TABLET FORMULATIONS CONTAINING 8-[-METHYL]-8-PHENYL-1,7-DIAZA-SPIRO[4.5]DECAN-2-ONE SALTS AND TABLETS MADE THEREFROM
Pharmaceutical formulations containing a salt of (5S,8S)-8-[{(1R)-1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diazaspiro[4.5]decan-2-one, represented by Formula I, which are suitable for forming into a tablet dosage form, as well as tablet dosage forms are disclosed. Disclosed also are methods of treatment utilizing such dosage forms.
1 .- 30 . (canceled)
31 . A method of treating and/or preventing emesis and/or nausea in a mammal comprising administering to the mammal a therapeutically effective amount of a powdered pharmaceutical formulation comprising:
(a) a granulate comprising at least one crystalline salt of (5S,8S)-8-[{(1R)-1-(3,5-bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diazaspiro[4.5]decan-2-one, intergranular microcrystalline cellulose, lactose monohydrate, a first disintegrant, and a binder; and
(b) extragranular microcrystalline cellulose, a second disintegrant, and magnesium stearate;
wherein the formulation provides upon compression in a tablet press, a tablet having a hardness of at least 10 kp.
32 .- 48 . (canceled)
49 . The method of claim 31 , wherein the emesis and/or nausea is delayed-phase chemically-induced emesis and/or delayed-phase chemically-induced nausea.
50 . The method of claim 31 , wherein the granulate comprises a crystalline hydrochloride salt form of (5S,8S)-8-[{(1R)-1-(3,5-bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diazaspiro[4.5]decan-2-one.
51 . The method of claim 31 , wherein the granulate comprises the crystalline monohydrate hydrochloride salt form of (5S,8S)-8-[{(1R)-1-(3,5-bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diazaspiro[4.5]decan-2-one.
52 . The method of claim 51 , wherein said crystalline hydrochloride monohydrate salt form (5S,8S)-8-[{(1R)-1-(3,5-bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diazaspiro[4.5]decan-2-one is characterized by an X-ray Powder Diffraction Pattern containing the following characteristic peaks expressed in terms of diffraction angle (in 2θ, all values reflect an accuracy of ±0.2): 16.1; 18.4; 21.6; and 23.5.
53 . The method of claim 31 , wherein the granulate comprises a tosylate salt form of (5S,8S)-8-[{(1R)-1-(3,5-bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diazaspiro[4.5]decan-2-one.
54 . The method of claim 31 , wherein said first and said second disintegrant are croscarmellose sodium.
55 . The method of claim 31 , wherein said binder is selected from povidone K30, pregelatinized starch, and hypromellose 2910, 6 cps.
56 . The method of claim 55 wherein the binder is pregelatinized starch.
57 . The method of claim 56 , wherein the pharmaceutical formulation comprises from about 10 wt. % to about 20 wt. % starch.
58 . The method of claim 55 , wherein the binder is povidone K30.
59 . The method of claim 58 , wherein the pharmaceutical formulation comprises from about 3 wt. % to about 10 wt. % of povidone K30.
60 . The method of claim 55 wherein the binder is hypromellose 2910, 6 cps.
61 . The method of claim 60 , wherein the pharmaceutical formulation comprises from about 3 wt. % to about 6 wt. % of hypromellose 2910, 6 cps.
62 . The method of claim 31 , wherein the intragranular microcrystalline cellulose is used in an amount comprising from about 2 wt. % to about 20 wt. % of the product formulation.