TWI527579B - 隔離水分及氧氣之包裝 - Google Patents
隔離水分及氧氣之包裝 Download PDFInfo
- Publication number
- TWI527579B TWI527579B TW097121640A TW97121640A TWI527579B TW I527579 B TWI527579 B TW I527579B TW 097121640 A TW097121640 A TW 097121640A TW 97121640 A TW97121640 A TW 97121640A TW I527579 B TWI527579 B TW I527579B
- Authority
- TW
- Taiwan
- Prior art keywords
- blister pack
- oxygen according
- tablet
- pvc
- isolating moisture
- Prior art date
Links
- 239000003826 tablet Substances 0.000 claims description 34
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 22
- 239000001301 oxygen Substances 0.000 claims description 22
- 229910052760 oxygen Inorganic materials 0.000 claims description 22
- 229910052782 aluminium Inorganic materials 0.000 claims description 16
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 16
- 239000011888 foil Substances 0.000 claims description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
- 239000007937 lozenge Substances 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 12
- 239000003963 antioxidant agent Substances 0.000 claims description 10
- 150000002148 esters Chemical class 0.000 claims description 9
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 8
- 229910052751 metal Inorganic materials 0.000 claims description 8
- 239000002184 metal Substances 0.000 claims description 8
- 230000003078 antioxidant effect Effects 0.000 claims description 6
- 150000002016 disaccharides Chemical class 0.000 claims description 6
- 150000002772 monosaccharides Chemical class 0.000 claims description 6
- 239000012298 atmosphere Substances 0.000 claims description 5
- 239000002738 chelating agent Substances 0.000 claims description 5
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 4
- 229930195725 Mannitol Natural products 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 239000008101 lactose Substances 0.000 claims description 4
- 235000019359 magnesium stearate Nutrition 0.000 claims description 4
- 239000000594 mannitol Substances 0.000 claims description 4
- 235000010355 mannitol Nutrition 0.000 claims description 4
- 239000001509 sodium citrate Substances 0.000 claims description 4
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 4
- 229910000838 Al alloy Inorganic materials 0.000 claims description 3
- 125000001931 aliphatic group Chemical group 0.000 claims description 3
- 229960001736 buprenorphine Drugs 0.000 claims description 3
- 229920000768 polyamine Polymers 0.000 claims description 3
- 239000004953 Aliphatic polyamide Substances 0.000 claims description 2
- 229920003231 aliphatic polyamide Polymers 0.000 claims description 2
- 239000002966 varnish Substances 0.000 claims description 2
- 244000248349 Citrus limon Species 0.000 claims 1
