Advances in the pulmonary delivery of poorly water-soluble drugs: influence of solubilization on pharmacokinetic properties

Background: Pulmonary drug delivery is an accepted route of drug administration for the management of lung conditions and diseases as well as an evolving route of administration for the systemic delivery of agents. Many inhaled drugs pose formulation and delivery challenges in part because of poor aqueous solubility. The influence of poor aqueous solubility and formulation-based solubility enhancements on the pharmacokinetic profile of inhaled agents was reviewed. Method: A systematic review was performed to identify literature that reported pharmacokinetic findings following the pulmonary delivery of a poorly water-soluble agent. Results: The influence of solubility and formulation-based solubility enhancements on pharmacokinetic parameters following inhalation of corticosteroids, antifungals, oligopeptides, and opioids, was compiled. Conclusion: Poor aqueous solubility did not uniformly affect the pharmacokinetic profile for inhaled agents. Physicochemical and formulation-based solubility enhancement did affect drug absorption from the lungs. Numerous drug- and formulation-dependant pharmacokinetic effects were identified.