IMMEDIATE RELEASE MULTILAYER TABLET
Described herein, in part, are tablets, such as immediate release multi-layer or bilayer tablets for orally delivering olanzapine and samidorphan, methods of using said tablets in the treatment of disorders described herein, and kits comprising said tablets.
1 . A pharmaceutically acceptable tablet for orally delivering a fixed dose of olanzapine and 10 mg of samidorphan, wherein the tablet comprises:
a first tablet layer comprising:
13.6 mg samidorphan malate, wherein the particle size distribution (D90) of the samidorphan malate is about 150 μm to about 300 μm;
about 75-90 wt % of a first diluent selected from the group consisting of lactose or a hydrate thereof, microcrystalline cellulose, mannitol, sorbitol, xylitol, dicalcium phosphate, starch and combinations thereof; based on the weight of the first tablet layer; and
about 0.5 wt % to about 2 wt % magnesium stearate; and
a second tablet layer comprising:
a dose of olanzapine selected from the group consisting of 5 mg, 10 mg, 15 mg and 20 mg of the olanzapine;
about 75-90 wt % of a second diluent; and
a lubricant selected from the group consisting of a stearate, stearic acid and combinations thereof;
wherein less than 0.5 wt % impurities from olanzapine degradation are detected, using HPLC, after the tablet is stored for 6 month in a closed container containing 250 g silica gel desiccant at 25° C. and 60% relative humidity.
2 . The pharmaceutically acceptable tablet of claim 1 , wherein the tablet releases at least 97% of olanzapine and at least 97% of the samidorphan after 30 minutes when the tablet is tested in 500 mL USP acetate buffer at pH 4.5 using a USP Apparatus II (Paddle Method) at 37° C., with a paddle speed of 75 rpm and using a three-prong sinker.
3 . The pharmaceutically acceptable tablet of claim 1 , further comprising a film coating over the tablet layers.
4 . The pharmaceutically acceptable tablet of claim 1 , wherein the dose of olanzapine is 5 mg.
5 . The pharmaceutically acceptable tablet of claim 1 , wherein the dose of olanzapine is 10 mg.
6 . The pharmaceutically acceptable tablet of claim 1 , wherein the dose of olanzapine is 15 mg.
7 . The pharmaceutically acceptable tablet of claim 1 , wherein the dose of olanzapine is 20 mg.
8 . A pharmaceutically acceptable immediate release tablet for orally delivering a fixed dose of olanzapine and 10 mg of samidorphan, wherein the tablet comprises:
a first tablet layer comprising:
13.6 mg samidorphan malate;
about 75-90 wt % of a first diluent; and
a lubricant selected from the group consisting of a stearate, stearic acid and combination thereof;
a second tablet layer comprising:
a dose of olanzapine selected from the group consisting of 5 mg, 10 mg, 15 mg and 20 mg of the olanzapine;
a second diluent; and
a lubricant selected from the group consisting of a stearate, stearic acid and combinations thereof;
wherein less than 0.5 wt % impurities from olanzapine degradation are detected, using HPLC, after the tablet is stored for 6 month in a closed container containing 250 g silica gel desiccant at 25° C. and 60% relative humidity.
9 . The pharmaceutically acceptable immediate release tablet of claim 8 , wherein the particle size distribution (D10) of the samidorphan malate is about 10 μm to about 80 μm.
10 . The pharmaceutically acceptable immediate release tablet of claim 8 , wherein first diluent and the second diluent are each independently selected from the group consisting of lactose or a hydrate thereof, microcrystalline cellulose, mannitol, sorbitol, xylitol, dicalcium phosphate, starch and combinations thereof.
11 . A pharmaceutically acceptable immediate release tablet for orally delivering olanzapine and 10 mg of samidorphan as a fixed dose, comprising:
a first tablet layer comprising:
10 mg samidorphan or a pharmaceutically acceptable salt of samidorphan in an amount to deliver 10 mg samidorphan; a diluent and a disintegrant; and
a second tablet layer comprising:
a dose of olanzapine selected from the group consisting of 5 mg, 10 mg, 15 mg and 20 mg of the olanzapine; a diluent and a disintegrant;
wherein less than 0.5 wt % impurities from olanzapine degradation are detected, using HPLC, after the tablet is stored for 6 month in a closed container containing 250 g silica gel desiccant at 25° C. and 60% relative humidity.
12 . The pharmaceutically acceptable tablet of claim 11 , wherein the tablet releases at least 97% of olanzapine and at least 97% of the samidorphan after 30 minutes when the tablet is tested in 500 mL USP acetate buffer at pH 4.5 using a USP Apparatus II (Paddle Method) at 37° C., with a paddle speed of 75 rpm and using a three-prong sinker.
13 . The pharmaceutically acceptable tablet of claim 11 , further comprising a film coating over the tablet layers.