TWI419716B - 奈韋拉平(nevirapine)之延長釋放調配劑 - Google Patents
奈韋拉平(nevirapine)之延長釋放調配劑 Download PDFInfo
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Description
本發明係關於一種包含奈韋拉平(nevirapine)的醫藥組合物。
奈韋拉平,或11-環丙基-5,11-二氫-4-甲基-6H-二吡啶并[3,2-b:2',3'-e][1,4]二氮呯-6-酮,為治療由HIV-1(人類免疫不全病毒,類型1)引起之感染的一種已知製劑,其經由HIV-1逆轉錄酶之專一性抑制來發揮作用。其合成與用途闡述在多種出版物中,尤其包含美國專利5,366,972及歐洲專利0429987B1。Viramune錠劑,一種包含奈韋拉平的藥物,在很多國家已批准用於治療HIV-1感染。
目前市售的Viramune錠劑為一種立即釋放(IR)的調配劑,需每天投藥兩次以保持活性成份(奈韋拉平)在治療上適當的血中含量。欲方便病人,並幫助確保適當之投藥依從性,長期需求一種每天僅投藥一次,且仍保持活性成份在治療上適宜的血中含量的奈韋拉平之經口投藥延時釋放(XR)調配劑。
擅長醫藥技術且熟悉奈韋拉平者認知奈韋拉平具有會使XR調配劑可行性產生問題的物化性質。更具體言之,已知XR調配劑一般是設計在經過pH高之腸期間逐漸被吸收。奈韋拉平為弱鹼性,因此,可預期其在腸內表現低溶解性。(根據生物藥劑學分類系統,奈韋拉平為等級Ⅱ藥品。)因此,合理地預測奈韋拉平XR調配劑可能經過胃腸
(GI)道且在奈韋拉平未完全溶解且吸收的情況下排出。這使XR調配劑未能發揮作用。
奈韋拉平具有至少一個使XR調配劑的發展異常艱難的缺點:為達安全、可耐受且有效,血漿中含量不許低於抑制病毒複製之臨界值,且必須絕不能高至具有毒性或無法耐受的含量。就奈韋拉平而言,兩者之間的區域相對狹窄。此點表示Cmax,ss
/Cmin,ss
必須相當平坦。先前已測定立即釋放調配劑的安全性/耐受性及效力,在每天投藥兩次後,在穩定狀態下,發現非常"平坦"的PK曲線(Cmax,ss
/Cmin,ss
=約1.8)。雖然XR每天投藥一次,但任何延時釋放(XR)調配劑皆會表現的等於或甚至小於一天投藥兩次的IR調配劑的峰/谷比。但是,具有比IR更大的峰/谷比之XR調配劑的臨床風險/效益性質較差。
在此等艱鉅挑戰之下,本發明之目的係提供一種奈韋拉平的經口投藥XR調配劑。
本發明為一種適於每天投藥一次且仍保持活性成分在治療上適合的血中含量的奈韋拉平延長釋放(XR)調配劑。
在最廣態樣中,本發明提供的延長釋放調配劑在單劑投與空腹健康自願者之後,表現特殊的藥物代謝動力學曲線,其特徵為包含300 mg奈韋拉平之劑型的下列兩項參數:(a)Cmax
幾何平均值為1,000至2,300 ng/mL;及
(b)AUC0-∞
幾何平均值為73,400至178,100 ng.h/mL;及包含400 mg奈韋拉平劑型的下列兩項參數:(a)Cmax
幾何平均值為1,210至2,740 ng/mL;及(b)AUC0-∞
幾何平均值為109,000至237,000 ng.h/mL。
本發明提供的延長釋放調配劑進一步特徵為Tmax
幾何平均值為10至48小時(仍是在空腹投與單劑後)。
本發明提供的延長釋放調配劑進一步特徵為在穩定狀態情況下重複每天投藥一次後觀察到下列PK參數如下:於300 mg劑量:(a)Cmax,ss
幾何平均值為2,300至3,700 ng/mL;及(b)AUC0-24h,ss
幾何平均值為45,000至75,000 ng.h/mL;且於400 mg劑量:(a)Cmax,ss
幾何平均值為3,100至4,900 ng/mL;及(b)AUC0-24h,ss
幾何平均值為60,000至99,000 ng.h/mL。
以上註明的多劑量PK參數係在藥物血漿含量已達到穩定態後的24小時期間於禁食下測量。
本發明提供的延長釋放調配劑進一步特徵為於300與400 mg兩種劑量下,Cmax,ss
/Cmin,ss
比率幅度極窄,在1.1至2範圍中,該參數係於穩定態期間測量。
應注意此等PK參數係自觀察數據而非模擬數據得到。
本發明延長釋放調配劑進一步特徵為具有一體外溶解曲線,使得在2小時釋放至少2% w/w及最多30% w/w奈韋拉平;在8小時釋放至少20% w/w及最多100% w/w奈韋拉平;在14小時釋放至少40% w/w及最多100% w/w奈韋拉
平;此時溶解係在體積900 mL之包含6% w/w十二烷基硫酸鈉在37℃下pH為6.8的水性緩衝液中,以50 rpm之USP漿法(USP Paddle Method)測量。
在較佳實施例中,本發明之延長釋放調配劑的特徵為具有一體外溶解曲線,使得在2小時釋放至少5% w/w及最多20% w/w奈韋拉平;在8小時釋放至少30% w/w及最多80% w/w奈韋拉平;在14小時釋放至少50% w/w及最多100% w/w奈韋拉平,此時溶解係在體積900 mL包含6% w/w十二烷基硫酸鈉在37℃下pH為6.8的水性緩衝液中,以50 rpm之USP漿法測量。
