JP4897479B2 - 濫用抵抗性経皮的剤形 - Google Patents
濫用抵抗性経皮的剤形 Download PDFInfo
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- JP4897479B2 JP4897479B2 JP2006507486A JP2006507486A JP4897479B2 JP 4897479 B2 JP4897479 B2 JP 4897479B2 JP 2006507486 A JP2006507486 A JP 2006507486A JP 2006507486 A JP2006507486 A JP 2006507486A JP 4897479 B2 JP4897479 B2 JP 4897479B2
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- 239000004702 low-density polyethylene Substances 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- 229960001252 methamphetamine Drugs 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229960001344 methylphenidate Drugs 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- NETZHAKZCGBWSS-CEDHKZHLSA-N nalbuphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]1(O)CC[C@@H]3O)CN2CC1CCC1 NETZHAKZCGBWSS-CEDHKZHLSA-N 0.000 description 1
- 229960000805 nalbuphine Drugs 0.000 description 1
- 229960004127 naloxone Drugs 0.000 description 1
- RGPDIGOSVORSAK-STHHAXOLSA-N naloxone hydrochloride Chemical compound Cl.O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4CC=C RGPDIGOSVORSAK-STHHAXOLSA-N 0.000 description 1
- 230000003533 narcotic effect Effects 0.000 description 1
- 239000004745 nonwoven fabric Substances 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 229940055577 oleyl alcohol Drugs 0.000 description 1
- XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 1
- 239000003402 opiate agonist Substances 0.000 description 1
- 239000003401 opiate antagonist Substances 0.000 description 1
- 229940005483 opioid analgesics Drugs 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- ADIMAYPTOBDMTL-UHFFFAOYSA-N oxazepam Chemical compound C12=CC(Cl)=CC=C2NC(=O)C(O)N=C1C1=CC=CC=C1 ADIMAYPTOBDMTL-UHFFFAOYSA-N 0.000 description 1
- 229960004535 oxazepam Drugs 0.000 description 1
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- 239000002245 particle Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000012254 powdered material Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 229940001470 psychoactive drug Drugs 0.000 description 1
- 239000004089 psychotropic agent Substances 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000007650 screen-printing Methods 0.000 description 1
- 239000012056 semi-solid material Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- GGCSSNBKKAUURC-UHFFFAOYSA-N sufentanil Chemical compound C1CN(CCC=2SC=CC=2)CCC1(COC)N(C(=O)CC)C1=CC=CC=C1 GGCSSNBKKAUURC-UHFFFAOYSA-N 0.000 description 1
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- 238000010345 tape casting Methods 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 235000007586 terpenes Nutrition 0.000 description 1
- 229940116411 terpineol Drugs 0.000 description 1
- 229920001897 terpolymer Polymers 0.000 description 1
- ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 1
- BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
- 239000004753 textile Substances 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 125000002889 tridecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Images
