JPWO2019163822A1 - 粒状組成物、粒状組成物の製造方法、および粒状組成物の溶出性改善方法 - Google Patents
粒状組成物、粒状組成物の製造方法、および粒状組成物の溶出性改善方法 Download PDFInfo
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Abstract
Description
本実施形態の粒状組成物は、例えば、顆粒剤、散剤、細粒剤、粒状錠、ドライシロップ剤などを包含する。また、粒状組成物は例えば直接に内服するための内服固形剤として使用することができる。また、粒状組成物は例えば水またはシロップなどに分散させた懸濁剤として使用することもできる。また、粒状組成物をカプセルに充填して使用することもできる。すなわち、粒状組成物をカプセル剤の充填物として利用することができる。
(2)II型結晶は、粉末X線回折図がCu Kα放射線(λ=1.54Å)を用いて得られるものであって、化合物(I)の粉末X線回折スペクトルにおいて、次の回折角2θ:9.0°、12.9°、20.7°及び22.6°で回折ピークを示す。
(3)III型結晶は、粉末X線回折図がCu Kα放射線(λ=1.54Å)を用いて得られるものであって、化合物(I)の粉末X線回折スペクトルにおいて、次の回折角2θ:9.3°、9.7°、16.8°、20.6°及び23.5°で回折ピークを示す。
次に、粒状組成物の製造方法について説明する。図4は、粒状組成物の製造工程を示す工程図である。製造工程は、混合工程、圧縮成形工程、破砕工程、分級工程、及び付加工程を有する。なお、粒状組成物における化合物(I)の溶出性を改善する溶出性改善方法も製造方法と同様に行われる。
混合工程では、粉末状の化合物(I)と、糖アルコール類、デンプン類、および糖類からなる群から選択される少なくとも1つ以上の粉末状の賦形剤とを均一に混合して混合物を得る。なお、「混合」には、化合物(I)と賦形剤とを均一に混ぜ合わせて、複数の小さい粒子を相互に付着凝集させて大きい粒子に成長させるいわゆる「造粒」が行われる場合も含まれる。
混合工程後の圧縮成形工程では、混合工程で調製された混合物を圧縮成形して圧縮成形物を得る。この時、圧縮成形物の空隙率は45%以下であると好ましい。圧縮成形工程は圧縮成形機を用いて行われる。圧縮成形方法に特に限定はなく、例えばローラー圧縮法、打錠圧縮法、ブリケット法、スラッグ法、または押出造粒法が好ましい。
圧縮成形工程後の破砕工程において、破砕機などを用いて圧縮成形物を破砕する。破砕工程により、圧縮成形物から粒状の破砕物が形成される。以下の説明において、「粒状の破砕物」を「成粒物」という場合がある。
破砕工程後の分級工程では、気流式分級機または篩などを用いて破砕物を分級する。これにより、所望の粒径の成粒物を容易に得ることができる。なお、破砕が不十分なために分級工程の際に除去された破砕物を再度、破砕工程で破砕してもよい。
分級工程後の付加工程では、分級工程で分級された成粒物を医薬品添加物と混合する。付加工程における混合方法は、上述の混合工程における混合方法と同様である。付加工程により、成粒物に医薬品添加物を添加する。
実施例1に対して圧縮成形工程以降を経ていない混合物20mgを比較例1とした。その他は実施例1と同様に調製した。
実施例2に対して圧縮成形工程以降を経ていない混合物20mgを比較例2とした。その他は実施例2と同様に調製した。
実施例3に対して圧縮成形工程以降を経ていない混合物20mgを比較例3とした。その他は実施例3と同様に調製した。
実施例4に対して圧縮成形工程以降を経ていない混合物20mgを比較例4とした。その他は実施例4と同様に調製した。
実施例5に対して圧縮成形工程以降を経ていない混合物20mgを比較例5とした。その他は実施例5と同様に調製した。
実施例7に対して圧縮成形工程以降を経ていない混合物を比較例6とした。その他は実施例7と同様に調製した。
比較例7として、賦形剤を使用せずに化合物(I)のみを実施例1と同様の方法で圧縮成形した。その他は実施例1と同様に調製した。
圧縮成形していない化合物(I)を比較例8とした。その他は比較例7と同様に調製した。
Claims (18)
- 前記粒状組成物における前記化合物(I)の溶出性が前記圧縮成形工程前の前記混合物における前記化合物(I)の溶出性よりも高い、請求項1に記載の粒状組成物の製造方法。
- 前記粒状組成物の空隙率が45%以下である、請求項1または請求項2に記載の粒状組成物の製造方法。
- 前記粒状組成物の粒径が5mmよりも小さい、請求項1〜請求項3のいずれかに記載の粒状組成物の製造方法。
- 前記圧縮成形工程が、ローラー圧縮法、打錠圧縮法、ブリケット法、スラッグ法、および押出造粒法のいずれか一つにより行われる、請求項1〜請求項4のいずれかに記載の粒状組成物の製造方法。
- 前記圧縮成形工程において、
孔部を介して前記混合物を押出す押出機を用いて前記押出造粒法を行い、
前記孔部の径が0.2mm〜0.5mmである、請求項5に記載の粒状組成物の製造方法。 - 前記圧縮成形物を破砕する破砕工程をさらに含む、請求項1〜請求項6のいずれかに記載の粒状組成物の製造方法。
- 前記粒状組成物が顆粒剤、散剤、カプセル剤の充填物、粒状錠、ドライシロップ剤または細粒剤である、請求項1〜請求項7のいずれかに記載の粒状組成物の製造方法。
- 前記粒状組成物における化合物(I)の溶出性が前記圧縮成形工程前の前記混合物における化合物(I)の溶出性よりも高い、請求項9に記載の溶出性改善方法。
- 前記粒状組成物の空隙率が45%以下である、請求項9または請求項10に記載の溶出性改善方法。
- 前記粒状組成物の粒径が5mmよりも小さい、請求項9〜請求項11のいずれかに記載の溶出性改善方法。
- 前記圧縮成形工程が、ローラー圧縮法、打錠圧縮法、ブリケット法、スラッグ法、および押出造粒法のいずれか一つにより行われる、請求項9〜請求項12のいずれかに記載の溶出性改善方法。
- 前記圧縮成形工程において、
孔部を介して前記混合物を押出す押出機を用いて前記押出造粒法を行い、
前記孔部の径が0.2mm〜0.5mmである、請求項13に記載の溶出性改善方法。 - 前記圧縮成形物を破砕する破砕工程をさらに含む、請求項9〜請求項14のいずれかに記載の溶出性改善方法。
- 前記粒状組成物が顆粒剤、散剤、カプセル剤の充填物、粒状錠、ドライシロップ剤または細粒剤である、請求項9〜請求項15のいずれかに記載の溶出性改善方法。
- 粒径が5mmよりも小さい、請求項17に記載の粒状組成物。
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