چکیده (انگلیسی):

The objective of the study was to produce rapidly dissolving
formulations of the poorly water-soluble drug repaglinide
using an innovative new technology, ultra-rapid freezing
(URF), and to investigate the influence of excipient type
on repaglinide stability. Repaglinide compositions containing
different types and levels of excipients and different drug
potencies (50%-86%) were produced by the URF technology.
Repaglinide/excipient solutions were frozen on a cryogenic
substrate, collected, and lyophilized to form a dry
powder. Surfactants, including sodium dodecyl sulfate, and
alkalizing agents such as diethanolamine (DEA) and tromethamine
(TRIS) were incorporated into the compositions.
Forced degradation of repaglinide was conducted under
stressed conditions (eg, elevated temperature, exposure to
peroxide) to determine the stability of the drug in such
environments. The solubility of repaglinide increased as a
function of increasing pH; therefore, incorporation of an
alkalizing agent into the URF formulations increased the
drug’s solubility. Drug instability resulted when the drug
was exposed to pH values above 9.0. URF formulations
containing alkalizing agents showed no degradation or spontaneous
recrystallization in the formulation, indicating
that increased stability was afforded by processing. URF
processing created nanostructured drug/excipient particles
with higher dissolution rates than were achieved for unprocessed
drug. Alkalizing agents such as TRIS and DEA,
present at levels of 25% to 33% wt/wt in the formulations,
did not cause degradation of the drug when processed using
URF. URF processing, therefore, yielded fast-dissolving formulations
that were physically and chemically stable, resistant
to alkali degradation or spontaneous recrystallization
in the formulation.