Microspherical Particles of Solid Dispersion of Polyvinylpyrrolidone K29-32 for Inhalation Administration

© 2018 L. S. Usmanova et al. Inhalation administration is a promising alternative to the invasive drug delivery methods. The particle size required for ideal drug aerosol preparation is between 1 and 3 μm. The application of microspherical particles of solid dispersions enhances bioavailability of poorly soluble drugs due to the solubilization. In the present work, the spray drying process of the production of microspherical particles of solid dispersions of polyvinylpyrrolidone K29-32 with model hydrophobic drug, phenacetin, was optimized using the results of DSC, PXRD, and viscometry. The diameter of the obtained particles is within 1-3 μm range. The Gibbs energy of dissolution in water was shown to be negative for the mixture with polymer/phenacetin mass ratio 5: 1. We have demonstrated that the optimal size distribution for the inhalation administration is obtained for microspherical particles produced using spray caps with 7.0 μm hole size. The dissolution rates of phenacetin from the produced microspherical particles were faster than that of drug powder. As evidenced by powder X-ray diffraction data, phenacetin stayed in amorphous state for 4 months in microspherical particles of solid dispersions. According to the obtained results, strategic application of the spray drying process could be beneficial for the improvement of the pharmaceutical properties of model drug, phenacetin

Effect of acetonitrile on the binding of competitive inhibitor proflavin and on the catalytic activity of bovine pancreatic α-chymotrypsin

The binding of competitive inhibitor proflavin by the α-chymotrypsin enzyme in water-acetonitrile mixtures over the entire range of thermodynamic water activities was studied. The data on the binding of proflavin were compared to the results on the catalytic activity of the enzyme preliminary incubated in water-acetonitrile mixtures. Based on an analysis of the shape of the concentration dependences, it was demonstrated that the leading factor in controlling the behavior of the enzyme at low water activities is interprotein contacts formed during its drying. At high water activities, the functional properties of the enzyme are largely determined by the interaction with the organic solvent. The interplay of these two factors manifests itself through a complex shape of the isotherm of binding of proflavin, with the maximum being positioned in the range of moderate water activities. © Pleiades Publishing, Inc., 2006

Effect of dioxane on the binding of competitive inhibitor proflavin and catalytic activity of bovine pancreatic α-chymotrypsin

The binding of competitive inhibitor proflavin by α-chymotrypsin in water-dioxane mixtures over the entire range of thermodynamic activities of water a w was studied. The data on the degree of binding of proflavin were compared to the results on the catalytic activity of the enzyme preliminary incubated in water-dioxane mixtures. An analysis of the behavior of the concentration dependences of these characteristics demonstrated that, at low a w values, the behavior of the interprotein contacts in the enzyme formed during its drying largely governs its functional properties, while at high a w values, they are determined by the interaction of the enzyme with the organic solvent. Interplay of these two factors is responsible for the observed complex shape of the isotherm of binding of proflavin, with the maximum degree of binding being attained at moderate a w values. © 2007 Pleiades Publishing, Ltd

Additive scheme for calculation of solvation enthalpies of heterocyclic aromatic compounds. Sublimation/vaporization enthalpy at 298.15 K

© 2016 Elsevier B.V. All rights reserved.Hereby we propose a method for determination of vaporization and sublimation enthalpies of heterocyclic and carbonyl-containing aromatic compounds at 298.15 K. According to this method vaporization and sublimation enthalpies at 298.15 K are determined based on enthalpies of solvation and solution. Solvation enthalpies of heteroatomatic and carbonyl-containing compounds are calculated using an additive scheme from the solvation enthalpy of closest aromatic hydrocarbon and contributions related to the exchange of CH-groups of hydrocarbon with corresponding substituent atoms or groups. Measured solution enthalpies together with calculated solvation enthalpies allowed to calculate corresponding vaporization and sublimation enthalpies at 298.15 K for a large number of heterocyclic and carbonyl-containing compounds. We have also found that in a number of cases instead of solution enthalpy in benzene at 298.15 K fusion enthalpy at the melting temperature can be used. Comparison between literature data and calculated vaporization and sublimation enthalpies demonstrates satisfactory performance of the proposed method

