Comparison of a Miniaturized Shake-Flask Solubility Method with Automated Potentiometric Acid/Base Titrations and Calculated Solubilities A. Glomme,

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Presentation transcript:

Comparison of a Miniaturized Shake-Flask Solubility Method with Automated Potentiometric Acid/Base Titrations and Calculated Solubilities A. Glomme, J. März, J.B. Dressman Journal of Pharmaceutical Sciences Volume 94, Issue 1, Pages 1-16 (January 2005) DOI: 10.1002/jps.20212 Copyright © 2004 Wiley-Liss, Inc., A Wiley Company Terms and Conditions

Figure 1 Potentiometric titration curve of mefenamic acid, measured with the pSol instrument at 37°C. Journal of Pharmaceutical Sciences 2005 94, 1-16DOI: (10.1002/jps.20212) Copyright © 2004 Wiley-Liss, Inc., A Wiley Company Terms and Conditions

Figure 2 Bjerrum plot of mefenamic acid measured with the pSol instrument at 37°C. Journal of Pharmaceutical Sciences 2005 94, 1-16DOI: (10.1002/jps.20212) Copyright © 2004 Wiley-Liss, Inc., A Wiley Company Terms and Conditions

Figure 3 (a) Schematic of Whatman Processor™. (b) Photograph of Whatman Processor™. Journal of Pharmaceutical Sciences 2005 94, 1-16DOI: (10.1002/jps.20212) Copyright © 2004 Wiley-Liss, Inc., A Wiley Company Terms and Conditions

Figure 4 (a) Schematic of pSol instrument (Sirius‐Analytics, Riverside, UK). (b) Photograph of pSol instrument. Journal of Pharmaceutical Sciences 2005 94, 1-16DOI: (10.1002/jps.20212) Copyright © 2004 Wiley-Liss, Inc., A Wiley Company Terms and Conditions

Figure 5 Solubility determinations of glyburide with the pSol instrument using ACN as cosolvent. Journal of Pharmaceutical Sciences 2005 94, 1-16DOI: (10.1002/jps.20212) Copyright © 2004 Wiley-Liss, Inc., A Wiley Company Terms and Conditions

Figure 6 Solubility determinations of glyburide with the pSol instrument using methanol as cosolvent. Journal of Pharmaceutical Sciences 2005 94, 1-16DOI: (10.1002/jps.20212) Copyright © 2004 Wiley-Liss, Inc., A Wiley Company Terms and Conditions

Figure 7 pH/solubility profile for glyburide, determined with the miniaturized shake‐flask method (▴) and the pSol instrument (×). Journal of Pharmaceutical Sciences 2005 94, 1-16DOI: (10.1002/jps.20212) Copyright © 2004 Wiley-Liss, Inc., A Wiley Company Terms and Conditions

Figure 8 Correlation between measured (miniaturized shake‐flask) and solubilities calculated with WSKOWWIN version 1.40 with calculated logP and mp (▴) and experimental logP and mp (+). Journal of Pharmaceutical Sciences 2005 94, 1-16DOI: (10.1002/jps.20212) Copyright © 2004 Wiley-Liss, Inc., A Wiley Company Terms and Conditions

Figure 9 Correlation between the measured (miniaturized shake‐flask) solubilities with those calculated with the WSKOWWIN version 1.40 program (+), and with the Yalkowsky equation (). Journal of Pharmaceutical Sciences 2005 94, 1-16DOI: (10.1002/jps.20212) Copyright © 2004 Wiley-Liss, Inc., A Wiley Company Terms and Conditions