在更佳實施例中,本發明之延長釋放調配劑的特徵為具有體外溶解曲線,使得在2小時釋放至少8% w/w及最多15% w/w奈韋拉平;在8小時釋放至少45% w/w及最多60% w/w奈韋拉平在;在14小時釋放至少75% w/w及最多95% w/w奈韋拉平,此時溶解係在體積900 mL包含6% w/w十二烷基硫酸鈉在37℃下pH為6.8的水性緩衝液中,以50 rpm之USP漿法測量。
本發明之醫藥組合物可藉由組合奈韋拉平與習用載體或賦形劑來調配。
本發明較佳實施例為錠劑。
亦較佳為包含延長釋放基質的本發明實施例,該基質包含賦予奈韋拉平之控制釋放的親水性聚合物。該親水性聚合物係為但不限制於羥丙基甲基纖維素(HPMC,亦稱為羥丙甲纖維素(hypromellose))、羥丙基纖維素(HPC)、羥乙基
纖維素(HEC)、三仙膠、藻酸鈉、聚氧化乙烯及丙烯酸之交聯均聚物與共聚物。亦可使用上述親水性聚合物的混合物。較佳親水性聚合物為HPMC(羥丙甲纖維素),尤其羥丙基甲基纖維素2910 USP、羥丙基甲基纖維素2906 USP或羥丙基甲基纖維素2208 USP或其混合物。
本發明提供的調配劑可視需要亦包含其它習用賦形劑,例如填料、稀釋劑、助流劑及黏合劑。
本發明提供的調配劑可經由混合單獨組分(奈韋拉平藥物、親水性聚合物及視需要的填料、稀釋劑、助流劑及黏合劑)然後使用製粒溶液製粒直至完全而製備。顆粒然後經乾燥。將乾燥的顆粒磨碎,與潤滑劑合併並混合以製備用以壓製為錠劑的最終摻合物。錠劑經約10-25 kN,較佳11-19 kN,及更佳13-17 kN之力壓製為硬度為約11-26 kP,較佳為16-21 kP的所需大小及形狀。
包含有包含約20%至25重量%羥丙基甲基纖維素之延長釋放基質的調配劑較佳。
更佳為包含羥丙基甲基纖維素2208
(MethocelTM
K4M Premium CR)的調配劑。
最佳為一種醫藥錠劑,其中每個錠劑包含:(a)400 mg無水奈韋拉平;(b)270 mg羥丙基甲基纖維素2208(MethocelTM
K4M Premium CR);(c)400 mg乳糖單水合物;及(d)10 mg硬脂酸鎂;
其中每個錠劑經約10-25 kN之力壓製。
可經由以下描述具體錠劑調配劑的非限制性實例來進一步理解本發明。
400 mg強度奈韋拉平XR錠劑
加工方法
混合乳糖、奈韋拉平藥物物質與羥丙基甲基纖維素,然後經由水製粒至完全。隨後將顆粒乾燥。乾燥顆粒經碾碎,與潤滑劑(硬脂酸鎂)合併及混合以製備用以壓製為錠劑的最終摻合物。錠劑經由約10-25 kN之力壓製為9.3×19.0 mm錠劑。
300 mg強度奈韋拉平XR錠劑
加工方法
混合乳糖、奈韋拉平藥物原料與羥丙基甲基纖維素,然後經由水製粒至完全。顆粒再經乾燥。乾燥顆粒經碾碎,與潤滑劑(硬脂酸鎂)合併及混合以製備壓製為錠劑的最終摻合物。錠劑經由約10-25 kN之力壓製為9.3×19.0 mm錠劑。
400 mg強度奈韋拉平XR錠劑
加工方法
混合乳糖、奈韋拉平藥物原料與羥丙基甲基纖維素,然後經由水製粒至完全。顆粒再經乾燥。乾燥顆粒經碾碎,與潤滑劑(硬脂酸鎂)合併及混合以製備壓製為錠劑的最終摻合物。錠劑壓製為9.3×19.0 mm錠劑。
300 mg強度奈韋拉平XR錠劑
加工方法
混合乳糖、奈韋拉平藥物原料與羥丙基甲基纖維素,然後經由水製粒至完全。顆粒再經乾燥。乾燥顆粒經碾碎,與潤滑劑(硬脂酸鎂)合併及混合以製備壓製為錠劑的最終摻合物。錠劑經由約10-25 kN之力壓製為9.3×19.0 mm錠劑。
上述調配劑的藥物動力學參數在單劑投藥之後於N=17之健康個體進行評估。結果總列於下表1。
上述調配劑的藥物動力學參數亦在投與感染HIV且先前經Viramune立即釋放錠劑治療的病人多劑投藥(每日一次奈韋拉平歷經17日)後評估。結果之總表列顯示於下表2。
溶解
實例1、2、3及4闡述的五種調配劑的溶解曲線係描述於圖4。所述的溶解資料係藉下述試驗方法得到。
溶解試驗方法
USP漿法為例如U.S.Pharmacopoeia XXII(1990)中描述的漿法。
USP裝置1(吊籃)於50 rpm在37℃的900 mL介質中。該吊籃(#10篩目)用於確保錠劑不黏附於容器底部且因此使測試期間可到達溶液的表面積減至最小。
錠劑溶解係使用VanKel VK 750 D加熱器/循環器型號65-3000,VanKel VK 7000或7010溶解試驗台,及VanKel泵型號17-2200(VanKel,Cary,NC)進行。
藥物物質溶解速率使用聯機Cary 50紫外光-可見光分光光度計(Varian Australia Pty LTD)在330 nm下相對於外標準物測量。
試驗溶解介質:調節至pH 6.8的含6%十二烷基硫酸鈉(去離子水中含13%十二烷基硫酸鈉,Anachemia Chemicals,Rouses Point,NY或十二烷基硫酸鈉,Spectrum Chemical MFG.CORP.)的0.05 M磷酸緩衝液(NaH2
