JP5297194B2 - 初期溶解率が改善されたプランルカスト固体分散体の薬剤学的組成物およびその製造方法 - Google Patents
初期溶解率が改善されたプランルカスト固体分散体の薬剤学的組成物およびその製造方法 Download PDFInfo
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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Description
本発明は以下の実施例に依拠して更に詳細に説明されているが、以下実施例は本発明を説明するだけであり、本発明の範囲に限定されるべきではない。
固体状のプランルカストを水溶性高分子の1種であるコポビドンと熱溶融を行いプランルカスト固体分散体を製造し、製造されたプランルカスト固体分散体が無定形であることをXRD(X線回折法)を用いて確認した。
前記実施例1〜3で使用されたものと同一のプランルカスト固体分散体を使用し、広く使用されている下記表2の3種類のスーパー崩壊剤を混合し、プランルカスト固体分散体の薬剤学的組成物を製造した。これに潤滑剤を添加して混合した後、前記実施例1〜3と同様な方法にてカプセルに充填した。
前記実施例1〜3で使用されたものと同一のプランルカスト固体分散体と潤滑剤を混合し、前記実施例1〜3と同様な方法にてカプセルに充填したが、抗凝固剤と崩壊剤は使用しなかった。
市販されている東亜製薬(韓国)のオノン(登録商標)カプセル(1カプセル当りプランルカスト225mg含有)および本発明のプランルカスト固体分散体の薬剤学的組成物を比較した。
前記実施例1〜3で使用されたものと同一のプランルカスト固体分散体1gと下記表3の比率の抗凝固剤を60℃で混合した後、前記実施例1〜3と同様の方法にて顆粒状のプランルカスト固体分散体の薬剤学的組成物を製造した。
前記実施例1〜15および比較例1〜4にて製造したカプセルと、比較例5の市販のオノン(登録商標)カプセルを、37.5℃の温度およびpH6.8の溶出溶媒で、50rpmの速度で60分間攪拌して溶解テストを行った。各時間帯別の溶解度をHPLCで分析し、下記数学式1により求め、その結果を下記表4に示した。
溶解試験機(パドル法、50rpm)を使用し、下記のpH条件で実施例4および比較例1にて製造したカプセルの崩壊様相を60分間観察し、その結果を下記表5に示した。
前記実施例4および比較例1にて製造したカプセル(プランルカスト100mg含有)を6人の健康な成人に経口投与した後、薬物の血漿濃度をLC−Massで分析し、下記表6のように生体内利用効率を決定した。
Claims (5)
- プランルカスト固体分散体100重量部に対して、HLBが10〜40であり、室温で固体状または半固体状である凝集防止剤0.1〜10重量部を含むこと、
前記プランルカスト固体分散体は、結晶性プランルカストと水溶性高分子を混合し、噴霧乾燥または熱溶融方式により製造したものであり、無定形構造を有することを特徴とするプランルカスト固体分散体のゼラチンカプセル化した薬剤学的組成物。 - 前記プランルカスト固体分散体は、結晶性プランルカストと水溶性高分子を混合し、熱溶融方式により製造したものであり、無定形構造を有することを特徴とする、請求項1記載のプランルカスト固体分散体のゼラチンカプセル化した薬剤学的組成物。
- 前記凝集防止剤は、ポリエチレングリコール群、ポリエチレングリコールの脂肪酸エステル誘導体群、ポリソルベート群、ポロキサマー群、ショ糖脂肪酸エステル群およびラウリル硫酸ナトリウムからなる群から選択された1種または2種以上の混合物であることを特徴とする、請求項1記載のプランルカスト固体分散体のゼラチンカプセル化した薬剤学的組成物。
- 前記凝集防止剤は、ポリエチレングリコール群、ポリエチレングリコールの脂肪酸エステル誘導体群、ラウリルマクロゴールグリセリド(laurylmacrogolglyceride)およびラウリル硫酸ナトリウムからなる群から選択された1種または2種以上の混合物であることを特徴とする、請求項2記載のプランルカスト固体分散体のゼラチンカプセル化した薬剤学的組成物。
- (a)プランルカスト固体分散体と、HLBが10〜40であり、室温で固体状または半固体状である凝集防止剤を40〜90℃の範囲に調節しながら混合する工程、および
(b)前記混合物を冷却および顆粒化する工程を含み、
前記プランルカスト固体分散体は、結晶性プランルカストと水溶性高分子を混合し、噴霧乾燥または熱溶融方式により製造したものであり、無定形構造を有することを特徴とするプランルカスト固体分散体のゼラチンカプセル化した薬剤学的組成物の製造方法。
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PCT/KR2006/003368 WO2007024123A1 (en) | 2005-08-26 | 2006-08-25 | Pharmaceutical composition of pranlukast solid-dispersion with improved initial dissolution rate and the method of preparing the same |
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US10729687B1 (en) | 2019-07-09 | 2020-08-04 | Orexo Ab | Pharmaceutical composition for nasal delivery |
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