Abstract
Background: The solubilization of poorly water-soluble drugs remains challenging. The purpose of this study was to design a liquid formulation that can improve the solubility of poorly water-soluble and weakly acidic ST-246, an anti-smallpox drug.
Methods: Soluble ternary cyclodextrin complexations (t-CDs) containing ST-246, 2-hydroxypropyl-β- cyclodextrin (HP-β-CD) and meglumine (MEG) were prepared and optimized. The optimized t-CDs were further characterized using a scanning electron microscope (SEM), Powder X-ray Diffractometry (PXRD), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR) and Nuclear Magnetic Resonance Spectroscopy (NMR).
Results: The solubility of ST-246 improved dramatically from 3 µg/ml (in water, 37°C) to 50 mg/ml in the optimized t-CDs (ST-246/MEG/HP-β-CD, 1:2:6 weight ratio). The results suggested that the drug was associated with MEG through hydrogen bonds and then included into the hydrophobic cavity of HP-β-CD, which might be a major factor for solubility improvement. To determine the exact inclusion mechanism, a Phase Soluble Study (PSS) was also conducted, and it indicated that a 1:1 soluble complex was formed between ST-246 and HP-β-CD and that the action mechanism of MEG was complicated and relied on more than pH modulation.
Conclusion: Generally, the optimized ternary cyclodextrin complexation might be a potential formulation strategy for enhancing the solubility and bioavailability of poorly water-soluble ST-246.
Keywords: Poorly water-soluble drug, solubilization, inclusion complex, 2-hydroxypropyl-β-cyclodextrin, meglumine, scanning electron microscope (SEM).
Current Drug Delivery
Title:Formulation and Characterization of a Ternary Inclusion Complex Containing Hydroxypropyl-β-cyclodextrin and Meglumine for Solubility Enhancement of Poorly Water-Soluble ST-246, an Anti-Smallpox Drug
Volume: 14 Issue: 8
Author(s): Xiaoxi Li, Meiyan Yang, Yueqing Li, Wei Gong, Yuli Wang, Li Shan, Shuai Shao, Chunsheng Gao*Wu zhong*
Affiliation:
- State key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850,China
- State key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850,China
Keywords: Poorly water-soluble drug, solubilization, inclusion complex, 2-hydroxypropyl-β-cyclodextrin, meglumine, scanning electron microscope (SEM).
Abstract: Background: The solubilization of poorly water-soluble drugs remains challenging. The purpose of this study was to design a liquid formulation that can improve the solubility of poorly water-soluble and weakly acidic ST-246, an anti-smallpox drug.
Methods: Soluble ternary cyclodextrin complexations (t-CDs) containing ST-246, 2-hydroxypropyl-β- cyclodextrin (HP-β-CD) and meglumine (MEG) were prepared and optimized. The optimized t-CDs were further characterized using a scanning electron microscope (SEM), Powder X-ray Diffractometry (PXRD), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR) and Nuclear Magnetic Resonance Spectroscopy (NMR).
Results: The solubility of ST-246 improved dramatically from 3 µg/ml (in water, 37°C) to 50 mg/ml in the optimized t-CDs (ST-246/MEG/HP-β-CD, 1:2:6 weight ratio). The results suggested that the drug was associated with MEG through hydrogen bonds and then included into the hydrophobic cavity of HP-β-CD, which might be a major factor for solubility improvement. To determine the exact inclusion mechanism, a Phase Soluble Study (PSS) was also conducted, and it indicated that a 1:1 soluble complex was formed between ST-246 and HP-β-CD and that the action mechanism of MEG was complicated and relied on more than pH modulation.
Conclusion: Generally, the optimized ternary cyclodextrin complexation might be a potential formulation strategy for enhancing the solubility and bioavailability of poorly water-soluble ST-246.
Export Options
About this article
Cite this article as:
Li Xiaoxi, Yang Meiyan, Li Yueqing, Gong Wei, Wang Yuli, Shan Li, Shao Shuai, Gao Chunsheng*, zhong Wu*, Formulation and Characterization of a Ternary Inclusion Complex Containing Hydroxypropyl-β-cyclodextrin and Meglumine for Solubility Enhancement of Poorly Water-Soluble ST-246, an Anti-Smallpox Drug, Current Drug Delivery 2017; 14 (8) . https://dx.doi.org/10.2174/1567201813666161003151225
DOI https://dx.doi.org/10.2174/1567201813666161003151225 |
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
-
The Gut Mucosa as a Site for Induction of Regulatory T-Cells
Current Pharmaceutical Design Structure Function Analysis of West Nile Virus RNA Dependent RNA Polymerase: Molecular Model and Implications for Drug Design
Medicinal Chemistry Suicide Gene Therapy Against Malignant Gliomas by the Local Delivery of Genetically Engineered Umbilical Cord Mesenchymal Stem Cells as Cellular Vehicles
Current Gene Therapy Applied Proteomics in Companion Animal Medicine
Current Proteomics Neuroprotective Properties of Peroxisome Proliferator-Activated Receptor Alpha (PPARα) and its Lipid Ligands
Current Medicinal Chemistry Brain Endothelial Cell-Cell Junctions: How to “Open” the Blood Brain Barrier
Current Neuropharmacology Epigenetic Drugs for Multiple Sclerosis
Current Neuropharmacology Biosafety of Gene Therapy Vectors Derived From Herpes Simplex Virus Type 1
Current Gene Therapy Altering the Tropism of Lentiviral Vectors through Pseudotyping
Current Gene Therapy Tau in Alzheimer's Disease: Mechanisms and Therapeutic Strategies
Current Alzheimer Research The Beneficial Role of Vitamin D in Human Immunodeficiency Virus Infection
Current HIV Research HIV Vaccines: A Global Perspective
Current Molecular Medicine Angiotensin-Converting Enzyme 2 Roles in the Pathogenesis of COVID-19
Current Hypertension Reviews Role of Ischemic Blood-Brain Barrier on Amyloid Plaques Development in Alzheimers Disease Brain
Current Neurovascular Research Himalayan Plant Species as Pesticidal Agents
Mini-Reviews in Organic Chemistry Improving Safety of Gene Therapy
Current Drug Safety Use of Intravenous Immunoglobulin in the Treatment of Immune-Mediated Demyelinating Diseases of the Nervous System
Current Pharmaceutical Design Withdrawn: Effects of Tofacitinib on Tfr/Tfh Balance and Expression of CXCL13 and TGF-β1 in Experimental Autoimmune Encephalomyelitis Rats
CNS & Neurological Disorders - Drug Targets The Effects of Psychopharmacologic and Therapeutic Approaches on Neuro-imaging in Obsessive-compulsive Disorder
Current Neuropharmacology Human Parvovirus B19: An Infectious Agent with the Potential to Induce and Trigger Rheumatic Disease
Current Rheumatology Reviews