- 235000005979 Citrus limon Nutrition 0.000 claims 1
- RMRJXGBAOAMLHD-IHFGGWKQSA-N buprenorphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@]3([C@H](C1)[C@](C)(O)C(C)(C)C)OC)CN2CC1CC1 RMRJXGBAOAMLHD-IHFGGWKQSA-N 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 7
- 239000000126 substance Substances 0.000 description 6
- 238000002144 chemical decomposition reaction Methods 0.000 description 5
- 230000004888 barrier function Effects 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- RMRJXGBAOAMLHD-CTAPUXPBSA-N buprenorphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@@]3([C@H](C1)[C@](C)(O)C(C)(C)C)OC)CN2CC1CC1 RMRJXGBAOAMLHD-CTAPUXPBSA-N 0.000 description 3
- 239000011261 inert gas Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 239000007916 tablet composition Substances 0.000 description 3
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 2
- 229960004543 anhydrous citric acid Drugs 0.000 description 2
- UAIXRPCCYXNJMQ-RZIPZOSSSA-N buprenorphine hydrochlorie Chemical compound [Cl-].C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@]3([C@H](C1)[C@](C)(O)C(C)(C)C)OC)C[NH+]2CC1CC1 UAIXRPCCYXNJMQ-RZIPZOSSSA-N 0.000 description 2
- 235000015116 cappuccino Nutrition 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 229910001425 magnesium ion Inorganic materials 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000007769 metal material Substances 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 150000005846 sugar alcohols Chemical class 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- WJBLNOPPDWQMCH-MBPVOVBZSA-N Nalmefene Chemical compound N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CCC5=C)O)CC1)O)CC1CC1 WJBLNOPPDWQMCH-MBPVOVBZSA-N 0.000 description 1
- 208000026251 Opioid-Related disease Diseases 0.000 description 1
- 229920001328 Polyvinylidene chloride Polymers 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 229960001889 buprenorphine hydrochloride Drugs 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000002650 laminated plastic Substances 0.000 description 1
- 229960005297 nalmefene Drugs 0.000 description 1
- UZHSEJADLWPNLE-GRGSLBFTSA-N naloxone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4CC=C UZHSEJADLWPNLE-GRGSLBFTSA-N 0.000 description 1
- 229960004127 naloxone Drugs 0.000 description 1
- 229960003086 naltrexone Drugs 0.000 description 1
- DQCKKXVULJGBQN-XFWGSAIBSA-N naltrexone Chemical compound N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CCC5=O)O)CC1)O)CC1CC1 DQCKKXVULJGBQN-XFWGSAIBSA-N 0.000 description 1
- 201000005040 opiate dependence Diseases 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000009512 pharmaceutical packaging Methods 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 239000005033 polyvinylidene chloride Substances 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229940053209 suboxone Drugs 0.000 description 1
