Formulation and evaluation of mouth dissolving film of clozapine

Objective: The aim of the present study was to develop the mouth dissolving film of Clozapine to treat the symptoms of schizophrenia. Solubility of drug was enhanced by cyclodextrin inclusion complexes, β-CD and HP β-CD, from which HP β-CD shows high solubility.Clozapine is a tricyclic dibenzodiazepine, classified as an atypical antipsychotic agent. Schizophrenia is a mental disorder characterized by a breakdown of thought processes and by a deficit of typical emotional responses. Schizophrenia is a challenging disorder that makes it difficult to distinguish between what is real and unreal, think clearly, manages emotions, and functions normally. So, dosage form which gives quick onset of action is needed. MDF was suitable dosage form. The objective was to formulate MDF having least disintegration time with a better mechanical strength which ultimately gives faster onset of action. Experimental work: The films were formulated by various film forming polymers (PVA, HPMC E15, PVP K30, Guar Gum and Xanthan Gum), Plasticizers (PEG 400, PG, and Glycerin), saliva stimulating agent (citric acid), sweetening agent (mannitol) and surfactant (tween 80), solubility enhancer (Hydroxyl propyl β- cyclodextrine). MDF were prepared by solvent casting technique. Trial batches were formulated to optimize plasticizer, polymer and polymer combination. The optimized plasticizer and polymer combination was selected, 32 factorial designs was applied and from factorial batches the batch with least DT and good mechanical properties was optimized and kept for stability study for 1 month.
Result: Trail batches, PG was optimized as plasticizer. While single polymer was not able to produce the film with desired quality, polymer combination was used. The polymer combination of HPMC E15 and PVA was optimized. Solubility of clozapine has been enhanced by Hydroxyl propyl β-cyclodextrin inclusion complex. Further factorial design was applied, the batch with 1000mg of HPMC E15 and 200mg of PVA was optimized and found stable after 1 month.The optimized batch of clozapine film having desired DT and mechanical propertiesthat is potentially usefulfor the treatment of depression were fast onset of action is required.