Carfilzomib Ready-to-Dilute Composition for Room-Temperature Stability
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Solution Overview
Problem
The commercially available formulation of carfilzomib is complex to reconstitute, prone to foam formation, and sensitive to degradation, requiring improved stability and ease of administration.
Innovation Solution
A room temperature stable, ready-to-dilute injectable formulation of carfilzomib is developed, comprising pharmaceutically acceptable derivatives, which can be mixed with an acidifying agent to form a reconstituted solution that is stable for at least six months at 25°C and 60% humidity, reducing impurities to less than 6%.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If lyophilized carfilzomib is reconstituted using sterile water for injection, then the drug becomes soluble and ready for administration, but foam formation occurs and the reconstitution process becomes complex and cumbersome
Solution Approach 1:
The patent changes the physical-chemical parameters of the formulation by using a solvent system containing N,N-dimethylacetamide and ethanol instead of plain sterile water. This parameter change prevents foam formation during reconstitution and simplifies the administration process, as the pre-diluted solution can be directly infused without complex reconstitution steps.
Solution Approach 2:
The formulation is prepared in advance as a pre-diluted solution containing carfilzomib, N,N-dimethylacetamide, and ethanol. This preliminary preparation eliminates the need for complex reconstitution procedures at the time of administration, as the solution is already optimized for direct infusion.
2Temperature
If carfilzomib is stored at room temperature, then storage cost is reduced and accessibility is improved, but the drug is sensitive to degradation and impurity formation
Solution Approach 1:
The patent creates a composite formulation system combining carfilzomib with specific excipients (N,N-dimethylacetamide and ethanol) that work synergistically to stabilize the drug at room temperature. This composite approach prevents degradation while maintaining ease of storage and administration.
Solution Approach 2:
The patent modifies the chemical environment parameters by incorporating specific solvents and excipients that create a stable formulation at room temperature. This parameter change prevents degradation pathways while maintaining the drug's activity, allowing storage at 25°C without significant impurity formation.
3Adaptability or versatility
If multiple vials are used for dilution, then dosing flexibility is achieved, but the administration process becomes more complex and time-consuming
Solution Approach 1:
The patent develops a universal formulation that can be directly diluted to various dosing concentrations in a single step using a standardized protocol. The pre-diluted formulation with optimized solvent system can be adapted to different patient requirements through simple dilution rather than complex multi-vial manipulation.
Data Source
AI summary
The invention is directed to room temperature stable injectable formulations of carfilzomib or its pharmaceutically acceptable derivatives thereof in the form of ready to dilute solution and concentrates with no hemolytic potential. Further the invention is directed to a method for treating patients with relapsed or refractory multiple myeloma by administering such composition.