Crystal Form I of Hex-4-Inoic Acid Derivative for Stable Tablet Processing
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing crystal forms of 3-(4-(benzyloxy)phenyl)hex-4-inoic acid derivatives exhibit varying physicochemical properties, affecting their suitability for pharmaceutical applications, particularly in terms of dissolution rate, bioavailability, and stability, necessitating the development of a form with improved properties.
Innovation Solution
The development of a novel crystal form I of 3-(4-(benzyloxy)phenyl)hex-4-inoic acid derivative, characterized by specific X-ray diffraction patterns, which is prepared by dissolving the compound in methanol and adding isopropyl acetate, offering enhanced thermal stability, compressibility, and reduced static electricity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If amorphous form or crystal form II is used, then dissolution rate may be faster, but thermal stability and storage stability deteriorate
Solution Approach 1:
The patent applies parameter changes by modifying the crystalline structure parameters of the compound. Crystal form I has a specific crystal structure with defined unit cell parameters (a=14.25±0.05Å, b=17.80±0.05Å, c=21.35±0.05Å, α=90°, β=90°, γ=90°) that differs from crystal form II and amorphous forms. This structural parameter change results in superior thermal stability while maintaining adequate dissolution properties, resolving the contradiction between dissolution rate and thermal stability.
Solution Approach 2:
The patent utilizes phase transitions by establishing a specific crystalline phase (Crystal form I) with distinct X-ray diffraction patterns showing peaks at characteristic 2θ values (4.61±0.2°, 5.49±0.2°, 6.84±0.2°, etc.). This phase transition from amorphous or less stable crystal forms to the well-defined Crystal form I provides enhanced thermal stability and storage stability while maintaining pharmaceutical utility.
2Ease of manufacture
If crystal form II is used, then manufacturing may be simpler, but flowability and compressibility worsen
Solution Approach 1:
The patent applies parameter changes by optimizing the crystal structure parameters of Crystal form I, which exhibits superior flowability and compressibility characteristics compared to Crystal form II. The specific unit cell parameters and molecular packing arrangement in Crystal form I result in improved powder flow properties and tablet compression characteristics, resolving the contradiction between ease of manufacture and ease of operation.
3Speed
If amorphous form is used, then dissolution rate may be improved, but stability during storage deteriorates
Solution Approach 1:
The patent utilizes phase transitions by transforming the compound from an amorphous phase to a well-defined crystalline phase (Crystal form I). The crystalline structure provides a stable, ordered arrangement of molecules that resists degradation during storage, while the specific crystal lattice parameters and surface area characteristics maintain adequate dissolution rates. This phase transition resolves the contradiction between dissolution rate and storage stability.
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
Crystal form I demonstrates superior thermal stability, compressibility, and reduced static electricity, facilitating better formulation and long-term storage compared to amorphous and crystal form II, making it suitable for pharmaceutical compositions.
Implementation Method 1
dissolving the compound in methanol
Implementation Method 2
adding isopropyl acetate, and obtaining a crystal form I of a compound of Chemical Formula 1 from the reaction product
Data Source
Figure 1
Figure 2
Figure 3
AI summary
The present invention relates to a novel crystal form of a 3-(4-(benzyloxy)phenyl)hex-4-inoic acid derivative, a production method therefore and a pharmaceutical composition comprising same. A crystal form I of a compound of chemical formula 1, according to the present invention, exhibits more excellent physicochemical properties such as thermal stability, static electricity-inducing capability, compressibility, etc. compared to an amorphous form or a crystal form II, and thus is especially useful for preparation and long-term storage.