Didanosine-loaded Chitosan Microspheres Optimized By Surface-response Methodology: A Modified Maximum Likelihood Classification" Approach Formulation For Reverse Transcriptase Inhibitors."

Didanosine-loaded chitosan microspheres were developed applying a surface-response methodology and using a modified Maximum Likelihood Classification. The operational conditions were optimized with the aim of maintaining the active form of didanosine (ddI), which is sensitive to acid pH, and to develop a modified and mucoadhesive formulation. The loading of the drug within the chitosan microspheres was carried out by ionotropic gelation technique with sodium tripolyphosphate (TPP) as cross-linking agent and magnesium hydroxide (Mg(OH)2) to assure the stability of ddI. The optimization conditions were set using a surface-response methodology and applying the Maximum Likelihood Classification, where the initial chitosan concentration, TPP and ddI concentration were set as the independent variables. The maximum ddI-loaded in microspheres (i.e. 1433mg of ddI/g chitosan), was obtained with 2% (w/v) chitosan and 10% TPP. The microspheres depicted an average diameter of 11.42μm and ddI was gradually released during 2h in simulated enteric fluid.

Impact Of Drug Formulation And Free Platinum/cisplatin Ratio On Hypersensitivity Reactions To Cisplatin: Formulation Matters.

Use of cisplatin can induce type I hypersensitivity reactions that may also be linked to the quality of the drug utilized. We observed cases of hypersensitivity that appeared to be associated with the brand of cisplatin used. The aim of this study was to compare two different brands of cisplatin in relation to type I hypersensitivity reactions. Brand A was used in a tertiary care teaching hospital until 2012, and use of brand B started from January 2013, when the first hypersensitivity cases were observed. Patients were categorized based on symptom. Cisplatin of both brands was analysed by high-performance liquid chromatography (HPLC) and high-resolution electrospray ionization mass spectrometry (ESI-(+)-MS) and characterized according to US Pharmacopeia. There were no cases of hypersensitivity associated with the use of cisplatin brand A, whereas four of 127 outpatients that used cisplatin brand B were affected. The two brands were in accordance with the US Pharmacopeia parameters, and there was no significant difference in the total platinum levels between the two brands when analysed by HPLC. However, high-resolution ESI-(+)-MS analyses show that brand B contains approximately 2.7 times more hydrolysed cisplatin than brand A. The increase in the hydrolysed form of cisplatin found in brand B may be the cause of the hypersensitivity reaction observed in a subset of patients. We present the first study of the quality of drugs by high-resolution ESI-(+)-MS. Drug regulatory agencies and manufacturers should consider including measurement of hydrolysed cisplatin as a quality criterion for cisplatin formulations.

The use of a graphite-silicone rubber composite electrode in the determination of rutin in pharmaceutical formulation

The possibility of using a graphite silicone-rubber composite electrode (GSR) in a differential pulse voltammetric(DPV) procedure for rutin (vitamin P) determination is described. Cyclic voltammograms of rutin presented a reversible pair of oxidation/reduction peaks respectively at 0.411 and 0.390 V (vs. SCE) at the GSR surface in Britton-Robinson(B-R) buffer solution pH 4.0. In DPV after optimization of conditions, an oxidation peak at 0.370 V (vs. SCE) was used to quantitative determination of rutin in B-R buffer solution pH 4.0. In this case a linear dynamic range of 5.0×10-8 to 50.0×10-8 mol L-1 was observed with a detection limit of 1.8×10-8 mol L-1 for the analyte. Recoveries from 94 to 113% were observed. The electrode surface was renewed by polishing after each determination, with a repeatability of 1.09 ± 0.06 µA (n = 10) peak current. Rutin was determined in a pharmaceutical formulation using the proposed electrode and the results agreed with those from an official method within 95% confidence level.

A positional FEM Formulation for geometrical non-linear analysis of shells

This work presents a fully non-linear finite element formulation for shell analysis comprising linear strain variation along the thickness of the shell and geometrically exact description for curved triangular elements. The developed formulation assumes positions and generalized unconstrained vectors as the variables of the problem, not displacements and finite rotations. The full 3D Saint-Venant-Kirchhoff constitutive relation is adopted and, to avoid locking, the rate of thickness variation enhancement is introduced. As a consequence, the second Piola-Kirchhoff stress tensor and the Green strain measure are employed to derive the specific strain energy potential. Curved triangular elements with cubic approximation are adopted using simple notation. Selected numerical simulations illustrate and confirm the objectivity, accuracy, path independence and applicability of the proposed technique.

