A new drug delivery system using plasma-irradiated pharmaceutical aids. VIII. Delayed-release of theophylline from double-compressed tablet composed of eudragit as wall material.

The rapid release from a double-compressed tablet containing theophylline as a core drug with the pH-dependent water-soluble polymers, Eudragit L100, S100 or L100-55 used as a wall material was suppressed by argon plasma-irradiation due to an effect of inter-segmental cross-link reactions on the decrease in the surface polymer solubility of outer layer. In addition, the rapid theophylline release from the double-compressed tablet of Eudragit L100-55 with a lower glass transition temperature (Tg) has converted into the delayed-release system under a set of plasma operational conditions due to an additional effect of plasma heat flux on softening of Eudragit L100-55 surface resulting in the formation of the film-like surface with a particle-particle interlinking of the outer layer.     

Comparison of the fragility index of different eudragit polymers determined by activation enthalpies

The present study aimed to apply fragility index (m) of polymers in the determination of the optimal amount of plasticizer in polymer films. The fragility index of different Eudragit polymers (RS, RL, EPO) was assessed by differential scanning calorimerty (DSC), applying the Arrhenius connection (logq–1/T _g). The fragility of Eudragit EPO films proved to be the highest, while in the case of RS and RL, the increase of the alkyl-chain length caused the increase of fragility. Studying the effect of plasticizer (triethyl citrate, TEC) on the m value of Eudragit RL and RS films, a near linear reduction of the fragility index could be observed between 5–30% TEC concentration, but above 30%, this value leveled out to constant.     

Control of prolonged drug release and compression properties of ibuprofen microspheres with acrylic polymer, eudragit RS, by changing their intraparticle porosity [corrected]

Prolonged-release spherical micro-matrices of ibuprofen with Eudragit RS were prepared using a novel emulsion-solvent diffusion method. Those particles were termed "microspheres" due to their characteristic sponge-like texture and unique dissolution and compression properties unlike conventional microcapsules or microspheres. The internal porosity of microspheres could be easily controlled by changing the concentration of the drug and the polymer in the emulsion droplet (ethanol). With lower concentration of ibuprofen in the ethanol, the resultant microspheres had a higher porosity, about 50%. The drug release rate from the microspheres was interpreted by the Higuchi model of spherical matrices, which depended only on their internal porosity of the microspheres when size distribution and drug content were the same. The tortuosities in the microspheres were found to be almost constant (3-4) irrespective of porosity, suggesting the same internal texture. Microsphere compressibility was much improved over the physical mixture of the drug and polymer owing to the plastic deformation of their sponge-like structure. The more porous microspheres produced stronger tablets [corrected].     

Development of extended release coevaporates and coprecipitates of promethazine HCl with acrylic polymers: formulation considerations

The present investigation studied a novel extended release system of promethazine hydrochloride (PHC) with acrylic polymers Eudragit RLPO and Eudragit RS100 in different weight ratios (1 : 1 and 1 : 5) using coevaporation and coprecipitation techniques. Solid dispersions were characterized by Fourier-transformed infrared spectroscopy (FT-IR), Differential scanning calorimetry (DSC), Powder X-ray diffractometry (PXRD), Nuclear magnetic resonance (NMR), Scanning electron microscopy (SEM) as well as solubility and in vitro dissolution studies in 0.1 n HCl (pH 1.2), double distilled water and phosphate buffer (pH 7.4). Adsorption test from drug solution to solid polymers were also performed. Selected solid dispersion system was subjected to direct compression and compressed tablets were evaluated for in vitro dissolution studies. The progressive disappearance of drug peaks in thermotropic profiles of coevaporates were related to increasing amount of polymers while SEM studies suggested homogenous dispersion of drug in polymer. Eudragit RLPO had a greater adsorptive capacity than Eudragit RS100 and thus its coevaporates in 1 : 5 ratio exhibited higher dissolution rate with 91.90% drug release for 12 h. Among different formulations, tablets prepared by Eudragit RLPO coevaporates (1 : 5) displayed extended release of drug for 12 h with 90.87% release followed by zero order kinetics (r(2)=0.9808).     

