PH12014501944B1 - Medicinal product package - Google Patents
Medicinal product package Download PDFInfo
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- PH12014501944B1 PH12014501944B1 PH12014501944A PH12014501944A PH12014501944B1 PH 12014501944 B1 PH12014501944 B1 PH 12014501944B1 PH 12014501944 A PH12014501944 A PH 12014501944A PH 12014501944 A PH12014501944 A PH 12014501944A PH 12014501944 B1 PH12014501944 B1 PH 12014501944B1
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- Philippines
- Prior art keywords
- layer
- package
- granular composition
- medicinal product
- product package
- Prior art date
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- 229940126601 medicinal product Drugs 0.000 title claims abstract description 17
- 239000000203 mixture Substances 0.000 claims abstract description 33
- 229910021536 Zeolite Inorganic materials 0.000 claims abstract description 27
- HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical compound O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 claims abstract description 27
- 239000010457 zeolite Substances 0.000 claims abstract description 27
- 230000003115 biocidal effect Effects 0.000 claims abstract description 24
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims abstract description 22
- 229910052782 aluminium Inorganic materials 0.000 claims abstract description 22
- HHXMXAQDOUCLDN-RXMQYKEDSA-N penem Chemical compound S1C=CN2C(=O)C[C@H]21 HHXMXAQDOUCLDN-RXMQYKEDSA-N 0.000 claims abstract description 22
- 239000011888 foil Substances 0.000 claims abstract description 20
- 238000001179 sorption measurement Methods 0.000 claims abstract description 19
- 229920005989 resin Polymers 0.000 claims abstract description 14
- 239000011347 resin Substances 0.000 claims abstract description 14
- 229920001684 low density polyethylene Polymers 0.000 claims abstract description 11
- 239000004702 low-density polyethylene Substances 0.000 claims abstract description 11
- 229920000092 linear low density polyethylene Polymers 0.000 claims abstract description 8
- 239000004707 linear low-density polyethylene Substances 0.000 claims abstract description 8
- 229920005992 thermoplastic resin Polymers 0.000 claims abstract description 7
- 239000004480 active ingredient Substances 0.000 claims abstract description 4
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims abstract 2
- 229960000379 faropenem Drugs 0.000 claims description 29
- HGGAKXAHAYOLDJ-FHZUQPTBSA-N 6alpha-[(R)-1-hydroxyethyl]-2-[(R)-tetrahydrofuran-2-yl]pen-2-em-3-carboxylic acid Chemical compound S([C@@H]1[C@H](C(N1C=1C(O)=O)=O)[C@H](O)C)C=1[C@H]1CCCO1 HGGAKXAHAYOLDJ-FHZUQPTBSA-N 0.000 claims description 19
- 239000006188 syrup Substances 0.000 claims description 11
- 235000020357 syrup Nutrition 0.000 claims description 11
- MOGICMVNWAUWMK-HIXRZVNASA-L disodium;(5r,6s)-6-[(1r)-1-hydroxyethyl]-7-oxo-3-[(2r)-oxolan-2-yl]-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate;pentahydrate Chemical compound O.O.O.O.O.[Na+].[Na+].S([C@@H]1[C@H](C(N1C=1C([O-])=O)=O)[C@H](O)C)C=1[C@H]1CCCO1.S([C@@H]1[C@H](C(N1C=1C([O-])=O)=O)[C@H](O)C)C=1[C@H]1CCCO1 MOGICMVNWAUWMK-HIXRZVNASA-L 0.000 claims description 9
- 239000004503 fine granule Substances 0.000 claims description 3
- 239000008187 granular material Substances 0.000 claims description 3
- 239000000843 powder Substances 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 239000000463 material Substances 0.000 abstract description 13
- 238000004806 packaging method and process Methods 0.000 abstract description 7
- 239000011148 porous material Substances 0.000 abstract description 3
- 229940127554 medical product Drugs 0.000 abstract 1
- 239000010410 layer Substances 0.000 description 72
- 238000003475 lamination Methods 0.000 description 19
- 230000000052 comparative effect Effects 0.000 description 18
- 239000012086 standard solution Substances 0.000 description 14
- 238000000034 method Methods 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 238000011156 evaluation Methods 0.000 description 9
- 239000000243 solution Substances 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 239000000853 adhesive Substances 0.000 description 7
- 230000001070 adhesive effect Effects 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 239000012488 sample solution Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 239000002808 molecular sieve Substances 0.000 description 5
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 5
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 238000004811 liquid chromatography Methods 0.000 description 4
- 230000014759 maintenance of location Effects 0.000 description 4
- 238000007789 sealing Methods 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000004576 sand Substances 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- QIVUCLWGARAQIO-OLIXTKCUSA-N (3s)-n-[(3s,5s,6r)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,6-trifluorophenyl)piperidin-3-yl]-2-oxospiro[1h-pyrrolo[2,3-b]pyridine-3,6'-5,7-dihydrocyclopenta[b]pyridine]-3'-carboxamide Chemical compound C1([C@H]2[C@H](N(C(=O)[C@@H](NC(=O)C=3C=C4C[C@]5(CC4=NC=3)C3=CC=CN=C3NC5=O)C2)CC(F)(F)F)C)=C(F)C=CC(F)=C1F QIVUCLWGARAQIO-OLIXTKCUSA-N 0.000 description 2
- RTTZISZSHSCFRH-UHFFFAOYSA-N 1,3-bis(isocyanatomethyl)benzene Chemical compound O=C=NCC1=CC=CC(CN=C=O)=C1 RTTZISZSHSCFRH-UHFFFAOYSA-N 0.000 description 2