- 229940095172 subutex Drugs 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
Classifications
-
- 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
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
- B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
- B65D81/00—Containers, packaging elements, or packages, for contents presenting particular transport or storage problems, or adapted to be used for non-packaging purposes after removal of contents
- B65D81/18—Containers, packaging elements, or packages, for contents presenting particular transport or storage problems, or adapted to be used for non-packaging purposes after removal of contents providing specific environment for contents, e.g. temperature above or below ambient
- B65D81/20—Containers, packaging elements, or packages, for contents presenting particular transport or storage problems, or adapted to be used for non-packaging purposes after removal of contents providing specific environment for contents, e.g. temperature above or below ambient under vacuum or superatmospheric pressure, or in a special atmosphere, e.g. of inert gas
- B65D81/2069—Containers, packaging elements, or packages, for contents presenting particular transport or storage problems, or adapted to be used for non-packaging purposes after removal of contents providing specific environment for contents, e.g. temperature above or below ambient under vacuum or superatmospheric pressure, or in a special atmosphere, e.g. of inert gas in a special atmosphere
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
- B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
- B65D81/00—Containers, packaging elements, or packages, for contents presenting particular transport or storage problems, or adapted to be used for non-packaging purposes after removal of contents
- B65D81/24—Adaptations for preventing deterioration or decay of contents; Applications to the container or packaging material of food preservatives, fungicides, pesticides or animal repellants
-
- 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
- B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
- B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
- B65D75/00—Packages comprising articles or materials partially or wholly enclosed in strips, sheets, blanks, tubes or webs of flexible sheet material, e.g. in folded wrappers
- B65D75/28—Articles or materials wholly enclosed in composite wrappers, i.e. wrappers formed by associating or interconnecting two or more sheets or blanks
