalu, M.; S Si; Gupta, R.

    2008-01-01

    The present study was undertaken to find out the potential of gum from Moringa oleifera to act as a binder and release retardant in tablet formulations. The effect of calcium sulphate dihydrate (water insoluble) and lactose (water soluble) diluent on the release of propranolol hydrochloride was studied. The DSC thermograms of drug, gum and mixture of gum/drug indicated no chemical interaction. Tablets (F1, F2, F3, and F4) were prepared containing calcium sulphate dihydrate as diluent, propran...

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

    Science.gov (United States)

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

    2013-01-01

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

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

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    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.

  12. Slow-release formulations of the herbicide picloram by using Fe-Al pillared montmorillonite.

    Science.gov (United States)

    Marco-Brown, Jose L; Undabeytia, Tomás; Torres Sánchez, Rosa M; Dos Santos Afonso, María

    2017-04-01

    Slow-release formulations of the herbicide picloram (PCM, 4-amino-3,5,6-trichloropyridine-2-carboxylic acid) were designed based on its adsorption on pillared clays (pillared clays (PILCs)) for reducing the water-polluting risk derived from its use in conventional formulations. Fe-Al PILCs were synthesized by the reaction of Na(+)-montmorillonite (SWy-2) with base-hydrolyzed solutions of Fe and Al. The Fe/(Fe + Al) ratios used were 0.15 and 0.50. The PCM adsorption isotherms on Fe-Al PILCs were well fitted to Langmuir and Freundlich models. The PCM adsorption capacity depended on the Fe content in the PILCs. Slow-release formulations were prepared by enhanced adsorption of the herbicide from PCM-cyclodextrin (CD) complexes in solution. CDs were able to enhance up to 2.5-fold the solubility of PCM by the formation of inclusion complexes where the ring moiety of the herbicide was partially trapped within the CD cavity. Competitive adsorption of anions such as sulfate, phosphate, and chloride as well as the FTIR analysis of PCM-PILC complexes provided evidence of formation of inner sphere complexes of PCM-CD on Fe-Al PILCs. Release of the herbicide in a sandy soil was lower from Fe-Al PILC formulations relative to a PCM commercial formulation.

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

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    Ena J

    2012-11-01

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

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

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    Gurpreet Arora

    2011-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  16. Design and optimization of thermosensitive nanoemulsion hydrogel for sustained-release of praziquantel.

    Science.gov (United States)

    Cong, Zhaotong; Shi, Yanbin; Peng, Xue; Wei, Bei; Wang, Yu; Li, Jincheng; Li, Jianyong; Li, Jiazhong

    2017-04-01

    This work aimed to develop an alternative sustained-release thermosensitive praziquantel-loaded nanoemulsion (PZQ-NE) hydrogel for better schistosomiasis treatment. PZQ-NE-dispersed chitosan/glycerol 2-phosphate disodium/HPMC (NE/CS/β-GP/HMPC) hydrogel was successfully prepared to improve bioavailability of PZQ. Solubility tests and pseudo-ternary phase diagrams were applied to screen optimal oils, surfactants and co-surfactants of NE. The hydrogels were characterized for gelling time, surface exudates, rheological properties and in vitro drug release. Formulation optimization of NE/CS/β-GP/HMPC hydrogel was conducted by Box-Behnken experimental design combined with response surface methodology. In vitro cytotoxicity of hydrogel was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide method. The sustained-release property of PZQ in NE and optimized hydrogel was evaluated by pharmacokinetic study in rabbits. The formulation of PZQ-NE consisted of mass ratio of 12.5% capryol 90 containing PZQ (160 mg/g), 40% cremophor RH 40/tween 20 and transcutol HP (S/CoS = 2:1), 47.5% deionized water. PZQ releasing from NE/CS/β-GP/HMPC hydrogels was best fitted to Higuchi model and governed by diffusion. Rheological investigation evidenced the themosensitive gelation of different hydrogel systems and their gel-like character at 37 °C. The optimized hydrogel formulation consisted of HPMC solution (103.69 mg/g), 3.03% (w/v) chitosan and 14.1% (w/v) β-GP showed no cytotoxicity when the addition of NE was no more than 100 mg/g. Pharmacokinetic parameters indicated that NE/CS/β-GP/HMPC hydrogel can significantly slow down drug elimination, prolong mean residence time and improve bioavailability of PZQ. NE/CS/β-GP/HMPC hydrogel possessed sustained-release property and could be an alternative antischistosomal drug delivery system with improved therapeutic effect.

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

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    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

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

    Science.gov (United States)

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

    2017-01-01

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

  19. Phytantriol and glyceryl monooleate cubic liquid crystalline phases as sustained-release oral drug delivery systems for poorly water-soluble drugs II. In-vivo evaluation.

    Science.gov (United States)

    Nguyen, Tri-Hung; Hanley, Tracey; Porter, Christopher J H; Larson, Ian; Boyd, Ben J

    2010-07-01

    Lipid-based liquid crystals formed from phytantriol (PHY) and glyceryl monooleate (GMO) retain their cubic-phase structure on dilution in physiologically relevant simulated gastrointestinal media, suggesting their potential application as sustained-release drug-delivery systems for poorly water-soluble drugs. In this study the potential of PHY and GMO to serve as sustained-release lipid vehicles for a model poorly-water-soluble drug, cinnarizine, was assessed and compared to that of an aqueous suspension formulation. Small-angle X-ray scattering was used to confirm the nanostructure of the liquid-crystalline matrix in the presence of the selected model drug, cinnarizine. Oral bioavailability studies were conducted in rats, and disposition of lipid and drug in segments of the gastrointestinal tract was determined over time. Differences in the digestibility and stability of formulations under digestion conditions were investigated using an in-vitro lipolysis model. The oral bioavailability of cinnarizine using the PHY formulation was 41%, compared to 19% for the GMO formulation and 6% for an aqueous suspension. The PHY formulation provided a T(max) for cinnarizine of 33 h, with absorption apparent up to 55 h after administration. In contrast, the T(max) for the GMO formulation was only 5 h. The PHY formulation was retained in the stomach for extended periods of time, with 56% of lipid remaining in the stomach after 24 h, in contrast to less than 1% of the GMO formulation after 8 h, suggesting that gastric retention was a key aspect of the prolonged period of absorption, which correlated with the formulations' relative susceptibility to in-vitro lipolysis and degradation. PHY provides a dramatic sustained-release effect for cinnarizine on oral administration, which is linked to gastric retention of the formulation and its ability to resist digestive processing. Poorly digested liquid crystal lipid formulations therefore offer a novel class of sustained-release

  20. Assembly of a Tripeptide and Anti-Inflammatory Drugs into Supramolecular Hydrogels for Sustained Release

    Directory of Open Access Journals (Sweden)

    Marina Kurbasic

    2017-08-01

    Full Text Available Supramolecular hydrogels offer interesting opportunities for co-assembly with drugs towards sustained release over time, which could be achieved given that the drug participates in the hydrogel nanostructure, and it is not simply physically entrapped within the gel matrix. dLeu-Phe-Phe is an attractive building block of biomaterials in light of the peptide’s inherent biocompatibility and biodegradability. This study evaluates the assembly of the tripeptide in the presence of either of the anti-inflammatory drugs ketoprofen or naproxen at levels analogous to commercial gel formulations. Fourier-transformed infrared (FT-IR, circular dichroism, Thioflavin T fluorescence, transmission electron microscopy (TEM, and oscillatory rheometry are used. Drug release over time is monitored by means of reverse-phase high performance liquid chromatography, and shows different kinetics for the two drugs.

  1. Development of subcutaneous sustained release nanoparticles encapsulating low molecular weight heparin

    Directory of Open Access Journals (Sweden)

    Satheesh Jogala

    2015-01-01

    Full Text Available The objective of the present research work was to prepare and evaluate sustained release subcutaneous (s.c. nanoparticles of low molecular weight heparin (LMWH. The nanoparticles were prepared by water-in-oil in-water (w/o/w emulsion and evaporation method using different grades of polylactide co-glycolide (50:50, 85:15, and different concentrations of polyvinyl alcohol (0.1%, 0.5%, 1% aqueous solution as surfactant. The fabricated nanoparticles were evaluated for size, shape, zeta potential, encapsulation efficiency, in vitro drug release, and in vivo biological activity (anti-factor Xa activity using the standard kit. The drug and excipient compatibility was analyzed by Fourier transform infrared spectroscopy (FTIR, differential scanning calorimetry (DSC and X-ray diffraction (XRD studies. The formation of nanoparticles was confirmed by scanning electron microscopy; nanoparticles were spherical in shape. The size of prepared nanoparticles was found between 195 nm and 251 nm. The encapsulation efficiency of the nanoparticles was found between 46% and 70%. In vitro drug, release was about 16-38% for 10 days. In vivo drug, release shows the sustained release of drug for 10 days in rats. FTIR studies indicated that there was no loss in chemical integrity of the drug upon fabrication into nanoparticles. DSC and XRD results demonstrated that the drug was changed from the crystalline form to the amorphous form in the formulation during the fabrication process. The results of this study revealed that the s.c. nanoparticles were suitable candidates for sustained delivery of LMWH.

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

    Directory of Open Access Journals (Sweden)

    Yoon S

    2014-01-01

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

  3. New Poly(3-hydroxybutyrate) Microparticles with Paclitaxel Sustained Release for Intraperitoneal Administration.

    Science.gov (United States)

    Bonartsev, Anton P; Zernov, Anton L; Yakovlev, Sergey G; Zharkova, Irina I; Myshkina, Vera L; Mahina, Tatiana K; Bonartseva, Garina A; Andronova, Natalia V; Smirnova, Galina B; Borisova, Juliya A; Kalishjan, Mikhail S; Shaitan, Konstantin V; Treshalina, Helena M

    2017-01-01

    Poly(hydroxyalkanoates) (PHA) have recently attracted increasing attention due to their biodegradability and high biocompatibility, which makes them suitable for the development of new prolong drug formulations. This study was conducted to develop new prolong paclitaxel (PTX) formulation based on poly(3- hydroxybutyrate) (PHB) microparticles. PHB microparticles loaded with antitumor cytostatic drug PTX were obtained by spray-drying method using Nano Spray Dryer B-90. The PTX release kinetics in vitro from PHB microparticles and their cytotoxity on murine hepatoma cell line MH-22a were studied. Microparticles antitumor activity in vivo was studied using intraperitoneally (i.p.) transplanted tumor models: murine Lewis lung carcinoma and xenografts of human breast cancer RMG1. Uniform PTX release from PHB-microparticles during 2 months was observed. PTX-loaded PHB microparticles have demonstrated a significant antitumor activity versus pure drug both in vitro in murine hepatoma cells and in vivo when administered i.p. to mice with murine Lewis lung carcinoma and xenografts of human breast cancer RMG1. The developed technique of PTX sustained delivery from PHB-microparticles has therapeutic potential as prolong anticancer drug formulation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Gastro-floating bilayer tablets for the sustained release of metformin and immediate release of pioglitazone: preparation and in vitro/in vivo evaluation.

    Science.gov (United States)

    He, Wei; Li, Yongji; Zhang, Rao; Wu, Zhannan; Yin, Lifang

    2014-12-10

    Owing to the complementary mechanisms of action of metformin hydrochloride (MH) and pioglitazone hydrochloride (PG), combination therapy for type 2 diabetes mellitus using the two drugs is highly desired; on the other hand, MH is not well absorbed in lower gastrointestinal tract and has a short half-life, therefore compromising the therapeutic effects. Herein, the present study was to develop gastro-floating bilayer matrix tablets in which the two drugs were incorporated into two separate layers, aiming at sustaining MH release with enhanced absorption and achieving immediate release of PG. The tablets of the optimized formulation floated on the test medium for more than 24 h with 5 min of floating lag time, and sustained MH release for 12 h via a diffusion-dependent manner; and complete release of PG within 5 min were achieved. Moreover, a steady plasma concentration of MH with a 1.5-fold increase in bioavailability, decreased C(max) and reduced T(max) was obtained, and the in vivo behavior of PG was similar to the marked product. Summarily, sustained MH release with improved absorption and immediate release of PG were obtained simultaneously using the gastro-floating bilayer tablet, allowing strengthened combination therapy for diabetes mellitus. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. 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.

  6. Sustainable conjunctive water management in irrigated agriculture: Model formulation and application to the Yaqui Valley, Mexico

    Science.gov (United States)

    Schoups, Gerrit; Addams, C. Lee; Minjares, José Luis; Gorelick, Steven M.

    2006-10-01

    This paper investigates strategies to alleviate the effects of droughts on the profitability and sustainability of irrigated agriculture. These strategies include conjunctive management of surface water and groundwater resources, and engineered improvements such as lining of irrigation canals and addition of regional pumping well capacity. A spatially distributed simulation-optimization model was developed for an irrigated system consisting of multiple surface water reservoirs and an alluvial aquifer. The simulation model consists of an agronomic component and simulators describing the hydrologic system. The physical models account for storage and flow through the reservoirs, routing through the irrigation canals, and regional groundwater flow. The agronomic model describes crop productivity as a function of irrigation quantity and salinity, and determines agricultural profit. A profit maximization problem was formulated and solved using large-scale constrained gradient-based optimization. The model was applied to a real-world conjunctive surface water/groundwater management problem in the Yaqui Valley, an irrigated agricultural region in Sonora, Mexico. The model reproduces recorded reductions in agricultural production during a historical drought. These reductions were caused by a decline in surface water availability and limited installed pumping capacity. Results indicate that the impact of the historical 8-year drought could have been significantly reduced without affecting profit in wet years by better managing surface water and groundwater resources. Namely, groundwater could have been more heavily relied upon and surface water allocation capped at a sustainable level as an operating rule. Lining the irrigation canals would have resulted in water savings of 30% of historical reservoir releases during wet years, which could have been used in subsequent drier years to increase agricultural production. The benefits of a greater reliance on groundwater pumping

  7. Development of transdermal system containing nicotine by using sustained release dosage design.

    Science.gov (United States)

    Tirnaksiz, Figen; Yuce, Zeynep

    2005-09-01

    This study was carried out to develop a membrane-controlled transdermal formulation (TF) of nicotine by using sustained release dosage design (SRDD). TFs were prepared with polyethylene membrane as a rate-controlling barrier; a carbomer was used as the gel reservoir with or without propylene glycol (PG). The in vitro target flux (0.0535 mg cm(-2) h(-1)) was calculated according to SRDD calculations. Nicotine permeation through the membrane with or without transfer adhesive was also studied using diffusion cells. Nicotine permeated through membrane (without adhesive) with a flux of 0.0555 mg cm(-2) h(-1) and this value was similar to that of the in vitro target flux. The release from the TFs and from a commercial product (Nicotinell, 52.5 mg 30 cm(-2)) was studied using the FDA paddle method. The nicotine amount was increased from 22.7 to 56.5 mg in gel reservoir, and a plateau was reached beyond 45.4 mg of drug; the system attained the maximum thermodynamic activity with 56.5 mg of nicotine. The release rate from TFs (without adhesive layer) containing PG in the reservoir was very similar to the target release rate (1.07 mg h(-1)). The fluxes of nicotine from Nicotinell and TF containing 45.4 mg of nicotine were close to the in vitro target release rate.

  8. Therapeutic Efficacy of pH-Dependent Release Formulation of Mesalazine on Active Ulcerative Colitis Resistant to Time-Dependent Release Formulation: Analysis of Fecal Calprotectin Concentration

    Directory of Open Access Journals (Sweden)

    Kousaku Kawashima

    2014-01-01

    Full Text Available Purpose. Few reports have compared the clinical efficacy of a pH-dependent release formulation of mesalazine (pH-5-ASA with a time-dependent release formulation (time-5-ASA. We examined whether pH-5-ASA is effective for active ulcerative colitis (UC in patients resistant to time-5-ASA. Methods. We retrospectively and prospectively analyzed the efficacy of pH-5-ASA in mildly to moderately active UC patients in whom time-5-ASA did not successfully induce or maintain remission. The clinical efficacy of pH-5-ASA was assessed by clinical activity index (CAI before and after switching from time-5-ASA. In addition, the efficacy of pH-5-ASA on mucosal healing (MH was evaluated in a prospective manner by measuring fecal calprotectin concentration. Results. Thirty patients were analyzed in a retrospective manner. CAI was significantly reduced at both 4 and 8 weeks after switching to pH-5-ASA. In the prospective study (n=14, administration of pH-5-ASA also significantly reduced CAI scores at 4 and 8 weeks in these patients who were resistant to time-5-ASA. In addition, fecal calprotectin concentration was significantly decreased along with improvement in CAI after switching to pH-5-ASA. Conclusions. Our results suggest that pH-5-ASA has clinical efficacy for mildly to moderately active patients with UC in whom time-5-ASA did not successfully induce or maintain remission.

  9. The influence of metoprolol dosage release formulation on the pharmacokinetic drug interaction with paroxetine

    Science.gov (United States)

    Stout, Stephen M.; Nielsen, Jace; Welage, Lynda S.; Shea, Michael; Brook, Robert; Kerber, Kevin; Bleske, Barry E.

    2010-01-01

    Studies have demonstrated an influence of dosage release formulations on drug interactions and enantiomeric plasma concentrations. Metoprolol is a commonly used β-adrenergic antagonist metabolized by CYP2D6. The CYP2D6 inhibitor paroxetine has previously been shown to interact with metoprolol tartrate. This open-label, randomized, 4 phase crossover study assessed the potential differential effects of paroxetine on stereoselective pharmacokinetics of immediate release (IR) tartrate and extended release (ER) succinate metoprolol formulations. Ten healthy subjects received metoprolol IR (50 mg) and ER (100 mg) with and without paroxetine coadministration. Blood samples were collected over 24 hours for determination of metoprolol plasma enantiomer concentrations. Paroxetine coadministration significantly increased S and R metoprolol AUC0–24h by 4 and 5 fold, respectively for IR, and 3 and 4 fold, respectively for ER. S/R AUC ratios significantly decreased. These results demonstrate a pharmacokinetic interaction between paroxetine and both formulations of metoprolol. The interaction is greater with R metoprolol and stereoselective metabolism is lost. This could theoretically result in greater β-blockade and lost cardioselectivity. The magnitude of the interaction was similar between metoprolol formulations, which may be attributable to low doses / drug input rates employed. PMID:20400652

  10. Double-layer weekly sustained release transdermal patch containing gestodene and ethinylestradiol.

    Science.gov (United States)

    Gao, Yanli; Liang, Jinying; Liu, Jianping; Xiao, Yan

    2009-07-30

    The combination therapy of gestodene (GEST) and ethinylestradiol (EE) has shown advanced contraception effect and lower side effect. The present study was designed to develop a weekly sustained release matrix type transdermal patch containing GEST and EE using blends of different polymeric combinations. The multiple-layer technique was adopted in order to maintain a steady permeation flux for 7 days. The effects of polymer types, polymer ratios, permeation enhancers, drug loadings and drug ratios in different layers on the skin permeations of the drugs were evaluated using excised mice skin. Polariscope examination was carried out to observe the drug distribution behavior. The formulation with the mixture of polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP) (7:1) was found to provide the regular release and propylene glycol (PG) could enhance the permeation fluxes of drugs. Double-layer transdermal drug delivery system (TDDS) could sustain the steady permeation flux of drugs for 7 days when the ratio of drug in drug release layer and drug reservoir layer was 1:4 with the identical total drug amount. The in vitro transdermal permeation fluxes were 0.377 microg/cm(2)/h and 0.092 microg/cm(2)/h, for GEST and EE respectively. The uniformity of dosage units test showed that the distribution of drugs in the matrix was homogeneous, which was further demonstrated by the polariscope result. The developed transdermal delivery system containing GEST and EE could be a promising non-oral contraceptive method.

  11. Didanosine extended-release matrix tablets: optimization of formulation variables using statistical experimental design.

    Science.gov (United States)

    Sánchez-Lafuente, Carla; Furlanetto, Sandra; Fernández-Arévalo, Mercedes; Alvarez-Fuentes, Josefa; Rabasco, Antonio M; Faucci, M Teresa; Pinzauti, Sergio; Mura, Paola

    2002-04-26

    Statistical experimental design was applied to evaluate the influence of some process and formulation variables and possible interactions among such variables, on didanosine release from directly-compressed matrix tablets based on blends of two insoluble polymers, Eudragit RS-PM and Ethocel 100, with the final goal of drug release behavior optimization. The considered responses were the percent of drug released at three determined times, the dissolution efficiency at 6 h and the time to dissolve 10% of drug. Four independent variables were considered: tablet compression force, ratio between the polymers and their particle size, and drug content. The preliminary screening step, carried out by means of a 12-run asymmetric screening matrix according to a D-optimal design strategy, allowed evaluation of the effects of different levels of each variable. The drug content and the polymers ratio had the most important effect on drug release, which, moreover, was favored by greater polymers particle size; on the contrary the compression force did not have a significant effect. The Doehlert design was then applied for a response-surface study, in order to study in depth the effects of the most important variables. The desirability function was used to simultaneously optimize the five considered responses, each having a different target. This procedure allowed selection, in the studied experimental domain, of the best formulation conditions to optimize drug release rate. The experimental values obtained from the optimized formulation highly agreed with the predicted values. The results demonstrated the reliability of the model in the preparation of extended-release matrix tablets with predictable drug release profiles.

  12. Modified-Release Formulations of Second-Generation Antiepileptic Drugs: Pharmacokinetic and Clinical Aspects.

    Science.gov (United States)

    Anderson, Gail D; Saneto, Russell P

    2015-08-01

    Modified-release or extended-release (XR) formulations are used to decrease the frequency of dosing for drugs with rapid elimination, to improve convenience and adherence. Use of a modified-release formulation can decrease the peak to trough fluctuations in serum concentrations and theoretically improve the therapeutic benefit of the drug, by decreasing adverse events associated with the higher peak concentrations. Once-daily formulations of lamotrigine (Lamictal XR(®)), levetiracetam (Keppra XR(®)), oxcarbazepine (Oxtellar XR(®), Apydan(®) extent) and topiramate (Qudexy XR™, Trokendi XR™) are approved for the treatment of focal and/or generalized onset seizures. Other seizure medications have been approved for non-epileptic symptoms. Gabapentin XR (Gralise(®)) is approved for the treatment of post-herpetic neuralgias. Gabapentin enacarbil XR (Horizant(®)) is a prodrug of gabapentin and is indicated for treatment of post-herpetic neuralgia and restless leg syndrome, a novel indication. For all but Qudexy XR™, the tablets/capsules must be swallowed whole, without cutting, crushing or chewing, in order to maintain the XR properties of the formulation. Qudexy XR™ can be swallowed intact or the capsules can be opened and sprinkled onto soft food for those with swallowing difficulties, for example, children and the elderly. The bioavailability of Gralise(®) and Horizant(®) is significantly affected by food, specifically fat content, and should be taken with a meal to maximize absorption. Overall, the primary advantage of the newly released XR formulations is the once-daily dosing to improve convenience and adherence, with very limited data suggesting improved tolerability.

  13. Generic sustained release tablets of trimetazidine hydrochloride: Preparation and in vitro–in vivo correlation studies

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    Longmei Wang

    2016-06-01

    Full Text Available The aim of the current work was to develop generic sustained-release tablets containing 35 mg trimetazidine dihydrochloride and to establish an in vitro–in vivo correlation that could predict the bioavailability. The marketed sustained release tablet (Vastarel MR used as reference, a sustained-release matrix tablet was prepared using hydroxypropyl methylcellulose (HPMC as matrix by wet granulation and the in vitro dissolution profiles of the self-made tablets were determined in four different dissolution media (0.1 M HCl, pH 4.5 PBS, pH 6.8 PBS and water. A higher similarity between prepared tablets and Vastarel MR was established, with similarity factor (f2 ranging from 60 to 75 in the four media. The in vivo pharmacokinetics was studied in six healthy beagles. Compared with Vastarel MR, the Cmax of self-made tablets was slightly decreased, while the Tmax and MRT0–t were slightly prolonged, but with no significant difference (P > 0.05. The average of relative bioavailability (F was 102.52% based on AUC0–t. For log-transformed AUC0–t and Cmax, the upper confidence limit on the appropriate criterion is <0, indicating these two formulations were population bioequivalent. The in vivo–in vitro correlation coefficient obtained from point-to-point analysis of self-made tablets was 0.9720. In conclusion, the prepared tablets were bioequivalent to the marketed tablets, according to both the in vitro release rate and extent of absorption, and a good in vivo–in vitro correlation was established for the self-made tablets that indicated in vitro dissolution tests could be used as a surrogate for bioavailability studies.

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

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    Adedokun Musiliu O.

    2014-09-01

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

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

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    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.

  16. Sustained-release effervescent floating matrix tablets of baclofen: development, optimization and in vitro-in vivo evaluation in healthy human volunteers

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    YM Rao

    2011-07-01

    Full Text Available "n  Background and the purpose of the study: Baclofen, a centrally acting skeletal muscle relaxant, is indicated in the long-term treatment of spasticity. It is difficult to formulate baclofen sustained release dosage forms because its absorption on arrival to colon (or even before is low or nonexistent. In the present investigation efforts were made to improve the bioavailability of baclofen by increasing the residence time of the drug through sustained-release matrix tablet formulation via gastroretentive mechanism. "n  Methods: Tablets were prepared by wet granulation technique. The influence of gas generating and gel forming agents, amount of baclofen and total weight of tablet on physical properties, in vitro buoyancy, floating lag time, drug release, DSC, X-ray studies were investigated. The release mechanisms were explored and explained by applying zero order, first order, Higuchi and Korsmeyer equations. The selected formulations were subjected to stability study for the period of three months. "n  Results: For all formulations, kinetics of drug release from tablet followed Higuchi's square root of time kinetic treatment heralding diffusion as predominant mechanism of drug release. Formulations containing 20 mg and 40 mg (F-1 and F-7 showed similar release profiles. There was no significant change in the selected formulations, when subjected to accelerated stability conditions over a period of three months. X-ray imaging in six healthy human volunteers revealed a mean gastric retention period of 5.50±0.7 hrs for the selected formulation. "n  Conclusion:Stable, sustained release effervescent floating matrix tablets of baclofen could be prepared by wet granulation technique.

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

    Science.gov (United States)

    Caixàs, Assumpta; Albert, Lara; Capel, Ismael; Rigla, Mercedes

    2014-01-01

    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. PMID:25258511

  18. Slow-release formulations of the herbicide MCPA by using clay-protein composites.

    Science.gov (United States)

    Alromeed, Alaa Aldin; Scrano, Laura; Bufo, Sabino A; Undabeytia, Tomás

    2015-09-01

    MCPA [(4-chloro-2-methylphenoxy) acetic acid] is a widely used herbicide showing high leaching in the soil. In this study, clay-protein-based formulations of this herbicide were designed to reduce the risk of water pollution resulting from conventional formulations. Clay-gelatin formulations of MCPA were prepared, and the influence of synthesis parameters such as pH and the presence of a plasticiser (glycerol) on the active substance content and performance of the new formulations was examined. Differential scanning calorimetry measurements provided information on the stability of the gelatin matrix in the gelatin-clay complex. Fourier transform infrared spectroscopy showed that the herbicide was retained by the formation of hydrogen bonds with side amino groups of the protein backbone and polyion complexation. Clay-protein-based formulations prepared at a pH below the isoelectric point value of the protein and in the absence of glycerol provided the slowest release of MCPA in water. Soil column experiments showed a fourfold reduction in leaching and improved bioactivity in the upper soil layer for the new formulation compared with a commercial product used as a control. A reduction in the recommended dose of MCPA can be achieved by employing clay-gelatin, which reduces the environmental risk associated with herbicide applications. © 2014 Society of Chemical Industry.

  19. Polymeric macroporous formulations for the control release of mosquitocidal Bacillus sphaericus ISPC-8.

    Science.gov (United States)

    Tripathi, Anuj; Hadapad, Ashok B; Hire, Ramesh S; Melo, Jose S; D'Souza, Stanislaus F

    2013-12-10

    Bio-polymeric mosquitocidal formulations were developed for the control release of Bacillus sphaericus ISPC-8 by the immobilization of its spore-crystal complex onto the macroporous polymeric matrices. The biodegradable formulations were synthesized at sub-zero temperature using natural polymeric substrates like agarose, alginate, cellulose, non-adsorbent cotton, wooden cork powder and also magnetite nanoparticles. The obtained polymeric matrices were morphologically characterized, which showed 85-90% porosity, uniform pores distribution, high permeability and controlled degradation (19-30%) in 4 weeks depending upon the composition of formulations. Further, the polymeric macroporous formulations were tested for persistence of mosquitocidal activity against Culex quinquefasciatus larvae. Unformulated B. sphaericus ISPC-8 spores retained 54% of larvicidal activity after 7 days, which completely reduced after 35 days of treatment. However, the immobilized B. sphaericus spores in agarose-alginate formulations showed high larvicidal activity on day 7 and retained about 45% activity even after 35 days of treatments. Studies on UV-B and pH dependent inactivation of toxins and spore viability showed that these formulations were significantly protecting the spores as compared to the unformulated spores, which suggest its potential application for the mosquito control program. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. High-throughput NIR-chemometric methods for chemical and pharmaceutical characterization of sustained release tablets.

    Science.gov (United States)

    Porfire, Alina; Filip, Cristina; Tomuta, Ioan

    2017-05-10

    The aim of this study was the development and validation of methods based on near-infrared spectroscopy (NIRS) and chemometry, useful for characterization of sustained release (SR) tablets with indapamide, in terms of tablet composition (API and two excipients), in vitro drug release mechanism (k and n Peppas) and crushing strength. A calibration set consisting of 25 different tablets formulations containing API, HPMC and lactose at five different content levels in the range 100±20% relative to a targeted tablet composition, were manufactured by direct compression in order to develop the methods for prediction of tablet composition, and in vitro drug release mechanism. On the other hand, a 15 batches calibration set prepared at five different compression forces was used for development of methods for prediction of crushing strength. Moreover, independent batches were manufactured for validation of all methods Intact tablets were analyzed by transmission mode with NIRS, the spectra were pre-processed, and partial least square (PLS) regression was used to build prediction models. Cross-validation was carried out in order to select the optimal number of PLS factors for all models, and the best model was chosen based on their RMSECV and bias. All developed methods were validated in terms of trueness, precision and accuracy. Based on the validation results, the methods proposed in this work can successfully be applied for routine determination of indapamide, HPMC and lactose content of sustained release tablets, as well as for prediction of their in vitro drug release mechanism (k and n Peppas) and crushing strength. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Pharmaceutical suspension containing both immediate/sustained-release amoxicillin-loaded gelatin nanoparticles: preparation and in vitro characterization

    Science.gov (United States)

    Harsha, Sree

    2013-01-01

    Pharmaceutical suspension containing oral dosage forms delivering both immediate-release and sustained-release amoxicillin was developed as a new dosage form to eradicate Helicobacter pylori. Amoxicillin-loaded gelatin nanoparticles are able to bind with the mucosal membrane after delivery to the stomach and could escalate the effectiveness of a drug, providing dual release. The objective of this study was to develop amoxicillin nanoparticles using innovative new technology – the Büchi Nano Spray Dryer B-90 – and investigate such features as drug content, particle morphology, yield, in vitro release, flow properties, and stability. The nanoparticles had an average particle size of 571 nm. The drug content and percentage yield was 89.2% ± 0.5% and 93.3% ± 0.6%, respectively. Angle of repose of nanoparticle suspension was 26.3° and bulk density was 0.59 g/cm3. In vitro drug release of formulations was best fitted by first-order and Peppas models with R2 of 0.9841 and 0.9837 respectively; release profile was 15.9%, while; for the original drug, amoxicillin, under the same conditions, 90% was released in the first 30 minutes. The nanoparticles used in this study enabled sustained release of amoxicillin over an extended period of time, up to 12 hours, and were stable for 12 months under accelerated storage conditions of 25°C ± 2°C and 60% ± 5% relative humidity. PMID:24101859

  2. Characterizing and designing polycation-clay nanocomposites as a basis for imazapyr controlled release formulations.

    Science.gov (United States)

    Radian, Adi; Mishael, Yael G

    2008-03-01

    A novel controlled release formulation (CRF) of the herbicide imazapyr (IMP) was designed to reduce its leaching,which causes soil and water contamination. The anionic herbicide IMP was bound to polydiallyldimethylammonium-chloride (PDADMAC)-montmorillonite composites. PDADMAC adsorption reached a high loading of polymer, which resulted in charge reversal of the clay and promoted IMP binding. The composites were characterized by Fourier transform infrared, zeta potential, and X-ray diffraction measurements, indicating electrostatic interactions of the polycation with the surface, polycation intercalation in the clay and suggesting a configuration as loops and tails on the surface at high loadings. IMP binding to the composites is affected by polycation loading and flocculation. Upon adding high concentrations of IMP to a composite of 0.16 g/g, we obtained high herbicide loadings (66% active ingredient). IMP release from the CRFs applied on a thin layer of soil was substantially slower than its release from the commercial formulation (Arsenal). Accordingly, soil column bioassays indicated reduced herbicide leaching (nearly 2-fold) upon applying the CRFs while maintaining good herbicidal activity. The new PDADMAC-clay formulations are promising from the environmental and weed control management points of view.

  3. Arsenic release from glass containers by action of intravenous nutrition formulation constituents.

    Science.gov (United States)

    Bohrer, Denise; Becker, Emilene; Nascimento, Paulo Cícero; Mörschbächer, Vanessa; de Carvalho, Leandro Machado; da Silva Marques, Marieli

    2006-06-06

    Pharmacopoeias prescribe tests to determine the levels of arsenic in raw materials and glass containers. In this study, glass ampoules for injectables containing individually the main components of intravenous nutrition formulations were submitted to the hydrolytic resistance test by heating at 121 degrees C for 30 min. As(V) and As(III) levels in these solutions after heating were determined by hydride generation atomic absorption spectrometry. The arsenic content of substances used in these formulations was previously determined, as well as the arsenic content of the glass containers. The results showed that raw substances as well as glass containers contain arsenic. Moreover, arsenic is released during the heating (hydrolytic resistance test). However, the amount released and the arsenic species present in solution depend on the solution composition. While As(V) was the predominant specie in glass, solutions containing reducing substances such as glucose and vitamins had As(III) in higher concentration. Therefore, arsenic is released from glass containers during the heating for sterilization, and reacts with formulation constituents depending on their reducing properties.