- LUJMEECXHPYQOF-UHFFFAOYSA-N 3-hydroxyacetophenone Chemical compound CC(=O)C1=CC=CC(O)=C1 LUJMEECXHPYQOF-UHFFFAOYSA-N 0.000 description 2
- 229920002799 BoPET Polymers 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 239000002274 desiccant Substances 0.000 description 2
- DGLRDKLJZLEJCY-UHFFFAOYSA-L disodium hydrogenphosphate dodecahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].OP([O-])([O-])=O DGLRDKLJZLEJCY-UHFFFAOYSA-L 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 2
- 235000019796 monopotassium phosphate Nutrition 0.000 description 2
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 2
- -1 polyethylene terephthalate Polymers 0.000 description 2
- 229920000139 polyethylene terephthalate Polymers 0.000 description 2
- 239000005020 polyethylene terephthalate Substances 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 238000013094 purity test Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000002356 single layer Substances 0.000 description 2
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 2
- AWFYPPSBLUWMFQ-UHFFFAOYSA-N 2-[5-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]-1-(1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NN=C(O1)CC(=O)N1CC2=C(CC1)NN=C2 AWFYPPSBLUWMFQ-UHFFFAOYSA-N 0.000 description 1
- 229930186147 Cephalosporin Chemical class 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 238000004380 ashing Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000003750 conditioning effect Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000005443 coulometric titration Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000009820 dry lamination Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 239000003230 hygroscopic agent Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- AYOOGWWGECJQPI-NSHDSACASA-N n-[(1s)-1-(5-fluoropyrimidin-2-yl)ethyl]-3-(3-propan-2-yloxy-1h-pyrazol-5-yl)imidazo[4,5-b]pyridin-5-amine Chemical compound N1C(OC(C)C)=CC(N2C3=NC(N[C@@H](C)C=4N=CC(F)=CN=4)=CC=C3N=C2)=N1 AYOOGWWGECJQPI-NSHDSACASA-N 0.000 description 1
- XULSCZPZVQIMFM-IPZQJPLYSA-N odevixibat Chemical compound C12=CC(SC)=C(OCC(=O)N[C@@H](C(=O)N[C@@H](CC)C(O)=O)C=3C=CC(O)=CC=3)C=C2S(=O)(=O)NC(CCCC)(CCCC)CN1C1=CC=CC=C1 XULSCZPZVQIMFM-IPZQJPLYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920000098 polyolefin Polymers 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000000790 scattering method Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B32—LAYERED PRODUCTS
- B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
- B32B15/00—Layered products comprising a layer of metal
- B32B15/20—Layered products comprising a layer of metal comprising aluminium or copper
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B32—LAYERED PRODUCTS
- B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
- B32B15/00—Layered products comprising a layer of metal
- B32B15/04—Layered products comprising a layer of metal comprising metal as the main or only constituent of a layer, which is next to another layer of the same or of a different material
- B32B15/08—Layered products comprising a layer of metal comprising metal as the main or only constituent of a layer, which is next to another layer of the same or of a different material of synthetic resin
- B32B15/085—Layered products comprising a layer of metal comprising metal as the main or only constituent of a layer, which is next to another layer of the same or of a different material of synthetic resin comprising polyolefins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
- A61J1/03—Containers specially adapted for medical or pharmaceutical purposes for pills or tablets
- A61J1/035—Blister-type containers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B32—LAYERED PRODUCTS
- B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
- B32B2307/00—Properties of the layers or laminate
- B32B2307/70—Other properties
- B32B2307/724—Permeability to gases, adsorption
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B32—LAYERED PRODUCTS
- B32B—LAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
- B32B2439/00—Containers; Receptacles
- B32B2439/80—Medical packaging
Landscapes
- Packages (AREA)
- Laminated Bodies (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
- Wrappers (AREA)
- Medicinal Preparation (AREA)
Abstract
Provided is a medical product package in which the humidity can be controlled properly to prevent overdry thereof, and which is suitable for the packaging of a granular composition containing a penem antibiotic. A medicinal product package comprising a bag-type packaging body and a granular composition containing a penem antibiotic as an active ingredient and enclosed in the packaging body, wherein the packaging body comprises a packaging body film that comprises at least one base material layer comprising a thermoplastic resin, an aluminum foil and an adsorption layer all laminated in this order, the adsorption layer is arranged on a side on which the granular composition is to be housed and comprises an outer skin layer, an intermediate layer and an inner skin layer laminated in this order when observed from the aluminum foil side, the intermediate layer comprises an LDPE resin and contains a zeolite having a pore diameter of 1 nm or more at a density of 0.2 to 0.4 mg/cm2, and the inner skin layer comprises an LLDPE resin and has a layer thickness of 20 to 30 mm.
