Cabozantinib L-(+)-Tartaric Acid Salt Solid Forms
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Solution Overview
Problem
Existing Cabozantinib salts exhibit poor solubility, low crystallinity, and hygroscopicity, which limits their therapeutic efficacy and stability.
Innovation Solution
Development of solid forms of Cabozantinib salt with L-(+)-tartaric acid, specifically Forms 1, 2, 3, and 4, which are characterized by improved solubility, crystallinity, and reduced hygroscopicity through specific preparation processes involving solvents like tetrahydrofurane, methanol, and water.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If Cabozantinib malate salt is used, then the compound is orally bioavailable, but the solubility remains poor
Solution Approach 1:
The patent applies parameter changes by switching from malate salt to L-(+)-tartaric acid salt of Cabozantinib. This chemical parameter change (salt form modification) results in improved solubility while maintaining oral bioavailability, directly resolving the contradiction between poor solubility and required bioavailability
2Stability of the object's composition
If Cabozantinib tartrate salt is prepared, then the crystallinity is low, but the solubility is also low
Solution Approach 1:
The patent resolves this contradiction by changing the salt form parameter from tartrate to L-(+)-tartaric acid, and进一步优化 through specific crystallization conditions (solvent system, temperature, pH) to achieve both high crystallinity and improved solubility simultaneously
3Reliability
If Cabozantinib salts are formulated, then the therapeutic efficacy is limited, but the stability is also compromised due to hygroscopicity
Solution Approach 1:
The patent changes the salt form parameter to L-(+)-tartaric acid salt, which reduces hygroscopicity and improves stability. This parameter change simultaneously enhances therapeutic efficacy through improved solubility and bioavailability while maintaining formulation stability
Solution Approach 2:
The patent applies preliminary action by optimizing the crystallization process conditions (solvent selection, temperature control, pH adjustment) to pre-establish the desired crystal structure and properties before formulation, ensuring both stability and efficacy are achieved in the final product
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 solid forms of Cabozantinib salt with L-(+)-tartaric acid demonstrate enhanced solubility, crystallinity, and stability compared to previously known salts, potentially improving bioavailability and therapeutic outcomes.
Implementation Method 1
Cabozantinib salt with L-(+)-tartaric acid
Implementation Method 2
preparation processes involving solvents like tetrahydrofurane, methanol, and water
Implementation Method 3
solid forms of Cabozantinib salt with L-(+)-tartaric acid, specifically Forms 1, 2, 3, and 4
Data Source
AI summary
The invention relates to solid forms of Cabozantinib, compound of formula (1), salt with L-(+)-tartaric acid and processes for preparation thereof,