Adsorbent embedded pharmaceutical packaging

Abstract

The present invention generally relates to packaging systems embedded with adsorbent materials, more particularly, it relates to materials used in packaging of pharmaceuticals for actively adsorbing volatile compounds and moisture.

Description

ADSORBENT EMBEDDED PHARMACEUTICAL PACKAGINGField of the Invention

[0001] The present invention generally relates to packaging systems embedded with adsorbent materials, more particularly, it relates to materials used in packaging of pharmaceuticals for actively adsorbing volatile compounds and moisture.Background of the Invention

[0002] Stability of pharmaceuticals primarily refers to a drug's ability to maintain its chemical nature, strength, and efficacy within pharmacopoeial limits, and hence is a critical attribute. Pharmacological stability can be defined as ability of a pharmaceutical product to preserve its original pharmacological effect to same extent throughout its shelf life. Whereas, physical stability means that physical characteristics of the pharmaceutical product, such as size, shape, hardness, appearance, brittleness, and particle size, stay unchanged over its shelf life. Stability also includes considerations regarding palatability uniformity of content, dissolution rate, suspendability, resistance, to microbial growth, and most importantly, therapeutic effect without significant increases in toxicity during its shelf life.

[0003] However, pharmaceutical products comprise of certain unwanted chemicals known as impurities in APIs which develop during formulation. These impurities, especially present in solid dosage forms such as tablets and capsules, tend to degrade. The degradation caused by the impurities includes a variety of chemical reactions which are initiated by different factors including pH, temperature, and light thereby releasing various toxic substance. Further, physicochemical properties of the pharmaceuticals can also get altered during their use, storage, and transport owing to the impurities. The toxic substances consequently released by the degraded pharmaceuticals have deleterious effects on users consuming them.

[0004] For instance, Fanconi syndrome – a defect of proximal tubule leading to malabsorption of various electrolytes and substances – is known to be caused due to the toxicity of epianhydrotetracycline, which is a degraded product of tetracycline. Further still, genotoxic impurities such as N-nitrosamines have been not only detected in pharmaceuticals, but also have been detected in various foods, beverages, water, tobacco products and cosmetic products. The N-nitrosamines have a carcinogenic potential which results from metabolic activation by enzymes of cytochrome P450 family, leading to the formation of reactive species, diazonium ions, which can further form DNA adducts and cause mutations. One of the N-nitrosamine impurity is N- Nitrosodimethylamine (NDMA), an organic compound with the formula (CH3)2NNO which is formed by the combination of dimethyl amine with nitrites. Whilst NDMA is a known common environmental contaminant, nitrosamine such as NDMA are known to be carcinogenic. Chronic ingestion of NDMA is postulated to cause an increase in liver and other cancers. A Dutch study (Pottegard A, et al., Use of N-nitroso-dimethylamine (NDMA) contaminated valsartan products and risk of cancer: Danish nationwide cohort study, BMJ, 2018;362) has reported that NDMA-contaminated medicines are associated with a small increase in risk for overall cancer, and the cancer-causing impact of NDMA is understood to be cumulative so that contamination of medicines taken over long periods for chronic conditions are particularly of concern.

[0005] Nitrosamine impurities can be formed during manufacturing or subsequent storage or during stability studies of the drug product. Such impurities may be formed due to use of variety of commonly utilized excipients or due to degradation of active pharmaceutical ingredients containing primary, secondary, tertiary or quaternary amine groups in their structures.

[0006] As per FDA guidance for industry for Control of Nitrosamine Impurities in Human Drugs, FDA has identified seven nitrosamine impurities that theoretically could be present in drug products: N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitroso-N-methyl-4-aminobutanoic acid (NMBA), N-nitrosoisopropylethylamine (NIPEA), N-nitrosodiisopropylamine (NDIPA), N-nitrosodibutylamine (NDBA), and N-nitrosomethylphenylamine (NMPA). Five of them (NDMA, NDEA, NMBA, NIPEA, and NMPA) have actually been detected in drug substances or drug products. Such Nitrosamine compounds are potent genotoxic agents in several animal species and some are classified as probable or possible human carcinogens by the International Agency for Research on Cancer (IARC).