Description
oF + 3 “ J 4 [ } : . - ’
MEDICINAL PRODUCT PACKAGE To i. . " ed .
Loa i i] : . . . * a mete [Detailed Description of the Invention] : vi > ‘ ce
Ay Io » [Technical Field] Kies, Py. + " Ely <0 J
The present invention relates to a medicinal product package, and more ~~
Ne _ specifically relates to a medicinal product package in which a granular composition o : [Sn containing a penem antibiotic is encapsulated in a bag-type package. RES [rot [Background Art]
A penem antibiotic-containing granular composition £asily absorbs humidity, and when the granular composition absorbs humidity, causes nasty smell, + caking, color tone change, and reduction in titer to reduce the quality of the granular composition; therefore, a package is required to have a configuration in which the : inside is kept in a dry state. Thus, in the prior art, a package is formed of a packaging material including a barrier material such as an aluminum foil, and a desiccant such as silica gel is separately encapsulated in the package.
Meanwhile, the penem antibiotic-containing granular composition has such a property that when it is stored under a humidity of not more than a certain level (overdrying), the moisture content of the granular composition is reduced, and collapse and performance degradation (reduction in purity and titer) occur.
Therefore, a package of the penem antibiotic-containing granular composition is also required to have a performance for holding a proper humidity.
Patent Literature 1 discloses a container formed of a humidity conditioning composition in which specific magnesium sulfate is compounded with a thermoplastic resin. However, as a result of evaluation tests for a configuration similar to that of the Patent Literature 1, since magnesium sulfate is used as a
So ' oo -
Pd desiccant, the humidity absorption performance is insufficient as the package of the o penem antibiotic-containing granular composition, and it was found that the purity - was particularly reduced and was less than a specification value. i» : La
Further, Patent Literature 2 discloses a humidity regulation laminated bag "
Jo having a sandwich-like inner face material layer holding a humidity absorbing layer, composed of a blend of polyolefin and a hygroscopic agent, with a heat sealable film = pu layer. However, the example describes only a humidity absorbing layer in which = 1% by weight of zeolite having a particle diameter of 10 pm or 50 pm is compounded with an LDPE, and thickness of an innermost heat sealable film layer is only 10 pm. Thus, the configuration for holding a proper humidity required when packaging the penem antibiotic-containing granular composition is not considered. [Prior Art Documents] [Patent Documents] [Patent Document 1] Japanese Unexamined Patent Publication No. 5-39379 [Patent Document 2] Japanese Unexamined Patent Publication No. 8-26348 [Summary of the Invention] [Problem to be Solved by the Invention] :
Thus, an object of the present invention is to provide a medicinal product package which can prevent humidity absorption or overdrying in a penem antibiotic-containing granular composition by properly controlling humidity in a package and is suitable for preservation of the penem antibiotic-containing granular composition. ,
¢ i : . LEH) . : 5 [Means for Solving the Problem] -
More specifically, the present invention relates to = (1) a medicinal product package in which a granular composition containing . a penem antibiotic as an active ingredient is encapsulated in a bag-type package, the + package is formed of a package film including one or more base material layers - formed of a thermoplastic resin, an aluminum foil, and an adsorption layer stacked in = sequence, the adsorption layer is provided on a side where the granular composition x is stored and configured that an outer skin layer, an intermediate layer, and an inner skin layer are stacked in this order from the aluminum foil side, the intermediate layer is formed of an LDPE resin and contains 0.2 to 0.4 mg/cm2 of zeolite having a micropore diameter of not less than 1 nm, and the inner skin layer is formed. of an
LLDPE resin and has a layer thickness of 20 to 30 um, (2) the medicinal product package described in (1) in which the penem antibiotic is faropenem or a pharmaceutically acceptable salt or hydrate thereof, (3) the medicinal product package described in (1) in which the penem antibiotic is a faropenem sodium hydrate, and (4) the medicinal product package described in (1), (2), or (3) in which the granular composition is a granule, a fine granule, a powder, or dry syrup. [Effects of the Invention]
According to the present invention, since the inside of a package is not in an overdried state and can be kept at a proper humidity, a penem antibiotic-containing granular composition encapsulated in the package can be protected without degrading its performance. . [Mode for Carrying Out the Invention] ,
A medicinal product package of the present invention is a medicinal product iy ho package in which a granular composition containing a penem antibiotic as an active © ingredient is encapsulated in a bag-type package. The penem antibiotic is an ; antibiotic having a hybrid skeleton of penicillin and cephalosporin and is classified a into PB-lactam antibiotic, and examples of the penem antibiotic include faropenem o and a pharmaceutically acceptable salt or hydrate of it. As a currently = commercially available penem antibiotic, there has been known (+)-(5R, 6S)-6- iS [(R)-1-hydroxyethyl] -7-0x0-3- [(R)-2-tetrahydrofuryl] -4-thia-1-azabicyclo [3. 2. 0] hept -2-ene-2-sodium carboxylate hemipentahydrate (faropenem sodium hydrate).
