Formulation Development and Optimization of Asenapine Maleate Sunlingual Film Using QbD Approach

Abstract

Asenapine is an atypical anti psychotic approved for the treatment of schizophrenia and bipolar disorder. Due to hepatic first-pass it has very little oral bio availability, but comparatively good sublingual bio availability. A sublingual dosage form has been selected hence. It has also been time and again observed that film is more acceptable than tablet for systemic administration via oral cavity. A sublingual film of polyethylene oxide and hypromellose was thus developed. Polyethylene oxide was used for its self-plasticizing property and hypromellose was added to counter the tackiness of polyethylene oxide. Maltitol was added as a humectant to retain moisture. Design of experiment was used as a tool to optimize the proportion of the filmforming polymers in order to ensure the film having most desirable quality attributes. Over the years many methods have been developed for manufacturing films but the solvent casting remains the simplest and most economical. The process was studied in detail by assessing risk of each process step and studying the parameters and material attributes to reduce the risk to a minimum. A control strategy was defined to ensure manufacture of films according to the target product profile by evaluation of intermediate quality attributes at the end of each process step. The final formulation was found to have a performance similar to the marketed sublingual tablet in vitro and good sublingual bio availability in in vivo animal studies..