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Sustained release of acetaminophen from heterogeneous matrix tablets: influence of polymer ratio, polymer loading, and co-active on drug release.

The aim of this research was to investigate the effect of pseudoephedrine (PE), polymer ratio, and polymer loading on the release of acetaminophen (APAP) from hydroxypropyl methyl cellulose (HPMC)/polyvinylpyrrolidone (PVP) matrices. Granules formulated with APAP or both APAP and PE, and various blends of HPMC and PVP were compressed into tablets at varying compression forces ranging from 2000 to 6000 Ib. In vitro drug release from the matrix tablets was determined and the results correlated with those of tablet water uptake and erosion studies. Drug release from the formulations containing both APAP and PE was slower than those containing only APAP (P < 0.05, F = 3.10). Drug release from tablets formulated with APAP only showed an initial burst at pH 1.16 or 7.45, and at high total polymer loading (> or = 9.6%). Formulations containing both APAP and PE showed slower drug release at pH 1.16 than at pH 7.45. At pH 1.16, a decline in the percentage of APAP released occurred after 18 hours. This was due to the hydrolysis of APAP to p-aminophenol. The drug dissolution data showed good fit to the Korsmeyer and Peppas model, and the values of the release exponents ranged from 0.20 to 0.62, indicating a complex drug release pattern. Tablet erosion studies indicated that the amount of APAP released was linearly related to the percentage of tablet weight loss. The kinetics of tablet water uptake was consistent with a diffusion and stress relaxation controlled mechanism. Overall, the results of this study indicated that PE, as a co-active in the formulation, modified the matrix, and hence retarded APAP release.

Acetaminophen↗

Influence of polymers weight ratio and pH of polymers solution on the characteristics of chitosan-carboxymethyl cellulose microspheres containing theophylline.

Optimization of formulation for chitosan-carboxymethyl cellulose (CH-CMC) microspheres that contain a drug of narrrow therapeutic index was the interest of this study. Theophylline (TPH) was chosen as a model drug. The effects of chitosan:sodium carboxymethyl cellulose (CH:SCMC) weight ratio (X1) and pH of polymers solution (X2) as independent variables on the physical characteristics of the microspheres as well as release profile of TPH from microspheres prepared by the emulsion coacervation-phase separation technique were studied. The influence of each of the two variables on responses such as angle of repose, compressibility index, incorporation efficiency particle size, initial drug release, time for 50% drug release (T50%) and % drug released in 8 hours was investigated. Generally, the increase in CH:SCMC weight ratio showed to increase the incorporation efficiency of the drug, increase the particle size and decrease the flowability of the microspheres. The increase of CH:SCMC ratio was also responsible to get low initial drug release, slow drug release (long T50%) and incomplete total drug released in 8 hours. On the other hand, high and low pHs of polymers solution were responsible to decrease drug incorporation in the microspheres and to produce small particles while, good flowability was obtained at pHs 2.5 and 4. A full factorial experimental design was employed to investigate the effect of the two independent variables on the responses. The results were analyzed by a general quadratic equation and response surfaces generated. From the obtained regression, it was concluded that the effect of CH:SCMC polymers ratio is more significant in changing the values of flowability particle size and drug release in 8 hours while pH values were more significant in changing the values of initial drug release and T50%. On the other hand the interaction coefficients of the two variables showed synergistic effect on flowability and drug release in 8 hours while, there were antagonist effects on particle sizes and T50%. From the optimization studies it is possible to choose the conditions required for the preparation of microspheres with the desired characteristics.

Bronchodilator Agents↗

[Enzymatic conversion of polymers. Nature of apparent product inhibition in the course of enzymatic degradation of polymer substrates].

The general regularities for the kinetics of enzymatic conversion of polymers were studied. It was proposed that the formal kinetic analysis of progress kinetic curves for enzymatic degradation of polymers inevitably results in the apparent effects of product inhibition, even in the case when the products are not virtually bound to the enzyme and there is no real product inhibition at all. An experimental verification of this hypothesis was performed, using maltodextrins hydrolysis by Aspergillus niger glucoamylase as an example. It was shown that a progressive decrease of the enzyme reactivity with respect to a polymer substrate in the course of its degradation is kinetically equivalent to a progressive decrease of the velocity of an enzymatic reaction due to the product inhibition. These two cases cannot practically be distinguished by conventional methods of analysis of progress kinetic curves.

