RESUMO
BACKGROUND: Silicate (Si) and aluminum (Al) may be concomitant impurities in solutions for parenteral nutrition (PN). Silicate can bind to Al to form stable hydroxyaluminosilicates (HAS), thus reducing Al availability. This possibility is investigated by heating solutions containing constituents of PN in glass containers to promote the release of Si and Al. METHODS: The total amount of Si and Al in solution is measured by atomic absorption spectrometry, and the Al not bound to Si is evaluated by reaction with morin. RESULTS: When the Si:Al molar ratio is >5, no free Al is found in solution. For ratios <5, it is found that the lower the ratio, the higher the free Al fraction. However, in solutions of some amino acids, even with a low Si:Al ratio (<2), the amount of free Al is lower than that found in other solutions. The same tendency is observed among commercial formulations. Although in salt solutions the free fraction of Al reaches almost 100% when the Si concentration is low, in amino acid formulations the free fraction of Al does not surpass 50%. Moreover, even for Si:Al ratios >5, there is a "residual" fraction of free Al in amino acid formulations. CONCLUSIONS: The concomitant presence of Al and Si in solutions for PN reduces the amount of Al available attributable to the formation of HAS. In amino acid formulations this effect may be slightly reduced given the affinity of certain amino acids for Al. Therefore, amino acids may behave in the same fashion as silicate.
Assuntos
Alumínio/química , Aminoácidos , Contaminação de Alimentos , Alimentos Formulados , Nutrição Parenteral , Silicatos/química , Aminoácidos/química , Flavonoides/química , Temperatura Alta , Indicadores e Reagentes , Espectrofotometria Atômica/métodosRESUMO
Glass is made of polymeric silica and other minor components, which are necessary for turning the silica into a material more easily moldable and resistant to temperature changes. Glass containers for pharmaceutical usage are classified according to their resistance to a chemical attack, a test carried out in the presence of water and heat. The test is designed to show the released alkalinity, a variable dependent on the amount of sodium oxide, one of the minor components added to the glass mass. In this work, the release of silica from glass by action of constituents from pharmaceutical formulations was investigated. The study included products used in large volumes and usually stored in glass containers. Solutions of amino acids, electrolytes, glucose, oligoelements and others such as heparin and sodium bicarbonate were individually stored in glass containers and heated at 121 degrees C for 30min, as in the water attack test. The test was also carried out only with water, where the pH varied from 2 to 12. The released silicate was measured either by photometry or atomic absorption spectrometry, depending on the nature of the sample. The results showed that silicate is released during the heating cycle even if the contact is with pure water only. The pH exerts a considerable influence on the release, being that the higher the pH, the higher the silica dissolved. An elevated pH, however, is not the only factor responsible for silica dissolution. While in the solutions of NaCl, KCl, Mg Cl2 and ZnSO4 and in most of the amino acids, the concentration of silicate was as high as in pure water (0.1-1.0mg Si/L). In the solutions of sodium acetate, bicarbonate and gluconate, its concentration was much higher, over 30mg Si/L. These results were confirmed by the analysis of commercial products, where in solutions of amino acids the level of silicate ranged from 0.14 to 0.19mg Si/L. On the other hand, calcium gluconate, sodium bicarbonate and potassium phosphate presented silicate levels from 1 to 4mg/L. Although silica is not considered a toxic substance for humans, it is necessary to be aware of its presence in solutions for parenteral nutrition due to the direct introduction into the bloodstream and the large volume usually administrated, even to pre-term infants.
Assuntos
Embalagem de Medicamentos , Vidro/química , Silicatos/química , Química Farmacêutica , Contaminação de Medicamentos , Eletrólitos , Alimentos Formulados , Temperatura Alta , Concentração de Íons de Hidrogênio , Indicadores e Reagentes , Nutrição Parenteral , Soluções Farmacêuticas , Plásticos , Espectrofotometria AtômicaRESUMO
As prescribed by pharmacopoeias, containers should meet certain condition of stability to be used for pharmaceutical products. Glass containers are classified according to their resistance to chemical attack, a test executed by heating the glass in contact with water for 30 min at 121 degrees C. The USP powdered glass test for glass containers was applied to different kinds of glasses used as containers for parenteral formulations. In this experiment not only the released alkalinity was measured but also the release of glass constituents: silicate, borate, sodium, and aluminum, and also the release of some impurities as copper and lead. The USP powdered glass test was also carried out with glass ampoules, clear and amber, in the presence of solution of some inorganic salts, NaCl, KCl, CaCl2, MgCl2, NaHCO3, NaH2PO4, KH2PO4, and sodium gluconate, citric acid and glucose. The results showed that even when releasing very low alkalinity, glasses also released their constituents, in concentration ranges from 8.8 to 33 mg/l for silicate, 0.9 to 6.9 mg/l for borate, 3 to 37 for mg/l for sodium and 0.5 to 2.4 mg/l for aluminum. More expressive results were found, however, for the tests done with solutions instead of pure water. The tests showed that, for most of the solutions, while the measured alkalinity was very low, high levels of the other constituents were found. Basic solutions of bicarbonate and gluconate presented the higher levels of all investigated constituents, confirming the ability of basic solutions to attack and dissolve the glass network. Glucose and citric acid interacted with the glass surface, selectively extracting aluminum, copper, and lead. Whereas silicate, borate and sodium found in these solutions were at levels similar to those found with pure water, the aluminum level was almost 20 times higher. This specific action of citrate and glucose could be related to their metal-complexing ability. The results indicate that even so-called "chemical-resistant glasses," as measured by the hydrolytic resistance test, react with many substances when packaged in contact with them. The hydrolytic resistance test, when used as the sole measure of potential drug-container compatibility, is not reliable.