Nitroxoline Base Addition Salts for Solubility and Stability
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Solution Overview
Problem
Nitroxoline has low solubility in water and stability issues, leading to challenges in drug formulation and administration, including rapid metabolism and frequent dosing, which affects bioavailability and compliance.
Innovation Solution
Development of novel base addition salts of nitroxoline, such as nitroxoline choline and amine salts, with improved solubility and stability, allowing for optimized pharmaceutical compositions and formulations, including controlled release and injectable forms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If nitroxoline is used in immediate-release formulations, then rapid absorption occurs, but frequent dosing is required due to short half-life and low solubility
Solution Approach 1:
The patent applies parameter changes by converting nitroxoline from its base form to salt forms (sodium salt, potassium salt, calcium salt, magnesium salt) which fundamentally alter its solubility parameters. These salt forms exhibit improved aqueous solubility compared to the base compound, enabling controlled release formulations that maintain drug levels over extended periods and reduce dosing frequency while preserving rapid absorption characteristics
2Reliability
If nitroxoline is administered to maintain continuous drug exposure, then adequate bioavailability is achieved, but patient compliance deteriorates due to frequent dosing
Solution Approach 1:
The patent employs parameter changes by developing salt forms of nitroxoline with modified solubility and release characteristics. The sodium, potassium, calcium, and magnesium salts provide sustained release profiles that maintain continuous drug exposure and adequate bioavailability while reducing dosing frequency to twice daily or less, thereby significantly improving patient compliance without compromising therapeutic efficacy
3Productivity
If nitroxoline is manufactured at high temperatures, then processing efficiency improves, but stability deteriorates due to sublimation causing contamination
Solution Approach 1:
The patent applies parameter changes by transforming nitroxoline into salt forms (sodium, potassium, calcium, magnesium salts) that exhibit enhanced thermal stability compared to the base compound. These salt forms resist sublimation at manufacturing temperatures, preventing contamination of equipment and product while allowing efficient high-temperature processing and formulation manufacturing
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 novel salts enhance solubility and stability, enabling less frequent dosing, improved bioavailability, and reduced adverse effects, while facilitating the development of liquid compositions and sustained-release formulations.
Implementation Method 1
Base addition salts of nitroxoline according to the invention have improved solubility in water and other aqueous media
Implementation Method 2
Base addition salts of nitroxoline according to the invention have improved solubility in water and other aqueous media, and improved stability as compared to nitroxoline
Data Source
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AI summary
Novel base addition salts of nitroxoline with improved solubility and increased urine secretion under physiological conditions are described. Pharmaceutical compositions and methods of treatment using the pharmaceutical compositions are also described. The present invention relates to novel base addition salts of nitroxoline having improved solubility and stability in aqueous solutions as compared to nitroxoline or other salts of nitroxoline. The present invention also relates to pharmaceutical compositions comprising the base addition salts of nitroxoline, and methods of treating or preventing diseases, disorders, and conditions using these pharmaceutical compositions.