Solid oral formulations and crystalline forms of an inhibitor of apoptosis protein
AssigneeNovartis AG
InventorsJeewan Thakur, Dong Yang, Lili Feng
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Abstract
The present disclosure relates to crystalline form of (S)—N—((S)-1-cyclohexyl-2-{(S)-2-[4-(4-fluoro-benzoyl)-thiazol-2-yl]-pyrrolidin-1-yl}-2-oxo-ethyl)-2-methylamino-propionamide, salts and hydrates thereof. This disclosure also relates to solid oral formulation of (S)—N—((S)-1-cyclohexyl-2-{(S)-2-[4-(4-fluoro-benzoyl)-thiazol-2-yl]-pyrrolidin-1-yl}-2-oxo-ethyl)-2-methylamino-propionamide, pharmaceutically acceptable salts, solvates (including hydrates) thereof, as well as methods of treatment using the same.
Claims22
A pharmaceutical formulation comprising active ingredient (S)—N—((S)-1-cyclohexyl-2-{(S)-2-[4-(4-fluoro-benzoyl)-thiazol-2-yl]-pyrrolidin-1-yl}-2-oxo-ethyl)-2-methylamino-propionamide of crystalline hemihydrate Form HA or a pharmaceutically acceptable salt thereof in an amount higher than 100 mg, and pharmaceutically acceptable excipients thereof and wherein the active ingredient is more than 40% (w/w) of the total formulation.
A pharmaceutical formulation comprising an internal granular portion and an extra granular portion,
- wherein the internal granular portion comprises:
- (1) about 40-60% (w/w) active ingredient (S)—N—((S)-1-cyclohexyl-2-{(S)-2-[4-(4-fluoro-benzoyl)-thiazol-2-yl]-pyrrolidin-1-yl}-2-oxo-ethyl)-2-methylamino-propionamide of crystalline hemihydrate Form HA or a pharmaceutically acceptable salt thereof in an amount higher than 100 mg, and pharmaceutically acceptable excipients thereof,
- (2) about 15.0-37.4% (w/w) microcrystalline cellulose, and
- (3) about 3.0-10.0% (w/w) polyvinylpyrrolidone or povidone;
- and
- wherein the extra granular portion comprises:
- (1) up to 22.4% (w/w) of binder or filler,
- (2) about 2.0-80% (w/w) of disintegrant, and
- (3) about 0.5-1.5% (w/w) of lubricant.
A pharmaceutical formulation comprising active ingredient (S)—N—((S)-1-cyclohexyl-2-{(S)-2-[4-(4-fluoro-benzoyl)-thiazol-2-yl]-pyrrolidin-1-yl}-2-oxo-ethyl)-2-methylamino-propionamide of crystalline hemihydrate Form HA or a pharmaceutically acceptable salt thereof and pharmaceutically acceptable excipients thereof.
Dependencies are inferred from the claim text.