Design and development of nanoemulsion drug delivery system of amlodipine besilate for improvement of oral bioavailability

Nanoemulsion (NE) of amlodipine besilate (AB) was developed by spontaneous emulsification method with the aim to enhance the solubility and oral bioavailability of AB and to achieve localized delivery of drug at target site. Pseudoternary phase diagrams were constructed to identify the NE region. The selected formulations from NE region were subjected to droplet size analysis, partitioning study and in vitro drug release. The partition coefficient was calculated and correlated with percent dissolution efficiency as a tool to predict in vitro drug release from NEs. The release of drug from NEs was significantly higher (p < 0.01) than the marketed tablet formulation. The optimal formulation contained 15% Labrafil M, 35% [Tween 80: ethanol (2:1)], and 50% by weight aqueous phase (NE3) was characterized by transmission electron microscopy (TEM) and for thermodynamic stability. The pharmacokinetics and biodistribution studies of the optimized radiolabeled formulation (99mTc-labeled) in mice (p.o.) demonstrated a relative bioavailability of 475% against AB suspension. In almost all the tested organs, the uptake of AB from NE was significantly higher (p < 0.05) than AB suspension especially in heart with a drug targeting index of 44.1%, also confirming the efficacy of nanosized formulation at therapeutic site. A three times increase in the overall residence time of NE further signifies the advantage of NEs as drug carriers for enhancing bioavailability of AB.     

Effect of dynamic strain aging on the appearance of the rare earth texture component in magnesium alloys

Binary Mg alloys were prepared containing Zn, Ce and Gd. These were extruded and the resulting mechanical properties were determined. The intensities of the rare earth (RE) texture components were measured and linked to the extrusion conditions. Tension and compression testing was carried out on samples taken from extruded bars and a Mg-0.5Ce cast alloy. Over particular temperature and strain rate ranges, dynamic strain aging (DSA) was observed. The ranges over which DSA occurred during testing are compared with the conditions under which the RE texture components were produced during extrusion. It is concluded that formation of the RE texture components can be enhanced by extruding when the rate sensitivity is negative, i.e. under conditions where DSA is taking place.     

A new strain hardening model for rate-dependent crystal plasticity

This paper presents a crystal plasticity based finite element analysis employing the new microstructure-based strain hardening model recently presented by Saimoto and Van Houtte (2011) [7] to simulate formability and texture evolution in the commercial aluminum alloy 5754. Simulations are performed to compare the predictive capability of the new hardening model against the common work hardening models using a rate-dependent plasticity formulation. The parameters in the numerical models are calibrated using the X-ray data published by Iadicola et al. (2008) [9] for the aluminum sheet alloy 5754. The predictions of the model for balanced biaxial tension and in-plane plane-strain tests are compared against experimental observations presented in Iadicola et al. (2008) [9]. It is concluded that the new model provides the best predictions of the large strain behavior of Aluminum sheet alloy 5754 subjected to various strain paths.