[0007] Global regulatory bodies including FDA and EMEA has set guidelines for mitigating the risk associated with nitrosamine impurities and outlined the various issues impacting on the drug product. FDA strongly urges applicants “to develop control strategies and / or design approaches to control nitrosamine drug substance-related impurities within acceptable levels.

[0008] Various references have talked about methods to optimize the level of nitrosamine impurities by using approaches. However, there are limited disclosures available which are actually enabled to control the nitrosamine impurities in drug product during storage period.

[0009] Hence, there is a need in the art for a packaging material which can adsorb the various impurities released by finished pharmaceutical formulations.

[0010] The present invention provides a packaging system comprising a pharmaceutical composition, wherein the packaging is embedded with adsorbents to remove unwanted volatile impurities.

[0011] In one embodiment, the present invention provides a packaging system comprising a pharmaceutical composition, comprising at least one amine containing pharmaceutically active agent wherein the packaging system comprises of,

[0012] a first face (10),

[0013] second face (20,), is embedded with adsorbent in the form of pellets (200),

[0014] wherein, the packaging system reduces or removes nitrosamine impurity.

[0015] In one aspect of the invention, the first face (10) comprises of plurality of sublayers.

[0016] In yet another aspect of the invention, the second face (20) comprises of plurality of sublayers and the innermost sub-layer of the second face (20) lies adjacent to the finished dosage form (30).

[0017] In yet another aspect of the invention, the adsorbent pellet ranges in size from between 5 microns to 60 micron.

[0018] In another aspect of the invention, the pellet comprises adsorbent in a concentration range of 10% w / w to 30% w / w of pellets, more preferably 15% w / w to 25% w / w.

[0019] In another aspect of the invention, the pellet further comprises Low-density polyethylene (LDPE), Polyvinyl chloride (PVC), Polyethylene Terephthalate (PET) Polyvinylidene chloride (PVDC) or combination thereof.

[0020] In another aspect of the invention, the adsorbent is selected from activated charcoal, or Palm Kernel Shell 10 (PKS) charcoal, Coconut shell charcoal, Bamboo charcoal, hard wood-based charcoal like oak, maple, and birch tree-based charcoal or any other similar compounds having activated carbon.

[0021] In another aspect of the invention, the first face (10) is selected from aluminium, Oriented polyamide (OPA), Polyvinyl Chloride (PVC), Polyethylene terephthalate (PET), High-density polyethylene (HDPE), Low-density polyethylene (LDPE), Polypropylene (PP), Polyvinyl chloride (PVC), Polystyrene (PS) or Polystyrene (PS).

[0022] In yet another aspect of the invention, the first face (10) is selected from Biodegradable plastics, Polylactic acid (PLA), Polyhydroxyalkanoates (PHAs), Cellulose acetate (CA), Biodegradable polyethylene (PE) or Bio-based PET (PET).

[0023] In another aspect of the invention, the second face (20) is selected from aluminium, Oriented polyamide (OPA), Polyvinyl Chloride (PVC), Polyethylene terephthalate (PET), High-density polyethylene (HDPE), Low-density polyethylene (LDPE), Polypropylene (PP), Polyvinyl chloride (PVC), Polystyrene (PS) or Polystyrene (PS).

[0024] In yet another aspect of the invention, the second face (20) is selected from Biodegradable plastics, Polylactic acid (PLA), Polyhydroxyalkanoates (PHAs), Cellulose acetate (CA), Biodegradable polyethylene (PE) or Bio-based PET (PET).

[0025] In another embodiment, the present invention provides a packaging system comprising a pharmaceutical composition comprising at least one amine containing pharmaceutically active agent, wherein the packaging is embedded with activated carbon to remove nitrosamine impurities.