Oligomeric polyaromatic ether-ketone-sulfones with acetylenic end groups. X

Two new oligomeric polyaromatic ether-ketone-sulfones with acetylenic end groups have been synthesized. These acetylene-terminated oligomers are soluble in common organic solvents and can be cured under thermal conditions to give the crosslinked polymers which do not soften below 240°C. In the case of oligomer which is incorporated with terephthaloyl chloride, the cured polymer shows almost no penetration below 400°C. Isothermal aging studies show that the cured polymers are stable in circulating air at 300°C with less than 10% weight loss in 3 days.     

Evaluation of phenomena occurring during the preparation of matrix granules by the hot melt technique

The aim of this study was to evaluate the applicability of hot melt granulation for the formulation of a pH-sensitive intelligent tablet containing heat- and moisture-sensitive components. An appropriate combination of magnesium trisilicate, aluminium hydroxide, sodium bicarbonate, and basic butylated methacrylate copolymer (Eudragit E PO) exhibited a good disintegration profile, but poor processibility. Hot melt granulation was applied with the aid of polyethylene glycol 2000 to increase the tablettability. The effects of the composition and the process on the properties of the granules and tablets formed were assessed with thermoanalytical and conventional testing methods. The heating of mixtures containing basic butylated methacrylate copolymer (Eudragit E PO) below its glass transition caused a relevant change in the wettability of the granules. This was induced by an alteration in the microstructure of the agglomerates. Tablets prepared from the granules containing an appropriate ratio of polymers exhibited an appropriate mechanical and disintegration profile. The thermal behaviour of the mixture of polymers cannot be predicted from the properties of the starting materials. Their interaction, demonstrated by DSC, can cause significant structure-forming problems in the matrices. The parameters of the granules and tablets varied with the quantity of the polymer applied. With an appropriate combination of polymers, hot melt granulation can be a suitable method for the preparation of intermediates for the formulation of controlled-release antacid tablets. Thermal analysis can promote an understanding of the process and determination of its operational parameters.     

Characterization of the inhibition of enveloped virus infectivity by the cationic acrylate polymer eudragit E100

The antiviral effects of the cationic acrylate polymer E100 on a panel of lipid-enveloped viruses and the interactions involved are studied. The treatment of several common viruses with E100 induced a dose-dependent inhibition of the infectivity of viruses below the detection limit of the assays employed. Similarly, the treatment of human sera infected with HIV or HCV reduced virus RNA plasma levels to undetectable values. This implies that Eudragit E100 can interact with enveloped viruses, even in the presence of proteins, through a mechanism that is not reversed by titration of the positively charged groups of the polymer, opening the possibility to remove viral particles with the polymer as it is eliminated.     

Novel Shape-Memory Polymer with Two Transition Temperature Based on Two Different Memory Mechanism

