Methods and assemblies for control of formation of nitrosamine impurities in solid active pharmaceutical ingredients
AssigneeOlon S.P.A.
InventorsNatwar PANCHAL, Madhu SADASHIVAIAH, Venu Babu GORIPARTHI, Sanjani VANGULE, Sandip PAWAR
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Abstract
The present invention relates to the field of impurities control, in particular genotoxic impurities, in active pharmaceutical ingredients (APIs). In particular, the present invention relates to a packaging method and assembly for the control of the formation of a nitrosamine, for example 1-methyl-4-nitrosopiperazine (MeNP), in a solid active pharmaceutical ingredient (API), for example rifampicin, during storage.
Claims20
A packaging method for control of formation of nitrosamine in solid active pharmaceutical ingredient (API), the packaging method comprising:
- providing the solid API with a predetermined starting content of a nitrosamine selected from the group consisting of 1-methyl-4-nitrosopiperazine, 1-cyclopentyl-4-nitrosopiperazine, and N-Nitroso-3-azabicyclo[3.3.0]octane;
- loading, under a first inert atmosphere, the API in a first bag that comprises first thermoplastic material, and closing the first bag;
- placing, under a second inert atmosphere, the closed first bag, a first oxygen-scavenging agent, and a first moisture-absorbing agent in a second bag that comprises second thermoplastic material, and closing the second bag;
- and
- placing, under a third inert atmosphere, the closed second bag, a second oxygen-scavenging agent, and a second moisture-absorbing agent in a third bag that comprises aluminium-based material, and sealing the third bag;
- wherein when the nitrosamine is 1-methyl-4-nitrosopiperazine, then the predetermined starting content is less than or equal to 0.16 parts per million (ppm),
- wherein when the nitrosamine is 1-cyclopentyl-4-nitrosopiperazine, then the predetermined starting content is less than or equal to 0.1 ppm, and
- wherein when the nitrosamine is N-Nitroso-3-azabicyclo[3.3.0]octane, then the predetermined starting content is less than or equal to 2 ppm.
A first assembly for control of formation of nitrosamine in solid active pharmaceutical ingredient (API), the first assembly comprising:
- a first bag comprising first thermoplastic material, containing the solid API having a predetermined starting content of a nitrosamine selected from the group consisting of 1-methyl-4-nitrosopiperazine, 1-cyclopentyl-4-nitrosopiperazine, and N-Nitroso-3-azabicyclo[3.3.0]octane, filled with a first inert gas and closed;
- a second bag comprising second thermoplastic material, containing the first bag provided with a first oxygen-scavenging agent and a first moisture-absorbing agent, filled with a second inert gas and closed;
- and
- a third bag comprising aluminium-based material, containing the second bag provided with a second oxygen-scavenging agent and a second moisture-absorbing agent, filled with a third inert gas and sealed;
- wherein when the nitrosamine is 1-methyl-4-nitrosopiperazine, then the predetermined starting content is less than or equal to 0.16 parts per million (ppm),
- wherein when the nitrosamine is 1-cyclopentyl-4-nitrosopiperazine, then the predetermined starting content is less than or equal to 0.1 ppm, and
- wherein when the nitrosamine is N-Nitroso-3-azabicyclo[3.3.0]octane, then the predetermined starting content is less than or equal to 2 ppm.
A process for control of formation of nitrosamine in a solid active pharmaceutical ingredient (API) using an assembly, the API having a predetermined starting content of a nitrosamine selected from the group consisting of 1-methyl-4-nitrosopiperazine, 1-cyclopentyl-4-nitrosopiperazine, and N-Nitroso-3-azabicyclo[3.3.0]octane, wherein the assembly comprises:
- a closable first bag comprising first thermoplastic material;
- a closable second bag comprising second thermoplastic material;
- a sealable third bag comprising aluminium-based material;
- a first oxygen-scavenging agent and a first moisture-absorbing agent;
- and
- a second oxygen-scavenging agent and a second moisture-absorbing agent;
- wherein the process comprises, under inert atmosphere:
- loading the API in the first bag, and closing the first bag after being loaded;
- placing the closed first bag, the first oxygen-scavenging agent, and the first moisture-absorbing agent in the second bag, and closing the second bag after the placing of the closed first bag;
- and
- placing the closed second bag, the second oxygen-scavenging agent, and the second moisture-absorbing agent in the third bag, and sealing the third bag after the placing of the closed second bag;
- wherein when the nitrosamine is 1-methyl-4-nitrosopiperazine (MeNP), then the predetermined starting content is less than or equal to 0.16 parts per million (ppm),
- wherein when the nitrosamine is 1-cyclopentyl-4-nitrosopiperazine, then the predetermined starting content is less than or equal to 0.1 ppm, and
- wherein when the nitrosamine is N-Nitroso-3-azabicyclo[3.3.0]octane, then the predetermined starting content is less than or equal to 2 ppm.
Dependencies are inferred from the claim text.