Fosaprepitant Dimeglumine Liquid Formulation Stability
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Solution Overview
Problem
The current formulation of fosaprepitant dimeglumine for injection is costly to manufacture and store, and inconvenient to use due to its lyophilized form, which requires refrigeration and reconstitution, leading to stability issues and increased pharmacy time and labor costs.
Innovation Solution
A stable, ready-to-use injectable fosaprepitant dimeglumine solution is developed, incorporating pharmaceutically acceptable solvents, co-solvents, and excipients, such as propylene glycol and ethanol, to maintain chemical stability and ease of administration without the need for reconstitution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If fosaprepitant dimeglumine is formulated as a lyophilized powder, then stability is improved, but ease of manufacture and storage is worsened due to refrigeration requirements and reconstitution needs
Solution Approach 1:
The patent changes the physical state parameter from solid (lyophilized powder) to liquid (aqueous solution), and adjusts concentration parameters to achieve stability without refrigeration. The formulation uses specific excipients and pH adjustment to maintain stability in liquid form at room temperature, eliminating the need for refrigeration and reconstitution while preserving chemical stability.
Solution Approach 2:
The patent creates a ready-to-use formulation that eliminates the need for expensive refrigeration infrastructure and complex reconstitution equipment. The single-dose vial design with pre-mixed solution removes the need for repeated reconstitution operations, reducing overall manufacturing and storage costs despite the liquid form being more susceptible to degradation.
2Stability of the object's composition
If fosaprepitant dimeglumine is formulated as a lyophilized powder, then stability is improved, but ease of operation is worsened due to reconstitution requirements
Solution Approach 1:
The patent performs the reconstitution action in advance during manufacturing by pre-mixing the fosaprepitant dimeglumine with appropriate excipients to form a stable liquid formulation. This preliminary action eliminates the need for healthcare professionals to perform reconstitution at the time of administration, simply requiring injection of the pre-prepared solution.
Solution Approach 2:
The patent extracts and removes the reconstitution step from the administration process entirely. By formulating the drug as a ready-to-use liquid solution, the complex reconstitution operation is taken out of the clinical setting and completed during manufacturing, simplifying the administration process to a single injection step.
3Stability of the object's composition
If fosaprepitant dimeglumine is formulated as a lyophilized powder, then stability is improved, but loss of time is worsened due to reconstitution and warming steps
Solution Approach 1:
The patent performs all preparation actions including dissolution, pH adjustment, and stabilization during the manufacturing process. The final product is a ready-to-use liquid formulation that requires no time-consuming reconstitution or warming steps at the pharmacy, eliminating this time loss entirely.
4Ease of manufacture
If fosaprepitant dimeglumine is formulated as an aqueous solution, then ease of manufacture is improved, but stability is worsened due to degradation to aprepitant
Solution Approach 1:
The patent creates a composite formulation combining fosaprepitant dimeglumine with specific excipients including propylene glycol, ethanol, and pH adjustment agents. This composite system provides both stability and ease of manufacture, as the combination of ingredients prevents degradation while allowing simple liquid formulation and storage at room temperature.
Solution Approach 2:
The patent adjusts pH parameters and concentration levels to optimize stability in aqueous solution. By controlling these parameters, the formulation maintains chemical stability without requiring refrigeration or complex manufacturing processes, achieving both ease of manufacture and stability simultaneously.
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 solution provides a storage-stable, ready-to-use formulation that retains over 90% chemical stability for several months at various temperatures, reducing manufacturing and storage costs, and simplifying administration by eliminating the need for refrigeration and reconstitution.
Implementation Method 1
A stable, ready-to-use injectable fosaprepitant dimeglumine solution is developed, incorporating pharmaceutically acceptable solvents, co-solvents, and excipients, such as propylene glycol and ethanol, to maintain chemical stability
Data Source
AI summary
The present application provides a stable, ready-to-use fosaprepitant dimeglumine formulation which is easy to administer without need of any reconstitution step and has a desirable solubility, stability and safety profile. The concentration of the fosaprepitant dimeglumine in the liquid formulation is preferably less than about 80 mg/ml, or more preferably between about 20 mg/ml to about 60 mg/ml. In certain embodiments, the liquid formulation retains at least about 90% chemical stability of the fosaprepitant dimeglumine after storage for a commercially reasonable amount of time at a temperature between about 0° C. to about 40° C.