- B65D75/30—Articles or materials enclosed between two opposed sheets or blanks having their margins united, e.g. by pressure-sensitive adhesive, crimping, heat-sealing, or welding
- B65D75/32—Articles or materials enclosed between two opposed sheets or blanks having their margins united, e.g. by pressure-sensitive adhesive, crimping, heat-sealing, or welding one or both sheets or blanks being recessed to accommodate contents
- B65D75/36—Articles or materials enclosed between two opposed sheets or blanks having their margins united, e.g. by pressure-sensitive adhesive, crimping, heat-sealing, or welding one or both sheets or blanks being recessed to accommodate contents one sheet or blank being recessed and the other formed of relatively stiff flat sheet material, e.g. blister packages, the recess or recesses being preformed
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Mechanical Engineering (AREA)
- Emergency Medicine (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Food Science & Technology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Packages (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
Description
本發明係關於一種藥用錠劑之包裝，特別係關於含有布普諾芬(buprenorphine)或其鹽或其酯，就此或作為活性成分之一種，之藥用錠劑之包裝。
含有鹽酸布普諾芬之現有產品為添吉西(TEMGESIC)(商品名)、蘇布泰(SUBUTEX)(商品名)及蘇柏松(SUBOXONE)(商品名)，用於治療中度至重度疼痛或治療鴉片劑成癮之產品。添吉西及蘇布泰含有鹽酸布普諾芬作為唯一活性成分；蘇柏松含有鹽酸布普諾芬及拿洛松(naloxone)作為共同活性成分。
WO 2005/117838敘述鹽酸布普諾芬於酸性條件或鹼性條件下分解且可藉氧化分解。
穩定化布普諾芬之一項嘗試提供於US 6,365,596，該案揭示含有布普諾芬及至少一種抗氧化劑之醫藥組成物，抗氧化劑對布普諾芬之莫耳比係於1：1至3：1之範圍。US 6,365,596也述及經由避免鎂離子及聚乙烯基吡咯啶酮之存在可改良安定性。
於WO 2005/117838之發明中，改良部分係經由使用比US 6,365,596更低濃度之抗氧化劑(較佳為1：1000－1：10莫耳比之抗氧化劑：布普諾芬)及螯合劑(較佳為0.01－5% wt：wt)用以穩定化布普諾芬。
發明人瞭解原本就不宜使用大量抗氧化劑(依據US 6,365,596)或共同使用抗氧化劑與螯合劑(依據WO 2005/117838)俾便安定化布普諾芬及/或其鹽類或其酯類。
根據本發明之第一態樣，提供一種隔離水分及氧氣之包裝，該包裝包圍含有藥用錠劑之惰性氣氛，其中該等錠劑含有布普諾芬(buprenorphine)或其鹽或其酯。
較佳該惰性氣體為氮氣。
傳統含鹽酸布普諾芬之錠劑用之包裝為PVC/PVdC泡胞罩板包裝(blister pack)。PVC/PVdC為聚氯乙烯與聚偏氯乙烯之疊積體。一般接受PVC/PVdC作為適合用於多種藥品包裝之良好氧氣與水分之障體。雖言如此，發明人發現於此種包裝內儲存的錠劑，特別為活性成分鹽酸布普諾芬可能受到水分及氧氣二者的影響。
於本發明中，組合使用隔離水分及氧氣之障壁材料且維持錠劑於惰性氣體下，保護該(等)活性成分免於顯著化學分解。
後文於本發明所述辦法係與US 6,365,596及WO 2005/117838等先前技術方法相反，先前技術方法皆遵照藉改良化學配方來尋求安定性改良之辦法。
較佳各錠劑含有至少0.2毫克布普諾芬，較佳至少0.4毫克。
較佳各錠劑含有至多20毫克布普諾芬，較佳至多16毫克，較佳至多12毫克，較佳至多10毫克，較佳至多8毫克，較佳至多4毫克，較佳至多2毫克。
若存在有鹽類或酯類等形式，則經由單純的算術定規可將此等述及布普諾芬之數量轉成布普諾芬之鹽類或酯類之數量。
如此，當存在有鹽酸布普諾芬時，各錠較佳含有至少0.21毫克鹽酸布普諾芬，較佳至少0.43毫克；且較佳至多22毫克鹽酸布普諾芬，較佳至多18毫克，及更佳至多13毫克。於特佳實施例中，含鹽酸布普諾芬之各個錠劑含有至多11毫克鹽酸布普諾芬，較佳至多9毫克，較佳至多4.5毫克，較佳至多2.4毫克。
可存在有共同活性成分，以拿崔松(naltrexone)、拿米芬(nalmefene)且特別為拿洛松為佳。較佳此等共同活性成分之重量(或共同活性成分之總重)係不超過布普諾芬之重量；且較佳不大於布普諾芬之重量之50% wt/wt(比較非鹽、非酯化合物)。於錠劑中，布普諾芬對此種共同活性成分之重量比或對共同活性成分總重之重量比較佳係於2：1至8：1且更佳於3：1至5：1之範圍。
於此等及其它定義中，「布普諾芬」之重量也表示換算成為布普諾芬含量(亦即鹼)之鹽或酯之重量。若有多於一種布普諾芬化合物(例如布普諾芬及鹽酸布普諾芬)，則於定義中係使用換算成為布普諾芬之總重。
較佳錠劑包含至少一種單醣或雙醣或其混合物。
