Background: Ezetimibe is a cholesterol-lowering agent with an oral bioavailability of
50% by virtue of its poor solubility and extensive hepatic and intestinal metabolism.
Objective: The study aimed to overcome low bioavailability issues of ezetimibe by formulating an
oral disintegrating film.
Methods: The low solubility of ezetimibe was undertaken, preparing solid dispersions using mannitol,
β-cyclodextrin, and urea. The mannitol solid dispersion assimilated oral disintegrating film was
prepared and optimized using 23 factorial design, where the concentration of film formers hydroxypropyl
methylcellulose (K5& K15) (X1and X2) and super disintegrant, sodium starch glycolate
(X3) was used as factors on the response disintegration time (Y). The films were evaluated for
physical properties, time of disintegration, and drug release profiles.
Results: Mannitol solid dispersion (1:2 ratio) based on the superior drug content, solubility and in
vitro release profile was preferred in film formation. The low crystalline nature of the solid dispersion
was very evident by the absence of prominent peaks in the X-Ray diffraction pattern and the
reduced peak intensity of melting endotherms. The correlation coefficient (R2) and statistical parameter
analysis of variance specify the implication of linear factors on responses, which is apparent
from confidence intervals (P-values) less than 0.05. The in vitro release profile of all the eight formulations
(F1-F8) in a phosphate buffer solution of pH 6.8 revealed a significant increment in comparison
Conclusion: The study revealed that the formulation approach could overcome the biopharmaceutical
challenge of solubility as well as low bioavailability issues of ezetimibe.