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

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

Volume: 15 Issue: 4

Author(s): Juilee A. Kulkarni, Amelia M. Avachat*, Charul M. Avachat, Rohan Pradhan, Tushar S. Suryawanshi, Ejazuddin M. Khan, Elvis A. F. Martis, Evans C. Coutinho and Subhash Padhye

Affiliation:

• Sinhgad College of Pharmacy, Off Sinhgad Road, 44/1, Vadgaon, Pune 411041,India

Keywords: Asenapine maleate, bioavailability, Captisol®, cyclodextrin, MM-PBSA, molecular dynamics, solubility enhancement.

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. βCD, HPβCD and sulphobutylether-βCD (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 1:1 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.

Cite this article as:

Kulkarni A. Juilee , Avachat M. Amelia *, Avachat M. Charul , Pradhan Rohan , Suryawanshi S. Tushar , Khan M. Ejazuddin, Martis A. F. Elvis , Coutinho C. Evans and Padhye Subhash , Preferential Formulation of Second Generation Antipsychotic Asenapine as Inclusion Complex with Sulphobutylether-βCD (Captisol): In vitro and In vivo Evaluation, Current Drug Delivery 2018; 15 (4) . https://dx.doi.org/10.2174/1567201814666171120121217