Effect of tetrahydrofuran on the binding of the competitive inhibitor proflavin and the storage stability of bovine pancreatic α-chymotrypsin

The binding of the competitive inhibitor proflavin by bovine pancreatic α-chymotrypsin in water-tetrahydrofuran mixtures was studied in the entire range of thermodynamic water activities at 25°C. The data on the binding of proflavin were compared with the results on the storage stability of α-chymotrypsin in water-organic mixtures. An analysis of the concentration dependency of these characteristics demonstrated that, at low water activity values, the interprotein contacts in the enzyme formed during its drying largely govern its functional properties, while at high water activity, they are determined by the interaction of the enzyme with the organic solvent. The interplay of these two factors is responsible for the complex shape observed for the isotherm of binding of proflavin, with a maximum degree of binding being attained at medium water activity values. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Fast scanning calorimetry of lysozyme unfolding at scanning rates from 5 K/min to 500,000 K/min

© 2018 Elsevier B.V. Background: Protein denaturation is often studied using differential scanning calorimetry (DSC). However, conventional instruments are limited in the temperature scanning rate available. Fast scanning calorimetry (FSC) provides an ability to study processes at much higher rates while using extremely small sample masses [ng]. This makes it a very interesting technique for protein investigation. Methods: A combination of conventional DSC and fast scanning calorimeters was used to study denaturation of lysozyme dissolved in glycerol. Glycerol was chosen as a solvent to prevent evaporation from the micro-sized samples of the fast scanning calorimeter. Results: The lysozyme denaturation temperatures in the range of scanning rates from 5 K/min to ca. 500,000 K/min follow the Arrhenius law. The experimental results for FSC and conventional DSC fall into two distinct clusters in a Kissinger plot, which are well approximated by two parallel straight lines. Conclusions: The transition temperatures for the unfolding process measured on fast scanning calorimetry sensor are significantly lower than what could be expected from the results of conventional DSC using extrapolation to high scanning rates. Evidence for the influence of the relative surface area on the unfolding temperature was found. General significance: For the first time, fast scanning calorimetry was employed to study protein denaturation with a range of temperature scanning rates of 5 orders of magnitude. Decreased thermal stability of the micro-sized samples on the fast scanning calorimeter raise caution over using bulk solution thermal stability data of proteins for applications where micro-sized dispersed protein solutions are used, e.g., spray drying

Enthalpies of solution, enthalpies of fusion and enthalpies of solvation of polyaromatic hydrocarbons: Instruments for determination of sublimation enthalpy at 298.15K

© 2015. In this work a simple method for calculation of solvation enthalpies of polyaromatic hydrocarbons (PAHs) in various solvents at 298.15. K was proposed. According to this method the enthalpy of solvation of any polyaromatic hydrocarbon in a particular solvent can be calculated on the basis of the general formula of the compound, the solvation enthalpy of benzene in the same solvent and parameter related to the contribution of hydrogen atom into solvation enthalpy. The validity of the proposed method was confirmed by the comparison of calculated and experimentally measured values of solvation enthalpies of PAHs in benzene, tetrahydrofuran and acetonitrile. This method was used for determination of the sublimation enthalpy of PAHs at 298.15. K based on the general relationship between the enthalpy of sublimation/vaporization of the compound of interest and its enthalpies of solution and solvation in the same solvent at 298.15. K. Enthalpies of solution at infinite dilution of several PAHs were measured in acetonitrile, benzene and tetrahydrofuran at 298.15. K. It was shown that solution enthalpies of PAHs in benzene at 298.15. K are approximately equal to their fusion enthalpies at the melting temperature. Solvation enthalpies of 15 PAHs at 298.15. K calculated according to the proposed method together with corresponding fusion enthalpy values (at the melting temperature) were used to calculate the sublimation enthalpy values at 298.15. K. Comparison of the obtained results with recommended values of sublimation enthalpy shows that fusion enthalpies at the melting temperature can be used instead of the solution enthalpies in benzene at 298.15. K for calculation of the sublimation enthalpy at 298.15. K