  4. Development and Optimization of a Novel Prolonged Release Formulation to Resist Alcohol-Induced Dose Dumping.

    Science.gov (United States)

    Gujjar, Chaitanya Yogananda; Rallabandi, Balaramesha Chary; Gannu, Ramesh; Deulkar, Vallabh Subashrao

    2016-04-01

    Alcohol-induced dose dumping is a serious concern for the orally administered prolonged release dosage forms. The study was designed to optimize the independent variables, propylene glycol alginate (PGA), Eudragit RS PO (ERS) and coating in mucoadhesive quetiapine prolonged release tablets 200 mg required for preventing the alcohol-induced dose dumping. Optimal design based on response surface methodology was employed for the optimization of the composition. The formulations are evaluated for in vitro drug release in hydrochloric acid alone and with 40% v/v ethanol. The responses, dissolution at 120 min without alcohol (R1) and dissolution at 120 min with alcohol (R2), were statistically evaluated and regression equations are generated. PGA as a hydrophilic polymeric matrix was dumping the dose when dissolutions are carried in 0.1 N hydrochloric acid containing 40% v/v ethanol. ERS addition was giving structural support to the swelling and gelling property of PGA, and thus, was reducing the PGA erosion in dissolution media containing ethanol. Among the formulations, four formulations with diverse composition were meeting the target dissolution (30-40%) in both the conditions. The statistical validity of the mathematical equations was established, and the optimum concentration of the factors was established. Validation of the study with six confirmatory runs indicated high degree of prognostic ability of response surface methodology. Further coating with ReadiLycoat was providing an additional resistance to the alcohol-induced dose dumping. Optimized compositions showed resistance to dose dumping in the presence of alcohol.

  5. A Strategy to Develop Bioactive Nanoarchitecture Cellulose: Sustained Release and Multifarious Applications.

    Science.gov (United States)

    Karuppusamy, Sembanadar; Pratheepkumar, Annamalai; Dhandapani, Perumal; Maruthamuthu, Sundaram; Kulandainathan, Manickam Anbu

    2015-09-01

    Cellulose membranes were engineered to produce hydrophobic surfaces via a simple and soft chemical process to introduce multifunctional properties of an otherwise hydrophilic cellulose surface with polymer-grafted nanosilver to form a core-shell nanostructure. A superhydrophobic domain of the polymer on cellulose was created through the amide bond formation between the anhydride units of the polymer and the aminosiloxane-functionalized cellulose through layer-over-layer formulation. This formulation was confirmed through XPS, XRD, 29Si-NMR, and FTIR studies. Further, SEM and TEM analysis revealed that short linear silver nanowires were uniformly obtained with an average diameter of 60 nm and length of 288 nm, using a mild reducing agent at 60 degrees C, which resulted in a hierarchical cellulose surface. The nanosilver colloids released from the hierarchical cellulose surface were stabilized by the polymer matrix in solution, which led to a decrease in the rate of formation of Ag+ enhancing the material's killing efficacy against microbes. This biodegradable nanocomposite-based cellulose hierarchical surface development has potential for application as superhydrophobic membranes for oil-water separation, antimicrobial activity, and pH-triggered sustained release of colloidal silver for wound healing, which could possibly be applied for use as smart bandages.

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

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    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.

  7. Organically modified titania nanoparticles for sustained drug release applications.

    Science.gov (United States)

    Sethi, Komal; Roy, Indrajit

    2015-10-15

    In this paper, we report the synthesis, characterization of drug-doped organically modified titania nanoparticles, and their applications in sustained drug release. The drug-doped nanoparticles were synthesized in the hydrophobic core of oil-in-water microemulsion medium. Structural aspects obtained through TEM and FESEM depicted that organically modified titania nanoparticles are monodispersed with spherical morphology, with an average size of around 200 nm. Their polymorphic forms and porosity were determined using powder XRD and BET, respectively, which showed that they are present in the anatase form, with a surface area of 136.5 m(2)/g and pore-diameter of 5.23 nm. After synthesis and basic structural characterizations, optical properties were studied for both fluorophore and drug encapsulated nanoparticles. The results showed that though the optical properties of the fluorophore are partially diminished upon nanoencapsulation, it became more stable against chemical quenching. The nanoparticles showed pH-dependent drug release pattern. In vitro studies showed that the nanoparticles were efficiently uptaken by cells. Cell viability assay results showed that though the placebo nanoparticles are non-cytotoxic, the drug-doped nanoparticles show drug-induced toxicity. Therefore, such porous nanoparticles can be used in non-toxic drug delivery applications. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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    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.

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

    Science.gov (United States)

    Refaat, Ahmed; Sokar, Magda; Ismail, Fatma; Boraei, Nabila

    2016-12-01

    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.

  10. 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

  11. Influence of paints formulations on nanoparticles release during their life cycle

    Science.gov (United States)

    Fiorentino, Brice; Golanski, Luana; Guiot, Arnaud; Damlencourt, Jean-François; Boutry, Delphine

    2015-03-01

    Pristine nanoparticles (NPs) may present a hazard to humans and the environment, and hence it is important to know to what extent NPs can be freely released from commercialized products in which they are added. The purpose of this study was to identify the parameters of the paint formulation containing SiO2 NPs of 19-nm diameter that could have an impact on the release induced by aging and abrasion. In order to simulate outdoor aging during the life cycle of the product, painted panels were exposed to accelerated weathering experiments in accordance with the norm EN ISO 16474-3:2013. The surface modification of these paints was characterized by scanning electron microscope coupled with energy dispersive spectrometry (SEM-EDS). These analyses showed that the acrylic copolymer binder has undergone a more significant chemical degradation compared with the styrene-acrylic copolymer. To simulate a mechanical aging, abrasion tests were conducted using a Taber Abraser, simulating critical scenarios of the abrasion standard. The particle size distributions and particle concentrations of the abraded particles were measured using an electric low-pressure impactor. After accelerated aging and abrasion tests, we observed a link between the paint degradations occurring with the release of pristine NPs and the embedded pristine NPs. Surface degradation of acrylic copolymer paints was more significant than that of the styrene-acrylic copolymer paints, and this induced a release of NPs 2.7 times higher. Other parameters like TiO2 addition as pigments induced a strong stability of paint against light and water, decreasing the total number of NPs released from paints from 30,000 to 1200 particles/cm3. These results revealed that formulations can be tuned to decrease the number of free NPs released and get a "safe-by-design" product.

  12. Influence of paints formulations on nanoparticles release during their life cycle

    Energy Technology Data Exchange (ETDEWEB)

    Fiorentino, Brice, E-mail: brice.fiorentino@cea.fr; Golanski, Luana; Guiot, Arnaud; Damlencourt, Jean-François; Boutry, Delphine [Commissariat à l’énergie atomique et aux énergies alternatives (France)

    2015-03-15

    Pristine nanoparticles (NPs) may present a hazard to humans and the environment, and hence it is important to know to what extent NPs can be freely released from commercialized products in which they are added. The purpose of this study was to identify the parameters of the paint formulation containing SiO{sub 2} NPs of 19-nm diameter that could have an impact on the release induced by aging and abrasion. In order to simulate outdoor aging during the life cycle of the product, painted panels were exposed to accelerated weathering experiments in accordance with the norm EN ISO 16474-3:2013. The surface modification of these paints was characterized by scanning electron microscope coupled with energy dispersive spectrometry (SEM–EDS). These analyses showed that the acrylic copolymer binder has undergone a more significant chemical degradation compared with the styrene-acrylic copolymer. To simulate a mechanical aging, abrasion tests were conducted using a Taber Abraser, simulating critical scenarios of the abrasion standard. The particle size distributions and particle concentrations of the abraded particles were measured using an electric low-pressure impactor. After accelerated aging and abrasion tests, we observed a link between the paint degradations occurring with the release of pristine NPs and the embedded pristine NPs. Surface degradation of acrylic copolymer paints was more significant than that of the styrene-acrylic copolymer paints, and this induced a release of NPs 2.7 times higher. Other parameters like TiO{sub 2} addition as pigments induced a strong stability of paint against light and water, decreasing the total number of NPs released from paints from 30,000 to 1200 particles/cm{sup 3}. These results revealed that formulations can be tuned to decrease the number of free NPs released and get a “safe-by-design” product.

  13. A Prospective Survey on Safety of Sustained-Release Theophylline in Treatment of Asthma and COPD

    Directory of Open Access Journals (Sweden)

    Sohei Makino

    2006-01-01

    Conclusions: The present survey demonstrates that sustained-release theophylline is safe, as long as used appropriately, although adverse reactions tend to develop early after initiation of administration.

  14. A comparative study between melt granulation/compression and hot melt extrusion/injection molding for the manufacturing of oral sustained release thermoplastic polyurethane matrices.

    Science.gov (United States)

    Verstraete, G; Mertens, P; Grymonpré, W; Van Bockstal, P J; De Beer, T; Boone, M N; Van Hoorebeke, L; Remon, J P; Vervaet, C

    2016-11-20

    During this project 3 techniques (twin screw melt granulation/compression (TSMG), hot melt extrusion (HME) and injection molding (IM)) were evaluated for the manufacturing of thermoplastic polyurethane (TPU)-based oral sustained release matrices, containing a high dose of the highly soluble metformin hydrochloride. Whereas formulations with a drug load between 0 and 70% (w/w) could be processed via HME/(IM), the drug content of granules prepared via melt granulation could only be varied between 85 and 90% (w/w) as these formulations contained the proper concentration of binder (i.e. TPU) to obtain a good size distribution of the granules. While release from HME matrices and IM tablets could be sustained over 24h, release from the TPU-based TSMG tablets was too fast (complete release within about 6h) linked to their higher drug load and porosity. By mixing hydrophilic and hydrophobic TPUs the in vitro release kinetics of both formulations could be adjusted: a higher content of hydrophobic TPU was correlated with a slower release rate. Although mini-matrices showed faster release kinetics than IM tablets, this observation was successfully countered by changing the hydrophobic/hydrophilic TPU ratio. In vivo experiments via oral administration to dogs confirmed the versatile potential of the TPU platform as intermediate-strong and low-intermediate sustained characteristics were obtained for the IM tablets and HME mini-matrices, respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. [Preparation and evaluation of sustained-release microsphere of Sanguis Draconis in vitro].

    Science.gov (United States)

    Ding, Li-Yu; Xia, Peng-Fei; Yang, Cai-Qin; Lin, Yu-Long; Wang, Jing

    2007-03-01

    To prepare sustained-release microsphere containing extract of Sanguis Draconis and to measure its dissolution in vitro. Sustained-release microsphere was prepared with polylactic acid (PLA) as carriers using the oil-in-water (O/W) emulsion solvent evaporation method. The powder particle's characteristics of sustainded-release microsphere were evaluated comprehensively, and its dissolution characteristics in vitro were studied. The microsphere was round and its surface was smooth, drug-loading rate was 21.97% and the entrapment rate was 55.76%, the accumulative release percentage was 76. 71% in 16 hours. The sustained release effect of Sanguis Draconis microspheres was formed with potentially wide applications.

  16. Bromelain Loading and Release from a Hydrogel Formulated Using Alginate and Arabic Gum.

    Science.gov (United States)

    Ataide, Janaína Artem; Cefali, Letícia Caramori; Rebelo, Marcia de Araujo; Spir, Lívia Genovez; Tambourgi, Elias Basile; Jozala, Angela Faustino; Chaud, Marco Vinícius; Silveira, Edgar; Gu, Xiaochen; Gava Mazzola, Priscila

    2017-07-01

    An ideal wound dressing ensures a moist environment around the wound area and absorbs exudates from the wound surface. Topical application of bromelain to incised wounds has been shown to reprogram the wound microenvironment to promote effective tissue repair. Combining the characteristics of hydrogels and bromelain is therefore of great interest. Herein, we describe the development of a hydrogel, formulated using alginate and Arabic gum, for bromelain loading and release. The hydrogel formulation was evaluated using response surface methodology, considering the pH value and the concentration of alginate and Arabic gum. Bromelain loading and release were evaluated based on passive diffusion. Differential scanning calorimetry and Fourier transform infrared spectroscopy were performed to confirm bromelain immobilization in the hydrogel. The final hydrogel formulation had a swelling ratio of 227 % and incorporated 19 % of bromelain from a bromelain solution. Bromelain immobilization in the hydrogel was the result of hydrogen bond formation and was optimal at 4 °C after 4 h of contact. This evidence suggests that bromelain entrapment into a hydrogel is a promising strategy for the development of wound dressings that support the debridement of burns and wounds. Georg Thieme Verlag KG Stuttgart · New York.

  17. Formulation effects on the release of silica dioxide nanoparticles from paint debris to water.

    Science.gov (United States)

    Zuin, Stefano; Massari, Andrea; Ferrari, Arlen; Golanski, Luana

    2014-04-01

    Waterborne paints with integrated nanoparticles have been recently introduced into the market as nanoparticles offer improved or novel functionalities to paints. However, the release of nanoparticles during the life cycle of nano-enhanced paint has only been studied to a very limited extent. The paint composition could determine in what quantities and forms the nanoparticles are released. In this work, paint formulations containing the same amount of silicon dioxide (SiO2) nanoparticles but differing in the pigment volume concentration (PVC) and in amount and type of binder and pigment, were studied through leaching test to investigate the influence of these parameters on release of Si from paint. The results indicate greater release of Si, about 1.7 wt.% of the SiO2 nanoparticles in the paint, for paint formulated with higher PVC value (63%), suggesting that the PVC is a crucial factor for release of SiO2 nanoparticles from paints. This hypothesis was also based on the fact that agglomerates of SiO2 nanoparticles were only found in leachates from paint with higher PVC. A paint sample with the higher amount of binder and less calcite filler exhibited a lower release of Si among the paints with a low PVC value (35%), and no SiO2 particles were detected in leachates collected from this paint. This could be due to the fact that a high portion of binder forms a suitable matrix to hold the SiO2 ENPs in paint. The paint sample in which the amount of calcite was partially substituted with TiO2 pigment did not show an important reduction on Si release. Our work suggests that paint debris containing SiO2 nanoparticles may release a limited amount of Si into the environment, and that by adjusting the properties of the binder in combination with common pigments it is possible to reduce the release of SiO2 nanoparticles. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. The preparation of the sustained release metformin hydrochloride microcapsules by the Wurster fluidized bed.

    Science.gov (United States)

    Cao, Jin; Liu, Hongfei; Pan, Weisan; Sun, Changshan; Feng, Yingshu; Zhong, Hui; Shi, Shuang Shuang; He, Yan

    2014-07-01

    The main objective of this study was to prepare sustained release metformin hydrochloride microcapsules by the Wurster fluidized bed and to obtain the optimized coating process and formulation. Fine microcapsules without agglomeration were obtained in a continuous coating process with the atomization air pressure of 0.2Mpa and an appropriate coating speed temperature. With other design variables of coating process fixed, the effects of different fluidizing air volume, coating temperature, coating speed, coating material, coating materials amount, plasticizer type and plasticizer amount on drug release were investigated respectively. Coating solution was achieved by dissolving EC45cps of 21 g, EC100cps of 7 g, DBS of 2.8 g and talcum powder of 8 g in ethanol to get a final volume of 500 ml. Particles of 150g along with 500mL coating solution would be fine. The results showed that with the air volume of 35 m3•h-1, coating temperature of 35o, coating speed of 6 mL•min-1 and proper amount of coating solution, fine microcapsules were obtained. The mean diameter of the microcapsules obtained eventually were 213 μm and the drug content were 23%, which was suitable for producing a suspension. Particle diameter distribution corresponded to the normal distribution and obviously prolonged drug-release was achieved.

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

    Directory of Open Access Journals (Sweden)

    El Nabarawi MA

    2017-04-01

    Full Text Available Mohamed A El Nabarawi,1 Mahmoud H Teaima,1 Rehab A Abd El-Monem,2 Nagla A El Nabarawy,3 Dalia A Gaber4 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Misr University for Science and Technology, 6th of October, Egypt; 3National Egyptian Center of Environment and Toxicological Research (NECTER, Faculty of Medicine, Cairo University, Cairo, Egypt; 4Department of Quality Control, Holding Company for Biological Products and Vaccines, Cairo, Egypt Abstract: To prolong the residence time of dosage forms within the gastrointestinal tract until all drug is released at the desired rate is one of the real challenges for oral controlled-release drug delivery systems. This study was designed to develop a controlled-release floating matrix tablet and floating raft system of Mebeverine HCl (MbH and evaluate different excipients for their floating behavior and in vitro controlled-release profiles. Oral pharmacokinetics of the optimum matrix tablet, raft system formula, and marketed Duspatalin® 200 mg retard as reference were studied in beagle dogs. The optimized tablet formula (FT-10 and raft system formula (FRS-11 were found to float within 34±5 sec and 15±7 sec, respectively, and both remain buoyant over a period of 12 h in simulated gastric fluid. FT-10 (Compritol/HPMC K,100M 1:1 showed the slowest drug release among all prepared tablet formulations, releasing about 80.2% of MbH over 8 h. In contrast, FRS-11 (Sodium alginate 3%/HPMC K,100M 1%/Precirol 2% had the greatest retardation, providing sustained release of 82.1% within 8 h. Compared with the marketed MbH product, the Cmax of FT-10 was almost the same, while FRS-11 maximum concentration was higher. The tmax was 3.33, 2.167, and 3.0 h for marketed MbH product, FT-10, and FRS-11, respectively. In addition, the oral bioavailability experiment showed that the relative

  20. Preparation and evaluation of sustained-release matrix tablets based on metoprolol and an acrylic carrier using injection moulding.

    Science.gov (United States)

    Quinten, T; Andrews, G P; De Beer, T; Saerens, L; Bouquet, W; Jones, D S; Hornsby, P; Remon, J P; Vervaet, C

    2012-12-01

    Sustained-release matrix tablets based on Eudragit RL and RS were manufactured by injection moulding. The influence of process temperature; matrix composition; drug load, plasticizer level; and salt form of metoprolol: tartrate (MPT), fumarate (MPF) and succinate (MPS) on ease of processing and drug release were evaluated. Formulations composed of 70/30% Eudragit RL/MPT showed the fastest drug release, substituting part of Eudragit RL by RS resulted in slower drug release, all following first-order release kinetics. Drug load only affected drug release of matrices composed of Eudragit RS: a higher MPT concentration yielded faster release rates. Adding triethyl citrate enhanced the processability, but was detrimental to long-term stability. The process temperature and plasticizer level had no effect on drug release, whereas metoprolol salt form significantly influenced release properties. The moulded tablets had a low porosity and a smooth surface morphology. A plasticizing effect of MPT, MPS and MPF on Eudragit RS and Eudragit RL was observed via DSC and DMA. Solubility parameter assessment, thermal analysis and X-ray diffraction demonstrated the formation of a solid solution immediately after production, in which H-bonds were formed between metoprolol and Eudragit as evidenced by near-infrared spectroscopy. However, high drug loadings of MPS and MPF showed a tendency to recrystallise during storage. The in vivo performance of injection-moulded tablets was strongly dependent upon drug loading.

  1. FORMULATION AND IN VITRO STUDY OF PROPRANOLOL HYDROCHLORIDE CONTROLLED RELEASE FROM CARBOXYMETHYL CHITOSAN-BASED MATRIX TABLETS

    Directory of Open Access Journals (Sweden)

    Hernawan Hernawan

    2013-12-01

    Full Text Available Formulation and in vitro study of propranolol hydrochloride controlled release from carboxymethyl chitosan-based matrix tablets have been conducted. Formulations with various concentrations of carboxymethyl chitosan 2% (F1, 4% (F2, 6% (F3 were done by wet granulation method. Compatibility test was conducted by XRD and FTIR spectroscopy to determine interaction between propranolol hydrochloride and polymer excipients. Dissolution profiles was obtained through in vitro tests release using simulated gastric fluid (without enzymes, pH 1.2 for the first 2 h and followed by simulated intestinal fluid (phosphate buffer solution without enzyme, pH 7.2 for 2 h remaining. The dissolution profile of each formulation was fitted with five kinetics modeling of drug release (zero order, first order, Higuchi, Peppas-Korsmeyer, and Hixson-Crowell. The compatibility test results showed that formulation caused physical interactions between propranolol hydrochloride and polymer excipient but doesn't make crystallinity nature of propranolol hydrochloride disturbed even after formulation. Dissolution profiles of each formulation showed that controlled release of propranolol hydrochloride from the tablet followed Peppas-Korsmeyer model. It is concluded that carboxymethyl chitosan in appropriate proportions is suitable for formulating propranolol hydrochloride controlled release tablets which exhibit Peppas-Korsmeyer release kinetics.

  2. Formulation factors affecting the release of ezetimibe from different liquisolid compacts.

    Science.gov (United States)

    Khanfar, M; Sheikh Salem, M; Hawari, R

    2013-01-01

    Liquisolid technique is one of the methods used to improve the dissolution rate of the poorly water soluble drugs utilizing non volatile liquids. Enhancement of the release of ezetimibe from different liquisolid formulations. Four liquid vehicles were used to prepare the liquid medications with different drug concentrations. The interaction between the drug and the excipients in liquisolid powders were characterized by DSC, X-ray, FTIR and SEM. Furthermore, the powder characteristics were evaluated by Carr's Index and powder wetting time determinations, respectively. All prepared formulations were compressed at different pressures to end with the same constant porosity and the tablets were evaluated by different tests and compared with conventional formula. No interaction had been detected in all liquisolid formulations as shown in the results of XRD, FTIR, DSC and SEM. In addition to that, all liquisolid compacts had expressed faster dissolution profiles compared with that of conventional formula. The dissolution rate was affected by the drug concentration, solubility of the drug in the liquid vehicle and type of carrier. In addition, the presence of the liquid vehicle has been found to affect the mechanical properties of the liquisolid formulations.

  3. Formulation and drying of alginate beads for controlled release and stabilization of invertase.

    Science.gov (United States)

    Santagapita, Patricio R; Mazzobre, M Florencia; Buera, M Pilar

    2011-09-12

    Several alternatives to the conventional alginate beads formulation were studied for encapsulation of invertase. Pectin was added to the alginate/enzyme solution while trehalose and β-cyclodextrin were added to the calcium gelation media. The effect of composition changes, freezing, drying methods (freeze, vacuum, or air drying), and thermal treatment were evaluated on invertase stability and its release kinetics from beads. The enzyme release mechanism from wet beads depended on pH. The addition of trehalose, pectin, and β-cyclodextrin modified the bead structure, leading in some cases to a release mechanism that included the relaxation of the polymer chains, besides Fickian diffusion. Enzyme release from vacuum-dried beads was much faster than from freeze-dried beads, probably due to their higher pore size. The inclusion of β-cyclodextrin and especially of pectin prevented enzyme activity losses during bead generation, and trehalose addition was fundamental for achieving adequate invertase protection during freezing, drying, and thermal treatment. Present results showed that several alternatives such as drying method, composition, as well as pH of the relese medium can be managed to control enzyme release.

  4. Residue and bio-efficacy evaluation of controlled release formulations of metribuzin against weeds in wheat.

    Science.gov (United States)

    Kumar, Jitendra; Nisar, Keyath; Shakil, N A; Sharma, Rajvir

    2010-09-01

    Controlled release formulations of metribuzin in polyvinyl chloride, (emulsion); carboxy methyl cellulose, CMC and carboxy methyl cellulose- kaolinite composite, CMC-KAO are reported. The MET-CMC-KAO-3 (T(9)) formulation provided a superior control (76.1%) of weeds in field grown wheat in comparison to metribuzin 75 DF (57.14%) at the dose (350 g a.i. ha(-1)) after 90 days of sowing. The treatment (T(9)) reduced the dry weight of the weed flora after 30 days of sowing (4.0 g m(-2)) and significantly superior over metribuzin 75 DF (6.0 g m(-2)) and control (17.72 g m(-2)). There were nil to negligible metribuzin residue in soil at harvest of wheat crop and were within prescribed limit of 10 mg L(-1) in drinking water (EPA).

  5. Abuse and Diversion of Immediate Release Opioid Analgesics as Compared to Extended Release Formulations in the United States.

    Science.gov (United States)

    Iwanicki, Janetta L; Severtson, S Geoff; McDaniel, Heather; Rosenblum, Andrew; Fong, Chunki; Cicero, Theodore J; Ellis, Matthew S; Kurtz, Steven P; Buttram, Mance E; Dart, Richard C

    2016-01-01

    Therapeutic use and abuse of prescription opioids in the United States increased substantially between 1990 and 2010. The Centers for Disease Control estimated deaths related to pharmaceutical opioids reached nearly 19,000 in 2014. Of prescription opioids sold, 10% are extended release (ER) and 90% immediate release (IR). However, most regulations and interventions have focused on decreasing ER abuse. Our objective was to compare rates of abuse and diversion of ER and IR opioid analgesics over time using multiple surveillance programs. Rates of abuse and diversion of ER and IR opioid formulations were compared using data from four surveillance programs in the Researched Abuse, Diversion and Addiction Related Surveillance (RADARS®) System. Data were evaluated from 2009 through 2015, and Poisson regression used to compare IR and ER opioid cases over time. From 2009 to 2015, IR opioids were prescribed at a rate 12 to 16 times higher than ER. In the Poison Center Program, population-adjusted rates of Intentional Abuse for IR were 4.6 fold higher than ER opioids (popioids (pOpioid Treatment Program, population-adjusted rates of endorsements for abuse were 1.6 fold higher for IR opioids than ER (p = 0.002). In the Survey of Key Informants' Patients Program, population-adjusted rates of endorsements for abuse were 1.5 fold higher for IR opioids than ER (popioids were prescribed at a much higher rate than ER opioids. Results from four surveillance programs show population-adjusted rates of prescription opioid abuse were markedly higher for IR than ER medications. For the greatest public health benefit, future interventions to decrease prescription opioid abuse should focus on both IR and ER formulations.

  6. Once-daily prolonged-release tacrolimus formulations for kidney transplantation: what the nephrologist needs to know.

    Science.gov (United States)

    Piotti, Giovanni; Cremaschi, Elena; Maggiore, Umberto

    2017-02-01

    Tacrolimus has long been the cornerstone of the immunosuppressive standard-of-care in kidney transplantation. Until recently, only an immediate-release formulation of tacrolimus was available in the clinic for twice-daily administration, a schedule that is known to hamper prescription adherence and contributes to the already significant tacrolimus interactions with other drugs and meals. In order to improve patient compliance, two once-daily prolonged-release formulations of tacrolimus have recently been developed and approved. Here we will analyze the main characteristics of these two prolonged-release formulations with the aim to provide practical clinical information for a fully aware drug prescription. Finally, the theoretical advantages of the prolonged-release formulations in terms of prescription adherence, blood level steadiness and drug efficacy and tolerability will be critically reviewed, in order to define the profile of renal recipients who may benefit most from the switch to once-daily tacrolimus.

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

    NARCIS (Netherlands)

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

    2005-01-01

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

  8. Polymer nanocomposite particles of S-nitrosoglutathione: A suitable formulation for protection and sustained oral delivery.

    Science.gov (United States)

    Wu, Wen; Gaucher, Caroline; Fries, Isabelle; Hu, Xian-ming; Maincent, Philippe; Sapin-Minet, Anne

    2015-11-10

    S-nitrosoglutathione (GSNO) is a nitric oxide (NO) donor with therapeutic potential for cardiovascular disease treatment. Chronic oral treatment with GSNO is limited by high drug sensitivity to the environment and limited oral bioavailability, requiring the development of delivery systems able to sustain NO release. The present work describes new platforms based on polymer nanocomposite particles for the delivery of GSNO. Five types of optimized nanocomposite particles have been developed (three based on chitosan, two based on alginate sodium). Those nanocomposite particles encapsulate GSNO with high efficiency from 64% to 70% and an average size of 13 to 61 μm compatible with oral delivery. Sustained release of GSNO in vitro was achieved. Indeed, chitosan nanocomposites discharged their payload within 24h; whereas alginate nanocomposites released GSNO more slowly (10% of GSNO was still remaining in the dosage form after 24h). Their cytocompatibility toward intestinal Caco-2 cells (MTT assay) was acceptable (IC50: 6.07 ± 0.07-9.46 ± 0.08 mg/mL), demonstrating their suitability as oral delivery systems for GSNO. These delivery systems presented efficient GSNO loading and sustained release as well as cytocompatibility, showing their promise as a means of improving the oral bioavailability of GSNO and as a potential new treatment. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. A pharmacokinetic comparison of the modified release capsule and a plain tablet formulation of mebeverine.

    Science.gov (United States)

    Winsemius, A; Meuwsen, I M; Boon, C; van der Laan, A; Brekle, A; de Vries, M

    2002-11-01

    This study was conducted to compare the pharmacokinetic properties of the modified release 200 mg capsule of mebeverine and the plain 135 mg tablet of mebeverine after single and multiple doses in 12 healthy subjects in a randomised, crossover design. Single doses were given on days 1 and 7 and multiple doses (200 mg b.i.d. for the capsule and 135 mg t.i.d. for the tablet) on days 2-6 of the study. The 200 mg modified release capsule of mebeverine has extended release properties, as indicated by a lower Cmax, a later tmax and a longer elimination half-life than the plain tablet, while the bioavailability is optimal. No significant accumulation occurs after multiple doses of either formulation. The twice-daily dosage regimen of the 200 mg modified release capsule is a good alternative to the three times daily dosage regimen of the 135 mg plain tablet, because the reduced daily intake is likely to benefit patient compliance.

  10. Enhanced efficiency fertilisers: a review of formulation and nutrient release patterns.

    Science.gov (United States)

    Timilsena, Yakindra Prasad; Adhikari, Raju; Casey, Phil; Muster, Tim; Gill, Harsharn; Adhikari, Benu

    2015-04-01

    Fertilisers are one of the most important elements of modern agriculture. The application of fertilisers in agricultural practices has markedly increased the production of food, feed, fuel, fibre and other plant products. However, a significant portion of nutrients applied in the field is not taken up by plants and is lost through leaching, volatilisation, nitrification, or other means. Such a loss increases the cost of fertiliser and severely pollutes the environment. To alleviate these problems, enhanced efficiency fertilisers (EEFs) are produced and used in the form of controlled release fertilisers and nitrification/urease inhibitors. The application of biopolymers for coating in EEFs, tailoring the release pattern of nutrients to closely match the growth requirement of plants and development of realistic models to predict the release pattern of common nutrients have been the foci of fertiliser research. In this context, this paper intends to review relevant aspects of new developments in fertiliser production and use, agronomic, economic and environmental drives for enhanced efficiency fertilisers and their formulation process and the nutrient release behaviour. Application of biopolymers and complex coacervation technique for nutrient encapsulation is also explored as a promising technology to produce EEFs. © 2014 Society of Chemical Industry.

  11. The Multimedia Environmental Pollutant Assessment System (MEPAS){reg_sign}: Source-term release formulations

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-11-01

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

  12. A new formulation of controlled release amitriptyline pellets and its in vivo/in vitro assessments.

    Science.gov (United States)

    Park, Eun-Seok; Lee, Dong-Soo; Kwon, Seok-Young; Chi, Sang-Cheol

    2003-07-01

    Controlled-release amitriptyline pellets (ATP) were formulated and its oral bioavailability was assessed in human volunteers after oral administration under fasting conditions. Core pellets were prepared using a CF granulator by two different methods (powder layering and solvent spraying) and coated with Eudragit RS or RL 100. Physical characteristics and dissolution rates of core pellets and coated pellets were evaluated to optimize the formulation. Powder layering method resulted in a better surface morphology than solvent spraying method. However, physical properties of the products were poorer when prepared by powder layering method with respect to hardness, friability and density. The dissolution profile of amitriptyline coated with Eudragit RS 100 was comparable to that of commercially available amitriptyline enteric-coated pellets (Saroten retard). After the oral administration of both products at the dose of 50 mg, the mean maximum concentrations (Cmax) were 36.4 and 29.7 ng/mL, and the mean areas under the concentration-time curve (AUC(0-96)) were 1180.2 and 1010.7 ng.h/mL for ATP and Saroten retard, respectively. The time to reach the maximum concentrations (Tmax) was 6 h for both formulations. Statistical evaluation suggested that ATP was bioequivalent to Saroten retard.

  13. Selection of excipients for extended release formulations of glipizide through drug-excipient compatibility testing.

    Science.gov (United States)

    Verma, Rajan K; Garg, Sanjay

    2005-07-15

    For the development of extended release formulations of glipizide, techniques of thermal and isothermal stress testing (IST) were used to assess the compatibility of glipizide with selected excipients. Initially, differential scanning calorimeter (DSC) was used to evaluate the compatibility. IR spectrum of drug-excipient mixture was also compared with that of pure drug and excipient. Compatibility of excipients defined in the prototype formula was tested using IST. Based on the DSC results alone, magnesium stearate, meglumine, TRIS buffer, and lactose, were found to exhibit interaction with glipizide. Stressed binary mixtures (stored at 50 degrees C for 3 weeks) of glipizide and meglumine showed yellow coloration indicating potential incompatibility. Based on the results of DSC, IR, and/or HPLC, excipients defined in the prototype formula were found to be compatible with glipizide. The optimized formulation developed using the compatible excipients were found to be stable after 3 months of accelerated stability studies (40 degrees C and 75% RH). Overall, compatibility of excipients with glipizide was successfully evaluated using the combination of thermal and IST methods and the formulations developed using the compatible excipients was found to be stable.

  14. 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.

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

    African Journals Online (AJOL)

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

  16. Propolis Varnish: Antimicrobial Properties against Cariogenic Bacteria, Cytotoxicity, and Sustained-Release Profile

    Directory of Open Access Journals (Sweden)

    Mariana P. De Luca

    2014-01-01

    Full Text Available Varnishes are preparations that differ in the polymeric matrix and therapeutical agents. In dentistry they are used to prevent caries. In this study we developed a propolis varnish, considering propolis properties against cariogenic bacteria. To a chitosan polymeric base (CHV was added ethanolic propolis extract in different concentrations: PV1 (5%, PV2 (10%, and PV3 (15%. Antimicrobial activity was carried out against Streptococcus mutans (SM, Streptococcus sanguinis (SG, Streptococcus salivarius (SS, and Lactobacillus casei (LC through agar diffusion method. The three propolis concentrations incorporated were effective in inhibiting the growth of all microorganisms, but without significant difference between the zones of inhibition observed. Cytotoxicity assay was done by MTT method. Data were analyzed by one-way ANOVA and Bonferroni test. None of the varnishes were cytotoxic, keeping 80% of viable cells, while CHV allowed cellular proliferation (120%. Sustained-release test was carried out by applying 40 μL of each varnish in the buccal surface of bovine teeth and kept in an ethanol/water solution removed in regular times. According to the “independent model approach,” the release profiles were distinct from each varnish and the most prolonged was PV3 (8 weeks. Varnish formulations had satisfactory antimicrobial activity against cariogenic bacteria and have a low cytotoxicity (<50%.

