Development and characterization of a mucoadhesive sublingual formulation for pain control: extemporaneous oxycodone films in personalized therapy

Objective: The aim of this work was the development of mucoadhesive sublingual films, prepared using a casting method, for the administration of oxycodone.

Materials and methods: A solvent casting method was employed to prepare the mucoadhesive films. A calibrated pipette was used to deposit single aliquots of different polymeric solutions on a polystyrene plate lid. Among the various tested polymers, hydroxypropylcellulose at low and medium molecular weight (HPC) and pectin at two different degrees of esterification (PC) were chosen for preparing solutions with good casting properties, capable of producing films suitable for mucosal application.

Results and discussion: The obtained films showed excellent drug content uniformity and stability and rapid drug release, which, at 8?min, ranged from 60% to 80%. All films presented satisfactory mucoadhesive and mechanical properties, also confirmed by a test on healthy volunteers, who did not experience irritation or mucosa damages. Pectin films based on pectin at lower degrees of esterification have been further evaluated to study the influence of two different amounts of drug on the physicochemical properties of the formulation. A slight reduction in elasticity has been observed in films containing a higher drug dose; nevertheless, the formulation maintained satisfactory flexibility and resistance to elongation.

Conclusions: HPC and PC sublingual films, obtained by a simple casting method, could be proposed to realize personalized hospital pharmacy preparations on a small scale.     

On Ilyashenko’s statistical attractors

We define a minimal α-observability of Ilyashenko’s statistical attractors. We prove that the space is always full Lebesgue decomposable into pairwise disjoint sets that are Lebesgue-bounded away from zero and included in the basins of a finite family of minimal α-observable statistical attractors. Among other examples, we analyse the Bowen homeomorphisms with non-robust topological heteroclinic cycles. We prove the existence of three types of statistical behaviours for these examples.     

Electrochemical chlorination of azulene derivatives: Insight into the mechanism of anodic oxidative chlorination

The cyclic voltammetry behavior of a series of five 1-substituted azulenes has been investigated as well as the electrochemical chlorination of these compounds. In the case of azulene compounds containing electron withdrawing groups which have higher oxidation potentials than that of the chloride ion, the electrochemical chlorination led usually to 3-chloro derivatives. The electrochemical chlorination fails for azulenes with lower oxidation potentials. Additionally some polyhalogenated compounds were obtained by controlled potential electrolyses. The paper also discusses the reaction mechanism of the electrochemical halogenation of 1-substituted azulenes.     

Polymeric nanoparticles as drug controlled release systems: a new formulation strategy for drugs with small or large molecular weight

We report a study evaluating the encapsulation and release modalities from poly(D,L lactic acid) (PLA) or poly(D,L-lactide-co-glicolide) (PLGA) micro- and nano-particles of the antiischemic drug N6-cyclopentyladenosine (CPA) and bovine serum albumin (BSA), chosen as protein model. The results obtained by classical preparation methods (nanoprecipitation, single or double emulsion/solvent evaporation) of the particles were compared with those obtained by their formulation with a novel method, employing a thermosensible gel of Pluronic F-127, whose aqueous solutions can be liquid when refrigerated, but gel upon warming. Our results indicate that CPA-loaded nanoparticles, obtained by classical methods, drastically reduce their drug content showing, moreover, any control of the drug release with respect to CPA-loaded microparticles. The novel preparation method allowed us to obtain, instead, CPA encapsulation values in nanoparticles similar to those obtained for microparticles, achieving also a weak control of the drug release. Any drastic reduction of BSA particle content was obtained by decreasing their size from micro- to nano-scales, independently on the employment of classical or novel preparation methods. Moreover, the size reduction induced only a weak increase of the BSA release rate. The patterns of protein released from micro- and nano-particles obtained by the same formulation method were similar. In particular, the micro- and nano-spheres prepared by double emulsion technique showed an incomplete BSA release, characterized by an elevated burst effect followed by a very slow phase. On the other hand, the release from micro- and nano-particles obtained by the novel method was complete and quite regular, being characterized by a little burst release followed by a fast phase. These results have been related to the strong BSA distribution (observed by confocal laser scanning microscope) in the surface or in the core of microparticles obtained by the classical or novel methods, respectively.     

