Melatonin Oral Solution Stability via Propylene Glycol and Sorbitol
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current melatonin oral solutions face challenges with solubility, stability, and antimicrobial preservation, particularly in multi-dose containers, due to air oxidation and the use of potentially harmful preservatives, which affect their shelf life and safety.
Innovation Solution
Aqueous oral pharmaceutical solutions comprising melatonin with propylene glycol and sorbitol within specific concentration ranges, pH adjustment between 3.0 and 5.0, and the absence of certain preservatives, providing physicochemical stability and antimicrobial activity without the need for additional preservatives.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If melatonin is dissolved in water to create an oral solution, then the solution is suitable for oral administration, but the solubility is poor (only 2 mg/ml at 20°C)
Solution Approach 1:
The patent uses propylene glycol as an intermediary substance to bridge the solubility gap. Propylene glycol acts as a co-solvent that is miscible with both water and melatonin, enabling higher concentrations of melatonin to be dissolved in the aqueous oral solution without using harmful substances like ethanol.
2Ease of manufacture
If melatonin oral solutions are stored at room temperature to avoid refrigeration costs, then distribution and storage costs are reduced, but the solutions become unstable over time
Solution Approach 1:
The patent modifies the chemical parameters of the solution by adjusting pH to a specific range (3.0-5.0) and optimizing the concentration ratio of propylene glycol to water. These parameter changes create a stable environment for melatonin at room temperature, preventing degradation without requiring refrigeration.
Solution Approach 2:
The patent creates a composite solvent system combining propylene glycol and water in specific proportions. This composite material provides both the solubility enhancement needed for high melatonin concentrations and the stability required for room temperature storage, eliminating the need for refrigeration while maintaining solution integrity.
3Ease of operation
If multi-dose containers are used for melatonin solutions, then convenience of administration is improved, but air oxidation and microbial contamination increase
Solution Approach 1:
The patent converts the harmful effect of air exposure in multi-dose containers into a beneficial outcome by formulating the solution with antioxidants and a pH buffer system. The pH 3.0-5.0 range creates an environment that is inherently resistant to microbial growth, while the antioxidant components neutralize oxidation from air exposure, allowing multi-dose containers to remain safe and effective.
4Reliability
If common preservatives are used to prevent microbial contamination, then antimicrobial activity is improved, but safety and toxicity issues arise
Solution Approach 1:
The patent enables the solution to preserve itself without adding harmful preservatives. By formulating with pH 3.0-5.0 and specific concentrations of propylene glycol (20-500 mg/ml) and sorbitol (20-400 mg/ml), the solution creates an environment that is naturally resistant to microbial growth. The propylene glycol and sorbitol combination provides both solubility enhancement and inherent antimicrobial properties, making additional preservatives unnecessary.
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 solutions exhibit excellent shelf life and antimicrobial preservation, maintaining stability and safety without using ethanol or common preservatives, even when stored at room temperature and opened frequently, reducing the risk of microbial contamination and oxidation.
Implementation Method 1
aqueous oral pharmaceutical solutions comprising melatonin with propylene glycol and sorbitol within specific concentration ranges
Implementation Method 2
pH adjustment between 3.0 and 5.0, and the absence of certain preservatives, providing physicochemical stability
Implementation Method 3
Current melatonin oral solutions face challenges with solubility, stability, and antimicrobial preservation, particularly in multi-dose containers, due to air oxidation
Data Source
AI summary
Pharmaceutical solutions suitable for oral administration comprising melatonin as active ingredient and a pharmaceutically acceptable aqueous carrier comprising propylene glycol and sorbitol. The pH of the solution is adjusted to the range of 3.0 to 5.0. The solutions of the present invention are physicochemically stable and effectively preserved even in the absence of further stabilizing agents and antimicrobial preservatives.