Aprepitant Emulsion Composition for Intravenous Infusion
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Solution Overview
Problem
Current aprepitant formulations for intravenous administration, such as Cinvanti®, require dilution and contain ethanol, which can lead to contamination risks and side effects like drowsiness, and have stability issues.
Innovation Solution
A ready-to-use emulsion composition of aprepitant with medium chain triglycerides that is free of ethanol, allowing direct intravenous infusion without dilution and is terminally sterilized for enhanced sterility and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If aprepitant is formulated as a water-soluble prodrug salt form (fosaprepitant dimeglumine), then water solubility is improved, but synthesis complexity and cost increase
Solution Approach 1:
The patent changes the physical state and solubility parameters of aprepitant by formulating it as an emulsion with medium chain triglycerides, allowing the drug to be administered without conversion to a prodrug, thus simplifying the synthesis process while maintaining water compatibility through emulsification
Solution Approach 2:
The patent extracts the solubility enhancement function from the prodrug approach and achieves it through emulsion formulation with medium chain triglycerides, eliminating the need for phosphate prodrug synthesis while maintaining water solubility and bioavailability
2Stability of the object's composition
If aprepitant emulsion is prepared using long-chain-triglycerides (soybean oil), then solubility and bioavailability are improved, but ethanol content increases causing drowsiness and contamination risks
Solution Approach 1:
The patent changes the triglyceride chain length parameter from long-chain to medium-chain triglycerides, which fundamentally alters the emulsion properties to eliminate ethanol content while maintaining solubility and bioavailability, thus removing the harmful side effects
Solution Approach 2:
The patent converts the harmful ethanol content in long-chain triglyceride emulsions into a beneficial formulation by using medium-chain triglycerides, which provide the necessary solubility and emulsification properties without any ethanol, thereby eliminating drowsiness and contamination risks
3Quantity of substance
If aprepitant emulsion requires dilution before administration, then concentration control is improved, but contamination risks and administration time increase
Solution Approach 1:
The patent optimizes the concentration parameter of the emulsion formulation to achieve a ready-to-use concentration that requires no dilution, thereby eliminating the contamination risks and time associated with dilution while maintaining proper dosage control
Solution Approach 2:
The patent performs the concentration optimization and emulsion stabilization actions during manufacturing, creating a ready-to-use formulation that is pre-prepared for administration, eliminating the need for post-manufacturing dilution and reducing contamination risks
4Stability of the object's composition
If aprepitant is formulated as oral nanoparticulate composition, then solubility problems are addressed, but bioavailability remains limited to 60-65%
Solution Approach 1:
The patent changes the administration route from oral to intravenous emulsion formulation, fundamentally altering the bioavailability parameter from 60-65% to near-complete bioavailability while maintaining solubility through the emulsion system
Solution Approach 2:
The patent introduces medium chain triglycerides as an intermediary emulsifying agent that facilitates the intravenous administration of aprepitant, enabling complete bioavailability while solving the solubility issue through the emulsion 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 emulsion composition provides a stable and effective aprepitant formulation that reduces ethanol-related side effects and contamination risks, maintaining potency and stability during storage and administration.
Implementation Method 1
emulsion compositions comprising aprepitant for the treatment of emesis. More specifically, the field of the invention relates to ready-to-use emulsion compositions of aprepitant comprising medium chain triglycerides for intravenous infusion administration
Implementation Method 2
terminally sterilized for enhanced sterility and stability
Data Source
AI summary
The present invention provides an emulsion composition comprising aprepitant for treatment of emesis. Particularly, the invention is a ready-to-use emulsion compositions comprising aprepitant and medium chain triglycerides for administration by intravenous infusion, wherein the emulsion composition is also free of ethanol. Further, the invention also provides processes of preparing such compositions and their use for the prevention and control of acute and delayed chemotherapy-induced nausea and vomiting, and/or for prevention of postoperative nausea and vomiting.