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.
Current Drug Delivery
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.
Export Options
About this article
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
DOI https://dx.doi.org/10.2174/1567201814666171120121217 |
Print ISSN 1567-2018 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5704 |
Call for Papers in Thematic Issues
Advances of natural products, bio-actives and novel drug delivery system against emerging viral infections
Due to the increasing prevalence of viral infections and the ability of these human pathogens to develop resistance to current treatment strategies, there is a great need to find and develop new compounds to combat them. These molecules must have low toxicity, specific activity and high bioavailability. The most suitable ...read more
Electrospun Fibers as Drug Delivery Systems
In recent years, electrospun fibers have attracted considerable attention as potential platforms for drug delivery due to their distinctive properties and adaptability. These fibers feature a notable surface area-to-volume ratio and can be intentionally designed with high porosity, facilitating an increased capacity for drug loading and rendering them suitable for ...read more
Emerging Nanotherapeutics for Mitigation of Neurodegenerative Disorders
Conditions affecting the central nervous system (CNS) present a significant hurdle due to limited access of both treatments and diagnostic tools for the brain. The blood-brain barrier (BBB) acts as a barrier, restricting the passage of molecules from the bloodstream into the brain. The most formidable challenge facing scientists is ...read more
Nanotechnology Based Chemotherapy for the treatment of Head & Neck Cancer
The escalating recurrence rates observed in Head and Neck cancer, particularly within the chemo-therapeutically treated cohort (50-60%), can be attributed to the non-selective nature of current anticancer drug delivery modalities. In this context, nanotechnology-based drug delivery systems emerge as a promising avenue for achieving precise localization of therapeutic agents to ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Differential Effects of the Interaction Between the Education and APOE ε4 Allele on Amyloid-beta Retention and Memory Performances in Cognitively Normal Older Adults and Alzheimer's Disease Patients
Current Alzheimer Research Common and Distinct Interactions of Chemical Inhibitors with Cytochrome P450 CYP1A2, CYP2A6 and CYP2B6 Enzymes
Drug Metabolism Letters Inhibitors of Glutamine Synthetase and their Potential Application in Medicine
Mini-Reviews in Medicinal Chemistry The Effects of Herbal Medicines on Women Sexual Dysfunction: A Systematic Review
Current Drug Discovery Technologies Target-directed Discovery and Bioprocess Engineering of New Enzymes for Environmentally Benign Production of High-Value Chiral Chemicals
Current Organic Chemistry Therapeutic Potential of <i>Citrus sinensis</i> Peels Against Rotenone Induced Parkinsonism in Rats
Current Bioactive Compounds Pre-Clinical Evidence that Corticotropin-Releasing Factor (CRF) Receptor Antagonists are Promising Targets for Pharmacological Treatment of Alcoholism
CNS & Neurological Disorders - Drug Targets Apoptosis: A Potential Therapeutic Target for Retinal Degenerations
Current Neurovascular Research Lab-on-Chip for Pharmacogenomics: An Embedded System Organization
Micro and Nanosystems Amine Oxidase Inhibitors and Development of Neuroprotective Drugs
Current Neuropharmacology Biomarker Validation of a New Case Definition of Menstrual Cycle-Associated Syndrome (MCAS) Opinion Paper
CNS & Neurological Disorders - Drug Targets Conformational Changes and Aggregation of Expanded Polyglutamine Proteins as Therapeutic Targets of the Polyglutamine Diseases: Exposed β-Sheet Hypothesis
Current Pharmaceutical Design Neuroprotective Gene Therapy for Parkinson’s Disease
Current Gene Therapy Clopidogrel, Aspirin and Proton Pump Inhibition after Percutaneous Valve Implants: An Update
Current Pharmaceutical Design The Relationship between Social Cognition and Executive Functions in Alzheimer’s Disease: A Systematic Review
Current Alzheimer Research Neural Stem Cell Niches in Health and Diseases
Current Pharmaceutical Design Meet Our Editorial Board Member
Current Alzheimer Research Low-Dose Methotrexate (LD-MTX) in Rheumatology Practice - A Most Widely Misunderstood Drug
Current Rheumatology Reviews The Start of a New Era for Stroke Treatment: Mechanical Thrombectomy Devices
Current Neurovascular Research Effectiveness of Psychoeducational Interventions for Improving Symptoms, Health-Related Quality of Life, and Psychological well Being in Patients with Stable Angina
Current Cardiology Reviews