Lenvatinib Mesylate Crystal Form X Solubility Stability
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Solution Overview
Problem
Existing crystal forms of lenvatinib mesylate lack improved solubility and stability, which are crucial for pharmaceutical applications, particularly in industrialized mass production and bioavailability.
Innovation Solution
A new crystal form X of lenvatinib mesylate with enhanced solubility and stability is developed, characterized by specific X-ray powder diffraction peaks and a preparation method involving the use of methanesulfonic acid in a solvent system of water and alcohols, such as methanol, to achieve improved crystallization and purity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing crystal forms of lenvatinib mesylate are used, then the drug can be produced, but the solubility and stability are insufficient for industrialized mass production
Solution Approach 1:
The patent identifies and utilizes polymorphic forms (crystal forms A, B, C, F, I, and M) of lenvatinib mesylate, each representing different structural parameters. The invention specifically selects and optimizes certain polymorphic forms that exhibit superior solubility and stability characteristics, thereby resolving the contradiction between manufacturing ease and reliability through parameter changes in crystal structure.
2Reliability
If existing crystal forms are used, then production can proceed, but solubility and bioavailability are limited
Solution Approach 1:
The patent employs polymorphic forms with optimized crystal structures that enhance solubility and bioavailability. By selecting specific polymorphic forms (such as form A, C, F, I, or M) and controlling crystallization parameters, the invention achieves improved dissolution rates and pharmacokinetic properties, directly addressing the contradiction between bioavailability and solubility.
3Productivity
If conventional crystallization methods are used, then lenvatinib mesylate can be produced, but solvent usage is high and production efficiency is low
Solution Approach 1:
The patent optimizes crystallization parameters including solvent selection, temperature profiles, and cooling rates to achieve efficient crystal formation. By controlling these parameters, the invention reduces solvent consumption and improves production efficiency while maintaining high product quality and purity.
Solution Approach 2:
The patent utilizes controlled phase transitions during crystallization, including dissolution, nucleation, and crystal growth stages. By managing these phase changes through optimized temperature and solvent conditions, the invention achieves high production efficiency with reduced solvent usage, resolving the contradiction between productivity and substance loss.
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
Crystal form X exhibits significantly improved solubility and stability, facilitating efficient industrial production with reduced solvent use, high purity, and enhanced bioavailability, as demonstrated by improved dissolution rates and pharmacokinetic studies.
Implementation Method 1
a preparation method involving the use of methanesulfonic acid in a solvent system of water and alcohols, such as methanol, to achieve improved crystallization and purity
Implementation Method 2
An X-ray powder diffraction spectrum of crystal form X of the mesylate provided by the invention has characteristic peaks at 2 theta values of 22.84°±0.2°, 20.16°±0.2°, and 9.46°±0.2°
Data Source
AI summary
A new crystal form of lenvatinib mesylate, a preparation method thereof and a use thereof in the preparation of a drug for treating cancer.