Crystalline 3-phenyl-4-propyl-pyrazol-5-ol Hydrochloride Stability
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Solution Overview
Problem
Existing non-crystalline forms of 3-phenyl-4-propyl-1-(pyridin-2-yl)-1H-pyrazol-5-ol hydrochloride lack stability and thermodynamic stability, leading to potential polymorphic transitions and decomposition under storage conditions, which affects their pharmaceutical applications.
Innovation Solution
A method to produce a crystalline form of the hydrochloride compound with specific X-ray diffraction angles and a maximum endothermic temperature of 134.25 ± 3°C, involving steps such as reacting 2-propyl-3-oxo-3-phenylpropionic acid ethyl ester with 2-hydrazinopyridine, cooling, filtering, and reacting with hydrochloric acid-isopropyl ether solution to stabilize the compound.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Use of energy by moving object
If non-crystalline form is used, then kinetic solubility is improved, but stability deteriorates
Solution Approach 1:
The patent transforms the compound from non-crystalline to crystalline form, changing its physical state parameters. This crystallization process modifies the molecular arrangement and lattice structure, thereby altering solubility characteristics while significantly improving storage stability and preventing polymorphic transitions.
Solution Approach 2:
The invention utilizes phase transition from amorphous/non-crystalline state to crystalline state. This phase change establishes a stable lattice structure with defined melting point (134.25 ± 3°C) and characteristic X-ray diffraction patterns, providing thermodynamic stability while maintaining pharmaceutical efficacy.
2Reliability
If crystalline form is used, then stability is improved, but solubility deteriorates
Solution Approach 1:
The patent optimizes crystalline form parameters including crystal habit, lattice energy, and surface area characteristics. By controlling crystallization conditions and selecting appropriate solvents, the invention achieves a balance where the crystalline structure provides stability while maintaining adequate solubility for pharmaceutical application.
3Shape
If polymorphic form changes occur, then physical properties are improved in some aspects, but decomposition and loss of pharmacological activity occur
Solution Approach 1:
The patent takes preliminary action to prevent polymorphic transitions by establishing a stable crystalline form with defined characteristics before pharmaceutical formulation. The crystalline structure with specific X-ray diffraction angles and melting point serves as a preventive measure against unwanted polymorphic changes that could lead to decomposition or loss of activity.
Solution Approach 2:
The invention employs characterization techniques including X-ray powder diffraction and differential scanning calorimetry to monitor and verify the crystalline form. This feedback mechanism ensures that the compound maintains its intended polymorphic form throughout storage and processing, preventing transitions to less stable forms.
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 form exhibits enhanced heat and moisture stability, preventing decomposition and polymorphic transitions, making it suitable for long-term storage and use in pharmaceutical formulations for treating diseases mediated by reactive oxygen species.
Implementation Method 1
having X-ray diffraction angles (2θ ± 0.2°) having a relative intensity of 15% or more, obtained through X-ray powder diffraction analysis, of 7.15, 10.72, 13.36, 15.99, 16.39, 16.71, 17.14, 19.61, 21.50, 21.82, 23.46, 24.08, 25.91 and 27.36
Implementation Method 2
having a maximum endothermic temperature, measured with a differential scanning calorimeter (DSC), of 134.25 ± 3°C
Data Source
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AI summary
The present invention relates to a novel crystalline 3-phenyl-4-propyl-1-(pyridin-2-yl)-1H-pyrazol-5-ol hydrochloride, a method for preparing the compound, and a pharmaceutical composition containing the compound as an active ingredient.