  17. Once-daily propranolol extended-release tablet dosage form: formulation design and in vitro/in vivo investigation.

    Science.gov (United States)

    Huang, Yaw-Bin; Tsai, Yi-Hung; Yang, Wan-Chiech; Chang, Jui-Sheng; Wu, Pao-Chu; Takayama, Kozo

    2004-11-01

    The purpose of this study was to develop and optimize the propranolol once-daily extended release formulations containing HPMC, Microcrystalline cellulose (MCC) and lactose. In vitro studies, the response surface methodology and multiple response optimization utilizing the polynomial equation were used to search for the optimal formulation with specific release rate at different time intervals. The constrained mixture experimental design was used to prepare systematic model formulations, which were composed of three formulation variables: the content of HPMC (X(1)) MCC (X(2)) and lactose (X(3)). The drug release percent at 1.5, 4, 8, 14 and 24 h were the target responses and were restricted to 15-30, 35-55, 55-75, 75-90 and 90-110%, respectively. The results showed that the optimized formulation provided a dissolution pattern equivalent to the predicted curve, which indicated that the optimal formulation could be obtained using response surface methodology. The mechanism of drug release from HMPC matrix tablets followed non-Fickian diffusion. In the vivo study, the MRT was prolonged for matrix tablets when compared with commercial immediate release tablets. Furthermore, a linear relationship between in vitro dissolution and in vivo absorption was observed in the beagle dogs.

  18. Sustained-Release Permanganate: Passive Reactive Barriers for Green and Sustainable Remediation

    Science.gov (United States)

    Dugan, P. J.

    2011-12-01

    Reactive materials in permeable reactive barriers (PRBs) have proven very useful for transforming or destroying organic waste in situ. Once emplaced they typically do not require a continued supply of electrical power and have the added benefit of creating a reactive zone for the destruction of contaminants in place. Controlled-release techniques have been utilized extensively in diverse fields such as pharmaceutical and agrochemical technologies. However, controlled- and sustained release of an oxidant during in situ chemical oxidation (ISCO) is an emerging concept that is extremely relevant to the field of environmental remediation, yet to-date has received little attention. ISCO using the oxidants permanganate, persulfate, and catalyzed hydrogen peroxide has shown great promise for remediation of many recalcitrant organic contaminants of concern (COC). Because the oxidant also reacts with natural organic matter, inorganic soil constituents, and other reduced compounds, the presence of a protective barrier that controls oxidant release may enhance the efficiency of ISCO and allow for long-term low-cost treatment of chlorinated solvents. To this end, sustained-release permanganate (SRP) was developed. Paraffin wax was used as the environmentally benign and biodegradable matrix material for encapsulating the solid potassium permanganate (KMnO4) particles. The paraffin matrix protects the solid KMnO4 particles from fast dissolution and potentially undesirable nonproductive reactions. The SRP material contains between 60%-80% permanganate and can be formed as candles for direct push applications in reactive barriers, or chipped material for hydro-fracturing into low permeability media. One-dimensional (1-D) SRP column experiments were conducted to evaluate permanganate release behavior using deionized (DI) water as the influent or COC removal efficiency using dissolved trichloroethene (TCE) as the influent. The influent dissolved TCE concentrations were 1 mg/L and

  19. Quantitative study on Vancomycin release from cement in 3 different formulations: preliminary results and antimicrobial activity.

    Science.gov (United States)

    Fenga, D; Currò, M; Rosi, M; Ortolà, D J; Cantivalli, A; Ientile, R; Rosa, M A

    2016-01-01

    The purpose of this study is to investigate the best preparation method of the cement powder mixture, solvent and antibiotic in order to obtain the greatest amount of antibiotic in the joint for the longest time as possible. At time T0 the three samples, packed in a sterile environment in different formulations, were placed in sterile tubes, adding to each one 5 ml of saline phosphate buffer solution (PBS) and put in a stove at 37°C for 24 h. A sample of PBS without cement (T control) was also created. Qualitative and quantitative assessment of the incubated liquid with cement was performed along with biochemical analysis with High Performance Liquid Chromatography (HPLC). The analysis of the raw data demonstrated that at T1 there was a prevalence of antibiotic release from sample , compared to sample 2 and 3. This difference was maintained until the T20; from T21 the antibiotic release gradually leveled in 3 samples. The elution of the antibiotic remained detectable up to T60. Our work shows that the sample preparation is decisive on the quantity of released antibiotic. These results are confirmed by microbiological tests. It is useful to know the actual kinetics of antibiotics in articulation. Further studies are necessary to determine the effectiveness of antibiotic against micro-organisms and how long it acts.

  20. Evaluation of free and liposome-encapsulated gentamycin for intramuscular sustained release in rabbits.

    Science.gov (United States)

    Cabanes, A; Reig, F; Garcia-Anton, J M; Arboix, M

    1998-01-01

    Gentamycin sulphate (GS) and gentamycin oleate (GO) were encapsulated in liposomes composed of phosphatidylcholine (HPC) and cholesterol (CHOL) (molar ratio 7:7:2 and 5:5:1, respectively), and were administered via intramuscular injection to rabbits, to evaluate their potential use as sustained release formulations. Five groups of five animals each were used for the pharmacokinetic study, and treatments were established as follows: 3 mg kg(-1) of GS i.v., 3 mg kg(-1) of GS i.m., 3 mg kg(-1) of liposome-containing gentamycin sulphate (LGS) i.m., 3 mg kg(-1) of GO i.m., and 3 mg kg(-1) of liposome-containing gentamycin oleate (LGO) i.m. Gentamycin plasma concentrations after i.m. administration of LGS were extremely low compared with those obtained after the i.m. administration of GS; the peak plasma concentration (Cmax) showed an eight-fold decrease with LGS, and the area under the concentration-time curve (AUC) was four-fold lower for the liposomal form. The apparent elimination half-life estimated after administration of LGS showed a three-fold increase compared with values calculated for free GS. After the administration of the same dose of LGO, Cmax obtained showed a 2.5-fold decrease in relation to peak concentrations of free GO, and the apparent beta-half life of encapsulated GO showed a three-fold increase compared with i.m. GO. Large-size liposomes containing gentamycin administered i.m. to rabbits gave sustained drug release from the injection site, providing prolonged plasma concentrations of the drug in the body.

  1. Pharmacokinetics of diltiazem hydrochloride delay-onset sustained-release pellet capsules in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Xi-Qing Yan

    2013-03-01

    Full Text Available The pharmacokinetics (PK of ordinary tablets and sustained release capsules of diltiazem hydrochloride in human clinical trials had been studied. The PK of diltiazem hydrochloride delay-onset sustained-release pellet capsules, a new dosage form, has not been reported, although it is very important to clinical use. In this paper, we investigated the PK of diltiazem hydrochloride delay-onset sustained-release pellet capsules and the food influence in Chinese healthy volunteers. The PK parameters indicated that the diltiazem hydrochloride delay-onset sustained-release pellet capsules appeared marked characteristics of delayed and controlled release. An opened-label, randomized and parallel clinical trial was conducted in 36 Chinese healthy volunteers with single oral dose (90 mg, 180 mg or 270 mg and a multiple oral dose (90 mg d-1×6 d administration. The effect of food on the PK of one single oral dose (360 mg was investigated in 24 healthy Chinese volunteers. Plasma diltiazem concentration was determined by reversed-phase high-performance liquid chromatography (RP-HPLC and the main pharmacokinetic parameters were analyzed by PKSolver (Ver 2.0. All clinical studies were conducted in the Clinical Pharmacological Center (No. JDX1999064 of Xiangya Hospital Affiliated Central South University, China. The PK parameters suggested that the new formulation had marked characteristics of delayed and controlled release of diltiazem, and food intake did not alter significantly diltiazem pharmacokinetic parameters.Embora a farmacocinética (PK do cloridrato de diltiazem nas formas de comprimidos de liberação imediata e cápsulas de liberação modificada em ensaios clínicos já tenha sido relatada, a pesquisa da PK do cloridrato de diltiazem na forma de cápsulas com peletes de liberação retardada e sustentada ainda é muito importante. Neste trabalho, propusemos avaliar a farmacocinética do cloridrato de diltiazem administrado através desta nova forma

  2. Comparison of gastroretentive microspheres and sustained-release preparations using theophylline pharmacokinetics.

    Science.gov (United States)

    Miyazaki, Yasunori; Yakou, Shigeru; Takayama, Kozo

    2008-06-01

    The objective of this study was to use the pharmacokinetics of theophylline to compare various gastroretentive microspheres. Three types of theophylline microspheres prepared from a hydrophobic dextran derivative were characterized in terms of drug release in-vitro and floating and mucoadhesive properties. Theophylline pharmacokinetic studies were conducted in Beagle dogs, comparing bulk powder, commercial sustained-release granules (Theodur), sustained-release microspheres, floatable microspheres and mucoadhesive microspheres. Theodur and sustained-release microspheres resulted in a lower maximum concentration (Cmax) (P mucoadhesive microspheres indicated an increase in AUC without decreasing the rate of bioavailability. Overall, the gastroretentive microspheres improved the extent of bioavailability of theophylline, which is absorbable from the entire gastrointestinal tract. The mucoadhesive microsphere showed a prolonged serum drug level, indicating a superior sustained-release delivery system for theophylline.

  3. In vitro biorelevant models for evaluating modified release mesalamine products to forecast the effect of formulation and meal intake on drug release.

    Science.gov (United States)

    Andreas, Cord J; Chen, Ying-Chen; Markopoulos, Constantinos; Reppas, Christos; Dressman, Jennifer

    2015-11-01

    Postprandial administration of solid oral dosage forms greatly changes the dissolution environment compared to fasted state administration. The aims of this study were to investigate and forecast the effect of co-administration of a meal on drug release for delayed and/or extended release mesalamine formulations as well as design of in vitro tests to distinguish among formulations in a biorelevant way. Five different mesalamine formulations (Asacol® 400 mg, Mezavant® 1200 mg, Pentasa® 500 mg and Salofalk® in the 250 mg and 500 mg strengths) were investigated with biorelevant dissolution methods using the USP apparatus III and USP apparatus IV (open loop mode) under both fasted and fed state conditions, as well as with the dissolution methods described in pharmacopeia for delayed and extended release mesalamine products. Using the biorelevant experimental conditions proposed in this study, changes in release in the proximal gut due to meal intake are forecast to be minimal for Asacol®, Mezavant®, Pentasa® and Salofalk® 500 mg, while for Salofalk® 250 mg release was predicted to occur much earlier under fed state conditions. The USP apparatus III generally tended to result in faster dissolution rates and forecast more pronounced food effects for Salofalk® 250 mg than the USP apparatus IV. The biorelevant dissolution gradients were also able to reflect the in vivo behavior of the formulations. In vitro biorelevant models can be useful in the comparison of the release behavior from different delayed and extended release mesalamine formulations as well as forecasting effects of concomitant meal intake on drug release. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Formule.

    Directory of Open Access Journals (Sweden)

    Le Comité de Rédaction d' EspacesTemps.net

    2004-09-01

    Full Text Available Vous découvrez aujourd’hui la nouvelle formule d’EspacesTemps. net. Ce basculement repose sur des changements techniques d’une certaine ampleur et nous vous demandons d’être indulgents si quelques imperfections subsistent dans les prochains jours. Il s’agit d’abord de la substitution du dispositif de mise en ligne : à partir de maintenant, nous utilisons le logiciel Lodel. Dans l’esprit de l’association Revues.org, à laquelle EspacesTemps adhère, l’unification du ...

  5. 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.......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....

  6. 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.

  7. Factors affecting the design of slow release formulations of herbicides based on clay-surfactant systems. A methodological approach.

    Directory of Open Access Journals (Sweden)

    María Del Carmen Galán-Jiménez

    Full Text Available A search for clay-surfactant based formulations with high percentage of the active ingredient, which can yield slow release of active molecules is described. The active ingredients were the herbicides metribuzin (MZ, mesotrione (MS and flurtamone (FL, whose solubilities were examined in the presence of four commercial surfactants; (i neutral: two berols (B048, B266 and an alkylpolyglucoside (AG6202; (ii cationic: an ethoxylated amine (ET/15. Significant percent of active ingredient (a.i. in the clay/surfactant/herbicide formulations could be achieved only when most of the surfactant was added as micelles. MZ and FL were well solubilized by berols, whereas MS by ET/15. Sorption of surfactants on the clay mineral sepiolite occurred mostly by sorption of micelles, and the loadings exceeded the CEC. Higher loadings were determined for B266 and ET/15. The sorption of surfactants was modeled by using the Langmuir-Scatchard equation which permitted the determination of binding coefficients that could be used for further predictions of the sorbed amounts of surfactants under a wide range of clay/surfactant ratios. A possibility was tested of designing clay-surfactant based formulations of certain herbicides by assuming the same ratio between herbicides and surfactants in the formulations as for herbicides incorporated in micelles in solution. Calculations indicated that satisfactory FL formulations could not be synthesized. The experimental fractions of herbicides in the formulations were in agreement with the predicted ones for MS and MZ. The validity of this approach was confirmed in in vitro release tests that showed a slowing down of the release of a.i. from the designed formulations relative to the technical products. Soil dissipation studies with MS formulations also showed improved bioactivity of the clay-surfactant formulation relative to the commercial one. This methodological approach can be extended to other clay-surfactant systems for

  8. Biodegradable Injectable In Situ Implants and Microparticles for Sustained Release of Montelukast: In Vitro Release, Pharmacokinetics, and Stability

    OpenAIRE

    Ahmed, Tarek A.; Ibrahim, Hany M.; Ahmed M Samy; Kaseem, Alaa; Nutan, Mohammad T. H.; Hussain, Muhammad Delwar

    2014-01-01

    The objective of this study was to investigate the sustained release of a hydrophilic drug, montelukast (MK), from two biodegradable polymeric drug delivery systems, in situ implant (ISI) and in situ microparticles (ISM). N-Methyl pyrrolidone (NMP), dimethyl sulfoxide (DMSO), triacetin, and ethyl acetate were selected as solvents. The release of 10% (w/v) MK from both systems containing poly-lactic-co-glycolic acid (PLGA) as the biodegradable polymer was compared. Upon contact with the aqueou...

  9. Pharmacokinetics of nifedipine slow-release during sustained tocolysis

    NARCIS (Netherlands)

    ter Laak, Maureen A.; Roos, Carolien; Touw, Daan J.; van Hattum, Paul R. M.; Kwee, Anneke; Lotgering, Frederik K.; Mol, Ben Willem J.; van Pampus, Mariëlle G.; Porath, Martina M.; Spaanderman, Marc E. A.; van der Post, Joris A. M.; Papatsonis, Dimitri N. M.; van 't Veer, Nils E.

    2015-01-01

    The pharmacokinetics of nifedipine as a tocolytic agent has not been studied in great detail in pregnant women and has instead focused on immediate release tablets and gastrointestinal therapeutic system (GITS) tablets. The aim of this study was to determine nifedipine slow-release half-life and

  10. Pharmacokinetics of nifedipine slow-release tablets during sustained tocolysis

    NARCIS (Netherlands)

    ter Laak, Maureen A.; Roos, Carolien; Touw, Daan J.; van Hattum, Paul R. M.; Kwee, Anneke; Lotgering, Frederik K.; Moi, Ben Willem J.; van Pampus, Marielle G.; Porath, Martina M.; Spaanderman, Marc E. A.; van der Post, Joris A. M.; Papatsonis, Dimitri N. M.; van 't Veer, Nils E.

    Objective: The pharmacokinetics of nifedipine as a tocolytic agent has not been studied in great detail in pregnant women and has instead focused on immediate release tablets and gastrointestinal therapeutic system (GITS) tablets. The aim of this study was to determine nifedipine slow-release

  11. An assessment of the clinical equivalence of valproate chrono and extended release divalproex formulations

    Directory of Open Access Journals (Sweden)

    Rajesh B

    2007-01-01

    Full Text Available Objective: No guideline currently exists to choose the clinically equivalent dose of divalproex extended release (ER formulation while switching over from valproate chrono formulation. To address this issue, we evaluated the serum valproate concentration following switch over from valproate chrono to divalproex ER in persons with epilepsy. Materials and Methods: An open label study was conducted in two parts, each for a period of two months. During Part I, patients on regular twice-daily dose of valproate chrono were switched over to once daily divalproex ER (DESVAL ER ® based on the dose escalation recommended when switching over from divalproex DR to ER formulation as the guideline. During Part II, we switched from valproate chrono to divalproex ER with same dosage. Serum valproate concentration, seizure frequency and side effects were assessed serially for two months after changeover and compared with the preswitch data. Results: During Part I, compared to the baseline level, there was a significant increase in mean serum valproate level at two months (67.0 ± 28.4 mg/ml versus 91.9 ± 3.5 mg/ml, P 0.004. With the same dose conversion during Part II, the mean valproate level did not significantly differ before and after the switch (81.5 mg/dl versus 85.7 mg/dl, P 0.08. The mean monthly seizure frequencies and serum ammonia levels did not change during either part. No significant adverse effects occurred. Conclusion: The results of this open label study with small number of patients need to be replicated among larger patient sample through a randomized control design before recommending same dose conversion from valproate chrono to divalproex ER without change in efficacy and tolerability,

  12. Optimization of sustained-release propranolol dosage form using factorial design and response surface methodology.

    Science.gov (United States)

    Huang, Yaw-Bin; Tsai, Yi-Hung; Yang, Wan-Chiech; Chang, Jui-Sheng; Wu, Pao-Chu

    2004-10-01

    The purpose of this study was to develop propranolol extended release formulations containing hydroxypropylmethylcellulose (HPMC). The results indicate that the drug release from the tablet form containing a high amount of HPMC was incomplete, and avicel addition could increase the release percent at a later stage. In order to readily obtain an optimal formulation, response surface methodology and multiple response optimization utilizing a quadratic polynomial equation was used. The model formulations were prepared according to a factorial design. The effects of causal factors including the HPMC/drug ratio (X1) and avicel level (X2), on drug release were also measured. The drug release percentage at 1.5, 4, 8, 14 and 24 h were the target response and were restricted to not more than 25%, 35-50%, 55-70%, 75-90%, and 95-110%, respectively. The results showed that the optimized formulation provided a dissolution pattern equivalent to the predicted curve, which indicated that the optimal formulation could be obtained using response surface methodology. The mechanism of drug release from HMPC matrices tablets followed quasi-Fickian diffusion.

  13. Nanostructure of liquid crystalline matrix determines in vitro sustained release and in vivo oral absorption kinetics for hydrophilic model drugs.

    Science.gov (United States)

    Lee, Kathy W Y; Nguyen, Tri-Hung; Hanley, Tracey; Boyd, Ben J

    2009-01-05

    Nanostructured lipid-based liquid crystalline systems have been proposed as sustained oral drug delivery systems, but the interplay between their intrinsic release rates, susceptibility to digestive processes, and the manner in which these effects impact on their application in vivo, are not well understood. In this study, two different bicontinuous cubic phases, prepared from glyceryl monooleate and phytantriol, and a reversed hexagonal phase formed by addition of a small amount of vitamin E to phytantriol (Q(II GMO), Q(II PHYT) and H(II PHYT+VitEA), respectively) were prepared. The release kinetics for a number of model hydrophilic drugs with increasing molecular weights (glucose, Allura Red and FITC-dextrans) was determined in in vitro release experiments. Diffusion-controlled release was observed in all cases as anticipated from previous studies with liquid crystalline systems, and it was discovered that the release rates of each drug decreased as the matrix was changed from Q(II GMO) to Q(II PHYT) to H(II PHYT+VitEA). Formulations containing (14)C-glucose, utilized as a rapidly absorbed marker of drug release, were then orally administered to rats to determine the relative in vivo absorption rates from the different formulations. The results showed a trend by which the rate of absorption of (14)C-glucose followed that observed in the corresponding in vitro release studies, providing the first indication that the nanostructure of these materials may provide the ability to tailor the absorption kinetics of hydrophilic drugs in vivo, and hence form the basis of a new drug delivery system.

  14. Slow-release formulation of a new biological pesticide, pyoluteorin, with mesoporous silica.

    Science.gov (United States)

    Chen, Jie; Wang, Wei; Xu, Yuquan; Zhang, Xuehong

    2011-01-12

    A slow-release formula of potential biological pesticide Pyoluteorin (Plt) was prepared by using nanophase material of silicon dioxide loading drugs. The final experimental formula was m(Plt:Brij56:TMOS:HCl(aq)) = 0.04:1.4:2:1, synthesized by a highly ordered monolith (HOM) method. This formula can continuously release 85.13 ± 2.03 % of Plt within 28 days. A characterization study showed the formula formed a well-ordered mesoporous structure, with a surface area of 822 m(2) g(-1), with a measured mesoporous volume of 0.41 cm(3) g(-1) and a narrow distribution for the pore size centered at 2.4 nm. A bioactivity experiment showed it authentically prolonged the antifungal effects. This study is the first to report mesoporous formulations for biological pesticides and indicates a potentially interesting drug carrier. The association of a nanostructured silica to the molecular state of the drug holds great interests for field applications as it overcomes the rapid loss of biological function during drug utilities.

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

    Indian Academy of Sciences (India)

    methoxysilane (APTMS) was added and the whole mixture was stirred further for 8 h. Then the mix- ture was centrifuged at 10,000 rpm for 20 min and air dried. The final dried formulation was used for further analysis such as drug loading and DR. 3.

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

    Directory of Open Access Journals (Sweden)

    Kizilbash A

    2014-03-01

    Full Text Available Arshi Kizilbash,1 Cường Ngô-Minh2 1Delta Health Services Inc., Mississauga, Ontario, Canada; 2Somerset West Community Health Centre, Ottawa, Ontario, Canada Abstract: Patients with chronic non-malignant pain report impairments of physical, social, and psychological well-being. The goal of pain management should include reducing pain and improving quality of life. Patients with chronic pain require medications that are able to provide adequate pain relief, have minimum dosing intervals to maintain efficacy, and avoid breakthrough pain. Tramadol has proven efficacy and a favourable safety profile. The positive efficacy and safety profile has been demonstrated historically in numerous published clinical studies as well as from post-marketing experience. It is a World Health Organization “Step 2” opioid analgesic that has been shown to be effective, well-tolerated, and valuable, where treatment with strong opioids is not required. A number of extended release formulations of Tramadol are available in Canada and the United States. An optimal extended release Tramadol formulation would be expected to provide consistent pain control with once daily dosing, few sleep interruptions, flexible dosing schedules, and no limitation on taking with meals. Appropriate treatment options should be based on the above proposed attributes. A comparative review of available extended release Tramadol formulations shows that these medications are not equivalent in their pharmacokinetic profile and this may have implications for selecting the optimal therapy for patients with pain syndromes where Tramadol is an appropriate analgesic agent. Differences in pharmacokinetics amongst the formulations may also translate into varied clinical responses in patients. Selection of the appropriate formulation by the health care provider should therefore be based on the patient's chronic pain condition, needs, and lifestyle. Keywords: analgesics, opioids, chronic pain, drug

  17. Poly(3-hydroxybutyrate)/metribuzin formulations: characterization, controlled release properties, herbicidal activity, and effect on soil microorganisms.

    Science.gov (United States)

    Volova, Tatiana; Zhila, Natalia; Kiselev, Evgeniy; Prudnikova, Svetlana; Vinogradova, Olga; Nikolaeva, Elena; Shumilova, Anna; Shershneva, Anna; Shishatskaya, Ekaterina

    2016-12-01

    Slow-release formulations of the herbicide metribuzin (MET) embedded in the polymer matrix of degradable poly-3-hydroxybutyrate [P(3HB)] in the form of microparticles, films, microgranules, and pellets were developed and tested. The kinetics of polymer degradation, MET release, and accumulation in soil were studied in laboratory soil microecosystems with higher plants. The study shows that MET release can be controlled by using different techniques of constructing formulations and by varying MET loading. MET accumulation in soil occurs gradually, as the polymer is degraded. The average P(3HB) degradation rates were determined by the geometry of the formulation, reaching 0.17, 0.12, 0.04, and 0.05 mg/day after 60 days for microparticles, films, microgranules, and pellets, respectively. The herbicidal activities of P(3HB)/MET formulations and commercial formulation Sencor Ultra were tested on the Agrostis stolonifera and Setaria macrocheata plants. The parameters used to evaluate the herbicidal activity were plant density and the weight of fresh green biomass measured at days 10, 20, and 30 after sowing. All P(3HB)/MET formulations had pronounced herbicidal activity, which varied depending on MET loading and the stage of the experiment. In the early phases of the experiment, the herbicidal effect of P(3HB)/MET formulations with the lowest MET loading (10 %) was comparable with that of the commercial formulation. The herbicidal effect of P(3HB)/MET formulations with higher MET loadings (25 and 50 %) at later stages of the experiment were stronger than the effect of Sencor Ultra.

  18. Sustained release myofascial release as treatment for a patient with complications of rheumatoid arthritis and collagenous colitis: a case report.

    Science.gov (United States)

    Cubick, Erin E; Quezada, Vanessa Y; Schumer, Ariel D; Davis, Carol M

    2011-01-01

    Myofascial release (MFR) is a manual therapeutic technique used to release fascial restrictions, which may cause neuromusculoskeletal and systemic pathology. This case report describes the use of sustained release MFR techniques in a patient with a primary diagnosis of rheumatoid arthritis (RA) and a secondary diagnosis of collagenous colitis. Changes in pain, cervical range of motion, fatigue, and gastrointestinal tract function, as well as the impact of RA on daily activities, were assessed. A 54-year-old white woman presented with signs and symptoms attributed to RA and collagenous colitis. Pre and post measurements were taken with each treatment and during the interim between the initial and final treatment series. The patient recorded changes in pain, fatigue, gastrointestinal tract function, and quality of life. Cervical range of motion was assessed. Six sustained release MFR treatment sessions were provided over a 2-week period. Following an 8-week interim, two more treatments were performed. The patient showed improvements in pain, fatigue, gastrointestinal tract function, cervical range of motion, and quality of life following the initial treatment series of six sessions. The patient maintained positive gains for 5 weeks following the final treatment, after which her symptoms returned to near baseline measurements. Following two more treatments, positive gains were achieved once again. In a patient with RA and collagenous colitis, the application of sustained release MFR techniques in addition to standard medical treatment may provide short-term and long-term improvements in comorbid symptoms and overall quality of life.

  19. 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.

  20. Isolation and physicochemical characterization of sustained releasing starches from Dioscorea of Jharkhand.

    Science.gov (United States)

    Deepika, V; Jayaram Kumar, K; Anima, P

    2013-04-01

    Starches were isolated from varieties of Dioscorea (Da1, Da2) grown in Jharkhand state of India and it was characterized in terms of moisture, ash, amylose content, bulk density, tapped density, true density, porosity, Carr's index, Hausner's ratio, swelling power, solubility, water holding capacity, paste clarity. Morphological, thermal and IR spectroscopic studies were also done to characterize the isolated starch. The shape and size of starch granules were round/oval to ellipsoid and 5-10μm. There were considerable differences in powder characteristics, amylose content, ash values, and water holding capacity, swelling and solubility power. Starch from variety Da2 showed high enthalpy of gelatinization temperature as compared to variety Da1. Peaks in FTIR spectra of both starches revealed its carbohydrate nature. In vitro studies revealed that both the starches from Da1 and Da2 can be used in developing sustained release formulations. The result showed that starches from both Dioscorea can be used in pharmaceutical industries as excipients with minimal modifications. Copyright © 2013. Published by Elsevier B.V.

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

    Directory of Open Access Journals (Sweden)

    Mariam Vbamiunomhene Lawal

    2015-07-01

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

  2. Comparative pharmacokinetics and bioavailability of tapentadol following oral administration of immediate- and prolonged-release formulations.

    Science.gov (United States)

    Göhler, Karin; Brett, Martin; Smit, Johan W; Rengelshausen, Jens; Terlinden, Rolf

    2013-04-01

    . Absolute bioavailability for both tapentadol IR and tapentadol PR was ~ 32% under fasted conditions. Extent of exposure (AUC) for tapentadol PR was very similar to tapentadol IR, whereas Cmax was lower and HVD/MRT longer for the prolonged-release formulation. Overall, the pharmacokinetic characteristics of tapentadol PR enable a twice-daily dosing regimen to be used; such a regimen is expected to improve patient compliance during chronic use.

  3. Evaluation of gum of Moringa oleifera as a binder and release retardant in tablet formulation

    OpenAIRE

    Panda D; Choudhury N.S.K; Yedukondalu M; Si S; Gupta R

    2008-01-01

    The present study was undertaken to find out the potential of gum from Moringa oleifera to act as a binder and release retardant in tablet formulations. The effect of calcium sulphate dihydrate (water insoluble) and lactose (water soluble) diluent on the release of propranolol hydrochloride was studied. The DSC thermograms of drug, gum and mixture of gum/drug indicated no chemical interaction. Tablets (F1, F2, F3, and F4) were prepared containing calcium sulphate dihydrate as diluent, propr...

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

    Directory of Open Access Journals (Sweden)

    Ikrima Khalid

    2014-09-01

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

  5. Pharmacokinetics of a new once-daily controlled-release formulation of aceclofenac in Korean healthy subjects compared with immediate-release aceclofenac and the effect of food: a randomized, open-label, three-period, crossover, single-centre study.

    Science.gov (United States)

    Bae, Soo Kyung; Kim, Soo-Hwan; Lee, Hae Won; Seong, Sook Jin; Shin, Su-Yeon; Lee, Sang Hun; Lim, Mi-Sun; Yoon, Young-Ran; Lee, Hye Jung

    2012-02-01

    A new controlled-release formulation of aceclofenac 200 mg (Clanza CR®) developed by Korea United Pharm., Inc., South Korea, for once-daily (od) dosing provides biphasic aceclofenac release consisting of immediate release of 85 mg followed by sustained release of 115 mg. Food has been known to affect the rate and extent of absorption of several drugs, in both immediate-release and controlled-release formulations. The aim of this study was to evaluate the relative bioavailability of a new controlled-release formulation of aceclofenac (200 mg od; Clanza CR®) in comparison with immediate-release aceclofenac (100 mg twice daily [bid], Airtal®) and to assess the effect of food on the pharmacokinetics of the new controlled-release aceclofenac formulation. This study was designed as a randomized, open-label, three treatment-period, crossover, single-centre study with a 1-week washout in 41 healthy adults. The three treatments consisted of immediate-release aceclofenac 100 mg bid administered under fasting conditions; controlled-release aceclofenac 200 mg od administered under fasting conditions; and controlled-release aceclofenac 200 mg od administered immediately after a standardized high-fat breakfast. Plasma concentrations of aceclofenac were determined using a high-performance liquid chromatography method. In the fasted state, the 90% confidence intervals (CIs) of the least squares geometric mean ratios (GMRs) for the area under the plasma concentration-time curve from time zero to 24 hours (AUC(24)) and the peak plasma concentration (C(max)) of aceclofenac for the controlled-release and immediate-release formulations of aceclofenac were all within the bioequivalence criteria range of 0.8-1.25. The 90% CIs of the GMRs for the AUC(24) and C(max) of aceclofenac for the controlled-release formulation of aceclofenac in the fed and fasted states were also within the bioequivalence range. Both aceclofenac formulations were well tolerated in all subjects

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

    African Journals Online (AJOL)

    therapeutic advantages over conventional oral tablets in terms of prolonged release and improvement of ... arthritic therapy. Non-steroidal anti-inflammatory drugs (NSAIDs) are prescribed frequently for the management of pain and local inflammation. (similar to gout) [5]. ... systems, transdermal films/patches are the most.

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

    African Journals Online (AJOL)

    Erah

    Available online at http://www.tjpr.org. Research Article ... diffraction (XRD), and atomic absorption spectroscopy (AAS) were also applied to investigate the physicochemical characteristics of the drug in ... Both calcium alginate beads and the beads treated with chitosan failed to release the drug at pH 1.2 over the period of ...

  8. Pharmacokinetics of nifedipine slow-release during sustained tocolysis

    NARCIS (Netherlands)

    Laak, M.A. Ter; Roos, C.; Touw, D.J.; Hattum, P.R. van; Kwee, A.; Lotgering, F.K.; Moi, B.W.J.; Pampus, M.G. van; Porath, M.M.; Spaanderman, M.E.; Post, J.A. van der; Papatsonis, D.N.; Veer, N.E. van 't

    2015-01-01

    OBJECTIVE: The pharmacokinetics of nifedipine as a tocolytic agent has not been studied in great detail in pregnant women and has instead focused on immediate release tablets and gastrointestinal therapeutic system (GITS) tablets. The aim of this study was to determine nifedipine slowrelease

  9. Pharmacokinetics of nifedipine slow-release tablets during sustained tocolysis

    NARCIS (Netherlands)

    Ter Laak, Maureen A.; Roos, Carolien; Touw, Daan J.; Van Hattum, Paul R M; Kwee, Anneke|info:eu-repo/dai/nl/290465648; Lotgering, Frederik K.; Mol, Ben Willem J; Van Pampus, Mariëlle G.; Porath, Martina M.; Spaanderman, Marc E A; Van Der Post, Joris A M; Papatsonis, Dimitri N M; Van'T Veer, Nils E.

    2015-01-01

    Objective: The pharmacokinetics of nifedipine as a tocolytic agent has not been studied in great detail in pregnant women and has instead focused on immediate release tablets and gastrointestinal therapeutic system (GITS) tablets. The aim of this study was to determine nifedipine slowrelease

  10. Performance Evaluation of Marketed Brands of Sustained Release ...

    African Journals Online (AJOL)

    Statistical tests such as repeated ANOVA, Friedman test, Friedman ANOVA, Kendall's coefficient of concordance and Tukey-Kramer multiple comparison tests were applied on the range of data obtained from different brands. The results indicated non-significant differences in physical parameters and in vitro drug release, ...

