Plinabulin Monohydrate Crystalline Form Stability
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Solution Overview
Problem
Current forms of plinabulin have stability and purity issues, with polymorphs showing weight change and degradation during drying and humidity tests, and existing compositions have high impurity levels, affecting their pharmaceutical efficacy and safety.
Innovation Solution
Development of a stable crystalline form of plinabulin monohydrate (Form 1) with specific X-ray powder diffraction patterns and high purity, along with methods for preparing plinabulin compositions with minimal impurities, including processes involving solvent systems and purification steps to achieve high-purity plinabulin formulations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing plinabulin forms are used, then pharmaceutical activity is achieved, but stability and purity issues occur with weight change and degradation during drying and humidity tests
Solution Approach 1:
The patent applies parameter changes by transforming plinabulin from an amorphous or unstable crystalline state to a stable crystalline monohydrate form through controlled crystallization processes. This phase transition changes the physical and chemical parameters of plinabulin, resulting in improved stability during drying and humidity tests while maintaining pharmaceutical activity
Solution Approach 2:
The patent creates a composite material system by forming plinabulin monohydrate, which combines plinabulin molecules with water molecules in a specific crystalline structure. This composite form enhances the stability and purity of plinabulin compared to its anhydrous form, resolving the contradiction between maintaining pharmaceutical activity and improving compositional stability
2Reliability
If existing plinabulin compositions are used, then therapeutic effect is achieved, but high impurity levels affect pharmaceutical efficacy and safety
Solution Approach 1:
The patent applies extraction by removing impurities from plinabulin compositions through purification processes. The crystallization method selectively extracts pure plinabulin monohydrate from impure starting materials, achieving high purity levels (>90% by weight) while maintaining the therapeutic efficacy of plinabulin
Solution Approach 2:
The patent applies preliminary action by performing purification and crystallization steps before final formulation. The plinabulin is pre-purified to high purity levels and converted to the stable monohydrate form before being incorporated into pharmaceutical compositions, ensuring both efficacy and safety
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 crystalline form of plinabulin monohydrate (Form 1) maintains stability during drying and humidity tests, and high-purity compositions ensure low impurity levels, enhancing pharmaceutical efficacy and safety profiles.
Implementation Method 1
Development of a stable crystalline form of plinabulin monohydrate (Form 1) with specific X-ray powder diffraction patterns
Data Source
AI summary
Disclosed herein are plinabulin polymorphs, compositions, their use and preparation as therapeutic agents. In particular, some embodiments relate to plinabulin monohydrate in a crystalline form.