Furosemide Composition With Tris Buffer for Stable Low-Volume Injection
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Furosemide, a potent loop diuretic, is poorly soluble and requires high concentrations for effective treatment, leading to stability issues in pharmaceutical formulations, especially when administered via auto-injection devices or minipumps, due to its limited oral bioavailability and need for intravenous or intramuscular delivery.
Innovation Solution
A pharmaceutical composition of furosemide with tris(hydroxymethyl)aminomethane (Tris) at a concentration of less than or equal to 40 mM and a pH value from about 8.0 to about 8.5, allowing for stable and higher concentration administration, suitable for subcutaneous and intravenous delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Volume of stationary object
If the concentration of furosemide is increased to reduce the volume of administration, then the volume of administration is reduced, but the stability of the pharmaceutical formulation deteriorates
Solution Approach 1:
The patent applies parameter changes by adjusting the pH value to a specific range (8.0-8.5) and controlling the concentration of Tris buffer (≤40 mM) to enable higher furosemide concentrations (10-30 mg/mL) while maintaining formulation stability. This resolves the contradiction by finding optimal parameter values that allow both reduced volume and maintained stability.
2Volume of stationary object
If the concentration of furosemide is increased to reduce the volume of administration, then the volume of administration is reduced, but additional challenges are presented for formulation stability
Solution Approach 1:
The patent changes critical formulation parameters including pH (8.0-8.5) and Tris buffer concentration (≤40 mM) to enable higher furosemide concentrations while maintaining reliability and stability of the pharmaceutical formulation, thus resolving the contradiction between reduced volume and maintained reliability.
3Reliability
If furosemide is administered intravenously or intramuscularly to patients with decompensated heart failure, then the therapeutic effect is achieved, but the complexity of administration increases
Solution Approach 1:
The patent uses Tris buffer as an intermediary substance that enables the formulation to be suitable for both intravenous and intramuscular administration, simplifying the administration process while maintaining therapeutic effectiveness. The buffer system facilitates easier delivery through various routes including patch pumps and injection devices.
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
Enables the administration of higher furosemide concentrations within a standard volume, maintaining stability and reducing osmolarity, facilitating self-administration through patch pumps and other devices.
Implementation Method 1
pharmaceutical composition of furosemide with tris(hydroxymethyl)aminomethane (Tris) at a concentration of less than or equal to 40 mM and a pH value from about 8.0 to about 8.5
Data Source
AI summary
A pharmaceutical composition and a method of administering the pharmaceutical composition to a patient suffering from edema, heart failure, kidney or liver disease or having symptoms thereof is disclosed. The pharmaceutical composition includes furosemide, or a pharmaceutically acceptable salt, hydrate or ester thereof and tris(hydroxymethyl)aminomethane. The furosemide is present in the pharmaceutical composition at a concentration from about 10 mg/mL to about 30 mg/mL and the tris(hydroxymethyl)aminomethane is present at a concentration of less than or equal to 40 mM. The pH value of the pharmaceutical composition is maintained between about 8.0 and about 8.5 for parenteral administration.