Capsule Based Aerosol Generation-Test Article Conservation during the Conduct of in vivo Lead Optimization Respiratory Safety Assessment Studies

In both clinical and non-clinical environments the inhaled delivery of drug substances to conscious subjects will typically require larger quantities of the test article than any other route of administration. This difference is greatest for dry powder formulations in which charge and proximity effects are most pronounced, but it is also due to the losses and inefficiencies in the delivery device and aerosol delivery system. Minimizing such losses, particularly when conducting in vivo lead optimization studies in rodents, provides a means of reducing the cost of drug development. Decreasing the amount of test article requirement enables the conduct of investigations utilising inhaled route earlier in a development programme, when the test article is most likely to have limited availability and greatest cost. Over the last three years GSK and Envigo have successfully collaborated to identify alternative aerosol generation methods to minimize powder usage for inhaled delivery to conscious non-clinical species. The principle alternative delivery methodology, intratrachael insufflation, achieves particulate deposition dissimilar to conscious inhaled delivery and can produce artefactual toxicological and pharmacological results. Results of work conducted by Envigo and GSK to characterize and redesign a capsulebased aerosol generator are presented. If further work is successfully concluded, the doser should facilitate the use of the inhaled route earlier in in vivo lead optimization studies, so increasing the quality of candidate drugs and reducing compound attrition precipitated by findings in later, resource intensive in vivo studies.

Author(s): S Moore, R Goodway, S Cracknell and G Paul

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