The granular composition is a composition obtained by granulating an active ingredient and an additive by mixing and granulation, for example, and is sold as a granule, a fine granule, a powder, dry syrup, or the like.
The package used in the medicinal product package of the present invention is constituted of a package film including one or more base material layers formed of a thermoplastic resin, an aluminum foil, and an adsorption layer stacked in sequence.
The base material layer is formed of a thermoplastic resin such as PET (polyethylene terephthalate) and may be constituted of a single layer or plural layers.
Although the thickness of the base material layer is not limited particularly, it is preferably 6 to 25 pm, more preferably 10 to 25 um in view of strength of the package, printability onto a package surface, tearability, and so on.
[0013]
The aluminum foil may be of pure aluminum or alloyed aluminum, and as long as the aluminum foil functions as a barrier layer against oxygen and humidity (water vapor), the thickness is not limited particularly, but is preferably 6 to 12 pm, more preferably 9 to 12 um.
ond
The adsorption layer includes an outer skin layer, an intermediate layer, and ~ an inner skin layer stacked in this order from the aluminum foil side and adsorbs ~ humidity (water vapor) and so on. poi
The intermediate layer is formed of an LDPE (low-density polyethylene) : resin and contains 0.2 to 0.4 mg/cm2 of zeolite having a micropore diameter of not = less than 1 nm. The content of zeolite is weight of zeolite contained in the entire ® thickness direction of an intermediate layer per unit area on a surface perpendicular o to a thickness direction of the intermediate layer.
Examples of zeolite include a commercially available molecular sieve.
The molecular sieve is a porous granular substance used for separating a substance according to a difference in size between molecules, has a structure having uniform fine pores, and is a typical synthetic zeolite absorbing small molecules entering a cavity of the fine pores and acting as a kind of sieve. The micropore diameter involves in adsorptivity of zeolite, and when the micropore diameter is less than Inm, the humidity adsorptivity is very strong, and the inside of the package is in an overdried state. The micropore diameter can be confirmed by an X-ray diffraction method, an X-ray small angle scattering method, a structural analysis using a gas adsorption method, and so on. When the content of zeolite is less than 0.2 mg/cm?2, the humidity adsorptivity is insufficient, and when the content of zeolite is more than 0.4 mg/cm2, the inside of the package is in an overdried state. Although the thickness of the intermediate layer is not limited particularly, it is preferably 20to 40 pum in view of the strength of the package, tearability, and so on.
The inner skin layer is formed of an LLDPE (linear low-density polyethylene) resin so as to pass humidity in the package therethrough and be easily adsorbed to zeolite in the intermediate layer. The thickness of the inner skin layer
Ie is 20 to 30 pm in view of humidity permeability, the strength of the package, ~ tearability, and so on. When the thickness of the inner skin layer is less than 20 pm, = an excessive amount of humidity in the package passes, and therefore this causes the ~ overdried state, and when the thickness of the inner skin layer is more than 30 um, - the tearability is degraded. ce
The outer skin layer is formed of a thermoplastic resin such as an LLDPE, 5 and the thickness is not limiter particularly, but is preferably comparable to the - thickness of the inner skin layer to prevent occurrence of warpage or contraction of the adsorption layer.
The adsorption layer can be obtained by coextrusion molding with the resin for the outer skin layer, an LDPE resin blended with zeolite for the intermediate layer, and the LLDPE resin for the inner skin layer by an inflation method, a T-die method, or the like.
In the lamination of the base material and the aluminum foil and the stacking of the aluminum foil and adsorption layer, the lamination may be performed by dry lamination, sand lamination using PE (polyethylene), or the like.
