ABSTRACT
The pharmaceutical industry is under continual pressure to speed up the drug develop-
ment process, reduce costs, and improve process design. At the same time, FDA’s new
Process Analytical Technology initiatives encourage the building in of product quality
and the development of meaningful product and process specifications that are ultimately
linked to clinical performance. Together, these two issues present significant challenges
to formulation and process scientists because of the complex, typically nonlinear, rela-
tionships that define the impact of multiple formulation and process variables (inde-
pendent variables), and such outcome responses (dependent variables) as drug release,
product stability, and others. The number of variables that must be addressed is sub-
stantial and include, for example, the level of drug substance, the types and levels of
various excipients, potential drug-excipient interactions, and their potential positive or
negative interactions with a host of process variables. Often, the relationships between
these variables and responses are not understood well enough to allow precise quanti-
tation. And, since an optimal formulation for one response is not necessarily an optimal
formulation for another response, product development is further confounded by the need
to optimize a number of responses simultaneously.
