JP5186159B2 - フェノフィブラート含有組成物 - Google Patents
フェノフィブラート含有組成物 Download PDFInfo
- Publication number
- JP5186159B2 JP5186159B2 JP2007224951A JP2007224951A JP5186159B2 JP 5186159 B2 JP5186159 B2 JP 5186159B2 JP 2007224951 A JP2007224951 A JP 2007224951A JP 2007224951 A JP2007224951 A JP 2007224951A JP 5186159 B2 JP5186159 B2 JP 5186159B2
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- JP
- Japan
- Prior art keywords
- fenofibrate
- fatty acid
- weight
- acid ester
- parts
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 229960002297 fenofibrate Drugs 0.000 title claims description 87
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
非イオン性脂肪酸エステル系界面活性剤(B)としては、多価アルコールの脂肪酸エステル、例えば、ショ糖脂肪酸エステル(ショ糖カプリル酸エステル、ショ糖カプリン酸エステル、ショ糖ラウリン酸エステル、ショ糖ミリスチン酸エステル、ショ糖パルミチン酸エステル、ショ糖ステアリン酸エステル、ショ糖アラキン酸エステル、ショ糖ベヘン酸エステル、ショ糖リンデル酸、ショ糖パルミトオレイン酸、ショ糖オレイン酸、ショ糖エライジン酸などのショ糖飽和又は不飽和C6−30脂肪酸エステル(ショ糖モノ又はポリC6−30脂肪酸エステルなど)など)、(ポリ)アルキレングリコール脂肪酸エステル(エチレングリコールモノ又はジステアリン酸エステル、ポリエチレングリコールモノ又はジラウリン酸エステル、ポリエチレングリコールモノ又はジオレイン酸エステル、ポリエチレングリコールモノ又はジステアリン酸エステル、ポリオキシエチレン硬化ヒマシ油などの(ポリ)C2−4アルキレングリコール飽和又は不飽和C6−30脂肪酸エステルなど)、グリセリン脂肪酸エステル(モノ又はジカプリル酸デカグリセリン、モノ又はジカプリル酸グリセリン、モノ又はジステアリン酸グリセリン、モノ又はジオレイン酸グリセリンなどの飽和又は不飽和C6−30脂肪酸のグリセリンエステルなど)、ソルビタン脂肪酸エステル(モノカプリル酸ソルビタン、モノラウリル酸ソルビタン、モノパルミチン酸ソルビタン、モノステアリン酸ソルビタン、ジステアリン酸ソルビタン、モノオレイン酸ソルビタン、トリオレイン酸ソルビタン、トリステアリン酸ソルビタン、セスキオレイン酸ソルビタンなどのソルビタン飽和又は不飽和C6−30脂肪酸エステルなど)、ソルビット脂肪酸エステル(前記ソルビタン脂肪酸エステルに対応するソルビット脂肪酸エステル、例えば、モノラウリル酸ソルビット、モノパルミチン酸ソルビット、モノステアリン酸ソルビット、モノオレイン酸ソルビットなどのソルビット飽和又は不飽和C6−30脂肪酸エステルなど)、脂肪酸(ポリ)オキシアルキレンソルビタン(モノラウリン酸オキシエチレンソルビタン、モノラウリン酸ポリオキシエチレンソルビタン、モノパルミチン酸ポリオキシエチレンソルビタン、モノステアリン酸ポリオキシエチレンソルビタン、モノオレイン酸ポリオキシエチレンソルビタン、トリオレイン酸ポリオキシエチレンソルビタン、モノヤシ油脂肪酸ポリオキシエチレンソルビタンなどの飽和又は不飽和C6−30脂肪酸(ポリ)C2−4オキシアルキレンソルビタンなど)、脂肪酸(ポリ)オキシアルキレンソルビット(前記脂肪酸ポリオキシアルキレンソルビタンに対応する脂肪酸(ポリ)オキシアルキレンソルビット、例えば、ステアリン酸ポリオキシエチレンソルビット、モノオレイン酸ポリオキシエチレンソルビット、テトラオレイン酸ポリオキシエチレンソルビットなどの飽和又は不飽和C6−30脂肪酸(ポリ)オキシC2−4アルキレンソルビットなど)などが挙げられる。これらの非イオン性脂肪酸エステル系界面活性剤は、単独で又は二種以上組み合わせて使用できる。
(1)微粉砕物の調製
未粉砕フェノフィブラート(原薬、粒子径100〜150μm)と表1に示す界面活性剤との混合粉末(フェノフィブラート/界面活性剤(重量比)=100/3.5)を、ジェットミルにより微細化処理し、表1に示す50%平均粒径(D50%)を有する共微粉砕物を得た(実施例1及び比較例2)。
(B2):ラウリル硫酸ナトリウム(和光純薬工業(株)製、SLS、HLB=40)。
(i)50%平均粒子径(D50%)
50%平均粒子径は、レーザ式粒度分布測定装置(島津製作所(株)製)にて、分散溶媒として水を用いる湿式測定法により測定した。
微粉砕物をゼラチンカプセルに充填し、得られたカプセル剤を用いて、日局溶出試験法第2法に準拠して、液量900mL、37℃±0.5℃、及びパドル回転数100rpmの条件で溶出試験を行った。なお、試験液には1重量%濃度のポリソルベート80溶液を用いた。また、フェノフィブラートの定量は、紫外可視吸光度測定法により行い、波長290nmにおける吸光度を測定した。
界面活性剤としてショ糖パルミチン酸エステル(B1)に代えて、下記の非イオン性脂肪酸エステル系界面活性剤を用いる以外は実施例1と同様にして試料を調製し、フェノフィブラートの溶出試験を行ったところ、実施例1と同様の溶出挙動を示した。
(ii)ショ糖ミリスチン酸エステル(HLB=16)
(iii)ショ糖ステアリン酸エステル(HLB=9)
(iv)モノステアリン酸グリセリン(HLB=3.8)
実施例3
下記の成分を混合し、ゼラチンカプセルに充填し、カプセル剤とした。
ショ糖パルミチン酸エステル 3.5 mg
乳糖 30.0 mg
トウモロコシデンプン 20.0 mg
ステアリン酸マグネシウム 1.5 mg
全量 150.0 mg。
Claims (5)
- (A)フェノフィブラートと(B)非イオン性脂肪酸エステル系界面活性剤とが共粉砕された粉粒状物を含むフェノフィブラート含有組成物であって、
非イオン性脂肪酸エステル系界面活性剤(B)が、ショ糖脂肪酸エステルであり、かつ非イオン性脂肪酸エステル系界面活性剤(B)のHLBが、3〜17.5であるフェノフィブラート含有組成物。 - フェノフィブラート(A)100重量部に対する非イオン性脂肪酸エステル系界面活性剤(B)の割合が1〜10重量部である請求項1記載のフェノフィブラート含有組成物。
- さらに、結合剤、賦形剤及び崩壊剤から選択された少なくとも一種の成分(C)を含有する請求項1又は2記載のフェノフィブラート含有組成物。
- フェノフィブラート(A)100重量部に対する成分(C)の割合が1〜70重量部である請求項3記載のフェノフィブラート含有組成物。
- さらに、滑沢剤を含む請求項1〜4のいずれかに記載のフェノフィブラート含有組成物。
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