As an important kind of intelligent materials, shape-memory materials have been received increasing attention on account of their interesting properties and potential applications in recent years. Particularly, the rise of shape-memory polymers by far surpasses well-known metallic shape-memory alloys in their shape-memory properties. The advantages of polymers compared to other materials are their easier availability and their wide range of mechanical and physical properties. The polymers designed to exhibit a shape-memory effect require two components on the molecular level: crosslinks to determine the permanent shape and switching segments with Ttrans to fix the temporary shape. Up to now almost all papers on shape-memory polymers introduce switching segments with the covalent linking method. On the other hand, only several cases concern non-covalent interaction. However, the research works mentioned above is based on a single Ttrans (i.e., Tm or Tg).Following our previous work, here, we first report a novel kind of polymer consisted of PMMA-PEG semi-interpenetrating polymer networks (semi-IPN), which exhibiting independently two shape memory effects based on Tm and Tg, respectively. This result can also extend the shape memory polymer categories from one Ttrans to two Ttrans, and the combination of Tm and Tg give rise to an extremely excellent shape-memory effect.Two different shape memory behaviors of this material based on two transition temperatures were evaluated by bending test as follows: a straight strip of the specimen was folded at a temperature above Ttrans and kept in this shape. The so-deformed sample was cooled down to a temperature Tlow＜ Ttrans and the deforming stress were released. When the sample was heated up to the measuring temperature Thigh ＞ Ttrans, it recovered its initial shape. The deformation angle θ f varied as a function of time and the ratio of the recovery was defined as θ f /180. The PMMA-PEG polymer behaved as a hard plastic at room temperature and did not deform at all under a given stress. However, if upon cooling; even after unloading, it did not recover the initial shape. When the polymer was ratio reach 90%. This observation illustrates that the shape memory phenomenon with 90%recovery ratio was found to be archived by changing the operation temperature below and above of Tm of crystalline PEG, which is based on a reversible order-disorder transition of crystalline aggregates. Similarly, the investigation on the shape memory transitin at Tg that when the sample (above Tg of the semi-IPN), the polymer showed second shape memory behavior, and quickly recovered to initial shape in 45s with shape recovery ratio more than 99%.     

Distinct difference in ionic transport behavior in polymer electrolytes depending on the matrix polymers and incorporated salts

Two different electrolyte salts, lithium bis(trifluoromethanesulfonyl)imide (LiTFSI), and a room temperature ionic liquid, 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide (EMITFSI), were incorporated into network polymers to obtain ion-conductive polymer electrolytes. Network polymers of poly(ethylene oxide-co-propylene oxide) (P(EO/PO)) and poly(methyl methacrylate) (PMMA) were chosen as matrixes for LiTFSI and EMITFSI, respectively. Both of the polymer electrolytes were single-phase materials and were completely amorphous. Ionic conductivity of the polymer electrolytes was measured over a wide temperature range, with the lowest temperatures close to or below the glass transition temperatures (Tg). The Arrhenius plots of the conductivity for both of the systems exhibited positively curved profiles and could be well fit to the Vogel-Tamman-Fulcher (VTF) equation. The conductivity of the PMMA/EMITFSI electrolytes was higher at most by 3 orders of magnitude than that of the LiTFSI/P(EO/ PO) electrolytes at ambient temperature. When the ideal glass transition temperature, T0 (one of the VTF fitting parameters), was compared with the Tg, a difference in the ionic conduction was apparent in these systems. In the P(EO/PO)/LiTFSI electrolytes, the T0 and Tg increased in parallel with salt concentration and the T0 was lower than the Tg by ca. 50 degrees C. On the contrary, the difference between the T0 and the Tg increased with increasing content of PMMA in the PMMA/EMITFSI electrolytes, with the observed difference in the concentration range studied reaching up to ca. 100 degrees C. The conductivity at the Tg, sigma(Tg), for the LiTFSI/P(EO/PO) electrolytes was on the order of 10(-14-)10(-13) S cm(-1) and increased with increasing salt concentration, whereas that for the PMMA/EMITFSI polymer electrolytes reached 10(-7) S cm(-1) when the concentration of PMMA was high. The ion transport mechanism was discussed in terms of the concepts of coupling/decoupling and strong/fragile for the two different polymer electrolytes.     

