JP5738509B2 - 内容物均一性が改善されたラサギリン製剤 - Google Patents
内容物均一性が改善されたラサギリン製剤 Download PDFInfo
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- JP5738509B2 JP5738509B2 JP2007557120A JP2007557120A JP5738509B2 JP 5738509 B2 JP5738509 B2 JP 5738509B2 JP 2007557120 A JP2007557120 A JP 2007557120A JP 2007557120 A JP2007557120 A JP 2007557120A JP 5738509 B2 JP5738509 B2 JP 5738509B2
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Images
Classifications
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
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Description
a) R(+)-N-プロパルギル-1-アミノインダンの医薬的に許容可能な塩の粒子の1バッチを粉砕に供する;
b) 工程a)の生成物と担体を混合し顆粒を形成する;
c) 顆粒の混合物均一性(blend uniformity)を決定する;および
d) 組成物を製造するため、顆粒の混合物均一性が予め決めた基準を満たす場合にのみ、顆粒を、顆粒由来の組成物へとする。
製粉前のR(+) PAIメシレートサンプルは、様々なサイズの、大きく、不規則な、平板状の粒子を含んでいる(図1参照)。4つの異なるバッチのPSDを、製粉の前後で測定した。PSDは、マスターサイザーSモデル(Mastersizer S model)を用いたマルバーンレーザー回折(Malvern Laser Diffraction)によって測定した。レーザー回折は、光の回折の角度は粒子のサイズに反比例するという事実に基づいている。粒子の特性が測定され、球体(1つの特有の数字によって記載することが可能な、唯一の形状である球体)の測定値として理解される。加えて、レーザー回折は、体積の項(volume terms)に基づいて粒子サイズ分布を算出し、従って粒子サイズの測定から粒子数は除外される。マスターサイザーSモデルは、単一の技術および単一の範囲の設定を用いて粒子を測定する。
実施例1より、原体の製粉はPSDを変化させ、それゆえより小さな粒子が得られることが明らかである。
製剤は、実施例1で使用された方法によって決定される調節されたPSDを有する幾つかのバッチのR(+) PAIを用いて、以下の方法に従って作製される。
試験したバッチの内容物均一性は、98.6%から100.6%にわたった。RSD(相対標準偏差、平均のパーセンテージで表される)は、錠剤の全バッチで2.0%未満であった。このことは、それぞれの錠剤における活性成分の量が少ないにも関わらず、錠剤の均一性は高いことを意味している。それゆえ、これらの結果は、USP内容物均一性試験の第1段階に設定される許容性基準を満たしている。
Claims (37)
- R(+)-N-プロパルギル-1-アミノインダンの医薬的に許容可能な塩の粒子の混合物であって、体積で表して全量の90%超のR(+)-N-プロパルギル-1-アミノインダン塩のメシレート塩の粒子が、250ミクロン未満であって6ミクロンより大きいサイズを有する混合物。
- 粒子のサイズがレーザー回折により測定される請求項1に記載の混合物。
- 請求項1に記載の混合物であって、体積で表して全量の90%超のR(+)-N-プロパルギル-1-アミノインダンメシレート塩の粒子が、220ミクロン未満のサイズを有する混合物。
- 請求項3に記載の混合物であって、体積で表して全量の90%超のR(+)-N-プロパルギル-1-アミノインダンメシレート塩の粒子が、200ミクロン未満のサイズを有する混合物。
- 経口剤形である、請求項1から請求項4の何れか1項に記載の粒子および担体の、ある量の(an amount of)混合物を含む固体組成物。
- 請求項5に記載の固体組成物であって、粒子および医薬的に許容可能な担体の、治療的に有効量の混合物を含む固体組成物。
- 請求項5または請求項6に記載の固体組成物であって、前記粒子および担体の混合物が顆粒を構成する固体組成物。
- 固体剤形である、請求項7に記載の組成物。
- 前記経口剤形が錠剤である、請求項5または請求項6に記載の組成物。
- 請求項8または請求項9に記載の組成物であって、前記固体剤形におけるR(+)-N-プロパルギル-1-アミノインダンのメシレート塩の内容物の内容物均一性の相対標準偏差(RSD)が、4%未満である組成物。
- 請求項10に記載の組成物であって、前記R(+)-N-プロパルギル-1-アミノインダンのメシレート塩の内容物の内容物均一性の相対標準偏差(RSD)が3%未満である組成物。
- 請求項11に記載の組成物であって、前記R(+)-N-プロパルギル-1-アミノインダンのメシレート塩の内容物の内容物均一性の相対標準偏差(RSD)が2%未満である組成物。
- 請求項8から請求項12の何れか1項に記載の組成物であって、内容物均一性が、95%から105%の間である組成物。
- パーキンソン病を患う患者を治療するための、請求項5から請求項13の何れか1項に記載の固体組成物。
- 体積で表して全量の90%超のR(+)-N-プロパルギル-1-アミノインダンのメシレート塩の粒子が、250ミクロン未満であって6ミクロンより大きい粒子サイズを有するように、R(+)-N-プロパルギル-1-アミノインダンのメシレート塩の粒子サイズを縮小することを含む、請求項5から14の何れか1項に記載の固体組成物の製造方法。
- 粒子のサイズがレーザー回折により測定される請求項15に記載の方法。
- 請求項15に記載の方法であって、体積で表して全量の90%超のR(+)-N-プロパルギル-1-アミノインダンのメシレート塩の粒子が、200ミクロン未満の粒子サイズを有する方法。
- 請求項16または請求項17に記載の方法であって、縮小する工程が、R(+)-N-プロパルギル-1-アミノインダンのメシレート塩の粒子の粉砕を含む方法。
- 請求項16から請求項18の何れか1項に記載の方法であって、さらに、R(+)-N-プロパルギル-1-アミノインダンの粒子と担体とを混合し顆粒を形成することを含む方法。
