Formulation strategy and use of excipients in pulmonary drug delivery

Pulmonary administration of drugs presents several advantages in the treatment of many diseases. Considering local and systemic delivery, drug inhalation enables a rapid and predictable onset of action and induces fewer side effects than other routes of administration. Three main inhalation systems have been developed for the aerosolization of drugs; namely, nebulizers, pressurized metered-dose inhalers (MDIs) and dry powder inhalers (DPIs). The latter are currently the most convenient alternative as they are breath-actuated and do not require the use of any propellants. The deposition site in the respiratory tract and the efficiency of inhaled aerosols are critically influenced by the aerodynamic diameter, size distribution, shape and density of particles. In the case of DPIs, since micronized particles are generally very cohesive and exhibit poor flow properties, drug particles are usually blended with coarse and fine carrier particles. This increases particle aerodynamic behavior and flow properties of the drugs and ensures accurate dosage of active ingredients. At present, particles with controlled properties are obtained by milling, spray drying or supercritical fluid techniques. Several excipients such as sugars, lipids, amino acids, surfactants, polymers and absorption enhancers have been tested for their efficacy in improving drug pulmonary administration. The purpose of this article is to describe various observations that have been made in the field of inhalation product development, especially for the dry powder inhalation formulation, and to review the use of various additives, their effectiveness and their potential toxicity for pulmonary administration. (C) 2010 Elsevier B.V. All rights reserved.