  11. 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. PMID:25006518

  12. Pharmacokinetics of SLI381 (ADDERALL XR), an extended-release formulation of Adderall.

    Science.gov (United States)

    McGough, James J; Biederman, Joseph; Greenhill, Laurence L; McCracken, James T; Spencer, Thomas J; Posner, Kelly; Wigal, Sharon; Gornbein, Jeffrey; Tulloch, Simon; Swanson, James M

    2003-06-01

    To assess the pharmacokinetic (PK) properties of a single daily dose of Adderall (mixed amphetamine salts) and the extended-release formulation, SLI381 (ADDERALL XR), in pediatric attention-deficit/hyperactivity disorder (ADHD). Fifty-one children (aged 6-12 years) with ADHD participated in a 6-week, seven-visit, PK and pharmacodynamic study. PK sampling occurred during visit 1 and again at visit 7. At visit 1, subjects received an initial oral dose of SLI381, 20 mg. At visit 7 subjects completed 1 week of medication treatment following random assignment to once-daily orally dosed SLI381 10 mg, 20 mg, or 30 mg; Adderall 10 mg; or placebo. PK parameters evidenced substantial intersubject variability (coefficients of variation = 28-56%). Time to maximum concentration (Tmax) for SLI381 versus Adderall showed average increases of 3.0 hours for dextroamphetamine (t = -2.35, p = .04, df = 8.6) and 3.2 hours for levoamphetamine (t = -2.39, p = .04, df = 9.2). The d- and l-isomer concentrations were highly correlated and approximated a 3:1 ratio. SLI381 showed extended Tmax values compared with Adderall and appears suitable for once-daily dosing. Intersubject variability underscores the need for individual dose titration.

  13. 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.

  14. Analysis of in vitro release through reconstructed human epidermis and synthetic membranes of multi-vitamins from cosmetic formulations.

    Science.gov (United States)

    Gabbanini, Simone; Matera, Riccardo; Beltramini, Claudia; Minghetti, Andrea; Valgimigli, Luca

    2010-08-01

    A convenient method for in vitro investigation of the release of lipid- and water-soluble vitamins from cosmetic formulations was developed. The permeation of (d)-alpha-tocopherol (vitamin E), retinyl acetate (pro-vitamin A), ascorbic acid (vitamin C) and pyridoxine (vitamin B6) through SkinEthic reconstructed human epidermis (RHE), and synthetic polyethersulfone and polycarbonate membranes was studied in vitro using a Franz-type diffusion apparatus, coupled either to a spectrophotometer for continuous reading (dynamic setting) or to HPLC-DAD analysis of the receptor medium (static setting). O/W and W/O emulsions were compared with simple aqueous solutions for their kinetic of vitamins release, to evaluate the influence of the cosmetic formulation on the bioavailability of active ingredients. Results indicate that synthetic membranes offer a limited barrier to the diffusion of vitamins, but may provide information on the release ability of the formulation. Penetration was more effective when water was the external phase of the formulation, i.e. W/O emulsions were less effective in the release of vitamins than O/W emulsion or aqueous solutions. RHE (17 days old) offered a significantly higher barrier to penetration of vitamins, as expected for native human epidermis. The relative ranking in coefficient of permeability (Ps (cm/h)) was: ascorbic acid>pyridoxine>retinyl acetate>alpha-tocopherol approximately 0, the absolute values depending on the formulation. The method herein described showed to be a practical and convenient tool for the quality-control and efficacy evaluation of cosmetic formulations. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  15. The impact of selected preparations of trace elements - magnesium, potassium, calcium, and zinc on the release of diclofenac sodium from enteric coated tablets and from sustained release capsules.

    Science.gov (United States)

    Biernat, Paweł; Musiał, Witold; Gosławska, Dorota; Pluta, Janusz

    2014-01-01

    In an aging society, many patients require long-term treatment. This fact is associated clearly with the simultaneous occurrence of lifestyle diseases such as hypertension, diabetes, and even osteoarthritis. Concomitant medications, which are a common practice, pose a major threat of an interaction between these drugs. Very popular now "fast way of life" that makes people have less and less time to prepare well-balanced meals of high nutritional value. The result of this lifestyle is an increased need for supplementation preparations necessary vitamins and minerals. Given the wide availability of dietary supplements (shops, kiosks, petrol stations) raises the question about the possibility of an interaction between the uncontrolled intake of dietary supplements and medications received in the most common diseases of civilization. The aim of this study was to investigate the effect of the most important minerals (magnesium, potassium, calcium, zinc) contained in the popular nutritional supplements, the release also often used as an anti-pain, anti-inflammatory, diclofenac sodium from the different formulations. Among the many as sodium diclofenac selected two most common: film-coated tablets and sustained release capsules. The study showed a significant effect of minerals on the release of diclofenac sodium and differences that impact, depending on the test form of the drug.

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

    Science.gov (United States)

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

    2007-06-01

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

  17. Comparison of neurofuzzy logic and decision trees in discovering knowledge from experimental data of an immediate release tablet formulation.

    Science.gov (United States)

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

    2007-06-01

    Understanding of the cause-effect relationships between formulation ingredients, process conditions and product properties is essential for developing a quality product. However, the formulation knowledge is often hidden in experimental data and not easily interpretable. This study compares neurofuzzy logic and decision tree approaches in discovering hidden knowledge from an immediate release tablet formulation database relating formulation ingredients (silica aerogel, magnesium stearate, microcrystalline cellulose and sodium carboxymethylcellulose) and process variables (dwell time and compression force) to tablet properties (tensile strength, disintegration time, friability, capping and drug dissolution at various time intervals). Both approaches successfully generated useful knowledge in the form of either "if then" rules or decision trees. Although different strategies are employed by the two approaches in generating rules/trees, similar knowledge was discovered in most cases. However, as decision trees are not able to deal with continuous dependent variables, data discretisation procedures are generally required.

  18. 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

  19. Sustained-release drug delivery of antimicrobials in controlling of supragingival oral biofilms.

    Science.gov (United States)

    Steinberg, Doron; Friedman, Michael

    2017-04-01

    Dental caries, a bacterial biofilm-associated disease, is a prevalent oral health problem. It is a bacterial biofilm-associated disease. Conventional means of combating this disease involves oral hygiene, mostly tooth brushing. Supplementary means of prevention and treatment is often necessary. The use of sustained-release delivery systems, locally applied to the oral cavity appears to be one of the most acceptable avenues for the delivery of antimicrobial agents. Area covered: The development and current approaches of local sustained delivery technologies applied to the oral cavity for treatment and prevention of dental caries is discussed. The use of polymeric drug delivery systems, varnishes, liposomes and nanoparticles is presented. Expert opinion: The use of local sustained-release delivery systems applied to the oral cavity has numerous clinical, pharmacological and toxicological advantages over conventional means. Various sustained-release technologies have been suggested over the course of several years. The current research on oral diseases concentrates predominantly on improving the drug delivery. With progress in pharmaceutical technology, sophisticated controlled-release platforms are being developed. The sustained release concept is innovative and there are few products available for the benefit of all populations. Harmonizing academic research with the dental industry will surely expedite the development and commercialization of more products of such pharmacological nature.

  20. 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

  1. Radiation crosslinked hydrogels as sustained release drug delivery systems

    Energy Technology Data Exchange (ETDEWEB)

    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 ..gamma..-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.

  2. Radiation crosslinked hydrogels as sustained release drug delivery systems

    Science.gov (United States)

    Pȩkala, W.; Rosiak, J.; Rucińska-Rybus, A.; Burczak, K.; Galant, S.; Czołlczyńska, T.

    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 j-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 the hydrogel matrix. This work has been carried out under IAEA research contract RB 3379/R-1 POL.

  3. 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.

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

    Science.gov (United States)

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

    2014-01-01

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

  5. 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.

  6. Synthetic geopolymers for controlled delivery of oxycodone: adjustable and nanostructured porosity enables tunable and sustained drug release.

    Science.gov (United States)

    Forsgren, Johan; Pedersen, Christian; Strømme, Maria; Engqvist, Håkan

    2011-03-15

    In this article we for the first time present a fully synthetic mesoporous geopolymer drug carrier for controlled release of opioids. Nanoparticulate precursor powders with different Al/Si-ratios were synthesized by a sol-gel route and used in the preparation of different geopolymers, which could be structurally tailored by adjusting the Al/Si-ratio and the curing temperatures. In particular, it was shown that the pore sizes of the geopolymers decreased with increasing Al/Si ratio and that completely mesoporous geopolymers could be produced from precursor particles with the Al/Si ratio 2:1. The mesoporosity was shown to be associated with a sustained and linear in vitro release profile of the opioid oxycodone. A clinically relevant release period of about 12 h was obtained by adjusting the size of the pellets. The easily fabricated and tunable geopolymers presented in this study constitute a novel approach in the development of controlled release formulations, not only for opioids, but whenever the clinical indication is best treated with a constant supply of drugs and when the mechanical stability of the delivery vehicle is crucial.

  7. Synthetic Geopolymers for Controlled Delivery of Oxycodone: Adjustable and Nanostructured Porosity Enables Tunable and Sustained Drug Release

    Science.gov (United States)

    Forsgren, Johan; Pedersen, Christian; Strømme, Maria; Engqvist, Håkan

    2011-01-01

    In this article we for the first time present a fully synthetic mesoporous geopolymer drug carrier for controlled release of opioids. Nanoparticulate precursor powders with different Al/Si-ratios were synthesized by a sol-gel route and used in the preparation of different geopolymers, which could be structurally tailored by adjusting the Al/Si-ratio and the curing temperatures. In particular, it was shown that the pore sizes of the geopolymers decreased with increasing Al/Si ratio and that completely mesoporous geopolymers could be produced from precursor particles with the Al/Si ratio 2∶1. The mesoporosity was shown to be associated with a sustained and linear in vitro release profile of the opioid oxycodone. A clinically relevant release period of about 12 h was obtained by adjusting the size of the pellets. The easily fabricated and tunable geopolymers presented in this study constitute a novel approach in the development of controlled release formulations, not only for opioids, but whenever the clinical indication is best treated with a constant supply of drugs and when the mechanical stability of the delivery vehicle is crucial. PMID:21423616

  8. Synthetic geopolymers for controlled delivery of oxycodone: adjustable and nanostructured porosity enables tunable and sustained drug release.

    Directory of Open Access Journals (Sweden)

    Johan Forsgren

    Full Text Available In this article we for the first time present a fully synthetic mesoporous geopolymer drug carrier for controlled release of opioids. Nanoparticulate precursor powders with different Al/Si-ratios were synthesized by a sol-gel route and used in the preparation of different geopolymers, which could be structurally tailored by adjusting the Al/Si-ratio and the curing temperatures. In particular, it was shown that the pore sizes of the geopolymers decreased with increasing Al/Si ratio and that completely mesoporous geopolymers could be produced from precursor particles with the Al/Si ratio 2:1. The mesoporosity was shown to be associated with a sustained and linear in vitro release profile of the opioid oxycodone. A clinically relevant release period of about 12 h was obtained by adjusting the size of the pellets. The easily fabricated and tunable geopolymers presented in this study constitute a novel approach in the development of controlled release formulations, not only for opioids, but whenever the clinical indication is best treated with a constant supply of drugs and when the mechanical stability of the delivery vehicle is crucial.

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

    Directory of Open Access Journals (Sweden)

    Praveen Kumar Gaur

    2014-12-01

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

  10. A lipid-based liquid crystalline matrix that provides sustained release and enhanced oral bioavailability for a model poorly water soluble drug in rats.

    Science.gov (United States)

    Boyd, Ben J; Khoo, Shui-Mei; Whittaker, Darryl V; Davey, Greg; Porter, Christopher J H

    2007-08-01

    Liquid crystalline phases that are stable in excess water, formed using lipids such as glyceryl monooleate (GMO) and oleyl glycerate (OG), are known to provide a sustained release matrix for poorly water soluble drugs in vitro, yet there has been no report of the use of these materials to impart oral sustained release behaviour in vivo. In the first part of this study, in vitro lipolysis experiments were used to compare the digestibility of GMO with a second structurally related lipid, oleyl glycerate, which was found to be less susceptible to hydrolysis by pancreatic lipase than GMO. Subsequent oral bioavailability studies were conducted in rats, in which a model poorly water soluble drug, cinnarizine (CIN), was administered orally as an aqueous suspension, or as a solution in GMO or OG. In the first bioavailability study, plasma samples were taken over a 30 h period and CIN concentrations determined by HPLC. Plasma CIN concentrations after administration in the GMO formulation were only sustained for a few hours after administration while for the OG formulation, the plasma concentration of cinnarizine was at its highest level 30 h after dosing, and appeared to be increasing. A second study in which CIN was again administered in OG, and plasma samples taken for 120 h, revealed a Tmax for CIN in rats of 36 h and a relative oral bioavailability of 344% when compared to the GMO formulation (117%) and the aqueous suspension formulation (assigned a nominal bioavailability of 100%). The results indicate that lipids that form liquid crystalline structures in excess water, may have application as an oral sustained release delivery system, providing they are not digested rapidly on administration.

  11. Use of xanthan and its binary blends with synthetic polymers to design controlled release formulations of buccoadhesive nystatin tablets.

    Science.gov (United States)

    Sakeer, Khalil; Al-Zein, Hind; Hassan, Issa; Martin, Gary P; Nokhodchi, Ali

    2010-01-01

    Various buccoadhesive nystatin tablets formulations containing xanthan, carbopols (934P, 971P, 974P), PVP K30 or PEG 6000 or their binary blends were prepared. The powders were compressed into tablets at a constant compression pressure. Drug release behaviour, swelling and erosion indices and strength of bioadhesion in vitro to a biological membrane were investigated. The interaction between nystatin and polymers was investigated by DSC and FT-IR. Tablets containing the different types of carbopol alone consistently showed an initial burst release of drug, whereas this was not observed for matrices containing xanthan or xanthan-carbopol. The presence of PEG in xanthan-containing formulations induced an increase in dissolution rate; however, in the absence of xanthan the amount of drug release from a PEG matrix was reduced to xanthan matrix as a result of interaction between the polymer and calcium ions. Xanthan can be used in potential mucoadhesive formulations containing nystatin to produce a controlled release of the drug and the outcomes of this work may provide a suitable strategy for matrix selection to provide more efficacious treatment alternatives for candidiasis and other disease processes for significant patient populations.

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

    Directory of Open Access Journals (Sweden)

    Gracy karla da Rocha Cortes

    2017-07-01

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

  13. 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.

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

    Science.gov (United States)

    Dai, Yu; Zhang, Xiaojin

    2017-05-01

    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( ɛ-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.

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

    OpenAIRE

    Yoon S; Lee H.; TE, Kim; Lee S; Chee DH; Cho JY; Yu KS; Jang IJ

    2014-01-01

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

  16. The Effect of Formulation Excipients and Thermal Treatment on the Release Properties of Lisinopril Spheres and Tablets

    Directory of Open Access Journals (Sweden)

    Zoriely Amador Ríos

    2015-01-01

    Full Text Available Multiparticulate systems are used in the development of controlled release systems. The objective of this study was to determine the effect of the wax level, the type of excipient, and the exposure of the tablets to thermal treatment on drug release. Spheres from multiparticulate system with different wax levels and excipients were developed using the drug Lisinopril and compressed into tablets; these tablets were analyzed to determine the drug release. All tablets contained constant level of Lisinopril (10% w/w and Compritol (30% and 50% w/w. Also, as a diluent, all of them contained 30% w/w Avicel and 30% w/w dibasic calcium phosphate or lactose, or 60% Avicel. Tablets compacted from spheres prepared by extruder/marumerizer and using 30% w/w lipid and 60% Avicel released 84% of drug at six hours of dissolution testing, while tablets of the same composition but prepared using 30% dibasic calcium phosphate and 30% Avicel released 101%. When the tablets were thermally treated, the drug release reduced. As the percent of lipid increased in the formulation, the drug release decreased. Compaction of tablets prepared from spheres with wax has potential for controlling the drug release.

  17. The Effect of Formulation Excipients and Thermal Treatment on the Release Properties of Lisinopril Spheres and Tablets

    Science.gov (United States)

    Amador Ríos, Zoriely; Ghaly, Evone Shehata

    2015-01-01

    Multiparticulate systems are used in the development of controlled release systems. The objective of this study was to determine the effect of the wax level, the type of excipient, and the exposure of the tablets to thermal treatment on drug release. Spheres from multiparticulate system with different wax levels and excipients were developed using the drug Lisinopril and compressed into tablets; these tablets were analyzed to determine the drug release. All tablets contained constant level of Lisinopril (10% w/w) and Compritol (30% and 50% w/w). Also, as a diluent, all of them contained 30% w/w Avicel and 30% w/w dibasic calcium phosphate or lactose, or 60% Avicel. Tablets compacted from spheres prepared by extruder/marumerizer and using 30% w/w lipid and 60% Avicel released 84% of drug at six hours of dissolution testing, while tablets of the same composition but prepared using 30% dibasic calcium phosphate and 30% Avicel released 101%. When the tablets were thermally treated, the drug release reduced. As the percent of lipid increased in the formulation, the drug release decreased. Compaction of tablets prepared from spheres with wax has potential for controlling the drug release. PMID:26185757

  18. Enhanced Vascularization in Hybrid PCL/Gelatin Fibrous Scaffolds with Sustained Release of VEGF

    Directory of Open Access Journals (Sweden)

    Kai Wang

    2015-01-01

    Full Text Available Creating a long-lasting and functional vasculature represents one of the most fundamental challenges in tissue engineering. VEGF has been widely accepted as a potent angiogenic factor involved in the early stages of blood vessel formation. In this study, fibrous scaffolds that consist of PCL and gelatin fibers were fabricated. The gelatin fibers were further functionalized by heparin immobilization, which provides binding sites for VEGF and thus enables the sustained release of VEGF. In vitro release test confirms the sustained releasing profile of VEGF, and stable release was observed over a time period of 25 days. In vitro cell assay indicates that VEGF release significantly promoted the proliferation of endothelial cells. More importantly, in vivo subcutaneous implantation reflects that vascularization has been effectively enhanced in the PCL/gelatin scaffolds compared with the PCL counterpart due to the sustained release of VEGF. Therefore, the heparinized PCL/gelatin scaffolds developed in this study may be a promising candidate for regeneration of complex tissues with sufficient vascularization.

  19. Comparative pharmacokinetics and bioavailability of tapentadol following oral administration of immediate- and prolonged-release formulations

    NARCIS (Netherlands)

    Gohler, K.; Brett, M.; Smit, J.W.A.; Rengelshausen, J.; Terlinden, R.

    2013-01-01

    OBJECTIVE: To evaluate the bioavailability and pharmacokinetics of orally administered tapentadol immediate release (IR) compared with tapentadol prolonged release (PR). METHODS: Three randomized, open-label, crossover studies were conducted in subjects under fasted conditions. Studies 1 and 2

  20. Sustained release matrix tablets prepared from cospray dried mixtures with starch hydrophobic esters.

    Science.gov (United States)

    Sakhnini, N; Al-Zoubi, N; Al-Obaidi, G H; Ardakani, A

    2015-03-01

    In this work, starch acetate and propanoate derivatives with moderate degree of substitution were synthesized and characterized for employment as matrix formers for sustained release from tablets. Matrix tablets were prepared from cospray-dried and simple physical mixtures of starch/starch derivatives and theophylline as a model drug. The release was rapid for matrix tablets prepared from simple physical mixtures. On the other hand, tablets prepared from cospray-dried mixtures with starch acetate and starch propanoate showed much slower and extended release. Scanning electron micrographs of tablet surfaces revealed enhanced inter-particulate bonding and plastification for cospray-dried agglomerates in comparison with physical mixtures.

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

    Science.gov (United States)

    Zaheer, Kamran; Langguth, Peter

    2018-03-01

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

  2. Sustained release of complexed DNA from films: Study of bioactivity and intracellular tracking.

    Science.gov (United States)

    Mondal, Debasish; Ramgopal, Yamini; Tiwari, Sandeep Kumar; Venkatraman, Subbu S

    2010-09-01

    Sustained DNA delivery from polymeric films provides a means for localized and prolonged gene therapy. However, in the case of bioactive molecules such as plasmid DNA (pDNA), there are limitations on the achievable release profiles as well as on the maintenance of bioactivity over time. In this report, the authors have investigated the bioactivity of the released DNA (naked and complexed with lipofectamine) from polymeric films using in vitro cell transfection of COS-7 cell lines. The polymeric system consists of a biodegradable semicrystalline polymer such as poly(ε-caprolactone) (PCL) with or without blended gelatin. Sustained release of lipoplexes and of pDNA is shown over several days. However, lipoplexes released from pure PCL films show no transfection on day 18, whereas lipoplexes released from PCL-gelatin films continue to transfect cells on day 18 of release. Confocal studies were used to determine the reasons for this difference in transfection efficiency, and it is proposed that association of the lipoplex with gelatin confers protection from degradation in the cytoplasm. The results also showed that the bioactivity of released lipoplexes was superior to that of the naked pDNA. For both naked pDNA and the lipoplexes, the presence of gelatin helped to maintain the bioactivity over several days.

  3. Sustained Release of BMP-2 in Bioprinted Alginate for Osteogenicity in Mice and Rats

    Science.gov (United States)

    Poldervaart, Michelle T.; Wang, Huanan; van der Stok, Johan; Weinans, Harrie; Leeuwenburgh, Sander C. G.; Öner, F. Cumhur; Dhert, Wouter J. A.; Alblas, Jacqueline

    2013-01-01

    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. PMID:23977328

  4. 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.

  5. Polymer excipients enable sustained drug release in low pH from mechanically strong inorganic geopolymers.

    Science.gov (United States)

    Jämstorp, Erik; Yarra, Tejaswi; Cai, Bing; Engqvist, Håkan; Bredenberg, Susanne; Strømme, Maria

    2012-01-01

    Improving acid resistance, while maintaining the excellent mechanical stability is crucial in the development of a sustained and safe oral geopolymer dosage form for highly potent opioids. In the present work, commercially available Methacrylic acid-ethyl acrylate copolymer, Polyethylene-glycol (PEG) and Alginate polymer excipients were included in dissolved or powder form in geopolymer pellets to improve the release properties of Zolpidem, herein acting as a model drug for the highly potent opioid Fentanyl. Scanning electron microscopy, compression strength tests and drug release experiments, in gastric pH 1 and intestinal pH 6.8 conditions, were performed. The polymer excipients, with an exception for PEG, reduced the drug release rate in pH 1 due to their ability to keep the pellets in shape, in combination with the introduction of an insoluble excipient, and thereby maintain a barrier towards drug diffusion and release. Neither geopolymer compression strength nor the release in pH 6.8 was considerably impaired by the incorporation of the polymer excipients. The geopolymer/polymer composites combine high mechanical strength and good release properties under both gastric and intestinal pH conditions, and are therefore promising oral dosage forms for sustained release of highly potent opioids.

  6. Assessing the risk of alcohol-induced dose dumping from sustained-release oral dosage forms: in vitro-in silico approach.

    Science.gov (United States)

    Cvijić, Sandra; Aleksić, Ivana; Ibrić, Svetlana; Parojčić, Jelena

    2017-10-29

    Consumption of alcoholic beverages with sustained-release oral dosage forms may pose a risk to patients due to potential alcohol-induced dose dumping (ADD). Regulatory guidances recommend in vitro dissolution testing to identify the risk of ADD, but the question remains whether currently proposed test conditions can be considered biopredictive. The purpose of this study was to evaluate different dissolution setups to assess ADD, and the potential of combined in vitro-in silico approach to predict drug absorption after concomitant alcohol intake for hydrophilic and lipophilic sustained-release tablets containing ibuprofen or diclofenac sodium. According to the obtained results, the impact of ethanol was predominantly governed by the influence on matrix integrity, with the increase in drug solubility being less significant. Hydrophilic matrix tablets were less susceptible to ADD than lipophilic matrices, although the conclusion on formulation ethanol-vulnerability depended on the employed experimental conditions. In silico predictions indicated that the observed changes in drug dissolution would not result in plasma concentrations beyond therapeutic window, but sustained-release characteristics of the formulations might be lost. Overall, the study demonstrated that in vitro-in silico approach may provide insight into the effect of ADD on drug clinical performance, and serve as a tool for ADD risk assessment.

  7. 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...

  8. Quality by Design Empowered Development and Optimisation of Time-Controlled Pulsatile Release Platform Formulation Employing Compression Coating Technology.

    Science.gov (United States)

    Patadia, Riddhish; Vora, Chintan; Mittal, Karan; Mashru, Rajashree C

    2017-05-01

    The research was envisaged for development of time-controlled pulsatile release (PR) platform formulation to facilitate management of early morning chronological attacks. The development was started using prednisone as a model drug wherein core tablets were prepared using direct compression method and subsequently compression-coated with ethylcellulose (EC)-hydroxypropyl methylcellulose (HPMC) excipient blend. Initially, quality target product profile was established and risk assessment was performed using failure mode and effect analysis. In an endeavour to accomplish the objective, central composite design was employed as a design of experiment (DoE) tool. Optimised compression-coated tablet (CCT) exhibited 4-6 h lag time followed by burst release profile under variegated dissolution conditions viz. multi-media, change in apparatus/agitation and biorelevant media. Afterwards, five different drugs, i.e. methylprednisolone, diclofenac sodium, diltiazem hydrochloride, nifedipine and lornoxicam, were one-by-one incorporated into the optimised prednisone formula with replacement of former drug. Change in drug precipitated the issues like poor solubility and flow property which were respectively resolved through formulation of solid dispersion and preparation of active pharmaceutical ingredient (API) granules. Albeit, all drug CCTs exhibited desired release profile similar to prednisone CCTs. In nutshell, tour de force of research epitomised the objective of incorporating diverse drug molecules and penultimately obtaining robust release profile at varying dissolution conditions.

  9. Preparation and characterization of anti-algal sustained-release granules and their inhibitory effects on algae.

    Science.gov (United States)

    Ni, Lixiao; Acharya, Kumud; Ren, Gaoxiang; Li, Shiyin; Li, Yiping; Li, Yong

    2013-04-01

    The objectives of this work were to prepare and characterize an anti-algal sustained-release granule, then study its mode of action on Microcystis aeruginosa. The anti-algal sustained-release granule was prepared with artemisinin using alginate-chitosan microcapsule technology and characterized by a high performance liquid chromatography with an evaporative light-scattering detector, Fourier transform infrared spectral analysis, and a scanning electron microscope. The optimum preparation (in %, w/v) using the orthogonal method was: 2.5 sodium alginate; 0.25 chloride; 0.6 artemisinin; 2 calcium chloride; and 1.5 mL of the cross-linking agent, glutaraldehyde. These artemisinin sustained-release granules had a high encapsulation efficiency (up to 68%) and good release properties (release time of more than 40 d). Artemisinin sustained-release granules released cumulatively in a solution containing M. aeruginosa, and the stress on algae increased gradually within 30 d. Artemisinin sustained-release granules decreased the content of the soluble protein, Chlorophyll a in 30 d, increased the superoxide dismutase activity of M. aeruginosa, but exerted no effect on the soluble sugar content. Compared to direct dosing of artemisinin, algae can be inhibited longer and more effectively by the artemisinin sustained-release granules. The results of our research can aid in the development of new anti-algal sustained-release granules and lead to further study of their application in the field. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Polymer Percolation Threshold in HPMC Extended Release Formulation of Carbamazepine and Verapamil HCl

    National Research Council Canada - National Science Library

    Gonçalves-Araújo, Tamara; Rajabi-Siahboomi, Ali R; Caraballo, Isidoro

    2010-01-01

    ...) extended release matrix tablets containing carbamazepine and verapamil HCl. This statistical theory studies disordered or chaotic systems where the components are randomly distributed in a lattice...

  11. Synthesis and Characteristics of Valeric Acid-Zinc Layered Hydroxide Intercalation Material for Insect Pheromone Controlled Release Formulation

    Directory of Open Access Journals (Sweden)

    Rozita Ahmad

    2016-01-01

    Full Text Available A new intercalation compound of insect pheromone, valeric acid (VA, based on zinc layered hydroxide (ZLH as host release material, was successfully prepared through coprecipitation method. The as-produced organic-inorganic nanolayered material, valerate nanohybrid, VAN, shows the formation of a new peak at lower 2θ angle with basal spacing of 19.8 Å with no ZnO reflections, which indicate that the intercalation of anion between the inorganic ZLH interlamellae was accomplished. The elemental, FTIR, and ATR analyses of the nanohybrid supported the fact that the intercalation with the percentage anion loading was calculated to be 23.0% (w/w. The thermal stability property of the resulting nanohybrid was enhanced compared to the unbound anion. Field emission scanning electron micrograph of the ZnO has a nonuniform granular structure but transforms into flake-like structure with various sizes after the intercalation process. Release kinetics of anion from the interlayer of intercalated compound exhibited a slow release behavior governed by the pseudo-second-order kinetic model at different pHs of aqueous media. The valerate anion was released from VAN with the highest release rate at pH 4. These findings provide the basis to further development of controlled release formulation for insect pheromone based on ZLH intercalation.

  12. Pharmacokinetics of 2 Novel Formulations of Modified-Release Oral Testosterone Alone and With Finasteride in Normal Men With Experimental Hypogonadism

    Science.gov (United States)

    Snyder, Christin N.; Clark, Richard V.; Caricofe, Ralph B.; Bush, Mark A.; Roth, Mara Y.; Page, Stephanie T.; Bremner, William J.; Amory, John K.

    2011-01-01

    Oral administration of testosterone might be useful for the treatment of testosterone deficiency. However, current “immediate-release” formulations of oral testosterone exhibit suboptimal pharmacokinetics, with supraphysiologic peaks of testosterone and its metabolite, dihydrotestosterone (DHT), immediately after dosing. To dampen these peaks, we have developed 2 novel modified-release formulations of oral testosterone designed to slow absorption from the gut and improve hormone delivery. We studied these testosterone formulations in 16 normal young men enrolled in a 2-arm, open-label clinical trial. Three hundred-mg and 600-mg doses of immediate-release and modified fast-release or slow-release formulations were administered sequentially to 8 normal men rendered hypogonadal by the administration of the gonadotropin-releasing hormone antagonist acyline. Blood for measurement of serum testosterone, DHT, and estradiol was obtained before and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after each dose. A second group of 8 men was studied with the coadministration of 1 mg of the 5α-reductase inhibitor finasteride daily throughout the treatment period. Serum testosterone was increased with all formulations of oral testosterone. The modified slow-release formulation significantly delayed the postdose peaks of serum testosterone and reduced peak concentrations of serum DHT compared with the immediate-release formulation. The addition of finasteride further increased serum testosterone and decreased serum DHT. We conclude that the oral modified slow-release testosterone formulation exhibits superior pharmacokinetics compared with immediate-release oral testosterone both alone and in combination with finasteride. This formulation might have efficacy for the treatment of testosterone deficiency. PMID:20378927

  13. 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.

  14. 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.

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

    Science.gov (United States)

    Li, Xiao; Zhao, Yang; Wang, Kaijie; Yang, Xiaohui; Zhu, Siquan

    2017-01-01

    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. PMID:29244868

  16. Coaxial Electrospray of Ranibizumab-Loaded Microparticles for Sustained Release of Anti-VEGF Therapies.

    Directory of Open Access Journals (Sweden)

    Leilei Zhang

    Full Text Available Age-related macular degeneration (AMD is the leading cause of vision loss and blindness in people over age 65 in industrialized nations. Intravitreous injection of anti-VEGF (vascular endothelial growth factor therapies, such as ranibizumab (trade name: Lucentis, provides an effective treatment option for neovascular AMD. We have developed an improved coaxial electrospray (CES process to encapsulate ranibizumab in poly(lactic-co-glycolic acid (PLGA microparticles (MPs for intravitreous injection and sustained drug release. This microencapsulation process is advantageous for maintaining the stability of the coaxial cone-jet configurations and producing drug-loaded MPs with as high as 70% encapsulation rate and minimal loss of bioactivitiy. The utility of this emerging process in intravitreous drug delivery has been demonstrated in both benchtop and in vivo experiments. The benchtop test simulates ocular drug release using PLGA MPs encapsulating a model drug. The in vivo experiment evaluates the inflammation and retinal cell death after intravitreal injection of the MPs in a chick model. The experimental results show that the drug-load MPs are able to facilitate sustained drug release for longer than one month. No significant long term microglia reaction or cell death is observed after intravitreal injection of 200 μg MPs. The present study demonstrates the technical feasibility of using the improved CES process to encapsulate water-soluble drugs at a high concentration for sustained release of anti-VEGF therapy.

  17. A (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer)-dispersed sustained-release tablet for imperialine to simultaneously prolong the drug release and improve the oral bioavailability.

    Science.gov (United States)

    Lin, Qing; Fu, Yu; Li, Jia; Qu, Mengke; Deng, Li; Gong, Tao; Zhang, Zhirong

    2015-11-15

    Imperialine, extracted from Bulbus Fritillariae Cirrhosae, is an efficient antitussive and expectorant medicine. However, its short half-life and stomach degradation limited imperialine from further clinical use. The current study was conducted to develop a sustained-release tablet for imperialine both to prolong absorption time and to improve the oral bioavailability of the drug. The tablets were prepared by a direct compression method formulated on optimized solid dispersion (SD) for imperialine based on polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus(®)) with imperialine/Soluplus(®) ratio of 1:8 (w/w). In order to obtain the optimized formulation, factors that affected the drug release were investigated by in vitro dissolution studies in the media of pH1.2, 5.8, 7.0 and 7.4. Powder X-ray diffraction and scanning electron microscope confirmed that the imperialine in SD was amorphous instead of crystalline, and still stayed amorphous even after the direct compression. And besides, pharmacokinetic study in Beagle dogs was performed to inspect the in vivo sustained release. Plasma concentration-time curves and pharmacokinetic parameters were gained. As a result, the Cmax of imperialine was one-fold reduced and Tmax was two-fold prolonged, and the mean AUC0-24 was expressed as 89.581±21.243μgh/L, which showed that the oral bioavailability of imperialine was 2.46-fold improved. Moreover, the in vitro-in vivo correlation was recommended to carry out, demonstrating the percentages of drug release in vitro were well-correlated with the absorptive fraction in vivo with the correlation coefficients above 0.9900. By mathematically modeling and moment imaging of the drug release, Peppas equation was selected as the most fitted model for the sustained-release tablets with the diffusional coefficient in the range of 0.59-0.62, indicating the release of imperialine from the sustained-release tablets was an anomalous process involving

  18. 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.