當存在有單醣時適合為糖例如葡萄糖、半乳糖、果糖或甘露糖，或糖醇例如甘露糖醇或山梨糖醇。較佳單醣數量或單醣總量係占組成物之15－50%wt/wt，較佳為20－40%wt/wt之範圍。糖醇類較佳為單醣類，尤其甘露糖醇。
當存在有雙醣時，適合為糖例如麥芽糖、乳糖或蔗糖。較佳雙醣之數量或雙醣之總量係於占組成物之20－70%wt/wt，且更佳為40－60%wt/wt之範圍。以乳糖為較佳雙醣。
較佳錠劑包含崩散劑。
當存在有崩散劑時，崩散劑適合為交聯羧甲基纖維素鈉、玉米澱粉或交聯普維隆(crospovidone)。較佳崩散劑數量或崩散劑總量係占組成物之1－30%wt/wt，且較佳為10－20%wt/wt之範圍。
較佳錠劑包含加壓助劑，其較佳含量係占組成物之0.1－2%wt/wt之範圍。較佳加壓助劑為硬脂酸鎂。
較佳錠劑包含無水檸檬酸與檸檬酸鈉較佳於2：1至1：1之重量比之混合物。較佳無水檸檬酸與檸檬酸鈉之總量係占組成物之0.5－4%wt/wt之範圍。
較佳該包裝具有隔離水分及氧氣之壁材。
較佳該包裝為有多個泡胞口袋各自含有一顆錠劑且各自含有惰性氣體進料之一種泡胞罩板包裝。
於較佳實施例中，該包裝係由具有隔離水分及隔離氧
氣之壁材之鋁或鋁－塑膠疊積體所製成，各個泡胞口袋含有氮氣之惰性氣氛及一顆錠劑。
本發明之隔離水分及隔離氧氣包裝具有由隔離水分且隔離氧氣之材料所製成之壁件或障壁件。隔離水分且隔離氧氣之材料一詞表示於25℃/60%相對濕度(RH)及40℃/75% RH之測試條件下具有比傳統PVC/PVdC材料更高度水分及氧氣隔離能力之材料。
於PVC/PVdC材料中，PVC被認為是「脆弱鏈接」。較佳本發明之泡胞罩板包裝包含金屬材料或由金屬材料所製成，例如鋁或鋁合金。最佳含有錠劑口袋之基底部分可由可冷成形箔所製成，該可冷成形箔包含一金屬層於其上方疊置一可藉錠劑撕裂之金屬箔來封閉該包裝。特佳為一種箔其包含一層金屬材料例如鋁或鋁合金疊積至一層脂肪族聚醯胺及/或一層PVC。特佳為一種箔具有厚10－40微米之一層脂肪族聚醯胺，然後為厚30－60微米之一金屬層，然後為厚40－80微米之PVC層，後者為產物接觸面。
該包裝可包裝以錠劑然後於惰性氣氛下密封。
較佳該泡胞罩板包裝至少含有6錠且更佳至少含有8錠。較佳該泡胞罩板包裝至多含有14錠且特別至多為12錠。
經由本發明所提供之保護表示無需添加非期望之成分諸如化學安定劑例如螯合劑或抗氧化劑至該錠劑配方俾便改良化學安定性。
較佳該等錠劑不含用以保護布普諾芬或其酸或其鹽之抗氧化劑。
較佳該等錠劑不含用以保護布普諾芬或其酸或其鹽之螯合劑。
較佳該等錠劑不含用以保護布普諾芬或其酸或其鹽之任一種組分。
本發明提供之保護表示無需刪除暗示可造成化學安定之某些成分；例如根據US 6,365,596之鎂離子或聚乙烯基吡咯啶酮。於本發明之包裝無需從錠劑中排除此等化合物。確實硬脂酸鎂為錠劑配方之較佳組分。
較佳本發明之包裝於包裝日期之後具有有效使用期至少為18個月；更佳至少為24個月。有效使用期可記錄於包裝本身上或記錄於二次包裝上。
根據第二態樣，提供一種製造第一態樣之包裝之方法，其中該等錠劑係於惰性氣氛下包圍於隔離水分及氧氣之材料中。
根據本發明之第三態樣，提供一種由該第一態樣之隔離水分及氧氣之包裝供給及/或投予錠劑之方法。
現在將參照下列實例進一步舉例說明本發明如下。
製造藥用錠劑含有下列成分。
該等錠劑製備如下。
全部賦形劑皆通過20號網眼篩網過篩。將乳糖、澱粉、甘露糖醇及普維隆徹底混合，使用先前藉攪拌溶解於純水與乙醇之混合物中之鹽酸布普諾芬、檸檬酸及檸檬酸鈉之溶液濕潤及造粒。所得顆粒於42－48℃乾燥至維持1－2%水含量。顆粒通過20號網眼篩網過篩及摻混。添加硬脂酸鎂至已過篩的顆粒及徹底混合。顆粒經過篩及再度摻混。混合物使用7/32吋(5.6毫米)衝頭打錠至錠劑重60毫克。
所得錠劑包裝成兩類型泡胞罩板包裝；一型係根據本發明，具有冷成形鋁箔托板，於惰性氮氣氣氛下藉可撕裂鋁箔蓋熱密封；另一類具有「250/60」PVC/PVdC托板(250 PVC，60 PVdC)及可撕裂鋁箔蓋。泡胞罩板包裝含有7顆錠
劑。本發明之包裝係於乾燥氮氣氣氛下進行俾便讓各個泡胞口袋含有氮氣。包裝於PVC/PVdC泡胞內部係於乾燥空氣下進行。各個錠劑口袋係藉可撕裂鋁箔蓋個別密封。錠劑包裝入泡胞托板內且於製造後即刻密封。
冷成形鋁箔托板具有厚25微米之脂肪族聚醯胺，厚46微米之鋁及厚60微米之PVC(產品接觸面)之疊積體。
可撕裂鋁箔蓋為12微米PET/25微米鋁/6－8克/平方米PVC/PVA清漆(產品接觸面)之50克/平方米罩蓋箔。
然後錠劑儲存於25℃溫度及60℃相對濕度(RH)及40℃/75% RH之恆定條件下。試樣於此等條件下於數個排定的時間點接受研究布普諾芬含量、發明人識別為主要分解產物之化合物含量及總相關分解產物。每錠含0.216毫克鹽酸布普諾芬共三批錠劑所得結果列表如下。此結果換算成0.2毫克布普諾芬，下列錠劑係引述布普諾芬含量(亦即100%＝0.2毫克)。
包裝於PVC/PVdC泡胞罩板包裝之錠劑之結果明白顯示活性成分布普諾芬之化學分解(或氧化)。當儲存時，布普諾芬含量有明確時間及溫度相依性之降低。此外，主要分解化合物含量及總布普諾芬相關分解產物含量有相對應之時間及溫度相依性增高。
於氮氣下包裝於鋁泡胞內部之錠劑結果於25℃/60% RH儲存36個月或於40℃/75% RH儲存12個月，並未顯示活性成分之明顯化學分解(或氧化)證據。布普諾芬含量並無時間或溫度相依性降低且分解產物含量並無時間或溫度相依性增高。
於PVC/PVdC包裝之錠劑明確顯示活性成分之化學分解，但Alu/N2
包裝之錠劑則否。
由本發明所提供之化學分解之保護表示無需添加非期望之成分諸如化學安定劑或抗氧化劑至錠劑配方用以改良化學安定性。
Claims (10)
- 一種隔離水分及氧氣之泡胞罩板(blister)包裝，其包圍惰性氣氛而其中含有藥用錠劑，其中該等錠劑含有布普諾芬(buprenorphine)或其鹽或其酯、以及無水檸檬酸與檸檬酸鈉之混合物，及其中該等錠劑未進一步包含用以保護該布普諾芬或其鹽或其酯之抗氧化劑或螯合劑，並且其中該泡胞罩板包裝包含含有金屬層之基底部分，於該金屬層上方疊置一可藉錠劑撕裂之金屬箔；其中該基底部分包含厚10-40微米之一層脂肪族聚醯胺，然後為厚30-60微米之一金屬層，然後為厚40-80微米之PVC層，該PVC層為產物接觸面；及其中該可藉錠劑撕裂之金屬箔係由50克/平方米之罩蓋箔構成，該罩蓋箔係由厚12微米之PET、厚25微米之鋁、及6-8克/平方米之PVC/PVA清漆所組成，該PVC/PVA為產品接觸面。
