Evenamide Hydrochloride Crystal Forms for Stable Drug Formulation

Solution Overview

Problem

There is a need for stable, non-hygroscopic, and highly soluble crystalline forms of evenamide hydrochloride salts suitable for pharmaceutical formulations, as well as intermediates for their preparation, which have not been previously disclosed.

Innovation Solution

The development of crystalline forms of evenamide hydrochloride salts, specifically forms I and II, characterized by X-ray powder diffraction, differential scanning calorimetry, and thermogravimetric analysis, along with a process for their preparation using solvents like acetone and hydrochloric acid, ensuring stability and solubility.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If crystalline forms of evenamide hydrochloride are developed, then stability and solubility are improved, but manufacturing complexity increases

Engineering Contradiction:

ImprovestabilityVSAvoidmanufacturing complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies parameter changes by controlling crystallization conditions including temperature ranges (0-50°C), solvent selection (acetone, ethanol, isopropanol, n-butanol), pH values (2-4), and evaporation rates to obtain specific crystalline forms of evenamide hydrochloride with enhanced stability and solubility characteristics

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent utilizes phase transitions through controlled crystallization processes where evenamide hydrochloride transitions from dissolved state to crystalline solid form, and through polymorphic transitions between different crystalline forms (Form I, Form II, Form III) to achieve desired stability and solubility properties

Inventive Principle:

Principle #36Phase transitions

2Quantity of substance

If crystalline forms of evenamide hydrochloride are developed, then solubility is improved, but manufacturing complexity increases

Engineering Contradiction:

ImprovesolubilityVSAvoidmanufacturing complexity

Core Design Contradiction:

Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent applies parameter changes by controlling crystallization conditions including temperature ranges (0-50°C), solvent selection (acetone, ethanol, isopropanol, n-butanol), pH values (2-4), and evaporation rates to obtain specific crystalline forms of evenamide hydrochloride with enhanced stability and solubility characteristics

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses solvents as intermediary substances (acetone, ethanol, isopropanol, n-butanol) to mediate the crystallization process, enabling control over crystal formation and achieving enhanced solubility through selective solvent-crystal interactions

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If crystalline forms of evenamide hydrochloride are developed, then pharmaceutical formulation effectiveness is improved, but process complexity increases

Engineering Contradiction:

Improvepharmaceutical formulation effectivenessVSAvoidprocess complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies parameter changes by controlling crystallization conditions including temperature ranges (0-50°C), solvent selection (acetone, ethanol, isopropanol, n-butanol), pH values (2-4), and evaporation rates to obtain specific crystalline forms of evenamide hydrochloride with enhanced stability and solubility characteristics

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent utilizes phase transitions through controlled crystallization processes where evenamide hydrochloride transitions from dissolved state to crystalline solid form, and through polymorphic transitions between different crystalline forms (Form I, Form II, Form III) to achieve desired stability and solubility properties

Inventive Principle:

Principle #36Phase transitions

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 crystalline forms of evenamide hydrochloride exhibit enhanced stability and solubility, enabling effective pharmaceutical formulations and prolonged storage, with a chemical purity of at least 98% and crystallinity above 90%, suitable for treating neurological and psychiatric disorders such as schizophrenia.

Implementation Method 1

The crystalline forms of evenamide hydrochloride were characterized by X-ray powder diffraction (XRPD)

Methodology Applied

Scientific EffectX-ray powder diffraction: X-Ray

Implementation Method 2

The crystalline forms of evenamide hydrochloride were characterized by differential scanning calorimetry (DSC)

Methodology Applied

Scientific EffectDifferential scanning calorimetry: Calorimetry

Implementation Method 3

The crystalline forms of evenamide hydrochloride were characterized by hot stage microscopy (HSM)

Methodology Applied

Scientific EffectHot stage microscopy:

Data Source

PatentEP4615820B1Crystalline forms of evenamide

Publication Date: 2026.02.04 NEWRON PHARMACEUTICALS SPA

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AI summary

The present invention relates to novel crystalline forms of evenamide salts, in particular forms I and II, their use a process for their preparation, and a pharmaceutical composition containing said novel crystalline forms.