JP2022058678A - ブプレノルフィンの乱用抵抗性粘膜付着性送達デバイス - Google Patents
ブプレノルフィンの乱用抵抗性粘膜付着性送達デバイス Download PDFInfo
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Abstract
Description
約4.0~約6.0のpHに緩衝されたブプレノルフィンを含む粘膜付着性層;および
約4.0~約4.8のpHに緩衝されたバッキング層
を含む。
約4.0~約6.0のpHに緩衝されたブプレノルフィンを含む粘膜付着性層;
および約4.0~約4.8のpHに緩衝されたバッキング層;
を含み:
ここで、デバイスから吸収されるブプレノルフィンのバイオアベイラビリティーは40%より大きい。いくつかの実施形態では、バイオアベイラビリティーは約60%である。いくつかの実施形態では、バイオアベイラビリティーは約65%である。いくつかの実施形態では、バイオアベイラビリティーは約75%である。
ブプレノルフィンを含み、第1のpHに緩衝された粘膜付着性層;
第2のpHに緩衝されたバッキング層;
を含み:
第2のpHは、ブプレノルフィンの経粘膜送達が妨げられないように、ブプレノルフィンのバイオアベイラビリティーが40%より大きくなるように選択される。いくつかの実施形態では、バッキング層はナロキソンを含み、ナロキソンの送達は妨げられる。
ブプレノルフィンを含み、第1のpHに緩衝された粘膜付着性層、
第2のpHに緩衝されたバッキング層、
を含み:
第1のpHおよび第2のpHは、ブプレノルフィンの粘膜への一方向送達勾配が妨げられないように、デバイスにより提供されるブプレノルフィンの総バイオアベイラビリティーが、バッキング層のpHを調節していない同じデバイスにより提供されるブプレノルフィンの総バイオアベイラビリティーと同等であるように選択される。1つの実施形態では、バッキング層はナロキソンを含み、ナロキソンの送達は妨げられる。
ブプレノルフィンを含み、第1のpHに緩衝された粘膜付着性層および第2のpHに緩衝されたバッキング層;
を含み:
ここで、第1のpHは、約4.0~約6.0であり、第2のpHは、約4.0~約4.8である。
ブプレノルフィンを含み、第1のpHに緩衝された粘膜付着性層および第2のpHに緩衝されたバッキング層;
を含み:
ここで、第1のpHは、約4.0~約6.0であり;第2のpHは、約4.0~約4.8であり;デバイスから吸収されるブプレノルフィンのバイオアベイラビリティーは40%より大きい。いくつかの実施形態では、バッキング層はナロキソンを含む。
ブプレノルフィンを含み、第1のpHに緩衝された粘膜付着性層およびナロキソンを含み、第2のpHに緩衝されたバッキング層;
を含み:
ここで、第1のpHは、約4.75であり;第2のpHは、約4.25であり;デバイスに配備されたブプレノルフィンおよびナロキソンは約6:1のブプレノルフィン:ナロキソンのw/w比率で存在する。
本発明の特定の側面は、オピオイド依存の被験体のための維持治療の提供方法を含む。現在では、ブプレノルフィン維持は、長期間の禁断に関して依存被験体のためのもっとも期待のできる行動方針の一つである。
本発明の特定の側面は、それを必要とする被検体への疼痛管理および/または軽減の提供方法を含む。疼痛は、全ての疾患、障害、状態および/または状況に起因する当該技術分野で知られる全ての痛みであり、慢性疼痛または急性疼痛であり得る。
本発明の特定の側面では、乱用抵抗性経粘膜送達デバイスが提供される。したがって、1つの実施形態では、本発明は、疼痛および/またはオピオイド依存の管理のための、被検体へのオピオイド薬剤の有効量の投与に適した乱用抵抗性粘膜付着性送達デバイスに関する。デバイスは、デバイスの粘膜表面への貼付の際に生じる一方向勾配(すなわち、粘膜に向かって流れる流れ)によりオピオイドアゴニストを送達することができる。
いくつかの実施形態では、粘膜付着性層は生体浸食性または水浸食性粘膜付着性層である。いくつかの実施形態では、本発明のデバイスは、粘膜付着性ポリマー拡散環境を含む生体浸食性粘膜付着性層を含む。デバイスは、適用(貼付)後約5秒以内に被検体の粘膜表面に付着する。
デバイスは、少なくとも1つの追加の非付着性ポリマー環境、例えばバッキング層を含む。この層、例えばバッキング層は粘膜付着性ポリマー拡散環境に隣接して配置され、ブプレノルフィンなどのオピオイドアゴニストの粘膜への送達を容易にするように機能するる。この追加の層は、粘膜付着性ポリマー拡散環境または非付着性ポリマー拡散環境と同じまたは異なる組み合わせのポリマーを含み得る。
以下の表1に記載するように、異なる薬用量のブプレノルフィンおよびナロキソンを含み、異なるpHに調製したバッキング層を有する、いくつかの製剤(formulation)を調製した。
これは、健常な被検体における非盲検(open label)、活性剤コントロール研究であり、製剤1および2からのブプレノルフィンおよびナロキソンの薬物動態パラメータをSuboxone(登録商標)舌下錠と比較した。分析のための血液サンプルを投与前並びに投与後0.5、1、1.5、2、3、4、6、8、12および16時間において採取し、液体クロマトグラフィーおよび質量分析法(LC/MS)を利用する確立された手法を使用して分析した。ブプレノルフィンおよび総ナロキソンの選択された薬物動態パラメータを表4および5に示す。
この研究は、製剤3および4からのブプレノルフィンおよびナロキソンの血漿薬物動態パラメータをSuboxone(登録商標)舌下錠と比較するために設計された。これは、24人の被験体において2人のうちから1人をランダム化した12-被検体の群における、単一薬用量で、2-期間、クロスオーバーデザインであった。各群は、ランダムな順序で、それぞれ少なくとも5日間離して、本発明のデバイスおよびSuboxone(登録商標)錠を受けた。群1の被検体は、単一低薬用量Suboxone(登録商標)錠(2.0mgのブプレノルフィンおよび0.5mgのナロキソンを含む)および製剤3の単一薬用量を受けた。群2の被検体は、単一高薬用量Suboxone(登録商標)錠(8.0mgのブプレノルフィンおよび2.0mgのナロキソンを含む)および製剤4の単一薬用量を受けた。単一研究薬剤投与前約12時間30分並びに単一研究薬剤投与後約12および24時間後にナルトレキソンを共に投与した。薬物動態分析のための連続血液サンプルを投与前並びに投与後15、30、45、60、75、90、105、120、135、150、165、180、210、240、270、300、330および360分および投与後8、10、12、24および48時間で採取した。血液サンプルを液体クロマトグラフィーおよび質量分析法(LC/MS)を利用する確立された手法を使用して分析した。ブプレノルフィンおよび遊離ナロキソンの選択された薬物動態パラメータを表6および7に示す。
この研究は、ブプレノルフィンのナロキソンに対して6:1のw/w比率で存在するブプレノルフィンおよびナロキソンを含み、pH4.25に処方されたバッキング層を有する製剤5、6および7の投与後のブプレノルフィンおよびナロキソン曝露の血漿薬物動態パラメータを評価するために設計された。この研究はまた、試験した薬用量の範囲にわたるブプレノルフィン曝露の直線性を立証するために設計された。加えて、製剤5により調製した4つのデバイス(4×0.875/0.15mg ブプレノルフィン/ナロキソン)の投与後の薬物動態プロファイルを、同等の薬用量の活性剤を含む製剤6により調製された単一デバイス(3.5/0.6mg ブプレノルフィン/ナロキソン)からのものと比較した。
