Accumulation of inspissated secretions that are difficult to clear and congest the airways is a feature of lung disease in patients with cystic fibrosis (CF). These secretions restrict airflow, harbour infection and limit the delivery of inhaled drugs including gene therapy vectors to the underlying target cells. Unfractionated heparin (UFH) has mucolytic properties suggesting that it may be a useful therapeutic agent for lung disease in these patients. For the pulmonary delivery of UFH to patients with CF, the dry powder inhaler has potential advantages over systems using nebulised suspensions. However, spray-dried particles in the appropriate size range (1-5 microm) may absorb atmospheric moisture, causing aggregation. UFH has been cospray-dried with L-leucine (1%, w/w) to produce particles that are less cohesive than UFH alone and show good aerosolisation performance. Rheological analysis has shown that spray-dried UFH and UFH cospray-dried with L-leucine significantly (p < 0.05) reduce the elasticity and yield stress of CF sputum. The superior physical properties of UFH/L-leucine indicate this is the preferred formulation for development as an inhaled mucolytic.