Aspergillus niger↗

Immune responses of inbred guinea pigs to the sequential polymer poly(L-Tyr-L-Ala-Gly): studies with the oligomers of the polymers.

Synthetic known sequence polypeptides poly(Tyrosine-Glutamic acid-Alanine-Glycine) T-G-A-Gly), were found to be very immunogenic in responder inbred guinea pigs. Two and one-half micrograms were enough to elicit both humoral and cellular responses. Only the alpha-helical oligomers were immunogenic and were able to inhibit the homologous antigen-antibody reactions. The random polymers of comparable amino acid composition, i.e., poly(glutamic acid60alanine40) (GA), poly(glutamic acid50 tyrosin50) (GT), poly(glutamic acid60alanine30tyrosine10)(GAT10), did not inhibit. The antibodies against (T-G-A-Gly)n did not bind to the closely related known sequence polymer poly tyrosine-alanine-glutamic acid-glycine) (T-A-G-Gly)n or to the above random polymers. It is thus concluded that antibodies against (T-G-A-Gly)n are directed against conformational determinats.

Alanine↗

[Polymer-containing eye drops. I. Rheological characteristics of polymer solutions].

Authors studied rheological features of opthalmic solutions. They found that water soluble polymer solutions of different characteristics (non-ionic, anionic, linear chain, and/or cross linked) are pseudoplastic in rheological aspect. Rheological features exponentially increase with the concentration of the polymer. With the calculation of the constants of the exponential line, polymer concentration providing an optimum viscosity can be determined.

Ophthalmic Solutions↗

The Monolayer Behavior of Amphiphilic Polymer and Heterostructure of Polymer LB Film/CdS Clusters.

In this paper we report the behavior of an amphiphilic polymer monolayer on pure water and Cd2+ subphase. This polymer was composed of hydrophilic ethylene diamine epichlorohydrin slightly crosslinked microgel and hydrophobic stearic chains, noted as ES-1. The introduction of Cd2+ ions in subphase had a marked effect on the process of the organization of the amphiphilic polymer at the air/water interface due to the association of Cd2+ ions with the hydrophilic network, which could be indicated by the pressure-area isotherms and Brewster Angle Microscopy. Ordered ES-1/Cd2+ LB multilayers were fabricated. After the multilayers reacted with H2S gas, CdS clusters were synthesized within the film, which was characterized by X-ray diffraction and UV-visible spectroscopy. Copyright 1999 Academic Press.

Journal Article↗

Cell partitioning in two-polymer aqueous phase systems and cell electrophoresis in aqueous polymer solutions. Red blood cells from different species.

A correlation, with some exceptions, between the partitioning behavior of red blood cells (RBCs) from different species in charge-sensitive dextran-poly(ethylene glycol) (PEG) aqueous phase systems and their relative electrophoretic mobilities (EPMs) in phosphate-buffered saline (PBS) has previously been reported. This relationship has now been further probed by carrying out RBC electrophoresis in media (i.e., dextran-rich bottom or PEG-rich top phases) more closely approximating the environment in which RBC partitioning takes place to see whether a better correlation would ensue. The ratios of viscosity-corrected EPMs of different species' RBCs in (diluted) dextran-rich or PEG-rich phases/EPMs of the respective species' RBCs in PBS differ for a number of species, and from each other, reflecting thereby differences in kind (i.e., dextran or PEG) and nature of polymer interaction with these RBCs. There is a general tendency for EPMs in any of the tested media to correlate with both the cells' relative partition ratios as well as with their relative EPMs in one of the other media. However, examination of the behavior of different species' RBCs taken two species at a time indicates that their relative EPMs in any two suspending media or in one suspending medium and partitioning often differ. Thus, both the cell partition ratio and the cell EPMs obtained in polymer media must, at least in some cases, reflect surface properties other than or in addition to the charge reflected by EPM measurements in PBS or saline. Cell electrophoresis in polymer solutions thereby provides an additional parameter for discriminating between surface properties of certain closely related cell populations.

