Ripretinib Solid-State Forms for Stability and Bioavailability
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Solution Overview
Problem
There is a need for a solid state form of ripretinib suitable for use in the pharmaceutical industry, as existing forms may lack desirable properties such as stability, solubility, and bioavailability, which are crucial for effective treatment of gastrointestinal stromal tumors (GIST), advanced systemic mastocytosis (ASM), gliomas, and other solid tumors driven by tyrosine-protein kinase KIT or platelet derived growth factor alpha (PDGFRα) kinase.
Innovation Solution
The development of various solid state forms of ripretinib, including crystalline and amorphous forms, characterized by specific PXRD and 13C NMR patterns, which offer improved chemical stability, solubility, and bioavailability, facilitating the preparation of pharmaceutical compositions and formulations for oral administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing solid state forms of ripretinib are used, then the compound can be administered orally, but the stability, solubility, and bioavailability are insufficient for effective treatment
Solution Approach 1:
The patent applies parameter changes by discovering and characterizing multiple polymorphic forms (Forms 1-6) of ripretinib, each with distinct crystal structures and physical properties. By changing the solid state form from one polymorph to another, the patent improves both stability and solubility parameters simultaneously, resolving the technical contradiction between these two properties.
Solution Approach 2:
The patent employs composite material strategies by creating cocrystals of ripretinib with various coformers (such as nicotinamide, caffeine, and other small molecules). These cocrystal forms combine ripretinib with complementary materials that enhance both stability and solubility, effectively resolving the contradiction between these two critical properties for pharmaceutical efficacy.
2Reliability
If existing solid state forms of ripretinib are used, then the compound can be formulated for oral administration, but the bioavailability is insufficient for effective treatment of targeted tumors
Solution Approach 1:
The patent improves bioavailability by changing the solid state form parameters of ripretinib. Different polymorphic forms and cocrystals exhibit enhanced dissolution rates and bioavailability compared to the original form. This parameter change approach allows for improved therapeutic efficacy without requiring complex formulation strategies, thereby resolving the contradiction between bioavailability and formulation complexity.
Data Source
AI summary
The present disclosure relates to solid state forms of ripretinib, processes for preparation thereof, as well as a pharmaceutical composition including the same.