Radio Labelling of Drugs in a Metered Dose Inhaler (MDI) and Lung Deposition in Human Subjects

The lung deposition (amount and distribution) of drugs from MDIs cannot be quantified using routine pharmacokinetic methods. A growing number of drugs from inhalers has been investigated in recent years using a radiolabel to overcome this difficulty. Fenoterol (Berotec(R)) and Flunisolide (Inhacort(R)) both from Boehringer Ingelheim KG are two drugs primarily used by inhalation in the treatment of asthma. These compounds were labelled with Technetium-99m (Tc) in the MDI. The Tc-99m label as observed with a gamma camera was shown to follow the same distribution pattern as the drug particles. Cascade impaction with eight stages resulted in the following distribution 63, 8, 5, 3, 6, 5, 8, and 2 % from Stage 1 to Stage 8. A clinical study with 12 healthy volunteers compared the deposition pattern derived from MDI alone and MDI with spacer. Regions Of Interest (ROIs) were the oropharyngal cavity, esophagus, stomach, and lung (central and peripheral zones). With MDI alone, 73 % of the drug was found in upper ROIs, whereas the addition of a spacer reduced deposition of the drug in the large airways to 3 %. This technique may also be a valuable tool in comparing different formulations; however the stability of Tc-99m binding to the drug particles should be evaluated before utilizing this technique.