Precision tests of a pH-solubility profile computer program

• Published in: International journal of pharmaceutics Vol. 164; no. 1; pp. 139 - 145
• Main Authors: Streng, William H, Yu, Daniel H.-S
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 13.04.1998; Elsevier
• Subjects: Biological and medical sciences; Compounds; General pharmacology; Ionization constant; Medical sciences; Non-linear regression analysis; pH-solubility; Pharmacology. Drug treatments; Physicochemical properties. Structure-activity relationships; pH-solubility; Ionization constant; Compounds; Non-linear regression analysis; Ionization; Estimation; Solubility; pH; Computer aid; Physicochemical properties
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(97)00428-6

The solubility of pharmaceutically important compounds as a function of pH is needed in order to optimize the formulation(s) and help to explain the observed behavior of the compounds during their development. The solubility of a weak acid or weak base is dependent upon its ionization constant, uncharged solubility and solubility product. Computer programs have been written to determine these parameters from experimental pH-solubility data and the parameters were found to be precise with random errors up to ±40% in { H}, ±0.05 in pH, ±40% in solubility and ±10% in both solubility and { H}. Systematic errors in the pH-solubility data result in systematic errors in p K a, p K sp and uncharged solubility. These results demonstrate that pH-solubility data can be used to precisely estimate p K as, p K sps and solubility of the neutral molecule. This technique may be a useful and practical alternative with low solubility compounds, particularly when there is no UV/VIS shift associated with species ionization.