- 如申請專利範圍第1項之隔離水分及氧氣之泡胞罩板包裝，其中該基底部分之金屬層係鋁或鋁合金。
- 如申請專利範圍第1項之隔離水分及氧氣之泡胞罩板包裝，其中該基底部分包含冷成形鋁箔疊積體，其為厚25微米之脂肪族聚醯胺、厚46微米之鋁及厚60微米之PVC，該PVC層為產物接觸面。
- 如申請專利範圍第1至3項中任一項之隔離水分及氧氣之泡胞罩板包裝，其中該等錠劑包含0.2毫克至20毫克 布普諾芬或標定數量之其鹽或其酯。
- 如申請專利範圍第1至3項中任一項之隔離水分及氧氣之泡胞罩板包裝，其中各錠劑含有由0.21毫克至22毫克之鹽酸布普諾芬。
- 如申請專利範圍第1至3項中任一項之隔離水分及氧氣之泡胞罩板包裝，其中該等錠劑包括單醣或雙醣或其混合物。
- 如申請專利範圍第1至3項中任一項之隔離水分及氧氣之泡胞罩板包裝，其中該等錠劑包含乳糖。
- 如申請專利範圍第1至3項中任一項之隔離水分及氧氣之泡胞罩板包裝，其中該等錠劑包含甘露糖醇。
- 如申請專利範圍第1至3項中任一項之隔離水分及氧氣之泡胞罩板包裝，其中該等錠劑包含崩散劑。
- 如申請專利範圍第1至3項中任一項之隔離水分及氧氣之泡胞罩板包裝，其中該等錠劑包含硬脂酸鎂。
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0711376A GB2450117A (en) | 2007-06-13 | 2007-06-13 | A water- and oxygen-occlusive blister tablet pack |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW200911217A TW200911217A (en) | 2009-03-16 |
| TWI527579B true TWI527579B (zh) | 2016-04-01 |
Family
ID=38331999
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW097121640A TWI527579B (zh) | 2007-06-13 | 2008-06-11 | 隔離水分及氧氣之包裝 |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US8697718B2 (zh) |
| EP (1) | EP2155139B1 (zh) |
| CN (1) | CN101715337A (zh) |
| AR (1) | AR066975A1 (zh) |
| AU (3) | AU2008263682A1 (zh) |
| BR (1) | BRPI0812476A2 (zh) |
| CA (1) | CA2690036C (zh) |
| CL (1) | CL2008001744A1 (zh) |
| ES (1) | ES2626628T3 (zh) |
| GB (1) | GB2450117A (zh) |
| MX (1) | MX2009013535A (zh) |
| NZ (1) | NZ581604A (zh) |
| PE (1) | PE20090373A1 (zh) |
| TW (1) | TWI527579B (zh) |
| WO (1) | WO2008152347A2 (zh) |
| ZA (1) | ZA200908588B (zh) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RS53995B1 (sr) | 2011-09-19 | 2015-10-30 | Orexo Ab | Nove farmaceutske kompozicije, otporne na zloupotrebu, za tretman zavisnosti od opioida |
| CN108079221A (zh) * | 2018-02-27 | 2018-05-29 | 湖南尔康制药股份有限公司 | 一种维c银翘泡腾片 |
| CN108313367A (zh) * | 2018-02-27 | 2018-07-24 | 湖南尔康制药股份有限公司 | 一种充惰性气体包装的维c银翘片 |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5549204A (en) * | 1992-02-26 | 1996-08-27 | Toren Consulting Pty. Ltd. | Blister packs |
| JP2736952B2 (ja) * | 1992-09-18 | 1998-04-08 | 小野薬品工業株式会社 | アミジノフェノール誘導体およびその誘導体を有効成分として含有する薬剤 |
| US5858490A (en) * | 1993-06-10 | 1999-01-12 | Nkk Corporation | Film formed from polyethylene-2,6-naphthalate resin, process for producing said film and package using said film |
| CH689305A5 (de) * | 1994-08-23 | 1999-02-15 | Alusuisse Lonza Services Ag | Blisterpackung. |
| US5799463A (en) * | 1996-05-28 | 1998-09-01 | Mitsubishi Gas Chemical Company, Inc. | Method for preservation of article |
| US6592869B2 (en) * | 1999-08-24 | 2003-07-15 | Teva Pharmaceutical Industries, Ltd. | Vaccine composition and method of using the same |
| PL354872A1 (en) * | 1999-10-23 | 2004-03-08 | Alkaloid Ad | Oral dosage form comprising a salt of morphine or a morphine derivative |
