Imatinib Mesylate Polymorphs for Flowability and Dissolution
Solution Overview
Problem
There is a need for new polymorphs and processes for preparing imatinib mesylate to improve its solid-state physical properties, such as flowability and dissolution rate, which are crucial for pharmaceutical formulations, as existing forms may not adequately address therapeutic and processing requirements.
Innovation Solution
The development of various crystalline and solvated forms of imatinib mesylate, characterized by specific XRD patterns and 13C NMR spectra, along with processes involving solvent selection and temperature control, to produce forms like Forms IV, V, VI, and others, which enhance flowability and bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If conventional forms of imatinib mesylate are used, then the compound can be administered orally, but the flowability and dissolution rate are insufficient for optimal pharmaceutical formulation
Solution Approach 1:
The patent applies parameter changes by creating multiple polymorphic forms (Forms I-XVI) with different crystal structures and physical properties. Each form is characterized by distinct XRD patterns and NMR spectra, representing different arrangements of molecules in the solid state. This allows optimization of flowability and dissolution rate by selecting or developing specific polymorphic forms that exhibit improved physical properties compared to conventional forms.
Solution Approach 2:
The patent utilizes phase transitions by transforming imatinib mesylate between different solid phases (polymorphic forms) and between solid and liquid states. The development of multiple crystalline forms represents different solid phases, and the ability to control which form is produced through various preparation methods enables optimization of pharmaceutical properties. The amorphous form represents a non-crystalline phase with different properties compared to crystalline forms.
2Ease of operation
If the solid-state form of imatinib mesylate is optimized for flowability, then handling during processing improves, but the dissolution rate may be affected
Solution Approach 1:
The patent demonstrates that different polymorphic forms have different physical parameters including flowability and dissolution characteristics. By changing the crystal structure parameter (through different forms I-XVI), the patent can optimize flowability for handling during processing while maintaining or improving dissolution rate. The distinct XRD patterns and NMR spectra of each form indicate different molecular arrangements that lead to different physical properties.
Solution Approach 2:
The patent creates composite characteristics by combining different polymorphic forms with appropriate pharmaceutical excipients and formulation techniques. The ability to produce multiple forms allows for composite formulation strategies where the physical properties of different forms can be leveraged to achieve both good flowability and dissolution rate in the final pharmaceutical product.
3Ease of operation
If new polymorphic forms are developed to improve physical properties, then flowability and dissolution rate enhance, but the complexity of preparation processes increases
Solution Approach 1:
The patent shows that by changing preparation parameters such as solvent selection, temperature, pH, and addition rate, different polymorphic forms can be obtained. This allows control over the solid-state structure without requiring complex equipment or multi-step processes. The distinct XRD patterns and NMR spectra confirm that parameter changes lead to different forms with optimized properties.
Solution Approach 2:
The patent uses solvents and intermediaries as mediators to control the formation of specific polymorphic forms. By selecting appropriate solvents and controlling the solvation process, the patent can guide the crystallization to produce desired forms with improved physical properties. The solvents act as intermediaries that facilitate the formation of specific crystal structures during the preparation process.
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 forms of imatinib mesylate exhibit improved flowability and dissolution rates, leading to better bioavailability and stability, making them attractive for pharmaceutical formulations with targeted release profiles.
Implementation Method 1
crystalline forms of imatinib mesylate... processes for preparation of novel crystalline forms... When a substance crystallizes out of solution, it may trap molecules of solvent at regular intervals in the crystal lattice
Implementation Method 2
solvates of imatinib mesylate... When a substance crystallizes out of solution, it may trap molecules of solvent at regular intervals in the crystal lattice... solvation also affects utilitarian physical properties of the solid-state
Implementation Method 3
cooling to a temperature of about 10° C. to about −50° C. to obtain a precipitate of the said crystalline form
Implementation Method 4
makes it possible to prepare new forms by the desolvation of solvates
Data Source
AI summary
Solvates and crystalline forms of imatinib mesylate are described. Further, methods for preparing such solvates and crystalline forms of imatinib mesylate are described.