Hydrocortisone Sodium Phosphate Oral Solution Stability
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Solution Overview
Problem
Current pharmaceutical solutions for hydrocortisone sodium phosphate are not suitable for oral administration and face challenges with stability and preservation, particularly in multi-dose containers, due to oxidative degradation and microbial contamination, with existing preservatives posing safety concerns and being ineffective at higher pH levels.
Innovation Solution
Aqueous pharmaceutical solutions comprising hydrocortisone sodium phosphate with propylene glycol and sorbitol, maintained at a pH of 7.0 to 8.0, which inhibit microbial growth and oxidation, allowing for storage in multi-dose containers without additional toxic stabilizers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional preservatives (sodium bisulfite, sodium formaldehyde sulfoxylate) are used to stabilize hydrocortisone sodium phosphate solutions, then oxidative degradation is prevented, but safety concerns arise particularly for asthmatic patients and the preservatives become ineffective at higher pH levels
Solution Approach 1:
The patent changes the chemical parameters by replacing conventional preservatives with a different chemical system (benzoic acid and/or sorbic acid) that functions effectively at the required pH range of 7.0-8.0 for hydrocortisone sodium phosphate stability
Solution Approach 2:
The patent introduces alternative preservative agents (benzoic acid and/or sorbic acid) as intermediary substances that mediate between the need for oxidation prevention and the safety requirements, particularly for sensitive patient populations
2Ease of operation
If multi-dose containers are used for oral administration, then patient convenience is improved, but microbial contamination and oxidative degradation occur upon repeated opening
Solution Approach 1:
The patent applies preservatives and antioxidants in advance to the formulation, creating a protective system that prevents microbial growth and oxidation before the container is opened and throughout multiple uses
Solution Approach 2:
The patent creates a chemically inert environment within the solution through the use of antioxidants and preservatives that prevent reactive degradation processes, effectively creating a protected microenvironment that remains stable despite repeated exposure to external conditions
3Stability of the object's composition
If additional stabilizing agents are added to prevent degradation, then solution stability is improved, but toxicological safety concerns increase
Solution Approach 1:
The patent selects stabilizing agents with specific safety profiles and appropriate concentrations, changing the parameter of chemical composition to achieve stability while maintaining safety for oral administration
Solution Approach 2:
The patent uses preservatives and antioxidants that are recognized as safe for oral use and can be effectively used in multi-dose formulations without requiring complex additional stabilization systems
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 preservation after first use, remaining physicochemically stable and effectively preventing microbial growth for at least three months at room temperature, even with repeated openings, without the need for additional stabilizing agents that could raise safety issues.
Implementation Method 1
U.S. Pat. No. 2,970,944 discloses that although aqueous solutions of steroid phosphate salts are colourless and free from insoluble matter when freshly made, these solutions, begin to deteriorate upon standing at room temperature or at elevated temperatures. The deterioration is evidenced by the formation of a precipitate and by the development of a yellow colour. This condition may be due to hydrolysis of the ester, whereby the free alcohol is precipitated or to other factors such as oxidative degradation.
Implementation Method 2
U.S. Pat. No. 2,970,944 discloses that although aqueous solutions of steroid phosphate salts are colourless and free from insoluble matter when freshly made, these solutions, begin to deteriorate upon standing at room temperature or at elevated temperatures. The deterioration is evidenced by the formation of a precipitate and by the development of a yellow colour. This condition may be due to hydrolysis of the ester, whereby the free alcohol is precipitated
Implementation Method 3
Technical Problem: Current pharmaceutical solutions for hydrocortisone sodium phosphate are not suitable for oral administration and face challenges with stability and preservation, particularly in multi-dose containers, due to oxidative degradation and microbial contamination
Data Source
AI summary
Pharmaceutical solutions suitable for oral administration comprising hydrocortisone sodium phosphate as active ingredient and a pharmaceutically acceptable aqueous carrier comprising sorbitol and propylene glycol. The pH of the solution is adjusted to the range of 7.0 to 8.0. The solutions of the present invention are physicochemically stable and effectively preserved even in the absence of further stabilizing agents and antimicrobial preservatives.