PO4
/NaOH或
NaH2
PO4
/Na2
HPO4
/NaOH-均為EM Science,Darmstadt,Germany)。
溶解使用10篩目不銹鋼吊籃進行。
溶解參數:-介質體積:900 mL-溫度:37.3℃-轉速:50 rpm-取樣時間點:開始四小時是每隔30分鐘,然後每隔一小時(4-24小時)-旋轉:250 rpm,15分鐘-聯機過濾器:10 μm滿流過濾器(VanKel,Cary,NC或Quality Lab Accessories L.L.S.)。
圖1與2,分別顯示將本發明奈韋拉平延長釋放劑形的單一400 mg或300 mg錠劑投與健康個體所得之奈韋拉平在血漿中隨時間變化的濃度。
圖3為重複每天一次將本發明奈韋拉平延長釋放劑形的400 mg錠劑投與健康個體所得之奈韋拉平在血漿中隨時間變化的穩定態濃度。
圖4為本發明延長釋放調配劑的溶解曲線。
(無元件符號說明)
Claims (3)
- 一種錠劑醫藥劑型,其中每個錠劑各包含:(a)400mg無水奈韋拉平(nevirapine);(b)選自202.50mg及270mg之量之羥丙基甲基纖維素(hypromellose)2208,或選自270mg及202.50mg之量之羥丙基甲基纖維素2910;(c)400mg乳糖單水合物;及(d)10mg硬脂酸鎂;或(a)300mg無水奈韋拉平;(b)選自151.875mg及202.50mg之量之羥丙基甲基纖維素2208,或選自151.875mg及202.50mg之量之羥丙基甲基纖維素2910;(c)300mg乳糖單水合物;及(d)7.5mg硬脂酸鎂;其中每個錠劑各經10-25kN之力壓製。
- 如請求項1之錠劑醫藥劑型,其中每個錠劑各包含:(a)400mg無水奈韋拉平;(b)270mg羥丙基甲基纖維素2208;(c)400mg乳糖單水合物;及(d)10mg硬脂酸鎂。其中每個錠劑各經10-25kN之力壓製。
- 一種製備如請求項1或2之錠劑醫藥劑型之方法,其中奈韋拉平及羥丙基甲基纖維素經混合且形成顆粒,該顆粒與硬脂酸鎂及乳糖單水合物合併以製備用以壓製為錠劑 的最終摻合物,且其中每個錠劑各經10-25kN之力壓製。
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US94276507P | 2007-06-08 | 2007-06-08 |
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PL (1) | PL2155169T3 (zh) |
TN (1) | TN2009000510A1 (zh) |
TW (1) | TWI419716B (zh) |
UA (1) | UA97971C2 (zh) |
UY (1) | UY31128A1 (zh) |
WO (1) | WO2008154234A2 (zh) |
ZA (1) | ZA200904939B (zh) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
MY149159A (en) | 2005-11-15 | 2013-07-31 | Hoffmann La Roche | Method for treating joint damage |
US20130172274A1 (en) | 2005-12-20 | 2013-07-04 | Duke University | Methods and compositions for delivering active agents with enhanced pharmacological properties |
PL2155169T3 (pl) | 2007-06-08 | 2016-09-30 | Formulacja newirapiny o przedłużonym uwalnianiu | |
EP4074327A1 (en) | 2008-06-27 | 2022-10-19 | Duke University | Therapeutic agents comprising elastin-like peptides |
EP2714045A1 (en) | 2011-05-30 | 2014-04-09 | Cipla Limited | Pharmaceutical antiretroviral composition |
EP4295858A1 (en) * | 2011-08-24 | 2023-12-27 | ImmunoForge Co., Ltd. | Formulations of active agents for sustained release |
