Apixaban Polymer Microspheres for Stable High-Load Encapsulation

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Solution Overview

Problem

Existing methods fail to effectively encapsulate Apixaban in biocompatible polymer microspheres due to low solubility and high crystallization tendencies, leading to low bioavailability and gastrointestinal bleeding risks with oral administration.

Innovation Solution

A method involving the addition of fatty acids or triglycerides to a dispersed phase containing Apixaban and biocompatible polymers like PLGA, PLA, and PCL, using a microfluidic process to stabilize high drug content encapsulation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If Apixaban is orally administered, then it can be conveniently taken, but bioavailability is low due to low water solubility

Engineering Contradiction:
Improveconvenience of administrationVSAvoidbioavailability
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent segments the drug delivery system by encapsulating Apixaban within biocompatible polymer microspheres, separating the drug from direct contact with gastrointestinal fluids that limit its solubility. This microencapsulation approach allows the drug to be delivered in a controlled manner while improving bioavailability through alternative administration routes.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces biocompatible polymers as intermediary materials that solubilize and protect Apixaban during delivery. These polymers act as mediators between the poorly water-soluble drug and the biological system, enabling enhanced absorption and reduced gastrointestinal irritation.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Ease of operation

If Apixaban is orally administered, then it can be taken easily, but gastrointestinal bleeding occurs due to local anticoagulant effects and corrosive actions

Engineering Contradiction:
Improveease of oral administrationVSAvoidgastrointestinal bleeding
Core Design Contradiction:
Ease of operationVSObject-affected harmful factors

Solution Approach 1:

The patent extracts Apixaban from direct contact with the gastrointestinal tract by encapsulating it within polymer microspheres. This removal of the drug from the harsh gastrointestinal environment eliminates local corrosive actions and non-coagulation-related biological actions that cause gastrointestinal bleeding, while still allowing systemic anticoagulant effects to occur.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent employs biocompatible polymers that are designed to degrade completely after delivering the drug. These temporary carriers provide protection during transit and administration, then naturally decompose in the body, eliminating long-term harmful effects while maintaining ease of administration.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Ease of manufacture

If conventional microsphere preparation methods are used, then the process is simple, but Apixaban crystallizes and cannot be stably encapsulated in high content

Engineering Contradiction:
Improvesimplicity of preparation methodVSAvoidencapsulation stability and drug content
Core Design Contradiction:
Ease of manufactureVSManufacturing precision

Solution Approach 1:

The patent optimizes critical parameters including polymer selection (PLGA, PLA, or PCL with specific molecular weights), solvent systems (dichloromethane, chloroform, or ethyl acetate), and processing conditions (emulsion formation, solvent evaporation temperature and time) to prevent Apixaban crystallization while maintaining high encapsulation efficiency and stability.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses composite material systems combining Apixaban with biocompatible polymers in specific ratios, creating a synergistic formulation where the polymer matrix prevents drug crystallization while enabling stable encapsulation. The composite approach integrates multiple functional components to achieve both manufacturability and product quality.

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

Stable encapsulation of high Apixaban content in microspheres for sustained release, enabling intramuscular or subcutaneous administration, improving bioavailability and reducing gastrointestinal bleeding risks.

Implementation Method 1

preparing microspheres using a microfluidic method, wherein the biocompatible polymer is any one or more selected from the group consisting of polylactic-co-glycolic acid (PLGA), polylactic acid (PLA), and polycaprolactone (PCL)

Methodology Applied
Scientific EffectEmulsion: Emulsion

Implementation Method 2

The known preparation methods for microspheres include i) a solvent evaporation method

Methodology Applied
Scientific EffectEvaporation: Evaporation

Data Source

PatentEP3946272B1Method for preparing biocompatible polymer-based apixaban-loaded microspheres
Publication Date: 2026.01.21 HLB PHARM CO LTD
  • EP3946272B1 patent drawingFigure 1~3
  • EP3946272B1 patent drawingFigure 4~5
  • EP3946272B1 patent drawingFigure 6~7

AI summary

The present invention relates to a method for preparing biocompatible polymer-based Apixaban-loaded microspheres. More specifically, the present invention relates to a method for preparing biocompatible polymer-based Apixaban-loaded microspheres, comprising: i) adding a fatty acid or triglyceride to a dispersed phase; and ii) preparing microspheres using a microfluidic method. The method for preparing biocompatible polymer-based Apixaban-loaded microspheres of the present invention can be effectively used in the preparation of microspheres in which Apixaban is stably encapsulated in high contents.