The role of stearic acid in ascorbic acid protection from degradation: a heterogeneous system for homogeneous thermodynamic data

International audienceA heterogeneous system between vitamin C and stearic acid was characterized by thermal and crystallographic analyses. The results showed that such a system prevents vitamin C from thermal decomposition. The evidence was provided by implementing a new protocol associating chromatic assays and thermal analyses in order to quantify the percentage of non-degraded vitamin C. The results collected with the vitamin C–stearic acid mixtures allowed deducing coherent interpretation of the results obtained with pure vitamin C at different heating scan rates. Vitamin C mainly degrades upon melting but also in the solid state for temperature close to the melting point when the heating rates are very low. Under these conditions, the temperature determined at the onset of the DSC graphs cannot be associated with the melting temperature but with a fusion-degradation phenomenon. At higher scan rates, the onset as well as the endothermic value of the signal increase to reach plateau values. These values have been identified as the temperature and enthalpy values of melting of vitamin C according to the results obtained from the heterogeneous system

Insights into the crystal structure, polymorphism and thermal behavior of menthol optical isomers and racemates

International audienceThe physico-chemical properties of the levo- and dextrorotatory menthol isomers as well as the corresponding racemic compound were studied using X-ray single-crystal or powder diffraction and differential scanning calorimetry experiments. As a result, the not yet determined crystal structure of DL-menthol was solved. Moreover, the stable and metastable experimental temperature-composition phase diagrams of the L-menthol/D-menthol binary system were determined. The thermodynamic relative stability of the different menthol polymorphs was also established. The present paper provides new physical, chemical and thermodynamic data of L-, D- and DL-menthol and offers new insight into their polymorphism as well as into the levorotatory-dextrorotatory menthol interactions. Both the thermodynamic and crystallographic approaches demonstrate unambiguously that racemic menthol is a racemate

Comprehensive determination of the solid state stability of bethanechol chloride active pharmaceutical ingredient using combined analytical tools

International audienceThe use of an integrative analytical approach allowed us to establish the intrinsic solid state stability of bethanechol chloride (BC), an active pharmaceutical ingredient used in the treatment of urinary retention. First, the crystal structure of the monoclinic form has been described using single crystal X-ray diffraction studies. Second, thermal analyses revealed that the compound degrades upon melting, with an apparent melting temperature estimated to be 231 °C. No transition from the monoclinic to the orthorhombic form has been observed, suggesting that the monoclinic form is the stable one. Third, the two-step melting–decomposition process has been elucidated by liquid chromatography and thermogravimetry coupled to mass spectrometry. The first step corresponds to the sample liquefaction, which consists of the gradual dissolution of bethanechol chloride in its liquid degradant, i.e. betamethylcholine chloride. This step is in agreement with Bawn kinetics and the activation energy of the reaction has been estimated at 35.5 kcal mol−1. The second step occurs with accelerated degradation in the melt. Elucidation of secondary decomposition pathways evidenced autocatalytic properties conferred by the formation of both isocyanic acid and methyl chloride. Finally, dynamic water vapor sorption analysis showed a substantial hygroscopicity of the drug substance. A deliquescent point has been determined at 56% relative humidity at 25 °C

Auto-assemblage d'une protéine fongique, l'hydrophobine SC3, aux interfaces : Applications à l'élaboration de surfaces catalytiques

The work performed in this thesis allowed understanding of the interfacial self-assembly of a fungal protein, SC3 hydrophobin, at a deeper mechanistic level. These fundamental studies were the starting point of an applied research on the possibilities of using hydrophobin as an agent retaining different molecules on solid surfaces. It was shown that enzymes, fullerene, calixarene and cyclodextrin derivatives could be immobilized on carbon, platinum, polytetrafluoroethylene, polystyrene or stainless steel surfaces, yielding functional materials. Moreover, it was shown that the SC3 hydrophobin with eight cystein sulfhydryl groups oxidized to sulfonates chelates cupric ions. The SC3-CuII incorporated in a lipid cubic phase deposited on electrodes formed a reversible, biomimetic redox system. The results obtained in this work show a way to easily manufacture stable surfaces with possible applications in electro-optical switching and electrochemical sensing.Le travail réalisé a permis de mieux appréhender les mécanismes régissant l'auto-assemblage interfacial d'une protéine fongique, l'hydrophobine SC3. Ces études fondamentales ont été suivies par des travaux à caractère appliqué, visant l'utilisation de l'hydrophobine en tant qu'agent fixateur de molécules sur différents supports solides. Ainsi, des molécules aussi diverses que des enzymes, un dérivé de fullerène, ou encore des macrocycles tels que des dérivés de calixarène et de cyclodextrine dotés de propriétés de complexation de cations métalliques, ont été immobilisées sur des surfaces en carbone, platine, polytétrafluoroéthylène, polystyrène ou encore acier inoxydable. Par ailleurs, l'utilisation de l'hydrophobine SC3 portant des groupements sulfonates issus de l'oxydation des groupements sulfhydryles des cystéines, a permis l'immobilisation directe d'ions cuivriques dans une matrice mixte hydrophobine - membrane lipidique. Les résultats obtenus montrent que les différentes techniques d'immobilisation utilisées sont intéressantes pour la préparation de systèmes fonctionnels tels que les interrupteurs moléculaires électro-optiques, ou les capteurs électrochimiques basés sur des processus catalytiques

