JP2011519967A - 副腎皮質ステロイドの経口送達のための組成物 - Google Patents
副腎皮質ステロイドの経口送達のための組成物 Download PDFInfo
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- JP2011519967A JP2011519967A JP2011508995A JP2011508995A JP2011519967A JP 2011519967 A JP2011519967 A JP 2011519967A JP 2011508995 A JP2011508995 A JP 2011508995A JP 2011508995 A JP2011508995 A JP 2011508995A JP 2011519967 A JP2011519967 A JP 2011519967A
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Abstract
Description
(a)副腎皮質ステロイド薬剤、アルカリ含有エチルセルロース物質および酸を含む徐放成分と、
(b)経口投与の後で、組成物が腸に到達するまで前記徐放成分の放出を実質的に防止する遅延放出成分と、
を含む経口ドラッグデリバリー組成物を提供する。
副腎皮質ステロイド薬剤、アルカリ含有エチルセルロース物質および酸を含む徐放成分、及び、経口投与後に、組成物が腸に到達するまで徐放成分の放出を実質的に防止する遅延放出成分、あるいは本発明の組成物の、消化管の炎症性疾患、例えばクローン病もしくは潰瘍性大腸炎、または糸球体腎炎などの治療のための薬剤の製造における使用。
(i)薬剤を含有するコーティング溶液
258gのヒドロキシプロピルメチルセルロース/ポリエチレングリコールブレンド(Opadry(登録商標)、Colorcon、Dartford、英国)を、勢いよく撹拌することによって2970gの水の中へ溶解した。次いで、72gの微粉化したブデソニド(Sicor、イタリア)をOpadry溶液中へと勢いよく撹拌することによって、均一な懸濁剤を形成した。水を用いて、懸濁剤を3300gの重量まで生成した。
144gのOpadry(上述の通り)および6gのクエン酸(Thornton and Ross)を、1350gの水の中に溶解した。水を用いて、この溶液を1500gの重量まで生成した。
Aeromatic-Fielder、MP-1流動床コーティング装置のコーティングチャンバーに、4000gの糖球(メッシュサイズ16〜18、Paulaur、米国)を充填し、以下の設定を使用した:
流動化空気容量=80m3/h
入口温度=70℃
噴霧圧力=29psi(2バール)
900gのSurelease(エチルセルロース水性分散液、固体25重量%)を、ビーカーに移した。45gのOpadry(ヒドロキシプロピルメチルセルロース/ポリエチレングリコールブレンド)を、555gの水の中に溶解し、生成した溶液を、Surelease分散液へと穏やかに混合した。
流動化空気容量=80m3/h
入口温度=70℃
噴霧圧力=29psi(2バール)
(a)カプセルの充填
ブデソニドビーズ(実施例1で作製)を、サイズ0のデンプンカプセル(Capsugel、Greenwood、S.C.、米国)中に充填した。各カプセル体に、282mgのビーズ、ブデソニド4mg当量を充填し、水/イソプロパノール混合物を用いて各体にふたをした。
47.5gのEudragit L100および15.8gのEudragit S100(Degussa、Darmstadt、ドイツ)を、714gのイソプロパノールおよび24.3gの水を含む混合物中に溶解した。12.2gのセバシン酸ジブチル(可塑剤)および15.8gタルク(抗粘着剤)を、コーティング溶液中に混合した。
以下の表は、実施例2において調製し、小児用安全ポリプロピレンキャップを装着したHDPEビンの中に30カ月間、25℃/60%RHで保存した、カプセル剤のブデソニドおよび不純物の含有量の一覧である。30カ月の時点で、両パラメーターは、十分規格内に留まり、これは、ビーズ製剤内のブデソニドの優れた安定性を示すものである。
2つのバッチのコーティングした糖球を、実施例1に記載の方法に従い作製した。
