Hydrophilic Polymer Matrix Research Articles

A novel nuclear magnetic resonance (NMR) imaging method for measuring the water front penetration rate in hydrophilic polymer matrix capsule plugs and its role in drug release.

An NMR imaging method was developed to estimate the rate of water movement in slow-release capsule matrices of pseudoephdrine HCl and hydroxypropyl cellulose (HPC). Test capsules were first placed in a USP method 2 (paddles, 50 rpm) dissolution apparatus. Each plug was removed from the dissolution medium at predetermined times, blotted dry, and placed within the magnetic field of a General Electric 400-MHz wide-bore NMR spectrometer equipped with a microimaging accessory. Images were recorded along the transverse plane of each plug. The water penetration rate was determined by comparison of the cut and weighed contour plots of the images acquired. After 1 hr, the plugs tamped to 200 N exhibited water penetration to the center, while only 45% of the drug was released. The percentage dry matrix was fitted to the Jost equation to obtain a diffusion coefficient of 4.15 x 10(-6) cm2/sec. NMR imaging is set forth as an important and practicable technique to investigate drug formulations. In the HPC matrix system of this study, the NMR imaging results convincingly revealed the rate of hydration front penetration not to be a rate-limiting step in the drug release process.

Resolution of Amino Acid Enantiomers by Ligand Exchange Chromatography on a New Chiral Packing

Abstract Resolution of α—amino acid enantiomers by ligand exchange chromatography on a new chiral packing, which the chiral ligands were linked onto a hydrophilic polymeric matrix through long spacers, was studied. The packing had high enantioselectivity for most of the amino acids tested. The mechanism of the resolution was discussed. The semi- preparative scale resolution was made.

Low temperature incorporation of bovine serum albumin into a bead formed macroporous hydrophilic polymer matrix with potential for sustained release.

A process of freeze-thaw polymerization involving the low temperature photopolymerization of a mixed solution of monomers and bovine serum albumin around frozen ice crystals has been used to generate a bead formed macroporous hydrophilic matrix with potential for sustained release. Beads over the size range 100-3000 microns were fabricated with surface and internal pores of between 0.7-2.6 microns whose diameter could be controlled by manipulation of the monomers to solvent ratio. Increasing both the proportion of monomers in the monomer solution and the percentage of BSA incorporated reduced the EWC of beads. The BSA release profile was characterized by an initial burst followed by a lower but sustained release lasting up to 1 month. The total cumulative release of BSA and the proportion of the incorporated BSA load subsequently released were both reduced in physiological saline compared with distilled water but enhanced by freeze drying, mild agitation and incubation at 37 degrees C.

Spin labels as a probe of the molecular environment of covalently bound ligands in an hydrophobic and an hydrophilic polymer

The molecular motions of spin-labelled ligands covalently bound by spacer groups to an hydrophobic and an hydrophilic polymer matrix were evaluated by ESR spectroscopy. The ligands were prepared by alkylation of 4- N-methylamino-TEMPO with the ω-bromocarboxylic esters, Br(CH 2) n COOEt, n = 1,4 and 10. The hydrolysed esters were coupled to a cross-linked aminoethylated polyacrylamide hydrogel ( n = 1,4,10) and to a surface hydroxylated elastomeric polyester ( n = 4). The rotational correlation times ( τ c ) of the nitroxide label in the hydrogels were measured in the dry state and after exposure to water at pH 4, 7.4 and 10.5. The τ c of the nitroxide label was insensitive to the length of the spacer group and to the degree of protonation of the tertiary amino group of the ligand. There was no evidence of self-association of the ligand and spacer, or more than a single phase within the polyacrylamide hydrogel. The τ c of the nitroxide labelled polyester was similarly insensitive to pH, but was sensitive to organic solvents. The low mobility of the spin label and its high concentration were consistent with the spin label being covalently bound within the hydrophobic polyester matrix to a depth of at least 5μ m.

External control of drug release. IV. Controlled release of 5-fluorouracil from a hydrophilic polymer matrix by microwave irradiation.

A polymeric system capable of delivering 5-fluorouracil (5-FU) at increased rates on demand by external microwave irradiation was developed. Sustained-release systems were made by incorporating 5-FU into an ethylene-vinyl alcohol copolymer. When exposed to release medium, the delivery systems released the drug slowly and continuously. Upon exposure to microwave irradiation, the drug was released at a much higher rate. Release rates returned to base line levels when the microwave irradiation was discontinued. This study demonstrated that release rates of 5-FU from a polymer matrix can be increased at desired times by external microwave irradiation.

Sustained release of insulin from a hydrophilic polymer matrix implanted in diabetic rats.

