Pridopidine Hydrobromide Salt Non-Hygroscopic Stability
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Solution Overview
Problem
The hydrochloride salt of Pridopidine becomes deliquescent at relative humidities above 86%, leading to instability and reduced bioavailability, whereas existing hydrobromide salts exhibit unpredictable hygroscopicity, affecting the drug's processability and stability.
Innovation Solution
A new, non-hygroscopic crystalline form of the hydrobromide salt of Pridopidine is developed, characterized by specific X-ray diffraction patterns, thermograms, and dynamic vapor sorption profiles, ensuring anhydrous and non-solvated stability up to 95% relative humidity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If the hydrochloride salt of Pridopidine is used, then the drug can be formulated and administered, but it becomes deliquescent at relative humidities above 86%, leading to instability and reduced bioavailability
Solution Approach 1:
The patent changes the counterion parameter from chloride to bromide, transforming the hydrochloride salt into a hydrobromide salt. This parameter change fundamentally alters the crystal lattice structure and intermolecular interactions, resulting in a salt form that is non-deliquescent and maintains stability at high relative humidities up to 95%, thereby resolving the hygroscopicity issue while preserving therapeutic properties
Solution Approach 2:
The invention creates a composite crystal structure comprising pridopidine molecules associated with hydrobromic acid in a specific stoichiometric ratio (1:1). This composite arrangement in the crystal lattice, characterized by specific X-ray diffraction patterns, produces a material with improved hygroscopic properties compared to the individual components or alternative salt forms
2Ease of manufacture
If existing hydrobromide salts are used, then the drug can be formulated, but they exhibit unpredictable hygroscopicity, affecting processability and stability
Solution Approach 1:
The patent optimizes the crystallization parameters including solvent selection (aqueous acid solutions), temperature control, and pH adjustment to produce a consistent, well-defined crystal structure. This controlled parameter optimization ensures reproducible manufacturing with predictable and improved stability characteristics
Solution Approach 2:
The invention replaces reliance on unpredictable physical properties with a systematically optimized crystallization process that uses controlled chemical parameters (pH, solvent composition, temperature) to produce a salt form with consistent and predictable hygroscopic behavior, thereby improving both manufacturability and stability
3Reliability
If a stable salt form is achieved, then bioavailability is improved, but the crystal structure must be precisely controlled and characterized
Solution Approach 1:
The hydrobromide salt exhibits self-organizing properties during crystallization, spontaneously forming a stable, well-defined crystal lattice structure when crystallized from aqueous hydrobromic acid solutions. This self-organizing behavior reduces the need for complex manufacturing controls while ensuring consistent crystal structure and improved bioavailability
Solution Approach 2:
The patent uses X-ray diffraction pattern analysis as a fingerprinting method to verify crystal structure. The specific diffraction patterns serve as unique identifiers that confirm the correct polymorphic form has been produced, enabling quality control without requiring complex structural analysis
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 new hydrobromide salt maintains therapeutic properties similar to the hydrochloride salt while being non-hygroscopic, ensuring stability and bioavailability, and is suitable for treating various central nervous system disorders, including Huntington's disease.
Implementation Method 1
The crystal lattice of a pharmaceutical salt is composed of ionized drug molecules and counter ions of opposite charge, which form a unique crystal structure
Implementation Method 2
The crystalline hydrobromide of the invention is characterised by a powder X-ray diffractogram having the d-spacing's shown in Table 1 below
Implementation Method 3
The crystalline hydrobromide of the invention is characterised by a powder X-ray diffractogram having the d-spacing's shown in Table 1 below
Implementation Method 4
ensuring anhydrous and non-solvated stability up to 95% relative humidity
Data Source
AI summary
This invention relates to a new salt of Pridopidine, a drug substance currently in development for the treatment of Huntington's disease. More specifically the invention provides the pharmaceutically acceptable hydrobromide salt, pharmaceutical compositions comprising this salt, and uses of this salt as a drug substance.