[0026] In another embodiment, the present invention provides a packaging system comprising a pharmaceutical composition comprising at least one amine containing pharmaceutically active agent, wherein the packaging is embedded with activated carbon in the form of pellets (200) in sub-layer (20c) which lies adjacent to the finished dosage form (30).

[0027] In yet another embodiment, the present invention provides a method of preventing or removing volatile impurities in a pharmaceutical composition comprising at least one amine containing pharmaceutically active agent, comprising providing the pharmaceutical composition in a packaging wherein the packaging is embedded with adsorbents.

[0028] In another embodiment, the present invention provides a method of preventing or removing nitrosamine impurities in a pharmaceutical composition comprising at least one amine containing pharmaceutically active agent, the method comprising providing the pharmaceutical composition in a packaging wherein the packaging is embedded with activated carbon.

[0029] In another embodiment, the present invention provides a method of preventing or removing nitrosamine impurities in a pharmaceutical composition comprising at least one amine containing pharmaceutically active agent, comprising providing the pharmaceutical composition in a packaging wherein the packaging is embedded with activated carbon in the form of pellets (200) in sub-layer (20c) which lies adjacent to the finished dosage form (30).

[0030] In another embodiment, the invention provides a method of preventing or removing nitrosamine impurities in a pharmaceutical composition wherein the composition is comprised in a packaging system comprising, a first face (10), and second face (20,) which is embedded with adsorbent in the form of pellets (200) wherein, the packaging system reduces or removes nitrosamine impurity.Brief Description of the Drawings

[0031] Reference will be made to embodiments of the invention, examples of which may be illustrated in accompanying figures. These figures are intended to be illustrative, not limiting. Although the invention is generally described in context of these embodiments, it should be understood that it is not intended to limit the scope of the invention to these particular embodiments.

[0032] shows a transverse section of an adsorbent embedded packaging in accordance with the embodiment of the invention.

[0033] shows one such example of an adsorbent embedded packaging to prevent or remove NDMA impurity.Detailed Description of Invention

[0034] As used herein the following definitions apply unless clearly indicated otherwise. It should be understood that unless expressly stated to the contrary, the singular forms “a” “an” and “the” include plural reference unless the context clearly dictates otherwise.

[0035] By “about” we mean a value, which is plus or minus 10 % of the stated value.

[0036] By “amine containing pharmaceutically active agent” we mean a pharmaceutically active agent (i.e., drug) containing one or more primary, secondary or tertiary amine groups.

[0037] “Accelerated stability studies” include stability conditions at 40°C / 75% RH.

[0038] Referring to, the present invention uses a typical blister pack 100 comprising of a plurality of individual cavities. Each of the individual cavities are meant to encapsulate pharmaceutical finished dosage forms 30.

[0039] In an embodiment of the invention, the finished dosage forms 30 may include, but not be limited to, tablets, soft gel capsules, hard gel capsules, pills, and caplets. In the present specification, the phrases “pharmaceutical composition” and “finished dosage forms” are used interchangeably.

[0040] In this regard, the blister pack 100 may comprise a first face 10. In an embodiment, the first face 10 may comprise a foil of aluminum. In yet another embodiment, and as shown in, the first face 10 may comprise a plurality of sub-layers 10a, 10b, 10c, of predetermined thicknesses. The plurality of sub-layers 10a, 10b, 10c, comprise of different materials including but not limited to the aluminum, Oriented polyamide (OPA) or Polyamide (PA), Polyvinyl Chloride (PVC), Polyethylene terephthalate (PET), High-density polyethylene (HDPE), Low-density polyethylene (LDPE), Polypropylene (PP), Polyvinyl chloride (PVC), Polystyrene (PS), Polystyrene (PS), Cyclo-olefin copolymers (COC) or Cyclo-olefin polymers (COP) or Ethyl Vinyl Alcohol (EVOH). Few of Biodegradable plastics can also be used for this purpose, such as Polylactic acid (PLA), Polyhydroxyalkanoates (PHAs), Cellulose acetate (CA), Biodegradable polyethylene (PE) or Bio-based PET (PET). These materials thereby imparts an overall strength and resilience to the first face 10. As seen in the figure, the sub-layer 10c of the first face 10 lies adjacent to the finished dosage form 30.

