Elagolix Pyrimethamine Eutectic Form A Stability
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Solution Overview
Problem
The existing form of Elagolix sodium, used as a GnRH receptor antagonist, is unstable under high temperature, high humidity, and light conditions, and exhibits high hygroscopicity, making it unsuitable for use as a pharmaceutical raw material.
Innovation Solution
The development of an eutectic form A of Elagolix and pyrimethamine, characterized by specific X-ray powder diffraction peaks and improved stability, which is achieved through a preparation method involving dissolution, addition of hydrochloric acid, and subsequent filtration and drying.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If Elagolix is produced as sodium salt form, then it can be prepared according to existing methods, but it exhibits poor stability under high temperature, high humidity and light conditions, and shows high hygroscopicity
Solution Approach 1:
The patent changes the chemical form parameter of Elagolix from sodium salt to a new crystal form (Form A), which fundamentally alters the physical and chemical properties including stability and hygroscopicity while maintaining the same active pharmaceutical ingredient
Solution Approach 2:
The patent creates a eutectic composite system by combining Elagolix with pyrimethamine in specific ratios, resulting in a new material with improved stability properties that neither component possesses alone
2Ease of manufacture
If Elagolix is produced as sodium salt form, then it can be prepared according to existing methods, but it exhibits high hygroscopicity under low humidity conditions
Solution Approach 1:
The patent changes the physical state parameter from amorphous sodium salt to crystalline Form A, which significantly reduces the surface energy and affinity for moisture, thereby lowering hygroscopicity
Solution Approach 2:
The eutectic composite of Elagolix and pyrimethamine creates a more stable crystal lattice structure that is less prone to absorbing moisture from the environment
3Ease of manufacture
If Elagolix is produced as amorphous form, then it can be prepared easily, but it is difficult to prepare crystal-form powder
Solution Approach 1:
The patent utilizes controlled phase transition from amorphous to crystalline state through specific processing conditions (solvent selection, temperature control, pH adjustment) to obtain stable crystal Form A with defined XRD patterns
Solution Approach 2:
The patent uses pyrimethamine as an intermediary substance that facilitates the formation of stable crystal Form A by acting as a template or structure-directing agent during the crystallization process
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 eutectic form A of Elagolix and pyrimethamine demonstrates high purity, excellent light stability, high temperature stability, and resistance to hygroscopicity, even under low humidity conditions, making it suitable for large-scale industrial production and use in pharmaceutical applications.
Implementation Method 1
an X-ray powder diffraction of the eutectic form A using Cu-Kα radiation has characteristic peaks at 2θ angles of 8.1±0.2°, 12.2±0.2°, 13.3±0.2° and 21.1±0.2°
Data Source
AI summary
Disclosed are eutectic form A of Elagolix and pyrimethamine, a preparation method therefor and a use thereof. Using Cu-Kα radiation, eutectic form A has characteristic peaks represented by a 2θ degree at 8.1±0.2°, 12.2±0.2°, 13.3±0.2° and 21.1±0.2° in an X-ray powder diffraction. Eutectic form A has a high purity, a good light radiation stability, a high temperature stability, a high humidity stability and an accelerated stability, is easy to store, and has a slow moisture absorption under the condition of relatively low humidity, wherein the weight gain of eutectic form A by moisture absorption is not more than 1.08% when the relative humidity increases from 0 to 60% RH. Production conditions for eutectic form A are easy to control, same has a simple preparation process and a stable quality, and is easy to industrially produce on a large-scale.