Solubility-enhancing
amorphous solid dispersions are used in the
oral delivery of hydrophobic, crystallizable drugs. Effective solid
dispersion excipients enable high supersaturation drug concentrations
and limit crystallization of the dissolved drug over extended times.
We prepared poly(N-isopropylacrylamide)-based
excipients of varying molar mass and with various end group identities,
and examined their ability to improve the aqueous solubility of the
Biopharmaceutical Class System Class II drug, phenytoin. Solid dispersions
of these excipients and phenytoin were prepared at 10 wt % drug loading.
Performance depended largely on the tendency of the polymer excipient
to form micellar aggregates in aqueous buffer. We present several
systems that achieved significant improvement of phenytoin solubility,
with no indication of drug crystallization over 6 h. This is among
the highest enhancement factors seen for phenytoin to date, and the
success of these systems is ascribed to the added stability of these
“self-micellizing” solid dispersions.
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