Preferential Formulation of Second Generation Antipsychotic Asenapine as Inclusion Complex with Sulphobutylether-ßCD (Captisol): In vitro and In vivo Evaluation.

ABSTRACT

BACKGROUND: Asenapine is an anti-psychotic agent approved by the US-FDA for treatment of acute schizophrenia and manic or bipolar I disorder in adults. It is poorly absorbed when administered orally, hence exhibits poor oral bioavailability, which limits its use in clinical practice. OBJECTIVE: Enhancement in solubility of asenapine through complexation with three different cyclodextrins, viz. ßCD, HPßCD and sulphobutylether-ßCD (Captisol®) was attempted and compared due to its poor bioavailability. METHOD: Kneading method was used for preparation of inclusion complexes which were characterized by FTIR, DSC, and XRD methods. Extent of binding and stability of the 11 inclusion complexes were evaluated by molecular modelling and phase solubility studies. Pharmacokinetic studies were also carried out of these inclusion complexes. RESULTS: Captisol® complex was the most stable amongst all complexes showing 4.9 times solubility enhancement of asenapine and 96% drug release at the end of 60 min, whereas asenapine maleate (uncomplexed drug) was released completely at the end of 120min. The Cmax and AUC values of Captisol® asenapine complex (AS-Captisol complex) were 2.8 and 2.3 times higher than the uncomplexed drug. CONCLUSION: This study thus demonstrated that Captisol® inclusion complex is an effective strategy for solubility and bioavailability enhancement of asenapine.