Practical Aspects of Solubility Determination in Pharmaceutical Preformulation

Part of the Biotechnology: Pharmaceutical Aspects book series (PHARMASP, volume VI)


Solubility is one of the most important physicochemical properties studied during pharmaceutical preformulation. For liquid dosage form development, accurate solubility data are essential to ensure the robustness of the finished product. For solid dosage forms, solubility data are important in determining if an adequate amount of drug is available for absorption in vivo. If a compound has a low aqueous solubility, it may be subject to dissolution rate-limited or solubility-limited absorption within the gastrointestinal (GI) residence time (Lobenberg et al., 2000). The importance of solubility, in biopharmaceutical terms, is highlighted by its use in the biopharmaceutics classification system (BCS) described by Amidon et al. (1995). This system defines low solubility compounds as those whose aqueous solubility in 250 mL of pH 1–7.5 aqueous solution is less than the total dose. Solubility data are also used to estimate the maximum absorbable dose (MAD) (Johnson and Swindell, 1996). MAD is a conceptual tool that relates the solubility requirement for oral absorption to the dose, permeability and GI volume and transit time. It is defined as:


High Performance Liquid Chromatography Drug Substance Practical Aspect Solubility Data Soluble Compound 
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© Springer 2007

Authors and Affiliations

    • 1
  1. 1.Novartis Pharmaceuticals Corporation, Pharmaceutical and Analytical DevelopmentEast Hanover

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