製剤1、3および5により調製された本発明の経粘膜デバイスは、比較的少ない薬用量のブプレノルフィンおよびナロキソン(同等のSuboxone(登録商標)錠に含まれる2mg/0.5mgブプレノルフィン/ナロキソンと比較して、0.75mg/0.19mgおよび0.875/0.15mgブプレノルフィン/ナロキソン)を含む。ナロキソンのより少ない薬用量は製品を正確に使用する患者にとっては有益であり得るが、フルアゴニストオピオイドに依存する患者により経験される予想忌避反応を生じ得ない。したがって、本研究の目的は、オピオイド依存被験体におけるブプレノルフィンの0.75mg薬用量と共に投与される場合に、退薬応答を生じるナロキソンの最小有効薬用量を決定することであった。研究の二次的な目的は、ナロキソンなしのブプレノルフィンの0.75mg薬用量の投与がオピオイド依存被験体における退薬応答を生じるかどうかを決定することであった。
研究は、4期間クロスオーバーを完了する全12人の成人被験体を含むように設計された。被検体は以下の基準に適合する場合に研究に含めることに適しているものとした:
研究の前に少なくとも3ヵ月間、1日につき>100mgモルヒネ同等量で治療されている慢性的な中等度から重度の癌ではない疼痛を経験している被験体;
ナロキソン検証(Naloxone Challenge)中のナロキソン投与後に退薬の徴候および症状(すなわち、COWSスコア>5)を示した被検体。
入院患者の治療中に、来院被験体は、単一の、3mL IVボーラス投与の、以下のそれぞれの治療を少なくとも72時間離して受けた。
b) ブプレノルフィン0.75mg+ナロキソン0.1mg(BN1)
c) ブプレノルフィン0.75mg+ナロキソン0.2mg(BN2)
d) プラセボ(5%デキストロース)(P)
研究手法
適格被験体は、8回までのナロキソンの0.05mg IV投与の投与後、退薬の徴候(例えばナロキソン退薬試験に対し肯定的な応答(COWS>5)を有する)を示した。
臨床オピエート退薬スケール(COWS)を用いて、オピオイド退薬の症状を評価した。スケールは、脈拍数、消化器不調、発汗、身震い、不穏状態、あくび、瞳孔径、不安または興奮性、骨または関節痛、鳥肌、鼻水、涙を含むオピオイド退薬の徴候および症状を評価するための11の項目を含む。それぞれの症状は固有のスケールで評価される。スケールにおける総スコアは0~48の範囲であり、5~12のスコアは軽い退薬を示し;13~24のスコアは中等度の退薬を示し;25~36のスコアはやや重度の退薬を示し;>36のスコアは重度の退薬を示す。
以下の項目:点頭、重いまたはだるい感覚、口渇、呑気、快然、活気的、胃のむかむか、皮膚のかゆみ、リラックス、惰性、ソープボックス、プレサントシック(pleasant sick)、気力、酔い、親しみやすさ、および神経質を、5ポイントリッカートスケール(0=全くなし、1=少し、2=中程度、3=かなり、4=ひどい)を使用して評価するために被検体への質問を行った。
記述統計を、公式の統計的検定なしで、それぞれの時点における、それぞれの治療群に対するPD分析からの結果をまとめるために使用した。混合効果モデルを、総スコアにおけるベースラインからの変化に対するデータにフィットさせた。ここで、モデルは、全体的な平均の変化;順序による固定効果;治療、時期および期間;並びに順序内に組み入れられる被検体に対するランダム効果の因子を含んでいた。
COWS総スコア、および救済結果
投与後最初の1時間で少なくとも7のCOWS総スコアを有する被検体の数を図4の左側に示す。ブプレノルフィンのみにおいては、8人の被験体が少なくとも7のCOWS値を有し、それと比較して、ブプレノルフィンとナロキソン0.1mgの群では9人、ブプレノルフィンとナロキソン0.2mgの群では12人の被検体、プラセボでは2人であった。同様に、COWS>13は、6人のブプレノルフィン被検体、9人のブプレノルフィンとナロキソン0.1mgの被検体、10人のブプレノルフィンとナロキソン0.2mgの被検体、2人のプラセボ患者であった。15人の被検体の内の2人が、プラセボを含む、それぞれの研究治療において退薬を経験した。
救済されなかった被検体における1時間での中央DEQ応答を、下記表11において示す。
本発明について様々な実施形態および実施例と共に記載してきたが、本開示はそのような実施形態または実施例に限定されるものではない。それどころか、本発明は、当業者に認識されるように、様々な代替案、改変、および等価物を含む。
(付記)
(付記1)
疼痛またはオピオイド依存を管理するのに使用するための乱用抑止粘膜付着性デバイスであって、
約4.0~約6.0のpHに緩衝された有効量のブプレノルフィンを含む粘膜付着性層;および
約4.0~約4.8のpHに緩衝されたバッキング層
を含む、前記デバイス。
(付記2)
バッキング層が有効量のナロキソンを含み、デバイスに存在するブプレノルフィンのナロキソンに対するw/w比率が1:1~10:1である、付記1に記載のデバイス。
(付記3)
デバイスに存在するブプレノルフィンのナロキソンに対するw/w比率が6:1である、付記2に記載のデバイス。
(付記4)
粘膜付着性層が約4.50~約5.50のpHに緩衝され、バッキング層が約4.10~約4.4のpHに緩衝されている、付記3に記載のデバイス。
(付記5)
粘膜付着性層が約4.75のpHに緩衝され、バッキング層が約4.25のpHに緩衝されている、付記4に記載のデバイス。
(付記6)
約0.075~12mgのブプレノルフィンを含む、付記1に記載のデバイス。
(付記7)
約0.0125~2mgのナロキソンを含む、付記2に記載のデバイス。
(付記8)
デバイスから吸収されたブプレノルフィンのバイオアベイラビリティーが40%より大きい、付記1に記載のデバイス。
Claims (1)
- 明細書に記載された発明。
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Families Citing this family (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101230804B1 (ko) * | 2006-07-21 | 2013-02-08 | 바이오딜리버리 사이언시스 인터내셔널 인코포레이티드 | 향상된 흡수를 갖는 경점막 전달 장치 |
CA2841785A1 (en) | 2011-07-06 | 2013-01-10 | The Parkinson's Institute | Compositions and methods for treatment of symptoms in parkinson's disease patients |
CA3119258A1 (en) * | 2011-08-18 | 2013-02-21 | Biodelivery Sciences International, Inc. | Abuse-resistant mucoadhesive devices for delivery of buprenorphine |
