Ready-to-use Ascorbic Acid Compositions for Parenteral Stability
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Solution Overview
Problem
Current pharmaceutical formulations of ascorbic acid for parenteral administration, such as those used to treat scurvy, require dilution before use and have stability issues due to oxidation, leading to challenges in maintaining effective concentrations and preventing contamination or miscalculations in dosing.
Innovation Solution
Development of ready-to-use pharmaceutical compositions of ascorbic acid that do not require reconstitution or dilution, stabilized with appropriate excipients like chelation agents and stored at controlled room temperature, ensuring stability and safety for at least one month.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If ascorbic acid is formulated as an aqueous solution for parenteral administration, then ease of operation is improved, but stability deteriorates due to oxidation
Solution Approach 1:
The ascorbic acid composition is prepared in advance with stabilizing agents (chelating agents like EDTA, antioxidants) and proper pH adjustment (to acidic range 3-6) to prevent oxidation during storage. This preliminary stabilization allows the solution to be ready for immediate use without requiring last-minute preparation or dilution, while maintaining stability throughout the intended shelf life and during administration.
2Stability of the object's composition
If ascorbic acid is provided in concentrated form requiring dilution, then stability is improved, but device complexity and risk of error increase
Solution Approach 1:
The concentration of ascorbic acid in the composition is carefully controlled within the range of 5-50 mg/mL, which is low enough to allow direct intravenous administration without requiring dilution, yet high enough to provide therapeutic efficacy. This parameter optimization eliminates the need for additional dilution steps, reducing administration complexity and minimizing risks of dosing errors while maintaining stability through proper formulation with stabilizing agents.
3Ease of operation
If ascorbic acid is stored in aqueous solution, then ease of operation is improved, but loss of substance increases due to degradation
Solution Approach 1:
Chelating agents (such as EDTA) and antioxidants are introduced as intermediary substances that bind to metal ions and prevent oxidative degradation of ascorbic acid. These intermediaries act as protective agents that sacrifice themselves or neutralize harmful oxidizing species, thereby preventing the degradation of ascorbic acid during storage and ensuring that the full therapeutic dose remains active and effective when administered.
4Productivity
If ascorbic acid is administered without dilution, then productivity is improved, but reliability may worsen due to stability concerns
Solution Approach 1:
The composition is pre-formulated with stabilizing agents and proper pH adjustment to ensure stability throughout storage and administration. This preliminary stabilization ensures that the ascorbic acid remains intact and effective, providing reliable dosing without requiring dilution. The inclusion of chelating agents and antioxidants in the correct concentrations guarantees that the therapeutic dose delivered is accurate and consistent.
Solution Approach 2:
The need for mechanical dilution steps is replaced by a chemically stable formulation that can be administered directly. Instead of requiring physical dilution with sterile water or other vehicles (which introduces opportunities for contamination and dosing errors), the composition is chemically engineered to be stable and effective at its formulation concentration, eliminating the mechanical dilution step while maintaining reliability.
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 ready-to-use compositions maintain therapeutic efficacy for treating scurvy, reduce waste and risk of contamination, and simplify administration by eliminating the need for pre-administration dilution, while ensuring stability and safety.
Implementation Method 1
stabilized with appropriate excipients like chelation agents
Implementation Method 2
Ascorbic acid is stable in dry conditions but is easily oxidized in aqueous solution. The degradation of ascorbic acid has been considered one of the major causes of quality and color changes within pharmaceutical preparations during processing and storage of ascorbic acid in aqueous solution. Dehydroascorbic acid, the oxidized form of ascorbic acid, is highly unstable in an aqueous solution
Data Source
AI summary
The invention described here provides ready-to-use (RTU) pharmaceutical compositions in single unit dose packaging, such compositions including ascorbic acid compound(s), such as sodium ascorbate, and one or more pharmaceutically acceptable excipients (e.g., a carrier and optionally other agents, such as a tonicity agent, a chelator, or both). The compositions provided by the invention are stable when stored at 20° C. to 25° C.±2° C. for at least about 3 months. Compositions provided by the invention comprise an osmolality of between about 270 mOsm/kg to about 340 mOsm/kg and do not require dilution or further manipulation prior to use. In certain aspects, the invention comprises methods of using such compositions in the treatment of diseases, conditions, or symptoms related to vitamin C deficiency, such as, in specific embodiments, scurvy.