Pridopidine Hydrochloride Form II Crystallization
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current development of Pridopidine for Huntington's disease is limited by the availability of only one crystalline form, Form I, which restricts optimization of pharmaceutical properties such as solubility, stability, and manufacturing characteristics, as no new polymorphic forms were discovered during initial synthesis and screening processes.
Innovation Solution
Identification and characterization of a new crystalline form, Form II of Pridopidine hydrochloride, along with a process for its preparation, which involves heating Form I to 203°C for re-crystallization, and the use of seed crystals to stabilize and produce Form II, resulting in distinct X-ray diffraction patterns, thermal profiles, and solubility characteristics.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Device complexity
If only Form I is available for development, then the development process is simpler with fewer forms to screen, but the optimization of pharmaceutical properties such as solubility, stability, and manufacturing characteristics is restricted
Solution Approach 1:
The patent applies parameter changes by modifying crystallization conditions including solvent selection (ethanol, isopropanol, acetone, toluene, dichloromethane), temperature variations (room temperature, 0°C, 40°C), and saturation levels to discover and characterize Form II, which exhibits different pharmaceutical properties such as improved bulk density (0.382 g/ml vs 0.212 g/ml) and particle shape (less needle-shaped) compared to Form I
2Ease of manufacture
If Form II is used for pharmaceutical processing, then bulk density and particle shape are improved for enhanced processing, but the form transforms rapidly to Form I at ambient conditions
Solution Approach 1:
The patent applies preliminary action by preparing Form II immediately before use through controlled crystallization from hot saturated solutions, filtering while hot, and using the form directly for pharmaceutical processing without prolonged storage at ambient conditions, thereby utilizing its superior bulk density and particle shape properties before transformation to Form I occurs
Solution Approach 2:
The patent utilizes phase transitions by controlling the crystallization process through temperature changes (heating to dissolve, cooling to crystallize), and by applying seeding techniques where small amounts of Form II crystals are introduced to induce and maintain the desired polymorphic form during the phase transition from solution to solid state
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
Form II exhibits improved bulk density and particle shape, allowing for enhanced pharmaceutical processing and potentially more stable formulations at elevated temperatures, although it transforms rapidly to Form I at ambient conditions, indicating Form I's stability at room temperature.
Implementation Method 1
heating Form I to 203°C for re-crystallization
Implementation Method 2
heating Form I to 203°C for re-crystallization
Implementation Method 3
the use of seed crystals to stabilize and produce Form II
Implementation Method 4
distinct X-ray diffraction patterns
Implementation Method 5
distinct X-ray diffraction patterns
Implementation Method 6
thermal profiles
Data Source
Figure 1
Figure 2
Figure 3
AI summary
This invention relates to a new crystalline form of Pridopidine, a drug substance currently in development for the treatment of Huntington's disease. More specifically the invention provides polymorphic Form II of the Pridopidine hydrochloride salt, a process for the preparation this polymorphic form, pharmaceutical compositions comprising polymorphic Form II, and methods of uses of this polymorphic form.