Animals↗

Mapping of endogenous lectins in macrophages colonizing an implanted polymer surface--effect of polymer structure.

The design of synthetic polymers may affect structural features of inflammatory cells, for example the expression of endogenous sugar receptor molecules like lectins in macrophages and foreign body giant multinucleate cells. This characteristic was studied histochemically by use of biotinylated (neo)glycoproteins. The results demonstrate the influence of polymer structure on the phenotypic expression of molecules recognizing carbohydrates in these cells. Very strong activity was observed for carrier-immobilized beta-galactose in cells colonizing hydrophobic polystyrene implants. Sialic acid moieties were not recognized by cells located on the surface of all types of polymeric implant. This study encourages investigation of the influence of polymer design on the differentiation of macrophages.

Animals↗

Partition of proteins in aqueous polymer two-phase systems and the effect of molecular weight of the polymer.

The partition of substances in aqueous polymer two-phase systems is influenced by the molecular weight of the phase-forming polymers. We investigate how the effect of the molecular weight of the polymers depends on the molecular weight of the partitioned protein. We show that the magnitude of change of the partition is very small for proteins of molecular weights around 10,000, but increases almost linearly up to molecular weights of 250,000.

Dextrans↗

1-3 connectivity piezoelectric ceramic-polymer composite transducers made with viscous polymer processing for high frequency ultrasound.

Potential applications of high frequency ultrasound exist because of the high spatial resolution consequent upon short wavelength. The frequencies of interest, typically from 25 MHz upwards, are easily supported by modern instrumentation but the capabilities of ultrasonic transducers have not kept pace and the transducers in high frequency commercial ultrasonic systems are still made with single-phase crystal, ceramic or piezopolymer materials. Despite potential performance advantages, the 1-3 connectivity piezoelectric ceramic-polymer composite materials now widely used at lower ultrasonic frequencies have not been adopted because of manufacturing difficulties. These difficulties are centred on fabrication of the 1-3 piezoceramic bristle-block comprising tall, thin pillars upstanding from a supporting stock. Fabrication techniques which have been explored already include injection moulding, mechanical dicing, and laser machining. Here, we describe an alternative technique based on viscous polymer processing (VPP) to produce net shape ceramic bristle-blocks. VPP produces green-state ceramic with rheological properties suitable for embossing. We outline how this can be created then report on our work to fabricate PZT bristle-blocks with lateral pillar dimensions of the order of 50 microm and height-to-width ratios of the order of 10. These have been backfilled with low pre-cure viscosity polymer and made into complete 1-3 piezocomposite transducer elements. We outline the performance of the transducers in terms of electrical impedance and pulse-echo behaviour and show that it corresponds well with computer modelling. We conclude that VPP is a promising technique to allow the established advantages of piezocomposite material to be exploited at higher frequencies than have been possible so far.

Journal Article↗

Insight into the chiral recognition of warfarin enantiomers by epichlorhydrin/beta-cyclodextrin polymer-based supports: determination of stoichiometry and stability of warfarin/beta-cyclodextrin polymer complexes.

The complexation of warfarin (W) enantiomers by a hydrosoluble high-molecular-weight beta-cyclodextrin/epichlohydrin polymer (EP/beta-CD polymer) was studied using HPLC with a mobile phase of methanol/0.1 M Na acetate/acetic acid (pH 4) at 22 degrees C. It was found that the complexes (W/beta-CD unit) have a 1:1 stoichiometry. The stability constants of the complex involving each enantiomer and the polymer beta-CD units were determined in the mobile phase, and the highest stability of the complex (S-warfarin/beta-CD unit) was observed. From the chromatographic separations of warfarin enantiomers on different beta-CD or its derivative supports, we have deduced the role of the simultaneous presence of several glyceryl (-O-CH(2)-CHOH-CH(2)-O-) and dihydroxypropyl (-O-CH(2)-CHOH-CH(2)OH) groups on one beta-CD ring in promoting the chiral recognition of warfarin enantiomers.

