Pharmaceutical composition
Inventors
Sasaki, Akihiko • Tanaka, Ko • Miyazaki, Masakazu • Takae, Seiji
Assignees
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Publication Number
US-12178814-B2
Publication Date
2024-12-31
Expiration Date
Abstract
Provided is a pharmaceutical composition containing 6-ethyl-3-{3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino}-5-[(oxan-4-yl)amino]pyrazine-2-carboxamide or a pharmaceutically acceptable salt thereof and a sweetener for reducing the bitterness of gilteritinib, suppressing the decrease in dissolution stability of gilteritinib due to, for example, stress such as heat and/or humidity over time, and having excellent dissolution stability. The pharmaceutical composition contains gilteritinib or a pharmaceutically acceptable salt thereof, a sweetener, and sugars and/or sugar alcohols.
Core Innovation
The invention relates to pharmaceutical compositions containing 6-ethyl-3-{3-methoxy-4-[4-(4-methylpiperazin-1-yl) piperidin-1-yl] anilino}-5-[(oxan-4-yl) amino] pyrazine-2-carboxamide (gilteritinib) or a pharmaceutically acceptable salt thereof, including gilteritinib hemifumarate. The compositions further include a sweetener and two or more sugars and/or sugar alcohols.
The compositions address dissolution stability under stress such as heat and humidity, while also reducing bitterness. The disclosure frames sugars and sugar alcohols as binding agents in combination with a sweetener, so that bitterness reduction is maintained while dissolution behavior is preserved during storage.
The disclosure describes formulation choices for the sweetener and for the sugars and sugar alcohols intended to maintain dissolution stability after storage under specified stress conditions. In particular, the compositions include selected sweeteners and use two or more sugars and/or sugar alcohols, including examples such as mannitol, isomalt hydrate, maltitol, sorbitol, lactose, sucrose, and trehalose, and may use hemifumarate as the salt form.
Claims Coverage
The independent claim identified covers a pharmaceutical composition defined by gilteritinib or a pharmaceutically acceptable salt, a sweetener, and two or more sugars and/or sugar alcohols. Dependent refinements add specific sweetener options, structural and quantitative constraints on sugars and sugar alcohols, a specified salt form, and optional presentation as dissolved or dispersed preparations.
Pharmaceutical composition with sweetener and two or more sugars/sugar alcohols
A pharmaceutical composition comprising 6-ethyl-3-{3-methoxy-4-[4-(4-methylpiperazin-1-yl) piperidin-1-yl] anilino}-5-[(oxan-4-yl) amino] pyrazine-2-carboxamide or a pharmaceutically acceptable salt thereof, a sweetener, and two or more sugars and/or sugar alcohols.
Selected sweeteners from saccharin family
The pharmaceutical composition includes a sweetener consisting of one or more selected compounds from saccharin, acesulfame potassium, aspartame, and sucralose.
Disaccharides and sugar alcohols with specific carbon counts
The pharmaceutical composition contains sugars that are disaccharides and sugar alcohols with 6 or 12 carbon atoms.
1% to 20% by weight sugars and/or sugar alcohols
The pharmaceutical composition includes one or more sugars and/or sugar alcohols in an amount of 1% to 20% by weight relative to the total weight of the composition.
Hemifumarate as the pharmaceutically acceptable salt
The pharmaceutical composition uses hemifumarate as the pharmaceutically acceptable salt.
Dissolved or dispersed preparation in suitable solvent
The pharmaceutical composition is formulated as a dissolved or dispersed preparation in a suitable solvent, in the form of a solution, suspension, paste, or gel.
Overall, the claim set centers on combining gilteritinib or a pharmaceutically acceptable salt with a sweetener and at least two sugars and/or sugar alcohols, with dependent limitations specifying particular sweetener candidates, sugar and sugar-alcohol structural and carbon-atom constraints, a defined 1% to 20% by-weight content range, an optional hemifumarate salt selection, and possible presentation as solution, suspension, paste, or gel.
Stated Advantages
Improved dissolution stability under stress such as heat and humidity compared with compositions using a single or insufficient sugar system, preserving dissolution behavior above specified thresholds.
Retained bitterness reduction while maintaining dissolution rates during storage.
Documented Applications
Pediatric-friendly pharmaceutical dosing contexts where bitterness reduction and dissolution stability under heat and humidity stress are relevant, including formulation as solid tablets or mini-tablets and as dissolved or dispersed preparations such as solution, suspension, paste, or gel.
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