Preparation of functional composite particles of salbutamol sulfate using a 4-fluid nozzle spray-drying technique

A previous study on spray-drying demonstrated that it could promote the solubility of poorly water-soluble drugs using water-soluble polymers. Here, the preparation of composite particles of salbutamol sulfate (Sb) with water-insoluble polymers, such as Eudragit RS (RS) or Eudragit RL (RL) as a carrier, was examined. Despite the water insolubility of both polymers, the permeability of water was low in the former but high in the latter. We attempted to prepare controlled release composite particles by exploiting the characteristics of these carriers. The composite particles of the three components (Sb, RS, and RL) were prepared using a 4-fluid nozzle spray-dryer, and their physico-chemical and dissolution properties were compared with physical mixtures. Examination of particle morphology by scanning electron microscopy (SEM) revealed that the particles from the spray-drying process had atomized to several microns and were spherical. Analysis by X-ray diffraction and differential scanning calorimetry revealed that diffraction peaks and heat of fusion of Sb in the spray-dried samples decreased, indicating that the drug was amorphous and formed a solid dispersion. FT-IR analysis suggested that the amino group of Sb and a carbonyl group of the polymers formed a hydrogen bond. A dissolution test of Sb-RS-RL particles prepared using the 4-fluid nozzle spray-drying method showed that release rates were depressed significantly compared to the physical mixture at pH 1.2 and 6.8, and the depression was greater when RS was used instead of RL, presumably because of the permeability difference. The compression of these particles into tablets revealed that desirable controlled released dosage forms could be prepared. In addition, Sb was used to simulate an anti-asthmatic drug. For this an Andersen cascade impactor for dry powder inhalers was used to investigate delivery to the lungs.     

Effect of preparation temperature in solvent evaporation process on Eudragit RS microsphere properties

Eudragit RS 100 microspheres containing ketoprofen as a model drug were prepared by the solvent evaporation method using an acetone/liquid paraffin solvent system. The influence of various preparation temperatures: 10, 25, 35, and 40 degrees C, on particle size and morphology, drug content and release kinetics, and drug crystal state was evaluated. With increasing temperature, microsphere average size was found to increase and particle size distribution to widen significantly. At 10 degrees C particles of irregular shape are formed, whereas higher temperatures gradually improve the sphericity of microspheres. As can be seen from SEM photographs, particle surface roughness decreases as preparation temperature increases. It was found that temperature had no effect either on ketoprofen microencapsulation efficiency or on its crystal state, but it does influence emulsion-stabilizer incorporation. Ketoprofen forms solid solution in Eudragit matrix and maintains amorphous state for significant period of time. Drug release rates from microspheres correlated with microspheres' surface roughness and to a lesser extent with particle size.     

Photoinduced intramolecular charge separation in a polymer solid below the glass transition temperature

Photoinduced intramolecular charge separation (CS) in a polar polymer glass, cyanoethylated pullulan (CN-PUL), was studied below the glass transition temperature (Tg=395 K). A series of three carbazole (Cz: donor)-cyclohexane (S: spacer)-acceptor (A: acceptor) molecules (Cz-S-A) was used as intramolecular donor-acceptor dyads. The photoinduced CS rate was evaluated by the fluorescence decay measurement at temperatures from 100 to 400 K. The CS rate (kCS) increased above 200 K even far below Tg where micro-Brownian motions of the whole polymer chain are frozen. Below 200 K, on the other hand, kCS showed weak dependence on temperature. The temperature dependence of kCS is discussed in terms of the dielectric relaxation time of the polymer matrix. Consequently, CS below Tg was well explained by a thermally nonequilibrium electron transfer (ET) formula above 200 K and by a two-mode quantum-mechanical ET formula below 200 K. The increase in kCS above 200 K is mainly caused by a thermally activated low-frequency matrix mode originating from the side-chain relaxation of polar cyano groups. The weak temperature dependence of kCS can be explained by a nuclear-tunneling effect caused by a high-frequency matrix mode (variant Planck's over 2piomegH=250 cm-1) and an intramolecular vibrational mode (variant Planck's over 2piomegaQ=1300 cm-1). The high-frequency mode of the polymer matrix was attributed to a vibrational or librational motion of polar groups in the CN-PUL glassy solid.     

