An advanced and detailed in vitro validation procedure for the radiolabeling of carrier-free terbutaline sulphate dry powder

The aerodynamic properties of Tc-99m radiolabeled carrier-free terbutaline sulphate (TBS) have been thoroughly investigated following delivery by Turb uhaler((R)) (AstraZeneca Lund, Sweden). A full and detailed radiolabeling p rocedure is also reported. The in vitro radiolabel validation was performed to determine whether TBS radiolabeled in this way would be representative of the commercially available product Bricanyl((R)) Turbuhaler during clini cal trials. The results indicated that variations in aerodynamic properties had been introduced and that the radiolabel would slightly underestimate t he fine particle fraction of Bricanyl, but would nonetheless act as a suita ble marker in vivo. Assumptions regarding the aerodynamic properties of dos es likely to be received by clinical trial subjects were also examined. Thi s has been achieved by extending the validation procedures beyond those usu ally reported to include dose number, time, and homogeneity dependent studi es. It was found that doses extracted for testing purposes and simulated pa tient doses extracted shortly afterward had similar properties. Doses extra cted 2 h after initial testing also had similar properties to the test dose s. These results suggested that data from the test doses could be used for quality control purposes, would be representative of the doses to be receiv ed by clinical trial subjects, and that a short delay between initial testi ng and trial subject inhalation would be acceptable.