Yonkenafil Hydrochloride A-Type Polymorph Crystallization
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Solution Overview
Problem
The variability in crystalline forms of pharmaceutical compounds like yonkenafil hydrochloride affects stability and clinical efficacy, making it crucial to identify and maintain a consistent stable form for reliable dosing and safety.
Innovation Solution
A stable A-type polymorphic form of yonkenafil hydrochloride is developed, characterized by specific X-ray powder diffraction and differential scanning calorimetry patterns, and produced through methods involving suspension in organic solvents, slow cooling, and drying, ensuring consistent physical and chemical stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If the crystalline form of yonkenafil hydrochloride is not controlled, then the compound can be prepared, but the stability and clinical efficacy vary between batches
Solution Approach 1:
The patent applies parameter changes by controlling crystallization conditions including solvent type (ethyl acetate, ethanol, isopropanol, or water), temperature range (0-25°C), and pH value (4.0-6.0) to obtain consistent A-type polymorphic form with superior stability and efficacy
Solution Approach 2:
The patent utilizes phase transitions during crystallization to convert yonkenafil hydrochloride into the stable A-type polymorphic form through controlled cooling and solvent evaporation, ensuring consistent crystalline structure across batches
2Adaptability or versatility
If multiple crystalline forms are possible, then the compound has polymorphic flexibility, but the dosage and efficacy cannot be compared between batches
Solution Approach 1:
The patent establishes specific parameter ranges (solvent: water content 0-50%, temperature: 0-25°C, pH: 4.0-6.0) that consistently produce the A-type polymorphic form, enabling accurate dosage comparison while maintaining polymorphic flexibility through controlled variation
3Adaptability or versatility
If the crystalline form converts with environmental changes, then the compound adapts to conditions, but the clinical efficacy and safety are compromised
Solution Approach 1:
The patent stabilizes the A-type polymorphic form against environmental-induced phase transitions by optimizing crystallization parameters and selecting appropriate solvents, preventing conversion to unstable forms while maintaining controlled adaptability
Solution Approach 2:
The patent creates a stable chemical environment during crystallization by controlling pH (4.0-6.0) and selecting chemically inert solvents, protecting the A-type polymorphic form from environmental changes that could compromise efficacy and safety
4Reliability
If a stable polymorphic form is developed, then the clinical effectiveness is ensured, but the preparation process requires precise control
Solution Approach 1:
The patent defines specific parameter ranges (solvent type, temperature 0-25°C, pH 4.0-6.0, crystallization time) that balance the need for precise control with clinical effectiveness, making the preparation process both reliable and controllable
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 A-type polymorphic form of yonkenafil hydrochloride exhibits excellent stability and ease of industrial production, ensuring consistent clinical effectiveness and safety, and is suitable for various pharmaceutical formulations including oral and parenteral administration.
Implementation Method 1
The X-ray powder diffraction pattern of the polymorphic substance comprises diffraction peaks at more than three 2θ values selected from 8.4°±0.2°, 11.3°±0.2°, 13.9°±0.2°, 14.2°±0.2°, 14.7°±0.2°, 16.8°±0.2°, 17.1°±0.2°, 19.7°±0.2°, 21.0°±0.2°, 21.7°±0.2°, 22.4°±0.2°, 23.3°±0.2°, 23.8°±0.2°, 26.8°±0.2°, 27.5°±0.2° and 28.0°±0.2°
Implementation Method 2
suspending yonkenafil hydrochloride in an organic solvent/water solution, heating to dissolve the yonkenafil hydrochloride, slowly cooling and crystallizing
Implementation Method 3
heating to dissolve the yonkenafil hydrochloride, slowly cooling and crystallizing
Implementation Method 4
characterized by specific X-ray powder diffraction and differential scanning calorimetry patterns
Data Source
Figure 1~2
Figure 3
AI summary
The present application discloses an A-type polymorphic substance of yonkenafil hydrochloride and a preparation method, a composition and use thereof. The powder diffraction pattern of the A-type polymorphic substance of yonkenafil hydrochloride comprises diffraction peaks at three or more 2θ values selected from: 8.4 ± 0.2°, 11.3 ± 0.2°, 13.9 ± 0.2°, 14.2 ± 0.2°, 14.7 ± 0.2°, 16.8 ± 0.2°, 17.1 ± 0.2°, 19.7 ± 0.2°, 21.0 ± 0.2°, 21.7 ± 0.2°, 22.4 ± 0.2°, 23.3 ± 0.2°, 23.8 ± 0.2°, 26.8 ± 0.2°, 27.5 ± 0.2°, 28.0 ± 0.2°.