Drug solubility is affected by several physicochemical and physiological factors. Solubility of a drug can be influenced by the solid state that it exists in. Crystalline forms of compound are less soluble than amorphous forms of the compound. Different crystalline forms (e.g., polymorphs, salts, solvates) may also exhibit different solubilities. Physiological factors such as pH and bile acid concentrations can also influence compound solubility. Many basic and acidic drugs often exhibit pH-dependent solubility profiles and therefore will have different solubilities in the stomach in comparison to the small intestine. Food intake can impact solubility by impacting stomach pH and also by increasing the concentration of bile acids.
The surface area for dissolution is directly correlated with particle size and shape. Dissolution rate can also be influenced by factors such as the wettability of the solid drug. Milling processes are often performed on solid drug in order to decrease particle size and improve solid drug dissolution.
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