Patterning on nonplanar substrates: flexible honeycomb films from a range of self-assembling star copolymers

The effect of glass transition temperature, Tg, on the self-assembly of "honeycomb" microstructures on nonplanar substrates was probed by the synthesis of a library of core cross-linked star polymers with different arm compositions. Star polymers based on poly(dimethyl siloxane), poly(ethyl acrylate), poly(methyl acrylate), poly(tert-butyl acrylate), and poly(methyl methacrylate) were synthesized by the "arm first" strategy using atom-transfer radical polymerization. Reaction conditions were optimized, and a series of high molecular weight star polymers were prepared in high yield. The glass transition temperature of the star polymers ranged from -123 to 100 degrees C which allowed the suitability for the formation of porous honeycomb-like films via the "breath figure" technique on nonplanar surfaces to be investigated. All star compositions successfully formed ordered films on flat surfaces. However, only star polymer compositions with a Tg below 48 degrees C could form homogeneous honeycomb coatings on the surface of nonplanar substrates.     

Floating and sustained-release characteristics of effervescent tablets prepared with a mixed matrix of Eudragit L-100-55 and Eudragit E PO

The aim of this study was to evaluate the influence of Na-bicarbonate as an effervescent agent on the floating and sustained-release characteristics in 0.1 M HCl of tablets made of Eudragit E PO (EE) and/or Eudragit L-100-55 (EL) as matrix formers at different EE:EL weight ratios: 0:100, 25:75, 50:50, 75:25, and 100:0. The tablets were made by direct compression utilizing metronidazole as a model drug. Effervescent tablets with 50EE/50EL (w/w) showed the best floating and sustained drug release properties in the dissolution medium. The corresponding noneffervescent tablets were nonfloating and showed significantly faster drug release. Effervescent tablets with single polymers showed an immediate drug release pattern. These results were explained by Fourier-transform infrared spectroscopy and elemental analysis, which showed strong evidence of interpolyelectrolyte complexation between EE and EL when they were exposed to 0.1 M HCl as an effervescent hybrid matrix, but not as a noneffervescent hybrid matrix. The role of Na-bicarbonate in allowing EE-EL complexation during dissolution was explained as due to raising the pH around EL particles for sufficient polymer ionization and ionic-interaction with the ionized EE.     

Ethylcellulose, polycaprolactone, and eudragit matrices for controlled release of piroxicam from tablets and microspheres

The present paper provides details of the preparation of polymeric tablets and microspheres based on piroxicam as a therapeutic active agent and the drug release study from these formulations. Tablets composed of ethylcellulose, Eudragit? or mixtures of Eudragit? and synthesised poly(oxepan-2-one) were prepared and tested. The effect of the matrix on the drug release at 37°C was studied. The drug-loaded microparticles were prepared using solvent evaporation microencapsulation. These systems were characterised by SEM and FTIR spectroscopy and the size and size distribution were also determined. The results demonstrated that the drug release could be modified by means of these formulations. Finally, piroxicam dissolution rate constants were calculated from Higuchi??s release model.     

pH-enzyme di-dependent chronotherapeutic drug delivery system of theophylline for nocturnal asthma

The purpose of this research work was to develop and evaluate a chronotherapeutic based colon-targeted drug delivery system of theophylline (THEO) exploiting pH-enzyme sensitive property for the prevention of episodic attack of asthma in early morning. Guar gum microspheres of theophylline were prepared by emulsification technique. Coating of microspheres was performed using solvent evaporation method with pH sensitive Eudragit(?) polymers. The particle size and surface morphology, entrapment efficiency and degree of swelling of microspheres were examined. The in vitro drug release studies were performed in pH progression medium and also in the presence of 2% rat caecal content. Theophylline was efficiently microencapsulated in guar gum microspheres at different polymer concentrations (1-4%). Fourier transform infrared (FT-IR)-spectroscopy confirmed the intermolecular interactions between guar gum and glutaraldehyde. Coating of guar gum microspheres by Eudragit led to decelerate the in vitro drug release of THEO. Moreover in vitro drug release studies also performed with 2% rat caecal content showed marked increment in drug release. The controlled release of THEO after a lag time was achieved with developed formulation for chronotherapeutic delivery. The pH dependent solubility behavior of Eudragit and gelling properties of guar gum are found to be responsible for delaying the release.     