US9901539B2 (en) | 2011-12-21 | 2018-02-27 | Biodelivery Sciences International, Inc. | Transmucosal drug delivery devices for use in chronic pain relief |
MA40074A (fr) * | 2014-05-30 | 2015-12-03 | Univ Columbia | Composés liant ras multivalents |
US20160144528A1 (en) | 2014-11-25 | 2016-05-26 | Biodelivery Sciences International, Inc. | Patch devices, methods and apparatus for forming, and testing pharmaceutical agent delivery patch devices |
US20160175296A1 (en) * | 2014-12-23 | 2016-06-23 | Arx, Llc | Method of producing uniform buprenorphine-containing formulations |
AU2016211330A1 (en) | 2015-01-28 | 2017-08-03 | Chrono Therapeutics Inc. | Drug delivery methods and systems |
US10679516B2 (en) | 2015-03-12 | 2020-06-09 | Morningside Venture Investments Limited | Craving input and support system |
WO2017196445A1 (en) * | 2016-05-11 | 2017-11-16 | Relmada Therapeutics, Inc. | Abrasion-resistant opioid formulations |
WO2018129304A1 (en) | 2017-01-06 | 2018-07-12 | Chrono Therapeutics Inc. | Transdermal drug delivery devices and methods |
US10058531B1 (en) * | 2017-06-01 | 2018-08-28 | Spartak LLC | Dosage delivery film |
JP2021515034A (ja) * | 2018-02-22 | 2021-06-17 | アビオール、インコーポレイテッド | 経粘膜フィルム組成物ならびにそれを作製及び使用する方法 |
EP3801732A4 (en) | 2018-05-29 | 2022-04-27 | Morningside Venture Investments Limited | DRUG DELIVERY METHODS AND SYSTEMS |
US11648197B2 (en) | 2018-06-28 | 2023-05-16 | Arx, Llc | Dispensing method for producing dissolvable unit dose film constructs |
US11318107B2 (en) | 2019-02-22 | 2022-05-03 | Avior, Inc. | Pharmaceutical active-containing film delivery device for oral transmucosal administration |
US11793980B2 (en) | 2019-08-31 | 2023-10-24 | Celero Systems, Inc. | Intestinal attachment device |
US11179331B1 (en) | 2020-04-21 | 2021-11-23 | Cure Pharmaceutcai Holding Corp | Oral soluble film containing sildenafil citrate |
Family Cites Families (133)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB981372A (en) | 1960-05-04 | 1965-01-27 | Pfizer Ltd | Pharmaceutical formulations for oral administration to animals |
US3640741A (en) | 1970-02-24 | 1972-02-08 | Hollister Inc | Composition containing gel |
US3996934A (en) | 1971-08-09 | 1976-12-14 | Alza Corporation | Medical bandage |
JPS5562012A (en) | 1978-11-06 | 1980-05-10 | Teijin Ltd | Slow-releasing preparation |
GB2042888B (en) | 1979-03-05 | 1983-09-28 | Teijin Ltd | Preparation for administration to the mucosa of the oral or nasal cavity |
US4285934A (en) | 1979-07-13 | 1981-08-25 | Tinnell James E | Treatment for herpes virus |
US4286592A (en) | 1980-02-04 | 1981-09-01 | Alza Corporation | Therapeutic system for administering drugs to the skin |
US4381296A (en) | 1980-06-23 | 1983-04-26 | Tinnell James E | Treatment for herpes virus |
JPS5758615A (en) | 1980-09-26 | 1982-04-08 | Nippon Soda Co Ltd | Film agnent and its preparation |
JPS5770816A (en) | 1980-10-17 | 1982-05-01 | Ono Pharmaceut Co Ltd | Multilayered film preparation of prostagladin of prolonged action |
JPS57110254A (en) | 1980-12-29 | 1982-07-09 | Teijin Ltd | Coating agent of injured membrane part of oral cavity |
