Brequinar Sodium Polymorphic Form C for Stable Large-Scale Manufacture
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Solution Overview
Problem
Existing technologies face challenges in formulating brequinar sodium salt for commercial-scale manufacturing due to instability and inconsistency in crystal forms, making it difficult to produce stable solid oral dosage forms.
Innovation Solution
Identification and utilization of polymorphic form C of brequinar sodium salt, which is stable under ambient conditions, allowing for the formulation of pharmaceutical compositions suitable for various routes of administration, including oral, intravenous, and others, and enabling large-scale manufacture and distribution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If crystalline brequinar sodium salt is manufactured at large scale, then production volume increases, but crystal form stability and consistency deteriorate
Solution Approach 1:
The patent applies parameter changes by controlling the crystallization process parameters (temperature, pH, concentration) to selectively obtain polymorphic form C of brequinar sodium salt. By maintaining specific process conditions, the patent ensures that large-scale manufacturing produces consistent and stable crystals of the desired polymorphic form, resolving the contradiction between production volume and crystal form stability.
2Adaptability or versatility
If multiple polymorphic forms of brequinar sodium salt are produced, then manufacturing flexibility increases, but product consistency and reliability deteriorate
Solution Approach 1:
The patent applies local quality by focusing the crystallization process on producing a specific local form (polymorphic form C) rather than allowing multiple forms to coexist. By optimizing the local crystallization conditions (temperature, pH, concentration gradients), the patent ensures that the entire batch consists of consistent polymorphic form C, thereby maintaining product reliability while preserving manufacturing flexibility through controlled process parameters.
3Ease of operation
If crystalline brequinar sodium salt is formulated for solid oral dosage forms, then patient self-administration ease increases, but manufacturing predictability deteriorates
Solution Approach 1:
The patent applies preliminary action by pre-establishing stable polymorphic form C through controlled crystallization before formulation. By preparing the crystal structure in advance under optimized conditions, the patent creates a predictable and stable starting material that can be reliably incorporated into solid oral dosage forms, thereby enabling both patient self-administration ease and manufacturing predictability.
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 stable polymorphic form C of brequinar sodium salt facilitates the production of consistent solid dosage forms, ensuring stability during manufacturing, distribution, and storage, and allows for versatile pharmaceutical formulations.
Implementation Method 1
crystals of brequinar sodium salt exist in multiple polymorphic forms and that one of those forms, polymorphic form C, is most stable under ambient conditions
Data Source
AI summary
The invention provides compositions containing a stable crystalline form of brequinar and methods of making such composition. The invention also provides methods of using such compositions to treat a condition in a subject.