A long-acting insulin preparation involving the sustained release of biologically active insulin from a hydrophilic ethylene-vinyl alcohol (EVAl) matrix was developed. A single subcutaneous implant of this insulin lowered the blood glucose levels of diabetic rats for more than one month. These results suggest that a long-acting insulin may be produced by the entrapment of insulin within a hydrophilic EVAl copolymer matrix.

Ammonia-sensitive fibre optic probe utilising an immobilised spectrophotometric indicator

The immobilisation of an indicator dye reagent for the development of fibre optic probes for detecting ammonia vapour has been investigated. The indicator dye reagent bromothymol blue was immobilised on a hydrophilic polymer matrix and the concentration of ammonia in the vapour phase determined in the range 1.5 × 10–3–60 × 10–3 mol l–1 by reflectance measurements. Some possible interferences from other vapours were also investigated.

Analysis of Proteins with new, mildly hydrophobic high-performance liquid chromatography packing materials

A series of packings that had alkyl and aryl groups incorporated into a hydrophilic polymeric matrix were developed for hydrophobic interaction chromatography. Using an inverse salt gradient of ammonium sulfate or sodium chloride, a series of proteins were purified and the activity of trypsin was monitored using post-column detection. Retention times of proteins generally increased in the following order of ligands: hydroxypropyl, propyl, benzyl, isopropyl, phenyl and pentyl.

Increased enzyme activity in immobilised cell composites with a highly hydrophilic polymer matrix

AbstractStreptomyces phaeochromogenes cells were immobilised by radiation polymerisation of hydrophilic monomers; highest levels of glucose isomerase activity were found in immobilised cell composites with highly hydrophilic polymer matrices. The enzyme activity in the composites from the copolymerisation of hydroxyethyl acrylate (or methacrylate) and N‐vinyl‐2‐pyrrolidone monomer increased markedly with increase in the content of the N‐vinyl‐2‐pyrrolidone monomer, owing to the higher water absorption by the polymer matrix, and was close to that of the non‐immobilised cells. The enzyme activity was affected by monomer concentration, the hydrophilicity, and chemical structure of the polymer matrix. The Michaelis constant of the composites from hydrophilic monomers was close to that of the intact cells.

Interaction of Enzyme with Polymer Matrix in Immobilized Enzymes

AbstractThermolysin was immobilized by radiation polymerization of hydroxyalkyl acrylate and tetradecaethylene glycol dimethacrylate monomers at low temperatures in the presence of the enzyme, and the degree of interaction of the enzyme with the polymer matrix was studied by measuring the thermal stability of the immobilized enzyme. The thermal stability was affected by the molecular structure of the monomer; the thermal stability of the immobilized enzyme from hydrophilic monofunctional monomers in the wet state was higher than that from hydrophobic bifunctional monomers. The thermal stability in polymers formed from hydroxy‐alkyl acrylates decreased with an increase in the number of methylene units in the monomer, owing to a change of the state of the enzyme trapped in the porous polymer matrix. The enzyme molecule trapped in a hydrophilic porous polymer matrix appeared to be stabilized by interaction with the polymer chains.

On the interaction of heparin-containing polymers with plasma proteins and blood

In vitro experiments showed that polymeric hydrogels containing covalently immobilized heparin affect the parameters of blood clotting system. This is not accounted for by the elution of heparin into the surrounding medium and this property of heparin-containing polymers is caused by specific interaction of immobilized heparin with plasma proteins. By the methods of coagulogramms and thromboelastography it was revealed that the decrease of total blood anticoagulant activity takes place due to the decrease in blood of fibrinogen, prothrombin and thrombin content and the supression of fibrinstabilizing factor activity. Free heparin content in blood was left unaffected. It was found that plasma proteins permeate the hydrophilic polymer matrix and interact with immobilized heparin. Binding strength for immobilized heparin is decreased in the array fibrinogen ⋍thrombin ⪢ ⪢ plasmin > serum albumin. Complexes of immobilized heparin with fibronogen, thrombin and plasmin display lytic action towards unstabilized fibrin.

Effect of Irradiation and Immobilization on Spinach Chloroplast Activities

Abstract The effect of y-ray irradiation and immobilization by means of radiation polymerization on PS II activity (O2 evolution) of isolated chloroplasts from spinach was investigated. Reduction of O2 evolution activity by irradiation was small at lower temperatures below – 24 °C, but the activity decreased slightly by freezing at extremely low temperature below –78 °C. So the optimum low temperature range for the treatment was observed. The immobilized chloroplast in a hydrophilic polymer matrix showed the stable duration of O2 evolution activity more than 700 h at 4 °C . Thermo-stability of chloroplast was also improved greatly by immobilization. The active center of PS II in immobilized chloroplasts was retained even after 60 min standing at 50 °C.