Succinate Salt Form of Benzimidazole Amine for Stable Solid Formulation
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Solution Overview
Problem
Existing salts of N-(3-(4-(3-(diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine, such as sulphate salts, face stability issues during drying and polymorphic form conversion, making them unsuitable for solid formulations, and other salts have hygroscopicity or toxicity concerns.
Innovation Solution
Development of succinate salts with stable polymorphic forms that are non-hygroscopic and obtainable through a one-pot salt formation/crystallization process, ensuring high crystallinity and stability, suitable for solid formulations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If free base forms or salt forms other than succinate salts are used, then the compound can be formulated, but the stability and solubility profile are insufficient for optimal pharmaceutical use
Solution Approach 1:
The patent applies parameter changes by selecting succinate salt specifically, which alters the chemical and physical parameters of the compound. The succinate salt form provides optimal balance between stability and solubility compared to other salt forms or free base, demonstrating how changing the salt parameter resolves the contradiction between stability and solubility profile
2Productivity
If conventional synthesis methods are used, then the compound can be produced, but the process is time-consuming and yields are not optimal
Solution Approach 1:
The patent employs preliminary action by performing protective group removal and salt formation in a one-pot process without isolation of intermediates. This approach eliminates time-consuming isolation and purification steps while maintaining high yields, directly addressing the contradiction between productivity and synthesis time
Solution Approach 2:
The patent merges multiple synthetic steps (protective group removal and salt formation) into a single operational step. By combining these steps and avoiding intermediate isolation, the process achieves both high yield and reduced synthesis time, resolving the contradiction between productivity and time loss
3Manufacturing precision
If multiple isolation and purification steps are performed, then the compound can be purified, but the process becomes complex and time-consuming
Solution Approach 1:
The patent extracts only the essential purification step by performing salt formation that simultaneously achieves purification. The succinate salt formation selectively precipitates or crystallizes the desired product while leaving impurities in solution, eliminating the need for multiple isolation and purification steps while maintaining manufacturing precision
Solution Approach 2:
The patent uses salt formation as an intermediary process that serves dual purposes: purification and product isolation. The succinate salt acts as an intermediary form that facilitates purification in a single step, reducing process complexity while maintaining the required manufacturing precision
Data Source
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AI summary
The present invention relates to succinate salts of N-(3-(4-(3- (diisobutylamino)propyl)piperazin-1-yl)propyl)-1H-benzo[d]imidazol-2-amine and pharmaceutically acceptable solvates thereof, preparation thereof, pharmaceutical compositions containing them and use of the same in the treatment and/or prevention of neurodegenerative diseases.