ABSTRACT
In formulation development or in the in vivo performance of the dosage form, the occasion may arise when a drug’s inherently low aqueous solubility does not m eet the solution concentration required. If the aqueous solubility of a drug is less than 10 mg/mL, bioavailability or absorption problems are likely to exist (Greene 1979). If the drug to be formulated as a liquid product possesses ionizable groups, adjustment of the pH in which the drug is to be dissolved might be sufficient to enhance the sol ubility. The solubility of an organic molecule is frequently enhanced more by an ion ized functional group than by any other single means. This is understandable since there are strong interactions between the solute ion and the ions and dipoles of water, possibly overcoming the drawback of a large hydrophobic portion of the drug mole cule. However, weak acids and weak bases may require extremes in pH that are out side acceptable physiologic limits or at which stability problems arise (Anderson 1985; Ansel, Popovich, and Allen 1995). In general, aqueous solubility is a function of chem ical structure, and salts represent the class of drugs that are m ost likely to attain the degree of water solubility desired (Motola and Agharkar 1984). The salt form of a drug is usually more soluble than the nonionized form in an aqueous medium, although it should be noted that not all salts have improved aqueous solubilities. Procaine peni cillin is often cited as an example of a poorly soluble salt.
