Compound I Solid Forms for Low Residual Solvent Control
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Solution Overview
Problem
Current manufacturing processes for Compound (I) result in high residual solvent levels, exceeding International Conference on Harmonization (ICH) guidelines, which is undesirable for active pharmaceutical ingredients (APIs), and there is a need for novel solid forms with specific physical and chemical properties suitable for pharmaceutical use.
Innovation Solution
Development of novel solid forms of Compound (I) with low residual solvent levels, characterized by specific physical properties such as mean bulk density, tapped density, Hausner ratio, and particle size distribution, and methods for producing these forms, including precipitation and spray drying processes, to achieve substantially pure and stable forms for pharmaceutical use.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional manufacturing processes are used to produce Compound (I), then production efficiency is maintained, but residual solvent levels exceed ICH guidelines
Solution Approach 1:
The patent changes physical parameters including solvent type, temperature, and pressure conditions during manufacturing to achieve low residual solvent levels while maintaining productivity. Specifically, the process uses controlled temperature ranges and solvent removal parameters to meet ICH guidelines without sacrificing production efficiency
Solution Approach 2:
The patent utilizes phase transition processes, particularly controlled crystallization and solvent removal phases, to achieve the desired solid forms with low residual solvent content. The phase change from solution to solid state is carefully controlled to minimize solvent retention while maintaining high production rates
2Reliability
If multiple solid forms are developed to achieve specific physical properties, then pharmaceutical suitability is improved, but development complexity increases
Solution Approach 1:
The patent segments the development into distinct solid forms (crystalline, amorphous, solvates) with specific characterized properties for different pharmaceutical applications. Each solid form is independently optimized for particular properties like solubility, stability, or bioavailability, allowing systematic selection based on therapeutic needs
Solution Approach 2:
The patent systematically varies physical parameters (temperature, solvent composition, cooling rates) to generate different solid forms with tailored properties. This parameter-based approach allows control over crystalline structure, particle size, and physical stability without requiring complex multi-step synthesis procedures
3Manufacturing precision
If residual solvent levels are reduced to meet ICH guidelines, then product purity is improved, but manufacturing process complexity increases
Solution Approach 1:
The patent employs extraction and removal processes to eliminate residual solvents from the final product. The manufacturing process includes dedicated solvent removal steps that efficiently extract trace solvents without requiring overly complex equipment or multiple processing cycles
Solution Approach 2:
The patent controls process parameters such as temperature, pressure, and solvent composition to minimize residual solvent incorporation during synthesis and crystallization. By optimizing these parameters, the process achieves high purity products through controlled chemistry rather than extensive post-processing
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 novel solid forms of Compound (I) achieve low residual solvent levels, improved stability, and specific physical properties, making them suitable for large-scale manufacturing and pharmaceutical applications, ensuring effective treatment of disorders mediated by Bruton's tyrosine kinase activity.
Implementation Method 1
spray drying processes, to achieve substantially pure and stable forms for pharmaceutical use
Data Source
AI summary
Solid forms of Compound (I):are disclosed. Pharmaceutical compositions comprising the same, methods of treating disorders and conditions mediated by BTK activity using the same, and methods for making Compound (I) and solid forms thereof are also disclosed.