Enthalpies of fusion and enthalpies of solvation of aromatic hydrocarbons derivatives: Estimation of sublimation enthalpies at 298.15 K

© 2016 Elsevier B.V. All rights reserved.Enthalpy of sublimation of solid compound can be found using the values of solution enthalpy and solvation enthalpy in any solvent. In this work enthalpies of solution at infinite dilution of a number of aromatic hydrocarbons derivatives in benzene were measured at 298.15 K. Comparison between experimental and literature solution enthalpies in benzene at 298.15 K and fusion enthalpies at melting temperature of aromatic hydrocarbon derivatives showed, that these values are approximately equal. Thereby, fusion enthalpies at melting temperature can be used instead of their solution enthalpies in benzene at 298.15 K for calculation of sublimation enthalpies at 298.15 K. Solvation enthalpies in benzene at 298.15 K required for this procedure were calculated using group additivity scheme. The sublimation enthalpies of 80 aromatic hydrocarbons derivatives at 298.15 K were evaluated as a difference between fusion enthalpies at melting temperature and solvation enthalpies in benzene at 298.15 K. Obtained in this work values of sublimation enthalpy at 298.15 K for studied compounds were in a good agreement with available literature data

Application of fast scanning calorimetry to the fusion thermochemistry of low-molecular-weight organic compounds: Fast-crystallizing m-terphenyl heat capacities in a deeply supercooled liquid state

© 2018 Elsevier B.V. Fusion enthalpy temperature dependence is related to the difference in heat capacity of the liquid and solid. Below the melting temperature, it is hard to measure the liquid heat capacity using conventional methods due to fast crystallization. Based on an indirect solution calorimetry approach, we previously concluded that the temperature dependence of heat capacities below the melting temperature is the extrapolation of the linear function above it. In this study, we employed a fast scanning calorimetry technique to test the validity of this conclusion. Three compounds were studied: two organic glass formers, benzophenone and o-terphenyl, for which the liquid and supercooled liquid heat capacities were known to be accurately described by a linear function of temperature, and m-terphenyl, which had never been studied in the supercooled liquid state. The results were in good agreement with the literature for liquid benzophenone and o-terphenyl heat capacities above and below the melting temperature. The heat capacity of the supercooled liquid and glassy m-terphenyl was obtained for the first time. The measured molar heat capacity of supercooled liquid m-terphenyl was the linear extrapolation of the temperature dependence of the heat capacity of the melt found in the literature. The molar heat capacity of the solid, the enthalpy and fusion temperature of m-terphenyl were determined by conventional DSC. Kirchhoff's integral, calculated from the measured molar heat capacities of solid and liquid m-terphenyl, was in accordance with the fusion and solution thermochemistry data

Influence of the cross-link density on the rate of crystallization of poly(ε-caprolactone)

© 2018 by the authors. Cross-linked poly(ε-caprolactone) (PCL) is a smart biocompatible polymer exhibiting two-way shape memory effect. PCL samples with different cross-link density were synthesized by heating the polymer with various amounts of radical initiator benzoyl peroxide (BPO). Non-isothermal crystallization kinetics was characterized by means of conventional differential scanning calorimetry (DSC) and fast scanning calorimetry (FSC). The latter technique was used to obtain the dependence of the degree of crystallinity on the preceding cooling rate by following the enthalpies of melting for each sample. It is shown that the cooling rate required to keep the cooled sample amorphous decreases with increasing cross-link density, i.e., crystallization process slows down monotonically. Covalent bonds between polymer chains impede the crystallization process. Consequently, FSC can be used as a rather quick and low sample consuming method to estimate the degree of cross-linking of PCL samples