Opadry(78%w/w)中に懸濁した、22%w/wブデソニドを含有する水溶液を調製した。1500gの糖球にこの分散液を6.4%の体重増加までコーティングした。最終の、コーティングした球は、1.3%w/wのブデソニドを含有した。
Opadry(78%w/w)中に懸濁した22%w/wブデソニドを含有する水溶液を調製した。1500gの糖球を、6%の体重増加までこの溶液でコーティングした。最終の、コーティングした球は、1.3%w/wのブデソニドを含有した。
Claims (22)
- 副腎皮質ステロイド薬剤を含む徐放成分であって、経口投与後に腸内で前記徐放成分がカプセルから優位に放出されるように処理されているカプセル内に含有された徐放成分を含む、経口ドラッグデリバリー組成物。
- カプセルが、デンプンカプセルである、請求項1に記載の組成物。
- (a)副腎皮質ステロイド薬剤、アルカリ含有エチルセルロース物質および酸を含む徐放成分と、
(b)経口投与の後で、組成物が腸に到達するまで前記徐放成分の放出を実質的に防止する遅延放出成分と
を含む、副腎皮質ステロイド薬剤を腸に送達するためのドラッグデリバリー組成物。 - 薬剤がブデソニドである、請求項1から3のいずれか一項に記載の組成物。
- アンモニア含有エチルセルロース物質を含む、請求項1から4のいずれか一項に記載の組成物。
- アンモニア含有エチルセルロース物質が、Surelease(登録商標)である、請求項5に記載の組成物。
- 徐放成分が、副腎皮質ステロイド薬剤を含むコアを含み、前記コアが、酸を含む層でコーティングされており、前記酸含有層が、アルカリ含有エチルセルロースを含む層でコーティングされている、請求項1から6のいずれか一項に記載の組成物。
- アルカリ含有エチルセルロースを含む層が、マンニトール、デキストロース、スクロース、ポリエチレングリコール、ヒドロキシプロピルメチルセルロース、ヒドロキシプロピルセルロース、メチルセルロース、トリアセチンおよびポリビニルアルコールから選択される水溶性物質をさらに含む、請求項7に記載の組成物。
- 酸が有機酸である、請求項3から8のいずれか一項に記載の組成物。
- 徐放成分が、コーティングされた薬剤粒子、コーティングされたペレット、コーティングされた顆粒剤またはコーティング錠を含む、請求項1から9のいずれか一項に記載の組成物。
- 徐放成分が、デンプンカプセル内に含有されている、請求項3から10のいずれか一項に記載の組成物。
- デンプンカプセルが、遅延放出成分(b)でコーティングされている、請求項11に記載の組成物。
- 副腎皮質ステロイド薬剤の徐放のための経口送達組成物の製造における、アルカリ含有エチルセルロース物質および酸の使用。
- 消化管の炎症性疾患の治療のための、請求項1から12のいずれか一項に記載の組成物。
- クローン病または潰瘍性大腸炎を治療するための、請求項14に記載の組成物。
- 糸球体腎炎の治療のための、請求項1から12のいずれか一項に記載の組成物。
- 副腎皮質ステロイド薬剤、アルカリ含有エチルセルロース物質および酸を含む徐放成分、及び、経口投与後に組成物が腸に到達するまで徐放成分の放出を実質的に防止する遅延放出成分、または、
請求項1から12のいずれか一項に記載の組成物の、
消化管の炎症性疾患の治療のための薬剤の製造における使用。 - クローン病または潰瘍性大腸炎を治療するための、請求項17に記載の組成物。
- (a)副腎皮質ステロイド薬剤、アルカリ含有エチルセルロース物質および酸を含む徐放成分、及び
(b)経口投与後に組成物が腸に到達するまで徐放成分の放出を実質的に防止する遅延放出成分、または、
請求項1から12のいずれか一項に記載の組成物の、
糸球体腎炎の治療のための薬剤の製造における使用。 - 請求項1から12のいずれか一項に定義された組成物を投与するステップを含む、消化管の炎症性疾患を治療する方法。
- 疾患が、クローン病または潰瘍性大腸炎である、請求項20に記載の方法。
- 請求項1から12のいずれか一項に定義された組成物を投与するステップを含む、糸球体腎炎を治療する方法。
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