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

[ Vol. 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   Pages 520 - 531 ( 12 )

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.

Keywords:

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

Affiliation:

Sinhgad College of Pharmacy, Off Sinhgad Road, 44/1, Vadgaon, Pune 411041, Sinhgad College of Pharmacy, Off Sinhgad Road, 44/1, Vadgaon, Pune 411041, North Eastern University, Boston, Interdisciplinary Science & Technology Research Academy (ISTRA), Azam Campus, University of Pune, Pune, Sinhgad College of Pharmacy, Off Sinhgad Road, 44/1, Vadgaon, Pune 411041, Interdisciplinary Science & Technology Research Academy (ISTRA), Azam Campus, University of Pune, Pune, Molecular Simulations Group, Department of Pharmaceutical Chemistry, Bombay College of Pharmacy, Kalina, Santacruz [E], Mumbai, 400 098, Molecular Simulations Group, Department of Pharmaceutical Chemistry, Bombay College of Pharmacy, Kalina, Santacruz [E], Mumbai, 400 098, Interdisciplinary Science & Technology Research Academy (ISTRA), Azam Campus, University of Pune, Pune

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