Formation and measurement of process induced disorder during the manufacture of inhalation medicines

The development and manufacture of inhalation medicines presents a number of complex challenges to the pharmaceutical scientist. Of paramount importance is delivering the drug particles with an optimal size for deposition in the desired regions of the lung. To achieve this, milling is typically applied to reduce the size of the drug particles destined for inhalation. Comminution has a number of important consequences for the physical properties of the processed drug particles. The generation of process induced disorder (PID) is a major issue which can lead to agglomeration of the powder and failure of the material to meet its specification. This review considers the challenges of achieving pulmonary delivery, the impact that particle size reduction during manufacture has on the properties of the inhaled drug particles and methods that may be employed to determine the extent of PID.