FORMULATION DEVELOPMENT, OPTIMIZATION, EVALUATION AND IN-VIVO ASSESSMENT STUDY OF OLANZAPINE INCLUSION COMPLEXES WITH BETA�CYCLODEXTRIN AND HYDROXYPROPYL BETA�CYCLODEXTRIN ORAL DISSOLVING FILMS

Olanzapine in its conventional dosage form is limited by poor aqueous solubility
and low bioavailability, leading to delayed therapeutic onset in Schizophrenia
treatment. To overcome these limitations and enhance patient compliance, the
present study focuses on developing an Oral Dissolving Film (ODF) of Olanzapine
cyclodextrin inclusion complex, employing β - cyclodextrin and hydroxypropyl β -
cyclodextrin for solubility enhancement by solvent evaporation method. Tamarind
Seed Polysaccharide (TSP) and HPMC E15 were explored individually and in blend
to assess their effect on film performance. Optimization of the Olanzapine –
cyclodextrin complexes was carried out using Design Expert software (Version 13).
Complexation interaction was confirmed by molecular docking studies using PyRX
(Version 1.2), Autodock Vina software. Olanzapine – Beta cyclodextrin and
Olanzapine – hydroxypropyl beta cyclodextrin complex were optimized using Box
– Behnken design, focusing on molar ratio and solvent composition. The ODF was
optimized and developed using 32 factorial design to study polymer grade and
concentration effects. Olanzapine showed stable docking with both β -
cyclodextrin and hydroxypropyl β -cyclodextrin. Optimized films showed rapid
disintegration (18 -20 sec), > 90% drug release. TSP and HPMC E15 blend yielded
superior tensile strength and flexibility. In vivo efficacy of the Optimized
Olanzapine – hydroxypropyl beta cyclodextrin complex loaded ODF was assessed
using the apomorphine induced climbing test in Swiss albino mice and the ANOVA
results showed significant p – value (<0.05). This study highlights the potential of
a natural polymer - based ODF system to improve the solubility, bioavailability
and therapeutic performance of Olanzapine in Schizophrenia treatment.
Keywords: Cyclodextrin complexation, Tamarind seed polysaccharide, Molecular
docking, Host-guest interaction, Natural polymer