  19. 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

  20. Lignin and ethylcellulose in controlled release formulations to reduce leaching of chloridazon and metribuzin in light-textured soils.

    Science.gov (United States)

    Flores-Céspedes, F; Daza-Fernández, I; Villafranca-Sánchez, M; Fernández-Pérez, M; Morillo, E; Undabeytia, T

    2018-02-05

    In this research, controlled release formulations (CRFs) of the herbicides chloridazon and metribuzin, identified as potential leachers, have been evaluated in soils with different texture. To prepare the CRFs, ethylcellulose (EC) and dibutylsebacate (DBS) have been used as coating agents in lignin-polyethylene glycol based formulations. Mobility experiments have been carried out in two light textured soils (sandy and sandy-loam). Breakthrough curves have shown that the use of CRFs reduces the presence of chloridazon and metribuzin in the leachate compared to technical and commercial products, being the lignin CRF coated with EC and DBS the most efficient to diminish the herbicide leaching. Mass balance study has shown a higher amount of chloridazon and metribuzin recovered in soils when these herbicides were tested as CRFs compared to technical and commercial products. The gradual release of herbicides from the CRFs resulting in a rather available levels of chloridazon and metribuzin in soil for a longer time. A good correlation between percentages of herbicide recovered in leachates and T50 values (time corresponding to 50% release of herbicide in water) was obtained, which allows to select the most appropriate CRF in each agro-environmental practice to reduce the potential pollution of groundwater by chloridazon and metribuzin. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Timed Release of Flurprimidol From a Granular Formulation With Mulches and Sand Soil

    Science.gov (United States)

    Flurprimidol is a Type II plant growth regulator widely used in the landscape industry. Leaching of the compound from a commercially available granular formulation and movement through 30-cm diameter columns of bark mulch covered to a depth of 1.5 cm with sand was evaluated in a greenhouse and labor...

  2. Polymeric formulations for drug release prepared by hot melt extrusion : application and characterization

    NARCIS (Netherlands)

    Stanković, Milica; Frijlink, Henderik W; Hinrichs, Wouter L J

    2015-01-01

    Over the past few decades hot melt extrusion (HME) has emerged as a powerful processing technology for the production of pharmaceutical solid dosage forms in which an active pharmaceutical ingredient (API) is dispersed into polymer matrices. It has been shown that formulations using HME can provide

  3. The design of controlled-release formulations resistant to alcohol-induced dose dumping--a review.

    Science.gov (United States)

    Jedinger, N; Khinast, J; Roblegg, E

    2014-07-01

    The concomitant intake of alcoholic beverages together with oral controlled-release opioid formulations poses a serious safety concern since alcohol has the potential to alter the release rate controlling mechanism of the dosage form which may result in an uncontrolled and immediate drug release. This effect, known as alcohol-induced dose dumping, has drawn attention of the regulatory authorities. Thus, the Food and Drug Administration (FDA) recommends that in vitro drug release studies of controlled-release dosage forms containing drugs with narrow therapeutic range should be conducted in ethanolic media up to 40%. So far, only a limited number of robust dosage forms that withstand the impact of alcohol are available and the development of such dosage forms is still a challenge. This review deals with the physico-chemical key factors which have to be considered for the preparation of alcohol-resistant controlling dosage forms. Furthermore, appropriate matrix systems and promising technological strategies, which are suitable to prevent alcohol-induced dose dumping, are discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Sustained release of diclofenac from polymer-containing suppository and the mechanism involved.

    Science.gov (United States)

    Azechi, Y; Ishikawa, K; Mizuno, N; Takahashi, K

    2000-11-01

    Sustained release of diclofenac sodium (DcNa) from suppositories composed of triglycerides and polymer was investigated by dissolution testing through an artificial membrane. DcNa was slowly released from a suppository containing carboxyvinyl polymer (CVP), and the extent of the release decreased with the amount of CVP added. Little effect was noted with the addition of other water-soluble polymers, such as hydroxyethylcellulose (HEC), xanthan gum, and polyvinylalcohol (PVA). When sodium benzoate was used instead of DcNa, a similar result was obtained with the addition of CVP. The result of release rate analysis together with the viscosity and pH in these cases showed that the reduction of solubility and diffusion due to sodium exchange between DcNa and CVP played an important role in the sustained release from the suppository. Also, in comparison with the results when CVP was not used, the plasma concentration profile of diclofenac after the administration of CVP suppository displayed a twofold longer half-life time.

  5. Sustained-releasing hollow microparticles with dual-anticancer drugs elicit greater shrinkage of tumor spheroids.

    Science.gov (United States)

    Baek, Jong-Suep; Choo, Chee Chong; Tan, Nguan Soon; Loo, Say Chye Joachim

    2017-10-06

    Polymeric particulate delivery systems are vastly explored for the delivery of chemotherapeutic agents. However, the preparation of polymeric particulate systems with the capability of providing sustained release of two or more drugs is still a challenge. Herein, poly (D, L-lactic-co-glycolic acid, 50:50) hollow microparticles co-loaded with doxorubicin and paclitaxel were developed through double-emulsion solvent evaporation technique. Hollow microparticles were formed through the addition of an osmolyte into the fabrication process. The benefits of hollow over solid microparticles were found to be higher encapsulation efficiency and a more rapid drug release rate. Further modification of the hollow microparticles was accomplished through the introduction of methyl-β-cyclodextrin. With this, a higher encapsulation efficiency of both drugs and an enhanced cumulative release were achieved. Spheroid study further demonstrated that the controlled release of the drugs from the methyl-β-cyclodextrin -loaded hollow microparticles exhibited enhanced tumor regressions of MCF-7 tumor spheroids. Such hollow dual-drug-loaded hollow microparticles with sustained releasing capabilities may have a potential for future applications in cancer therapy.

  6. 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.

  7. A Comparison of the Pharmacokinetics of Methylphenidate Extended-Release Orally Disintegrating Tablets With a Reference Extended-Release Formulation of Methylphenidate in Healthy Adults.

    Science.gov (United States)

    Childress, Ann; Stark, Jeffrey G; McMahen, Russ; Engelking, Dorothy; Sikes, Carolyn

    2018-02-01

    Extended-release (ER) methylphenidate (MPH) is a first-line treatment for attention-deficit/hyperactivity disorder. A methylphenidate extended-release orally disintegrating tablet (MPH XR-ODT) has recently been developed. This was a randomized, open-label, 3-period, 3-treatment study comparing the bioavailability and absorption of 2 MPH XR-ODT formulations with an MPH ER reference medication. Here we report the 2 treatments comparing the commercial MPH XR-ODT formulation and reference medication. Following a ≥10-hour fast, 42 healthy adults received 60 mg of reference medication or MPH XR-ODT (2 × 30 mg). The following pharmacokinetic (PK) parameters were calculated for total methylphenidate (d + l): maximum plasma concentration (C max ), time to maximum plasma concentration (T max ), terminal half-life (T 1/2 ), and areas under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC last ), and from time zero extrapolated to infinity (AUC inf ). Secondary PK end points included partial AUCs. Safety was also assessed. Overall systemic exposure to methylphenidate after MPH XR-ODT administration was similar to that of the reference product, and the concentration-time profiles for MPH XR-ODT and the reference drug were similar, although the C max was 25% higher for MPH XR-ODT. The most common treatment-emergent adverse events were nausea (6) and anxiety (4), which were similar across treatments. © 2017, The American College of Clinical Pharmacology.

  8. Vanadium(V) and -(IV) complexes of anionic polysaccharides: Controlled release pharmaceutical formulations and models of vanadium biotransformation products.

    Science.gov (United States)

    Kremer, Lauren E; McLeod, Andrew I; Aitken, Jade B; Levina, Aviva; Lay, Peter A

    2015-06-01

    Uncontrolled reactions in biological media are a main obstacle for clinical translation of V-based anti-diabetic or anti-cancer pro-drugs. We investigated the use of controlled-release pharmaceutical formulations to ameliorate this issue with a series of V(V) and (IV) complexes of anionic polysaccharides. Carboxymethyl cellulose, xanthan gum, or alginic acid formulations were prepared by the reactions of [VO4](3-) with one or two molar equivalents of biological reductants, L-ascorbic acid (AA) or L-cysteine (Cys), in the presence of excess polysaccharide at pH~7 or pH~4. XANES studies with the use of a previously developed library of model V(V), V(IV) and V(III) complexes showed that reactions in the presence of AA led mostly to the mixtures of five- and six-coordinate V(IV) species, while the reactions in the presence of Cys led predominantly to the mixtures of five- and six-coordinate V(V) species. The XANES spectra of some of these samples closely matched those reported previously for [VO4](3-) biotransformation products in isolated blood plasma, red blood cells, or cultured adipocytes, which supports the hypothesis that modified polysaccharides are major binders of V(V) and V(IV) in biological systems. Studies by EPR spectroscopy suggested predominant V(IV)-carboxylato binding in complexes with polysaccharides. One of the isolated products (a V(IV)-alginato complex) showed selective release of low-molecular-mass V species at pH~8, but not at pH~2, which makes it a promising lead for the development of V-containing formulations for oral administration that are stable in the stomach, but release the active ingredient in the intestines. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Vemula, Sateesh Kumar

    2015-12-01

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

  10. Comparison of neurofuzzy logic and neural networks in modelling experimental data of an immediate release tablet formulation.

    Science.gov (United States)

    Shao, Qun; Rowe, Raymond C; York, Peter

    2006-08-01

    This study compares the performance of neurofuzzy logic and neural networks using two software packages (INForm and FormRules) in generating predictive models for a published database for an immediate release tablet formulation. Both approaches were successful in developing good predictive models for tablet tensile strength and drug dissolution profiles. While neural networks demonstrated a slightly superior capability in predicting unseen data, neurofuzzy logic had the added advantage of generating rule sets representing the cause-effect relationships contained in the experimental data.

  11. Clinical Efficacy of Sustained-Release Buprenorphine with Meloxicam for Postoperative Analgesia in Beagle Dogs Undergoing Ovariohysterectomy

    Science.gov (United States)

    Nunamaker, Elizabeth A; Stolarik, DeAnne F; Ma, Junli; Wilsey, Amanda S; Jenkins, Gary J; Medina, Chris L

    2014-01-01

    The goal of the current study was to compare the efficacy, adverse effects, and plasma buprenorphine concentrations of sustained-release buprenorphine (SRB) and buprenorphine after subcutaneous administration in dogs undergoing ovariohysterectomy. In a prospective, randomized, blinded design, 20 healthy adult female Beagle dogs underwent routine ovariohysterectomy and received multimodal analgesia consisting of meloxicam and one of two buprenorphine formulations. Dogs were randomly assigned to receive either SRB (0.2 mg/kg SC, once) or buprenorphine (0.02 mg/kg SC every 12 h for 3 d). Blinded observers assessed all dogs by using sedation scores, pain scores, temperature, HR, RR, and general wellbeing. Dogs were provided rescue analgesia with 0.02 mg/kg buprenorphine SC if the postoperative pain score exceeded a predetermined threshold. Blood samples were collected, and mass spectrometry was used to determine plasma buprenorphine concentrations. Data were analyzed with a linear mixed model and Tukey–Kramer multiple comparison. Age, body weight, anesthetic duration, surgical duration, sevoflurane concentration, and cardiorespiratory variables did not differ significantly between groups. Dogs in both formulation groups had comparable postoperative sedation and pain scores. One dog from each formulation group had breakthrough pain requiring rescue analgesia. Plasma buprenorphine concentrations remained above a hypothesized therapeutic concentration of 0.6 ng/mL for 136.0 ± 11.3 and 10.67 ± 0.84 h for SRB and buprenorphine, respectively. Based on the results of this study, multimodal analgesic regimens consisting of meloxicam and either buprenorphine or SRB are equally efficacious in managing pain associated with an ovariohysterectomy and show comparable side effects. PMID:25255072

  12. Once-Daily, Controlled-Release Tramadol and Sustained-Release Diclofenac Relieve Chronic Pain due to Osteoarthritis: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    André D Beaulieu

    2008-01-01

    Full Text Available OBJECTIVE: The present study was a randomized, parallel, double-blind comparison between controlled-release (CR tramadol and sustained-release (SR diclofenac in patients with chronic pain due to osteoarthritis of the hips and/or knees.

  13. 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.

  14. Physical crosslinking modulates sustained drug release from recombinant silk-elastinlike protein polymer for ophthalmic applications.

    Science.gov (United States)

    Teng, Weibing; Cappello, Joseph; Wu, Xiaoyi

    2011-12-10

    We evaluated the drug release capability of optically transparent recombinant silk-elastinlike protein polymer, SELP-47K, films to sustainably deliver the common ocular antibiotic, ciprofloxacin. The ciprofloxacin release kinetics from drug-loaded SELP-47K films treated with ethanol or methanol vapor to induce different densities of physical crosslinking was investigated. Additionally, the drug-loaded protein films were embedded in a protein polymer coating to further prolong the release of the drug. Drug-loaded SELP-47K films released ciprofloxacin for up to 132 h with near first-order release kinetics. Polymer coating of drug-loaded films prolonged drug release for up to 220 h. The antimicrobial activity of ciprofloxacin released from the drug delivery matrices was not impaired by the film casting process or the ethanol or methanol treatments. The mechanism of drug release was elucidated by analyzing the physical properties of the film specimens, including equilibrium swelling, soluble fraction, surface roughness and hydrophobicity. Additionally, the conformation of the SELP-47K and its physical crosslinks in the films was analyzed by FTIR and Raman spectroscopy. A three-parameter physics based model accurately described the release rates observed for the various film and coating treatments and attributed the effects to the degree of physical crosslinking of the films and to an increasing affinity of the drug with the polymer network. Together, these results indicate that optically transparent silk-elastinlike protein films may be attractive material candidates for novel ophthalmic drug delivery devices. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Formulation of in situ chemically cross-linked hydrogel depots for protein release: from the blob model perspective.

    Science.gov (United States)

    Yu, Yu; Chau, Ying

    2015-01-12

    The fast release rate and the undesirable covalent binding are two major problems often encountered in formulating in situ chemically cross-linked hydrogel as protein release depot, particularly when prolonged release over months is desirable. In this study, we applied the De Gennes' blob theory to analyze and tackle these two problems using a vinylsulfone-thiol (VS-SH) reaction based in situ hydrogel system. We showed that the simple scaling relation ξb ≈ Rg(c/c*)(-v/(3v-1)) is applicable to the in situ hydrogel and the mesh size estimated from the precursor polymer parameters is a reasonable match to experimental results. On the other hand, as predicted by the theory and confirmed by experiments, the drug diffusion within hydrogel depends mainly on polymer concentration but not the degree of modification (DM). The covalent binding was found to be caused by the mismatch of location between the reactive groups and the entanglement points. The mismatch and, thus, the protein binding were minimized by increasing the DM and concentration of the SH polymer relative to the VS polymer, as predicted by theory. Using these principles, an in situ hydrogel system for the controlled release of an antiangiogenic antibody therapeutics bevacizumab for 3 months was developed.

  16. Development and in vitro characterization of floating sustained-release drug delivery systems of polyphenols.

    Science.gov (United States)

    Rosenzweig, Ohad; Lavy, Eran; Gati, Irith; Kohen, Ron; Friedman, Michael

    2013-01-01

    The aim of this study was to develop and characterize floating stomach-retentive matrix tablets that will deliver polyphenols in a controlled release manner. The tablets were prepared by direct compression. A number of polymers were examined and egg albumin was chosen in light of a better performance in terms of floating behavior and decomposition time. Dissolution studies for three representative polyphenols loaded into a number of formulations were performed using the "f₂" factor in order to compare release profiles of different polyphenols and formulations. The release data showed a good fit into the power law equation and zero-order kinetics has been determined for some of the systems. Erosion and textural analysis studies revealed that higher concentration of egg albumin results in a higher gel strength that is less susceptible to erosion, potentially leading to a prolonged delivery time of drug. The ability of egg albumin-based tablets to resist high mechanical forces was also determined, while comparison to cellulose-derived polymers revealed that the latter have a much lower ability to resist the same forces. The developed delivery system has the potential to increase the efficacy of the therapy for various pathological stomach conditions and to improve patient compliance.

  17. Comparison of two hydrogel formulations for drug release in ophthalmic lenses.

    Science.gov (United States)

    Paradiso, P; Galante, R; Santos, L; Alves de Matos, A P; Colaço, R; Serro, A P; Saramago, B

    2014-08-01

    In the present work two types of polymers were investigated as drug releasing contact lens materials: a poly-hydroxyethylmethacrylate (pHEMA) based hydrogel and a silicone hydrogel. The silicone hydrogel resulted from the addition of TRIS, a hydrophobic monomer containing silicon (3-tris(trimethylsilyloxy)silylpropyl 2-methylprop-2-enoate), to pHEMA. Both hydrogels were loaded with an antibiotic (levofloxacin) and an antiseptic (chlorhexidine) by soaking in the drug solutions. The hydrogel properties were determined to be within the range demanded for lens materials. The release profiles of both drugs from the hydrogels were obtained and eventual drug/polymer interactions were assessed with the help of Raman spectra. A mathematical model, developed to mimic the eye conditions, was applied to the experimental results in order to predict the in vivo efficacy of the studied systems. The release profiles were compared with those resulting from the application of commercial eyedrops. The pHEMA based hydrogel demonstrated to be the best material to achieve a controlled release of levofloxacin. In the case of chlorhexidine, the silicone hydrogel seems to lead to better results. In both cases, our results suggest that these materials are adequate for the preparation of daily disposable therapeutic contact lenses. © 2014 Wiley Periodicals, Inc.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    , the solubility of the AI, and diffusion transport with decay. The model gives acceptable predictions of the pesticides release from commercial CRFs in diffusion cells filled with quartz sand. This approach can be used to study the dynamics of the CRF-porous media interaction. It also could be implemented in fate...

  19. Chitosan based nanoparticles as a sustained protein release carrier for tissue engineering applications

    Science.gov (United States)

    Hou, Yaping; Hu, Junli; Park, Hyejin; Lee, Min

    2012-01-01

    Chitosan/tripolyphosphate/chondroitin sulfate (Chi/TPP/CS) nanoparticles were prepared by an ionic gelation method to obtain a controlled release of proteins. Using Nel-like molecule-1 (Nell-1), a novel osteogenic protein, as a model protein, it was demonstrated that adjusting the composition of the particles modulated the protein association and release kinetics of incorporated proteins. Increasing the amounts of chitosan crosslinking agents, TPP and CS, in the particles achieved sustained protein release. An increase in crosslinking density decreased degradation rates of the particles. Furthermore, the bioactivity of the protein was preserved during the encapsulating procedure into the particles. To demonstrate the feasibility of Chi/TPP/CS nanoparticles as sustained release carriers for tissue engineering scaffold applications, protein-loaded nanoparticles were successfully incorporated into collagen hydrogels or prefabricated porous poly (lactide-co-glycolide) (PLGA) scaffolds without obstructing the integrity of the hydrogels or porous structure of the scaffolds. Thus, we expect that these particles have a potential for efficient protein carriers in tissue engineering applications, and will be further evaluated in vivo. PMID:22275184

  20. Synthesis of multilayered alginate microcapsules for the sustained release of fibroblast growth factor-1

    Science.gov (United States)

    Khanna, Omaditya; Moya, Monica L; Opara, Emmanuel C; Brey, Eric M

    2010-01-01

    Alginate microcapsules coated with a permselective poly-L-ornithine (PLO) membrane have been investigated for the encapsulation and transplantation of islets as a treatment for type 1 diabetes. The therapeutic potential of this approach could be improved through local stimulation of microvascular networks in order to meet mass transport demands of the encapsulated cells. Fibroblast growth factor-1 (FGF-1) is a potent angiogenic factor with optimal effect occurring when it is delivered in a sustained manner. In this paper, a technique is described for the generation of multilayered alginate microcapsules with an outer alginate layer that can be used for the delivery of FGF-1. The influence of alginate concentration and composition (high mannuronic acid (M) or guluronic acid (G) content) on outer layer size and stability, protein encapsulation efficiency, and release kinetics was investigated. The technique results in a stable outer layer of alginate with a mean thickness between 113–164 µm, increasing with alginate concentration and G-content. The outer layer was able to encapsulate and release FGF-1 for up to thirty days, with 1.25% of high G alginate displaying the most sustained release. The released FGF-1 retained its biologic activity in the presence of heparin, and the addition of the outer layer did not alter the permselectivity of the PLO coat. This technique could be used to generate encapsulation systems that deliver proteins to stimulate local neovascularization around encapsulated islets. PMID:20725969

  1. Polypyrrole nanoparticles for tunable, pH-sensitive and sustained drug release

    Science.gov (United States)

    Samanta, Devleena; Meiser, Jana L.; Zare, Richard N.

    2015-05-01

    We report the development of a generalized pH-sensitive drug delivery system that can release any charged drug preferentially at the pH range of interest. Our system is based on polypyrrole nanoparticles (PPy NPs), synthesized via a simple one-step microemulsion technique. These nanoparticles are highly monodisperse, stable in solution over the period of a month, and have good drug loading capacity (~15 wt%). We show that PPy NPs can be tuned to release drugs at both acidic and basic pH by varying the pH, the charge of the drug, as well as by adding small amounts of charged amphiphiles. Moreover, these NPs may be delivered locally by immobilizing them in a hydrogel. Our studies show encapsulation within a calcium alginate hydrogel results in sustained release of the incorporated drug for more than 21 days. Such a nanoparticle-hydrogel composite drug delivery system is promising for treatment of long-lasting conditions such as cancer and chronic pain which require controlled, localized, and sustained drug release.

  2. Sustained release gastroretentive tablet of metformin hydrochloride based on poly (acrylic acid)-grafted-gellan.

    Science.gov (United States)

    Sarkar, Debjani; Nandi, Gouranga; Changder, Abhijit; Hudati, Prasenjit; Sarkar, Sayani; Ghosh, Lakshmi Kanta

    2017-03-01

    Development of a gastroretentive sustained release tablet of metformin based on poly (acrylic acid)-grafted-gellan (PAAc-g-GG) is the main purpose of this study. At first, PAAc-g-GG was synthesized by microwave-promoted free radical initiation method using cerric (IV) ammonium nitrate (CAN) as redox initiator and characterized by elemental analysis, FTIR, DSC-TGA, (13)C NMR, biodegradation and viscosity study. The synthetic parameters were optimized by 2(3) full factorial design using Design Expert software. Acute oral toxicity and histological studies were also performed as per OECD guideline. Tablets were then prepared employing wet granulation method using PAAc-g-GG and evaluated for various physical characters, in vitro drug release, ex-vivo mucoadhesion and swelling. Compatibility between drug and excipients was checked by DSC and FTIR analysis. The F3 batch showed excellent mucoadhesion and sustained drug release over a period of 10h with dissolution similarity factor, f2=77.43. Kinetic modeling unveiled Case-1 Fickian diffusion based drug release mechanism. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Chitosan-based nanoparticles as a sustained protein release carrier for tissue engineering applications.

    Science.gov (United States)

    Hou, Yaping; Hu, Junli; Park, Hyejin; Lee, Min

    2012-04-01

    Chitosan/tripolyphosphate/chondroitin sulfate (Chi/TPP/CS) nanoparticles were prepared by an ionic gelation method to obtain a controlled release of proteins. Using Nel-like molecule-1 (Nell-1), a novel osteogenic protein, as a model protein, it was demonstrated that adjusting the composition of the particles modulated the protein association and release kinetics of incorporated proteins. Increasing the amounts of Chi crosslinking agents, TPP and CS, in the particles achieved sustained protein release. An increase in crosslinking density decreased degradation rates of the particles. Furthermore, the bioactivity of the protein was preserved during the encapsulating procedure into the particles. To demonstrate the feasibility of Chi/TPP/CS nanoparticles as sustained release carriers for tissue engineering scaffold applications, protein-loaded nanoparticles were successfully incorporated into collagen hydrogels or prefabricated porous poly(lactide-co-glycolide) (PLGA) scaffolds without obstructing the integrity of the hydrogels or porous structure of the scaffolds. Thus, we expect that these particles have a potential for efficient protein carriers in tissue engineering applications, and will be further evaluated in vivo. Copyright © 2012 Wiley Periodicals, Inc.

  4. Physical solid-state properties and dissolution of sustained-release matrices of polyvinylacetate.

    Science.gov (United States)

    Gonzalez Novoa, Gelsys Ananay; Heinämäki, Jyrki; Mirza, Sabir; Antikainen, Osmo; Colarte, Antonio Iraizoz; Paz, Alberto Suzarte; Yliruusi, Jouko

    2005-02-01

    Solid-state compatibility and in vitro dissolution of direct-compressed sustained-release matrices of polyvinylacetate (PVAc) and polyvinylpyrrolidone (PVP) containing ibuprofen as a model drug were studied. Polyvinylalcohol (PVA) was used as an alternative water-soluble polymer to PVP. Differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD) were used for characterizing solid-state polymer-polymer and drug-polymer interactions. The mechanical treatment for preparing physical mixtures of polyvinyl polymers and the drug (i.e. simple blending or stressed cogrinding) was shown not to affect the physical state of the drug and the polymers. With the drug-polymer mixtures the endothermic effect due to drug melting was always evident, but a considerable modification of the melting point of the drug in physical binary mixtures (drug:PVP) was observed, suggesting some interaction between the two. On the other hand, the lack of a significant shift of the melting endothermic peak of the drug in physical tertiary drug-polymer mixtures revealed no evidence of solid-state interaction between the drug and the present polymers. Sustained-release dissolution profiles were achieved from the direct-compressed matrices made from powder mixtures of the drug and PVAc combined with PVP, and the proportion of PVAc in the mixture clearly altered the drug release profiles in vitro. The drug release from the present matrix systems is controlled by both diffusion of the drug through the hydrate matrix and the erosion of the matrix itself.

  5. Lenghty reverse poly(butylene oxide)-poly(ethylene oxide)-poly(butylene oxide) polymeric micelles and gels for sustained release of antifungal drugs.

    Science.gov (United States)

    Figueroa-Ochoa, Edgar B; Villar-Alvarez, Eva M; Cambón, Adriana; Mistry, Dharmista; Llovo, José; Attwood, David; Barbosa, Silvia; Soltero, J F Armando; Taboada, Pablo

    2016-08-20

    In this work, we present a detailed study of the potential application of polymeric micelles and gels of four different reverse triblock poly(butylene oxide)-poly(ethylene oxide)-poly(butylene oxide) copolymers (BOnEOmBOn, where n denotes the respective block lengths), specifically BO8EO90BO8, BO14EO378BO14, BO20EO411BO20 and BO21EO385BO21, as effective drug transport nanocarriers. In particular, we tested the use of this kind of polymeric nanostructures as reservoirs for the sustained delivery of the antifungals griseofulvin and fluconazole for oral and topical administration. Polymeric micelles and gels formed by these copolymers were shown to solubilize important amounts of these two drugs and to have a good stability in physiologically relevant conditions for oral or topical administration. These polymeric micellar nanocarriers were able to release drugs in a sustained manner, being the release rate slower as the copolymer chain hydrophobicity increased. Different sustained drug release profiles were observed depending on the medium conditions. Gel nanocarriers were shown to display longer sustained release rates than micellar formulations, with the existence of a pulsatile-like release mode under certain solution conditions as a result of their inner network structure. Certain bioadhesive properties were observed for the polymeric physical gels, being moderately tuned by the length and hydrophobicity of the polymeric chains. Furthermore, polymeric gels and micelles showed activity against the yeast Candida albicans and the mould demartophytes (Trichophyton rubrum and Microsporum canis) and, thus, may be useful for the treatment of different cutaneous fungal infections. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Sustained and controlled release of lipophilic drugs from a self-assembling amphiphilic peptide hydrogel

    DEFF Research Database (Denmark)

    Briuglia, Maria-Lucia; Urquhart, Andrew; Lamprou, Dimitrios A.

    2014-01-01

    Materials which undergo self-assembly to form supramolecular structures can provide alternative strategies to drug loading problems in controlled release application. RADA 16 is a simple and versatile self-assembling peptide with a designed structure formed of two distinct surfaces, one hydrophilic...... and one hydrophobic that are positioned in such a well-ordered fashion allowing precise assembly into a predetermined organization. A "smart" architecture in nanostructures can represent a good opportunity to use RADA16 as a carrier system for hydrophobic drugs solving problems of drugs delivery....... In this work, we have investigated the diffusion properties of Pindolol, Quinine and Timolol maleate from RADA16 in PBS and in BSS-PLUS at 37°C. A sustained, controlled, reproducible and efficient drug release has been detected for all the systems, which allows to understand the dependence of release kinetics...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-06-01

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

  8. Optimised process and formulation conditions for extended release dry polymer powder-coated pellets.

    Science.gov (United States)

    Terebesi, Ildikó; Bodmeier, Roland

    2010-05-01

    The objective of this study was to improve the film formation and permeability characteristics of extended release ethylcellulose coatings prepared by dry polymer powder coating for the release of drugs of varying solubility. Ethylcellulose (7 and 10 cp viscosity grades) and Eudragit(R) RS were used for dry powder coating of pellets in a fluidised bed ball coater. Pre-plasticised ethylcellulose powder was prepared by spray-drying aqueous ethylcellulose dispersions (Surelease(R) and Aquacoat(R)) or by hot melt extrusion/cryogenic grinding of plasticised ethylcellulose. Chlorpheniramine maleate and theophylline were used as model drugs of different solubilities. The film formation process, polymeric films and coated pellets were characterised by differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), scanning electron microscopy (SEM) and dissolution testing. Film formation and extended drug release was achieved with ethylcellulose, a polymer with a high glass transition temperature (T(g)) without the use of water, which is usually required in dry powder coating. DMA-measurements revealed that plasticised ethylcellulose had a modulus of elasticity (E') similar to the low T(g) Eudragit(R) RS. With increasing plasticiser concentration, the T(g) of ethylcellulose was reduced and the mechanical properties improved, thus facilitating coalescence of the polymer particles. SEM-pictures revealed the formation of a dense, homogeneous film. The lower viscosity grade ethylcellulose (7 cp) resulted in better film formation than the higher viscosity grade (10 cp) and required less stringent curing conditions. Successful extended release ethylcellulose coatings were also obtained by coating with pre-plasticised spray-dried ethylcellulose powders as an alternative to the separate application of pure ethylcellulose powder and plasticiser. The permeability of the extended release coating could be controlled by using powder blends of ethylcellulose with the

  9. Bupropion sustained release for pregnant smokers: a randomized, placebo-controlled trial.

    Science.gov (United States)

    Nanovskaya, Tatiana N; Oncken, Cheryl; Fokina, Valentina M; Feinn, Richard S; Clark, Shannon M; West, Holly; Jain, Sunil K; Ahmed, Mahmoud S; Hankins, Gary D V

    2017-04-01

    Bupropion is used to treat depression during pregnancy. However, its usefulness as a smoking cessation aid for pregnant women is not fully known. The objective of the study was to evaluate the preliminary efficacy of bupropion sustained release for smoking cessation during pregnancy. We conducted a randomized, prospective, double-blind, placebo-controlled, pilot trial. Pregnant women who smoked daily received individualized behavior counseling and were randomly assigned to a 12 week, twice-a-day treatment with 150 mg bupropion sustained release or placebo. The primary study objectives were to determine whether bupropion sustained release reduces nicotine withdrawal symptoms on the quit date and during the treatment period compared with placebo and whether it increases 7 day point prevalence abstinence at the end of the treatment period and at the end of pregnancy. Subjects in the bupropion (n = 30) and placebo (n = 35) groups were comparable in age, smoking history, number of daily smoked cigarettes, and nicotine dependence. After controlling for maternal age and race, bupropion sustained release reduced cigarette cravings (1.5 ± 1.1 vs 2.1 ± 1.2, P = .02) and total nicotine withdrawal symptoms (3.8 ± 4.3 vs 5.4 ± 5.1, P = .028) during the treatment period. Administration of bupropion sustained release reduced tobacco exposure, as determined by levels of carbon monoxide in exhaled air (7.4 ± 6.4 vs 9.1 ± 5.8, P = .053) and concentrations of cotinine in urine (348 ± 384 ng/mL vs 831 ± 727 ng/mL, P = .007) and increased overall abstinence rates during treatment (19% vs 2%, P = .003). However, there was no significant difference in 7 day point prevalence abstinence rates between the 2 groups at the end of medication treatment (17% vs 3%, P = .087) and at the end of pregnancy (10% vs 3%, P = .328). Individual smoking cessation counseling along with the twice-daily use of 150 mg bupropion

  10. Development of indomethacin sustained release microcapsules using chitosan-carboxymethylcellulose complex coacervation

    Directory of Open Access Journals (Sweden)

    Garnpimol C. Ritthidej

    2003-05-01

    Full Text Available Indomethacin sustained release microcapsules were prepared by complex coacervation of chitosan (CS and carboxymethylcellulose (CMC and then were hardened with glutaraldehyde (GA. The effects of concentration and pH of CS solution, amount of GA and hardening time on the physicochemical properties and drug release of these microcapsules were investigated. The SEM photomicrographs revealed that surface morphology of microcapsules depended on the pH of CS solution. Decreasing the pH increased the smoothness of the surface due to the relaxation of CS chain in acidic medium. The geometric mean diameters of the microcapsules were between 126-212 microns. Those prepared from CS solution of pH 4 and hardening time of 3 hours seemed to have the narrowest size distribution. The percent drug entrapment was comparable in the range of 40%-50% while the percent drug recovery varied between 60%-87%. The latter increased when decreasing the pH and increasing the concentration of CS solution but decreased when increasing the hardening time. Dissolution study showed that microcapsules prepared from CS solution of high pH initially released the drug faster than those from CS solution of lower pH. After 3 hours their release rate was similar.Increasing the amount of GA and hardening time decreased the drug release due to denser membrane. In contrast, the concentration of CS solution had no effect on drug release. The mechanism of drug release was prominently diffusion controlled through wall membrane and pore. The kinetics of drug release followed Higuchi’s model.

