Vittorio Berbenni

Effect of extended ball milling on graphite

Graphite has been milled for up to 1000 h in a laboratory scale tumbling ball mill under vacuum. Raman spectroscopy of the powders indicated the increasing dominance of D-type graphitic sp2 bonding over G-type bonding with increasing milling time. Diamond-like sp3 bonding and possibly fullerene-like bonding also became evident after milling. TEM of the 100 h sample showed the presence of ribbons which were composed of sheets showing defects, delamination, translation, warping and curvature. Interplanar spacings of 0.40–0.50 nm were measured with the spacing increasing towards the edge of the ribbons where delamination was evident. Thermogravimetric analysis in argon of the powder after exposure to air showed an increasing mass loss with milling time indicating the presence of chemisorbed gas. Using TG–FTIR the gas was found to be a mixture of CO2 and an unidentified gas (probably oxygen). BET surface area measurements showed a maximum in the surface area; however, this was shown to be massively in error for the longer milling times due to the presence of the chemisorbed gas.

Drug-Excipient Compatibility Studies. Search of interaction indicators

This paper is the first one of a research project aimed to find and optimize methods by which drug-excipient compatibility can be reliably and quickly assessed.A number of experimental techniques (simultaneous TG-DSC, FT-IR spectroscopy, X-ray powder diffraction, scanning electron microscopy) have been used to investigate the compatibility between a novel tricyclic β-lactam antibiotic developed by GlaxoWellcome (now GlaxoSmithKline), GV118819x, and some commonly used excipients (poly(vinylpyrrolidone), magnesium stearate and α-lactose). Binary mixtures of two different compositions have been analyzed: drug:excipient=80:20 and 20:80 (mass/mass). Both qualitative and quantitative interaction indicators have been identified. It is shown that simultaneous thermal analysis is the best suited technique in the search of interaction indicators. With a proper selection of experimental conditions it is able to reveal the thermal changes brought about by the early stages of interaction, i.e. those occurring during the measurement on physical mixtures not previously annealed under stress conditions. Such an ability is discussed, in particular, with respect to the role of the water vapour, which has been found to be a critical parameter for all our systems.

Effect of mechanical activation on the preparation of SrTiO3 and Sr2TiO4 ceramics from the solid state system SrCO3-TiO2

Abstract By thermoanalysis (TGA and DSC) and X-ray powder diffraction it has been shown that the compounds SrTiO 3 and Sr 2 TiO 4 can be prepared by mechanical activation of, respectively, 1:1 and 2:1 SrCO 3 –TiO 2 (rutile) mixtures followed by annealing for 12 h at 800–850°C. These compounds could not be obtained by heating the physical mixtures to temperatures as high as 1000°C. Moreover, the enthalpies of the reactions leading from Sr carbonate and rutile to the formation of these compounds have been determined. By combining these data with the enthalpy of SrCO 3 decomposition, also obtained in this work, the enthalpies of formation of SrTiO 3 and Sr 2 TiO 4 have been calculated. On the contrary, no Sr 3 Ti 2 O 7 was shown to form, by the same annealing procedure, when starting from a mechanically activated mixture. DSC and XRD results agree in indicating that a mixture of Sr 2 TiO 4 and SrTiO 3 forms instead.

On the thermal stability and defect structure of the solid solution LixNi1-xO

Abstract Li x Ni 1- x O solid solutions are both of scientific and technological interest as they have been proposed as cathodic material in MCFC. In this work TG, XRD and SEM measurements have been used to study the thermal stability of several solid solutions (of different initial composition) obtained starting from the reactive system Ni/Li 2 CO 3 . Composition changes, due to both lithium and oxygen loss, take place as a consequence of samples annealing. In some cases a sensible disagreement between the compositions deduced by TG and XRD data is showing, which is ascribed to the presence, in the final solid solutions, of lattice defects others than substitutional ones (namely cation vacancies). The TG and XRD measurements have been then worked out to obtain both the correct composition and vacancies concentration of the solid solutions. It is shown that solid solutions with similar lithium content but different vacancies concentration can be obtained depending on the preparation conditions.

Drug-excipient compatibility studies by physico-chemical techniques; The case of Atenolol

We apply a range of techniques (thermal methods, microscopy, X-ray diffraction, IR spectroscopy) to characterize a drug (atenolol), several excipients (PVP=polyvinylpyrrolidone, MGST=magnesium stearate, Avicel©) and drug-excipients mixtures either as prepared, annealed, and exposed to moisture. We compare the data of the mixtures with those computed from a weighted average of similarly treated pure compounds to find evidence of drug properties modified by the interaction with the excipient. We find that thermal response is by far the most sensitive indicator of interaction while IR is the least sensitive one. Avicel© has essentially no interaction with atenolol, while MGST modifies significantly only the thermal response of the drug in the MGST-rich mixtures. PVP interacts strongly with atenolol, and this interaction appears to be mediated by the substantial amount of hydration water the excipient brings in its mixtures with a water-free drug.