The package of the present invention is a bag-type package, the above-described package film is disposed so that the adsorption layer is located inside (the side where the granular composition is stored), and the package film is heat-sealed, whereby the package is can be obtained. [Examples] <Examples 1 to 3>
An aluminum foil (“BESPA” manufactured by Sumikei Aluminum Foil
Co., Ltd.) having a thickness of 9 um was dry-laminated on a PET film (base
: Pod material, “Ester Film E5100” manufactured by Toyobo Co., Ltd.) having a thickness = of 12 um by using an ester-based adhesive (main agent: TAKELAC A525, curing = - agent: TAKENATE A50 manufactured by Mitsui Chemicals Inc.) (thickness of the ~ adhesive was 3 um), and a base material film was obtained. :
Meanwhile, an LDPE (“Petrothene 202” manufactured by Tosoh ce corporation) containing 10 wt% of zeolite (“molecular sieves 13X” manufactured by >
UNION SHOWA K.K., micropore diameter: 1 nm) as a resin for an intermediate = layer and an LLDPE (“EVOLUE SP2520” manufactured by Prime Polymer Co.,
Ltd.) as a resin for an outer skin layer and an inner skin layer were coextruded, and an adsorption layer constituted of an outer skin layer of 10 pm, an intermediate layer of 20 um (Example 1), 30 pm (Example 2), or 40 um (Example 3), and an inner skin layer of 20 pm was obtained by an inflation method.
When the content of zeolite of the intermediate layer was measured by ashing test (JIS-K7250A (ISO3451A)), the content was 0.2 mg/cm2 in Example 1, 0.3 mg/cm2 in Example 2, and 0.4 mg/cm?2 in Example 3.
Next, the aluminum foil of the base material film and the outer skin layer of the adsorption layer were dry-laminated by using the ester-based adhesive so that they faced each other (the thickness of the adhesive was 3 um), and a package film having a thickness of 77 pm (Example 1), 87 pm (Example 2), or 97 um (Example 3) was obtained. The layer constitution of the package film is as follows.
Base material (12 um)/ ester-based adhesive (3 um)/ aluminum foil (9 pm)/ ester-based adhesive (3 pm)/ adsorption layer (Example 1: 50 pm, Example 2: 60 um, Example 3: 70 pum)
In each example, the obtained package film was cut into a rectangular shape (vertical 60 mm x horizontal 45 mm), and the two cut package films were i superposed so that the respective adsorption layer sides faced each other. Then, the bo three sides were heat-sealed with a long side sealing width of 5 mm and a short side = sealing width of 6 mm, and a package having an open short side was obtained. -
Faropenem sodium hydrate-containing dry syrup as a penem = antibiotic-containing granular composition was stored in the package, the opening was sealed with a sealing width of 6 mm by heat-sealing, and thereafter the package = was preserved for six months in a 40°C/75% RH environment. Ina state of a drug w 0 after preservation, moisture content, titer, and purity were measured according to the method described in “faropenem sodium for syrup” in the Japanese Pharmacopoeia - and evaluated according to the following specification. The results were shown in
Table 2. [Moisture content]
The moisture content of 80 mg of a granular composition was obtained by a coulometric titration method.
When the moisture content was 1.5 to 2.1%, “O” was used, and otherwise, “XX” was used. : [Titer] oo
When faropenem (C12H15NOSS: 285.32) corresponding to 93.0 to 106.0% of an indicated titer was contained according to the following determination method, “QO” was used, and otherwise, “X” was used. [Determination method]
The amount corresponding to about 25 mg (titer)! of faropenem (C12H15NOSS) is measured in accordance with the indicated amount, 10 mL of an internal standard solution is added, and thereafter the mixture is shaken and stirred well with water to be further added with water so that the volume is 50 mL and, thus, ” to be filtered. 10 mL of an initial filtrate is removed, and the next filtrate is a = sample solution. In addition, the amount corresponding to about 25 mg (titer) of . faropenem sodium reference standard is measured, 10 mL of an internal standard = solution is added, and thereafter the mixture is added with water to be dissolved so > that the volume is 50 mL and, thus, to prepare a standard solution. 20 pL of the - sample solution and 20 pL of the standard solution are tested by liquid - chromatography under the following conditions, and ratios QT and QS of a peak area of faropenem to a peak area of an internal standard substance are obtained.
Amount of faropenem [mg (titer)] = WS x QT/QS
WS: weighed amount of faropenem sodium reference standard [mg (titer)]
Internal standard solution 0.5 g of m-hydroxy acetophenone is dissolved in mL of acetonitrile and added with water so that the volume is 200 mL.
Test condition
Detector: ultraviolet absorptiometer (measurement wavelength: 305 nm) 20 Column: 5 pm of octadecyl-silylated silica gel for liquid chromatography is filled in a stainless pipe having an inner diameter of 4.6 mm and a length of 25 cm.
Column temperature: 40°C
Mobile phase: 4.8 g of potassium dihydrogen phosphate, 5.4 g of disodium hydrogen phosphate dodecahydrate, and 1.0 g of tetra-n-butylammonium bromide are dissolved in water, and a solution of 1000 mL is obtained. 870 mL of this solution is added with 130 mL of acetonitrile.
Flow rate: it 1s regulated so that a faropenem retention time is 11 minutes.
