9-ING-41 Crystalline Form II for Stability and Solubility Balance
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Solution Overview
Problem
There is a need for novel solid forms of 9-ING-41, including polymorphs and solvates, which exhibit advantageous properties such as chemical purity, flowability, solubility, dissolution rate, bioavailability, and stability, to enhance their therapeutic efficacy in treating cancers and traumatic brain injury.
Innovation Solution
The development of crystalline Form II of 3-(5-fluorobenzofuran-3-yl)-4-(5-methyl-5H-[1,3]dioxolo[4,5-f]indol-7-yl)pyrrole-2,5-dione (9-ING-41) characterized by specific X-ray powder diffraction patterns and differential scanning calorimetry profiles, prepared through solvent-based concentration and cooling processes, and formulated into pharmaceutical compositions with pharmaceutically acceptable excipients.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional solid forms of 9-ING-41 are used, then the compound can be administered for therapeutic purposes, but the chemical stability, solubility, and dissolution rate are insufficient for optimal therapeutic efficacy
Solution Approach 1:
The patent applies parameter changes by discovering and characterizing different polymorphic forms (Form I, Form II, Form III) and solvates (acetone solvate, isopropanol solvate) of 9-ING-41. Each solid form has distinct crystal structures with different physical properties including solubility, dissolution rate, and stability. By changing the crystalline parameters through controlled crystallization processes using specific solvents and conditions, the patent achieves optimal balances between chemical stability and solubility for therapeutic efficacy
Solution Approach 2:
The patent creates composite solid forms by forming solvates where 9-ING-41 molecules are incorporated into crystal structures with solvent molecules (acetone, isopropanol). These composite crystalline structures combine the active pharmaceutical ingredient with solvent molecules in specific ratios and arrangements, resulting in enhanced solubility and dissolution properties while maintaining chemical stability
2Ease of operation
If the solubility of 9-ING-41 is increased through solid form modification, then the dissolution rate and bioavailability improve, but the manufacturing process complexity increases
Solution Approach 1:
The patent applies preliminary action by pre-characterizing multiple solid forms (polymorphs and solvates) with defined crystallization conditions before actual pharmaceutical manufacturing. The patent provides detailed characterization data including X-ray powder diffraction patterns, differential scanning calorimetry profiles, and solubility measurements for each form. This preliminary characterization allows manufacturers to select the most appropriate solid form and use standardized crystallization protocols, reducing manufacturing complexity while ensuring consistent dissolution rate and bioavailability
Solution Approach 2:
The patent uses specific solvents (acetone, isopropanol, ethyl acetate, methyl tert-butyl ether) as intermediaries to facilitate the formation of desired solid forms. These solvent intermediaries mediate the crystallization process by interacting with 9-ING-41 molecules during crystal formation, enabling control over polymorph selection and solvate formation. The intermediaries provide a controlled pathway to achieve enhanced dissolution rates through relatively simple crystallization procedures
3Temperature
If thermal stability is enhanced through solid form selection, then the compound maintains stability during storage and processing, but the solubility may be reduced
Solution Approach 1:
The patent applies parameter changes by identifying and characterizing solid forms with different thermal and solubility properties. Differential scanning calorimetry analysis reveals distinct melting points and thermal transitions for each polymorph and solvate. By selecting specific crystal structures and solvate compositions, the patent optimizes the balance between thermal stability (important for storage and processing) and solubility (important for bioavailability), allowing formulation scientists to choose the appropriate form based on specific application requirements
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 Form II of 9-ING-41 demonstrates improved chemical stability, thermal stability, and solubility, facilitating effective treatment of various cancers and traumatic brain injury.
Implementation Method 1
dissolving 3-(5-fluorobenzofuran-3-yl)-4-(5-methyl-5H-[1,3]dioxolo[4,5-f]indol-7-yl)pyrrole-2,5-dione in a solvent to form a solution
Implementation Method 2
concentrating the solution
Implementation Method 3
cooling the solution
Data Source
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AI summary
The present disclosure relates to solid forms of 3-(5-Fluorobenzofuran-3-yl)-4-(5-methyl-5H-[1,3]dioxolo[4,5-f]indol-7-yl) pyrrole-2,5-dione, processes for preparation thereof, pharmaceutical compositions thereof, and uses thereof in treating disease.