GDC-0077 Solid Forms for Consistent Polymorph Manufacturing
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
The pharmaceutical industry faces challenges in manufacturing consistency due to the unpredictable behavior of multiple polymorphs of the same crystalline chemical entity, which affects bioavailability, shelf life, and processing behavior, and regulatory agencies require thorough understanding and identification of these polymorphs.
Innovation Solution
The development of specific polymorph forms of the PI3K inhibitor GDC-0077, characterized by distinct X-ray powder diffraction patterns, including Form A, Form D, and Form B, along with a process for preparing these forms, ensuring consistent manufacturing and pharmaceutical compositions for effective treatment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If multiple polymorph forms of a crystalline chemical entity are present, then the drug substance can exhibit different bioavailability and stability properties, but manufacturing consistency becomes unpredictable and difficult to control
Solution Approach 1:
The patent extracts and isolates specific polymorph forms (Form A, Form B, Form C) from the mixture of multiple polymorphs. By separating the desired polymorph form from others through controlled crystallization processes, the invention achieves manufacturing consistency while eliminating the unpredictable variability inherent in having multiple polymorph forms present simultaneously.
Solution Approach 2:
The patent employs parameter changes in the crystallization process (temperature, solvent composition, pH, addition rate) to selectively produce specific polymorph forms. By precisely controlling these parameters, the invention can reliably generate the desired polymorph form with consistent properties, thereby resolving the contradiction between manufacturing consistency and polymorph variability.
2Manufacturing precision
If thorough identification and understanding of multiple polymorphs is conducted to meet regulatory requirements, then drug product quality can be ensured, but the complexity and time required for characterization increases
Solution Approach 1:
The patent extracts and isolates specific polymorph forms (Form A, Form B, Form C) from the mixture of multiple polymorphs. By separating the desired polymorph form from others through controlled crystallization processes, the invention achieves manufacturing consistency while eliminating the unpredictable variability inherent in having multiple polymorph forms present simultaneously.
Solution Approach 2:
The patent employs parameter changes in the crystallization process (temperature, solvent composition, pH, addition rate) to selectively produce specific polymorph forms. By precisely controlling these parameters, the invention can reliably generate the desired polymorph form with consistent properties, thereby resolving the contradiction between manufacturing consistency and polymorph variability.
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 identified polymorphs provide consistent drug product quality, meeting regulatory requirements and enhancing therapeutic efficacy by providing predictable bioavailability and stability, facilitating the treatment of hyperproliferative disorders like cancer.
Implementation Method 1
Powder X-ray Diffraction is a powerful tool in identifying different crystal phases by their unique diffraction patterns
Implementation Method 2
exhibits an X-ray powder diffraction pattern having a characteristic peak expressed in degrees 2-theta at approximately 5.7
Data Source
AI summary
Crystalline polymorph forms of(S)-2-((2-((S)-4-(difluoromethyl)-2-oxooxazolidin-3-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)amino) propanamide (GDC-0077), having the structure, Formula I:or stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof, processes of preparing the polymorph forms, and uses of the polymorph forms for the treatment of cancer.