HS378 Crystal Forms for Impurity Removal and Uniform Particle Size
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Solution Overview
Problem
Existing methods for preparing crystal forms of HS378 fail to effectively remove impurities, leading to cumbersome processes and uneven particle sizes, which complicates industrial production and affects the purity and stability of the final product.
Innovation Solution
Development of new crystal forms A and B of HS378, characterized by specific X-ray diffraction patterns and preparation methods using isobutyl acetate and isopropanol solvents, which facilitate impurity removal and result in uniform, stable, and easily processable crystals.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If existing crystal forms (1, 2, 4, 5) are prepared using crystal form 2 as substrate, then the preparation process can be established, but two impurities with relative retention times of 0.96 and 1.04 cannot be effectively removed
Solution Approach 1:
The patent changes the crystallization parameters by using different solvents (isobutyl acetate for crystal form A, isopropanol for crystal form B) and different cooling rates to achieve effective separation of impurities with relative retention times of 0.96 and 1.04. This parameter optimization enables impurity removal while maintaining process feasibility.
Solution Approach 2:
The patent introduces specific solvent systems (isobutyl acetate/methanol mixture for crystal form A, isopropanol for crystal form B) as intermediaries that facilitate the separation and removal of impurities during crystallization. These solvents act as mediators between the crude material and the final pure crystal product.
2Manufacturing precision
If conventional crystallization methods are used, then crystal forms can be obtained, but the processes become cumbersome and particle sizes become uneven
Solution Approach 1:
The patent optimizes crystallization parameters including solvent selection (isobutyl acetate or isopropanol), cooling rates, and saturation concentrations to produce uniform particle sizes. These parameter changes simplify the manufacturing process while achieving consistent particle morphology and size distribution.
Solution Approach 2:
The patent applies local quality control by optimizing specific local conditions during crystallization (such as local cooling rates, local solvent concentration gradients) to ensure uniform particle formation throughout the batch process, resulting in consistent particle size and morphology.
3Stability of the object's composition
If existing crystal forms are used, then preparation methods are established, but the final product has poor stability and handling properties
Solution Approach 1:
The patent changes the crystallization parameters by selecting specific solvents (isobutyl acetate, isopropanol) and controlling cooling rates to produce crystal forms with improved stability and handling properties. The resulting crystals exhibit better flow characteristics and storage stability.
Solution Approach 2:
The patent creates composite crystal structures through the formation of solvate crystals (crystal form A with isobutyl acetate, crystal form B with isopropanol), where the solvent molecules are incorporated into the crystal lattice. This composite structure enhances both stability and handling properties of the final product.
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 new crystal forms exhibit good physical and chemical stability, regular crystal habits, and excellent fluidity, enabling simpler and more efficient industrial production with high purity and improved handling properties.
Implementation Method 1
a method for preparing the crystal forms, and medical uses thereof... the crystallization process of crystal forms 1, 2, 4, and 5... the preparation methods of the new crystal forms can effectively remove impurities
Implementation Method 2
crystal form A... is an isobutyl acetate solvate... crystal form B... is an isopropanol solvate... mixing a crude product of compound of formula (I) with a mixed solvent of alcohol and isobutyl acetate
Data Source
AI summary
The present invention relates to crystal forms A and B of a compound (HS378) of formula (I) and a preparation method therefor. The crystal forms A and B have a good physiochemical stability, a regular crystal habit, a good particle size uniformity, and a good fluidity; the preparation method for the crystal forms A and B is simple; moreover, a good impurity removal effect, easiness in filtration and a high yield are achieved, and samples with few impurities and a high purity can be obtained; and the purification problem of difficulties during impurity removal can be fully solved.