System suitability on
System performance: when operation is performed under the above : conditions with respect to 20 pL of the standard solution, the internal standard @ substance and faropenem are eluted in this order, and the degree of separation is not ’ less than 1.5. +=
System reproducibility: when a test is repeated six times under the above ” conditions with respect to 20 pL of the standard solution, a relative standard = deviation of the ratio of the peak area of faropenem to the peak area of the internal ; standard substance is not more than 1.0%. [Purity]
According to the following purity test, when a cleavage body as a specific analogous substance was not more than 1.5% and the total amount of an analogous substance was not more than 2.0%, “O” was used, and otherwise, “X” was used. [Purity test]
The amount corresponding to about 25 mg (titer) of “faropenem sodium hydrate” is measured in accordance with an indicated amount, about 10 mL of water is added, the mixture is shaken and stirred well, thereafter water is further added so that the volume was 50 mL, and filtration is performed. 10 mL of an initial filtrate is removed, and the next filtrate is a sample solution. 2 mL of this solution is measured to be added with water so that the volume is 200 mL and, thus, to prepare a standard solution. 20 pL of the sample solution and 20 pL of the standard solution are tested by liquid chromatography under the following conditions. When each peak area of those solutions is measured by an automatic integration method, the peak area of a cleavage body in which a relative retention time with respect to } faropenem of the sample solution is about 0.71 is less than 1.5 times the peak area of
= faropenem of the standard solution. The total of the peak areas other than . faropenem of the sample solution is less than twice the peak area of faropenem of the = standard solution. However, the peak area of the cleavage body in which the pet relative retention time with respect to faropenem is about 0.71 is a value obtained by - : multiplying an area, obtained by the automatic integration method, by a sensitivity ” coefficient 0.37. ®
Test condition .
Detector: ultraviolet absorptiometer (measurement wavelength: 240 nm)
Column: 5 um of octadecyl-silylated silica gel for liquid chromatography is filled in a stainless pipe having an inner diameter of 4 mm and a length of 25 cm.
Column temperature: 40°C
Mobile phase A: 6.12 g of potassium dihydrogen phosphate, 1.79 g of disodium hydrogen phosphate dodecahydrate, and 1.61 g of tetra-n-butylammonium bromide are dissolved in water, and a solution of 1000 mL is obtained.
Mobile phase B: mobile phase A/acetonitrile mixture (1:1)
Solution sending in mobile phase: a concentration gradient is controlled by changing the mixing ratio of the mobile phase A and the mobile phase B as shown in
Table 1. [Table 1] (minutes) (vol%) (vol%)
Flow rate: 1.5 mL per minute
Area measurement range: a range of 2.5 times a faropenem retention time
CE or . after the peak of a solvent =o
System suitability oo
Confirmation of detection: 2 mL of the standard solution is measured and . added with water so that the volume is 20 mL. It is confirmed that the peak area of i faropenem obtained from 20 pL of this solution is 7 to 13% of the peak area of . faropenem of the standard solution. .
System performance: when operation is performed under the above conditions with respect to 20 pl of the standard solution in the determination method, m-hydroxy acetophenone and faropenem are eluted in this order, and the degree of separation is not less than 11. | System reproducibility: when a test is repeated six times under the above conditions with respect to 20 pL of the standard solution, the relative standard deviation of the peak area of faropenem is not more than 3.0%. <Comparative Example 1>
A package was obtained in the same manner as in Example 2, except that an
LDPE single layer film (thickness: 60 pm) containing no zeolite was used instead of the adsorption layer. The results of evaluation of pharmaceutical performance are shown in Table 2. <Comparative Example 2>
A package was obtained in the same manner as in Example 2; except that the content of zeolite in a resin for an intermediate layer was 5 wt%. The content of zeolite of the intermediate layer and the results of evaluation of the pharmaceutical performance are shown in Table 2.
ow 5 <Comparative Examples 3 and 4> oo
A package was obtained in the same manner as in Example 2, except that = the intermediate layer had a thickness shown in Table 2. The content of zeolite of - the intermediate layer and the results of evaluation of the pharmaceutical = performance are shown in Table 2. on <Example 4> o on
A package was obtained in the same manner as in Example 2, except that an + ester-based adhesive (main agent: TAKELAC A525, curing agent: TAKENATE
A50 manufactured by Mitsui Chemicals Inc.) was anchor coated on a PET film, and an aluminum foil was subjected to sand-lamination with an LDPE (Suntec L1850K manufactured by Asahi Kasei Corporation) (thickness of LDPE: 15 pum). The content of zeolite of the intermediate layer and the results of evaluation of the pharmaceutical performance are shown in Table 2. <Examples 5 and 6, Comparative Example 5>
A package was obtained in the same manner as in Example 2, except that the inner skin layer had a thickness shown in Table 2 (however, in Example 5,aPET film and an aluminum foil were subjected to sand-lamination as in Example 4).
