ABSTRACT
Pharmaceutical formulation development difficulties often arise during scale-up since
significant increase in production and local strain rates occur. Such cases are commonly
encountered in technical transfer since there is limited understanding regarding the effect of process variables on material properties at either the pilot or commercial scale. Technical
difficulties can sometimes be managed with extreme engineering controls, but often the root
cause is the formulation. A tablet is only as robust as the components that form it. Often these
materials form differently under different compression speeds. This strain rate sensitivity has
lead to other well publicized manufacturing cases like the FDA-triggered recall in 2005 of all
lots of a controlled-release tablet made by a large multinational (1). It was found that the tablets
could split apart. This deficiency could cause patients to receive a portion of the tablets that
lack any active ingredient or, alternatively, a portion that contained the active without the intended controlled-release effect. Clearly, the materials chosen, the formulation, and
processing together defined the boundary of failure. How could these known risks have
been better managed?