CH653550A5 (de) | 1981-10-20 | 1986-01-15 | Sandoz Ag | Pharmazeutische zusammensetzung zur verzoegerten freigabe eines medikamentes im mundbereich. |
US4518721A (en) | 1982-03-26 | 1985-05-21 | Richardson-Vicks Inc. | Hydrophilic denture adhesive |
JPS5948409A (ja) | 1982-09-10 | 1984-03-19 | Teikoku Seiyaku Kk | 矯正的歯牙移動促進剤 |
CA1208558A (en) | 1982-10-07 | 1986-07-29 | Kazuo Kigasawa | Soft buccal |
JPS604120A (ja) | 1983-06-22 | 1985-01-10 | Shionogi & Co Ltd | 作用持続型ピナシジル製剤 |
GB8332556D0 (en) | 1983-12-06 | 1984-01-11 | Reckitt & Colmann Prod Ltd | Analgesic compositions |
US4713246A (en) | 1984-03-19 | 1987-12-15 | Bristol-Myers Company | Etoposide oral dosage form |
EP0159604B1 (en) | 1984-04-09 | 1990-11-07 | Toyo Boseki Kabushiki Kaisha | Sustained-release preparation applicable to mucous membrane in oral cavity |
EP0186019B1 (de) | 1984-12-22 | 1993-10-06 | Schwarz Pharma Ag | Wirkstoffpflaster |
US5288497A (en) | 1985-05-01 | 1994-02-22 | The University Of Utah | Compositions of oral dissolvable medicaments |
JPS61280423A (ja) | 1985-06-05 | 1986-12-11 | Kiyuukiyuu Yakuhin Kogyo Kk | 口腔内粘膜貼付剤 |
GB8521494D0 (en) | 1985-08-29 | 1985-10-02 | Zyma Sa | Controlled release tablet |
US4755386A (en) | 1986-01-22 | 1988-07-05 | Schering Corporation | Buccal formulation |
JPH0729915B2 (ja) | 1986-02-01 | 1995-04-05 | 帝國製薬株式会社 | シ−ト状口腔内貼付剤 |
US4764378A (en) | 1986-02-10 | 1988-08-16 | Zetachron, Inc. | Buccal drug dosage form |
US4713243A (en) | 1986-06-16 | 1987-12-15 | Johnson & Johnson Products, Inc. | Bioadhesive extruded film for intra-oral drug delivery and process |
CH668187A5 (de) | 1986-08-07 | 1988-12-15 | Ciba Geigy Ag | Therapeutisches system mit systemischer wirkung. |
JPH0794384B2 (ja) | 1986-09-01 | 1995-10-11 | 帝国製薬株式会社 | 徐放性口腔内用製剤 |
US5196202A (en) | 1986-09-01 | 1993-03-23 | Teikoku Seiyaku Kabushiki Kaisha | Sustained release dosage form |
US4906463A (en) | 1986-12-22 | 1990-03-06 | Cygnus Research Corporation | Transdermal drug-delivery composition |
JPH0744940B2 (ja) | 1986-12-24 | 1995-05-17 | ライオン株式会社 | 口腔貼付用基材 |
DE3714074A1 (de) | 1987-04-28 | 1988-11-10 | Hoechst Ag | Grundlage fuer schleimhaut- und prothesenhaft-pasten, verfahren zu ihrer herstellung sowie pasten auf basis dieser grundlage |
US4867970A (en) | 1987-05-21 | 1989-09-19 | E. R. Squibb & Sons, Inc. | Moistureless oral drug delivery formulation and method for preparing same |
US4915948A (en) | 1987-08-31 | 1990-04-10 | Warner-Lambert Company | Tablets having improved bioadhesion to mucous membranes |
US5059189A (en) | 1987-09-08 | 1991-10-22 | E. R. Squibb & Sons, Inc. | Method of preparing adhesive dressings containing a pharmaceutically active ingredient |
US4990339A (en) | 1987-11-16 | 1991-02-05 | H. B. Fuller Company | Dermal treatment film |
US5064654A (en) | 1989-01-11 | 1991-11-12 | Ciba-Geigy Corporation | Mixed solvent mutually enhanced transdermal therapeutic system |
GB8804164D0 (en) | 1988-02-23 | 1988-03-23 | Tucker J M | Bandage for administering physiologically active compound |
US4900552A (en) | 1988-03-30 | 1990-02-13 | Watson Laboratories, Inc. | Mucoadhesive buccal dosage forms |
US5081157A (en) | 1988-05-02 | 1992-01-14 | Zila Pharmaceuticals, Inc. | Compositions and in situ methods for forming films on body tissue |
