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Comparative study of different methods for the prediction of drug-polymer solubilityKnopp, M.M., Tajber, L., Tian, Y., Olesen, N.E., Jones, D.S., Kozyra, A., Lobmann, K., Paluch, Krzysztof J., Brennan, C.M., Holm, R., Healy, A.M., Andrews, G.P., Rades, T. 27 July 2015 (has links)
Yes / In this study, a comparison of different methods
to predict drug−polymer solubility was carried out on binary
systems consisting of five model drugs (paracetamol,
chloramphenicol, celecoxib, indomethacin, and felodipine)
and polyvinylpyrrolidone/vinyl acetate copolymers (PVP/VA)
of different monomer weight ratios. The drug−polymer
solubility at 25 °C was predicted using the Flory−Huggins
model, from data obtained at elevated temperature using
thermal analysis methods based on the recrystallization of a
supersaturated amorphous solid dispersion and two variations
of the melting point depression method. These predictions were compared with the solubility in the low molecular weight liquid
analogues of the PVP/VA copolymer (N-vinylpyrrolidone and vinyl acetate). The predicted solubilities at 25 °C varied
considerably depending on the method used. However, the three thermal analysis methods ranked the predicted solubilities in
the same order, except for the felodipine−PVP system. Furthermore, the magnitude of the predicted solubilities from the
recrystallization method and melting point depression method correlated well with the estimates based on the solubility in the
liquid analogues, which suggests that this method can be used as an initial screening tool if a liquid analogue is available. The
learnings of this important comparative study provided general guidance for the selection of the most suitable method(s) for the
screening of drug−polymer solubility. / The Irish Research Council and Eli Lilly S.A. through an Irish Research Council Enterprise Partnership Scholarship for C.M.B., in part by The Royal Society in the form of Industrial Fellowship awarded to G.A., and in part by a research grant from Science Foundation Ireland (SFI) under Grant Number SFI/12/RC/2275 (for A.M.H., L.T., K.P., and A.K.).
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Physical Transformations for Greener Chemical ProcessesWeikel, Ross R. 20 July 2005 (has links)
Homogenous acid catalysts are prevalent throughout the chemical industry but all have the drawback of requiring post reaction neutralization and subsequent downstream removal of the product salt. The use of a base to neutralize the acid and the processing of the salt are ancillary to the process and the disposal of the salt is an environmental concern. The work presented here shows the use of alkylcarbonic acids, which form in situ with CO₂ pressure and neutralize on loss of CO₂ pressure rather than requiring a base. Thus CO₂ can be used to "switch" the acid on and off.
The properties of alkylcarbonic acids are explored to gain understanding of the mechanisms by which they act. The acids are also used to catalyze the synthesis of α-pinene, methyl yellow, and benzyl iodide. These reactions are examples of common acid catalyzed reactions where this technology could be implemented.
The second half of the work explores two other "switches". The first is using temperature to break an emulsion with a novel thermally cleavable surfactant. This technology has potential applications in a wide range of fields where surfactants are used including polymerization, oil recovery, and biosynthesis. The second is using CO₂ to liquefy a solid ionic compound to allow its use as a solvent. This would greatly increase the number of ionic species available for use in ionic liquid-CO₂ biphasic systems.
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