Hidden vorticity in binary Bose-Einstein condensates

We consider a binary Bose-Einstein condensate (BEC) described by a system of two-dimensional (2D) Gross-Pitaevskii equations with the harmonic-oscillator trapping potential. The intraspecies interactions are attractive, while the interaction between the species may have either sign. The same model applies to the copropagation of bimodal beams in photonic-crystal fibers. We consider a family of trapped hidden-vorticity (HV) modes in the form of bound states of two components with opposite vorticities S(1,2) = +/- 1, the total angular momentum being zero. A challenging problem is the stability of the HV modes. By means of a linear-stability analysis and direct simulations, stability domains are identified in a relevant parameter plane. In direct simulations, stable HV modes feature robustness against large perturbations, while unstable ones split into fragments whose number is identical to the azimuthal index of the fastest growing perturbation eigenmode. Conditions allowing for the creation of the HV modes in the experiment are discussed too. For comparison, a similar but simpler problem is studied in an analytical form, viz., the modulational instability of an HV state in a one-dimensional (1D) system with periodic boundary conditions (this system models a counterflow in a binary BEC mixture loaded into a toroidal trap or a bimodal optical beam coupled into a cylindrical shell). We demonstrate that the stabilization of the 1D HV modes is impossible, which stresses the significance of the stabilization of the HV modes in the 2D setting.

Non-linear boundary element formulation applied to contact analysis using tangent operator

This work presents a non-linear boundary element formulation applied to analysis of contact problems. The boundary element method (BEM) is known as a robust and accurate numerical technique to handle this type of problem, because the contact among the solids occurs along their boundaries. The proposed non-linear formulation is based on the use of singular or hyper-singular integral equations by BEM, for multi-region contact. When the contact occurs between crack surfaces, the formulation adopted is the dual version of BEM, in which singular and hyper-singular integral equations are defined along the opposite sides of the contact boundaries. The structural non-linear behaviour on the contact is considered using Coulomb`s friction law. The non-linear formulation is based on the tangent operator in which one uses the derivate of the set of algebraic equations to construct the corrections for the non-linear process. This implicit formulation has shown accurate as the classical approach, however, it is faster to compute the solution. Examples of simple and multi-region contact problems are shown to illustrate the applicability of the proposed scheme. (C) 2011 Elsevier Ltd. All rights reserved.

Dual boundary element formulation applied to analysis of multi-fractured domains

This paper deals with analysis of multiple random crack propagation in two-dimensional domains using the boundary element method (BEM). BEM is known to be a robust and accurate numerical technique for analysing this type of problem. The formulation adopted in this work is based on the dual BEM, for which singular and hyper-singular integral equations are used. We propose an iterative scheme to predict the crack growth path and the crack length increment at each time step. The proposed scheme able us to simulate localisation and coalescence phenomena, which is the main contribution of this paper. Considering the fracture mechanics analysis, the displacement correlation technique is applied to evaluate the stress intensity factors. The propagation angle and the equivalent stress intensity factor are calculated using the theory of maximum circumferential stress. Examples of simple and multi-fractured domains, loaded up to the rupture, are considered to illustrate the applicability of the proposed scheme. (C) 2010 Elsevier Ltd. All rights reserved.

Analyzing static three-dimensional elastic domains with a new infinite boundary element formulation

A new two-dimensionally mapped infinite boundary element (IBE) is presented. The formulation is based on a triangular boundary element (BE) with linear shape functions instead of the quadrilateral IBEs usually found in the literature. The infinite solids analyzed are assumed to be three-dimensional, linear-elastic and isotropic, and Kelvin fundamental solutions are employed. One advantage of the proposed formulation over quadratic or higher order elements is that no additional degrees of freedom are added to the original BE mesh by the presence of the IBEs. Thus, the IBEs allow the mesh to be reduced without compromising the accuracy of the result. Two examples are presented, in which the numerical results show good agreement with authors using quadrilateral IBEs and analytical solutions. (C) 2010 Elsevier Ltd. All rights reserved.

A coupled boundary element/differential equation method formulation for plate-beam interaction analysis

In this work, a new boundary element formulation for the analysis of plate-beam interaction is presented. This formulation uses a three nodal value boundary elements and each beam element is replaced by its actions on the plate, i.e., a distributed load and end of element forces. From the solution of the differential equation of a beam with linearly distributed load the plate-beam interaction tractions can be written as a function of the nodal values of the beam. With this transformation a final system of equation in the nodal values of displacements of plate boundary and beam nodes is obtained and from it, all unknowns of the plate-beam system are obtained. Many examples are analyzed and the results show an excellent agreement with those from the analytical solution and other numerical methods. (C) 2009 Elsevier Ltd. All rights reserved.