  11. Solid dispersion in the development of a nimodipine delayed-release tablet formulation

    Directory of Open Access Journals (Sweden)

    Yang Zhao

    2014-02-01

    Full Text Available Nimodipine (NMD is a dihydropyridine calcium channel blocker with selectivity for cerebral blood vessels and the major therapeutic indication of NMD is for the prevention and treatment of delayed ischemic neurological disorders and other cerebrovascular disorders, such as stroke which is associated with biological rhythm. This study was mainly designed to solve the drawback of conventional NMD solid dosage form, low bioavailability and limited clinical efficacy, by preparing enteric solid dispersion (SD and the SD was prepared via melting method. The physical state of the dispersed NMD in the polymer matrix was characterized by differential scanning calorimetry (DSC, powder X-ray diffraction (PXRD and dissolution studies. Compared with pure drug and physical mixture, the dissolution of NMD-SD was enhanced dramatically (about 80%. Furthermore, in consideration of the biological rhythm of stroke, we first obtained a delayed-release tablet containing NMD-SD by a direct powder compression method. As shown in the dissolution studies, the tablet released less than 10% in the artificial gastric acid in the initial 2 h and released 32.1%, 75%, more than 90% at 4, 10 and 14 h respectively in the artificial intestinal fluid. This investigation has solved the problems of oral solid dosage forms of NMD, and it has the good industry prospect.

  12. Sustained nitric oxide (NO)-releasing compound reverses dysregulated NO signal transduction in priapism

    Science.gov (United States)

    Lagoda, Gwen; Sezen, Sena F.; Hurt, K. Joseph; Cabrini, Marcelo R.; Mohanty, Dillip K.; Burnett, Arthur L.

    2014-01-01

    We evaluated the therapeutic potential of a sustained nitric oxide (NO)-releasing compound to correct the molecular hallmarks and pathophysiology of priapism, an important but poorly characterized erectile disorder. 1,5-Bis-(dihexyl-N-nitrosoamino)-2,4-dinitrobenzene (C6′) and an inactive form of the compound [1,5-bis-(dihexylamino)-2,4-dinitrobenzene (C6)] were tested in neuronal cell cultures and penile lysates for NO release (Griess assay) and biological activity (cGMP production). The effect of local depot C6′ or C6 was evaluated in mice with a priapic phenotype due to double neuronal and endothelial NO synthase deletion (dNOS−/−) or human sickle hemoglobin transgenic expression (Sickle). Changes in NO signaling molecules and reactive oxygen species (ROS) surrogates were assessed by Western blot. The physiological response after C6′ treatment was assessed using an established model of electrically stimulated penile erection. C6′ generated NO, increased cGMP, and dose dependently increased NO metabolites. C6′ treatment reversed abnormalities in key penile erection signaling molecules, including phosphodiesterase type 5, phosphorylated endothelial nitric oxide synthase, and phosphorylated vasodilator-stimulated phosphoprotein. In Sickle mice, C6′ also attenuated the increased ROS markers gp91phox, 4-hydroxynonenal, and 3-nitrotyrosine. Finally, C6′ corrected the excessive priapic erection response of dNOS−/− mice. Exogenous sustained NO release from C6′ corrects pathological erectile signaling in mouse models of priapism and suggests novel approaches to human therapy.—Lagoda, G., Sezen, S. F., Hurt, K. J., Cabrini, M. R., Mohanty, D. K., Burnett, A. L. Sustained nitric oxide (NO)-releasing compound reverses dysregulated NO signal transduction in priapism. PMID:24076963

  13. A simple and sensitive high-performance liquid chromatography method for determination of ciprofloxacin in bioavailability studies of conventional and gastroretentive prolonged-release formulations

    Directory of Open Access Journals (Sweden)

    Jaber Emami

    2016-01-01

    Conclusion: This validated HPLC method was successfully used for the determination of ciprofloxacin in human plasma following oral administration of controlled release formulation, conventional immediate-release tablets and when administered concomitantly with divalent and trivalent cations such as aluminum-, magnesium-, or calcium-containing products under which the bioavailability of ciprofloxacin is significantly reduced.

  14. A novel formulation of tigecycline has enhanced stability and sustained antibacterial and antileukemic activity.

    Directory of Open Access Journals (Sweden)

    Yulia Jitkova

    Full Text Available Tigecycline is a broad-spectrum, first-in-class glycylcycline antibiotic currently used to treat complicated skin and intra-abdominal infections, as well as community-acquired pneumonia. In addition, we have demonstrated that tigecycline also has in vitro and in vivo activity against acute myeloid leukemia (AML due to its ability to inhibit mitochondrial translation. Tigecycline is relatively unstable after reconstitution, and this instability may limit the use of the drug in ambulatory infusions for the treatment of infection and may prevent the development of optimal dosing schedules for the treatment of AML. This study sought to identify a formulation that improved the stability of the drug after reconstitution and maintained its antimicrobial and antileukemic activity. A panel of chemical additives was tested to identify excipients that enhanced the stability of tigecycline in solution at room temperature for up to one week. We identified a novel formulation containing the oxygen-reducing agents ascorbic acid (3 mg/mL and pyruvate (60 mg/mL, in saline solution, pH 7.0, in which tigecycline (1 mg/mL remained intact when protected from light for at least 7 days. This formulation also preserved the drug's antibacterial and antileukemic activity in vitro. Moreover, the novel formulation retained tigecycline's antileukemic activity in vivo. Thus, we identified and characterized a novel formulation for tigecycline that preserves its stability and efficacy after reconstitution.

  15. Preparation and characterization of silk fibroin hydrogel as injectable implants for sustained release of Risperidone.

    Science.gov (United States)

    Ebrahimi, Atefeh; Sadrjavadi, Komail; Hajialyani, Marziyeh; Shokoohinia, Yalda; Fattahi, Ali

    2018-02-01

    The principal objective of the present study is to achieve a depot formulation of Risperidone by gelation of silk fibroin (SF). For this purpose, hydrochloric acid (HCl)/acetone-based and methanol-based hydrogels were prepared with different drug/polymer ratios (1:3, 1:6, and 1:15). For all the drug-loaded methanol-based hydrogels, gel transition of SF solutions occurred immediately and the gelation time was 1 min, while the gelation time of HCL/acetone-based hydrogels was around 360 min. According to the results obtined from Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) spectra, solvent systems and Risperidone could induce β-sheet structure, but HCL/acetone system had the lowest effect on induction of β-sheets. The crystallinity was increased by increasing the amount of Risperidone, and drug to polymer ratio of 1:3 possessed the highest crystallinity. Thermogravimetric analysis (TGA) indicated that increasing the amount of drug in formulation increased the stability of hydrogels, and methanol-based hydrogel with a ratio of 1:3 had the most stable structure. The release rate of Risperidone from methanol-based hydrogel at ratio of 1:3 was lower than that for HCl/acetone-based one, and it decreased by increasing the amount of Risperidone. The release of Risperidone from methanol hydrogel at ratios 1:3 and 1:6 continued up to 25 d which is acceptable for depot form of Risperidone and shows that the extended release of Risperidone was achieved successfully. In conclusion, SF hydrogel with the ability to respond to the environmental stimuli is an excellent candidate for injectable implants for extended release of Risperidone.

  16. PLGA-Based Microparticles for the Sustained Release of BMP-2

    Directory of Open Access Journals (Sweden)

    Maria A. Woodruff

    2011-03-01

    Full Text Available The development of growth factor delivery strategies to circumvent the burst release phenomenon prevalent in most current systems has driven research towards encapsulating molecules in resorbable polymer matrices. For these polymer release techniques to be efficacious in a clinical setting, several key points need to be addressed. This present study has investigated the encapsulation of the growth factor, BMP-2 within PLGA/PLGA-PEG-PLGA microparticles. Morphology, size distribution, encapsulation efficiency and release kinetics were investigated and we have demonstrated a sustained release of bioactive BMP-2. Furthermore, biocompatibility of the PLGA microparticles was established and released BMP-2 was shown to promote the differentiation of MC3T3-E1 cells towards the osteogenic lineage to a greater extent than osteogenic supplements (as early as day 10 in culture, as determined using alkaline phosphatase and alizarin red assays. This study showcases a potential BMP-2 delivery system which may now be translated into more complex delivery systems, such as 3D, mechanically robust scaffolds for bone tissue regeneration applications.

  17. Polyacrylamide-chitosan hydrogels: in vitro biocompatibility and sustained antibiotic release studies.

    Science.gov (United States)

    Risbud, M V; Bhonde, R R

    2000-01-01

    Controlled drug delivery is gaining importance over the conventional methods of drug administration because of its inherent benefits. Self-regulated release from the delivery vehicle may enhance drug potency with a sustained action. The present study describes a novel hydrogel blend of polyacrylamide with chitosan for controlled delivery of antibiotics. Hydrogel was synthesized by cross-linking acrylamide-chitosan mixture (8:2 v/v) with N,N' methylene bisacrylamide. Hydrogel was characterized for surface morphology, hydrophilicity, pH-dependent swelling properties, cytotoxicity, and control release properties. Scanning electron microscopy (SEM) revealed the macroporous surface morphology of the matrix with average pore size at 104 +/- 7.61 mu. Hydrogel was found to be highly hydrophilic as assessed by octane contact angle (154.5 + 0.572) measurement. Hydrogel showed no cytotoxic effects on NIH3T3 and HeLa cells up to 40% of extract concentrations as determined by MTT and neutral red assay. This showed hydrogel biocompatibility and thus absence of deleterious effects of the hydrogel on cell viability and functionality. Hydrogels did not show any pH-dependent swelling profile, and they swelled considerably to achieve a swelling ratio of approximately 16.0 at the end of 24 hr. Amoxicillin was incorporated in the hydrogel matrix as a candidate antibiotic for release studies. In vitro release studies of amoxicillin revealed the sustained nature of delivery and matrix released 56.47 + 1.12% and 77.096 + 1.72% of amoxicillin at the end of 24 and 75 hr, respectively. Although in vivo studies are awaited, the present study provides enough documentation to consider polyacrylamide-chiotsan hydrogel as a possible candidate for controlled delivery of antibiotics.

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

    Directory of Open Access Journals (Sweden)

    Claudia Weber

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Hong Lei

    2016-05-01

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

  20. Calcium-Alginate Hydrogel-Encapsulated Fibroblasts Provide Sustained Release of Vascular Endothelial Growth Factor

    Science.gov (United States)

    Hunt, Nicola C.; Shelton, Richard M.; Henderson, Deborah J.

    2013-01-01

    Vascularization of engineered or damaged tissues is essential to maintain cell viability and proper tissue function. Revascularization of the left ventricle (LV) of the heart after myocardial infarction is particularly important, since hypoxia can give rise to chronic heart failure due to inappropriate remodeling of the LV after death of cardiomyocytes (CMs). Fibroblasts can express vascular endothelial growth factor (VEGF), which plays a major role in angiogenesis and also acts as a chemoattractant and survival factor for CMs and cardiac progenitors. In this in vitro model study, mouse NIH 3T3 fibroblasts encapsulated in 2% w/v Ca-alginate were shown to remain viable for 150 days. Semiquantitative reverse transcription–polymerase chain reaction and immunohistochemistry demonstrated that over 21 days of encapsulation, fibroblasts continued to express VEGF, while enzyme-linked immunosorbent assay showed that there was sustained release of VEGF from the Ca-alginate during this period. The scaffold degraded gradually over the 21 days, without reduction in volume. Cells released from the Ca-alginate at 7 and 21 days as a result of scaffold degradation were shown to retain viability, to adhere to fibronectin in a normal manner, and continue to express VEGF, demonstrating their potential to further contribute to maintenance of cardiac function after scaffold degradation. This model in vitro study therefore demonstrates that fibroblasts encapsulated in Ca-alginate provide sustained release of VEGF. PMID:23082964

  1. 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.

  2. Effect of formulation parameters on the drug release and floating properties of gastric floating two-layer tablets with acetylsalicylic acid.

    Science.gov (United States)

    Hasçiçek, Canan; Yüksel-Tilkan, Günseli; Türkmen, Berna; Ozdemir, Nurten

    2011-09-01

    Floating dosage forms of acetylsalicylic acid, used for its antithrombotic effect, were developed to prolong gastric residence time and increase bioavailability. In the two-layer tablet formulation, hydroxypropyl methylcellulose (HPMC) of high viscosity and an effervescent mixture of citric acid and sodium bicarbonate formed the floating layer. The release layer contained the drug, direct tableting agent and different types of matrix-forming polymers such as HPMC of low viscosity, sodium carboxymethylcellulose and chitosan. Tablets were prepared using a direct compression technique. The effect of formulation variables on physicochemical and floating properties and the drug release from tablets were investigated. Floating ability was dependent on the amount of effervescent agent and gel-forming polymer of the floating layer. Drug release was prolonged to 8 hours by changing the type and viscosity of the matrix-forming polymer in the drug-loading layer and all formulations showed a diffusion release mechanisms.

  3. In vitro Evaluation of Nateglinide-Loaded Microspheres Formulated ...

    African Journals Online (AJOL)

    Purpose: To formulate and evaluate sustained release microspheres of nateglinide (NTG) for enhanced patient compliance. Methods: Nateglinide microspheres were prepared with varying proportions of biodegradable polymers (olibanum gum and guar gum) by calcium chloride/sodium alginate ionic gelation method.

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

    Science.gov (United States)

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

    2017-10-01

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

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

    Science.gov (United States)

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

    2017-10-21

    The primary aim of this study was to identify pharmaceutically acceptable amorphous polymers for producing 3D printed tablets of a model drug, haloperidol, for rapid release by fused deposition modeling (FDM). Filaments for 3D printing were prepared by hot melt extrusion at 150°C with 10 and 20% w/w of haloperidol using Kollidon(®) VA64, Kollicoat(®) IR, Affinsiol(™)15 cP and HPMCAS either individually or as binary blends (Kollidon(®) VA64+Affinisol(™)15 cP, 1:1; Kollidon(®) VA64+HPMCAS, 1:1). Dissolution of crushed extrudates was studied at pH 2 and 6.8, and formulations demonstrating rapid dissolution rates were then analyzed for drug-polymer, polymer-polymer and drug-polymer-polymer miscibility by film casting. Polymer-polymer (1:1) and drug-polymer-polymer (1:5:5 and 2:5:5) mixtures were found to be miscible. Tablets with 100 and 60 % infill were printed using MakerBot printer at 210°C, and dissolution tests of tablets were conducted at pH 2 and 6.8. Extruded filaments of Kollidon(®) VA64-Affinisol(™)15 cP mixtures were flexible and had optimum mechanical strength for 3D printing. Tablets containing 10% drug with 60 and 100% infill showed complete drug release at pH 2 in 45 and 120 min, respectively. Relatively high dissolution rates were also observed at pH 6.8. The 1:1-mixture of Kollidon(®) VA64 and Affinisol(™)15 cP was thus identified as a suitable polymer system for 3D printing and rapid drug release. Copyright © 2017. Published by Elsevier Inc.

  6. 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

  7. Modular approach for bimodal antibacterial surfaces combining photo-switchable activity and sustained biocidal release.

    Science.gov (United States)

    Pallavicini, Piersandro; Bassi, Barbara; Chirico, Giuseppe; Collini, Maddalena; Dacarro, Giacomo; Fratini, Emiliano; Grisoli, Pietro; Patrini, Maddalena; Sironi, Laura; Taglietti, Angelo; Moritz, Marcel; Sorzabal-Bellido, Ioritz; Susarrey-Arce, Arturo; Latter, Edward; Beckett, Alison J; Prior, Ian A; Raval, Rasmita; Diaz Fernandez, Yuri A

    2017-07-12

    Photo-responsive antibacterial surfaces combining both on-demand photo-switchable activity and sustained biocidal release were prepared using sequential chemical grafting of nano-objects with different geometries and functions. The multi-layered coating developed incorporates a monolayer of near-infrared active silica-coated gold nanostars (GNS) decorated by silver nanoparticles (AgNP). This modular approach also enables us to unravel static and photo-activated contributions to the overall antibacterial performance of the surfaces, demonstrating a remarkable synergy between these two mechanisms. Complementary microbiological and imaging evaluations on both planktonic and surface-attached bacteria provided new insights on these distinct but cooperative effects.

  8. Levels of sirolimus in saliva and blood following oral topical sustained-release varnish delivery system application.

    Science.gov (United States)

    Nudelman, Zakhar; Findler, Mordechai; Barasch, Dinorah; Nemirovski, Alina; Pikovsky, Anna; Kirmayer, David; Basheer, Maamoun; Gutkind, J Silvio; Friedman, Michael; Czerninski, Rakefet

    2015-05-01

    Sirolimus (rapamycin) is a mammalian target of rapamycin pathway blocker. The efficacy of sirolimus is currently studied for its antiproliferative properties in various malignancies and particularly in squamous cell carcinoma and other oral disorders. Topical application at the oral cavity can augment sirolimus availability at the site of action by increasing sirolimus levels in saliva and hence efficacy, along with improved safety (low levels in the blood to avoid side effects) and compliance. Our purpose was to evaluate the release profile and safety of a topical sirolimus sustained-release varnish drug delivery system. Sirolimus sustained-release varnish drug delivery system containing a total of 0.5 mg of the drug was applied to nine healthy male volunteers. Saliva and blood levels were determined utilizing mass spectrometry and chemiluminescent microparticle immunoassay, respectively. The prolonged release profile and safety were evaluated for the oral topical delivery system. After the application of the drug delivery system, a sustained-release profile was observed in the oral cavity. We have measured moderate sirolimus levels for up to 12 h. The safety was confirmed, and systemic sirolimus blood levels were negligible. After an application of sirolimus sustained-release varnish drug delivery system, prolonged drug levels can be achieved in the saliva. The oral topical sirolimus concentrations were potentially therapeutic along with minimal systemic exposure. These results broaden the potential clinical use of sustained-release oral topical rapalogs.

  9. Comparison of single-dose and multiple-dose pharmacokinetics between two formulations of hydrocodone bitartrate/acetaminophen: immediate-release versus biphasic immediate- release/extended release

    Directory of Open Access Journals (Sweden)

    Devarakonda K

    2015-09-01

    Full Text Available Krishna Devarakonda,1 Kenneth Kostenbader,2 Michael J Giuliani,3 Jim L Young4 1Department of Clinical Pharmacology, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA; 2Independent Pharmaceuticals Professional, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA; 3Research and Development, 4Clinical Affairs and Program Management, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA Objective: This study aimed to compare the single-dose and steady-state pharmacokinetics (PK of biphasic immediate-release (IR/extended-release (ER hydrocodone bitartrate (HB/acetaminophen (APAP and IR HB/APAP. Setting: The study was conducted in a contract research center. Participants: The study included healthy adults. Interventions: In a three-way crossover study, Study 1, participants received the following treatments: (A1 a single dose of IR/ER HB/APAP 7.5/325 mg one tablet, followed by one tablet every 12 hours (q12h; (B1 a single dose of IR/ER HB/APAP 7.5/325 mg two tablets, followed by two tablets q12h; (C1 a single dose of IR HB/APAP 7.5/325 mg two tablets (one tablet at hours 0 and 6, followed by one tablet q6h. In a two-way crossover study, Study 2, participants received the following treatments: (A2 an initial dose of IR/ER HB/APAP 7.5/325 mg three tablets, followed by two tablets q12h; (B2 three doses of IR HB/APAP 7.5/325 mg one tablet q4h, followed by one tablet q6h. Main outcome measures: PK values were compared, and adverse events were assessed. Results: Single-dose and steady-state area under the concentration–time curves for hydrocodone and APAP were similar for IR/ER and IR HB/APAP; the steady-state peak plasma concentrations (Cmax at steady state were also similar, but single-dose Cmax for hydrocodone was lower for IR/ER HB/APAP. For most PK parameters, 90% confidence intervals for geometric least squares mean ratios were not meaningfully different (80%–125%. Steady state was achieved in 2-3 days for IR/ER HB/APAP and in 2 days for IR HB/APAP. Median

  10. Sustained release of antibiotic from poly(2-hydroxyethyl methacrylate) to prevent blinding infections after cataract surgery.

    Science.gov (United States)

    Anderson, Erin M; Noble, Misty L; Garty, Shai; Ma, Hongyan; Bryers, James D; Shen, Tueng T; Ratner, Buddy D

    2009-10-01

    Intraocular lens implantation after opacified natural lens removal is the primary treatment for cataracts in developed countries. Cataract surgery is generally considered safe, but entails significant risks in countries where sophisticated sterile operating theaters are not widely available. Post-operative infection (endophthalmitis) is a potential blinding complication. Infection often results from bacterial colonization of the new lens implant and subsequent antibiotic-tolerant biofilm formation. To combat this risk, we developed a polymeric hydrogel system that can deliver effective levels of antibiotic over an extended period of time within the globe of the eye. Norfloxacin antibiotic was loaded into cross-linked poly(2-hydroxyethyl methacrylate) (pHEMA) gels, which were subsequently surface-modified with octadecyl isocyanate to produce a hydrophobic rate-limiting barrier controlling norfloxacin release. Octadecyl surface modification was characterized using scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). A 15-min modification leads to a uniform surface coating and near zero order release of norfloxacin from the matrix. Norfloxacin released from coated pHEMA kills Staphylococcus epidermidis in suspension and on a simulated medical implant surface. With these data, we demonstrate a new and effective system for sustained drug release from a hydrogel matrix with specific application for intraocular lens surgery.

  11. Polycaprolactone scaffold engineered for sustained release of resveratrol: therapeutic enhancement in bone tissue engineering

    Science.gov (United States)

    Kamath, Manjunath Srinivas; Ahmed, Shiek SSJ; Dhanasekaran, M; Santosh, S Winkins

    2014-01-01

    Biomaterials-based three-dimensional scaffolds are being extensively investigated in bone tissue engineering. A potential scaffold should be osteoconductive, osteoinductive, and osteogenic for enhanced bone formation. In this study, a three-dimensional porous polycapro-lactone (PCL) scaffold was engineered for prolonged release of resveratrol. Resveratrol-loaded albumin nanoparticles (RNP) were synthesized and entrapped into a PCL scaffold to form PCL-RNP by a solvent casting and leaching method. An X-ray diffraction study of RNP and PCL-RNP showed that resveratrol underwent amorphization, which is highly desired in drug delivery. Furthermore, Fourier transform infrared spectroscopy indicates that resveratrol was not chemically modified during the entrapment process. Release of resveratrol from PCL-RNP was sustained, with a cumulative release of 64% at the end of day 12. The scaffold was evaluated for its bone-forming potential in vitro using human bone marrow-derived mesenchymal stem cells for 16 days. Alkaline phosphatase activity assayed on days 8 and 12 showed a significant increase in activity (1.6-fold and 1.4-fold, respectively) induced by PCL-RNP compared with the PCL scaffold (the positive control). Moreover, von Kossa staining for calcium deposits on day 16 showed increased mineralization in PCL-RNP. These results suggest PCL-RNP significantly improves mineralization due to its controlled and prolonged release of resveratrol, thereby increasing the therapeutic potential in bone tissue engineering. PMID:24399875

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

    Science.gov (United States)

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

    2015-04-01

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

  13. Freeze-dried mucoadhesive polymeric system containing pegylated lipoplexes: Towards a vaginal sustained released system for siRNA.

    Science.gov (United States)

    Furst, Tania; Dakwar, George R; Zagato, Elisa; Lechanteur, Anna; Remaut, Katrien; Evrard, Brigitte; Braeckmans, Kevin; Piel, Geraldine

    2016-08-28

    Topical vaginal sustained delivery of siRNA presents a significant challenge due to the short residence time of formulations. Therefore, a drug delivery system capable to adhere to the vaginal mucosa is desirable, as it could allow a prolonged delivery and increase the effectiveness of the therapy. The aim of this project is to develop a polymeric solid mucoadhesive system, loaded with lipoplexes, able to be progressively rehydrated by the vaginal fluids to form a hydrogel and to deliver siRNA to vaginal tissues. To minimize adhesive interactions with vaginal mucus components, lipoplexes were coated with different derivatives of polyethylene glycol: DPSE-PEG2000, DPSE-PEG750 and ceramide-PEG2000. Based on stability and diffusion properties in simulated vaginal fluids, lipoplexes containing DSPE-PEG2000 were selected and incorporated in hydroxyethyl cellulose (HEC) hydrogels. Solid systems, called sponges, were then obtained by freeze-drying. Sponges meet acceptable mechanical characteristics and their hardness, deformability and mucoadhesive properties are not influenced by the presence of lipoplexes. Finally, mobility and stability of lipoplexes inside sponges rehydrated with vaginal mucus, mimicking in situ conditions, were evaluated by advanced fluorescence microscopy. The release rate was found to be influenced by the HEC concentration and consequently by the viscosity after rehydration. This study demonstrates the feasibility of entrapping pegylated lipoplexes into a solid matrix system for a prolonged delivery of siRNA into the vagina. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Antinociceptive effects of sustained-release buprenorphine in a model of incisional pain in rats (Rattus norvegicus).

    Science.gov (United States)

    Chum, Helen H; Jampachairsri, Katechan; McKeon, Gabriel P; Yeomans, David C; Pacharinsak, Cholawat; Felt, Stephen A

    2014-03-01

    Effective management of postoperative pain is an essential component of the care and welfare of laboratory animals. A sustained-release formulation of buprenorphine (Bup-SR) has recently been introduced to the veterinary market and has been reported to provide analgesia for as long as 72 h. Using evoked mechanical and thermal hypersensitivity tests, we here evaluated the antinociceptive effects of Bup-SR in a model of incisional pain in rats. Paw withdrawal responses were obtained before and 1 through 4 d after surgery. Rats are assigned to receive Bup-SR (0.3, 1.2, or 4.5 mg/kg SC once) or buprenorphine HCl (Bup HCl, 0.05 mg/kg SC twice daily for 3 d). Responses to mechanical and thermal stimuli in the 1.2 and 4.5 Bup-SR groups did not differ from those of rats in the Bup HCl group. Thermal latency on day 3 in rats that received 0.3 mg/kg Bup-SR was significantly different from baseline, indicating that this dose effectively decreased thermal hypersensitivity for at least 48 h. Marked sedation occurred in rats in the 4.5 Bup-SR group. Our findings indicate that Bup-SR at 0.3 or 1.2 mg/kg SC is effective in minimizing hypersensitivity with minimal sedation for at least 48 h (thermal hypersensitivity) and 72 h, respectively, in the incisional pain model in rats.

  15. 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.

  16. Current and future development of extended-release, abuse-deterrent opioid formulations in the United States.

    Science.gov (United States)

    Webster, Lynn R; Markman, John; Cone, Edward J; Niebler, Gwendolyn

    2017-01-01

    Prescription opioid misuse and abuse in the United States (US) is epidemic and is a major burden on health-care resources and costs to society. The need to significantly reduce the risks of prescription opioid misuse and abuse must be balanced with the important needs of patients with chronic pain who may benefit from treatment with opioids. The use of abuse-deterrent formulations (ADFs) of prescription opioids is one approach that could reduce the risk of prescription opioid abuse and misuse while maintaining access to opioids. ADF opioids have properties that make their abuse more difficult, less attractive, or less rewarding. In 2015, the US Food and Drug Administration issued final guidance to industry for the development of ADF opioids that recommended specific studies be conducted to demonstrate the abuse-deterrent properties of new opioid formulations. The technologies and the preclinical and clinical development of ADF opioids are rapidly evolving. This review provides an overview of the required testing for product labeling that includes language about the abuse-deterrent features of an ADF opioid. The objective of this review is to inform and help health-care providers understand the unique development of extended-release ADF opioids and their place in the treatment of patients with pain.

  17. Pharmacokinetics of a Novel Anagrelide Extended-Release Formulation in Healthy Subjects: Food Intake and Comparison With a Reference Product.

    Science.gov (United States)

    Petrides, Petro E; Schoergenhofer, Christian; Widmann, Rudolf; Jilma, Bernd; Klade, Christoph S

    2018-02-01

    Anagrelide is an established therapy for essential thrombocythemia. Common adverse effects have been linked to peak plasma concentrations of anagrelide and its 3OH metabolite. Our study was performed to investigate the pharmacokinetics (PK) of a novel anagrelide extended-release (AER) formulation and its active metabolites. Thirty healthy volunteers were randomized to receive either 2 mg AER (under fasting and fed conditions) or 2 mg commercially available reference product (CARP) in an open-label, 3-way crossover trial with washout periods of 6 days. Plasma concentrations of anagrelide and its active metabolites were assessed by tandem mass spectrometry. The PK differed significantly between all treatment periods. Bioavailability of AER was 55% of the CARP under fasting conditions and 60% under fed conditions. C max , AUCt, and AUC∞ were significantly higher and T max and T 1/2 were significantly shorter after the CARP compared with AER. Food had a significant impact on the PK of AER, increasing the C max and AUC t while reducing the T 1/2 , plateau, and mean residence time. Both formulations were well tolerated, with a trend toward more frequently occurring adverse events after the CARP. The PK of AER and the CARP differed significantly in all parameters. Food enhanced the bioavailability of AER. © 2017, The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

  18. Pharmacokinetics of a Novel Anagrelide Extended‐Release Formulation in Healthy Subjects: Food Intake and Comparison With a Reference Product

    Science.gov (United States)

    Petrides, Petro E.; Schoergenhofer, Christian; Widmann, Rudolf; Klade, Christoph S.

    2017-01-01

    Abstract Anagrelide is an established therapy for essential thrombocythemia. Common adverse effects have been linked to peak plasma concentrations of anagrelide and its 3OH metabolite. Our study was performed to investigate the pharmacokinetics (PK) of a novel anagrelide extended‐release (AER) formulation and its active metabolites. Thirty healthy volunteers were randomized to receive either 2 mg AER (under fasting and fed conditions) or 2 mg commercially available reference product (CARP) in an open‐label, 3‐way crossover trial with washout periods of 6 days. Plasma concentrations of anagrelide and its active metabolites were assessed by tandem mass spectrometry. The PK differed significantly between all treatment periods. Bioavailability of AER was 55% of the CARP under fasting conditions and 60% under fed conditions. Cmax, AUCt, and AUC∞ were significantly higher and Tmax and T1/2 were significantly shorter after the CARP compared with AER. Food had a significant impact on the PK of AER, increasing the Cmax and AUCt while reducing the T1/2, plateau, and mean residence time. Both formulations were well tolerated, with a trend toward more frequently occurring adverse events after the CARP. The PK of AER and the CARP differed significantly in all parameters. Food enhanced the bioavailability of AER. PMID:28301098

  19. Effects of naltrexone sustained-release/bupropion sustained-release combination therapy on body weight and glycemic parameters in overweight and obese patients with type 2 diabetes.

    Science.gov (United States)

    Hollander, Priscilla; Gupta, Alok K; Plodkowski, Raymond; Greenway, Frank; Bays, Harold; Burns, Colleen; Klassen, Preston; Fujioka, Ken

    2013-12-01

    To assess the efficacy and safety of 32 mg naltrexone sustained-release (SR)/360 mg bupropion SR (NB) in overweight/obese individuals with type 2 diabetes with or without background oral antidiabetes drugs. This was a 56-week, double-blind, placebo-controlled study in which 505 patients received standardized lifestyle intervention and were randomized 2:1 to NB or placebo. Coprimary end points were percent weight change and achievement of ≥5% weight loss. Secondary end points included achievement of HbA1c blood glucose, and lipids. In the modified intent-to-treat population (54% female, 80% Caucasian, and mean age 54 years, weight 106 kg, BMI 37 kg/m(2), and HbA1c 8.0% [64 mmol/mol]), NB resulted in significantly greater weight reduction (-5.0 vs. -1.8%; P select cardiovascular risk factors and was generally well tolerated with a safety profile similar to that in patients without diabetes.

  20. 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.

  1. Erroneous formulation of delayed-release omeprazole capsules: alert for importing countries.

    Science.gov (United States)

    Rahman, Mohammad Sofiqur; Yoshida, Naoko; Tsuboi, Hirohito; Keila, Tep; Sovannarith, Tey; Kiet, Heng Bun; Dararth, Eav; Zin, Theingi; Tanimoto, Tsuyoshi; Kimura, Kazuko

    2017-05-03

    Poor drug quality is a matter of serious concern, especially in countries where drug regulation and law enforcement are constrained by limited resources. This study was carried out to investigate the cause of quality failure of omeprazole in Cambodia in 2010 and Myanmar in 2014. We conducted pharmacopoeial quantity, content uniformity and dissolution tests of 156 samples of omeprazole capsules collected in Cambodia in 2010 and Myanmar in 2014. High failure rates were found, especially in dissolution testing, and detailed investigation of several unacceptable samples was carried out by means of in-vitro dissolution profiling, scanning electron microscopy (SEM) and X-ray computed tomography (X-ray CT) to identify the cause of failure. Dissolution profiling with and without the acid stage showed that acid caused premature omeprazole release, indicating that the enteric coating of the omeprazole granules was ineffective. SEM examination of two failed samples revealed cracked and broken granules mixed with apparently intact omeprazole granules in the capsule. X-ray CT examination indicated that some granules of failed samples completely lacked enteric coating, and others had incomplete and non-uniform enteric coating or malformation. Omeprazole capsules collected in Myanmar and Cambodia showed high failure rates in pharmacopoeial tests, especially dissolution tests. Some samples were found to have ineffective or absent enteric coating of the granules, resulting in premature dissolution and degradation in acidic conditions. This is a potentially serious public health issue that needs to be addressed by regulatory authorities in Cambodia and Myanmar, possibly through a collaborative initiative with manufacturers.

  2. 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

  3. Development of solid SEDDS, VII: Effect of pore size of silica on drug release from adsorbed self-emulsifying lipid-based formulations.

