Compatibility study of tobramycin and pharmaceutical excipients using differential scanning calorimetry,FTIR, DRX,and HPLC

Differential scanning calorimetry (DSC), isothermal stress testing–Fourier transform infrared spectroscopy (IST–FTIR), isothermal stress testing–high-performance liquid chromatography, and powder X-ray diffraction (PDRX) were used as screening techniques for assessing the compatibility of tobramycin with some currently employed ophthalmic excipients. In the first phase of the study, DSC was used as a tool to detect any interaction. The absolute value of the difference between the enthalpy of the pure tobramycin melting peak and that of its melting peak in the different analyzed mixtures was chosen as a parameter of the drug–excipient interaction degree. DSC results demonstrated that benzalkonium chloride, monobasic sodium phosphate, boric acid, edetate disodium, sodium metabisulfite, thimerosal, and potassium sorbate interact with tobramycin. Taking into account these results, it could be suggested that some of the changes observed in the IST–FTIR spectra of binary blends of tobramycin and some of the excipients would account for a possible interaction between the mixture component. In this study, PDRX did not provide much information, since only tobramycin–thimerosal interactions could be detected. DSC and IST–FTIR are suitable and simple methods for the detection of potential incompatibilities between active pharmaceutical ingredient (API) and excipients.

     

Discrete and selective absorption in crystalline molecular nanofilms

Recent research in nano-optical engineering and in nanomedicine as well, seeks for methods of construction of various types of nano-markers, nano-carriers, and ways to deliver drugs to the exactly determined regions of body. In this process it is important to find methods of recognition of certain types of molecules. It is obvious that optical recognition would be the easiest and the most effective way to do it. Our research presents a model of a molecular ultrathin crystalline film and generated exciton system inside it and corresponding methodology of analysis of their optical characteristics. Properties of these spatially very restricted structures are very sensitive to their surrounding surfaces. Using the two-time Green’s functions adapted for crystalline structures with symmetry breaking, and graphical-numerical software, we have calculated the energy spectra and possible exciton states. We have shown that the appearance and the presence of localized states on the surfaces and in the boundary layers of the film depend on the thickness of the film and the film surroundings, presented through the perturbation of parameters on surfaces. Optical properties in these structures demonstrate discrete and very selective resonant absorption spectra, depending on the perturbation on their surfaces.     

Design and construction of an quasi-adiabatic dissolution calorimeter with a novel dosing apparatus and a low heat capacity

A quasi-adiabatic calorimeter for determining the molar solution enthalpies (Δ_sol H) of non-volatile solids was constructed. The design of the instrument was adjusted to allow the determination of solution enthalpies of small amounts of solids. For that purpose, the novel apparatus for sample dosage with virtually negligible “blank heat” was built. The rather low heat capacity of the calorimeter was achieved by reducing the volume of the reaction cell (20 mL), the dosing unit, and electric elements (the thermistor and the heater). Good thermal isolation of the reaction cell from the surroundings was accomplished by placing the cell into an evacuated polypropylene vessel. A computer program for processing the calorimetric data according to modified Regnault–Pfaundler method was written. The performance of the calorimeter was tested by determining the heats of the reactions serving as thermochemical standards at 25 °C (the dissolution of KCl and NaCl in water and the dissolution of tris(hydroxymethyl)-aminomethane in 0.1 mol dm^?3 HCl(aq)). The obtained data were in very good agreement with the literature values.     

Layered Black Phosphorus: Strongly Anisotropic Magnetic,Electronic, and Electron‐Transfer Properties

Layered elemental materials, such as black phosphorus, exhibit unique properties originating from their highly anisotropic layered structure. The results presented herein demonstrate an anomalous anisotropy for the electrical, magnetic, and electrochemical properties of black phosphorus. It is shown that heterogeneous electron transfer from black phosphorus to outer‐ and inner‐sphere molecular probes is highly anisotropic. The electron‐transfer rates differ at the basal and edge planes. These unusual properties were interpreted by means of calculations, manifesting the metallic character of the edge planes as compared to the semiconducting properties of the basal plane. This indicates that black phosphorus belongs to a group of materials known as topological insulators. Consequently, these effects render the magnetic properties highly anisotropic, as both diamagnetic and paramagnetic behavior can be observed depending on the orientation in the magnetic field.     

PHA-L lectin and carbohydrate relationship: conjugation with CdSe/CdS nanoparticles, radiolabeling and in vitro affinities on MCF-7 cells

This research aims to investigate the interaction between phytohemagglutinin-L (PHA-L) and sialic acid, which is abundant on the breast cancer cell (MCF-7) surface and displays monosaccharide characteristics, by experimental and computational methods. Experimentally, CdSe/CdS nanoparticles (QDs) were synthesized; PHA-L was conjugated with QDs and labeled with ¹²⁵I. Radiolabeling yield was found to be 97 ± 1.2 %. Afterwards, in vitro bioaffinities of radiolabeled PHA-L conjugated QDs have been investigated on MCF-7 cells and it has been observed that the cell incorporation increased with time. The results indicated that ¹²⁵I labeled QD-PHA-L conjugates represent significant affinity on MCF-7 cells. In the second step of the study, the crystal structure of carbohydrate interaction surface of PHA-L was extracted from the crystal structure of PHA-L. The interactions between this surface and sialic acid were calculated by computational tools. These calculations revealed specific interactions between PHA-L and sialic acid. Semi-empirical methods, PM3 and AM1, were used in these calculations. Significant outcomes have been obtained from the experimental and computational studies and these results demonstrated that PHA-L may be an effective agent for imagining MCF-7 cells.     

A QM/MM study on the reaction pathway leading to 2‐Aceto‐2‐hydroxybutyrate in the catalytic cycle of AHAS

The reaction between the intermediate 2‐hydroxyethyl‐thiamin diphosphate (HEThDP^?) and 2‐ketobutyrate, in the third step of the catalytic cycle of acetodydroxy acid synthase, is addressed from a theoretical point of view by means of hybrid quantum/molecular mechanical calculations. The QM region includes one molecule of 2‐ketobutyrate, the HEThDP^? intermediate, and the residues Arg 380 y Glu 139; whereas the MM region includes the rest of the protein. The study includes potential energy surface scans to identify and characterize critical points on it, transition state search and activation barrier calculations. The results show that the reaction occurs via a two‐step mechanism corresponding to the carboligation and proton transfer in the first stage; and the product release in the second step. © 2014 Wiley Periodicals, Inc.