Rivoceranib Polymorph Selection for Stability and Dissolution
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Solution Overview
Problem
There is a need for additional solid state forms of Rivoceranib and Rivoceranib mesylate to improve processing, handling characteristics, dissolution profile, stability, and bioavailability, as existing forms may not adequately address these factors.
Innovation Solution
The development of new crystalline polymorphs, including Form RT2, RT4, and RT5 of Rivoceranib mesylate, and Form RT1 and RT3 of Rivoceranib, which possess distinct properties such as chemical stability, thermal stability, and solubility, achieved through processes involving slurry mixing and drying.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If existing solid state forms of Rivoceranib and Rivoceranib mesylate are used, then the basic pharmaceutical function is achieved, but processing and handling characteristics are insufficient
Solution Approach 1:
The patent applies parameter changes by discovering and utilizing different polymorphic forms (Form A, Form B, Form C, Form D, Form F, and Form II) of Rivoceranib mesylate, each with distinct crystal structures and physical properties. These polymorphs exhibit variations in melting point, thermal behavior, X-ray diffraction patterns, and dissolution profiles, allowing selection of the most suitable form for specific processing and handling requirements.
Solution Approach 2:
The patent utilizes phase transitions between different polymorphic forms to improve processing characteristics. By controlling crystallization conditions, solvent selection, and temperature profiles, the invention enables transition between polymorphs to achieve desired properties such as enhanced flowability, compressibility, or dissolution rate for optimal pharmaceutical formulation.
2Productivity
If existing solid state forms of Rivoceranib and Rivoceranib mesylate are used, then the drug delivery function is achieved, but dissolution profile is not optimized
Solution Approach 1:
The patent employs parameter changes by selecting specific polymorphic forms with optimized crystal structures that enhance dissolution properties. Different polymorphs display varying solubility and dissolution rates, allowing formulation scientists to select the form that maximizes bioavailability while maintaining consistent dissolution behavior across batches.
3Reliability
If existing solid state forms of Rivoceranib and Rivoceranib mesylate are used, then the basic stability is achieved, but chemical and physical stability can be improved
Solution Approach 1:
The patent applies parameter changes by identifying polymorphic forms with superior chemical and physical stability characteristics. Each polymorph exhibits different stability profiles under various storage conditions (temperature, humidity, light exposure), enabling selection of the most stable form to extend shelf-life and maintain drug potency over time.
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
These new polymorphs offer improved chemical stability, solubility, and handling characteristics, enhancing the potential for better pharmaceutical formulations and cancer treatment efficacy.
Implementation Method 1
processes involving slurry mixing and drying
Data Source
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AI summary
The present disclosure encompasses crystalline polymorphs of Rivoceranib and Rivoceranib mesylate (Apatinib mesylate), processes for preparation thereof, and pharmaceutical compositions thereof.