How To Find a Needle (or Anything Else) in a Haystack: Two-Dimensional Correlation Spectroscopy-Filtering with Iterative Random Sampling Applied to Pharmaceutical Heparin

Risks of contamination of the major clinical anticoagulant heparin can arise from deliberate adulteration with unnatural or natural polysaccharides, including heparin from other animal sources, other natural products, or artifacts of manufacture, and these can escape detection by conventional means. Currently, there is no generally applicable, objective test recommended by regulators that can detect these in pharmaceutical heparin, and this continues to leave heparin exposed to contamination risks. Two-dimensional correlation spectroscopic-filtering with iterative random sampling (2D-COS-firs) is reported. It employs a difference covariance matrix with iterative random sampling, and is capable of revealing contamination in pharmaceutical heparin to a high level of sensitivity irrespective of the nature of those features. The technique is suitable to any situation in which a comparison of a single entity to a family of heterogeneous entities, particularly natural products and biosimilars, needs to be made, and will find application in pharmaceutical monitoring, manufacturing quality control, materials science, biotechnology, and metabolomic investigations.     

Experimental Damage Criterion for Static and Fatigue Life Assessment of Commercial Aluminum Alloy Die Castings

Metallurgical and Materials Transactions A - Defects, particularly porosity and oxides, in high-pressure die casting can seriously compromise the in-service behavior and durability of products...     

In vitro antimicrobial properties of silver–polysaccharide coatings on porous fiber-reinforced composites for bone implants

Biostable fiber-reinforced composite (FRC) implants prepared from bisphenol-A-dimethacrylate and triethyleneglycoldimethacrylate resin reinforced with E-glass fibers have been successfully used in cranial reconstructions in 15 patients. Recently, porous FRC structures were suggested as potential implant materials. Compared with smooth surface, porous surface allows implant incorporation via bone ingrowth, but is also a subject to bacterial attachment. Non-cytotoxic silver–polysaccharide nanocomposite coatings may provide a way to decrease the risk of bacterial contamination of porous FRC structures. This study is focused on the in vitro characterization of the effect porosity on the antimicrobial efficiency of the coatings against Staphylococcus aureus and Pseudomonas aeruginosa by a series of microbiological tests (initial adhesion, antimicrobial efficacy, and biofilm formation). Characterization included confocal laser scanning microscopy and scanning electron microscopy. The effect of porosity on the initial attachment of S. aureus was pronounced, but in the case of P. aeruginosa the effect was negligible. There were no significant effects of the coatings on the initial bacterial attachment. In the antimicrobial efficacy test, the coatings were potent against both strains regardless of the sample morphology. In the biofilm tests, there were no clear effects either of morphology or of the coating. Further coating development is foreseen to achieve a longer-term antimicrobial effect to inhibiting bacterial implant colonization.     

Proteins as biomarkers of oxidative/nitrosative stress in diseases: the contribution of redox proteomics

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) contribute to the pathogenesis and/or progression of several human diseases. Proteins are important molecular signposts of oxidative/nitrosative damage. However, it is generally unresolved whether the presence of oxidatively/nitrosatively modified proteins has a causal role or simply reflects secondary epiphenomena. Only direct identification and characterization of the modified protein(s) in a given pathophysiological condition can decipher the potential roles played by ROS/RNS-induced protein modifications. During the last few years, mass spectrometry (MS)-based technologies have contributed in a significant way to foster a better understanding of disease processes. The study of oxidative/nitrosative modifications, investigated by redox proteomics, is contributing to establish a relationship between pathological hallmarks of disease and protein structural and functional abnormalities. MS-based technologies promise a contribution in a new era of molecular medicine, especially in the discovery of diagnostic biomarkers of oxidative/nitrosative stress, enabling early detection of diseases. Indeed, identification and characterization of oxidatively/nitrosatively modified proteins in human diseases has just begun.     

Removal of As(III) and As(V) from water using a natural Fe and Mn enriched sample

The arsenic removal capacity of a natural oxide sample consisting basically of Mn-minerals (birnessite, cryptomelane, todorokite), and Fe-oxides (goethite, hematite), collected in the Iron Quadrangle mineral province in Minas Gerais, Brazil, has been investigated. As-spiked tap water and an As-rich mining effluent with As-concentrations from 100 μg L⁻¹ to 100 mg L⁻¹ were used for the experiments. Sorbent fractions of different particle sizes (<38 μm to 0.5 mm), including spherical material (diameter 2 mm), have been used. Batch and column experiments (pH values of 3.0, 5.5, and 8.5 for batch, and about pH 7.0 for column) demonstrated the high adsorption capacity of the material, with the sorption of As(III) being higher than that of As(V). At pH 3.0, the maximum uptake for As(V) and for As(III)-treated materials were 8.5 and 14.7 mg g⁻¹, respectively. The Mn-minerals promoted the oxidation of As(III) to As(V), for both sorbed and dissolved As-species. Column experiments with the cFeMn-c sample for an initial As-concentration of 100 μg L⁻¹ demonstrated a very efficient elimination of As(III), since the drinking water limit of 10 μg L⁻¹ was exceeded only after 7400 BV total throughput. The As-release from the loaded samples was below the limit established by the toxicity characteristic leaching procedure, thus making the spent material suitable for discharge in landfill deposits.