Dexamethasone Sodium Phosphate Liquid Formulation Stability
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Solution Overview
Problem
Current liquid pharmaceutical preparations of dexamethasone sodium phosphate and betamethasone sodium phosphate have low stability in aqueous solutions, leading to short shelf life and restrictive storage conditions, and are not palatable, especially when using propylene glycol as a solvent.
Innovation Solution
A stable liquid formulation of dexamethasone sodium phosphate is achieved by combining it with an aqueous solution of propylene glycol and cyclodextrins, such as hydroxypropyl beta cyclodextrin, along with a buffer system to maintain pH between 7 and 8, and optionally including antioxidant agents and polyethylene glycols, which enhances stability and palatability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If propylene glycol is used as a solvent in liquid pharmaceutical preparations, then stability of the active ingredient is improved, but palatability deteriorates and liver toxicity increases
Solution Approach 1:
The patent introduces antioxidants (vitamin C, vitamin E, alpha-tocopherol, ascorbic acid, ascorbate) as intermediary substances that protect the active ingredient from oxidation without using propylene glycol. These antioxidants act as mediators between the active ingredient and the aqueous environment, providing stability through chemical protection rather than through propylene glycol solvation, thereby avoiding its toxic effects.
Solution Approach 2:
The patent changes the chemical parameters of the formulation by using antioxidants with specific redox potentials and stability characteristics. By selecting antioxidants that maintain effectiveness at pH 7-8 and at room temperature, the formulation achieves stability through parameter optimization rather than relying on propylene glycol, thus avoiding its harmful effects while maintaining reliability.
2Object-affected harmful factors
If aqueous solutions are used for liquid pharmaceutical preparations, then palatability is improved, but stability deteriorates due to oxidation
Solution Approach 1:
Antioxidants are introduced as intermediary substances that protect the active ingredient from oxidation in the aqueous environment. These intermediaries (vitamin C, vitamin E, alpha-tocopherol, ascorbic acid, ascorbate) create a protective chemical environment that allows aqueous solutions to maintain both palatability and stability simultaneously.
Solution Approach 2:
The antioxidants create a chemically inert environment within the aqueous solution by scavenging oxygen and free radicals. This inert chemical atmosphere prevents oxidation of the active ingredient while maintaining the beneficial properties of aqueous solutions, including good palatability and safety.
3Duration of action of stationary object
If pH is adjusted to maintain stability, then shelf life is extended, but storage conditions become more restrictive
Solution Approach 1:
The patent optimizes the pH parameter to range from 7 to 8, which is slightly alkaline. This specific pH range was selected to maximize stability of the active ingredient against oxidation while maintaining compatibility with physiological conditions. The antioxidants work synergistically at this pH range to extend shelf life to 24 months at room temperature without requiring restrictive storage conditions.
Solution Approach 2:
The formulation achieves self-stabilization through the combination of antioxidants and pH control, eliminating the need for external stabilization measures such as refrigeration. The system maintains its own stability through the inherent properties of the antioxidants and the buffered pH environment, allowing simple storage conditions while extending shelf life.
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 formulation exhibits significantly improved stability and reduced toxicity compared to existing formulations, with extended shelf life and improved palatability, making it suitable for oral administration, especially for children and elderly patients.
Implementation Method 1
combining it with an aqueous solution of propylene glycol and cyclodextrins, such as hydroxypropyl beta cyclodextrin
Implementation Method 2
along with a buffer system to maintain pH between 7 and 8
Implementation Method 3
optionally including antioxidant agents and polyethylene glycols, which enhances stability and palatability
Data Source
AI summary
The present invention relates to stabilised liquid pharmaceutical preparations comprising dexamethasone or betamethasone, or salts thereof. In particular, the invention relates to liquid pharmaceutical preparations wherein dexamethasone or betamethasone, or salts thereof, are kept stably in solution at a pH ranging from 7 to 8 by means of a particular solubilising system comprising aqueous solutions of propylene glycol and/or polyglycols and/or linear or cyclic polyalcohols in combination with stabilising agents.