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.

An Experimental and Numerical Study of the Static and Fatigue Performance of a Composite Adhesive Repair

Experimental static and fatigue tension-tension tests were carried out on 5HS/RTM6 composite intact coupons and coupons incorporating adhesively-bonded (FM300-2) stepped flush joints. The results show that the adhesive joint, which is widely used in repairs, significantly reduces the static strength as well as the fatigue life of the composite. Both, the static and the fatigue failure of the ‘repaired’ coupons occur at the adhesive joint and involve crack initiation and propagation. The latter is modelled using interface finite elements based on the decohezive zone approach. The material degradation in the interface constitutive law is described by a damage variable, which can evolve due to the applied loads as well as the number of fatigue cycles. The fatigue formulation, based on a published model, is adapted to fit the framework of the pseudotransient formulation that is used as a numerical tool to overcome convergence difficulties. The fatigue model requires three material parameters. Numerical tests show that a single set of these parameters can be used to recover, very accurately, the experimental S-N relationship. Sensitivity studies show that the results are not mesh dependent.