Thiamacrocyclic lactones: new Ag(I)-ionophores

The syntheses of novel adamantane thialactones 5-12 are reported, and the results of the heavy- and transition-metal cation extraction experiments are described. The results are compared with those obtained with similar thiamacrocyclic ligands that have flexible chains of methylene groups incorporated into the macrocyclic framework as in 13-20. The results show that most of the hosts studied are very good in complexing the Ag(+) ion. The formation of complexes has also been demonstrated using NMR titration experiments for macrocycles 13 and 14 with AgTFA. Introduction of a single polycyclic molecule into the 15- to 18-membered rings increases the rigidity and preorganizes the ligand for complexation. However, two adamantane molecules embedded in the ring usually diminish the complexing ability of the ligand, primarily due to sterical effects of the bulky adamantane moiety that obstructs formation of an optimal geometry for binding the desired metal ion. The structures of macrocycles 5, 7, 9, 11, and 19 were determined by X-ray structure analysis, and their conformational properties are discussed. In the solid state, 7, 11, and 19 are organized into tubular fashion using C-H...O interactions. Also, two silver complexes with thialactone 13, Ag13 and Ag(13)(2), were prepared and characterized. The structure analysis of Ag13 and Ag(13)(2) reveals the formation of mononuclear and binuclear species with silver in ambivalent, tetrahedral coordination via sulfur and oxygen from trifluoroacetate anion.     

Increasing the solubility characteristics of iomeglamic acid withβ-cyclodextrin

Iomeglamic acid has been successfully applied for radioscopy of the gall-bladder since 1972. This pharmacon has the disadvantageous property that it is practically insoluble in water. Preparations containing the drug in different concentrations were made with-cyclodextrin by different methods, and their dissolution characteristics were determined. In the best situation the solubility increased ten-fold. The tablets were made from the most suitable complex, with-cyclodextrin. The conditions of tableting, the parameters and the dissolution of the tablets were tested.     

Quantitative Determination of Crystallinity of α-Lactose Monohydrate by DSC

In pharmaceutical practice it is important and useful to know the crystallinity of materials and to monitor it during formulation development, production processes and storage. The purpose of this study was to assess the quantitative capability of DSC for determining crystallinity in crystalline/amorphous powder mixtures and to compare the accuracy of the DSC method with that of conventional powder X-ray diffraction. Alpha-lactose monohydrate was chosen as the model material. On the basis of this study it can be concluded, that DSC method can be applied safely for semiquantitative evaluation of the crystallinity of lactose samples consisting of an amorphous content higher than 20%. This revised version was published online in August 2006 with corrections to the Cover Date.     

Determination of lead in a minute blood sample by the spectrophotometric method

Summary The mono-colour dithizone method for the determination of small amounts of lead in blood (5 ml samples) has been improved to a certain extent and adapted for smaller blood samples (2 ml). Blood is mineralized by wet oxidation with nitric acid and hydrogen peroxide. The lead content is determined spectrophotometrically as Pb dithizonate after extraction with dithizone from the mineralized solution. The modified method has several advantages over the original one: (a) the sensitivity of the method is increased; (b) the amount of the blood necessary for the analysis is smaller; (c) the time needed for the lead determination is shorter. The results show that the modified method is accurate and reliable enough to meet the requirements of practical toxicology.

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Zusammenfassung Die für die Bestimmung kleiner Bleimengen in Blut mit Dithizon entwickelte Methode wurde verbessert und für sehr kleine Blutmengen modifiziert. Das organische Material wird mit Salpetersäure und Wasserstoffperoxid zerstört. Der Bleigehalt wird nach Extraktion aus der mineralisierten Lösung als Bleidithizonat spektrophotometrisch bestimmt.Gegenüber der ursprünglichen Methode ergaben sich einige Vorteile: a) die Empfindlichkeit der Methode wurde gesteigert; b) die für eine Analyse erforderliche Blutmenge ist geringer; c) die Dauer einer Bleibestimmung ist kürzer. Die Resultate zeigen, daß die modifizierte Methode für die Ansprüche der praktischen Toxikologie genügend genau und verläßlich ist.