| GB0015617D0 (en) * | 2000-06-26 | 2000-08-16 | Vectura Ltd | Improved preparations for dermal delivery of active substances |
| US7025992B2 (en) * | 2001-02-14 | 2006-04-11 | Gw Pharma Limited | Pharmaceutical formulations |
| EP1241110A1 (en) * | 2001-03-16 | 2002-09-18 | Pfizer Products Inc. | Dispensing unit for oxygen-sensitive drugs |
| SI21302A (sl) * | 2002-10-11 | 2004-04-30 | LEK farmacevtska dru�ba d.d. | Stabiliziran farmacevtski izdelek z amorfno aktivno učinkovino |
| WO2004064809A1 (en) * | 2003-01-22 | 2004-08-05 | Sandoz Ag | Solid pharmaceutical composition comprising ramipril |
| TWI322008B (en) * | 2003-01-31 | 2010-03-21 | Kaneka Corp | Fatigue improving agent including reduced coenzyme q10 |
| CA2553724A1 (en) * | 2004-02-03 | 2005-08-18 | Abbott Laboratories | Aminobenzoxazoles as therapeutic agents |
| ATE412404T1 (de) * | 2004-06-02 | 2008-11-15 | Galephar M F | Stabile orale pharmazeutische zusammensetzungen von buprenorphin und salz davon |
| CA2589283A1 (en) * | 2004-12-27 | 2006-07-06 | King Pharmaceuticals Research And Development, Inc. | Oxygen-impervious packaging and methods for storing thyroid hormone |
| TWI318571B (en) * | 2005-06-10 | 2009-12-21 | Lilly Co Eli | Formulation of a thienopyridine platelet aggregation inhibitor |
| US8148356B2 (en) * | 2005-08-24 | 2012-04-03 | Cumberland Pharmaceuticals, Inc. | Acetylcysteine composition and uses therefor |
| DE502005011092D1 (de) * | 2005-10-05 | 2011-04-21 | Berlin Chemie Ag | Pharmazeutische Schutzverpackung |
| WO2007084247A2 (en) * | 2005-12-28 | 2007-07-26 | Alza Corporation | Stable therapeutic formulations |
| EP1993607A4 (en) * | 2006-01-10 | 2012-03-28 | Pipex Inc | PHARMACEUTICAL COMPOSITIONS AND METHODS FOR OBTAINING AND MAINTAINING A TARGETABLE, STABLE COPPER RATE AND PREVENTING AND TREATING CENTRAL NERVOUS SYSTEM DISEASES RELATED TO SERIAL COPPER RATE |
-
2007
- 2007-06-13 GB GB0711376A patent/GB2450117A/en not_active Withdrawn
-
2008
- 2008-05-14 CA CA2690036A patent/CA2690036C/en not_active Expired - Fee Related
- 2008-05-14 MX MX2009013535A patent/MX2009013535A/es active IP Right Grant
- 2008-05-14 CN CN200880019695A patent/CN101715337A/zh active Pending
- 2008-05-14 WO PCT/GB2008/001659 patent/WO2008152347A2/en not_active Ceased
- 2008-05-14 NZ NZ581604A patent/NZ581604A/xx not_active IP Right Cessation
- 2008-05-14 US US12/664,285 patent/US8697718B2/en not_active Expired - Fee Related
- 2008-05-14 BR BRPI0812476-0A2A patent/BRPI0812476A2/pt not_active Application Discontinuation
- 2008-05-14 ES ES08750593.9T patent/ES2626628T3/es active Active
- 2008-05-14 AU AU2008263682A patent/AU2008263682A1/en not_active Abandoned