    Science.gov (United States)

    Gumaste, Suhas G; Serajuddin, Abu T M

    2017-12-15

    Lipid-based self-emulsifying drug delivery systems (SEDDS) are usually liquids, and they can be converted into solid dosage forms by adsorbing onto silicates. However, most commercially available silicates are mesoporous with small pore sizes of 1 to 50nm that lead to incomplete emulsification of SEDDS inside the pores and thus incomplete drug release. The objective of this study was to investigate the impact of silica pore size on the extent of drug release from SEDDS solidified by adsorbing onto macroporous silicas with different pore sizes. Silicas with average pore sizes of approx. 150nm, 500nm and 5μm were synthesized using the colloidal crystal templating method. A model poorly water-soluble drug, probucol, was dissolved in liquid SEDDS containing different lipid to surfactant ratios, and the formulations were then adsorbed onto equal weights of silicas (1:1 w/w ratio). Drug release from freshly prepared formulations and after storing at 40°C/60% RH for up to 6months was studied using a modified USP type 2 method with mini paddles and 50mL of 0.01M HCl (pH~2) at 37°C. Drug release was also studied similarly from silicas that were precoated with PVP K-30 at 5, 10, 20 and 30% w/w levels before adsorption of SEDDS. Freshly prepared formulations containing relatively higher lipid:surfactant ratio of 7:3% w/w exhibited 17, 40 and 60% drug release from uncoated (neat) silicas with pore sizes of 150nm, 500nm and 5μm, respectively, while the more hydrophilic formulations containing 3:7 w/w lipid:surfactant ratio had, respectively, 50, 65 and 85% drug release. No decrease in drug release was observed when the formulations were exposed to 40°C/60% RH for up to 6months. When the silicas were precoated with 20% PVP, the drug release was almost complete (>80%), which remained unchanged even after 6months of storage irrespective of the composition of adsorbed liquid SEDDS. Both pore size and composition of SEDDS had major impacts on drug release from silicas

  4. 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.

  5. Sustained Release of Prindopril Erbumine from Its Chitosan-Coated Magnetic Nanoparticles for Biomedical Applications

    Directory of Open Access Journals (Sweden)

    Dena Dorniani

    2013-12-01

    Full Text Available The preparation of magnetic nanoparticles coated with chitosan-prindopril erbumine was accomplished and confirmed by X-ray diffraction, TEM, magnetic measurements, thermal analysis and infrared spectroscopic studies. X-ray diffraction and TEM results demonstrated that the magnetic nanoparticles were pure iron oxide phase, having a spherical shape with a mean diameter of 6 nm, compared to 15 nm after coating with chitosan-prindopril erbumine (FCPE. Fourier transform infrared spectroscopy study shows that the coating of iron oxide nanoparticles takes place due to the presence of some bands that were emerging after the coating process, which belong to the prindopril erbumine (PE. The thermal stability of the PE in an FCPE nanocomposite was remarkably enhanced. The release study showed that around 89% of PE could be released within about 93 hours by a phosphate buffer solution at pH 7.4, which was found to be of sustained manner governed by first order kinetic. Compared to the control (untreated, cell viability study in 3T3 cells at 72 h post exposure to both the nanoparticles and the pure drug was found to be sustained above 80% using different doses.

  6. Poloxamer-hydroxyethyl cellulose-α-cyclodextrin supramolecular gels for sustained release of griseofulvin.

    Science.gov (United States)

    Marcos, Xelhua; Pérez-Casas, Silvia; Llovo, José; Concheiro, Angel; Alvarez-Lorenzo, Carmen

    2016-03-16

    Supramolecular gels of poloxamer-hydroxyethyl cellulose (HEC)-α-cyclodextrin (αCD) were developed aiming to obtain synergisms regarding solubilization and sustained release of griseofulvin for topical application. The effects of αCD concentration (0-10%w/w) on the phase behavior of aqueous dispersions of Pluronic(®) P123 (14%w/w) mixed with HEC (2%w/w) were evaluated at 4, 20 and 37°C. The cooperative effects of the inclusion complex formation between poly(ethylene oxide) (PEO) blocks and HEC with αCD prevented phase separation and led to supramolecular networks that solubilize the antifungal drug. Rheological and bioadhesive properties of gels with and without griseofulvin could be easily tuned modulating the polymers proportions. Supramolecular gels underwent sol-gel transition at lower temperature than P123 solely dispersions and enabled drug sustained release for at least three weeks. All gels demonstrated good biocompatibility in the HET-CAM test. Furthermore, the drug-loaded gels showed activity against Trichophyton rubrum and Trichophyton mentagrophytes and thus may be useful for the treatment of tinea capitis and other cutaneous fungal infections. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Higher quality quercetin sustained release ethyl cellulose nanofibers fabricated using a spinneret with a Teflon nozzle.

    Science.gov (United States)

    Li, Chen; Wang, Zhuan-Hua; Yu, Deng-Guang

    2014-02-01

    This study investigates the usage of a spinneret with a Teflon nozzle for fabrication of higher quality drug sustained-release electrospun nanofibers. Ethyl cellulose (EC) and quercetin were used as a filament-forming polymer matrix and an active pharmaceutical ingredient, respectively. The electrospinning was conducted using both a traditional stainless steel spinneret and a spinneret with a Teflon nozzle. Experimental results demonstrated that a Teflon-fluid interface at the spinneret's nozzle provided a better performance for implementing electrospinning than a traditional metal-fluid interface in the following aspects: (1) keeping more electrical energy on the working fluids for an efficacious process; (2) exerting less negative effect on the fluid to draw it back to the tube; and (3) making less possibility of clogging. The resulted nanofibers from the spinneret with a Teflon nozzle exhibited higher quality than those from the traditional spinneret in those: (1) smaller diameter and narrower distribution, 520±70 nm for the former and 750±280 nm for the later, as indicated by the field emission scanning electron microscopic images; and (2) better sustained-release profiles of quercetin from the former than the latter, as demonstrated by the in vitro dissolution tests. The new protocols about usage of Teflon as a spinneret's nozzle and the related knowledge disclosed here should promote the preparation and application of electrospun functional nanofibers. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. 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

    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...... as amorphous state. The release profiles and content of the microspheres stored at a temperature of 40 degrees C and a relative humidity of 75% were unchanged during 3 months of accelerating condition of storage. And the relative bioavailability of the sustained-release microspheres compared with the Baypress...

  9. Sustained release of a p38 inhibitor from non-inflammatory microspheres inhibits cardiac dysfunction

    Science.gov (United States)

    Sy, Jay C.; Seshadri, Gokulakrishnan; Yang, Stephen C.; Brown, Milton; Oh, Teresa; Dikalov, Sergey; Murthy, Niren; Davis, Michael E.

    2008-11-01

    Cardiac dysfunction following acute myocardial infarction is a major cause of death in the world and there is a compelling need for new therapeutic strategies. In this report we demonstrate that a direct cardiac injection of drug-loaded microparticles, formulated from the polymer poly(cyclohexane-1,4-diylacetone dimethylene ketal) (PCADK), improves cardiac function following myocardial infarction. Drug-delivery vehicles have great potential to improve the treatment of cardiac dysfunction by sustaining high concentrations of therapeutics within the damaged myocardium. PCADK is unique among currently used polymers in drug delivery in that its hydrolysis generates neutral degradation products. We show here that PCADK causes minimal tissue inflammatory response, thus enabling PCADK for the treatment of inflammatory diseases, such as cardiac dysfunction. PCADK holds great promise for treating myocardial infarction and other inflammatory diseases given its neutral, biocompatible degradation products and its ability to deliver a wide range of therapeutics.

  10. 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.

  11. Tablets compressed with gastric floating pellets coated with acrylic resin for gastro retention and sustained release of famotidine: in-vitro and in-vivo study.

    Science.gov (United States)

    Qi, Xiaole; Jiang, Yingchun; Zhang, Huiting; Wu, Zhenghong

    2015-04-01

    The aim of this study was to prepare a disintegrating gastric floating tablet composed of floating pellets coated with acrylic resin to prolong the gastric residence time and increase the oral bioavailability of famotidine. The gastric floating pellets containing famotidine, stearyl alcohol and microcrystalline cellulose (1 : 10 : 1) were prepared by extrusion-spheronization process and coated with acrylic resin, then compressed into tablets with Avicel PH 301 pellets and cross-linked polyvinylpyrrolidone. The coating weight, volume ratio of Eudragit RL30 D and RS30 D and solid content of coating fluid were optimized by Box-Behnken design. In 0.1 M HCl, tablets can immediately disintegrate into pellets which can remain floating and sustained drug releasing over 12 h. The AUC0-∞ of famotidine gastric floating pellets (7776.52 ± 1065.93 h ng/ml) administered into rats was significantly higher than that of marketed rapid release tablets Xingfading® (Xingyi, Shanghai, China) (4166.23 ± 312.43 h ng/ml), while the relative bioavailability was 187.01 ± 22.81%. The experimental results indicated that the optimized formulation did offer a new gastro retention and sustained release approach to enhance the oral absorption of famotidine. © 2014 Royal Pharmaceutical Society.

  12. Improved Mechanical Properties and Sustained Release Behavior of Cationic Cellulose Nanocrystals Reinforeced Cationic Cellulose Injectable Hydrogels.

    Science.gov (United States)

    You, Jun; Cao, Jinfeng; Zhao, Yanteng; Zhang, Lina; Zhou, Jinping; Chen, Yun

    2016-09-12

    Polysaccharide-based injectable hydrogels have several advantages in the context of biomedical use. However, the main obstruction associated with the utilization of these hydrogels in clinical application is their poor mechanical properties. Herein, we describe in situ gelling of nanocomposite hydrogels based on quaternized cellulose (QC) and rigid rod-like cationic cellulose nanocrystals (CCNCs), which can overcome this challenge. In all cases, gelation immediately occurred with an increase of temperature, and the CCNCs were evenly distributed throughout the hydrogels. The nanocomposite hydrogels exhibited increasing orders-of-magnitude in the mechanical strength, high extension in degradation and the sustained release time, because of the strong interaction between CCNCs and QC chains mediated by the cross-linking agent (β-glycerophosphate, β-GP). The results of the in vitro toxicity and in vivo biocompatibility tests revealed that the hydrogels did not show obvious cytotoxicity and inflammatory reaction to cells and tissue. Moreover, DOX-encapsulated hydrogels were injected beside the tumors of mice bearing liver cancer xenografts to assess the potential utility as localized and sustained drug delivery depot systems for anticancer therapy. The results suggested that the QC/CCNC/β-GP nanocomposite hydrogels had great potential for application in subcutaneous and sustained delivery of anticancer drug to increase therapeutic efficacy and improve patient compliance.

  13. HPLC determination and steady-state bioavailability study of levodropropizine sustained-release tablets in dogs.

    Science.gov (United States)

    Yan, Lin; Li, Tongling; Zhang, Rongqin; Xu, Xiaohong; Zheng, Pengcheng

    2006-06-01

    A simple HPLC method using UV detection was developed and validated for the determination of levodropropizine (LDP) in dog plasma. The sample was prepared for injection using a liquid-liquid extraction method with 1-phenypiperazine as the internal standard. The mobile phase was methanol-diethylamine solution (0.05 M) (20:80, v/v, pH adjusted to 3.0 with H3PO4) with a detection wavelength of 240 nm. The limit of quantitation (LOQ) of LDP in a biological matrix was determined to be 25.25 ng/mL. The calibration curve was linear across the concentration range of 25.25 to 2020 ng/mL. The intra-day and inter-day precision values (CV %) were within 7% and accuracy (R.E. %) was within 6% of the nominal values for medium (252.5 ng/mL) and high (2020 ng/mL) LDP concentrations. For the LDP concentration at the LOQ, the intra-day and inter-day precision and accuracy were within 20% and 10%, respectively. The average absolute recovery for LDP was 70.28%. This method was successfully used to analyze plasma samples in a steady-state bioavailability study of a newly developed sustained-release LDP tablets (SR) using immediate-release tablets (IR) as the reference. The relative bioavailability of the SR was determined to be 106.3 +/- 12.8% (n=6). The Cmax of the SR was significantly lower (P<0.05), and the tmax was significantly longer than that of the IR (P<0.05). The results of ANOVA and two one-sided tests indicated that the SR exhibited acceptable sustained release properties and was bioequivalent to the IR.

  14. Clinical Assessment of Urinary Tract Damage during Sustained-Release Estrogen Supplementation in Mice.

    Science.gov (United States)

    Collins, Dalis E; Mulka, Kathleen R; Hoenerhoff, Mark J; Taichman, Russell S; Villano, Jason S

    2017-02-01

    Estrogen supplementation is a key component of numerous mouse research models but can adversely affect the urinary system. The goal of this study was to develop a clinical scoring system and identify biomarkers of occult urinary tract lesions prior to the development of systemic illness in mice. Ovariectomized or sham-surgery SCID mice were implanted subcutaneously with a placebo pellet or one containing sustained-release estradiol (0.18 mg 60-d release 17β-estradiol). Mice were assessed twice weekly for 4 to 6 wk by using a clinical scoring system that included body condition, general activity, posture, hair coat, hydration, abdominal distension, urine staining of coat and skin, and ability to urinate. Samples were collected weekly for urinalysis, BUN, creatinine, and serum estradiol levels. Terminal samples were analyzed for histopathologic lesions. Compared with placebo controls, estradiolsupplemented mice had higher serum estradiol levels at weeks 2 and 3; significant differences in total clinical scores by the 3-wk time point; and in body condition, general activity, posture, hair coat, and urine staining scores by the 6-wk terminal time point. Urinary tract lesions included hydronephrosis, pyelonephritis, cystitis, and urolithiasis. All mice with urolithiasis had crystalluria, and 5 of the 6 mice with pyelonephritis or hydroureter had dilute urine (that is, specific gravity less than 1.030). However, these findings were not specific to mice with lesions. A total clinical score of 3.5 (maximum, 24) identified estradiol-supplemented mice with 83% specificity and 50% sensitivity, but no single clinical parameter, biomarker, or the total clinical score accurately predicted occult urinary tract lesions. Considering the lesions we observed, prudence is warranted when using pelleted sustained-release estradiol in mice, and important parameters to monitor for animal health include urine staining, body condition score, urine sediment, and urine specific gravity.

  15. Modified silicone elastomer vaginal gels for sustained release of antiretroviral HIV microbicides.

    Science.gov (United States)

    Forbes, Claire J; McCoy, Clare F; Murphy, Diarmaid J; Woolfson, A David; Moore, John P; Evans, Abbey; Shattock, Robin J; Malcolm, R Karl

    2014-05-01

    We previously reported nonaqueous silicone elastomer gels (SEGs) for sustained vaginal administration of the CCR5-targeted entry inhibitor maraviroc (MVC). Here, we describe chemically modified SEGs (h-SEGs) in which the hydrophobic cyclomethicone component was partially replaced with relatively hydrophilic silanol-terminated polydimethylsiloxanes (st-PDMS). MVC and emtricitabine (a nucleoside reverse transcriptase inhibitor), both currently under evaluation as topical microbicides to counter sexual transmission of human immunodeficiency virus type 1 (HIV-1), were used as model antiretroviral (ARV) drugs. Gel viscosity and in vitro ARV release were significantly influenced by st-PDMS molecular weight and concentration in the h-SEGs. Unexpectedly, gels prepared with lower molecular weight grades of st-PDMS showed higher viscosities. h-SEGs provided enhanced release over 24 h compared with aqueous hydroxyethylcellulose (HEC) gels, did not modify the pH of simulated vaginal fluid (SVF), and were shown to less cytotoxic than standard HEC vaginal gel. ARV solubility increased as st-PDMS molecular weight decreased (i.e., as percentage hydroxyl content increased), helping to explain the in vitro release trends. Dye ingression and SVF dilution studies confirmed the increased hydrophilicity of the h-SEGs. h-SEGs have potential for use in vaginal drug delivery, particularly for ARV-based HIV-1 microbicides. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  16. Injectable Chitosan/β-Glycerophosphate System for Sustained Release: Gelation Study, Structural Investigation, and Erosion Tests.

    Science.gov (United States)

    Dalmoro, Annalisa; Abrami, Michela; Galzerano, Barbara; Bochicchio, Sabrina; Barba, Anna Angela; Grassi, Mario; Larobina, Domenico

    2017-01-01

    Hydrogels can constitute reliable delivery systems of drugs, including those based on nucleic acids (NABDs) such as small interfering ribonucleic acid (siRNA). Their nature, structure, and response to physiological or external stimuli strongly influence the delivery mechanisms of entrapped active molecules, and, in turn, their possible uses in pharmacological and biomedical applications. In this study, a thermo-gelling chitosan/β-glycero-phosphate system has been optimized in order to assess its use as injectable system able to: i) gelling at physiological pH and temperature, and ii) modulate the release of included active ingredients. To this aim, we first analyzed the effect of acetic acid concentration on the gelation temperature. We then found the "optimized composition", namely, the one in which the Tgel is equal to the physiological temperature. The resulting gel was tested, by low field nuclear magnetic resonance (LF-NMR), to evaluate its average mesh-size, which can affect release kinetics of loaded drug. Finally, films of gelled chitosan, loaded with a model drug, have been tested in vitro to monitor their characteristic times, i.e. diffusion and erosion time, when they are exposed to a medium mimicking a physiological environment (buffer solution at pH 7.4). Results display that the optimized system is deemed to be an ideal candidate as injectable gelling material for a sustained release. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. IPX066 , a mixed immediate/sustained-release levodopa preparation for Parkinson's disease.

    Science.gov (United States)

    Ondo, William

    2014-10-01

    L-DOPA has long been the 'gold standard' treatment for Parkinson's disease (PD), but suffers from poor oral bioavailability and rapid pharmacokinetic elimination. A longer acting preparation has long been sought. We conducted PubMed search for IPX066 and reviewed abstracts from meetings that included the topic of PD. IPX066 is a novel mixed immediate release (IR) and sustained-release levodopa preparation designed to prolong the clinical effect of a single dose. Pharmacokinetic studies demonstrate similar time to peak dose as regular IR L-DOPA, but a longer duration of time with > 50% of peak dose. This contrasts with available controlled release preparations that have a delay to onset. Clinic trials in fluctuating PD patients show that IPX066 provided more 'on' time despite fewer daily doses, compared to IR L-DOPA. As expected, it was also superior to placebo in early PD. However, it is not known whether it can achieve l-DOPA levels that are continuous enough to delay the onset of fluctuations when given early in the disease. Although not a radical advance in L-DOPA therapy, the drug will clearly have a role in more advanced patients taking multiple L-DOPA doses and may have a role as first-line therapy when starting l-DOPA.

  18. Modified silicone elastomer vaginal gels for sustained release of antiretroviral HIV microbicides

    Science.gov (United States)

    Forbes, Claire J.; McCoy, Clare F.; Murphy, Diarmaid J.; Woolfson, A. David; Moore, John P.; Evans, Abbey; Shattock, Robin J.; Malcolm, R. Karl

    2014-01-01

    We previously reported non-aqueous silicone elastomer gels (SEGs) for sustained vaginal administration of the CCR5-targeted entry inhibitor maraviroc. Here, we describe chemically modified SEGs (h-SEGs) in which the hydrophobic cyclomethicone component was partially replaced with relatively hydrophilic silanol-terminated polydimethylsiloxanes (st-PDMS). Maraviroc and emtricitabine (a nucleoside reverse transcriptase inhibitor), both currently under evaluation as topical microbicides to counter sexual transmission of human immunodeficiency virus type 1 (HIV-1), were used as model antiretroviral (ARV) drugs. Gel viscosity and in vitro ARV release were significantly influenced by st-PDMS molecular weight and concentration in the h-SEGs. Unexpectedly, gels prepared with lower molecular weight grades of st-PDMS showed higher viscosities. h-SEGs provided enhanced release over 24 h compared with aqueous hydroxyethylcellulose (HEC) gels, did not modify the pH of simulated vaginal fluid (SVF), and were shown to less cytotoxic than standard hydroxyethylcellulose (HEC) vaginal gel. ARV solubility increased as st-PDMS molecular weight decreased (i.e. as percentage hydroxyl content increased), helping to explain the in vitro release trends. Dye ingression and SVF dilution studies confirmed the increased hydrophilicity of the h-SEGs. h-SEGs have potential for use in vaginal drug delivery, particularly for ARV-based HIV-1 microbicides. PMID:24585370

  19. 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.

  20. Effects of immediate-release opioid on memory functioning: a randomized-controlled study in patients receiving sustained-release opioids.

    Science.gov (United States)

    Kamboj, S K; Conroy, L; Tookman, A; Carroll, E; Jones, L; Curran, H V

    2014-11-01

    The effects of opioid medication on cognitive functioning in patients with cancer and non-cancer pain remain unclear. In this mechanistic randomized, double-blind, placebo-controlled, cross-over study of patients (n = 20) receiving sustained-release and immediate-release opioid medication as part of their palliative care, we examine memory effects of an additional dose of participants' immediate-release medication (oxycodone or morphine) or placebo. Immediate prose recall and recall of related and unrelated word pairs was assessed pre-and post-drug (placebo or immediate-release opioid). Memory for these stimuli was also tested after a delay on each testing occasion. Finally, performance on an 'interference' word pair task was assessed on the two testing occasions since proactive interference has been posited as a mechanism for acute opioid-induced memory impairment. Unlike previous work, we found no evidence of memory impairment for material presented before or after individually tailored, 'breakthrough' doses of immediate-release opioid. Furthermore, immediate-release opioid did not result in increased memory interference. On the other hand, we found enhanced performance on the interference word pair task after immediate-release opioid, possibly indicating lower levels of interference. These results suggest that carefully titrated immediate-release doses of opioid drugs may not cause extensive memory impairment as previously reported, and in fact, may improve memory in certain circumstances. Importantly, our findings contrast strikingly with those of a study using the same robust design that showed significant memory impairment. We propose that factors, such as depressive symptoms, education level and sustained-release opioid levels may influence whether impairment is observed following immediate-release opioid treatment. © 2014 European Pain Federation - EFIC®

  1. Thermoplastic polyurethanes for the manufacturing of highly dosed oral sustained release matrices via hot melt extrusion and injection molding.

    Science.gov (United States)

    Claeys, Bart; Vervaeck, Anouk; Hillewaere, Xander K D; Possemiers, Sam; Hansen, Laurent; De Beer, Thomas; Remon, Jean Paul; Vervaet, Chris

    2015-02-01

    This study evaluated thermoplastic polyurethanes (TPUR) as matrix excipients for the production of oral solid dosage forms via hot melt extrusion (HME) in combination with injection molding (IM). We demonstrated that TPURs enable the production of solid dispersions - crystalline API in a crystalline carrier - at an extrusion temperature below the drug melting temperature (Tm) with a drug content up to 65% (wt.%). The release of metoprolol tartrate was controlled over 24h, whereas a complete release of diprophylline was only possible in combination with a drug release modifier: polyethylene glycol 4000 (PEG 4000) or Tween 80. No burst release nor a change in tablet size and geometry was detected for any of the formulations after dissolution testing. The total matrix porosity increased gradually upon drug release. Oral administration of TPUR did not affect the GI ecosystem (pH, bacterial count, short chain fatty acids), monitored via the Simulator of the Human Intestinal Microbial Ecosystem (SHIME). The high drug load (65 wt.%) in combination with (in vitro and in vivo) controlled release capacity of the formulations, is noteworthy in the field of formulations produced via HME/IM. Copyright © 2014 Elsevier B.V. All rights reserved.

  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. Beyond Q1/Q2: The Impact of Manufacturing Conditions and Test Methods on Drug Release From PLGA-Based Microparticle Depot Formulations.

    Science.gov (United States)

    Garner, John; Skidmore, Sarah; Park, Haesun; Park, Kinam; Choi, Stephanie; Wang, Yan

    2018-01-01

    Drug-loaded polymeric microparticles have been used as long-acting injectable (LAI) depot formulations. To obtain U.S. Food and Drug Administration approval, a generic LAI depot product needs to be qualitatively (Q1) and quantitatively (Q2) the same in terms of inactive ingredients as its reference-listed drug. However, Q1/Q2 sameness as the reference-listed drug does not guarantee the same in vitro drug release profile and in vivo performance, especially when the manufacturing methods are different. There is little consensus on how the in vitro testing needs to be done to examine the release profiles of LAI depot formulations. This study examined the manufacturing differences in making risperidone-loaded poly(lactide-co-glycolide) microparticles and their impact on the release kinetics. It also examined the impacts of in vitro testing methods on the drug release profiles. Two in-house manufactured risperidone poly(lactide-co-glycolide) microparticles and Risperdal Consta® were used in the study. Of the in vitro release methods tested, the orbital agitation method provided the most reproducible release profiles. The results indicate that the in vitro release kinetics depend not only on manufacturing procedures but also on the in vitro testing conditions, such as the agitation speed, vessel-dimensions, solid beads, media exchange volume, and other parameters both under real-time and accelerated testing conditions. In the current case, the in vitro experimental condition seemed to affect the drug release kinetics more than the manufacturing differences. The developed orbital agitation release testing method is simple, robust, and reproducible, which allows the comparison of in vitro release profiles of formulations that are prepared with manufacturing differences. Copyright © 2018 American Pharmacists Association®. All rights reserved.

  4. Sustained-release genistein from nanostructured lipid carrier suppresses human lens epithelial cell growth

    Directory of Open Access Journals (Sweden)

    Jin-Lu Liu

    2016-05-01

    Full Text Available AIM: To design and investigate the efficacy of a modified nanostructured lipid carrier loaded with genistein (Gen-NLC to inhibit human lens epithelial cells (HLECs proliferation. METHODS: Gen-NLC was made by melt emulsification method. The morphology, particle size (PS, zeta potentials (ZP, encapsulation efficiency (EE and in vitro release were characterized. The inhibition effect of nanostructured lipid carrier (NLC, genistein (Gen and Gen-NLC on HLECs proliferation was evaluated by cell counting kit-8 (CCK-8 assay, gene and protein expression of the proliferation marker Ki67 were evaluated with real-time quantitative polymerase chain reaction (RT-qPCR and immunofluorescence analyses. RESULTS: The mean PS of Gen-NLC was 80.12±1.55 nm with a mean polydispersity index of 0.11±0.02. The mean ZP was -7.14±0.38 mV and the EE of Gen in the nanoparticles was 92.3%±0.73%. Transmission electron microscopy showed that Gen-NLC displayed spherical-shaped particles covered by an outer-layer structure. In vitro release experiments demonstrated a prolonged drug release for 72h. The CCK-8 assay results showed the NLC had no inhibitory effect on HLECs and Gen-NLC displayed a much more prominent inhibitory effect on cellular growth compared to Gen of the same concentration. The mRNA and protein expression of Ki67 in LECs decreased significantly in Gen-NLC group. CONCLUSION: Sustained drug release by Gen-NLCs may impede HLEC growth.

  5. Once daily, high-dose mesalazine controlled-release tablet for colonic delivery: optimization of formulation variables using Box-Behnken design.

    Science.gov (United States)

    Elbary, Ahmed Abd; Aboelwafa, Ahmed A; Al Sharabi, Ibrahim M

    2011-12-01

    The aim of this work was to statistically optimize a novel high-dose, mesalazine colonic delivery matrix system, potentially suitable for once daily administration, using simple wet granulation method. A hydrophobic-hydrophilic polymeric blend was used to manipulate drug release. A three-factor, three-level Box-Behnken design was used to construct polynomial models correlating the dependent and independent variables. Independent formulation variables were the percentages of the hydrophilic polymer Carbopol® 940, hydrophobic polymer Eudragit® RS, and the superdisintegrant croscarmellose sodium. The cumulative percentages of drug released at 6, 10, and 14 h were selected as dependent variables and restricted to 7.5-22.5% (Y(1)), 42.5-57.5 % (Y(2)), and 72.5-87.5% (Y(3)), respectively. A second-order polynomial equation fitted to the data was used to optimize the independent formulation variables. Based on Box-Behnken experimental design, different mesalazine release profiles were obtained. The optimized formulation containing 5.72% Carbopol®, 9.77% Eudragit® RS, and 1.45% croscarmellose sodium was prepared according to the software determined levels. It provided a release profile which was very close to the targeted release profile, where the calculated values of f(1) and f(2) were 8.47 and 67.70, respectively, and followed zero-order release kinetics.

  6. Poly(glycerol adipate-co-ω-pentadecalactone) spray-dried microparticles as sustained release carriers for pulmonary delivery.

    Science.gov (United States)

    Tawfeek, Hesham; Khidr, Sayed; Samy, Eman; Ahmed, Sayed; Murphy, Mark; Mohammed, Afzaal; Shabir, Anjum; Hutcheon, Gillian; Saleem, Imran

    2011-09-01

    The aim of this work was to optimize biodegradable polyester poly(glycerol adipate-co-ω-pentadecalactone), PGA-co-PDL, microparticles as sustained release (SR) carriers for pulmonary drug delivery. Microparticles were produced by spray drying directly from double emulsion with and without dispersibility enhancers ((L)-arginine and (L)-leucine) (0.5-1.5%w/w) using sodium fluorescein (SF) as a model hydrophilic drug. Spray-dried microparticles without dispersibility enhancers exhibited aggregated powders leading to low fine particle fraction (%FPF) (28.79 ± 3.24), fine particle dose (FPD) (14.42 ± 1.57 μg), with a mass median aerodynamic diameter (MMAD) 2.86 ± 0.24 μm. However, (L)-leucine was significantly superior in enhancing the aerosolization performance ((L-)arginine:%FPF 27.61 ± 4.49-26.57 ± 1.85; FPD 12.40 ± 0.99-19.54 ± 0.16 μg and MMAD 2.18 ± 0.35-2.98 ± 0.25 μm, (L)-leucine:%FPF 36.90 ± 3.6-43.38 ± 5.6; FPD 18.66 ± 2.90-21.58 ± 2.46 μg and MMAD 2.55 ± 0.03-3.68 ± 0.12 μm). Incorporating (L)-leucine (1.5%w/w) reduced the burst release (24.04 ± 3.87%) of SF compared to unmodified formulations (41.87 ± 2.46%), with both undergoing a square root of time (Higuchi's pattern) dependent release. Comparing the toxicity profiles of PGA-co-PDL with (L)-leucine (1.5%w/w) (5 mg/ml) and poly(lactide-co-glycolide), (5 mg/ml) spray-dried microparticles in human bronchial epithelial 16HBE14o- cell lines, resulted in cell viability of 85.57 ± 5.44 and 60.66 ± 6.75%, respectively, after 72 h treatment. The above data suggest that PGA-co-PDL may be a useful polymer for preparing SR microparticle carriers, together with dispersibility enhancers, for pulmonary delivery.

  7. Safety of IPX066 , an extended release carbidopa-levodopa formulation, for the treatment of Parkinson's disease.

    Science.gov (United States)

    Kestenbaum, Meir; Fahn, Stanley

    2015-05-01

    Levodopa (LD) is the most effective treatment for Parkinson's disease (PD). However, chronic use of LD commonly results in the development of motor complications, including wearing off and dyskinesia. The presumption that the short serum half-life of LD is associated with the development of motor complications has raised the need to develop treatments with increased durations of stable LD concentrations. We conducted a PubMed search for IPX066 articles and also reviewed abstracts from meetings that included this topic. IPX066 is a newly developed formulation of extended release carbidopa-LD (CD-LD) with a one to four ratio of CD to LD, that was approved by the FDA in January 2015 for the treatment of PD, post-encephalitic parkinsonism, and parkinsonism that may follow carbon monoxide or manganese intoxication. It will be marketed by the trade name Rytary®. A Phase III clinical trial showed that IPX066 is efficacious in improving motor symptoms in early PD patients. In advanced PD patients with motor fluctuations, IPX066 reduced off time and increased on time without troublesome dyskinesia compared to CD-LD immediate release and CD-LD with entacapone. IPX066 had an acceptable safety profile. Adverse events of IPX066 from the different trials are presented. IPX066 will probably have a role in the treatment of advanced PD with motor fluctuations. IPX066 could also be used initially when LD therapy is prescribed, but the question of whether this usage could reduce or prevent the development of motor complications is yet to be answered.

  8. Spectroscopic-Based Chemometric Models for Quantifying Low Levels of Solid-State Transitions in Extended Release Theophylline Formulations.

    Science.gov (United States)

    Korang-Yeboah, Maxwell; Rahman, Ziyaur; Shah, Dhaval A; Khan, Mansoor A

    2016-01-01

    Variations in the solid state form of a pharmaceutical solid have profound impact on the product quality and clinical performance. Quantitative models that allow rapid and accurate determination of polymorphic changes in pharmaceutical products are essential in ensuring product quality throughout its lifecycle. This study reports the development and validation of chemometric models of Raman and near infrared spectroscopy (NIR) for quantifying the extent of pseudopolymorphic transitions of theophylline in extended release formulations. The chemometric models were developed using sample matrices consisting of the commonly used excipients and at the ratios in commercially available products. A combination of scatter removal (multiplicative signal correction and standard normal variate) and derivatization (Savitzky-Golay second derivative) algorithm were used for data pretreatment. Partial least squares and principal component regression models were developed and their performance assessed. Diagnostic statistics such as the root mean square error, correlation coefficient, bias and Q(2) were used as parameters to test the model fit and performance. The models developed had a good fit and performance as shown by the values of the diagnostic statistics. The model diagnostic statistics were similar for MSC-SG and SNV-SG treated spectra. Similarly, PLSR and PCR models had comparable performance. Raman chemometric models were slightly better than their corresponding NIR model. The Raman and NIR chemometric models developed had good accuracy and precision as demonstrated by closeness of the predicted values for the independent observations to the actual TMO content hence the developed models can serve as useful tools in quantifying and controlling solid state transitions in extended release theophylline products. Copyright © 2016. Published by Elsevier Inc.

  9. 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.

  10. 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.

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

    Science.gov (United States)

    Chen, Xing; Zou, Li-Qiang; Niu, Jing; Liu, Wei; Peng, Sheng-Feng; Liu, Cheng-Mei

    2015-08-05

    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. Tiered application of the neutral red release and EpiOcular™ assays for evaluating the eye irritation potential of agrochemical formulations.

