Degradation of components in drug formulations: a comparison between HPLC and DSC methods.

Information about the stability of drug components and drug formulations is needed to predict the shelf-life of the final products. The studies on the interaction between the drug and the excipients may be carried out by means of accelerated stability tests followed by analytical determination of the active principle (HPLC and other methods) and by means of the differential scanning calorimetry (DSC). This research has been focused to the acetyl salicylic acid (ASA) physical-chemical characterisation by using DSC method in order to evaluate its compatibility with some of the most used excipients. It was possible to show, with the DSC method, the incompatibility of magnesium stearate with ASA; the HPLC data confirm the reduction of ASA concentration in the presence of magnesium stearate. With the other excipients the characteristic endotherms of the drug were always present and no or little degradation was observed with the accelerated stability tests. Therefore, the results with the DSC method are comparable and in good agreement with the results obtained with other methods.

Optimization of a tablet containing chlorthalidone.

In pharmaceutical technological research, optimization studies generally deal with the search for the formulation that is as effective and as functional as possible. The effect of a formulation parameter (the amount of lactose in the composition of the tablets) and of a technological parameter (compression pressure) on four physical characteristics (tablet thickness, friability, hardness, and drug dissolution rate) of tablets containing the antihypertensive drug chlorthalidone were studied. The results obtained indicate that, in the development of a tablet formulation, it is possible to identify the most suitable formulation by applying a simple optimization method. The effect of the microclimatic stress (temperature and humidity) was also evaluated, and it was found that the optimized tablets were no longer within limits that had been established for them. This may indicate that it is opportune to keep the storage conditions of the excipients under control before their use.

Gardening work and heavy metals in urban environment.

Urban soil may be a source of occupational exposure to various pollutants in gardening and land cultivation. This paper presents data of a one-year follow-up of lead, cadmium, nickel, chromium, and vanadium in the environment of the city of Bologna. Samples of soil and leaves were collected at three locations; gardens from the inner-city high-traffic area, parks in moderate-traffic area, and parks in suburban, low-traffic area. The top and deeper layers of soil and leaves were mainly polluted by lead at all locations, which corresponded to the traffic density. Personal samplers recorded greater concentrations of airborne metals than did the area samplers but the values kept below the threshold limit established by the American Conference of Governmental Industrial Hygienists for the working environment. Due to cumulative nature and interactive effects of toxic metals with other toxic and essential elements, long-term exposure to metals in the urban environment may be a health risk for occupationally exposed gardeners.

Ocular hypertonia and crystalline lens opacities in healthcare workers exposed to ionising radiation.

Some activities performed by healthcare workers may still involve total or partial exposure to ionising radiation exceeding the limit values. In addition to the appearance of crystalline lens opacities which may lead to rays-cataract, recent studies have indicated possible induction of ocular hypertonia in occupationally exposed subjects. The aim of this study was to establish the actual prevalence of ocular hypertonia and crystalline lens opacities in a group of healthcare workers exposed to ionising radiation. The collected data failed to show significant risk of ocular hypertonia and suggested that crystalline lens opacity was not an important indicator of exposure. Notwithstanding, preventive and periodic (every 5 years) ophthalmologic control may prove helpful for medicolegal purposes. Namely, such control would record congenital crystalline lens opacities in many individuals and would thus rule out unjustified claims of occupational disease due to exposure to ionising radiation. Additionally, ophthalmologic control should focus on different and probably more important ocular risks for the radiologists such as the ocular fatigue resulting from a prolonged use of a video display terminal or other diagnostic screens or electrodiaphanoscopes.

Interaction between trace elements: selenium and cadmium ions.

The interaction between several inorganic and organic selenium-containing compounds (selenite, selenate, selenourea and selenomethionine) and Cd2+ ions was studied by polarography. The changes in polarographic currents and half-wave potentials of the metal ions as a function of the Se-derivative concentration were followed. Experimental results suggest a different behaviour depending on the oxidation state of selenium. Any interaction between selenate and Cd2+ ions can be excluded. In the case of selenite, the presence of complexes in the solution was demonstrated. The shift in the Cd2+ reduction half-wave potential when a relatively high concentration of selenourea is present indicates formation of complexes, while the decrease in limiting current reflects the limited solubility of the complex itself. Results concerning selenomethionine suggest a very weak interaction with Cd2+ ions. These preliminary results are discussed in comparison with previous findings in cellular systems and may prove helpful in understanding cadmium ion toxicity and the in vivo altered distribution of various metal ions following the administration of selenium compounds.

Reactions of selenium dioxide free radicals with amino acids and enzymes.

Pulse radiolysis of selenium dioxide in aqueous solution has shown the presence of three selenite radicals in acid-base equilibrium within well defined pH ranges: (formula; see text) The selenite radicals react selectively with amino acids, preferentially with the aromatic ones in the order tryptophan greater than tyrosine greater than histidine, independently of the acid-base structure of the radical. Kinetic and spectroscopic data on the reaction of selenite radicals with some proteins and parallel inactivation studies generally reflect knowledge on the amino acid residues mainly involved in the radical attack. The investigations at different pH values on the reactivity of selenite radicals with amino acids and proteins and on the transient spectra of the reaction products exhibit different behaviour for the various acid-base structures of the selenite radicals, reflecting the influence of particular ionizable groups in the reacting molecules and the structure modifications at the level of proteins.

Further investigation on the radiation induced inactivation of ribonuclease and the radioprotective effect of some selenium-containing compounds.

Steady state inactivation data on dilute aqueous solutions of RNase show that all water radicals, e-aq, OH, and H are responsible for the inactivation, but the most efficient radical is H atom, only about 4 of them being required for one inactivating event. The data are, therefore, more in agreement with the conclusions of Mee et al. (1972). In the transient absorption spectra of pulse irradiated ribonuclease different components derived by the individual radicals are observed. Organic and inorganic selenium-containing compounds offer a great protection of the enzyme activity, in agreement with the data obtained in other chemical and biological systems. In particular the effects of two new secondary radicals (CNSe)-2 and SeO-3 are in good accord with the known structure of ribonuclease.

Selenourea and colloidal selenium: their role in radioprotection and radiosensitization of enzyme and cellular systems.

The effect of selenourea and of colloidal selenium on dilute aqueous solutions of the enzyme yeast alcoholdehydrogenase and on suspensions of E. coli B/r has been studied. Selenourea usually appears to protect meanwhile colloidal selenium radiosensitizes. The results are considered in terms of chemical stability of selenourea and of its free radical reactivity.