[0041] Referring yet to, the blister pack 100 of the present invention may comprise a second face 20. In an embodiment, the second face 20 may comprise a foil of aluminum. In yet another embodiment, and as shown in, the second face 20 may comprise a plurality of sub-layers 20a, 20b, 20c, of predetermined thicknesses. The plurality of sub-layers 20a, 20b, 20c, comprise of different materials including but not limited to the aluminum, Oriented polyamide (OPA), Polyvinyl Chloride (PVC), Polyethylene terephthalate (PET), High-density polyethylene (HDPE), Low-density polyethylene (LDPE), Polypropylene (PP), Polyvinyl chloride (PVC), Polystyrene (PS) or Polystyrene (PS). Few of Biodegradable plastics can also be used for this purpose, such as Polylactic acid (PLA), Polyhydroxyalkanoates (PHAs), Cellulose acetate (CA), Biodegradable polyethylene (PE) or Bio-based PET (PET). In a further embodiment of the invention, the second face 20 may comprise a film of Polyvinyl Chloride (PVC) being subjected to either thermo-forming or cold forming. In yet another embodiment, the second face 20 may comprise a plurality of sub-layers 20a, 20b, 20c, whereby the plurality of sub-layers 20a, 20b, 20c, comprise of different materials including but not limited to, Polyvinyl Chloride (PVC), Polyethylene Terephthalate (PET) Polyvinylidene chloride (PVDC), Polychlorotrifluoro-ethylene (PCTFE), High-density polyethylene (HDPE), Low-density polyethylene (LDPE), Polypropylene (PP), Polyvinyl chloride (PVC), Polystyrene (PS), Polystyrene (PS), Cyclic olefin copolymers (COC) or polymers (COP), and glycol-modified polyethylene terephthalate (PETg). Few of Biodegradable plastics can also be used for this purpose, such as Polylactic acid (PLA), Polyhydroxyalkanoates (PHAs), Cellulose acetate (CA), Biodegradable polyethylene (PE), Bio-based PET (PET).

[0042] As seen in the figure, the sub- layer 20c of the second face 20 lies adjacent to the finished dosage form 30. As seen in the Figure, according to the invention, the sub-layer 20c of the second face 20 of the blister pack 100 may be embedded with an adsorbent compound. In an embodiment, the adsorbent compound may be activated charcoal, or Palm Kernal Shell (PKS) charcoal, Coconut shell charcoal, Bamboo charcoal, hard wood based charcoal like oak, maple, and birch tree based charcoal or any other similar compounds having activated carbon. In another embodiment of the invention, the adsorbent compound, preferably, activated charcoal is powdered or pelletized and then embedded in the sub-layer 20c of the second face 20. More preferably, Palm Kernal Shell (PKS) charcoal and Coconut shell charcoal is pelletized and then embedded in the sub-layer 20c of the second face 20.

[0043] In yet another embodiment of the invention, larger particles size charcoal beads were broken down into smaller ones by milling process, these milled activated carbon particle then mixed with any of the carrier plastic like LDEP, PVC, PVDC, PET etc and then the pellet were formed. For making the plastic film, it can be directly mixed with carrier plastic granules to form the multilayer sheet of charcoal particle of size 5- 60 mic by extrusion blown film or cast process. Then this activated carbon embedded sheet is directly extruded on the film or pasted by the help of lamination on the desired surface to produce the final packaging components.

[0044] In yet another embodiment of the invention, the adsorbent compound is in the form of pellets or beads ranging in size from 5 micron to 60 micron. In the present specification “pellets” “beads” are used interchangeably. Preferably, the adsorbent compound is palm kernel shell charcoal. The pellets comprise of adsorbent compound in a concentration range of 5% w / w to 40% w / w of the pellets. For example, in a concentration of 55, 10%, 15%, 20%, 25%, 30%, 35% or 40%. Preferably, the pellet comprises adsorbent compound in a concentration range of 10% w / w to 30% w / w. More preferably, the pellet comprises adsorbent compound in a concentration range of 15% w / w to 25% w / w. More preferably, the pellet comprises activated charcoal in a concentration range of 10% w / w to 30% w / w.

