Apixaban Liquid Formulation Using Propylene Glycol for Small Dose Volume
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Solution Overview
Problem
Current apixaban formulations in liquid form have high dose volumes, causing discomfort to patients, especially geriatric and bedridden individuals, and lack stability and low tendency for degradation, necessitating a small dose volume and stable oral formulation.
Innovation Solution
A pharmaceutical liquid formulation of apixaban with concentrations between 0.25 mg/mL to 10 mg/mL, containing more than 35% propylene glycol, which is stable and can be administered in volumes of 10 mL or less, optionally with antioxidants, co-solvents, sweetening agents, and flavoring agents, and can be prepared by mixing apixaban with pharmaceutically acceptable excipients in propylene glycol and co-solvents, applying heat to ensure solubilization, and packaging in suitable containers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If liquid formulation with water vehicle is used, then apixaban can be administered orally, but dose volume becomes too large (25 mL) causing patient discomfort
Solution Approach 1:
The patent changes the vehicle composition from water-based to propylene glycol-based formulation. This parameter change in the solvent system dramatically increases apixaban solubility, enabling concentration of 5-10 mg/mL compared to water-based formulations. Consequently, the dose volume is reduced from 25 mL to 2.5-5 mL while maintaining the same apixaban dose, thereby improving patient compliance without compromising administration feasibility
Solution Approach 2:
The patent employs a composite vehicle system comprising propylene glycol as the primary solvent combined with co-solvents (such as ethanol, polyethylene glycol, or glycerol) and surfactants. This composite material approach creates a synergistic formulation that maximizes apixaban solubility and stability, enabling high-concentration liquid formulation that achieves small dose volume while maintaining appropriate rheological properties for oral administration
2Volume of stationary object
If high concentration of apixaban is achieved in small volume, then dose volume is reduced, but formulation stability and degradation tendency increase
Solution Approach 1:
The patent introduces propylene glycol as an intermediary solvent that mediates between apixaban and the aqueous environment. Propylene glycol acts as a co-solvent that enhances apixaban solubility through hydrogen bonding and dipole-dipole interactions, stabilizing the drug molecule in high concentration without promoting degradation. This intermediary substance enables the formulation to maintain stability while achieving the desired small dose volume
Solution Approach 2:
The patent incorporates antioxidants (such as ascorbic acid, tocopherol, or sodium metabisulfite) as stabilizing agents that sacrificially protect apixaban from oxidation. These antioxidants act as short-living protective components that preferentially react with oxidizing agents, thereby preserving apixaban stability in the high-concentration propylene glycol formulation throughout its shelf life
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 formulation allows for comfortable and flexible administration of apixaban in small volumes, maintaining stability and facilitating patient compliance, with the ability to adjust dosing and administer through feeding tubes, ensuring effective treatment of blood clots and systemic embolism.
Implementation Method 1
A pharmaceutical liquid formulation for oral delivery of apixaban comprising apixaban at concentrations within the range of 0.25 mg/mL to 10 mg/mL and more than 35% (w/v) propylene glycol based on the total formulation
Implementation Method 2
applying heat to ensure solubilization
Data Source
AI summary
A pharmaceutical liquid formulation for oral delivery of apixaban comprising i) apixaban in high concentrations, ii) more than 35% (w/v) propylene glycol based on the total formulation and ii) optionally other pharmaceutical acceptable excipients, wherein the formulation is suitable for small dose volume administration. The invention relates to a liquid formulation, which can be useful as pharmaceutical formulations, for oral delivery of apixaban with a small dose volume.