US20150104511A1 (en) * | 2012-03-05 | 2015-04-16 | Cipla Limited | Pharmaceutical Antiretroviral Combinations Comprising Lamivudine, Festinavir and Nevirapine |
CN104523630B (zh) * | 2015-01-22 | 2017-08-25 | 山东新时代药业有限公司 | 一种奈韦拉平片剂 |
EP3153157A1 (en) | 2015-10-09 | 2017-04-12 | Teva Pharmaceutical Works Private Limited Company | Pharmaceutical composition for prolonged release of nevirapine |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20020006439A1 (en) * | 1997-09-09 | 2002-01-17 | Robert R. Skluzacek | Dosage form comprising means for changing drug delivery shape |
Family Cites Families (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5366972A (en) | 1989-04-20 | 1994-11-22 | Boehringer Ingelheim Pharmaceuticals, Inc. | 5,11-dihydro-6H-dipyrido(3,2-B:2',3'-E)(1,4)diazepines and their use in the prevention or treatment of HIV infection |
US5133974A (en) | 1989-05-05 | 1992-07-28 | Kv Pharmaceutical Company | Extended release pharmaceutical formulations |
CA2030056C (en) | 1989-11-17 | 1995-10-17 | Karl D. Hargrave | 5,11-dihydro-6h-dipyrido[3,2-b:2',3'-e][1,4]diazepines and their use in the prevention or treatment of hiv infection |
US5419917A (en) * | 1994-02-14 | 1995-05-30 | Andrx Pharmaceuticals, Inc. | Controlled release hydrogel formulation |
ES2172944T3 (es) | 1997-12-05 | 2002-10-01 | Alza Corp | Forma de dosificacion osmotica que comprende un primer y un segundo revestimiento. |
CN1161101C (zh) | 1998-12-17 | 2004-08-11 | 阿尔扎有限公司 | 用多层包衣将填充液体的明胶胶囊转变成控制释放的系统 |
EP1611881A1 (en) * | 1999-03-31 | 2006-01-04 | Janssen Pharmaceutica N.V. | Pregelatinized starch in a controlled release formulation |
OA12029A (en) * | 1999-09-24 | 2006-04-28 | Janssen Pharmaceutica Nv | Antiviral compositions. |
CA2393601A1 (en) | 1999-12-09 | 2001-06-14 | Alza Corporation | Antiviral medication |
US6541014B2 (en) * | 2000-10-13 | 2003-04-01 | Advancis Pharmaceutical Corp. | Antiviral product, use and formulation thereof |
WO2002092095A1 (en) | 2001-05-11 | 2002-11-21 | Boehringer Ingelheim International Gmbh | Use of nevirapine to treat or prevent lipid pathology in patients with hiv that is resistant to nevirapine |
