Apixaban Controlled Release Osmotic System

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

There is a need for safe and effective methods to deliver Factor Xa inhibitors, such as apixaban, which are used to treat thromboembolic disorders, with improved solubility and controlled release profiles to enhance therapeutic efficacy and reduce side effects.

Innovation Solution

A solubility-improved form of apixaban is developed in a controlled release dosage form that provides sustained release characteristics, including osmotic and matrix controlled release systems, to maintain plasma concentrations of apixaban at therapeutic levels for extended periods, reducing peak concentrations and minimizing side effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Speed

If immediate release formulation is used, then rapid onset of action is achieved, but peak plasma concentrations cause increased side effects

Engineering Contradiction:
Improveonset of actionVSAvoidside effects from peak concentrations
Core Design Contradiction:
SpeedVSObject-generated harmful factors

Solution Approach 1:

The patent applies dynamic release control by using osmotic pressure-driven mechanisms that adjust drug release rates based on physiological conditions. The osmotic pump system dynamically regulates apixaban release to maintain therapeutic levels while avoiding excessive peaks, resolving the contradiction between rapid onset and side effect reduction.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent changes the release rate parameter over time through controlled osmotic mechanisms. By modifying the release kinetics from immediate to sustained, the system achieves therapeutic effect while controlling peak concentrations, thereby reducing side effects associated with high peak levels.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If twice-daily dosing is used, then therapeutic efficacy is maintained, but patient compliance and convenience are reduced

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoiddosing frequency
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent implements continuous drug delivery through osmotic controlled-release technology, maintaining steady plasma concentrations of apixaban over extended periods. This continuous action allows substitution of twice-daily dosing with once-daily dosing while preserving therapeutic efficacy, thereby improving patient compliance.

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

The patent uses extended-release mechanisms that provide drug delivery beyond the immediate therapeutic window, sustaining effective concentrations for 24 hours or more. This partial extension of release duration enables less frequent dosing while maintaining reliable therapeutic effect.

Inventive Principle:
Principle #16Partial or excessive action

3Quantity of substance

If solubility-enhancing formulations are used, then bioavailability is improved, but formulation complexity increases

Engineering Contradiction:
ImprovebioavailabilityVSAvoidformulation complexity
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent introduces osmotic agents and hydrophilic polymers as intermediary substances that enhance apixaban solubility and release. These mediators facilitate drug dissolution and controlled delivery without requiring complex formulation systems, improving bioavailability while managing formulation complexity.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 solubility-improved, controlled release form of apixaban achieves prolonged plasma concentrations, decreases peak drug levels, and allows for once-daily dosing, improving bioavailability and reducing side effects while maintaining effective Factor Xa inhibition for thromboembolic disorders like venous thromboembolism and acute coronary syndrome.

Implementation Method 1

Another preferred aspect of the B dosage form, designated the C dosage form, is an osmotic controlled release dosage form.

Methodology Applied
Scientific EffectOsmotic pressure: Osmotic Pressure

Data Source

PatentEP2442791B1Dosage forms of apixaban
Publication Date: 2019.11.27 PFIZER INC
  • EP2442791B1 patent drawingFigure 1
  • EP2442791B1 patent drawingFigure 2~3
  • EP2442791B1 patent drawingFigure 4

AI summary

The present invention relates to a Factor Xa inhibitor dosage form comprising apixaban in a solubility-improved form wherein the dosage form provides controlled release of apixaban and methods for preventing or treating venous thromboembolisms, deep vein thrombosis and acute coronary syndrome with said dosage form.