[0045] In yet another embodiment, the second face 20 may comprise a plurality of sub-layers 20a and 20b. In this embodiment, each of the sub-layers 20a and 20b may comprise additional sub-layers and the sub layer 20b may be disposed adjacent to the finished dosage form 30. In this regard, in an embodiment, the sub-layer 20a of the first face 20 may comprise a first film 20aa and a second film 20ab. In an embodiment, the first film 20aa and the second film 20ab of the sub-layer 20a may comprise of different materials including but not limited to aluminum, Oriented Polyamide (OPA) or Polyvinyl Chloride (PVC). In another embodiment, the first film 20aa of the sub-layer 20a may comprise Oriented Polyamide (OPA), while the second film 20ab of the sub-layer 10a may comprise aluminum. In this embodiment, the OPA film may be produced by a cast process and may be laminated over the aluminum film with a suitable adhesive. Further, in the same embodiment, the sub-layer 20b of the second face 20 may comprise a first film 20ba, a second film 20bb, and a third film 20bc. In this embodiment the first film 20ba and the third film 20bc may comprise of different materials including but not limited to Low Density Polyethylene (LDPE), or High Density Polyethylene (HDPE), or any combination thereof. The second film 20bb of the sub-layer 20b of the second face 20 may comprise either an adsorbent compound, or the adsorbent compound combined with Low Density Polyethylene (LDPE). In an embodiment, the adsorbent compound may be activated charcoal, or Palm Kernel Shell (PKS) charcoal, or any other similar compounds having activated carbon. The first film 20ba, the second film 20bb, and the third film 20bc of the sub-layer 20b of the second face 20 may be produced by extrusion blown film or cast process. In a further embodiment, the sub- layers 20a and 20b of the second face 20 may be laminated by a suitable adhesive.

[0046] As mentioned hereinabove, the sub-layer 20c that receives the adsorbent material lies adjacent to the finished dosage form 30. Therefore, the adsorbent material adsorbs all volatile impurities like N-nitrosodimethylamine, N-nitrosodiethylamine, N- nitrosomethylethylamine, N-nitrosodipropylamine, N-nitrosodiisopropylamine, N- nitrosoethylisopropylamine, N-nitrosodibutylamine, N-nitrosomethyl-2-phenylethylamine, N-nitrosopyrrolidine, N-nitrosopiperidine, N-nitrosomorpholine, Tiopronin ethyl ester, Dimethyl amine etc. released from the finished formulation 30 especially during times of storage, packaging, transport etc. Since the volatile impurities are adsorbed by the adsorbent, this advantageously ensures enhanced product stability and quality; extended shelf life and fewer degradation characteristics; improved resistance to environmental factors; and an overall decrease in generation of the impurities.

[0047] The FDA has stipulated an “Allowable Limit” of NDMA of 96 ng daily (see, for example, “Control of Nitrosamine Impurities in Human Drugs, Guidance for Industry”, published by the FDA, Revision 1, February 2021 and available at https: / www.fda.gov / regulatory-information / search-fda-guidance-documents / control-nitrosamine-impurities-human-drugs). The allowable amount of NDMA for a pharmaceutically active agent can be calculated in ppm as 96 ng / Maximum Daily Dosage (MDD) of the specific pharmaceutically active agent in mg. So, for example: metformin has an MDD of 2000 mg, so the maximum ppm allowable is 96 / 2000 = 0.048ppm.