US5081158A (en) | 1988-05-02 | 1992-01-14 | Zila Pharmaceuticals, Inc. | Compositions and in situ methods for forming films on body tissue |
US5047244A (en) | 1988-06-03 | 1991-09-10 | Watson Laboratories, Inc. | Mucoadhesive carrier for delivery of therapeutical agent |
US5236714A (en) | 1988-11-01 | 1993-08-17 | Alza Corporation | Abusable substance dosage form having reduced abuse potential |
JPH0645536B2 (ja) | 1989-01-31 | 1994-06-15 | 日東電工株式会社 | 口腔粘膜貼付剤および口腔粘膜貼付製剤 |
JP2656338B2 (ja) | 1989-01-31 | 1997-09-24 | 日東電工株式会社 | 口腔粘膜貼付製剤 |
US5750136A (en) | 1989-11-03 | 1998-05-12 | Riker Laboratories, Inc. | Bioadhesive composition and patch |
JP2839164B2 (ja) | 1989-12-25 | 1998-12-16 | 帝國製薬株式会社 | 消炎鎮痛貼付剤 |
US5298258A (en) | 1989-12-28 | 1994-03-29 | Nitto Denko Corporation | Acrylic oily gel bioadhesive material and acrylic oily gel preparation |
US5332576A (en) | 1991-02-27 | 1994-07-26 | Noven Pharmaceuticals, Inc. | Compositions and methods for topical administration of pharmaceutically active agents |
US5149538A (en) | 1991-06-14 | 1992-09-22 | Warner-Lambert Company | Misuse-resistive transdermal opioid dosage form |
US5192802A (en) | 1991-09-25 | 1993-03-09 | Mcneil-Ppc, Inc. | Bioadhesive pharmaceutical carrier |
US5254345A (en) | 1991-10-11 | 1993-10-19 | Merck & Co., Inc. | Poly(orthocarbonate acetal) bioerodible polymers |
GB2273044B (en) | 1992-12-02 | 1997-04-09 | Pacific Chem Co Ltd | Medicinal patches for percutaneous administration |
US5346701A (en) | 1993-02-22 | 1994-09-13 | Theratech, Inc. | Transmucosal delivery of macromolecular drugs |
AU7323794A (en) | 1993-07-09 | 1995-02-06 | Cygnus Therapeutic Systems | Method and device for providing nicotine replacement therapy transdermally/transbuccally |
AU7568394A (en) | 1993-08-19 | 1995-03-14 | Cygnus Therapeutic Systems | Water-soluble pressure-sensitive mucoadhesive and devices provided therewith for emplacement in a mucosa-lined body cavity |
US5540930A (en) | 1993-10-25 | 1996-07-30 | Pharmos Corporation | Suspension of loteprednol etabonate for ear, eye, or nose treatment |
FR2712807B1 (fr) | 1993-11-24 | 1996-02-23 | Vetoquinol Sa | Composition solide mucoadhésive, thérapeutique ou hygiénique, pour administration par application sur la muqueuse buccale ou nasale . |
DE4341442C2 (de) | 1993-12-04 | 1998-11-05 | Lohmann Therapie Syst Lts | Vorrichtung zur kontrollierten Freisetzung von Wirkstoffen sowie ihre Verwendung |
US5466465A (en) | 1993-12-30 | 1995-11-14 | Harrogate Holdings, Limited | Transdermal drug delivery system |
US5679714A (en) | 1995-06-07 | 1997-10-21 | Weg; Stuart L. | Administration of ketamine for detoxification and treatment of tobacco addiction |
WO1996000072A1 (en) | 1994-06-23 | 1996-01-04 | The Procter & Gamble Company | Treatment of nicotine craving and/or smoking withdrawal symptoms with a transdermal or transmucosal composition containing nicotine and caffeine or xanthine |
DE69625549T2 (de) | 1995-06-27 | 2003-05-15 | Kao Corp | Pflaster mit wasserlöslicher Klebeschicht |
US5849322A (en) | 1995-10-23 | 1998-12-15 | Theratech, Inc. | Compositions and methods for buccal delivery of pharmaceutical agents |
