Preparation and Evaluation of Sustained-Release Matrix Tablets Based on Metoprolol and an Acrylic Carrier Using Injection Moulding

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. © 2012 American Association of Pharmaceutical Scientists.

Mechanisms involved in drug release from silicone matrix intravaginal rings containing water soluble excipients

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MAP kinase pathway signalling is essential for extracellular matrix determined mammary epithelial cell survival

Mammary epithelial cells in primary cell culture require both growth factors and specific extracellular matrix (ECM)-attachment for survival. Here we demonstrate for the first time that inhibition of the ECM-induced Erk 1/Erk 2 (p42/44 MAPK) pathway, by PD 98059, leads to apoptosis in these cells. Associated with this cell death is a possible compensatory signalling through the p38 MAP kinase pathway the inhibition of which, by SB 203580, leads to a more rapid onset of apoptosis. This provides evidence for a hitherto undescribed Erk 1/Erk 2 to p38 MAP kinase pathway 'cross-talk' that is essential for the survival of these cells. The cell death associated with inhibition of these two MAP kinase pathways however, occurred in the presence of insulin that activates the classical PI-3 kinase-dependent Akt/PKB survival signals and Akt phosphorylation. Cell death induced by inhibition of the MAP kinase pathways did not affect Akt phosphorylation and may, thus, be independent of PI-3 kinase signalling.

Nitrofuran antibiotic metabolites detected at parts per million concentrations in retina of pigs - a new matrix for enhanced monitoring of nitrofuran abuse

Nitrofuran metabolite residues AOZ, AMOZ, AHD and SEM were detected at parts per million concentrations in retina of pigs fed therapeutic doses of nitrofuran antibiotics. Discovery of this residue depot may allow widespread technology transfer to laboratories lacking LC-MS/MS thus improving global monitoring of these drugs.

Dioxin and furan residues in wood mice (Apodemus sylvaticus) following a large scale polyvinyl chloride (PVC) fire

A forest ecosystem was contaminated as a result of a fire involving 600 t of PVC. A wide range of 2,3,7,8-substituted dioxin and furan congeners were elevated (by up to 4-fold) on soil adjacent to the factory compared to a site 200 m from the factory perimeter. Livers of wood mice (Apodemus sylvaticus) caught on these areas were also analysed for dioxins and furans. Toxic equivalents (TEQs) were 9-fold higher in wood mice caught on the site 10 m from the factory perimeter compared with the site 200 m from the perimeter, with individual 2,3,7,8-substituted congeners being elevated by up to 30-fold. Wood mouse liver TEQs were found to be highly correlated with cadmium kidney concentrations, cadmium also being found at elevated concentrations at the accident site. There was also a significant positive correlation between wood mouse liver TEQs and relative liver weights (wet weights expressed as a percentage of total body weight). The results of this study are discussed in the wider context of dioxin contamination in the environment.

Atomic harmonic generation in time-dependent R-matrix theory

We have developed the capability to determine accurate harmonic spectra for multielectron atoms within time-dependent R-matrix (TDRM) theory. Harmonic spectra can be calculated using the expectation value of the dipole length, velocity, or acceleration operator. We assess the calculation of the harmonic spectrum from He irradiated by 390-nm laser light with intensities up to 4 x 10(14) W cm(-2) using each form, including the influence of the multielectron basis used in the TDRM code. The spectra are consistent between the different forms, although the dipole acceleration calculation breaks down at lower harmonics. The results obtained from TDRM theory are compared with results from the HELIUM code, finding good quantitative agreement between the methods. We find that bases which include pseudostates give the best comparison with the HELIUM code, but models comprising only physical orbitals also produce accurate results.

BIT-LEVEL SYSTOLIC ARRAY CIRCUIT FOR MATRIX VECTOR MULTIPLICATION.

A bit-level systolic array for computing matrix x vector products is described. The operation is carried out on bit parallel input data words and the basic circuit takes the form of a 1-bit slice. Several bit-slice components must be connected together to form the final result, and authors outline two different ways in which this can be done. The basic array also has considerable potential as a stand-alone device, and its use in computing the Walsh-Hadamard transform and discrete Fourier transform operations is briefly discussed.

RELATIONSHIP BETWEEN WORD AND BIT LEVEL SYSTOLIC ARRAYS AS APPLIED TO MATRIX multiplied by MATRIX MULTIPLICATIONS.

The mapping of matrix multiplied by matrix multiplication onto both word and bit level systolic arrays has been investigated. It has been found that well defined word and bit level data flow constraints must be satisfied within such circuits. An efficient and highly regular bit level array has been generated by exploiting the basic compatibilities in data flow symmetries at each level of the problem. A description of the circuit which emerges is given and some details relating to its practical implementation are discussed.

A multi-fibre multi-layer representative volume element (M2RVE) for prediction of matrix and interfacial damage in composite laminates

Multiscale micro-mechanics theory is extensively used for the prediction of the material response and damage analysis of unidirectional lamina using a representative volume element (RVE). Th is paper presents a RVE-based approach to characterize the materi al response of a multi-fibre cross-ply laminate considering the effect of matrix damage and fibre-matrix interfacial strength. The framework of the homogenization theory for periodic media has been used for the analysis of a 'multi-fibre multi-layer representative volume element' (M2 RVE) representing cross-ply laminate. The non-homogeneous stress-strain fields within the M2RVE are related to the average stresses and strains by using Gauss theorem and the Hill-Mandal strain energy equivalence principle. The interfacial bonding strength affects the in-plane shear stress-strain response significantl y. The material response predicted by M2 RVE is in good agreement with the experimental results available in the literature. The maximum difference between the shear stress predicted using M2 RVE and the experimental results is ~15% for the bonding strength of 30MPa at the strain value of 1.1%

Microstrcutural evolution of SiC fibre embedded AA6061 matrix induced by ultrasonic consolidation

Ultrasonic consolidation (UC) uses high frequency (20-40KHz) mechanical vibrations to produce a solid-state metallurgical bond (weld) between metal foils. UC as a novel layered manufacturing technique is used in this research to embed reinforcing members such as silicon carbide fibers into the aluminium alloy 6061's matrices. It is known that UC induce volume and surface effect in the material it is acting on. Both effects are employed in embedding active/passive elements in the metal matrix. Whilst the process and the two effects are used and identified at macro level, what is happening at micro level is unknown and hardly studied. In this research we are investigating the phenomena occurring in the microstructure of the parts during UC process to obtain better understanding about how and why the process works. In this research, high-resolution electron backscatter diffraction is used to study the effects of the UC process on the evolution of microstructure in AA6061 with and without fibre elements. The inverse pole figures (IPF), pole figures (PF) and the correlated misorientation angle distribution of the mentioned samples are obtained. The characteristics of the crystallographic orientation, the grain structure and the grain boundary are analysed to find the effect of ultrasonic vibration and embedding fibre on the microstructure and texture of the bond. The ultrasonic vibration will lead to exceptional refinement of grains to a micron level along the bond area and affect the crystallographic orientation. Additional plastic flow occurs around the fibre which leads to the fibre embedding. © 2008 Materials Research Society.