[0048] In some embodiments according to the present invention the said blister pack is used to store the pharmaceuticals comprising at least one amine containing pharmaceutically active agent, for example such amine containing pharmaceutically active agent is containing one or more primary, secondary or tertiary amine groups. In one embodiment the amine containing pharmaceutically active agent is selected from but not limited to sartans, antidiabetic drugs, antihistamines, and antibiotics; for e.g. the active agent includes Amoxicillin, Bendroflumethiazide, Betahistine, Bisoprolol, Bromazepam, Carvedilol, Cetirizine, Desloratadine, Diclofenac, Doxylamine, Duloxetine, Enalapril, Ergometrine, Felodipine, Flecainide, Fluoxetine, Hydrochlorothiazide (HCT), Levofloxacin, Metoprolol, Metformin, Mirabegron, Mirtazapine, Moxifloxacin, Nebivolol, Opipramol, Pergolide, Propranolol, Quetiapine, Ramipril, Roxithromycin, Sertraline, Sotalol, Sumatriptan, Sitagliptin, Valsartan, Varenicline, Metformin, Ranitidine, Gliclazide, Sitagliptin, Prucalopride, Clarithromycin, Oxcarbazepine, Sunitinib, Rivaroxaban, Citalopram, Escitalopram, Tamsulosin, Diltiazem, Amlodipine, Sertraline, Tamsulosin or pharmaceutically acceptable salt thereof, and combination thereof.

[0049] In some embodiments according to the present invention the said blister pack as disclosed is used to store pharmaceuticals comprising combination products with amine containing drug, for example the said combination comprises at least an amine containing pharmaceutically active agent with one or more additional drug.

[0050] In one exemplary embodiment such amine drug is metformin present in combination with one or more drug selected from alogliptin, canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, glipizide, glyburide, linagliptin, saxagliptin, sitagliptin, pioglitazone, rosiglitazone, and pharmaceutically acceptable salts thereof. In one aspect such combination product is characterized by a reduced or controlled level of NDMA impurity in the product throughout the shelf life.

[0051] In one embodiment the disclosure contemplates the integration of the aforementioned adsorbent embedded components within a plastic matrix of the packaging. This involves strategically incorporating capsules, tablets, powders pellets or granules directly into the packaging during the manufacturing process. Such integration enhances the structural integrity of the packaging and provides a longer shelf life.

[0052] In some embodiments the disclosed film is having activated charcoal comprising a standard blister packaging system with the addition of activated charcoal layers strategically placed within the pack. In one aspect the said packing system with activated charcoal acts as a highly effective adsorbent, capturing and immobilizing volatile compounds that may be emitted by the product line in pharmaceutical product during storage and transportation and generate further chain of impurities.

[0053] In some embodiments the disclosure encompasses integration of adsorbent materials into closures caps, blister packings, or bottle container materials as embedded components within a plastic matrix of the packaging. The packaging may be a unit dose packaging or multidose packaging. The adsorbent embedded packaging may include blister, pouches or sachet, plastic bottles infusion bags, fill form seal containers, tubes, tin container, glass bottles, rigid containers such multilayer paper board containers.

[0054] In some embodiments the disclosure provides a packaging system comprising a pharmaceutical composition, wherein the packaging is embedded with adsorbents to remove unwanted volatile impurities.

[0055] In another embodiments the disclosure provides a packaging system comprising a pharmaceutical composition comprising at least one amine containing pharmaceutically active agent, wherein the packaging is embedded with activated carbon to remove nitrosamine impurities.

[0056] In yet another embodiment, the disclosure provides a packaging system comprising a pharmaceutical composition comprising at least one amine containing pharmaceutically active agent, wherein the packaging is embedded with activated carbon in the form of pellets (200) in sub-layer (20c) which lies adjacent to the finished dosage form (30).

[0057] In yet another embodiment, the disclosure provides a method of preventing or removing volatile impurities in a pharmaceutical composition comprising at least one amine containing pharmaceutically active agent, comprising providing the pharmaceutical composition in a packaging wherein the packaging is embedded with adsorbents.

[0058] In yet another embodiment, the disclosure provides a method of preventing or removing nitrosamine impurities in a pharmaceutical composition comprising at least one amine containing pharmaceutically active agent, comprising providing the pharmaceutical composition in a packaging wherein the packaging is embedded with activated carbon.