- 2008-05-14 EP EP08750593.9A patent/EP2155139B1/en not_active Not-in-force
- 2008-06-11 TW TW097121640A patent/TWI527579B/zh not_active IP Right Cessation
- 2008-06-12 PE PE2008001005A patent/PE20090373A1/es not_active Application Discontinuation
- 2008-06-12 AR ARP080102507A patent/AR066975A1/es unknown
- 2008-06-12 CL CL2008001744A patent/CL2008001744A1/es unknown
-
2009
- 2009-12-03 ZA ZA2009/08588A patent/ZA200908588B/en unknown
-
2014
- 2014-07-09 AU AU2014203766A patent/AU2014203766B2/en not_active Ceased
-
2016
- 2016-05-31 AU AU2016203632A patent/AU2016203632A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO2008152347A2 (en) | 2008-12-18 |
| US20100292265A1 (en) | 2010-11-18 |
| CA2690036A1 (en) | 2008-12-18 |
| ZA200908588B (en) | 2011-02-23 |
| US8697718B2 (en) | 2014-04-15 |
| CN101715337A (zh) | 2010-05-26 |
| WO2008152347A3 (en) | 2009-04-23 |
| EP2155139A2 (en) | 2010-02-24 |
| GB0711376D0 (en) | 2007-07-25 |
| MX2009013535A (es) | 2010-02-22 |
| CA2690036C (en) | 2016-07-05 |
| AU2014203766A1 (en) | 2014-07-31 |
| TW200911217A (en) | 2009-03-16 |
| AU2008263682A1 (en) | 2008-12-18 |
| GB2450117A (en) | 2008-12-17 |
| AR066975A1 (es) | 2009-09-23 |
| NZ581604A (en) | 2012-08-31 |
| CL2008001744A1 (es) | 2009-05-22 |
| EP2155139B1 (en) | 2017-04-05 |
| PE20090373A1 (es) | 2009-04-01 |
| AU2014203766B2 (en) | 2016-06-09 |
| AU2016203632A1 (en) | 2016-06-23 |
| ES2626628T3 (es) | 2017-07-25 |
| BRPI0812476A2 (pt) | 2014-12-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2233129B1 (en) | Oral cavity disintegrating tablet and method of producing the same | |
| JP5936542B2 (ja) | 包装体 | |
| BG65011B1 (bg) | Усъвършенствани бързоразпадащи се таблетки | |
| KR101461841B1 (ko) | 의약 | |
| CA2561856A1 (en) | Compressed composition comprising magnesium salt | |
| LT2011012A (lt) | Stabili derinių farmacinė kompozicija | |
| TWI527579B (zh) | 隔離水分及氧氣之包裝 | |
| JP2018076372A (ja) | アナグリプチン含有固形製剤 | |
| JPWO2019004452A1 (ja) | 医薬組成物 | |
| BG65503B1 (bg) | Таблетка за смучене, съдържаща амброксол | |
| JP2020070285A (ja) | 医薬品 | |
| HK1143520A (zh) | 药用片剂的包装 | |
| WO2005046646A2 (en) | Blister pack and solid dosage form comprising desmopressin | |
| EP2678006B1 (en) | Packaging of solid pharmaceutical preparations containing the active substance glyceryl trinitrate | |
| EP1353652A2 (en) | Pharmaceutical tablet comprising paroxetine mesylate | |
| EP1968552B1 (en) | blister pack | |
| TH69663A (th) | ฟลูดาราที่ให้ทางปากของสูตรผสมที่บริสุทธิ์สูงซึ่งมีการปลดปล่อยเร็วของส่วนผสมออกฤทธิ์ | |
| CZ27502U1 (cs) | Balení blistru nebo láhve obsahující tablety vardenafilu v inertní atmosféře |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Annulment or lapse of patent due to non-payment of fees |