PHARMACEUTICAL COMPOSITIONS COMPRISING AKT PROTEIN KINASE INHIBITORS

• Main Authors: PETER STEIDLE, ANDRE HELL, REINHARD REENTS, MARTIN WUNDERLICH, PIRMIN HIDBER, MARIE PEPELNJAK, FRANCIS GOSSELIN, EDWARD YOST
• Format: Patent
• Language: English; Japanese
• Published: 19.07.2023
• Subjects: HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

To provide a pharmaceutical composition which can effectively prevent the formation of cracks during compression tableting, in the production of a tablet having particles including amorphous ipatasertib monohydrochloride in a tablet core suitable for cancer treatment and the like, and to provide methods for producing the composition and a tablet or the like including the composition.SOLUTION: A pharmaceutical composition includes: an intragranular matrix including amorphous monohydrochloride of (S)-2-(4-chlorophenyl)-1-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-(isopropylamino)propane-1-one (ipatasertib) having a d90 value of 28-109 pm; one or more fillers selected from microcrystalline cellulose, pregelatinized starch and the like; colloidal silica as a moisture adsorbent; croscarmellose sodium as an extragranular disintegrant; and magnesium stearate as an extragranular lubricant.SELECTED DRAWING: Figure 1 【課題】がん等治療に有用な非晶質イパタセルチブモノ塩酸塩を含む粒子を錠剤コアに有する錠剤の製造において、圧縮製錠時のクラックの形成を効果的に防止可能な薬学的組成物、並びに前記組成物及び前記組成物を含む錠剤等の製造方法を提供する。【解決手段】２８～１０９ｐｍのｄ９０値を有する（Ｓ）－２－（４－クロロフェニル）－１－（４－（（５Ｒ，７Ｒ）－７－ヒドロキシ－５－メチル－６，７－ジヒドロ－５Ｈ－シクロペンタ［ｄ］ピリミジン－４－イル）ピペラジン－１－イル）－３－（イソプロピルアミノ）プロパン－１－オン（イパタセルチブ）の非晶質モノ塩酸塩を含む粒内マトリックス；微結晶性セルロース、アルファ化デンプン等から選択される一又は複数の充填剤；粒内吸湿剤としてコロイド状シリカ；粒外崩壊剤としてクロスカルメロースナトリウム；及び粒外潤滑剤としてステアリン酸マグネシウムを含む、薬学的組成物。【選択図】図１