JP2791317B2 (ja) | 1995-12-26 | 1998-08-27 | 株式会社三和化学研究所 | 多層フィルム製剤 |
FR2742989B1 (fr) | 1995-12-29 | 1998-01-23 | Adir | Composition pharmaceutique bioadhesive pour la liberation controlee de principes actifs |
US5985317A (en) | 1996-09-06 | 1999-11-16 | Theratech, Inc. | Pressure sensitive adhesive matrix patches for transdermal delivery of salts of pharmaceutical agents |
US5800832A (en) | 1996-10-18 | 1998-09-01 | Virotex Corporation | Bioerodable film for delivery of pharmaceutical compounds to mucosal surfaces |
DE19646392A1 (de) | 1996-11-11 | 1998-05-14 | Lohmann Therapie Syst Lts | Zubereitung zur Anwendung in der Mundhöhle mit einer an der Schleimhaut haftklebenden, Pharmazeutika oder Kosmetika zur dosierten Abgabe enthaltenden Schicht |
US6248358B1 (en) | 1998-08-25 | 2001-06-19 | Columbia Laboratories, Inc. | Bioadhesive progressive hydration tablets and methods of making and using the same |
DE69833000T2 (de) | 1997-09-26 | 2006-09-07 | Noven Pharmaceuticals, Inc., Miami | Bio-klebemittelzusammensetzungen |
US20040018241A1 (en) | 1997-09-26 | 2004-01-29 | Noven Pharmaceuticals, Inc. | Bioadhesive compositions and methods for topical administration of active agents |
US20050048102A1 (en) | 1997-10-16 | 2005-03-03 | Virotex Corporation | Pharmaceutical carrier device suitable for delivery of pharmaceutical compounds to mucosal surfaces |
US6375957B1 (en) | 1997-12-22 | 2002-04-23 | Euro-Celtique, S.A. | Opioid agonist/opioid antagonist/acetaminophen combinations |
UA53774C2 (uk) | 1997-12-22 | 2003-02-17 | Еро-Селтік, С.А. | Спосіб запобігання зловживанню лікарськими формами, що містять опіоїди |
WO1999032119A1 (en) | 1997-12-22 | 1999-07-01 | Euro-Celtique, S.A. | Opioid agonist/antagonist combinations |
US6200604B1 (en) | 1998-03-27 | 2001-03-13 | Cima Labs Inc. | Sublingual buccal effervescent |
EP1079813B1 (en) | 1998-04-29 | 2005-02-09 | Virotex Corporation | Pharmaceutical carrier device suitable for delivery of pharmaceutical compounds to mucosal surfaces |
SE9803239D0 (sv) | 1998-09-24 | 1998-09-24 | Diabact Ab | Composition for the treatment of acute pain |
US20030170195A1 (en) | 2000-01-10 | 2003-09-11 | Noven Pharmaceuticals, Inc. | Compositions and methods for drug delivery |
PT1061900E (pt) | 1999-01-14 | 2005-04-29 | Noven Pharma | Composicoes e metodos para libertacao de uma droga |
US6284262B1 (en) | 1999-01-26 | 2001-09-04 | Virgil A. Place | Compact dosage unit for buccal administration of a pharmacologically active agent |
DE19960154A1 (de) | 1999-12-14 | 2001-07-12 | Lohmann Therapie Syst Lts | Flache Arzneizubereitung zur transmucosalen Verabreichung von Oxycodon oder einem vergleichbaren Wirkstoff in der Mundhöhle, für die Anwendung in der Schmerztherapie und Suchttherapie |
US20030124176A1 (en) | 1999-12-16 | 2003-07-03 | Tsung-Min Hsu | Transdermal and topical administration of drugs using basic permeation enhancers |
US20030104041A1 (en) | 1999-12-16 | 2003-06-05 | Tsung-Min Hsu | Transdermal and topical administration of drugs using basic permeation enhancers |
US6582724B2 (en) | 1999-12-16 | 2003-06-24 | Dermatrends, Inc. | Dual enhancer composition for topical and transdermal drug delivery |
