posted on 2020-03-05, 16:34authored byShubhajit Paul, Lisa J. Taylor, Brendan Murphy, Joseph F. Krzyzaniak, Neil Dawson, Matthew P. Mullarney, Paul Meenan, Changquan Calvin Sun
Punch sticking during
tablet manufacturing is a common problem
facing the pharmaceutical industry. Using several model compounds,
effects of crystal size and shape of active pharmaceutical ingredients
(API) on punch sticking propensity were systematically investigated
in this work to provide molecular insights into the punch-sticking
phenomenon. In contrast to the common belief that smaller API particles
aggravate punch sticking, results show that particle size reduction
can either reduce or enhance API punch sticking, depending on the
complex interplay among the particle surface area, plasticity, cohesive
strength, and specific surface functional groups. Therefore, other
factors, such as crystal mechanical properties, surface chemistry
of crystal facets exposed to the punch face, and choice of excipients
in a formulation, should be considered for a more reliable prediction
of the initiation and progression of punch sticking. The exposure
of strong electronegative groups to the punch face facilitates the
onset of sticking, while higher plasticity and cohesive strength aggravate
sticking.