Hydroxytyrosol Nicotinamide Co-Crystal Stability

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Solution Overview

Problem

Hydroxytyrosol, a polyphenolic compound with strong antioxidant properties, is unstable, easily oxidized, and has a low melting point, making it unsuitable for direct use in capsules or tablets, and its embedding powders suffer from increased hygroscopicity and instability due to starch-based materials.

Innovation Solution

Formation of a co-crystal with nicotinamide through non-covalent molecular interactions, increasing the melting point and stability of hydroxytyrosol, and reducing hygroscopicity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If hydroxytyrosol is used directly in capsules or tablets, then the antioxidant capacity is available, but the low melting point and high hygroscopicity make it unsuitable for solid formulations

Engineering Contradiction:
Improvestability of hydroxytyrosolVSAvoidsuitability for solid formulations
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent changes the physical and chemical parameters of hydroxytyrosol by forming a co-crystal with nicotinamide. This co-crystal formation increases the melting point from 52°C to above 100°C and reduces hygroscopicity, transforming the material properties to enable solid formulation while maintaining stability.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite material system by forming a co-crystal between hydroxytyrosol and nicotinamide. This composite structure combines the antioxidant properties of hydroxytyrosol with the stabilizing properties of nicotinamide, resulting in a material that is both stable and suitable for solid formulations.

Inventive Principle:
Principle #40Composite materials

2Reliability

If embedding powder with starch-based auxiliary materials is used to protect hydroxytyrosol, then the powder properties are improved, but the hygroscopicity is further increased

Engineering Contradiction:
Improvestability of hydroxytyrosolVSAvoidhygroscopicity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses nicotinamide as an intermediary substance to form a co-crystal with hydroxytyrosol. This intermediary structure protects hydroxytyrosol from direct interaction with moisture while avoiding the hygroscopic properties of starch-based materials, thereby reducing overall hygroscopicity.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If embedding powder is used to protect hydroxytyrosol, then the powder properties are improved, but the embedding efficiency is not high due to amphiphilic nature

Engineering Contradiction:
Improvestability of hydroxytyrosolVSAvoidembedding efficiency
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The patent changes the molecular-level parameters by forming a co-crystal structure where hydroxytyrosol and nicotinamide are integrated at the molecular level. This co-crystal formation achieves complete incorporation of hydroxytyrosol (100% embedding efficiency) unlike conventional embedding methods that only achieve 20-30% efficiency.

Inventive Principle:
Principle #35Parameter changes

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 hydroxytyrosol-nicotinamide co-crystal exhibits a significantly higher melting point, improved chemical stability, and reduced hygroscopicity, enabling its use in solid formulations like capsules or tablets.

Implementation Method 1

adding an auxiliary compound which has non-covalent bond interaction with hydroxytyrosol at the molecular level

Methodology Applied
Scientific EffectNon-covalent bond interaction: Van der Waals Force

Implementation Method 2

the melting point of hydroxytyrosol is capable of being increased at molecular level

Methodology Applied
Scientific EffectMelting point elevation: Melting

Data Source

PatentEP4303212B1Hydroxytyrosol nicotinamide eutectic crystal, and preparation method therefor and composition thereof
Publication Date: 2025.10.01 COCRYSTAL TECHNOLOGY (JIAXING) CO LTD
  • EP4303212B1 patent drawingFigure 1~2
  • EP4303212B1 patent drawingFigure 3~4
  • EP4303212B1 patent drawingFigure 5~6

AI summary

The present invention relates to the technical field of medicines, and in particular to a hydroxytyrosol nicotinamide eutectic crystal, a preparation method therefor and a composition thereof. In the hydroxytyrosol nicotinamide eutectic crystal of the present invention, a molar ratio of hydroxytyrosol to nicotinamide is 1: 1, and cell parameters are as follows: a=9.4999, b=11.8285, c=11.4439, α=90°, β=96.628°, and δ=90°. The hydroxytyrosol nicotinamide eutectic crystal of the present invention is high in melting point, does not absorb moisture and is good in stability, and the application convenience of the hydroxytyrosol is greatly improved. The composition directly prepared by means of a grinding method has the advantages of high yield and low cost, and is suitable for large-scale application.