Pemetrexed Disodium Liquid Composition for Stable, Ready-to-Use Dosing
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Solution Overview
Problem
The existing pemetrexed disodium lyophilized powder injection requires reconstitution and dilution, which can lead to dose errors and microbial contamination risks, necessitating a more stable and convenient dosage form for clinical use.
Innovation Solution
A pemetrexed disodium liquid composition is developed, comprising active pharmaceutical ingredients and stabilizers such as organic solvents, pH adjusters, and antioxidants, with a preparation method that includes nitrogen introduction to minimize oxygen content, ensuring stability and safety.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If pemetrexed disodium is formulated as a lyophilized powder injection requiring reconstitution and dilution, then the drug can be stored stably, but the preparation process introduces dose errors and microbial contamination risks
Solution Approach 1:
The patent extracts the reconstitution and dilution steps from the administration process by providing a ready-to-use liquid formulation. The pemetrexed disodium is directly dissolved in water for injection at the required concentration (5-50 mg/mL), eliminating the need for separate reconstitution and dilution operations that were required with the lyophilized powder form.
Solution Approach 2:
The drug is prepared in advance in a stable liquid form with optimized pH (5.0-9.0) and appropriate stabilizers added during manufacturing. This preliminary preparation ensures dosage accuracy and microbial safety before the product reaches the clinical setting, removing the burden of complex preparation from the administration phase.
2Reliability
If pemetrexed disodium is formulated as a lyophilized powder injection, then the drug maintains stability during storage, but the reconstitution process increases microbial contamination risk
Solution Approach 1:
The patent removes the reconstitution step that creates microbial contamination risk. The liquid formulation is manufactured under controlled sterile conditions and supplied ready for use, extracting the vulnerable reconstitution operation from the clinical workflow.
Solution Approach 2:
The patent changes the physical state parameter from solid (lyophilized powder) to liquid form, and optimizes pH parameters (5.0-9.0) to ensure both stability and microbial safety. The liquid formulation maintains stability without requiring the powder form's protective dry state, thereby eliminating contamination risks associated with reconstitution.
3Stability of the object's composition
If pemetrexed disodium is prepared as a liquid composition with stabilizers, then the physical and chemical stability is improved, but the formulation complexity increases
Solution Approach 1:
The patent optimizes pH parameters to 5.0-9.0 range and controls oxygen content below 5 mg/L through nitrogen introduction during preparation. These parameter optimizations ensure physical and chemical stability of the liquid formulation without requiring complex stabilizing systems.
Solution Approach 2:
The patent introduces nitrogen gas during preparation to create an inert atmosphere that minimizes oxygen content to less than 5 mg/L. This prevents oxidation and chemical degradation of pemetrexed disodium, ensuring long-term stability without requiring additional chemical stabilizers that would increase formulation complexity.
4Quantity of substance
If the organic solvent content is increased to improve solubility, then the drug concentration can be increased, but the risk of hemolysis and irritation increases
Solution Approach 1:
The patent optimizes the concentration of organic solvent (polyethylene glycol 400) to a specific range of 70-300 mg/mL, with preferred concentrations of 90, 180, 260, or 280 mg/mL. This optimized parameter range achieves adequate solubility for drug concentrations of 5-50 mg/mL while maintaining safety by avoiding hemolysis and irritation.
Solution Approach 2:
The patent creates a composite formulation combining pemetrexed disodium with polyethylene glycol 400 as the organic solvent component. This composite system achieves enhanced solubility and stable drug concentration while the specific ratio of components is optimized to minimize harmful effects such as hemolysis and irritation.
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 liquid composition provides improved physical and chemical stability, reduces microbial contamination risk, and simplifies administration, making it suitable for industrial production and clinical use.
Implementation Method 1
a nitrogen introducing procedure; the nitrogen introducing procedure can be selected from liquid preparation nitrogen introducing and/or nitrogen filling
Implementation Method 2
the stabilizer is selected from one or more of an organic solvent, a pH adjuster, and an antioxidant
Data Source
AI summary
A pemetrexed disodium liquid composition, a preparation method therefor and use thereof are provided. The pemetrexed disodium liquid composition contains an active pharmaceutical ingredient and a stabilizer. The active pharmaceutical ingredient is one or more of pemetrexed disodium, and a pharmaceutically acceptable complex, a salt, a solvate and a hydrate of pemetrexed disodium. The stabilizer is one or more of an organic solvent, a pH regulator and an antioxidant.