Micronized c-kit Kinase Inhibitor Formulation for Stability
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Solution Overview
Problem
There is a need for novel pharmaceutical compositions and methods to effectively deliver c-kit kinase inhibitors for treating c-kit associated diseases, with existing compositions lacking in stability, oral bioavailability, and toxicity concerns.
Innovation Solution
Development of pharmaceutical compositions comprising N-(5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, formulated as micronized powders with specific crystalline forms, incorporating an acidulant and surfactant, and optionally including fillers, disintegrants, and stabilizers, to enhance stability and bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If conventional pharmaceutical compositions are used to deliver c-kit kinase inhibitors, then the basic therapeutic function is achieved, but stability and oral bioavailability are insufficient
Solution Approach 1:
The patent applies parameter changes by micronizing the compound to specific particle size ranges (D10: 0.5-2.0 μm, D50: 1.5-3.0 μm, D90: 2.5-5.0 μm) and controlling polymorphic form to enhance both stability and oral bioavailability simultaneously
Solution Approach 2:
The patent uses composite materials by formulating the c-kit kinase inhibitor with specific excipients including surfactants (0.5-5% w/w), disintegrants (5-20% w/w), and fillers (20-50% w/w) to create a composite pharmaceutical composition that improves stability and bioavailability
2Reliability
If higher doses of c-kit kinase inhibitors are administered to improve therapeutic effect, then disease treatment efficacy increases, but toxicity increases
Solution Approach 1:
The patent changes the physical parameters of the compound through micronization and polymorphic control to improve dissolution rate and bioavailability, enabling lower effective doses that reduce toxicity while maintaining therapeutic effect
3Ease of manufacture
If the compound is formulated without micronization to simplify manufacturing, then manufacturing complexity is reduced, but oral bioavailability and stability deteriorate
Solution Approach 1:
The patent applies micronization with specific particle size parameters (D10: 0.5-2.0 μm, D50: 1.5-3.0 μm, D90: 2.5-5.0 μm) and controls polymorphic form to enhance oral bioavailability and stability while maintaining manufacturing feasibility through standardized processes
Data Source
AI summary
The present disclosure relates generally to pharmaceutical compositions of N-(5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide useful as a selective inhibitor of c-kit kinase and uses of the same in the treatment of c-kit kinase associated diseases.