Olaparib Crystalline Form III Preparation Process
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Solution Overview
Problem
Current pharmaceutical formulations of olaparib lack new solid forms that could enhance its efficacy in cancer treatment and improve manufacturing processes, despite existing crystalline forms being disclosed.
Innovation Solution
A novel crystalline form III of olaparib is characterized and a process for preparing it, involving forming a solution with crude olaparib and an organic solvent, adding it to an anti-solvent to form a slurry, isolating the precipitate, and drying it, which is suitable for large-scale production and maintains stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing crystalline forms of olaparib are used, then the compound can be manufactured and stored, but the treatment efficacy and manufacturing process efficiency are not optimized
Solution Approach 1:
The patent applies parameter changes by discovering and characterizing multiple crystalline forms (Form I, Form II, Form III) of olaparib with different molecular packing arrangements. Each crystalline form exhibits distinct physical properties including different melting points, solubilities, and stabilities. This allows selection of optimal crystalline forms for specific therapeutic applications and manufacturing requirements, thereby improving treatment efficacy while providing manufacturing efficiency through standardized production processes for each form.
2Reliability
If new solid forms are developed to enhance efficacy, then treatment effectiveness improves, but the complexity of characterizing and manufacturing multiple forms increases
Solution Approach 1:
The patent applies segmentation by systematically categorizing and characterizing each crystalline form as a distinct entity with unique identification parameters. Form I, Form II, and Form III are separately characterized using X-ray diffraction patterns, differential scanning calorimetry, and thermogravimetric analysis. This segmentation approach simplifies the overall complexity by breaking down the characterization of multiple solid forms into manageable, standardized protocols for each individual form, facilitating both regulatory approval and manufacturing quality control.
3Stability of the object's composition
If crystalline forms are optimized for stability, then storage and shelf-life improve, but the manufacturing process complexity increases
Solution Approach 1:
The patent applies phase transitions by utilizing controlled crystallization processes to transform olaparib from solution or melt phases into specific stable crystalline forms. The manufacturing processes described involve dissolving olaparib in appropriate solvents followed by controlled cooling or evaporation to induce crystallization of the desired polymorph. This approach achieves high stability in the final crystalline product while maintaining relatively simple manufacturing processes that can be scaled up for commercial production.
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 crystalline form III of olaparib exhibits exceptional crystallinity and stability, allowing for high-yielding production and storage without converting to non-crystalline forms, thus potentially improving treatment efficacy and manufacturing efficiency.
Implementation Method 1
forming a solution comprising crude olaparib and an organic solvent
Implementation Method 2
adding the solution to an anti-solvent to form a slurry comprising a precipitate
Implementation Method 3
drying the precipitate to obtain the crystalline form III of olaparib
Data Source
AI summary
In certain aspects, the invention provides a novel crystalline form of olaparib (4-[(3-[(4-cyclopropylcarbonyl)piperazin-4-yl]carbonyl)-4-fluorophenyl]methyl(2H)phthalazin-1-one). In related aspects, the invention provides a processe for preparing the novel crystalline form of olaparib. The process includes forming a solution comprising crude olaparib and an organic solvent; adding the solution to an anti-solvent to form a slurry comprising a precipitate; isolating the precipitate; and drying the precipitate to obtain a crystalline form III of olaparib.