Apixaban Liquid Formulation Solubility via Composite Solubilizers

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

The low aqueous solubility of apixaban poses a challenge in developing a liquid formulation, as it limits the concentration and volume of the drug that can be effectively administered, particularly in pediatric and adult populations who cannot swallow solid dosage forms.

Innovation Solution

A liquid formulation of apixaban is developed using a vehicle comprising water and at least two solubilizers such as non-ionic surfactants, ionic surfactants, hydrophilic polymers, ethanol, polyhydric alcohols, polyethylene glycol, and carbohydrates, achieving a solubility of at least 0.50 mg/mL, which supports a therapeutically effective concentration range and is suitable for oral and nasogastric administration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If a liquid formulation of apixaban is developed, then it enables administration to pediatric and adult populations who cannot swallow solid dosage forms, but the low aqueous solubility of apixaban limits the concentration and volume of the drug that can be effectively administered

Engineering Contradiction:

Improveadminist ration convenienceVSAvoiddrug concentration

Core Design Contradiction:

Ease of operationVSQuantity of substance

Solution Approach 1:

The patent changes the physical-chemical parameters of the formulation system by introducing multiple solubilizers (surfactants, co-solvents, and hydrophilic polymers) to alter the solubility characteristics of apixaban in aqueous medium. This enables achieving a solubility of at least 0.50 mg/mL, which provides sufficient drug concentration for effective dosing while maintaining liquid formulation advantages for patient populations who cannot swallow tablets.

Inventive Principle:

Principle #35Parameter changes

2Quantity of substance

If multiple solubilizers are used to increase apixaban solubility, then the solubility reaches at least 0.50 mg/mL, but the formulation complexity increases

Engineering Contradiction:

ImprovesolubilityVSAvoidformulation complexity

Core Design Contradiction:

Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent employs a composite solubilizer system comprising multiple components with different mechanisms of action: ionic and non-ionic surfactants, co-solvents (alcohols, polyethylene glycol), and hydrophilic polymers. This composite approach synergistically enhances apixaban solubility beyond what any single solubilizer could achieve, reaching at least 0.50 mg/mL while maintaining formulation stability and compatibility for clinical use.

Inventive Principle:

Principle #40Composite materials

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 provides robust solubility and bioavailability comparable to apixaban tablets, allowing for accurate and convenient administration in various patient populations, including those requiring antithrombotic treatment for thromboembolic disorders.

Implementation Method 1

The vehicle can comprise water and at least two solubilizers selected from the group consisting of a non-ionic surfactant, an ionic surfactant, a hydrophilic polymer, ethanol, a polyhydric alcohol, a polyethylene glycol, and a carbohydrate

Methodology Applied

Scientific EffectSolvation: Solvation