Crystalline Asciminib Mesylate for Stable Drug Processing
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Solution Overview
Problem
There is a need for additional solid state forms of Asciminib, including solvates, to improve processing, handling, stability, and bioavailability for the treatment of Chronic Myeloid Leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia.
Innovation Solution
The development of crystalline Asciminib mesylate and its use in preparing other solid state forms and pharmaceutical compositions, which can be combined with pharmaceutically acceptable excipients for medicinal use.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If additional solid state forms and solvates of Asciminib are developed, then processing characteristics, handling, stability, and bioavailability are improved, but device complexity and preparation process complexity increase
Solution Approach 1:
The patent applies parameter changes by systematically varying crystallization conditions (temperature, pH, solvent composition, cooling rates) to obtain different solid state forms and solvates of Asciminib. Each form is characterized by distinct physical properties such as melting point, solubility, and crystal structure, allowing optimization of stability and processing characteristics through controlled parameter modification during formulation development.
2Productivity
If multiple crystalline forms and polymorphs are obtained, then formulation optimization and bioavailability are improved, but manufacturing precision and process control requirements increase
Solution Approach 1:
The patent employs feedback mechanisms through comprehensive characterization techniques (X-ray diffraction, thermal analysis, NMR spectroscopy) to monitor and verify the formation of specific crystalline forms and polymorphs. This feedback allows real-time adjustment of crystallization parameters to ensure consistent production of desired solid state forms with controlled properties, thereby optimizing bioavailability while maintaining manufacturing precision.
3Ease of operation
If new solid state forms with desirable properties are discovered, then processing and handling characteristics are improved, but loss of time in discovery and characterization increases
Solution Approach 1:
The patent applies preliminary action by pre-establishing a systematic approach to crystallization and polymorph screening before formulation development begins. Critical crystallization parameters are optimized in advance, and characterization methods are predetermined, allowing efficient discovery and evaluation of new solid state forms with desirable processing characteristics without time-consuming trial-and-error processes during later formulation stages.
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 crystalline Asciminib mesylate provides improved processing characteristics, stability, and bioavailability, enhancing the effectiveness of treatments for CML and Philadelphia chromosome-positive acute lymphoblastic leukemia.
Implementation Method 1
crystalline Asciminib mesylate... processes for preparation thereof... solid state forms
Data Source
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AI summary
The present disclosure encompasses solid state forms of Asciminib and salts thereof, in embodiments crystalline polymorphs of Asciminib and salts thereof, processes for preparation thereof, and pharmaceutical compositions thereof.