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Revista de Chimie (Rev. Chim.), Year 2016, Volume 67, Issue 10,





KELEMEN HAJNAL, GABRIEL HANCU, DANIELA LUCIA MUNTEAN, JEANINA PANDELE CUSU
Optimization of Diazepam Solubility with Auxiliary Substances and Thermo Analytical Investigation of Binary Systems

Abstract:

Diazepam is one of the most frequently prescribed anxiolytics in psychotherapy. However, its solubility characteristics are very unfavorable. To improve these, different auxiliary substances like cyclodextrin derivatives and non-ionic macromolecular materials can be used. The binary systems between diazepam and auxiliary substances were prepared in four molar ratios, and by several methods (mixing, kneading, co-precipitation and spray drying) and the solubility and the dissolution rate were studied. All binary systems showed superior dissolution compared to pure diazepam. Differential scanning calorimetry and thermogravimetric analysis were used to characterize solid state interactions between diazepam and the auxiliary substances. Various kinetic parameters, as activation energy, virtual reaction order, pre-exponential factor were calculated. Taking in consideration the kinetic and thermodynamic parameters, the solubility results are in correlation with the stability order of the binary systems. The thermoanalytical investigation demonstrates that the thermic stability of diazepam is increased by the inclusion complexes. The thermoanalytical analysis sustains the hypothesis of formation of partial inclusion complexes between diazepam and cyclodextrins. Keywords: diazepam, cyclodextrins, solubility, differential scanning calorimetry, thermogravimetric analysis


Issue: 2016, Volume 67, Issue 10
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