Enavogliflozin Form E Crystallization for Stability and Low Hygroscopicity
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Solution Overview
Problem
Existing crystalline forms of enavogliflozin lack thermodynamic stability and exhibit high hygroscopicity, affecting their suitability for long-term storage and pharmaceutical stability, as well as the speed of drug action.
Innovation Solution
A novel crystalline form of enavogliflozin (form E) with a distinct X-ray diffraction pattern and endothermic peaks, prepared by adding water, heating, and drying, which enhances thermodynamic stability and reduces hygroscopicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If existing crystalline forms of enavogliflozin are used, then the manufacturing process can be implemented, but the crystalline forms lack thermodynamic stability and exhibit high hygroscopicity
Solution Approach 1:
The patent applies parameter changes by discovering and utilizing a specific polymorphic form (Form E) of enavogliflozin with distinct crystal lattice parameters and molecular packing arrangements. This polymorphic transformation changes the physical parameters of the compound, resulting in superior thermodynamic stability and reduced hygroscopicity compared to other crystalline forms
Solution Approach 2:
The invention utilizes phase transition principles by converting enavogliflozin from less stable crystalline phases to the thermodynamically stable Form E through controlled crystallization processes. The patent describes specific crystallization conditions that induce the phase transition to the desired polymorphic form with improved properties
2Speed
If existing crystalline forms are used, then drug production can proceed, but the speed of drug action is reduced
Solution Approach 1:
The patent changes the crystalline parameters by selecting Form E with specific X-ray diffraction patterns and molecular arrangements that optimize both dissolution kinetics and stability. The unique crystal packing in Form E facilitates faster dissolution while maintaining thermodynamic stability
3Manufacturing precision
If recrystallization processes are optimized for existing forms, then purity can be improved, but process speed and productivity are affected
Solution Approach 1:
The patent utilizes phase transition during crystallization to achieve both high purity and efficient processing. The transformation to Form E during controlled crystallization provides spontaneous purification while maintaining fast crystallization kinetics, thereby achieving both high purity and productivity
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 novel crystalline form E exhibits superior stability and reduced hygroscopicity, ensuring excellent long-term storage and faster drug action with a 1.25 times quicker onset compared to conventional forms.
Implementation Method 1
adding water, heating, and drying
Implementation Method 2
adding water, heating, and drying
Implementation Method 3
Powder X-ray diffraction (PXRD) analysis, the novel crystalline form has a crystal structure different from the conventional four types
Implementation Method 4
X-ray powder diffraction (PXRD) analysis, the novel crystalline form has a crystal structure different from the conventional four types
Implementation Method 5
endothermic peaks
Implementation Method 6
endothermic peaks
Data Source
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AI summary
The present invention relates to a novel crystalline form of enavogliflozin, and a preparation method therefor. The novel crystalline form of enavogliflozin, according to the present invention, has thermodynamic stability and a hygroscopic property that are superior to those of a conventionally reported crystalline form of enavogliflozin, and thus has excellent long-term storage and pharmaceutical stability. In addition, the time to reach Cmax is shorter than that of the conventionally reported crystalline form of enavogliflozin such that drug effects can be rapidly exhibited, and thus the present invention can be effectively used.