The content of zeolite of the intermediate layer and the results of evaluation of the pharmaceutical performance are shown in Table 2. <Comparative Examples 6 and 7>
A package was obtained in the same manner as in Example 2, except that a “molecular sieve 3A” (manufactured by UNION SHOWA KXK., micropore diameter: 0.3 nm) was used in Comparative Example 6, and a “molecular sieve 4A” (manufactured by UNION SHOWA KK, micropore diameter: 0.4 nm) was used in ey
CE po,
Fd
Comparative Example 7. The content of zeolite of the intermediate layer and the “ ot : © results of evaluation of the pharmaceutical performance are shown in Table 2. et ic] ad [Table 2] .
Thickness of adsorption layer . Pharmaceutical performance +=
Zeolite Lamination of | Thickness [een] (um) evaluation aluminum foil | of package
Outer Inner Micropore A pe)
Intermediate Content onto base film Moisture btn skin skin | Total | diameter Titer | Purity oT layer wo [mg/cm*} material [1m] content hd layer layer [nm] [RS
Dry tn
C ti cnparative lamination 87 X Lr
Examplel (3m)
Dry
Comparative 20 1 0.15 lamination 87 X
Example2 (Bum
Dry
Examplel 10 20 20 50 1 0.2 lamination 77 (3m) ’ Dry
Example2 10 30 20 1 0.3 lamination 87.
Bum )
Dry
Example3 10 20 70 1 0.4 lamination 97 (3um) . Dry
Comparative 10 50 20 1 0.5 lamination 107 xX X X
Example3 « (3m) . . Dry
Comparative 10 20 1 lamination 117 X X X
Example4 (Bum
Dry
Comparative 10 30 10 50 1 0.3 lamination x
Exampleb (3um)
Sand
Example4 10 30 20 1 0.3 lamination (15 um)
Sand
Example5 10 30 25 65 1 0.3 lamination 104 (15pm)
Dry
Example6 10 30 30 70 1 0.3 lamination 97 (Bum : Dry
Comparative 10 30 20 0.3 0.3 lamination 87 X
Example6 (3um)
Dry
Comparative
Ea 10 30 20 0.4 0.3 lamination 87 X
Example? (Bum
: oo : fd
The following is shown from the evaluation results in Table 2. =o
In Comparative Examples 1 and 2, since the content of zeolite of the o intermediate layer 1s less than 0.2 mg/cm2, humidity is not adsorbed very much, dry ~ syrup is deteriorated, and the titer is lowered. : : =
Le
In Comparative Example 5, since the thickness of the inner skin layer is less Le than 20 pm, an excessive amount of humidity in the package passes through the 5 pod inner skin layer to cause overdrying, and the purity of dry syrup is lowered. o
In Comparative Examples 6 and 7, since the micropore diameter of zeolite is less than 1 nm, the adsorption capacity is too high to cause overdrying, and the purity of dry syrup 1s lowered. | In Comparative Examples 3 and 4, since the content of zeolite of the intermediate layer is more than 0.4 mg/cm2, an excessive amount of humidity is adsorbed compared to Comparative Examples 5 to 7 to cause overdrying, and the purity, the moisture content, and the titer of dry syrup are lowered.
In contrast, in Examples 1 to 6, the humidity in the package is properly maintained, and consequently, the purity, the moisture content, and the titer of dry : syrup are not lowered, so that these examples are suitable for packaging faropenem sodium hydrate-containing dry syrup.
Claims (3)
- pes . . fo CLAIMS oo | dE oy . CATE 2 . ne 7p ae frets Qy ] . : Re. yp[Claim 1] “, 7 0 bt “on a 1 A medicinal product package in which a granular composition coptajuifig a . penem antibiotic as an active ingredient is encapsulated in a bag-typ¢/package, the - package comprising a package film including one or more base mate layers formed © of a thermoplastic resin, an aluminum foil, and an adsorptigh layer stacked in fo sequence, the adsorption layer being provided on a side where the granular composition is stored and comprising an outer skin layer, an intermediate layer, and : an inner skin layer stacked in this order from the aluminum foil side, the intermediate layer being formed of an LDPE resin and containing 0.2 to 0.4 mg/ cm? of zeolite having a micropore diameter of not less than 1 nm, and the inner skin layer being formed of an LLDPE resin and having a layer thickness of 20 to 30 um.
- [Claim 2] The medicinal product package according to claim 1, wherein the penem antibiotic is faropenem or a pharmaceutically acceptable salt or hydrate thereof.
