Ranitidine Composition Iron Removal NDMA Prevention
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Ranitidine compositions contain high levels of iron species, which lead to the formation of N-nitrosodimethylamine (NDMA), a probable human carcinogen, due to the presence of iron species during processing, transportation, and in raw materials.
Innovation Solution
Developing compositions with ranitidine or its pharmaceutically acceptable salts that have low iron species content, preferably less than 1 ppm, by avoiding contact with iron during production and using chelating agents like cysteamine to complex and remove iron species.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If ranitidine compositions are produced using conventional processing equipment, then production efficiency is maintained, but iron species contaminate the composition leading to NDMA formation
Solution Approach 1:
The patent removes iron species from the ranitidine composition through extraction using chelating agents that selectively bind and remove iron contaminants from the pharmaceutical composition, thereby eliminating the source of NDMA formation while preserving the therapeutic ranitidine compound
Solution Approach 2:
The patent introduces chelating agents as intermediary substances that mediate between the iron species and the ranitidine composition. These agents complex with iron species, forming removable complexes that prevent direct interaction between iron and ranitidine, thus preventing NDMA formation without affecting ranitidine efficacy
2Reliability
If iron species are removed from ranitidine compositions, then NDMA formation is reduced, but production complexity increases
Solution Approach 1:
The patent changes the chemical state of iron species by adjusting parameters such as pH, temperature, and chelating agent concentration to optimize iron complexation and removal efficiency. These parameter adjustments enable effective iron removal through standard pharmaceutical processing equipment without requiring complex specialized apparatus
Solution Approach 2:
The patent employs disposable or easily replaceable chelating agents that can be added in controlled amounts, perform their iron-binding function, and then be removed or degraded. This approach avoids the need for complex, expensive, or difficult-to-clean specialized equipment, maintaining production simplicity while ensuring iron removal
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 resulting compositions have significantly reduced NDMA content, ensuring safety and compliance with regulatory standards, even after storage under stability test conditions.
Implementation Method 1
the present inventors have surprisingly found alternatives to reduce the iron species content in compositions containing ranitidine... less than 1 ppm, preferably less than 900 ppb, more preferably less than 600 ppb and even more preferably less than 300 ppb of iron species that are not under complexed form with a chelating agent
Data Source
Figure 1
AI summary
The present invention concerns compositions containing ranitidine or one of its pharmaceutically acceptable salts having low iron species content. The present invention also concerns compositions having low content of iron species that are not under complexed form with a chelating agent and/or having low content of iron species that are partially or completely under complexed form with a chelating agent and/or having low content of iron species that are under complexed form with a chelating agent other than ranitidine and/or having low content of complexes formed between ranitidine and iron species. The present invention also concerns a process for the preparation of said compositions. The present invention also concerns the second medical use of said compositions.