7 research outputs found
Impact of Solid-State Form on the Disproportionation of Miconazole Mesylate
Approximately
50% of solid oral dosage forms utilize salt forms
of the active pharmaceutical ingredient (API). A major challenge with
the salt form is its tendency to disproportionate to produce the un-ionized
API form, decreasing the solubility and negatively impacting product
stability. However, many of the factors dictating the tendency of
a given salt to undergo disproportionation remain to be elucidated.
In particular, the role of the solid-state properties of the salt
on the disproportionation reaction is unknown. Herein, various solid
forms of a model salt, miconazole mesylate (MM), were evaluated for
their tendency to undergo disproportionation when mixed with basic
excipients, namely tribasic sodium phosphate dodecahydrate (TSPd)
and croscarmellose sodium (CCS), and exposed to moderate relative
humidity storage conditions. It was observed that the rate and extent
of salt disproportionation were significantly different for the various
solid forms of MM. As expected, the amorphous salt was highly susceptible
to disproportionation, while the dihydrate salt form was resistant
to conversion under the conditions tested. In addition, binary excipient
blends of amorphous and anhydrous forms exhibited a reduced extent
of disproportionation at a higher relative humidity storage condition.
This was due to the competitive kinetics between disproportionation
to the free base and conversion to the dihydrate salt form. The results
of this study provide important insights into the impact of solid-state
form on susceptibility to disproportionation that can be utilized
for rationally designing robust pharmaceutical formulations