Acetylcholinesterase Inhibitor Crystal Forms With Low Hygroscopicity
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Solution Overview
Problem
Different crystalline forms of acetylcholinesterase inhibitors can affect the in vivo dissolution and absorption of drugs, impacting their clinical efficacy and safety, particularly for insoluble oral solid or semi-solid preparations, necessitating the development of a stable and low-hygroscopic form for improved processing and therapeutic efficacy.
Innovation Solution
The development of crystalline forms A, B, and C of the compound 2-((1-(2-fluorobenzyl)-4-fluoropiperidin-4-yl)methylene)-5,6-dimethoxy-2,3-dihydro-1-indanone, characterized by specific X-ray powder diffraction patterns, thermal stability, and low moisture absorption, facilitating easy processing and pharmaceutical applications.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If different crystalline forms of acetylcholinesterase inhibitor are used, then the drug can be provided with specific physical properties, but the in vivo dissolution and absorption are affected, impacting clinical efficacy and safety
Solution Approach 1:
The patent identifies and characterizes multiple crystalline forms (Form A, Form B, Form C) of the acetylcholinesterase inhibitor by changing physical parameters such as melting point, solubility, and X-ray diffraction patterns. Each form exhibits different dissolution and absorption characteristics in vivo, allowing optimization of clinical efficacy and safety through selection of appropriate crystalline forms.
2Ease of manufacture
If crystalline forms with high stability are developed, then processing becomes easier, but hygroscopicity may increase affecting drug stability
Solution Approach 1:
The patent systematically evaluates different crystalline forms by changing physical and chemical parameters to achieve optimal balance between processing ease and hygroscopicity. Form A, for example, exhibits high stability and ease of processing while maintaining low hygroscopicity, whereas other forms may sacrifice one property for the other.
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 exhibit high stability, low hygroscopicity, and ease of processing, enhancing the clinical efficacy and safety of acetylcholinesterase inhibitor drugs, particularly for treating neurological diseases like Alzheimer's disease.
Implementation Method 1
the X-ray powder diffraction pattern of Form A has characteristic peaks at three or more 2θ values selected from the group consisting of 14.914±0.2°, 15.593±0.2°, 17.617±0.2°, 18.022±0.2°, 19.525±0.2°, 20.806±0.2°
Implementation Method 2
the DSC pattern of the Form A has a characteristic absorption peak at a peak of 123±5° C. (or ±3° C., or 1° C.)
Implementation Method 3
the Form A has a moisture-absorption weight gain of ≤1%, preferably 0.6％±0.2％, under a relative humidity of 0-95%
Data Source
AI summary
The present invention provides a crystalline form of an acetylcholinesterase inhibitor, a preparation method therefor and application thereof. Specifically, the crystalline form is crystalline form A, crystalline form B and crystalline form C of 2-((1-(2-fluorobenzyl)-4-fluoropiperidin-4-yl) methylene)-5, 6-dimethoxy-2, 3-dihydro-1-indanone. The crystalline form of the present invention does not contain water and solvent, has high stability and low hygroscopicity, is easy to process, and is very suitable for preparing drugs for preventing and/or treating neurodegenerative diseases.