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Abstract: The aim of this work was to evaluate the feasibility of using solid lipid particles of glyceryl monostearate, produced using supercritical fluids, as carriers for active substances. Studies of melting point depression were carried out to pressures up to 24MPa and the solubility of carbon dioxide in the lipid matrix was measured for three different temperatures in a range from 10 to 20MPa. This matrix was then processed by PGSS® technique (particles from gas saturated solutions) with and without active substance. Caffeine was used as a model molecule. The particles produced were analyzed by laser diffraction for particle size distribution and by SEM (scanning electron microscopy) for morphology assessment. The particles loaded with caffeine were also analyzed by HPLC (high performance liquid chromatography). [Copyright &y& Elsevier]

Capillary electrophoresis (CE) has emerged as an important tool for evaluating the ionisation characteristics of compounds and their corresponding pKa values. A particular strength of CE in this context is that its relative selectivity allows one to measure the extent of ionisation of materials that are impure. In this study, using CE, we have measured the pKa values of a series of anti-inflammatory aminoindanones, which underwent degradation to indenone during the course of the determination. We subsequently monitored the elimination reactions measuring remaining indanone over the pH range 2.6–10 at constant ionic strength and temperature. The decomposition of the tertiary amino derivatives was especially fast with first-order half-lives of less than 10 min observed at pH 7.4. The resulting sigmoidal pH rate profiles can be accounted for by assuming unimolecular elimination of the protonated (slow) and neutral (fast) forms of the amines. This study provides further support for the use of CE in evaluating amino ionisation especially in cases where degradation might be expected. [Copyright &y& Elsevier]

Abstract: Fullerene (C60), the third carbon allotrope, is a classical engineered material with the potential application in biomedicine. However, extremely high hydrophobicity of fullerene hampers its direct biomedical evaluation and application. In this work, we investigated the solubilization of fullerene using 9 different solubility enhancers: Tween 20, Tween 60, Tween 80, Triton X-100, PVP, polyoxyethylene (10) lauryl ether, n-dodecyl trimethylammonium chloride, myristyl trimethylammonium bromide and sodium dodecyl sulphate and evaluated its antioxidant activity in biorelevant media. The presence of C60 entrapped in surfactant micelles was confirmed by UV/VIS spectrometry. The efficacy of each modifier was evaluated by chemometric analysis using experimental data for investigating the relationship between solubilization and particle size distribution. Hierarchical clustering and principal component analysis was applied and showed that non-ionic surfactants provide better solubilization efficacy (>85%). A correlation was established (r = 0.975) between the degree of solubilization and the surfactant structure. This correlation may be used for prediction of C60 solubilization with non-tested solubility modifiers. Since the main potential biomedical applications of fullerene are based on its free radical quenching ability, we tested the antioxidant potential of fullerene micellar solutions. Lipid peroxidation tests showed that the micellar solutions of fullerene with Triton and polyoxyethylene lauryl ether kept high radical scavenging activity, comparable to that of aqueous suspension of fullerene and BHT. The results of this work provide a platform for further solubilization and testing of pristine fullerene and its hydrophobic derivatives in a biological benign environment. [ABSTRACT FROM AUTHOR]

Abstract: This work studies the possibility of enhancing the solubility of 1,3-diphenyl-2-propenone, the core structure of chalcones, through lipidic formulations under supercritical CO2 processing. Microparticles of chalcone, alone and with lipid carriers, were produced by PGSS®, a method which involves the quick depressurization of a gas saturated solution through a nozzle, and takes advantage of the lower melting temperatures obtained from the presence of carbon dioxide in the bulk mixture. The particles obtained were analysed by scanning electron microscopy (SEM), laser diffraction and attenuated total reflection Fourier infrared (ATR-FTIR) spectroscopic imaging. Solubility tests in simulated gastric and intestinal fluids, without enzymes, were performed. The presence of the lipid carriers can influence the solubility of trans-chalcone in the solutions tested. [Copyright &y& Elsevier]

N-Mannich bases have been widely applied as prodrugs of amine drugs. The analogous C-Mannich bases (beta-aminoketones) have received rather less attention probably because they are not sufficiently susceptible to elimination at pHs encountered in vivo. Compounds in which there is a thermodynamic advantage to elimination may be an exception. In this study, the physicochemical characteristics of a series of Michael amino addition adducts of chalcone and other carbonyl compounds is explored. The ketone adducts rapidly eliminate at around pH 7.4 (t(1/2) < 15 min) releasing the amine and the ketone but they are stable under acidic conditions. The Michael adducts are more lipophilic than the parent amines and have significantly suppressed ionisation characteristics at biologically relevant pH values.