- 請求項19に記載の方法であって、前記顆粒の混合物均一性が90%から110%の間であり、および混合物均一性の相対標準偏差(RSD)が2%未満である方法。
- 請求項20に記載の方法であって、前記混合物均一性が95%から105%の間であり、および前記混合物均一性の相対標準偏差(RSD)が2%未満である方法。
- 請求項19から請求項21の何れか1項に記載の方法であって、さらに、250ミクロン未満の粒子サイズを有するR(+)-N-プロパルギル-1-アミノインダンのメシレート塩の粒子を含む顆粒を、固体剤形に圧縮することを含む方法。
- 前記固体剤形が錠剤である請求項22に記載の方法。
- 以下を含む、固体組成物を製造する方法:
a) R(+)-N-プロパルギル-1-アミノインダンのメシレート塩の粒子の1バッチを粉砕に供すること、ここにおいて、体積で表して全量の90%超のR(+)-N-プロパルギル-1-アミノインダンのメシレート塩の粒子が、250ミクロン未満であって6ミクロンより大きい粒子サイズを有する;
b) 工程a)の生成物と担体を混合し顆粒を形成すること;
c) 顆粒の混合物均一性を決定すること;および
d) 顆粒の混合物均一性が予め決めた基準を満たす場合にのみ、顆粒から組成物を形成して、組成物を製造すること、ここにおいて、前記予め決めた基準は、90%から110%の間の混合物均一性および2%の未満の相対標準偏差である。 - 粒子のサイズがレーザー回折により測定される請求項24に記載の方法。
- 請求項24に記載の方法であって、前記予め決めた基準が、95%から105%の間の混合物均一性および2%の未満の相対標準偏差である方法。
- 請求項24から請求項26のいずれか1項に記載の方法であって、形成工程d)が固体剤形の製造を含む方法。
- 請求項27に記載の方法であって、前記形成工程d)が経口剤形の製造を含む方法。
- 請求項28に記載の方法であって、前記経口剤形が錠剤である方法。
- 請求項27から請求項29の何れか1項に記載の方法であって、さらに、固体剤形の内容物均一性の決定を含む方法。
- 請求項30に記載の方法であって、さらに、内容物均一性が予め決めた基準を満たす場合にのみ、許容可能な組成物として固体剤形を定量する工程を含み、ここにおいて、前記予め決めた基準は、95%から105%の間の内容物均一性および4%未満の内容物均一性の相対標準偏差である方法。
- 請求項31に記載の方法であって、前記予め決めた基準が、3%未満の内容物均一性の相対標準偏差である方法。
- 請求項31に記載の方法であって、前記予め決めた基準が、2%未満の内容物均一性の相対標準偏差である方法。
- 請求項25から請求項33の何れか1項に記載の方法であって、さらに、工程d)の前記予め決めた基準を満たさない何れかのバッチのR(+)-N-プロパルギル-1-アミノインダンのメシレート塩の粒子のサイズを縮小する工程を含む方法。
- 請求項25から請求項33の何れか1項に記載の方法であって、工程b)が、R(+)-N-プロパルギル-1-アミノインダンのメシレート塩の粒子のサイズの縮小を含む方法。
- 請求項34または請求項35の何れか1項に記載の方法であって、縮小する工程が、R(+)-N-プロパルギル-1-アミノインダンのメシレート塩の粒子を製粉する方法。
- 請求項15から請求項36の何れか1項に記載の方法によって製造される、治療的な有効量のR(+)-N-プロパルギル-1-アミノインダンのメシレート塩を含む、固体医薬組成物。
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PCT/US2006/006252 WO2006091657A1 (en) | 2005-02-23 | 2006-02-22 | Rasagiline formulations of improved content uniformity |
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EP1848402B1 (en) | 2016-05-11 |
KR20130129300A (ko) | 2013-11-27 |
ES2586412T5 (es) | 2019-05-16 |
WO2006091657A1 (en) | 2006-08-31 |
EP1848402B2 (en) | 2019-02-20 |
US7815942B2 (en) | 2010-10-19 |
AU2006216696A1 (en) | 2006-08-31 |
ES2586412T3 (es) | 2016-10-14 |
JP2013139452A (ja) | 2013-07-18 |
CA2600011C (en) | 2015-11-10 |
HK1103366A1 (zh) | 2007-12-21 |
KR20140103356A (ko) | 2014-08-26 |
EP1848402A1 (en) | 2007-10-31 |
IL184033A0 (en) | 2007-10-31 |
KR20180026580A (ko) | 2018-03-12 |
JP2008531572A (ja) | 2008-08-14 |
KR20070111534A (ko) | 2007-11-21 |
EP1848402A4 (en) | 2012-01-18 |
NO20074823L (no) | 2007-11-16 |
IS8669A (is) | 2007-08-15 |
RU2007135169A (ru) | 2009-03-27 |
KR20170023211A (ko) | 2017-03-02 |
AU2006216696B2 (en) | 2011-08-18 |
IL244802A0 (en) | 2016-04-21 |
MX2007010233A (es) | 2007-11-07 |
IL244802A (en) | 2016-08-31 |
NZ560660A (en) | 2010-11-26 |
CA2600011A1 (en) | 2006-08-31 |
CA2901244A1 (en) | 2006-08-31 |
BRPI0608209A2 (pt) | 2010-11-09 |
RU2404746C2 (ru) | 2010-11-27 |
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