Plinabulin Micelle Composition for Water Solubility and Stability
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Solution Overview
Problem
There is a need for an injectable formulation of Plinabulin with appropriate physicochemical properties that enhances water solubility, stability, and extends biological half-life.
Innovation Solution
A Plinabulin micelle composition is prepared by mixing poly(ethylene glycol) 15-hydroxystearate with propylene glycol, encapsulating Plinabulin in micelles, and diluting it with a D5W solution to form a stable injectable formulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If Plinabulin is formulated as a single agent, then the drug can be administered, but the water solubility is insufficient and stability is poor
Solution Approach 1:
The patent employs a composite micellar formulation consisting of Plinabulin encapsulated within poly(ethylene glycol) 15-hydroxystearate micelles in propylene glycol solution. This composite structure combines the hydrophobic drug with hydrophilic surfactant micelles, achieving enhanced water solubility while maintaining drug stability through encapsulation.
2Duration of action of moving object
If Plinabulin is administered without micelle encapsulation, then the administration is simple, but the biological half-life is short
Solution Approach 1:
The patent introduces poly(ethylene glycol) 15-hydroxystearate micelles as an intermediary carrier system. These micelles serve as a mediator between the hydrophobic Plinabulin and the aqueous physiological environment, extending the drug's circulation time and biological half-life through enhanced permeability and retention effects while providing a relatively simple preparation process.
3Manufacturing precision
If Plinabulin is dissolved directly in water, then the preparation is simple, but the encapsulation efficiency is low and impurity content is high
Solution Approach 1:
The patent optimizes several parameters including the surfactant-to-drug ratio, propylene glycol concentration (10-50%), and incubation temperature (25-37°C) to achieve high encapsulation efficiency. These parameter optimizations maintain relatively simple preparation procedures while significantly improving the quality of the micellar formulation.
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 formulation exhibits excellent electrochemical, dilution, and storage stability, with high encapsulation efficiency and low impurity content, suitable for clinical use.
Implementation Method 1
mixing poly(ethylene glycol) 15-hydroxystearate with propylene glycol at 35°C-65°C to prepare a clear mixed solution; mixing the clear mixed liquid from step 1) with Plinabulin at 35°C-65°C and stirring to obtain the Plinabulin micelle composition
Data Source
Figure 1~2
AI summary
A Plinabulin micelle composition and a preparation method therefor. Specifically, the Plinabulin micelle composition is essentially composed of Plinabulin, polyoxyl 15-hydroxystearate and propylene glycol, wherein at least part of Plinabulin is encapsulated in the micelle, and can be mixed with a dextrose injection to obtain the Plinabulin micelle preparation for injection, which is used for the clinical treatment of tumor diseases. Both the Plinabulin micelle composition and the micelle preparation have an excellent electrochemical stability, dilution stability and storage stability.