US20030050620A1 (en) | 2001-09-07 | 2003-03-13 | Isa Odidi | Combinatorial type controlled release drug delivery device |
WO2004043435A2 (en) | 2002-11-13 | 2004-05-27 | Control Delivery Systems, Inc. | Systemic delivery of antiviral agents |
AU2004249295A1 (en) | 2003-06-20 | 2004-12-29 | Viral Genomix, Inc. | Compositions for and methods for treating HIV |
UA82564C2 (uk) | 2003-10-01 | 2008-04-25 | Люпин Лимитед | Антиретровірусна фармацевтична композиція керованого вивільнення та спосіб її виготовлення |
NZ547619A (en) | 2003-11-13 | 2009-06-26 | Psivida Inc | Injectable sustained release implant having a bioerodible matrix core and a bioerodible skin |
KR101284361B1 (ko) * | 2004-09-02 | 2013-07-15 | 얀센 파마슈티카 엔.브이. | 4-((4-((4-(2-시아노에텐일)-2,6-디메틸페닐)아미노-2-피리미딘일)아미노)벤조니트릴의 하이드로클로라이드 |
WO2006114709A1 (en) * | 2005-04-25 | 2006-11-02 | Aurobindo Pharma Limited | Pharmaceutical compositions of antiretrovirals |
US20090099154A1 (en) | 2005-06-29 | 2009-04-16 | Panacea Biotec Ltd. | Pharmaceutical Sustained Release Compositions and Processes Thereof |
WO2007052289A2 (en) * | 2005-07-22 | 2007-05-10 | Rubicon Research Pvt Ltd. | Novel dispersible tablet composition |
FR2891459B1 (fr) | 2005-09-30 | 2007-12-28 | Flamel Technologies Sa | Microparticules a liberation modifiee d'au moins un principe actif et forme galenique orale en comprenant |
WO2007047371A2 (en) * | 2005-10-14 | 2007-04-26 | Microdose Technologies, Inc. | Pharmaceutical packaging of an oral dosage combination |
PL2155169T3 (pl) | 2007-06-08 | 2016-09-30 | Formulacja newirapiny o przedłużonym uwalnianiu |
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Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20020006439A1 (en) * | 1997-09-09 | 2002-01-17 | Robert R. Skluzacek | Dosage form comprising means for changing drug delivery shape |
Non-Patent Citations (1)
Title |
---|
G. S.Rekhi et al., "Identification of critical formulation and processing variables for metoprolol tartrate extended-release (ER) matrix tablets", Journal of Controlled Release, 1999, 59: 327-342 * |
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