Controlled Release Injectable Aprepitant Formulation
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Solution Overview
Problem
Current treatments for chemotherapy-induced nausea and vomiting (CINV) using neurokinin 1 receptor antagonists like Aprepitant or Fosaprepitant face challenges with side effects, patient compliance, and the need for frequent dosing, which can lead to discomfort and increased corticosteroid use.
Innovation Solution
A controlled release injectable formulation of Aprepitant or Fosaprepitant is developed, providing a stable, long-acting, and uniform release over an extended period, eliminating the need for frequent dosing and reducing corticosteroid use, while maintaining efficacy in preventing CINV symptoms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If frequent dosing of neurokinin 1 receptor antagonists is used to prevent CINV symptoms, then therapeutic efficacy is maintained, but patient compliance deteriorates and discomfort increases
Solution Approach 1:
The patent segments the drug delivery process by using a two-component system where Component A (aqueous phase) and Component B (lipid phase) are mixed at the time of administration. This segmentation allows the drug to be stored stable in separate components and only forms the controlled-release formulation when needed, enabling single-dose administration while maintaining therapeutic efficacy.
Solution Approach 2:
The patent applies preliminary action by pre-formulating the drug in a controlled-release matrix that gradually releases the neurokinin 1 receptor antagonist over an extended period. This eliminates the need for frequent dosing while maintaining therapeutic efficacy, as the drug is released slowly over days rather than requiring multiple administrations.
2Reliability
If multiple dosing of 5-HT3 receptor antagonist is used to prevent delayed CINV, then prevention of delayed symptoms is achieved, but adverse effects such as headache and constipation increase
Solution Approach 1:
The patent merges the neurokinin 1 receptor antagonist with a 5-HT3 receptor antagonist in a single controlled-release injectable formulation. This combination allows both drugs to be administered together with coordinated release profiles, achieving prevention of both acute and delayed CINV while reducing the need for multiple separate dosing regimens and associated adverse effects.
Solution Approach 2:
The patent ensures continuity of useful action by designing a controlled-release system that maintains therapeutic levels of both neurokinin 1 and 5-HT3 antagonists continuously over an extended period. This continuous release provides sustained prevention of CINV symptoms without the peaks and valleys associated with multiple dosing, thereby reducing adverse effects.
3Reliability
If corticosteroids are added to treatment regimen to prevent delayed CINV, then prevention efficacy is improved, but side effects increase
Solution Approach 1:
The patent changes the pharmacokinetic parameters of the treatment regimen by using a controlled-release injectable formulation that maintains steady drug levels over time. This eliminates the need for high-dose corticosteroid pulses while maintaining prevention efficacy, as the sustained release of neurokinin 1 and 5-HT3 antagonists provides continuous protection against CINV without corticosteroid-related side effects.
4Reliability
If oral administration of Aprepitant is used, then therapeutic effect is achieved, but patient compliance deteriorates due to frequent dosing requirements
Solution Approach 1:
The patent replaces the mechanical system of oral administration with parenteral (injectable) administration. This substitution eliminates the need for patient actions such as swallowing pills and adhering to complex oral dosing schedules, thereby improving compliance while maintaining therapeutic effect through controlled release over an extended period.
Data Source
AI summary
The present invention relates to a controlled release sterile injectable formulation in the form of solution, suspension or sol-gel formulation for intramuscular or subcutaneous administration comprising a therapeutically effective amount of a neurokinin 1 receptor antagonist, in particular Aprepitant or Fosaprepitant or pharmaceutical acceptable salt, derivative or metabolite thereof. It also relates to a process for developing such formulations.