Counterfeit drugs: analytical techniques for their identification

In recent years, the number of counterfeit drugs has increased dramatically, including not only “lifestyle” products but also vital medicines. Besides the threat to public health, the financial and reputational damage to pharmaceutical companies is substantial. The lack of robust information on the prevalence of fake drugs is an obstacle in the fight against drug counterfeiting. It is generally accepted that approximately 10% of drugs worldwide could be counterfeit, but it is also well known that this number covers very different situations depending on the country, the places where the drugs are purchased, and the definition of what constitutes a counterfeit drug. The chemical analysis of drugs suspected to be fake is a crucial step as counterfeiters are becoming increasingly sophisticated, rendering visual inspection insufficient to distinguish the genuine products from the counterfeit ones. This article critically reviews the recent analytical methods employed to control the quality of drug formulations, using as an example artemisinin derivatives, medicines particularly targeted by counterfeiters. Indeed, a broad panel of techniques have been reported for their analysis, ranging from simple and cheap in-field ones (colorimetry and thin-layer chromatography) to more advanced laboratory methods (mass spectrometry, nuclear magnetic resonance, and vibrational spectroscopies) through chromatographic methods, which remain the most widely used. The conclusion section of the article highlights the questions to be posed before selecting the most appropriate analytical approach.     

Enhancement of temozolomide stability by loading in chitosan-carboxylated polylactide-based nanoparticles

In the presented work, amphiphilic nanoparticles based on chitosan and carboxy-enriched polylactic acid have been prepared to improve the stability of the pro-drug temozolomide in physiological media by encapsulation. The carrier, with a diameter in the range of 150–180 nm, was able to accommodate up to 800 μg of temozolomide per mg of polymer. The obtained formulation showed good stability in physiological condition and preparation media up to 1 month. Temozolomide loaded inside the carrier exhibited greater stability than the free drug, in particular in simulated physiological solution at pH 7.4 where the hydrolysis in the inactive metabolite was clearly delayed. CS-SPLA nanoparticles demonstrated a pH-dependent TMZ release kinetics with the opportunity to increase or decrease the rate. Mass spectroscopy, UV-Vis analysis, and in vitro cell tests confirmed the improvement in temozolomide stability and effectiveness when loaded into the polymeric carrier, in comparison with the free drug.     

Asymptotic spherical symmetry of the free boundary in degenerate diffusion equations

Summary A general class of nonlinear degenerate parabolic equations in many space dimensions is considered and two main results concerning the free boundary are proved: (i) the «eventual» Lipschitz continuity in the space variable, (ii) the asymptotic spherical symmetry in a stronger sense than the «almost radiality» proved by Aronson & Caffarelli [2] for the porous medium equation. The proofs make use of geometric ideas based on the comparison principle and the method of moving planes.     

Graphs with prescribed Levi form trace

Abstract We prove existence and uniqueness of a viscosity solution of the Dirichlet problem related to the prescribed Levi mean curvature equation, under suitable assumptions on the boundary data and on the Levi curvature of the domain. We also show that such a solution is Lipschitz continuous by proving that it is the uniform limit of a sequence of classical solutions of elliptic problems and by building Lipschitz continuous barriers. Keywords: Levi mean curvature, Quasilinear degenerate elliptic PDE’s, Viscosity solutions, Comparison principle, Global Lipschitz estimates     

Averaging, Conley index continuation and recurrent dynamics in almost-periodic parabolic equations

We study a non-autonomous parabolic equation with almost-periodic, rapidly oscillating principal part and nonlinear interactions. We associate to the equation a skew-product semiflow and, for a special class of nonlinearities, we define the Conley index of isolated compact invariant sets. As the frequency of the oscillations tends to infinity, we prove that every isolated compact invariant set of the averaged autonomous equation can be continued to an isolated compact invariant set of the skew-product semiflow associated to the non-autonomous equation. Finally, we illustrate some examples in which the Conley index can be explicitly computed and can be exploited to detect the existence of recurrent dynamics in the equation.     

Existence and concentration of positive solutions for a super-critical fourth order equation

In this paper we investigate the problem of existence of solutions for a super-critical fourth order Yamabe type equation and we exhibit a family of solutions concentrating at two points, provided the domain contains one hole and we give a multiplicity result if we are given multiple holes.     

Unitary equivalence of automorphisms of separable C*-algebras

We prove that the automorphisms of any separable C*-algebra that does not have continuous trace are not classifiable by countable structures up to unitary equivalence. This implies a dichotomy for the Borel complexity of the relation of unitary equivalence of automorphisms of a separable unital C*-algebra: Such relation is either smooth or not even classifiable by countable structures.     

Cohomology of groups with metacyclic Sylow -subgroups

We determine the cohomology algebras for all groups with a metacyclic Sylow -subgroup. The complete -local stable decomposition of the classifying space is also determined.