Chromatography, High Pressure Liquid↗

Molded monolithic rod of macroporous poly(styrene-co-divinylbenzene) as a separation medium for HPLC of synthetic polymers: on-column precipitation--redissolution chromatography as an alternative to size exclusion chromatography of styrene oligomers and polymers.

A process for the separation of styrene oligomers and polymers by size and composition using a novel separation medium has been demonstrated. The process involves precipitation of the macromolecules on the molded macroporous rod columns, followed by progressive elution utilizing a simple gradient of the mobile phase. Molded macroporous rod columns are ideally suited for this technique because convection through the large pores of the rod enhances the mass transport of large analyte molecules and accelerates the separation process. Styrene oligomers and polymers are separated in a 50-mm x 8-mm-i.d. column using a solvent gradient composed of a poor solvent such as water, methanol, or acetonitrile and increasing amounts of a good solvent, tetrahydrofuran. Excellent separations are obtained, demonstrating that precipitation-redissolution can be a suitable alternate to size exclusion chromatography (SEC) of some polymers. Compared to SEC, the gradient elution separation can be achieved at higher flow rates in a much shorter time. Precipitation-redissolution with gradient elution can also be used for the separation of copolymers, for which the process is controlled not only by molecular weight but also by the composition of the copolymers.

Chromatography, Gel↗

Self-assembly of chiral coordination polymers and macrocycles: a metal template effect on the polymer-macrocycle equilibrium.

The self-assembly of racemic and enantiopure binaphthyl-bis(amidopyridyl) ligands 1,1'-C(20)H(12){NHC(=O)-4-C(5)H(4)N}(2), 1, and 1,1'-C(20)H(12){NHC(=O)-3-C(5)H(4)N}(2), 2, with mercury(II) halides (HgX(2); X = Cl, Br, I) to form extended metal-containing arrays is described. It is shown that the self-assembly can lead to homochiral or heterochiral polymers or macrocycles, through self-recognition or self-discrimination of the ligand units, and the primary materials can further self-assemble through hydrogen bonding between amide substituents. In addition, the formation of macrocycles or polymers can be influenced by the presence or absence of excess mercury(II) halide, through a template effect, and mercury(II) halide inclusion complexes may be formed. In one case, an unusual polymeric compound was obtained, with 1 guest HgX(2) molecule for every 12 mercury halide units in the polymer.

Journal Article↗

Metal-containing ligands for mixed-metal polymers: novel Cu(II)-Ag(I) mixed-metal coordination polymers generated from [Cu(2-methylpyrazine-5-carboxylate)2(H2O)].3H2O and silver(I) salts.

One Cu(II)-containing ligand and two Cu(II)-Ag(I) mixed-metal coordination polymers have been synthesized. [Cu(2-methylpyrazine-5-carboxylate)2(H2O)].3H2O (1) was obtained as a molecular complex with two uncoordinated nitrogen donors by the reaction of 2-methylpyrazine-5-carboxylate sodium with CuCl(2).2H2O in water. Compound 1 crystallized in the triclinic space group P1, with a = 10.498(2) A, b = 11.000(2) A, c = 8.1424(16) A, alpha = 98.33(3) degrees, beta = 101.83(3) degrees, gamma = 66.68(3) degrees, and Z = 2. Reactions of 1 with silver(I) salts have been studied. Two Cu(II)-Ag(I) mixed-metal coordination polymers, namely, Ag[Cu(2-methylpyrazine-5-carboxylate)2.(H2O)2](BF4) (2) and Ag[Cu(2-methylpyrazine-5-carboxylate)2.(H2O)2](NO3) (3), have been generated by treating 1 with AgBF4 and AgNO3, respectively. Compound 2 crystallized in the monoclinic space group C2/c, with a = 25.827(5) A, b = 9.6430(19) A, c = 7.4525(15) A, beta = 94.74(3) degrees, and Z = 4. Compound 3 also crystallized in the monoclinic space group C2/c, with a = 25.855(5) A, b = 9.782(2) A, c = 7.1201(14) A, beta = 96.90(3) degrees, and Z = 4. The main structural feature in both 2 and 3 is a zigzag Cu(II)-Ag(I) mixed-metal chain, in which the alternating Cu(II) and Ag(I) centers are linked by 2-methylpyrazine-5-carboxylate spacers. The effect of the nitrate counterion was illustrated by compound 3, in which a novel [Ag+...NO3-] coordination chain has been found which acts as the connector to cross-link the one-dimensional zigzag chains into a three-dimensional network. In addition, an identical interchain O-H...O hydrogen bonding system has been found in both 2 and 3 and has been shown to play a significant role in directing the alignment of the one-dimensional mixed-metal polymer chains in the crystalline state. The magnetic susceptibilities of 2 and 3 were measured and found to follow the Curie law (mu eff = 1.85 for 2 and 1.83 for 3).

