Crystalline and Amorphous Solid Forms for Myeloma Drug Stability
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Solution Overview
Problem
Current therapies and methods for treating multiple myeloma, including for patients whose multiple myeloma are newly diagnosed or refractory to standard treatments, while reducing or avoiding the toxicities and/or side effects associated with the conventional therapies, and there is a need for alternative solid forms of pharmaceutical compounds to modulate or enhance physical and chemical properties for improved efficacy.
Innovation Solution
Development and characterization of various crystalline and amorphous solid forms of (S)-4-(4-(4-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)methyl)benzyl)piperazin-1-yl)-3-fluorobenzonitrile and its salts, including specific X-ray powder diffraction patterns for identification and characterization.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional therapies are used to treat multiple myeloma, then disease treatment is achieved, but toxicities and side effects increase
Solution Approach 1:
The patent applies parameter changes by developing novel solid forms (crystalline polymorphs, amorphous forms, salts, solvates, and hydrates) of the pharmaceutical compound. These different solid forms have varying physical and chemical properties including solubility, dissolution rate, and stability, allowing optimization of therapeutic effectiveness while reducing toxicities and side effects associated with conventional formulations
2Reliability
If solid forms of pharmaceutical compounds are developed to improve efficacy, then bioavailability and stability are enhanced, but manufacturing complexity increases
Solution Approach 1:
The patent systematically explores different solid forms by changing physical and chemical parameters such as crystalline structure (polymorphs), molecular arrangement (amorphous vs. crystalline), ionic associations (salts), and solvent incorporation (solvates and hydrates). Each solid form offers optimized bioavailability and stability profiles while providing manufacturers with multiple options to select from based on processing requirements
Solution Approach 2:
The patent describes composite solid forms including salts formed with various counterions, solvates with different solvent molecules, and hydrates with water molecules. These composite structures combine the active pharmaceutical ingredient with other molecules in specific ratios and arrangements, enhancing overall formulation performance while maintaining manufacturability
Data Source
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AI summary
Provided herein are formulations, processes, solid forms and methods of use relating to salts of and solid forms comprising free base or salts of (S)-4-(4-(4-(((2-(2,6- dioxopiperidin-3-yl)-l-oxoisoindolin-4-yl)oxy)methyl)benzyl)piperazin-l-yl)-3- fluorobenzonitrile.