    Science.gov (United States)

    Settivari, Raja S; Amado, Ricardo Acosta; Corvaro, Marco; Visconti, Nicolo R; Kan, Lynn; Carney, Edward W; Boverhof, Darrell R; Gehen, Sean C

    2016-11-01

    Agrochemical formulations have been underrepresented in validation efforts for implementing alternative eye irritation approaches but represent a significant opportunity to reduce animal testing. This study assesses the utility of the neutral red release assay (NRR) and EpiOcular™ assay (EO) for predicting the eye irritation potential of 64 agrochemical formulations relative to Draize data. In the NRR, formulations with an NRR50 value ≤ 50 mg/mL were categorized as UN GHS Cat 1 and those >250 mg/mL were classified as UN GHS Non Classified (NC). The accuracy, sensitivity, and specificity were 78, 85 and 76% and 73, 85 and 61% for identifying UN GHS 1 and NC formulations, respectively. Specificity was poor for formulations with NRR50 > 50 to ≤250 mg/mL. The EO (ET-40 method) was explored to differentiate formulations that were UN GHS 1/2 and UN GHS NC. The EO resulted in accuracy, sensitivity, and specificity of 65%, 58% and 75% for identifying UN GHS NC formulations. To improve the overall performance, the assays were implemented using a tiered-approach where the NRR was run as a first-tier followed by the EO. The tiered-approach resulted in improved accuracy (75%) and balanced sensitivity (73%) and specificity (77%) for distinguishing between irritating and non-irritating agrochemical formulations. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Pharmacokinetics of 3 Formulations of Meloxicam in Cynomolgus Macaques (Macaca fascicularis)

    Science.gov (United States)

    Bauer, Cassondra; Frost, Patrice; Kirschner, Stephen

    2014-01-01

    Meloxicam is a commonly used COX2-preferential NSAID in both human and veterinary patients. Minimal information has been published regarding appropriate dosing in nonhuman primates. Here we investigated the pharmacokinetic parameters of 3 formulations of meloxicam in cynomolgus macaques. A single dose of meloxicam SR, an extended-release formulation purported to provide therapeutic levels for as long as 72 h, was compared with the intramuscular and oral formulations dosed for 3 consecutive days and as a single dose. The oral formulation, both over 3 d and as a single dose, yielded lower plasma levels and a shorter duration than did intramuscular and sustained-release subcutaneous formulations. The intramuscular formulation, both over 3 d and as a single dose, provided lower plasma levels and a shorter duration than did a sustained-release subcutaneous formulation. The sustained-release formulations generated the highest plasma concentrations for the longest periods of time. None of the formulations caused significant effects on kidney or liver function. Our results indicate that the sustained-release formulation of meloxicam can achieve an adequate steady-state plasma concentration for 2 to 3 d in nonhuman primates. The standard intramuscular formulation provides adequate plasma concentrations for 12 to 24 h, with waxing and waning levels associated with daily dosing. The oral formulation has limited utility in nonhuman primates because of low circulating levels of drug. PMID:25255073

  14. SLI381 (Adderall XR), a two-component, extended-release formulation of mixed amphetamine salts: bioavailability of three test formulations and comparison of fasted, fed, and sprinkled administration.

    Science.gov (United States)

    Tulloch, Simon J; Zhang, Yuxin; McLean, Angus; Wolf, Kathleen N

    2002-11-01

    To assess the bioavailability of three test formulations of a single dose of extended-release Adderall 20-mg capsules compared with two doses of immediate-release Adderall 10-mg tablets, and to assess the bioequivalence of a single 30-mg dose of the chosen extended-release Adderall formulation (designated as SLI381) administered in applesauce (sprinkled) and the same dose administered as an intact capsule with or without food. Randomized, open-label, crossover study. Clinical research unit. Forty-one healthy adults. Study A had four treatment sequences: three test formulations (A, B, and C) of a single dose of extended-release Adderall 20 mg, and two 10-mg doses of Adderall given 4 hours apart. Study B had three treatment sequences: a single dose of SLI381 30 mg as an intact capsule after overnight fast, an intact capsule after a high-fat breakfast, and the contents of a capsule sprinkled in 1 tablespoon of applesauce. The 20-mg test formulation A had comparable pharmacokinetic profiles and bioequivalence in rate and extent of drug absorption to Adderall 10 mg twice/day for both d- and l-amphetamine. Formulations B and C had statistically significant differences from the reference drug in some pharmacokinetic parameters. A 30-mg dose of SLI381 showed no significant differences in rate and extent of absorption of d- and l-amphetamine for fasted or sprinkled conditions compared with the high-fat meal condition. SLI381 20 mg/day is bioequivalent to Adderall 10 mg twice/day. SLI381 30 mg administered in applesauce is bioequivalent in terms of both rate and extent of absorption to the same dose administered as an intact capsule in both fasted and fed states.

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

    Science.gov (United States)

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

  16. Effects of food on pharmacokinetics of immediate release oral formulations of aspirin, dipyrone, paracetamol and NSAIDs – a systematic review

    Science.gov (United States)

    Moore, Robert Andrew; Derry, Sheena; Wiffen, Philip J; Straube, Sebastian

    2015-01-01

    Aims It is common to advise that analgesics, and especially non-steroidal anti-inflammatory drugs (NSAIDs), be taken with food to reduce unwanted gastrointestinal adverse effects. The efficacy of single dose analgesics depends on producing high, early, plasma concentrations; food may interfere with this. This review sought evidence from single dose pharmacokinetic studies on the extent and timing of peak plasma concentrations of analgesic drugs in the fed and fasting states. Methods A systematic review of comparisons of oral analgesics in fed and fasting states published to October 2014 reporting kinetic parameters of bioavailability, time to maximum plasma concentration (tmax), and its extent (Cmax) was conducted. Delayed-release formulations were not included. Results Bioavailability was not different between fasted and fed states. Food typically delayed absorption for all drugs where the fasting tmax was less than 4 h. For the common analgesics (aspirin, diclofenac, ibuprofen, paracetamol) fed tmax was 1.30 to 2.80 times longer than fasted tmax. Cmax was typically reduced, with greater reduction seen with more rapid absorption (fed Cmax only 44–85% of the fasted Cmax for aspirin, diclofenac, ibuprofen and paracetamol). Conclusion There is evidence that high, early plasma concentrations produces better early pain relief, better overall pain relief, longer lasting pain relief and lower rates of remedication. Taking analgesics with food may make them less effective, resulting in greater population exposure. It may be time to rethink research priorities and advice to professionals, patients and the public. PMID:25784216

  17. Regulatory framework on bioequivalence criteria for locally acting gastrointestinal drugs: the case for oral modified release mesalamine formulations.

    Science.gov (United States)

    Sferrazza, Gianluca; Siviero, Paolo D; Nicotera, Giuseppe; Turella, Paola; Serafino, Annalucia; Blandizzi, Corrado; Pierimarchi, Pasquale

    2017-09-01

    Bioequivalence testing for locally acting gastrointestinal drugs is a challenging issue for both regulatory authorities and pharmaceutical industries. The international regulatory framework has been characterized by the lack of specific bioequivalence tests that has generated a negative impact on the market competition and drug use in clinical practice. Areas covered: This review article provides an overview of the European Union and United States regulatory frameworks on bioequivalence criteria for locally acting gastrointestinal drugs, also discussing the most prominent scientific issues and advances that has been made in this field. A focus on oral modified release mesalamine formulations will be also provided, with practical examples of the regulatory pathways followed by pharmaceutical companies to determine bioequivalence. Expert commentary: The development of a scientific rationale to demonstrate bioequivalence in this field has been complex and often associated with uncertainties related to scientific and regulatory aspects. Only in recent years, thanks to advanced knowledge in this field, the criteria for bioequivalence assessment are undergoing substantial changes. This new scenario will likely result in a significant impact on pharmaceutical companies, promoting more competition through a clearer regulatory approach, conceived for streamlining the demonstration of therapeutic equivalence for locally acting gastrointestinal drugs.

  18. Sublethal effect of pyriproxyfen released from a fumigant formulation on fecundity, fertility, and ovicidal action in Aedes aegypti (Diptera: Culicidae).

    Science.gov (United States)

    Harburguer, Laura; Zerba, Eduardo; Licastro, Susana

    2014-03-01

    Dengue and dengue hemorrhagic fever are mosquito-borne viral diseases that coincide with the distribution of Aedes aegypti (L.), the primary vector in the tropical and semitropical world. With no available vaccine, controlling the dengue vector is essential to prevent epidemics. The effects of the insect growth regulator pyriproxyfen on Ae. aegypti adults that survived a treatment with a sublethal dose were investigated in the laboratory, including effects on their reproductive potential. Pyriproxyfen was released from a fumigant formulation at a dose causing 20 or 40% emergence inhibition (%EI). Females were dissected before and after blood feeding and the basal follicle number was counted. There were no differences between the control and treated group on the basal follicle number for both doses used. Fertility and fecundity were reduced at a concentration of EI40 but no at EI20. There was no ovicidal effect of pyriproxyfen by immersion of eggs in treated water neither when the females laid their eggs on a pyriproxyfen-treated surface. This work shows that sublethal doses of pyriproxyfen can have effects on fertility and fecundity ofAe. aegypti females, which together with its larvicidal activity could contribute to an overall decrease in a given population.

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

    Science.gov (United States)

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

    2016-12-01

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

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

    Directory of Open Access Journals (Sweden)

    John Rojas

    2011-09-01

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

  1. In vitro evaluation of sustained released matrix tablets containing ibuprofen: a model poorly water-soluble drug

    Directory of Open Access Journals (Sweden)

    Wendy Leticia Guerra-Ponce

    Full Text Available ABSTRACT A matrix system was developed that releases ibuprofen (IB over a 12-hour period and the influence of the polymer type and concentration on the release rate of the drug was evaluated. Tablets containing different concentrations of Carbopol (CP, hydroxypropyl methylcellulose (HPMC, or ethyl cellulose (EC were prepared using direct compression and the drug content, content uniformity, hardness, friability, dissolution performance, and in vitro release kinetics were examined. Formulated tablets were found to be within acceptable limits for physical and chemical parameters. The release kinetics of the Carbopol(r971P 8% formulation showed the best linearity (r 2 =0.977 in fitting zero-order kinetics, suggesting the release rate was time independent. The drug release from tablets containing 8% CP was extended over approximately 18 hours and the release kinetics were nearly linear, suggesting that this system has the potential to maintain constant plasma drug concentrations over 12 hours, which could reduce the frequency of administration and the occurrence of adverse effects associated with repeated administration of conventional IB tablets.

  2. 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.

  3. 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

  4. Policy framework for formulating environmental management strategy for sustainable development of tanneries in India.

    Science.gov (United States)

    Ingle, Kapilkumar N; Harada, Koichi; Wei, Chang Nian; Minamoto, Keiko; Ueda, Atsushi

    2011-03-01

    The leather industry is one of the main examples of industries which play an important role in the Indian economy in terms of exports and employment opportunities, while being blamed for environmental pollution. The objective of this study was to find the advances or improvements in the Japanese leather industry which are not found in typical leather industries in developing countries. We examined the Japanese leather industry in this context because Japan is a developed country in which tanning processes have been a traditional business from ancient times, and also the leather industry has played an important role in the process of economic development of Japan. The study was based both on information collected from various areas related to the leather industry or leather industry stakeholders, and also on a review of published information. Information was collected through site visits, interviews, questionnaires, and detailed discussions with these stakeholders, as well as from their websites. The framework of a typical leather industry is discussed in three sections: pollution prevention, pollution control, and pollution mitigation related to sources, processes, and impact possibilities, respectively. Eleven basic differences were noted between the Japanese and Indian leather industries. The availability of melting centers is the main important feature of the Japanese leather sector. Guidelines are suggested which focus on some changes that are expected to lead to both environmental and economic benefits, with better pollution management, which should lead to continuous improvement of the environmental performance of the industry, and, finally, sustainable development.

  5. Biofabrication of a PLGA-TCP-based porous bioactive bone substitute with sustained release of icaritin.

    Science.gov (United States)

    Xie, Xin-Hui; Wang, Xin-Luan; Zhang, Ge; He, Yi-Xin; Leng, Yang; Tang, Ting-Ting; Pan, Xiaohua; Qin, Ling

    2015-08-01

    A phytomolecule, icaritin, has been identified and shown to be osteopromotive for the prevention of osteoporosis and osteonecrosis. This study aimed to produce a bioactive poly (l-lactide-co-glycolide)-tricalcium phosphate (PLGA-TCP)-based porous scaffold incorporating the osteopromotive phytomolecule icaritin, using a fine spinning technology. Both the structure and the composition of icaritin-releasing PLGA-TCP-based scaffolds were evaluated by scanning electron microscopy (SEM). The porosity was quantified by both water absorption and micro-computed tomography (micro-CT). The mechanical properties were evaluated using a compression test. In vitro release of icaritin from the PLGA-TCP scaffold was quantified by high-performance liquid chromatography (HPLC). The attachment, proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) on the composite scaffold were evaluated. Both an in vitro cytotoxicity test and an in vivo test via muscular implantation were conducted to confirm the scaffold's biocompatibility. The results showed that the PLGA-TCP-icaritin composite scaffold was porous, with interconnected macro- (about 480 µm) and micropores (2-15 µm). The mechanical properties of the PLGA-TCP-icaritin scaffold were comparable with those of the pure PLGA-TCP scaffold, yet was spinning direction-dependent. Icaritin content was detected in the medium and increased with time. The PLGA-TCP-icaritin scaffold facilitated the attachment, proliferation and osteogenic differentiation of BMSCs. In vitro cytotoxicity test and in vivo intramuscular implantation showed that the composite scaffold had no toxicity with good biocompatibility. In conclusion, an osteopromotive phytomolecule, icaritin, was successfully incorporated into PLGA-TCP to form an innovative porous composite scaffold with sustained release of osteopromotive icaritin, and this scaffold had good biocompatibility and osteopromotion, suggesting its potential for orthopaedic

  6. Evaluation of the durability of pain relief throughout a 12 hour dosing interval of a novel, extended-release, abuse-deterrent formulation of oxycodone.

    Science.gov (United States)

    Nalamachu, Srinivas; Kopecky, Ernest A; Taylor, Robert; Vaughn, Ben; O'Connor, Melinda

    2016-07-01

    Abuse deterrent formulations (ADF) are designed to prevent the misuse of opioids by tampering (e.g. physical and chemical manipulation) in order to ingest the opioid in a manner other than intended. Extended-release (ER) formulations are formulated with a larger drug load than immediate-release (IR) formulations, which makes ER opioids more desirable to drug abusers than I.R. formulations. ADFs, therefore, are particularly useful with ER opioid agents, which are designed to produce consistent analgesia over prolonged dosing intervals. However, the drug release properties of these formulations vary and sometimes may not provide adequate pain relief throughout the intended dosing interval, requiring patients to take additional medication for pain relief. Oxycodone DETERx* (Xtampza ER * ) is a novel, microsphere-in-capsule opioid formulation, which allows for twice daily dosing (i.e. every 12 hours) and mitigates the ability to tamper with the formulation. To evaluate the durability of pain relief of a novel formulation of oxycodone throughout the 12 hour dosing interval. This study is a post-hoc analysis of 193 subjects in a Phase 3 randomized withdrawal, double-blind, placebo-controlled, enriched-enrollment, parallel-group, multicenter, 12-week clinical study. The analysis evaluated the frequency and distribution of use of oxycodone ER and rescue medication during the Double-blind Maintenance Phase of the study. Usage patterns captured by an electronic diary indicated limited overall and limited per-day use of rescue medication with no increase in rescue medication consumption 8 to 12 hours post-dose, suggesting that subjects did not experience end-of-dose failure during this time period. This study is limited in that it is a post-hoc analysis based on data gathered electronically from a large, prospective, double-blind, randomized, placebo-controlled, Phase 3 clinical study. The evaluation of dosing patterns indicates that this ER oxycodone capsule

  7. 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.

  8. Sustained release nitrite therapy results in myocardial protection in a porcine model of metabolic syndrome with peripheral vascular disease.

    Science.gov (United States)

    Bradley, Jessica M; Islam, Kazi N; Polhemus, David J; Donnarumma, Erminia; Brewster, Luke P; Tao, Ya-Xiong; Goodchild, Traci T; Lefer, David J

    2015-07-15

    Metabolic syndrome (MetS) reduces endothelial nitric oxide (NO) bioavailability and exacerbates vascular dysfunction in patients with preexisting vascular diseases. Nitrite, a storage form of NO, can mediate vascular function during pathological conditions when endogenous NO is reduced. The aims of the present study were to characterize the effects of severe MetS and obesity on dyslipidemia, myocardial oxidative stress, and endothelial NO synthase (eNOS) regulation in the obese Ossabaw swine (OS) model and to examine the effects of a novel, sustained-release formulation of sodium nitrite (SR-nitrite) on coronary vascular reactivity and myocardial redox status in obese OS subjected to critical limb ischemia (CLI). After 6 mo of an atherogenic diet, obese OS displayed a MetS phenotype. Obese OS had decreased eNOS functionality and NO bioavailability. In addition, obese OS exhibited increased oxidative stress and a significant reduction in antioxidant enzymes. The efficacy of SR-nitrite therapy was examined in obese OS subjected to CLI. After 3 wk of treatment, SR-nitrite (80 mg · kg(-1) · day(-1) bid po) increased myocardial nitrite levels and eNOS function. Treatment with SR-nitrite reduced myocardial oxidative stress while increasing myocardial antioxidant capacity. Ex vivo assessment of vascular reactivity of left anterior descending coronary artery segments demonstrated marked improvement in vasoreactivity to sodium nitroprusside but not to substance P and bradykinin in SR-nitrite-treated animals compared with placebo-treated animals. In conclusion, in a clinically relevant, large-animal model of MetS and CLI, treatment with SR-nitrite enhanced myocardial NO bioavailability, attenuated oxidative stress, and improved ex vivo coronary artery vasorelaxation.

  9. The role of combination anthelmintic formulations in the sustainable control of sheep nematodes.

    Science.gov (United States)

    Bartram, David J; Leathwick, Dave M; Taylor, Mike A; Geurden, Thomas; Maeder, Steven J

    2012-05-25

    are not a panacea and should always be used in accordance with contemporary principles for sustainable anthelmintic use. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Capacity Development and Strengthening for Energy Policy formulation and implementation of Sustainable Energy Projects in Indonesia CASINDO. Deliverable No. 38. Pro-poor Energy Strategy in Central Java

    Energy Technology Data Exchange (ETDEWEB)

    Sumardi, R. Rizal Isnanto; Firdausi, Aulia Latifah Insan [Diponegoro University, Semarang (Indonesia)

    2012-01-15

    The overall objective of the CASINDO programme is to establish a self-sustaining and self-developing structure at both the national and regional level to build and strengthen human capacity to enable the provinces of North Sumatra, Yogyakarta, Central Java, West Nusa Tenggara and Papua to formulate sound policies for renewable energy and energy efficiency and to develop and implement sustainable energy projects.

  11. Polymeric emulsion and crosslink-mediated synthesis of super-stable nanoparticles as sustained-release anti-tuberculosis drug carriers.

    Science.gov (United States)

    Choonara, Yahya E; Pillay, Viness; Ndesendo, Valence M K; du Toit, Lisa C; Kumar, Pradeep; Khan, Riaz A; Murphy, Caragh S; Jarvis, Debbie-Leigh

    2011-10-15

    This study focused on evaluating four emulsion-based processing strategies for polymeric nanoparticle synthesis to explicate the mechanisms of nanoparticle formation and the influence on achieving sustained-release of two anti-tuberculosis drugs, isoniazid and rifampicin. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were formulated with and without sorbitan mono-oleate as a stabilizer using emulsion-solvent-surfactant-evaporation (ESSE) and emulsion-solvent-evaporation (ESE) approaches. An alginate solution gelled by ionic crosslinking with calcium chloride was employed to prepare alginate hydrogel nanoparticles via reverse-emulsion-cationic-gelification (RECG) and reverse-emulsion-surfactant-cationic-gelification (RESCG) approaches. In vitro drug release analysis was performed. The size, zeta potential and morphology of the nanoparticles were analyzed. Molecular mechanics energy relationships (MMER) were employed to explore the spatial disposition of alginate and PLGA with respect to the emulsifying profile of sorbitan monooleate and to corroborate the experimental findings. Results revealed that particle size of the PLGA nanoparticles was influenced by the stabilizer concentration. Nanoparticles synthesized by the ESSE approach had smaller sizes of 240±8.7 nm and 195.5±5.4 nm for rifampicin- and isoniazid-loaded nanoparticles, respectively. This was a substantial size reduction from nanoparticles generated by the ESE approach (>1000 nm). The RESCG approach produced stable and higher nanoparticle yields with desirable size (277±1.0 nm; 289±1.2 nm), a low polydispersity index (27.1±0.3 mV; 28.5±0.5 mV) and drug entrapment efficiency of 73% and 75% for isoniazid and rifampicin, respectively. Drug release from the ESSE and RESCG synthesized nanoparticles displayed desirable release of the two anti-TB drugs with sustained zero-order kinetics over a period of 8h. MMER supported the mechanisms of nanoparticle formation with a sphericalized interlaced network

  12. Cardioprotective Effects of a Novel Hydrogen Sulfide Agent–Controlled Release Formulation of S-Propargyl-Cysteine on Heart Failure Rats and Molecular Mechanisms

    Science.gov (United States)

    Liu, Xu; Ma, Fenfen; Tran, Ba Hieu; Zou, Yunzeng; Wang, Shujun; Zhu, Yi Zhun

    2013-01-01

    Objective Heart failure (HF) is one of the most serious diseases worldwide. S-propargyl-cysteine (SPRC), a novel modulator of endogenous hydrogen sulfide, is proved to be able to protect against acute myocardial ischemia. In order to produce more stable and sustainable hydrogen sulfide, we used controlled release formulation of SPRC (CR-SPRC) to elucidate possible cardioprotective effects on HF rats and investigate involved mechanisms on apoptosis and oxidation. Methods Left coronary artery was occluded to induce HF model of rat. The survival rats were randomly divided into 7 groups after 24 hours and treated with drugs for 6 weeks. Echocardiographic indexes were recorded to determine cardiac function. TTC staining was performed to determine infarct size. Plasmatic level of hydrogen sulfide was detected by modified sulfide electrode. Activity of enzyme and expression of protein were determined by colorimetry and Western blot, respectively. Results The cardioprotective effects of CR-SPRC on HF rats were confirmed by significant reduction of infarct size and improvement of cardiac function, with better effects compared to normal SPRC. CR-SPRC modulated antioxidant defenses by preserving levels of GSH, CAT and SOD and reducing CK leakage. In addition, CR-SPRC elevated ratio of Bcl-2/Bax and inhibited activity of caspases to protect against myocardial apoptosis. The cardioprotective effects of CR-SPRC were mediated by hydrogen sulfide. Conclusions All experiment data indicated cardioprotective effects of CR-SPRC on HF rats. More importantly, CR-SPRC exerted better effects than normal SPRC in all respects, providing a new perspective on hydrogen sulfide-mediated drug therapy. PMID:23874913

  13. 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.

  14. Comparative pharmacokinetics of two modified-release oral morphine formulations (Reliadol® and Kapanol®) and an immediate-release morphine tablet (Morfin 'DAK') in healthy volunteers

    DEFF Research Database (Denmark)

    Bochner, F.; Somogyi, A.A.; Danz, C.

    1999-01-01

    Objective: Reliadol® (Nycomed Denmark A/S) is a new modified-release morphine formulation undergoing clinical evaluation. It consists of a mixture of rapid- and modified-release microencapsulated granules of morphine. The study aims were to investigate the single-dose pharmacokinetics of morphine...... adverse events were nausea and headache. Conclusions: Reliadol® is likely to be suitable for once-daily administration in patients with chronic pain because of its unique plasma concentration versus time profile resulting from the mixture of rapid- and modified-release morphine pellets....

  15. 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

  16. Influence of Molecular Weight of Carriers and Processing Parameters on the Extrudability, Drug Release, and Stability of Fenofibrate Formulations Processed by Hot-Melt Extrusion.

    Science.gov (United States)

    Alsulays, Bader B; Park, Jun-Bom; Alshehri, Sultan M; Morott, Joseph T; Alshahrani, Saad M; Tiwari, Roshan V; Alshetaili, Abdullah S; Majumdar, Soumyajit; Langley, Nigel; Kolter, Karl; Gryczke, Andreas; Repka, Michael A

    2015-10-01

    The objective of this study was to investigate the extrudability, drug release, and stability of fenofibrate (FF) formulations utilizing various hot-melt extrusion processing parameters and polyvinylpyrrolidone (PVP) polymers of various molecular weights. The different PVP grades selected for this study were Kollidon(®) 12 PF (K12), Kollidon(®) 30 (K30), and Kollidon(®) 90 F (K90). FF was extruded with these polymers at three drug loadings (15%, 25%, and 35% w/w). Additionally, for FF combined with each of the successfully extruded PVP grades (K12 and K30), the effects of two levels of processing parameters for screw design, screw speed, and barrel temperature were assessed. It was found that the FF with (K90) was not extrudable up to 35% drug loading. With low drug loading, the polymer viscosity significantly influenced the release of FF. The crystallinity remaining was vital in the highest drug-loaded formulation dissolution profile, and the glass transition temperature of the polymer significantly affected its stability. Modifying the screw configuration resulted in more than 95% post-extrusion drug content of the FF-K30 formulations. In contrast to FF-K30 formulations, FF release and stability with K12 were significantly influenced by the extrusion temperature and screw speed.

  17. Effects of drying methods on the physicochemical and compressional characteristics of Okra powder and the release properties of its metronidazole tablet formulation.

    Science.gov (United States)

    Bakre, L G; Jaiyeoba, K T

    2009-02-01

    A study has been made of the effects of sun and oven drying methods on the physicochemical characteristics and compressibility of Okra powder and the release properties of its metronidazole tablet formulation. Corn starch was used as the reference standard. The mechanical properties of the tablets were evaluated using crushing strength and friability, while the release properties were determined using the disintegration times and dissolution rates. The results obtained showed that sun-dried Okra powder had smaller particle size, exhibited good flow and possessed higher hydration and swelling capacities compared to the oven dried samples. The compressibility of Okra powders assessed by the indices of plasticity from Heckel (Py) and Kawakita plots (Pk) showed that sun dried Okra powders had higher Py but lower Pk values than the oven-dried Okra powder. Metronidazole tablets formulated with oven dried Okra powder formed stronger tablets than tablets containing sun dried Okra powder. Generally, tablets containing sun dried Okra powders had faster disintegration and dissolution than tablets formulated with oven-dried powder. The results suggest that the choice of drying method during the processing of pharmaceutical raw materials is critical to its physicochemical properties and the release properties of its tablet formulations.

  18. Formulation and in-vitro characterisation of fulvestrant loaded ...

    African Journals Online (AJOL)

    Formulation B with Lecithin: Cholesterol ratio of 1:2 showed the highest drug loading, the highest percentage cumulative released of the drug (in a sustained manner for a prolonged period of time) and adequately internalized in the MCF-7 breast cancer cell line in vitro. Conclusion: Therefore formulation B is more suitable ...

  19. Design and release characteristics of sustained release tablet containing metformin HCl Planejamento e características de liberação de comprimidos de liberação controlada de cloridrato de metformina

    Directory of Open Access Journals (Sweden)

    Subal Chandra Basak

    2008-09-01

    Full Text Available Metformin hydrochloride (metformin HCl was formulated as a hydrophobic matrix sustained release tablet employing wax materials and the sustained release behavior of the fabricated tablet was investigated. Sustained release matrix tablets containing 500 mg metformin HCl were developed using different bees wax combinations. The tablets were prepared by wet granulation technique. The formulation was optimized on the basis of acceptable tablet properties and in vitro drug release. The resulting formulation produced monolithic tablets with optimum hardness, uniform thickness, consistent weight uniformity and low friability. Statistically significant differences were found among the drug release profile from different bees wax combination matrices. The results of dissolution studies indicated that formulations F-III, F-IV and F-V (bees wax and cetyl alcohol combination matrices, exhibited drug release pattern very close to theoretical release profile. Applying kinetic equation models, the mechanism of release of the drug from the three formulations was found to be followed Higuchi model, as the plots showed high linearity, with correlation coefficient (R² value of 0.98 or more. Tablet matrices containing cetyl alcohol gave better release of the drug than other materials studied. However, the rate of release varied with amount of cetyl alcohol in the matrix. The 'n' value lies below 0.5 (Korsmeyer-Peppas model demonstrating that the mechanism controlling the drug release was the quasi Fickian. Therefore, the results of the kinetic study obtained permit us to conclude that the fabricated hydrophobic matrix tablets, in this case, delivers the drug through diffusion dominated mechanism.O cloridrato de metformina (metformina.HCl foi formulado como comprimido de liberação controlada, empregando materiais cerosos como matriz hidrofóbica, e o comportamento dessa formulação foi investigado. Comprimidos com matriz de liberação controlada contendo 500 mg

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

    Directory of Open Access Journals (Sweden)

    Carol M Ulloa

    2009-09-01

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

  1. Pharmacokinetics of an extended release formulation of alprazolam (Xanax XR) in healthy normal adolescent and adult volunteers.

    Science.gov (United States)

    Glue, Paul; Fang, Annie; Gandelman, Kuan; Klee, Brian

    2006-01-01

    The purpose of this study was to estimate pharmacokinetics, safety, and tolerability of single doses of an extended release formulation of alprazolam (Xanax XR) in adolescent and adult healthy volunteers. This was a randomized, open-label, single-dose, 2-period crossover study. Twelve adolescent healthy volunteers (13-17 years) and 12 adult healthy volunteers (20-45 years) received single doses of Xanax XR 1 mg or 3 mg tablets. Blood samples were obtained predose and for 48 hours postdose. Plasma samples were assayed for alprazolam and its two active metabolites alpha-hydroxy-alprazolam and 4-hydroxy-alprazolam using a validated LC-MS/MS method. Safety assessments included clinical laboratory tests, vital signs, and adverse event monitoring. At both dose levels, mean plasma concentration-time profiles of alprazolam, alpha-hydroxy-alprazolam, and 4-hydroxy-alprazolam were similar in adolescent and adult subjects. The ratios of estimated geometric means for AUC(0-infinity) and Cmax between adolescents and adults for both dose levels were 115% (95% CI: [93, 143]) and 111% (95% CI: [95, 129]), respectively. An assessment of dose proportionality between the 3 mg and 1 mg alprazolam doses within both age groups indicated that the AUC(0-infinity) and Cmax were both within 80-125% equivalence limits. Parent-metabolite ratios were similar in both age groups and were consistent with those previously reported. Alprazolam was well tolerated by both age groups. The most common adverse event was somnolence, which occurred in a dose-related manner. Based on the similar pharmacokinetic profiles, dosing of Xanax XR should be similar in adolescents and adults.

  2. Intrathecal treatment of neoplastic meningitis due to breast cancer with a slow-release formulation of cytarabine

    Science.gov (United States)

    Jaeckle, K A; Phuphanich, S; Bent, M J van den; Aiken, R; Batchelor, T; Campbell, T; Fulton, D; Gilbert, M; Heros, D; Rogers, L; O'Day, S J; Akerley, W; Allen, J; Baidas, S; Gertler, S Z; Greenberg, H S; LaFollette, S; Lesser, G; Mason, W; Recht, L; Wong, E; Chamberlain, M C; Cohn, A; Glantz, M J; Gutheil, J C; Maria, B; Moots, P; New, P; Russell, C; Shapiro, W; Swinnen, L; Howell, S B

    2001-01-01

    DepoCyte is a slow-release formulation of cytarabine designed for intrathecal administration. The goal of this multi-centre cohort study was to determine the safety and efficacy of DepoCyte for the intrathecal treatment of neoplastic meningitis due to breast cancer. DepoCyte 50 mg was injected once every 2 weeks for one month of induction therapy; responding patients were treated with an additional 3 months of consolidation therapy. All patients had metastatic breast cancer and a positive CSF cytology or neurologic findings characteristic of neoplastic meningitis. The median number of DepoCyte doses was 3, and 85% of patients completed the planned 1 month induction. Median follow up is currently 19 months. The primary endpoint was response, defined as conversion of the CSF cytology from positive to negative at all sites known to be positive, and the absence of neurologic progression at the time the cytologic conversion was documented. The response rate among the 43 evaluable patients was 28% (CI 95%: 14–41%); the intent-to-treat response rate was 21% (CI 95%: 12–34%). Median time to neurologic progression was 49 days (range 1–515+); median survival was 88 days (range 1–515+), and 1 year survival is projected to be 19%. The major adverse events were headache and arachnoiditis. When drug-related, these were largely of low grade, transient and reversible. Headache occurred on 11% of cycles; 90% were grade 1 or 2. Arachnoiditis occurred on 19% of cycles; 88% were grade 1 or 2. DepoCyte demonstrated activity in neoplastic meningitis due to breast cancer that is comparable to results reported with conventional intrathecal agents. However, this activity was achieved with one fourth as many intrathecal injections as typically required in conventional therapy. The every 2 week dose schedule is a major advantage for both patients and physicians. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11161370

  3. Development of in vitro-in vivo correlation for extended-release niacin after administration of hypromellose-based matrix formulations to healthy volunteers.

    Science.gov (United States)

    Kesisoglou, Filippos; Rossenu, Stefaan; Farrell, Colm; Van Den Heuvel, Michiel; Prohn, Marita; Fitzpatrick, Shaun; De Kam, Pieter-Jan; Vargo, Ryan

    2014-11-01

    Development of in vitro-in vivo correlations (IVIVCs) for extended-release (ER) products is commonly pursued during pharmaceutical development to increase product understanding, set release specifications, and support biowaivers. This manuscript details the development of Level C and Level A IVIVCs for ER formulations of niacin, a highly variable and extensively metabolized compound. Three ER formulations were screened in a cross-over study against immediate-release niacin. A Multiple Level C IVIVC was established for both niacin and its primary metabolite nicotinuric acid (NUA) as well as total niacin metabolites urinary excretion. For NUA, but not for niacin, Level A IVIVC models with acceptable prediction errors were achievable via a modified IVIVC rather than a traditional deconvolution/convolution approach. Hence, this is in contradiction with current regulatory guidelines that suggest that when a Multiple Level C IVIVC is established, Level A models should also be readily achievable. We demonstrate that for a highly variable, highly metabolized compound such as niacin, development of a Level A IVIVC model fully validated according to agency guidelines may be challenging. However, Multiple Level C models are achievable and could be used to guide release specifications and formulation/manufacturing changes. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  4. 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...

  5. A pillar[5]arene based gel from a low-molecular-weight gelator for sustained dye release in water.

    Science.gov (United States)

    Yao, Yong; Sun, Yan; Yu, Huaxu; Chen, Wenrui; Dai, Hong; Shi, Yujun

    2017-11-24

    A soft gel based on pillar[5]arene was successfully prepared using a carbazone reaction. Furthermore, dyes such as TPP or TPPE can be incorporated into this gel and were observed to be released in a sustain