Journal Article↗

Preparation of micro- and nanopatterns of polymer chains grafted onto flexible polymer substrates.

In this work a simple novel method for preparing micro- and nanoscale patterns of polymer chains grafted onto flexible polymer substrates is described. A combination of the two techniques of radiation grafting and "grafting-from" has been made. This combination makes it possible to prepare grafted structures having micro- or nanoscale lateral dimensions that are determined by the electron beam or X-ray irradiation patterns used. The height of the grafted features can be controlled by the irradiation dose or such grafting reaction conditions as time, temperature, or monomer concentration. Our first results for nanopatterned samples demonstrate resolution comparable to those of other polymer-based lithography processes.

Journal Article↗

Liquid-crystalline polymers from cationic dendronized polymer-anionic lipid complexes.

The use of cationic dendronized polymers as a polyelectrolytic system for templating thermotropic liquid-crystalline phases (LC) via complexation and self-assembly with counter-charged ionic lipids is described. The topology of the LC phases resulting from the self-assembly process, their lattice parameter, and the interpenetration of lipid chains is discussed via birefringency analysis and small-angle X-ray scattering. Depending on the generation of the dendronized polymer and the length of the alkyl chains, amorphous, lamellar, and columnar tetragonal phases are observed. A structural model is proposed which accounts for the systematic variations of alkyl chain length as well as polymer generation. Owing to the reversible nature of the ionic complexation, this process proves high relevance for nanoporous channels, biomimetic, transport, and nanotemplating applications.

Journal Article↗

Mixed polymer brushes by sequential polymer addition: anchoring layer effect.

Smart surfaces can be described as surfaces that have the ability to respond in a controllable fashion to specific environmental stimuli. A heterogeneous (mixed) polymer brush (HPB) can provide a synthetic route to designing smart polymer surfaces. In this research we study HPB comprised of end-grafted polystyrene (PS) and poly(2-vinyl pyridine) (P2VP). The synthesis of the HPB involves the use of an "intermolecular glue" acting as a binding/anchoring interlayer between the polymer brush and the substrate, a silicon wafer. We compare anchoring layers of epoxysilane (GPS), which forms a self-assembled monolayer with epoxy functionality, to poly(glycidyl methacrylate) (PGMA), which forms a macromolecular monolayer with epoxy functionality. The PS and P2VP were deposited onto the wafers in a sequential fashion to chemically graft PS in a first step and subsequently graft P2VP. Rinsing the HPB in selective solvents and observing the change in water contact angle as a function of the HPB composition studied the switching nature of the HPB. Scanning probe microscopy was used to probe the topography and phase imagery of the HPB. The nature of the anchoring layer significantly affected the wettability and morphology of the mixed brushes.

Journal Article↗

Post-coordination of multinuclear transitional metal clusters to azulene-based polymers: a novel strategy for tuning properties in pi-conjugated polymers.

Direct treatment of azulene-thiophene copolymers with Ru(3)(CO)(12) led to unique examples of coordination of a multinuclear transition metal cluster to conjugated polymers. The polymer-metal cluster formation could be confirmed by (1)H NMR spectroscopic studies, and the coordination mode could be deduced from the crystallographic structure of model compounds. The composition of ruthenium carbonyl cluster could be used as a governing factor to tune the electronic, optical, and morphological properties of the organometallic polymers. [structure: see text]

Journal Article↗