Drug-excipient compatibility studies by physico-chemical techniques; The case of Indomethacin

This work exemplifies a general method of studying the drug excipient interactions, with the aim of predicting rapidly and inexpensively the long term stability of their mixtures. We study the physico-chemical properties of a drug (indomethacin) in the solid state and in different combinations with several excipients (PVP=polyvinylpyrrolidone, MGST=magnesium stearate, Avicel©). We compare the properties of pure compounds (untreated, or moisture/temperature conditioned) with those of binary mixtures drug:excipient which underwent the same treatment. The purpose is to find indications of interactions within the mixtures, which means a potential incompatibility of the excipient. Both morphological and thermal properties are sensitive to interactions which leave mostly unmodified the IR spectra and the X-rays patterns. In particular, we find that indomethacin does interact with PVP and MGST, but is certainly compatible with Avicel©.

Increased chemisorption onto activated carbon after ball-milling

Abstract Activated carbon has been milled for up to 1000 h in a laboratory-scale tumbling ball mill under a vacuum. Thermogravimetric (TG) analysis of the powder in argon showed an increasing mass loss with milling time indicating the presence of chemisorbed gas. TG Fourier transform infrared spectrometry showed the gas was a mixture of water, CO2 and an unidentified gas (probably oxygen). BET surface area measurements showed a decreasing surface area with milling time, however, this was shown to be massively in error for the longer milling times due to the presence of the chemisorbed gas. The area occupied by the chemisorbed gas increased from 40 to 80% of the true surface area which was almost constant at 1258±27 m2 g−1 for all three powders. These results show that extremely large errors may be made when using BET analysis to determine the surface area of powders, especially those where the surface activity is substantially increased during processing.

DEHYDRATION OF THE CYCLODEXTRINS : A MODEL SYSTEM FOR THE INTERACTIONS OF BIOMOLECULES WITH WATER

The thermodynamics of hydration of biomolecules is experimentally studied in the β‐cyclodextrin (β‐CD), which contains water molecules in a range of configurations and has been proposed as a model system for complex biomolecules. The thermal measurements point to the role of a structural transition from the hydrated β‐CD (phase I) to a ‘‘dehydrated’’ form (phase II). We show that dehydration in phase I is assisted by a ‘‘compensation mechanism’’ for which β‐CD contributes a constant amount of energy for each H2O mole. Despite the presence of different types of H2O’s, water losses in phase I are accurately described in terms of this energy and the isosteric molar enthalpy of dehydration. Moreover, in going from the fully hydrated to the fully dehydrated form, the contribution of β‐CD to dehydration is over all equal to the enthalpy of transition from phase I to phase II. Our analysis yields the changes of an enthalpy associated with the biomolecule alone as a function of the water content. In the case of β...

On the role of lithium carbonate in the preparation of doped nickel oxide cathodes for molten carbonate fuel cells

Abstract Clear evidence was obtained by dilatation and density measurements that the amount of lithium carbonate in the starting mixture sensibly affects the sintering behaviour of mixed lithium-nickel oxide cathodes. Porosimetric, diffractometric and microscopic measurements were then performed to understand and put on a quantitative basis such an influence. It is shown that, when the sintering temperature is low enough to prevent lithium oxide loss from the mixed oxide, cathodes total porosity increases with increasing lithium content up to a limiting composition beyond which a porosity decrease takes place. Lithium oxide loss, on the other hand, leads to a total porosity decrease which is related both to the initial lithium content and to the amount of the lithium oxide lost. Such a behaviour can be explained on the basis of the different mechanism by which the mixed oxide is obtained depending on the relative amounts of nickel and lithium carbonate in the starting mixture. Moreover it is shown that the observed total porosity changes are mainly a consequence of microporosity changes.

Preparation and Physicochemical Characterization of Acyclovir Cocrystals with Improved Dissolution Properties

Acyclovir is a well-known antiviral agent. It can be administered in very high doses (from 200 to 1000 mg even three-four times daily). It has absorption problems mainly due to its poor solubility in water (about 0.2 g/100 mL at 25°C) and its oral bioavailability is approximately 15%-20% with a half-life of about 3 h. To improve acyclovir solubility and/or its dissolution properties, two cocrystals of this drug were successfully produced with glutaric acid (AGA1:1) and fumaric acid (AFA1:1) as conformers, using a cogrinding method. Their effective formation was investigated by a broad range of techniques: thermal analysis, Fourier transform infrared spectroscopy, X-ray powder diffraction, solid state nuclear magnetic resonance, and scanning electron microscopy coupled with energy dispersive X-ray spectrometry. The water solubility of the AGA1:1 cocrystal was not improved in comparison to acyclovir, while AFA1:1 showed a slight increased solubility at equilibrium. The main difference was detected in terms of intrinsic dissolution rates (IDR). The IDR of the new phases were much faster compared with acyclovir, particularly at neutral pH. AFA1:1 showed the most rapid dissolution behavior in water; within 10 min, the drug was released completely, while just 60% of acyclovir was dissolved in 1 h.