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  • Title: Temperature and solvent effects in the solubility of some pharmaceutical compounds: Measurements and modeling.
    Author: Mota FL, Carneiro AP, Queimada AJ, Pinho SP, Macedo EA.
    Journal: Eur J Pharm Sci; 2009 Jun 28; 37(3-4):499-507. PubMed ID: 19406228.
    Abstract:
    In this work, pure solvent solubilities of drugs, such as paracetamol, allopurinol, furosemide and budesonide, measured in the temperature range between 298.2-315.2K are presented. The solvents under study were water, ethanol, acetone, ethyl acetate, carbon tetrachloride and n-hexane. Measurements were performed using the shake-flask method for generating the saturated solutions followed by compositional analysis by HPLC. Previous literature values on the solubilities of paracetamol were used to assess the experimental methodology employed in this work. No literature data was found for any of the other drugs studied in this assay. Melting properties of the pure drugs were also determined by differential scanning calorimetry (DSC) to provide a broader knowledge about the solubilization process and also for modeling purposes. The solubility data as a function of temperature were used to determine the thermodynamic properties of dissolution like, Gibbs energy, enthalpy and entropy. Theoretical work was essentially focused on the evaluation of the Nonrandom Two-Liquid Segment Activity Coefficient (NRTL-SAC) model, which has been referred as a simple and practical thermodynamic framework for drug solubility estimation. A satisfactory agreement was found between experimental and calculated values: the absolute average deviation was 68% for the correlation in the organic solvents and 38% for the prediction in water, where the best results in prediction could be related to the selected solvents.
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