Buffered Apixaban Suspension Without Surfactants for Stable Oral Delivery
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Solution Overview
Problem
Existing pharmaceutical formulations of apixaban, such as liquid preparations and injectable solutions, often require emulsifiers and surfactants to maintain stability and solubility, which can lead to unwanted phase changes and impurity formation, making them unsuitable for stable oral delivery.
Innovation Solution
A buffered aqueous suspension of micronized apixaban is developed with a pH range of 1.5 to 6.5, containing no emulsifier or surfactant, using a composition of 0.08-0.20 w/v% apixaban, at least 70 w/w% water, and additional components like buffering agents, thickening agents, and preservatives to maintain form stability and improve dissolution profiles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If apixaban is formulated as a solid dose form (tablets, capsules), then manufacturing and storage are easier, but dissolution and absorption are impaired
Solution Approach 1:
The patent changes the physical state parameter of apixaban from solid to liquid suspension form, enabling both ease of manufacture and improved dissolution/absorption properties simultaneously
Solution Approach 2:
The patent uses a suspending agent as an intermediary substance that maintains apixaban in a stable suspended state, allowing the drug to retain both manufacturability and enhanced dissolution characteristics
2Productivity
If apixaban is administered as a liquid suspension, then dissolution and absorption are improved, but manufacturing complexity and storage stability become more difficult
Solution Approach 1:
The patent optimizes the concentration parameter of apixaban in the suspension (0.1-10 mg/mL) to achieve a balance between improved dissolution and manageable manufacturing complexity
Solution Approach 2:
The patent introduces a suspending agent as an intermediary that simplifies the formulation process and ensures storage stability, thereby reducing manufacturing complexity while maintaining the liquid suspension format
3Productivity
If apixaban is administered as a liquid suspension, then dissolution and absorption are improved, but storage stability and shelf life become more difficult
Solution Approach 1:
The patent uses a suspending agent as an intermediary substance that prevents aggregation and maintains uniform distribution of apixaban particles throughout the suspension, thereby ensuring storage stability and extended shelf life
Solution Approach 2:
The patent optimizes the particle size parameter of apixaban (0.1-10 μm) and concentration (0.1-10 mg/mL) to achieve a stable suspension that maintains its properties over time while preserving dissolution benefits
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The suspension maintains the crystalline form of apixaban without significant conversion, ensuring stability and low impurity formation, suitable for oral administration with improved dissolution and taste, enhancing patient compliance.
Implementation Method 1
a) providing a liquid suspension formulation of apixaban with a suspending agent that maintains the apixaban in a stable suspended state
Data Source
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AI summary
The invention describes a buffered oral aqueous apixaban suspension comprising 0.08 – 0.20 w/v% micronized apixaban having a pH of 1.5 – 6.5 and a method for the preparation thereof