US20050074487A1 (en) | 1999-12-16 | 2005-04-07 | Tsung-Min Hsu | Transdermal and topical administration of drugs using basic permeation enhancers |
US6719997B2 (en) | 2000-06-30 | 2004-04-13 | Dermatrends, Inc. | Transdermal administration of pharmacologically active amines using hydroxide-releasing agents as permeation enhancers |
HU229705B1 (en) | 2000-02-08 | 2014-05-28 | Euro Celtique Sa | Tamper-resistant oral opioid agonist formulations |
US6716449B2 (en) | 2000-02-08 | 2004-04-06 | Euro-Celtique S.A. | Controlled-release compositions containing opioid agonist and antagonist |
GB0026137D0 (en) | 2000-10-25 | 2000-12-13 | Euro Celtique Sa | Transdermal dosage form |
DE10195984D2 (de) | 2001-02-09 | 2004-01-22 | Hager & Werken Gmbh & Co Kg | Injektionsspritze sowie Entsorgungsbehälter für Injektionsnadeleinheiten |
US20020160043A1 (en) | 2001-02-27 | 2002-10-31 | Dennis Coleman | Compositions and method of manufacture for oral dissolvable dosage forms |
DE60230138D1 (de) | 2001-05-01 | 2009-01-15 | Euro Celtique Sa | Vor missbrauch geschützte opioid-haltige transdermale systeme |
ES2275868T3 (es) * | 2001-05-11 | 2007-06-16 | Endo Pharmaceuticals Inc. | Forma de dosificacion de opioide para impedir el consumo abusivo. |
US7144587B2 (en) | 2001-08-06 | 2006-12-05 | Euro-Celtique S.A. | Pharmaceutical formulation containing opioid agonist, opioid antagonist and bittering agent |
US7157103B2 (en) | 2001-08-06 | 2007-01-02 | Euro-Celtique S.A. | Pharmaceutical formulation containing irritant |
US20110033542A1 (en) * | 2009-08-07 | 2011-02-10 | Monosol Rx, Llc | Sublingual and buccal film compositions |
US7666876B2 (en) | 2002-03-19 | 2010-02-23 | Vernalis (R&D) Limited | Buprenorphine formulations for intranasal delivery |
US20030194420A1 (en) | 2002-04-11 | 2003-10-16 | Richard Holl | Process for loading a drug delivery device |
AU2003234395B2 (en) | 2002-05-13 | 2008-01-24 | Endo Pharmaceuticals Inc. | Abuse-resistant opioid solid dosage form |
KR101407131B1 (ko) | 2002-06-10 | 2014-06-19 | 유로-셀티크 소시에떼 아노뉨 | 경피 전달 장치에 포함된 활성 성분의 오용을 방지하는 경피 전달 장치의 처리 시스템 |
JP4642467B2 (ja) | 2002-08-20 | 2011-03-02 | ユーロ−セルティーク エス.エイ. | 活性剤及び塩並びに副作用物質の遊離塩基形を含む経皮剤形 |
NZ540318A (en) | 2002-10-31 | 2007-09-28 | Umd Inc | Therapeutic compositions for drug delivery to and through covering epithelia |
US20050013845A1 (en) | 2002-11-12 | 2005-01-20 | Warren Stephen L. | Adhesive bioerodible ocular drug delivery system |
US20040110781A1 (en) | 2002-12-05 | 2004-06-10 | Harmon Troy M. | Pharmaceutical compositions containing indistinguishable drug components |
DK1572167T3 (da) | 2002-12-13 | 2008-10-13 | Euro Celtique Sa | Transdermal buprenophindoseringsbehandlingsplan for analgesi |
US20040191301A1 (en) | 2003-03-27 | 2004-09-30 | Van Duren Albert Philip | Transdermal device having a phase change material |
US20040213828A1 (en) | 2003-04-23 | 2004-10-28 | Smith David J. | Pain relief lollipop compositions and methods |
US8778382B2 (en) | 2003-04-30 | 2014-07-15 | Purdue Pharma L.P. | Tamper resistant transdermal dosage form |
US20040219195A1 (en) | 2003-04-30 | 2004-11-04 | 3M Innovative Properties Company | Abuse-resistant transdermal dosage form |
