1 research outputs found
Mechanistic and Kinetic Insight into Spontaneous Cocrystallization of Isoniazid and Benzoic Acid
Solid-state
cocrystallization is of contemporary interest because
it offers an easy and efficient way to produce cocrystals, which are
recognized as prospective pharmaceutical materials. Research explaining
solid-state cocrystallization mechanisms is important but still too
scarce to give a broad understanding of factors governing and limiting
these reactions. Here we report an investigation of the mechanism
and kinetics of isoniazid cocrystallization with benzoic acid. This
reaction is spontaneous; however, its rate is greatly influenced by
environmental conditions (humidity and temperature) and pretreatment
(milling) of the sample. The acceleration of cocrystallization in
the presence of moisture is demonstrated by kinetic studies at elevated
humidity. The rate dependence on humidity stems from moisture facilitated
rearrangements on the surface of isoniazid crystallites, which lead
to cocrystallization in the presence of benzoic acid vapor. Furthermore,
premilling the mixture of the cocrystal ingredients eliminated the
induction time of the reaction and considerably increased its rate