ABSTRACT
Particle size reduction offers a significant opportunity for formulators to solve the product development hurdles inherent with poorly water-soluble compounds. In the case of formulations intended for oral administration, poorly water-soluble com pounds typically suffer from an inadequate or highly variable rate and /or extent of drug absorption. Particle size reduction of the drug substance prior to formulating will increase the specific surface area significantly and, subsequently, the rate of dis solution of the drug in the gut milieu. Therefore, for poorly water-soluble compounds for which absorption is dissolution limited, particle size reduction of the drug may result in significant improvement in the rate and extent of drug absorption such that the bioavailability requirements of the drug are met. In the case of formulations intended for intravenous adm inistration, size reduction of drug substance to nanometer-sized particles renders a sterile aqueous dispersion of such particles infusible. Indeed, particle-size-reduction methodologies have advanced to the point where nanometer-sized crystalline drug particles can be realized. This size-reduction approach provides a valuable formulation alternative to the traditional formulation approach of ensuring that a drug is solubilized prior to intravenous administration. It alleviates the complexity associated with utilizing high concentrations of aqueous com patible cosolvents and surfactants to solubilize the drug. In addition, size reduction can
also enhance delivery of poorly water-soluble drugs to the respiratory tract. Specifi cally, aerosolized particles should have aerodynamic diameters in the range of 1-5 pm . With larger particles, deposition occurs primarily on the back of the throat, which can lead to systemic side effects.
