Torsemide Cyclodextrin Composition for Physiological pH Delivery
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Solution Overview
Problem
Torsemide, a loop diuretic, is poorly soluble at physiological pH, leading to challenges in parenteral administration, including subcutaneous administration and use in infusion fluids, which can result in precipitation and drug irritation.
Innovation Solution
A pharmaceutical composition comprising torsemide and a β-cyclodextrin, specifically a sulfobutyl ether derivative like captisol, with a molar ratio greater than 2 and a pH of 7.0 to 7.8, enhancing solubility and stability for subcutaneous and intravenous administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If the pH of the formulation is increased to 9.0 or higher to improve torsemide solubility, then solubility is improved, but this precludes subcutaneous administration and use in certain infusion fluids due to precipitation and stability issues
Solution Approach 1:
The invention changes the pH parameter from conventional high pH (9.0 or higher) to physiological pH (7.0-7.8), and simultaneously changes the formulation composition by incorporating cyclodextrins (10%-40% w/w) to achieve enhanced solubility at the new pH level, enabling subcutaneous and intravenous administration
Solution Approach 2:
Cyclodextrins are introduced as intermediary substances that form inclusion complexes with torsemide, mediating between the drug and the physiological pH environment to maintain solubility without requiring high pH conditions
2Adaptability or versatility
If the pH of the formulation is reduced to achieve physiological pH compatibility, then administration compatibility is improved, but torsemide precipitation occurs and formulation stability is impacted
Solution Approach 1:
The invention adjusts the pH parameter to physiological range (7.0-7.8) while simultaneously modifying the formulation composition by adding cyclodextrins (10%-40% w/w) to prevent drug precipitation and maintain stability at the new pH level
Solution Approach 2:
Cyclodextrins act as intermediary agents that stabilize torsemide in the physiological pH environment by forming protective inclusion complexes, preventing precipitation while maintaining formulation stability
3Reliability
If conventional loop diuretics are used for edema management, then treatment is provided, but they have shorter duration of action and lower bioavailability compared to torsemide
Solution Approach 1:
The pharmaceutical composition leverages the inherent pharmacological properties of torsemide (prolonged duration of action, higher bioavailability) and enhances them through optimized formulation with cyclodextrins, allowing the drug to self-deliver sustained therapeutic effect without requiring frequent dosing
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 composition allows for effective delivery of torsemide with minimal adverse effects, enabling higher doses in smaller volumes and compatibility with infusion fluids, suitable for treating conditions like edema, heart failure, and liver disease.
Implementation Method 1
a pharmaceutical composition containing torsemide or a pharmaceutically acceptable form of the torsemide and a β-cyclodextrin... the molar ratio of β-cyclodextrin to torsemide is greater than 2
Data Source
Figure 1
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 thereofaredisclosed. The pharmaceutical composition includes torsemide, or a pharmaceutically acceptable salt, hydrate or esterthereof and a cyclodextrin.