Axitinib Molecular Assembly for Stable, Soluble Solid Form

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Solution Overview

Problem

Existing axitinib polymorphs face issues with thermodynamic instability, photochemical instability, and poor processing properties, leading to challenges in preparation and stability.

Innovation Solution

A molecular association of axitinib is physically bonded, exhibiting X-ray diffraction peaks at specific angles, a single endothermic temperature in DSC, and a defined particle size and shape, enhancing solubility and stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional axitinib polymorphs (Form IV, XXV, or XLI) are used, then thermodynamic stability or photostability is improved, but preparation time and processing complexity remain excessive

Engineering Contradiction:

ImprovestabilityVSAvoidpreparation time

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The invention changes the molecular state parameter from individual polymorph crystals to molecular associates (aggregates of multiple molecules), creating a new physical form that simultaneously achieves rapid preparation and excellent stability. This parameter change in molecular organization resolves the contradiction between preparation speed and stability.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If conventional axitinib polymorphs are used, then stability is improved, but solubility remains insufficient

Engineering Contradiction:

ImprovestabilityVSAvoidsolubility

Core Design Contradiction:

ReliabilityVSQuantity of substance

Solution Approach 1:

The invention creates a composite molecular structure where multiple axitinib molecules associate together to form molecular associates. This composite approach combines the stability of crystalline structures with enhanced solubility properties, resolving the contradiction between stability and solubility.

Inventive Principle:

Principle #40Composite materials

3Shape

If Form IV is prepared using n-heptane, then crystalline structure is achieved, but flash point and toxicity problems occur

Engineering Contradiction:

Improvecrystal formVSAvoidtoxicity

Core Design Contradiction:

ShapeVSObject-affected harmful factors

Solution Approach 1:

The invention adopts ethanol as a replacement for n-heptane in the preparation process. Ethanol has higher flash point and lower toxicity, making it a safer solvent that eliminates the harmful effects associated with conventional preparation methods while still enabling successful molecular associate formation.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

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 novel molecular association of axitinib demonstrates superior solubility and stability, facilitating easy preparation and improved bioavailability.

Implementation Method 1

the X-ray powder diffraction spectrum of the molecular association has X-ray diffraction peaks at diffraction angles 2θ of 24.99°±0.1° and 26.32°±0.1°

Methodology Applied

Scientific EffectX-ray diffraction: X-Ray

Implementation Method 2

the molecular association of the present invention may have a differential scanning calorimetry (DSC) profile characterized by a glass transition at a single endothermic temperature of 220.4±2.0 °C

Methodology Applied

Scientific EffectDifferential scanning calorimetry: Calorimetry

Data Source

PatentEP4656185A1Novel molecular assembly of axitinib

Publication Date: 2025.12.03 SCAI THERAPEUTICS CO LTD

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AI summary

The present invention relates to a molecular association, which is a novel axitinib polymorph in which axitinib is physically bonded.