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- B09—DISPOSAL OF SOLID WASTE; RECLAMATION OF CONTAMINATED SOIL
- B09B—DISPOSAL OF SOLID WASTE NOT OTHERWISE PROVIDED FOR
- B09B3/00—Destroying solid waste or transforming solid waste into something useful or harmless
- B09B3/0075—Disposal of medical waste
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- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4468—Non condensed piperidines, e.g. piperocaine having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
- A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
- A61K9/7061—Polyacrylates
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7092—Transdermal patches having multiple drug layers or reservoirs, e.g. for obtaining a specific release pattern, or for combining different drugs
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- B09B—DISPOSAL OF SOLID WASTE NOT OTHERWISE PROVIDED FOR
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Description
下の実施例に示す皮膚浸透データは、以下の試験方法を使用して得られた。試験サンプルは、5.0cm2の総面積を有する経皮的デバイスであり、2.0cm2の活性薬剤含有領域を試験サンプルとして使用した。剥離ライナーを除去してパッチをヒト死体皮膚に被着し、圧迫して皮膚と均一に接触させた。得られたパッチ/皮膚ラミネートをパッチ面を上にして、垂直拡散セルの下位部のオリフィスを横切って置いた。拡散セルをアセンブルして、受容体流体が皮膚に接触するように、下位部に25mLの温(32℃)受容体流体(0.1Mリン酸塩緩衝液、pH6.8)を満たした。使用時以外はサンプリングポートを覆った。
試験サンプルは3.3cm2の経皮パッチであった。抽出溶液を以下の溶液の1つから選択した。酸緩衝生理食塩水(PBS、0.06Mリン酸塩緩衝液、pH6.5、0.5M塩化ナトリウム);ジエチルエーテル(BHT防腐剤添加試薬等級);脱イオン(DI)水;エタノール(USP、無水);酢酸エチル(HPLC等級)。
試験サンプルは20.0cm2のオーバーレイ経皮パッチ(活性領域10.5cm2)であった。4人の個人が、各タイプの単一パッチを試験した。試験者は、パッチの個々の層を示すダイヤグラムを与えられた。被験者はまた工具として使用するための小刀、ピンセット、および接着テープを提供された。各試験者には1時間が与えられ、ナルトレキソンからのフェンタニル分離を試みるため、パッチを機械的に分離するように指示された。フェンタニルを含有しナルトレキソンを含まないと思われる分離された材料を40mLバイアルに入れて、およそ5mLのメタノールで抽出してHPLCでフェンタニルおよびナルトレキソン含量の双方について試験した。結果を各パッチから回収されたフェンタニルの平均量、各パッチから回収されたナルトレキソンの平均量、および回収されたフェンタニルとナルトレキソンの比率として報告する。
イソオクチルアクリレート(714.00g)、2−ヒドロキシエチルアクリレート(523.00g)、エルバサイト(ELVACITE)(登録商標)1010(ICIアクリリック(Acrylics)から入手できる)のポリメチルメタクリレートマクロモノマー(52.00g)、2,2’−アゾビス(2−メチルブチロニトリル)(2.60g)、酢酸エチル(1245.50g)およびイソプロパノール(45.50g)を組み合わせて、マスターバッチを調製した。得られた溶液を等分に分割し、6本の1クォート(0.95L)こはく色ガラスびんに入れた。びんを窒素1分あたり1Lの流速で2分間パージした。びんを密封して57℃の回転水浴中に24時間入れた。24時間目にびんを回転水浴から取り出して開封し、びん毎に76gのメタノールで希釈して均質になるまで混和し、1ガロン(3.8L)のガラスジャー中で再度合わせた。得られた共重合体の固形分百分率は40.5%であった。インヘレント粘度I.V.(27℃で測定された酢酸エチル中の0.15g/dLポリマー溶液の)は、0.77dL/gであった。
2−エチルヘキシルアクリレート(234g)、ジメチルアミノエチルアクリラートメチル四級塩化物(90g)、メトキシポリエチレングリコール400アクリレート(54g)、メタノール(200.84g)、およびアセトン(221.14g)を組み合わせてマスターバッチを調製した。得られた溶液を等分に分割し、2本の1クォート(0.95L)こはく色ガラスびんに入れた。びんを窒素で1分あたり1Lの流速で2分間パージした。びんを密封して57℃の回転水浴中に24時間入れた。24時間目にびんを回転水浴から取り出して冷却した。メタノール(50g)およびアセトン(50g)をそれぞれのびんに添加して、均質になるまで混和した。次に得られた溶液をラジカルスカベンジャーでさらに6時間57℃で処理して、残留モノマーの量を低下させた。2本のびんの中の得られた共重合体溶液を1ガロン(3.8L)ガラスジャー中で合わせた。得られた共重合体の固形分百分率は36.3%であった。ブルックフィールド粘度は835センチポアズであった。
図3に従った経皮的剤形を次のようにして調製した。
図3に従った経皮的剤形を次のようにして調製した。
乾燥フェンタニルコーティングが8.0mg/cm2の付着量を有し、9.6%のフェンタニルを含有したこと以外は、実施例1と同一の概要に従って、経皮的剤形を調製した。上述の試験方法を使用して、緩衝生理食塩水中への溶剤抽出を測定した。結果を表1に示す。
