Furosemide Formulation With Tris Buffer for High-Concentration Stability
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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 a stable and higher concentration of furosemide, suitable for subcutaneous and intravenous administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Volume of moving 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 changes the pH parameter of the formulation to a specific range (pH 8.0-8.5) to enable higher furosemide concentrations while maintaining stability. This parameter change allows the formulation to achieve both reduced volume and maintained stability simultaneously
Solution Approach 2:
The patent introduces an intermediary substance (buffering agent) that mediates between the furosemide and the formulation environment. This intermediary allows the high concentration of furosemide to be maintained without compromising stability by buffering the pH within the optimal range
2Quantity of substance
If the concentration of furosemide is increased, then the therapeutic effectiveness is improved, but the stability of the pharmaceutical formulation deteriorates
Solution Approach 1:
The patent optimizes the pH parameter to a specific range (pH 8.0-8.5) which enables higher furosemide concentrations to be maintained without degradation. This parameter optimization allows simultaneous achievement of improved therapeutic effectiveness and maintained formulation stability
Solution Approach 2:
The patent employs an intermediary buffering agent that protects the furosemide from degradation at high concentrations. This intermediary substance maintains the pH within the optimal range, allowing high therapeutic concentrations to be achieved while preserving formulation stability
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 compatibility for treatment of conditions like edema and heart failure, using devices like patch pumps.
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.