Application of a Stable Isotope Approach to Evaluate Impact of Changes in Manufacturing Parameters for an Immediate-Release Tablet.

There is continued emphasis from the various worldwide regulatory agencies to ensure that the pharmaceutical industry fully understands the products they are developing. This emphasis is seen via development of quality-by-design (QbD) publications and guidelines generated by the International Committee on Harmonization. The challenge to meet these expectations is primarily associated with the generation of in vivo data (eg, pharmacokinetic data) that is resource intensive. A technique reducing the resources needed to generate this in vivo data permits a more extensive application of QbD principles. This paper presents the application of stable isotopes in pharmacokinetic studies. The data show that the use of stable isotopes can significantly reduce the number of subjects required for a study. This reduction in subjects thus translates into a significant reduction in resources and time needed to generate the required in vivo data to support QbD.