Paracetamol Aqueous Solution Oxidation Stabilization
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Solution Overview
Problem
Existing methods for producing stable injectable aqueous paracetamol solutions face challenges due to the susceptibility of paracetamol to hydrolysis and oxidation, requiring stringent oxygen-free conditions that are difficult to maintain, leading to reduced shelf-life and increased production complexity.
Innovation Solution
A method involving dissolving paracetamol in an aqueous solvent at elevated temperatures (65° C - 95° C) with a pH of 5.0 - 6.0, cooling under a nitrogen atmosphere, and adding cysteine hydrochloride and sodium hydroxide without stirring, which stabilizes the solution and allows for reduced oxygen levels without the need for extensive deoxygenation protocols.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If stringent oxygen-free conditions are imposed to prevent oxidation, then oxidation resistance is improved, but production complexity increases
Solution Approach 1:
The patent applies inert atmosphere by conducting the dissolution and cooling process under nitrogen gas flow, creating an oxygen-free environment that prevents oxidation of paracetamol without requiring complex vacuum systems or multiple deoxygenation steps
Solution Approach 2:
The patent applies preliminary action by removing dissolved oxygen from the aqueous solvent before paracetamol dissolution through nitrogen sparging and heating, preventing oxidation from the outset rather than requiring continuous complex oxygen exclusion during the entire process
2Reliability
If extensive deoxygenation protocols are implemented, then oxidation resistance is improved, but production time increases
Solution Approach 1:
The patent applies phase transitions by utilizing heating to evaporate dissolved oxygen from the aqueous solvent and by cooling the solution to below 40°C to optimize oxygen removal efficiency, achieving deoxygenation through temperature-driven phase changes rather than prolonged chemical processes
Solution Approach 2:
The patent applies skipping by consolidating multiple deoxygenation steps into a single integrated process of heating, nitrogen sparging, and cooling, eliminating the need for multiple separate deoxygenation protocols and reducing overall production time
3Reliability
If special equipment and protocols are used to ensure total oxygen absence, then oxidation resistance is improved, but manufacturing precision requirements increase
Solution Approach 1:
The patent applies intermediary by using nitrogen gas as a mediator to displace and remove dissolved oxygen from the aqueous solvent, providing a practical and controllable method for oxygen exclusion that does not require complex vacuum systems or ultra-precise oxygen sensing and control equipment
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 method results in a stable paracetamol formulation that is resistant to oxidation, enabling prolonged storage and simplifying the production process by eliminating the need for rigorous oxygen control, thereby extending shelf-life and reducing production complexity.
Implementation Method 1
paracetamol in aqueous solution is liable to undergo hydrolysis to form p-aminophenol
Implementation Method 2
adding cysteine hydrochloride and sodium hydroxide simultaneously to the solution without stirring... The method results in a stable paracetamol formulation that is resistant to oxidation
Data Source
AI summary
The present invention concerns a liquid formulation that is stable to oxidation and that is based on paracetamol in an aqueous solvent obtainable by the following steps: (i) dissolving in a reaction vessel paracetamol in an aqueous solvent having a temperature between 65° C. and 95° C., and having pH between 5.0 and 6.0; (ii) cooling the solution so formed to a temperature equal to or above 35° C. and below 40° C. under an atmosphere of nitrogen; (iii) adding cysteine hydrochloride and sodium hydroxide simultaneously to the solution without stirring; (iv) closing the reaction vessel, and stirring the solution of step iii) in a nitrogen atmosphere. It further relates to a method for preparing the formulation.