Emraclidine Crystal Forms for Humidity and Mechanical Stability

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Solution Overview

Problem

Existing Emraclidine (CVL-231) formulations face issues with varying physicochemical properties, including stability, hygroscopicity, and mechanical stability, which affect drug quality and production processes.

Innovation Solution

Development of distinct crystal forms (CSI, CSII, CSIII, CSIV, and CSV) of Emraclidine, characterized by specific X-ray diffraction patterns, prepared through solvation and stirring methods, exhibiting improved physicochemical and mechanical stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If different crystal forms of Emraclidine are used, then physicochemical properties (stability, solubility, hygroscopicity) vary, but this leads to inconsistent drug quality and affects clinical efficacy

Engineering Contradiction:
Improvephysicochemical stabilityVSAvoiddrug quality consistency
Core Design Contradiction:
Stability of the object's compositionVSReliability

Solution Approach 1:

The patent applies parameter changes by systematically varying crystallization conditions (solvent type, temperature, pH, concentration) to obtain different crystal forms with optimized physicochemical properties. Each crystal form (I-V) represents a specific set of parameters that delivers consistent stability, solubility, and hygroscopicity characteristics, thereby ensuring reliable drug quality across different batches and storage conditions.

Inventive Principle:
Principle #35Parameter changes

2Ease of manufacture

If existing Emraclidine formulations are used, then production can proceed, but varying hygroscopicity and mechanical stability affect manufacturing processes and production costs

Engineering Contradiction:
Improvemanufacturing processabilityVSAvoidproduction efficiency
Core Design Contradiction:
Ease of manufactureVSProductivity

Solution Approach 1:

The patent applies local quality by optimizing specific properties of the crystal forms for different manufacturing requirements. For example, certain crystal forms are designed with enhanced mechanical stability for tableting processes, while others exhibit controlled hygroscopicity for improved flow properties during formulation. This targeted optimization of local properties enhances overall manufacturability and production efficiency.

Inventive Principle:
Principle #3Local quality

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 crystal forms demonstrate enhanced stability under high humidity and mechanical stress, reducing the risk of transformation and maintaining purity during storage and processing, thus ensuring consistent drug quality and lowering production costs.

Implementation Method 1

an X-ray powder diffraction pattern of the crystal form CSI comprises a characteristic peak at a diffraction angle 2θ value of 1, or 2, or 3 of 11.9°±0.2°, 5.9°±0.2°, and 9.5°±0.2° using Cu-Kα radiation

Methodology Applied
Scientific EffectX-ray diffraction: X-Ray

Implementation Method 2

dissolving Emraclidine in a ketone solvent to obtain the crystal form CSI via volatilization

Methodology Applied
Scientific EffectSolvation: Solvation

Implementation Method 3

dissolving Emraclidine in a ketone solvent to obtain the crystal form CSI via volatilization

Methodology Applied
Scientific EffectEvaporation: Evaporation

Data Source

PatentEP4592288A1Crystal form of emraclidine, preparation method therefor, and use thereof
Publication Date: 2025.07.30 CEREVEL THERAPEUTICS LLC
  • EP4592288A1 patent drawingFigure 1~3
  • EP4592288A1 patent drawingFigure 4~5
  • EP4592288A1 patent drawingFigure 6~7

AI summary

The present invention relates to a crystal form of Emraclidine (hereinafter referred to as "compound I"), a preparation method therefor, a pharmaceutical composition containing the crystal form, and use of the crystal form in the preparation of an M4 receptor modulator medicament and a medicament for treating schizophrenia.