- [Claim 3]fo. Lh The medicinal product package according to claim 1, wherein the penem rd o antibiotic is a faropenem sodium hydrate. > [Claim 4] sr 25 The medicinal product package according to claim 1, 2, or 3, wherein the pei] . oh granular composition is a granule, a fine granule, a powder, or dry syrup. posed . fa! . hol
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/JP2012/055178 WO2013128608A1 (en) | 2012-03-01 | 2012-03-01 | Medicinal product package |
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| Publication Number | Publication Date |
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| PH12014501944B1 true PH12014501944B1 (en) | 2014-11-24 |
| PH12014501944A1 PH12014501944A1 (en) | 2014-11-24 |
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| JP (1) | JP5922757B2 (en) |
| CN (1) | CN102970959B (en) |
| AU (1) | AU2012371888B2 (en) |
| BR (1) | BR112014021667B1 (en) |
| HK (1) | HK1183226A1 (en) |
| MX (1) | MX352703B (en) |
| MY (1) | MY167571A (en) |
| PH (1) | PH12014501944A1 (en) |
| RU (1) | RU2589826C2 (en) |
| SG (1) | SG11201405153UA (en) |
| TW (1) | TWI539944B (en) |
| WO (1) | WO2013128608A1 (en) |
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| CN103434214B (en) * | 2013-09-23 | 2016-03-16 | 上海海顺新型药用包装材料股份有限公司 | A kind of antibiosis and self-cleaning PTP aluminium foil and preparation method thereof |
| JP6584199B2 (en) * | 2014-12-10 | 2019-10-02 | 共同印刷株式会社 | Packaging bag and manufacturing method thereof |
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| JP2838237B2 (en) * | 1991-02-27 | 1998-12-16 | 武内プレス工業株式会社 | Laminated tube container |
| JPH06205817A (en) * | 1993-01-12 | 1994-07-26 | Dainippon Printing Co Ltd | Plastic container being suitable for storing medfical care product or food product |
| JP2885079B2 (en) * | 1994-07-11 | 1999-04-19 | 東洋製罐株式会社 | Humidity control laminated bag |
| GB0214667D0 (en) * | 2002-06-26 | 2002-08-07 | Aventis Pharma Ltd | Method and packaging for pressurized containers |
| EP1818091B1 (en) * | 2003-12-03 | 2011-06-08 | Kyodo Printing Co., Ltd. | Moisture absorbent material with indicator function, humidity indicator and packaging bag |
| JP4413675B2 (en) * | 2004-03-30 | 2010-02-10 | 共同印刷株式会社 | Desiccant film and production method thereof |
| JP4659523B2 (en) * | 2005-04-26 | 2011-03-30 | 共同印刷株式会社 | Blister film and blister packaging container |
| JP2006346888A (en) * | 2005-06-13 | 2006-12-28 | Kyodo Printing Co Ltd | Selective hygroscopic film and multilayered film |
| EP2068812B9 (en) * | 2006-09-25 | 2012-08-08 | Takeda Pharmaceutical Company Limited | Medicinal package |
| KR101400653B1 (en) * | 2006-10-25 | 2014-05-27 | 다이이찌 산쿄 가부시키가이샤 | Packaging material |
| JP4849684B2 (en) * | 2007-09-20 | 2012-01-11 | リケンテクノス株式会社 | Composite multilayer film |
| TWI488746B (en) * | 2009-02-13 | 2015-06-21 | Toyo Aluminium Kk | Laminated body and container |
| WO2011099129A1 (en) * | 2010-02-10 | 2011-08-18 | リケンテクノス株式会社 | Composite multilayer film |
| WO2012029899A1 (en) * | 2010-09-01 | 2012-03-08 | アステラス製薬株式会社 | Package |
-
2012
- 2012-03-01 SG SG11201405153UA patent/SG11201405153UA/en unknown
- 2012-03-01 BR BR112014021667-3A patent/BR112014021667B1/en not_active IP Right Cessation
- 2012-03-01 CN CN201280001086.9A patent/CN102970959B/en active Active
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Also Published As
| Publication number | Publication date |
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| MX352703B (en) | 2017-12-05 |
| RU2014137243A (en) | 2016-04-20 |
| TWI539944B (en) | 2016-07-01 |
| HK1183226A1 (en) | 2013-12-20 |
| JP5922757B2 (en) | 2016-05-24 |
| AU2012371888A1 (en) | 2014-09-25 |
| SG11201405153UA (en) | 2014-10-30 |
| CN102970959B (en) | 2014-07-30 |
| RU2589826C2 (en) | 2016-07-10 |
| MY167571A (en) | 2018-09-20 |
| AU2012371888B2 (en) | 2015-03-26 |
| MX2014010440A (en) | 2015-04-13 |
| CN102970959A (en) | 2013-03-13 |
| WO2013128608A1 (en) | 2013-09-06 |
| BR112014021667B1 (en) | 2020-09-24 |
| TW201336488A (en) | 2013-09-16 |
| JPWO2013128608A1 (en) | 2015-07-30 |
| PH12014501944A1 (en) | 2014-11-24 |
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