Olanzapine orodispersible films: a feasibility study

Olanzapine (OLZ) is an effective atypical antipsychotic drug with an acceptable safety profile widely used in the treatment of psychiatric disorders. The administration as orodispersible tablets meets the patients’ preferences improving the medication adherence [1]. However, this drug presents some formulative issues due to the conversion into different polymorphic and pseudopolymorphic forms as a function of the preparation process and in presence of water [2]. This feature is particularly relevant in the design OLZ loaded orodispersible films (ODF) which represent a valuable alternative to orodispersible tables [3]. ODF are generally manufactured by hot-melt extrusion or solvent-casting. In this preliminary study, the feasibility to prepare OLZ loaded ODF by a water-based process was investigated. In particular, ODF were obtained by laminating and casting an aqueous dispersion of OLZ and maltodextrins (MDX) plasticized with glycerol and dried by a solvent casting technique in order to obtain the theorical drug content of 10 mg per 6 cm2 ODF. ODF were characterized in terms of disintegration time and dissolution profile in deionized water and phosphate buffer pH 6. The solid-state of OLZ loaded ODF was studied using X-ray diffraction (XRP) and ATR-FTIR spectroscopy. ODF visually appeared homogeneous with smooth surface and yellow colored due to the presence of olanzapine. They were easy-to-handle and easy-to-cut into desired dimensions without cracks. The film thickness was about 140±4.5 μm. The disintegration time was about 40 s, complying the requirements of Ph. Eur. monograph. An erratic drug release pattern was observed during the in vitro dissolution of ODF with a concomitant formation of a yellow precipitate after 3 min. XRD patterns of OLZ loaded into ODF evidenced the phase conversion from anhydrous form into dihydrate one. This feature was in line with a variation in ATR-FTIR spectra since a shift in the stretching bands of CN group of OLZ loaded in films was evident with respect the pure drug. Overall data suggested that OLZ undergoes to phase transition after solvent casting compromising the biopharmaceutical performances due to its variation in solubility. Hence, a solvent-free preparation process or different excipients must be evaluated to avoid the variation in OLZ solid-state.