ABSTRACT
Drug discovery occurs in silico, in chemistry laboratories, in cell-free assays or tissue culture
systems, or in vivo in animal models on a molecule synthesized by the chemist. Final drug
usage however occurs in patients using tablets, creams, injections, or other products that are
a combination of the drug and various excipients, which together constitute the final
medicinal product intended to produce the desired therapeutic effect. Preformulation is the
initial stage of the conversion of molecule to drug where various important pharmaceutical
(physical, chemical, and biological) properties of the putative drug molecule are assessed. It
is difficult to define fully what constitutes preformulation (Fig. 1) or where it starts and ends
within a drug discovery/development program. In an innovator setting, studies will be
conducted in an expedient fashion on the small experimental amounts of material available
in competition with other equally or more important studies related to preclinical
pharmacology. Assuming acceptable results and continuation of drug development the
drug quantities available will increase and the range of preformulation studies (including
pharmacology) expanded to encompass all aspects of preclinical and preformulation
development of drugs. In a generic development setting, these restrictions in general will not
apply since preexisting information may be available and compound supplies are already
established. Excessive early studies in an innovator program on candidate drugs that may
never progress beyond preclinical development is a resource drain. This development
dilemma is an important consideration that controls the application of preformulation studies
and is difficult to reconcile to minimize development time and resource waste, while
maximizing success potential. In general the various studies will be conducted where
possible in parallel with the most immediate required information generated as early as
possible.