US7182955B2 (en) | 2003-04-30 | 2007-02-27 | 3M Innovative Properties Company | Abuse-resistant transdermal dosage form |
US20050042281A1 (en) | 2003-08-21 | 2005-02-24 | Singh Nikhilesh N. | Compositions for delivering therapeutic agents across the oral mucosa |
CA2542778C (en) | 2003-10-28 | 2012-05-29 | Noven Pharmaceuticals, Inc. | Transdermal drug delivery composition |
EP2269606A3 (en) | 2003-10-30 | 2012-04-25 | ALZA Corporation | Transdermal analgesic systems having reduced abuse potential |
WO2005055981A2 (en) | 2003-12-09 | 2005-06-23 | Euro-Celtique S.A. | Tamper resistant co-extruded dosage form containing an active agent and an adverse agent and process of making same |
WO2005067889A1 (en) | 2003-12-30 | 2005-07-28 | Durect Corporation | Polymeric implants, preferably containing a mixture of peg and plg, for controlled release of active agents, preferably a gnrh |
DE602005013490D1 (de) | 2004-02-23 | 2009-05-07 | Euro Celtique Sa | Missbrauchsichere transdermale abgabevorrichtung für opioide, enthaltend opioidantagonist in form von mikrokügelchen |
EP1584335A3 (en) | 2004-04-05 | 2006-02-22 | Laboratorios Del Dr. Esteve, S.A. | Active substance combination comprising a carbinol composition and an opioid |
AU2005286733B2 (en) | 2004-09-23 | 2009-11-05 | Alexander Michalow | Methods for regulating neurotransmitter systems by inducing counteradaptations |
US7827983B2 (en) | 2004-12-20 | 2010-11-09 | Hewlett-Packard Development Company, L.P. | Method for making a pharmaceutically active ingredient abuse-prevention device |
AU2006326377B2 (en) * | 2005-12-13 | 2010-10-07 | Biodelivery Sciences International, Inc. | Abuse resistant transmucosal drug delivery device |
WO2007096489A1 (fr) * | 2006-02-17 | 2007-08-30 | Trimaran Limited | Nouvelles compositions pharmaceutiques destinees a optimiser des traitements de substitution et elargir la pharmacopee au traitement global des addictions |
KR101230804B1 (ko) * | 2006-07-21 | 2013-02-08 | 바이오딜리버리 사이언시스 인터내셔널 인코포레이티드 | 향상된 흡수를 갖는 경점막 전달 장치 |
EP2562177A3 (en) | 2006-09-22 | 2013-04-10 | AllTranz Inc. | Transdermally deliverable buprenorphine prodrugs and abuse-resistant compositions thereof |
US20090270438A1 (en) | 2006-10-18 | 2009-10-29 | Clive Booles | Novel compositions and formulations |
WO2008100434A1 (en) * | 2007-02-09 | 2008-08-21 | Durect Corporation | Transoral dosage forms comprising sufentanil and naloxone |
GB2447015A (en) | 2007-03-01 | 2008-09-03 | Reckitt Benckiser Healthcare | Analgesic composition comprising a specific ratio of buprenorphine and naltrexone |
GB2447016A (en) * | 2007-03-01 | 2008-09-03 | Reckitt Benckiser Healthcare | Buprenorphine/naloxone compositions |
ES2663777T3 (es) | 2008-06-23 | 2018-04-17 | Biodelivery Sciences International, Inc. | Dispositivos de administración mucosa multidireccionales y métodos de uso |
US8475832B2 (en) | 2009-08-07 | 2013-07-02 | Rb Pharmaceuticals Limited | Sublingual and buccal film compositions |
CA3119258A1 (en) * | 2011-08-18 | 2013-02-21 | Biodelivery Sciences International, Inc. | Abuse-resistant mucoadhesive devices for delivery of buprenorphine |
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