Studies on phthalocyanine sheet polymers

Cobalt, nickel and copper phthalocyanine sheet polymers are synthesized by heating their respective metal (II) phthalocyanine tetracarboxylic acids at 400 °C in nitrogen atmosphere. These polymers are characterized using UV-Visible spectra, IR spectra, magnetic susceptibility, X-ray powder diffraction and thermogravimetric analysis. Electrical conductivity studies are carried out using two-probe technique in the temperature range 25-200 °C for each polymer. These polymeric materials showed room temperature electrical conductivity 10-1000 times higher values compared to earlier reported values for this type of sheet polymers.     

高分子链的去拥挤转变及低温流动

简述了拥挤理论的基本原理,运用拥挤理论来说明高分子链间弱相互作用对高分子链所处的状态的影响,特别是对高分子玻璃化转变的影响.在实验中,采用固体核磁共振方法探测高分子的链间邻近度,并比较了不同链间邻近度的高分子样品在玻璃化转变温度以下的压力诱导流行行为,发现即使测试温度比高分子玻璃化转变温度低132℃,高分子链在压力下依...     

Physical Properties of the Biodegradable Polymer Compositions Containing Natural Polyesters and their Synthetic Analogues

The thermal, mechanical and thermo-mechanical properties of polymer compositions, containing synthetic biodegradable polymers i.e. polylacide (PLA) and aliphatic-aromatic copolyester (BTA), natural biopolyester n-PHB and its synthetic atactic analog (a-PHB) were investigated. Thermal properties of the polymer compositions were studied by means of DSC . The compositions of various polymer weight ratio were tested. Compositions containing BTA and n-PHB create polyphase systems, what was confirmed by DSC. In this case the two Tg and two Tm values were observed. Polymer compositions containing PLA and BTA showed different behaviours. At the BTA content up to 30 weight % only one Tg and one Tm were indicated. At the increase of the BTA content to 50% weight and above, the two Tg, and two Tm were observed. Mixtures of BTA with n-PHB, PLA and with a-PHB show considerably greater values of the strain (ε) in comparison with initial polymers (n-PHB, PLA). It was found that in contrary to mixtures containing PLA, at the BTA content in the mixture with n-PHB above 50% of weights increases not only the strain, but also the stress at break (σ). Strong increase of the ε value in PLA/a-PHB mixtures with the content of a-PHB above 30% of weights were observed.     

Molecular dynamics simulation of the glass transition temperature of fullerene filled cis-1,4-polybutadiene nanocomposites

t In this work,the effect of the fullerene (C60) weight fraction and PB-C60 interaction on the glass transition temperature (Tg) of polymer chains has been systemically investigated by adopting the united atom model of cis-1,4-poly(butadiene) (cis-PB).Various chain dynamics properties,such as atom translational mobility,bond/segment reorientation dynamics,torsional dynamics,conformational transition rate and dynamic heterogeneity of the cis-PB chains,are analyzed in detail.It is found that Tg could be affected by the C60 weight fraction due to its inhibition effect on the mobility of the cis-PB chains.However,Tg is different,which depends on different dynamics scales.Among the chain dynamics properties,Tg is the lowest from atom translational mobility,while it is the highest from the dynamic heterogeneity.In addition,Tg can be more clearly distinguished from the dynamic heterogeneity;however,the conformational transition rate seems to be not very sensitive to the C60 weight fraction compared with others.For pure cis-PB chains,Tg and the activation energy in this work can be compared with those of other polymers.In addition,the temperature dependence of the dynamic properties has different Arrhenius behaviors above and below Tg.The activation energy below Tg is lower than that above Tg.This work can help to understand the effect of the C60 on the dynamic properties and glass transition temperature of the cis-PB chains from different scales.