Amorphous Solid Dispersion Based Oral Disintegrating Film of Ezetimibe: Development and Evaluation

Abstract

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 to ezetimibe.

Conclusion: The study revealed that the formulation approach could overcome the biopharmaceutical challenge of solubility as well as low bioavailability issues of ezetimibe.

Keywords: BCS; Ezetimibe; HPMC; ODF; factors.; in vitro release; mannitol; solid dispersion.