Adjustment of the pH value is the simplest and most commonly used method of increasing the water solubility of ionisable compounds. The system works on the principle that natural changes in pH value within the gastrointestinal tract influence the bioavailability of pharmaceuticals.
Drug absorption is largely dependent on diffusion, and this varies with the pH value of different regions within the gastrointestinal tract, and the acid dissociation constant (pKa) and permeability of the drug. The absorption process is moderated by the surface area of the region of release and its pH value, which affects drug ionisation. If the pH value of a drug product with low water solubility is changed, parts of the molecule that may be protonated (base) or deprotonated (acid) may acquire the potential to be dissolved in water.
While parameters like salt selection and pH value are critical in the pre-formulation stages, the use of excipients to make pH adjustments is also a significant factor in designing the drug’s formulation and delivery, and should not be overlooked.
Adjusting the pH value can also be useful in the development of parenteral formulations, where physiologies of areas other than the gastrointestinal tract are involved.
