Caspofungin Acetate Salt Succinate Buffer Stability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Caspofungin compositions are highly unstable, leading to the formation of degradation products and impurities during storage, with existing buffer systems contributing to this instability, necessitating a more effective stabilizing solution.
Innovation Solution
A composition comprising an acetate salt of caspofungin with succinate as a buffering agent, along with pharmaceutically acceptable excipients like sucrose and mannitol, is developed to enhance stability and reduce impurity formation during storage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If acetate buffer is used in caspofungin composition, then pH stability is improved, but degradation product formation increases
Solution Approach 1:
The patent changes the buffer system parameter from acetate to succinate, which fundamentally alters the chemical environment. Succinate buffer maintains pH stability while having different chemical interaction properties with caspofungin, thereby reducing degradation product formation compared to acetate buffer
Solution Approach 2:
Succinate buffer acts as an intermediary substance that mediates between the requirement for pH stability and the need to minimize degradation. It provides the necessary buffering capacity without promoting the hydrolysis or dimerization reactions that acetate buffer facilitates
2Object-generated harmful factors
If no buffering agent is used in caspofungin composition, then degradation product formation is reduced, but pH stability deteriorates
Solution Approach 1:
The patent introduces succinate buffer at optimized concentration levels, changing the buffering parameter from zero or low (in prior art) to a specific range that provides sufficient pH stability without excessive buffer capacity that could promote degradation
3Stability of the object's composition
If traditional buffer systems are used in caspofungin composition, then pH control is improved, but impurity formation increases
Solution Approach 1:
The patent changes the buffer system parameter from traditional acetate or tartrate buffers to succinate buffer, which has different chemical properties that reduce impurity formation during manufacturing and storage while maintaining adequate pH control
Solution Approach 2:
The patent converts the potential harm of having any buffer (which can promote degradation) into a benefit by selecting succinate buffer that provides necessary pH control while minimizing degradation and impurity formation compared to traditional buffer systems
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 use of succinate as a buffering agent in the caspofungin composition significantly reduces the formation of degradation products and impurities, providing improved stability compared to traditional acetate buffer systems and compositions without buffering agents.
Implementation Method 1
A composition comprising a) a pharmaceutically effective amount of an acetate salt of caspofungin; b) a pharmaceutically acceptable amount of one or more pharmaceutically acceptable excipients effective to form a lyophilized cake; and c) a pharmaceutically effective amount of a buffering agent, wherein said buffering agent is succinate
Data Source
Figure 1
Figure 2
Figure 3
AI summary
The present invention relates to a composition comprising caspofungin or a pharmaceutical acceptable salt thereof and succinate or lactate as a buffering agent.