[0059] In yet another embodiment, the disclosure provides a method of preventing or removing nitrosamine impurities in a pharmaceutical composition comprising at least one amine containing pharmaceutically active agent, comprising providing the pharmaceutical composition in a upackaging wherein the packaging is embedded with activated carbon in the form of pellets (200) in sub-layer (20c) which lies adjacent to the finished dosage form (30).

[0060] The foregoing description of the invention has been set merely to illustrate the invention and is not intended to be limiting. Since the modifications of the disclosed embodiments incorporating the spirit and substance of the invention may occur to the person skilled in the art, the invention should be construed to include everything within the scope of the disclosure.Examples

[0061] EXAMPLE 1

[0062] Sitagliptin + Metformin (50mg / 1000mg) tablets were provided in a conventional blister pack and separately in charcoal embedded blister pack of the invention. The NDMA impurity was determined after storing for 15 days at room temperature in these different packaging.Sitagliptin+ metformin (50mg / 1000mg) tablets Pack DetailsNDMA (µg / g)ConditionConventional CFB batch0.037215 days at Room temperatureCharcoal embedded cold form blister0.0037

[0063] The NDMA impurity was determined after storing for 1 month at 40°C / 75%RH in different packaging.S.No.Sitagliptin+ Metformin (50mg / 500mg) tabletsPack detailStrength (mg)NDMAContent (µg / g) after 1 month1Charcoal embedded cold form blister50+500ND2Conventional cold form blister50+5000.0071ND: Not detected

[0064] As seen, the NDMA impurity is reduced / controlled in the Sitagliptin + Metformin tablet formulation by the use of charcoal embedded packaging compared to conventional blister package.

Claims

A packaging system comprising a pharmaceutical composition, comprising at least one amine containing pharmaceutically active agent wherein the packaging system comprises of,a first face (10),second face (20), embedded with adsorbent in the form of pellets (200),wherein, the packaging system reduces or removes nitrosamine impurity.A packaging system according to claim 1, wherein a first face (10) comprises of plurality of sublayers.A packaging system according to claim 1, wherein a second face (20) comprises of plurality of sublayers.A packaging system according to claim 3, wherein plurality of sublayers comprises of innermost sub-layer (20c).A packaging system according to claim 4, wherein the innermost sub-layer (20c) lies adjacent to the finished dosage form (30).A packaging system according to claim 1, wherein the pellet size ranges from 5 micron to 60 micron.A packaging system according to claim 1, wherein the pellet comprises adsorbent in a concentration range of 10% w / w to 30% w / w of pellets.A packaging system according to claim 1, wherein the pellet comprises adsorbent in a concentration range of 15% w / w to 25% w / w of pellets.A packaging system according to claim 1, wherein the pellet further comprises of LDEP, PVC, PVDC, PET or combination thereof.A packaging system according to claim 1, wherein the adsorbent is selected from activated charcoal, or Palm Kernel Shell 10 (PKS) charcoal, Coconut shell charcoal, Bamboo charcoal, Hard wood-based charcoal like oak, maple, and birch tree-based charcoal or any other similar compounds having activated carbon.A packaging system according to claim 1, wherein the first face (10) or second face (20) is selected from aluminium, Oriented polyamide (OPA), Polyvinyl Chloride (PVC), Polyethylene terephthalate (PET), High-density polyethylene (HDPE), Low-density polyethylene (LDPE), Polypropylene (PP), Polyvinyl chloride (PVC), Polystyrene (PS) or Polystyrene (PS).A packaging system according to claim 1, wherein the first face (10) or second face (20) is selected from Biodegradable plastics, Polylactic acid (PLA), Polyhydroxyalkanoates (PHAs), Cellulose acetate (CA), Biodegradable polyethylene (PE) or Bio-based PET (PET).A method of preventing or removing nitrosamine impurities in a pharmaceutical composition wherein the composition is comprised in a packaging system according to claim 1.

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