Furosemide Formulation with Tris Buffer for Subcutaneous Stability
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Solution Overview
Problem
Existing furosemide formulations for subcutaneous administration suffer from instability, high pH, and osmotic imbalances, leading to discomfort and poor patient compliance.
Innovation Solution
A stable, liquid pharmaceutical formulation is achieved by incorporating a molar excess of tris(hydroxymethyl)aminomethane (Tris) with a concentration greater than or equal to 50 mM and a pH between 7 to 8.5, ensuring the formulation is isosmotic, which enhances stability and suitability for subcutaneous delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If furosemide is formulated for subcutaneous administration with conventional pH adjusters, then the drug can be administered, but the formulation becomes unstable and requires high pH which causes discomfort and pain
Solution Approach 1:
The patent changes the pH parameter from conventional high pH (9-11) to a physiological range (7-8.5) by using Tris buffer instead of traditional pH adjusters, thereby improving patient comfort while maintaining formulation stability through the unique buffering capacity of Tris at this pH range
Solution Approach 2:
Tris(hydroxymethyl)aminomethane serves as an intermediary buffering agent that mediates between the acidic nature of furosemide and the physiological pH requirement, enabling stable formulation at comfortable pH levels without requiring extreme alkalinity
2Speed
If furosemide is administered intravenously, then rapid therapeutic effect is achieved, but it requires trained healthcare professionals and cannot be self-administered
Solution Approach 1:
The formulation enables self-service administration by allowing patients to administer the drug subcutaneously themselves using auto-injection devices or minipumps, eliminating the need for trained healthcare professionals while maintaining therapeutic effectiveness
3Ease of operation
If furosemide is administered orally, then convenience is improved, but absorption is highly variable due to limited solubility and decreased stability at acidic pH
Solution Approach 1:
The patent changes the administration route parameter from oral to subcutaneous, and simultaneously optimizes the pH parameter to physiological range, thereby achieving reliable bioavailability through direct absorption into the bloodstream while maintaining formulation stability
4Object-affected harmful factors
If the formulation pH is lowered to reduce discomfort, then patient comfort improves, but furosemide stability decreases due to acidic pH degradation
Solution Approach 1:
Tris buffer acts as an intermediary that protects furosemide from acidic pH degradation while allowing the formulation pH to be lowered to comfortable levels, thereby simultaneously improving patient comfort and maintaining drug stability through its buffering action
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 formulation provides improved stability, reduced discomfort, and increased patient compliance by maintaining physiological pH and osmotic balance, making it suitable for self-administration via devices like micropumps or patch devices.
Implementation Method 1
incorporating a molar excess of tris(hydroxymethyl)aminomethane (Tris) with a concentration greater than or equal to 50 mM and a pH between 7 to 8.5, ensuring the formulation is isosmotic, which enhances stability and suitability for subcutaneous delivery
Data Source
AI summary
The present teachings relate to liquid pharmaceutical formulations of furosemide, where the pharmaceutical formulations include a molar excess of tris(hydroxymethyl)aminomethane to furosemide, have a pH in the range of 7 to 8.5, and a concentration of tris(hydroxymethyl)aminomethane greater than or equal to about 50 mM. The present teachings can improve the stability of liquid pharmaceutical formulations including furosemide and the suitability of such pharmaceutical formulations for subcutaneous administration or delivery.