乾燥フェンタニルコーティングが18.6mg/cm2の付着量を有したこと以外は、実施例1と同一の概要に従って経皮的剤形を調製した。上述の試験方法を使用して、緩衝生理食塩水中への溶剤抽出を測定した。結果を表1に示す。
図1に従った経皮的剤形を次のようにして調製した。乾燥フェンタニルコーティングが14.4mg/cm2の付着量を有し、乾燥ナルトレキソンコーティングが11.4mg/cm2の付着量を有したこと以外は、実施例1と同一の概要に従って乾燥フェンタニルおよびナルトレキソンコーティングを調製した。乾燥ナルトレキソンコーティングを乾燥フェンタニルコーティングのエチレンビニル酢酸側にラミネートして調製したマルチラミネート構造体を10.5cm2のパーツに転換した。
ナルトレキソンレザバー層が、実施例2で述べるような交互の乾燥ナルトレキソンコーティングとPVA層の5層ラミネートであったこと以外は、実施例5と同一の概要に従って経皮的剤形を調製した。上の方法で述べたようにして機械的分離試験を実施した。結果を表2に示す。
図1に従った経皮的剤形を次のようにして調製した。
実施例5で述べるようにして乾燥フェンタニルコーティングを調製したこと以外は、実施例7と同一の概要に従って経皮的剤形を調製した。上述の試験方法を使用して、ヒト死体皮膚を通したフェンタニルおよびナルトレキソン双方の浸透を測定した。結果を表3および4に示す。
Claims (5)
- ポリマー材料および活性薬剤を含んでなる活性薬剤構成要素、
オーバーレイバッキング、
濫用可能原薬に対する拮抗薬を含んでなる逆作用薬剤構成要素、
および前記逆作用薬剤構成要素と隣接し隣り合う多孔性材料
を含んでなる経皮的剤形であって、
前記活性薬剤構成要素が近位の皮膚接触面および前記近位表面に対向する遠位表面を有し、
前記逆作用薬剤構成要素が前記活性薬剤構成要素の前記遠位表面と前記オーバーレイバッキングとの間に挿入され、
前記多孔性材料と前記活性薬剤構成要素の前記近位表面との間で液体が自由に流れることができる、経皮的剤形。 - 前記活性薬剤構成要素と前記逆作用薬剤構成要素との間に挿入されるバリアをさらに含んでなる、請求項1に記載の経皮的剤形。
- 剥離ライナー、
オーバーレイバッキング、
前記剥離ライナーと前記オーバーレイバッキングとの間に挿入される活性薬剤構成要素、
前記活性薬剤構成要素と前記オーバーレイバッキングとの間に挿入されるバリア、
前記活性薬剤に対する拮抗薬を含んでなる逆作用薬剤構成要素、および
前記逆作用薬剤構成要素と隣接し隣り合う多孔性材料
を含んでなる経皮的剤形であって、
前記活性薬剤が前記剥離ライナーと拡散連通し、
前記逆作用薬剤構成要素が前記バリアと前記オーバーレイバッキングとの間に挿入され、
前記多孔性材料と前記剥離ライナーとの間で液体が自由に流れることができる、
経皮的剤形。 - 前記逆作用薬剤構成要素がマイクロ多孔性フィルムを含んでなる、請求項2又は3に記載の経皮的剤形。
- 前記活性薬剤がフェンタニルである、請求項1又は3に記載の経皮的剤形。
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US46723503P | 2003-04-30 | 2003-04-30 | |
US60/467,235 | 2003-04-30 | ||
US10/744,996 US7182955B2 (en) | 2003-04-30 | 2003-12-23 | Abuse-resistant transdermal dosage form |
US10/744,996 | 2003-12-23 | ||
PCT/US2004/008857 WO2004098576A1 (en) | 2003-04-30 | 2004-03-23 | Abuse-resistant transdermal dosage form |
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JP2006525316A JP2006525316A (ja) | 2006-11-09 |
JP2006525316A5 JP2006525316A5 (ja) | 2007-05-10 |
JP4897479B2 true JP4897479B2 (ja) | 2012-03-14 |
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US (1) | US7182955B2 (ja) |
EP (1) | EP1620080B1 (ja) |
JP (1) | JP4897479B2 (ja) |
AU (2) | AU2004237580A1 (ja) |
CA (1) | CA2523425A1 (ja) |
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US20040219195A1 (en) * | 2003-04-30 | 2004-11-04 | 3M Innovative Properties Company | Abuse-resistant transdermal dosage form |
US8790689B2 (en) * | 2003-04-30 | 2014-07-29 | Purdue Pharma L.P. | Tamper resistant transdermal dosage form |
MY141815A (en) * | 2003-04-30 | 2010-06-30 | Purdue Pharma Lp | Tamper-resistant transdermal dosage form comprising an active agent component and an adverse agent component at the distal site of the active agent layer |
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US20040219196A1 (en) | 2004-11-04 |
EP1620080A1 (en) | 2006-02-01 |
AU2010203118B2 (en) | 2011-05-12 |
CA2523425A1 (en) | 2004-11-18 |
US7182955B2 (en) | 2007-02-27 |
JP2006525316A (ja) | 2006-11-09 |
EP1620080B1 (en) | 2018-06-20 |
AU2010203118A1 (en) | 2010-08-12 |
AU2004237580A1 (en) | 2004-11-18 |
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