     

Comprehensive studies of Tolperisone·HCl-cyclodextrin complexes

Solid inclusion complexes of TolperisoneHCl with five various cyclodextrins were prepared by kneading and spray drying. The complex formation between the drug and the cyclodextrins were proven using thermoanalytical methods, X-ray diffraction, IR spectroscopy. The results of the solid state investigations were supported by the liquid phase investigations, such solubility and parition constant measurements and stability constant determination. Among all cyclodextrins used the - and -CD-s were found to be the best complexing agents.     

Preparation and Investigation of Inclusion Complexes Containing Nifluminic Acid and Cyclodextrins

Nifluminic acid (N) is a frequently used anti-inflammatory drug,but its poor aqueous solubility is a disadvantageous property. Inclusion complexation with cyclodextrinderivatives (CDs) affords a possibility to increase its solubility properties. For thispurpose, different CDs were used, primarily hydroxypropyl--CD (HP--CD), to prepareproducts by powder mixing or kneading in four molecular ratios. The dissolution and in vitromembrane diffusion of the products were investigated. The wetting angles of pure N andHP--CD and of the products, and the n-octanol/water partition coefficients were determined.The interaction, leading to complex formation between the components of the products was examined by thermoanalytical methods.     

Improvement of the Physicochemical Properties of Clotrimazole by Cyclodextrin Complexation

Complex formation between CDs and a very poorly water-soluble antifungal agent, clotrimazole (CLT), was studied. Products containing -CD were prepared in two molecular ratios by four methods. The rates of dissolution ofthe 1 : 1 drug/CD combinations revealed better dissolution properties than thoseof the 1 : 2 products. Drug/CD interactions in both aqueous solution and the solidstate were studied by phase solubility and thermal analysis. The effects of differentauxiliary materials (polymers, hydroxy acids and surfactants) on the aqueous solubilityof CLT were investigated. The aqueous solubility of CLT was increased significantly bythe addition of the auxiliary materials. Particle size distribution, partition coefficient,surface tension, heat of dissolution and wettability studies were also carried out.     

DNA hybridization enhancement using piezoelectric microagitation through a liquid coupling medium

In conventional DNA microarray hybridization, delivery of target cDNAs to surface-bounded probes depends solely on diffusion, which is notoriously slow, and thus typically requires 6-20 h to complete. In this study, piezoelectric microagitation through a liquid coupling medium is employed to enhance DNA hybridization efficiency and the results are compared with the standard static hybridization method. DNA hybridization was performed in a sealed aluminium chamber containing DNA microarray glass chip, coupling medium and piezoelectric transducers. 3×SSC (Saline Sodium Citrate) was used as a coupling medium to prevent overheating of the piezoelectric transducers and to effectively transmit ultrasonic wave to the glass chip. Flow visualization using fluidic dye and velocimetry (PTV) technique was applied to observe fluid transport in the hybridization chamber. It was revealed that the dye solution was homogeneously distributed within 10 min under dynamic agitation while it took over 1 h to reach the same level of homogeneity in static condition. Plasmodium falciparum DNA microarrays and total RNA extracted from parasite cells were used as a model for DNA microarray experiments. It was found that the required hybridization time may be substantially reduced from 16 h to 4 h by the use of dynamic hybridization scheme. With the same hybridization time of 16 h, dynamic hybridization resulted in higher fluorescent signals of ～33% and ～24% compared to static hybridization in Cy3 and Cy5 channels, respectively. Additionally, good/effective spots, some of which were not formed by static method, were enhanced and distributed more uniformly over the microarray. Therefore, the developed dynamic hybridization with integrated piezoelectric microagitation platform is highly promising for DNA analysis in molecular biology and medical applications.