Solubility is the most important physicochemical property of drug molecules, which can affect the drug absorption. The drug molecules have to be dissolved in the solution for the absorption to occur in the intestinal tract. The solubility of a solute is the maximum quantity of solute that can dissolve in a certain quantity of solvent or quantity of solution at a specified temperature. The extent of ionization and oil/water partition coefficient K of the drug contribute to both drug solubility and membrane permeability. In general, low K indicates high solubility in water and high K indicates high solubility in lipid. However, the drug molecules with high lipid solubility usually possess high membrane permeability.
Ionization and pH play an important role in drug water solubility (Zhou et al., 2005). Ionized form is usually more water soluble than unionized form, but unionized form is easier for absorption in the GI tract by passive diffusion than ionized form. For weakly basic drugs, more unionized form would be predominant in intestine at high pH (5-8), which favors absorption. For weakly acid drug, more ionized form would be predominant in intestine. Although in theory that ionized weak acid is not favorable for absorption in intestine, the larger surface area of intestine will compensate this weakness to produce complete absorption for many weakly acidic drug.
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