Trilaciclib Polymorphs for Stability and Bioavailability
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Solution Overview
Problem
There is a need for additional solid state forms, including solvated forms, of Trilaciclib and its salts to improve processing properties, stability, and bioavailability for pharmaceutical applications, particularly for treating myelosuppression during chemotherapy.
Innovation Solution
The disclosure provides crystalline polymorphs of Trilaciclib and Trilaciclib citrate salt, along with processes for their preparation and pharmaceutical compositions thereof, which can be used to prepare other forms of Trilaciclib or its salts, thereby enhancing their stability and bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If additional solid state forms of Trilaciclib are developed, then stability and bioavailability are improved, but manufacturing complexity increases
Solution Approach 1:
The patent applies parameter changes by developing multiple crystalline polymorphs of Trilaciclib with different physical properties. Each polymorph represents a different arrangement of molecules in the solid state, creating distinct forms (Form 1, Form 2, Form 3) with varying stability, solubility, and dissolution characteristics. This allows optimization of the drug's performance parameters while maintaining the same chemical identity.
Solution Approach 2:
The patent utilizes phase transitions in the development of different crystalline forms. By controlling the crystallization process and identifying multiple stable phases (polymorphs), the invention creates different solid state forms that can be selected based on their transition properties, stability, and bioavailability characteristics.
2Productivity
If multiple crystalline polymorphs are produced, then bioavailability and solubility are improved, but process complexity increases
Solution Approach 1:
The patent employs parameter changes by systematically varying crystallization conditions (temperature, pH, solvent composition, cooling rates) to produce different polymorphic forms. Each form is characterized by specific physical parameters such as X-ray diffraction patterns, melting points, and solubility profiles, enabling selection based on desired bioavailability characteristics.
Solution Approach 2:
The patent creates multiple copies of the same molecule in different crystalline arrangements. By producing Form 1, Form 2, and Form 3 polymorphs, the invention provides alternative structural representations of Trilaciclib that can be selected based on their dissolution and bioavailability properties, effectively copying the molecule in different functional configurations.
3Ease of manufacture
If different solid state forms are developed, then processing properties are improved, but characterization requirements increase
Solution Approach 1:
The patent utilizes characteristic physical properties of different polymorphs for identification and characterization. Each crystalline form exhibits distinct properties such as X-ray diffraction patterns, melting points, and solubility characteristics that serve as identification markers, allowing differentiation between Form 1, Form 2, and Form 3 without requiring complex analysis.
Solution Approach 2:
The patent replaces complex mechanical characterization methods with more straightforward analytical techniques. By using X-ray diffraction, differential scanning calorimetry, and NMR spectroscopy, the invention can efficiently characterize polymorphic forms without requiring complex mechanical testing or extensive manual analysis procedures.
Data Source
AI summary
The present disclosure encompasses solid state forms of Trilaciclib and Trilaciclib citrate salt, in embodiments poly-morphs of Trilaciclib and Trilaciclib citrate salt, processes for preparation thereof, pharmaceutical compositions and uses thereof.