A boundary element formulation for analysis of elastoplastic plates with geometrical nonlinearity

In this paper a new boundary element method formulation for elastoplastic analysis of plates with geometrical nonlinearities is presented. The von Mises criterion with linear isotropic hardening is considered to evaluate the plastic zone. Large deflections are assumed but within the context of small strain. To derive the boundary integral equations the von Karman`s hypothesis is taken into account. An initial stress field is applied to correct the true stresses according to the adopted criterion. Isoparametric linear elements are used to approximate the boundary unknown values while triangular internal cells with linear shape function are adopted to evaluate the domain value influences. The nonlinear system of equations is solved by using an implicit scheme together with the consistent tangent operator derived along the paper. Numerical examples are presented to demonstrate the accuracy and the validity of the proposed formulation.

Non-linear boundary element formulation with tangent operator to analyse crack propagation in quasi-brittle materials

This work deals with analysis of cracked structures using BEM. Two formulations to analyse the crack growth process in quasi-brittle materials are discussed. They are based on the dual formulation of BEM where two different integral equations are employed along the opposite sides of the crack surface. The first presented formulation uses the concept of constant operator, in which the corrections of the nonlinear process are made only by applying appropriate tractions along the crack surfaces. The second presented BEM formulation to analyse crack growth problems is an implicit technique based on the use of a consistent tangent operator. This formulation is accurate, stable and always requires much less iterations to reach the equilibrium within a given load increment in comparison with the classical approach. Comparison examples of classical problem of crack growth are shown to illustrate the performance of the two formulations. (C) 2009 Elsevier Ltd. All rights reserved.

BEM formulation for von Karman plates

This work deals with nonlinear geometric plates in the context of von Karman`s theory. The formulation is written such that only the boundary in-plane displacement and deflection integral equations for boundary collocations are required. At internal points, only out-of-plane rotation, curvature and in-plane internal force representations are used. Thus, only integral representations of these values are derived. The nonlinear system of equations is derived by approximating all densities in the domain integrals as single values, which therefore reduces the computational effort needed to evaluate the domain value influences. Hyper-singular equations are avoided by approximating the domain values using only internal nodes. The solution is obtained using a Newton scheme for which a consistent tangent operator was derived. (C) 2009 Elsevier Ltd. All rights reserved.

An extended BEM formulation for plates reinforced by rectangular beams

This article presents a BEM formulation developed particularly for analysis of plates reinforced by rectangular beams. This is an extended version of a Previous paper that only took into account bending effects. The problem is now re-formulated to consider bending and membrane force effects. The effects of the reinforcements are taken into account by using a simplified scheme that requires application of ail initial stress field to locally correct the bending and stretching stiffness of the reinforcement regions. The domain integrals due to the presence of the reinforcements are then transformed to the reinforcement/plate interface. To reduce the number of degrees of freedom related to the presence of the reinforcement, the proposed model was simplified to consider only bending and stretching rigidities in the direction of the beams. The complete model can be recovered by applying all six internal force correctors, corresponding to six degrees of freedom per node. Examples are presented to confirm the accuracy of the formulation and to illustrate the level of simplification introduced by this strong reduction in the number of degrees of freedom. (C) 2008 Elsevier Ltd. All rights reserved.

BEM formulation for reinforced plates

This article presents a BEM formulation developed to analyse reinforced plate bending. The reinforcements are formulated using a simplified scheme based on applying an initial moment field adopted to locally correct the stiffness of the reinforcement regions. The domain integrals due to the presence of the reinforcements are then transformed to the reinforcement/plate interface. The increase in system stiffness due to the reinforcements can be taken into account independently for each coefficient. Thus, one can conveniently reduce the number of degrees of freedom required in considering the reinforcement. Only one degree-of-freedom is required at each internal node when taking into account only the flexural stiffness of beams. Examples are presented to confirm the accuracy of the formulation. (C) 2009 Elsevier Ltd. All rights reserved.

A hybrid-Trefftz formulation for plane elasticity with selective enrichment of the approximations

This work is related to the so-called non-conventional finite element formulations. Essentially, a methodology for the enrichment of the initial approximation which is typical of the meshless methods and based on the clouds concept is introduced in the hybrid-Trefftz formulation for plane elasticity. The formulation presented allows for the approximation and direct enrichment of two independent fields: stresses in the domains and displacements on the boundaries of the elements. Defined by a set of elements and interior boundaries sharing a common node, the cloud notion is employed to select the enrichment support for the approximation fields. The numerical analysis performed reveals an excellent performance of the resulting formulation, characterized by the good approximation ability and a reduced computational effort. Copyright (C) 2009 John Wiley & Sons, Ltd.