Auto-assemblage d'une protéine fongique, l'hydrophobine SC3, aux interfaces (Applications à l'élaboration de surfaces catalytiques)

Le travail réalisé a permis de mieux appréhender les mécanismes régissant l'auto-assemblage interfacial d'une protéine fongique, l'hydrophobine SC3. Ces études fondamentales ont été suivies par des travaux à caractère appliqué, visant l'utilisation de l'hydrophobine en tant qu'agent fixateur de molécules sur différents supports solides. Ainsi, des molécules aussi diverses que des enzymes, un dérivé de fullerène, ou encore des macrocycles tels que des dérivés de calixarène et de cyclodextrine dotés de propriétés de complexation de cations métalliques, ont été immobilisées sur des surfaces en carbone, platine, polytétrafluoroéthylène, polystyrène ou encore acier inoxydable. Par ailleurs, l'utilisation de l'hydrophobine SC3 portant des groupements sulfonates issus de l'oxydation des groupements sulfhydryles des cystéines, a permis l'immobilisation directe d'ions cuivriques dans une matrice mixte hydrophobine - membrane lipidique. Les résultats obtenus montrent que les différentes techniques d'immobilisation utilisées sont intéressantes pour la préparation de systèmes fonctionnels tels que les interrupteurs moléculaires électro-optiques, ou les capteurs électrochimiques basés sur des processus catalytiques.The work performed in this thesis allowed understanding of the interfacial self-assembly of a fungal protein, SC3 hydrophobin, at a deeper mechanistic level. These fundamental studies were the starting point of an applied research on the possibilities of using hydrophobin as an agent retaining different molecules on solid surfaces. It was shown that enzymes, fullerene, calixarene and cyclodextrin derivatives could be immobilized on carbon, platinum, polytetrafluoroethylene, polystyrene or stainless steel surfaces, yielding functional materials. Moreover, it was shown that the SC3 hydrophobin with eight cystein sulfhydryl groups oxidized to sulfonates chelates cupric ions. The SC3-CuII incorporated in a lipid cubic phase deposited on electrodes formed a reversible, biomimetic redox system. The results obtained in this work show a way to easily manufacture stable surfaces with possible applications in electro-optical switching and electrochemical sensing.NANCY1-SCD Sciences & Techniques (545782101) / SudocSudocFranceF

Interpretation of the Global Heat of Melting in Eutectic Binary Systems

International audienc

Phase Behavior and Relative Stability of Malonamide Polymorphs

International audienceThe three known polymorphs of malonamide have been characterized by thermal analysis and X-ray powder diffraction. The melting thermodynamic characteristics of the three forms are thus proposed in the present paper. From these data, the relative thermodynamic stability of these three solid forms has been determined. It appears that an enantiotropic behavior is established between the bmonoclinic and the orthorhombic phases while the quadratic one is monotropic with respect to the other two

Physicochemical Stability of Solid Dispersions of Enantiomeric or Racemic Ibuprofen in Stearic Acid

The aim of this study was to investigate the solid dispersion phase behavior of s- or rs-ibuprofen in stearic acid. By means of thermal analysis, we have demonstrated the total immiscibility, in solid state, of the corresponding binary mixtures. This indicates that no specific interactions exist between the chosen excipient and active pharmaceutical ingredient (API) that lead to eutectic systems. Furthermore, based on calorimetric and X-ray diffraction experiments, we have showed that upon cooling of the molten state, only stearic acid recrystallizes in the presence of s-ibuprofen, whereas a quaternary phase mixture is obtained for the racemic ibuprofen/stearic acid preparation. The solubility of stearic acid in s-ibuprofen liquid in all proportions was also determined. Overall, the results presented here offer an approach for the study of API/excipient interactions

Characterization of Unknown Solid States of the Drug Substance Quinacrine Dihydrochloride: Two Anhydrous Forms and a Tetrahydrate Revealed

International audienc