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, where the pharmaceutically acceptable tablet is prepared by a process comprising:
mixing samidorphon or a pharmaceutically acceptable salt thereof, and microcrystalline silicon dioxide to form a samidorphan premix;
blending the samidorphan premix with a composition comprising: microcrystalline cellulose, lactose monohydrate and crospovidone, to form a samidorphan blend;
blending olanzapine with a composition comprising microcrystalline cellulose and crospovidone to form an olanzapine blend;
lubricating the olanzapine blend and the samidorphan blend with a lubricant selected from the group consisting of a stearate, stearic acid and combinations thereof, to form lubrication blends; and
compressing the lubrication blends to form the pharmaceutically acceptable tablet;
wherein the tablet comprises:
the 10 mg samidorphan or a pharmaceutically acceptable salt of samidorphan in an amount to deliver the 10 mg samidorphan; and
a fixed dose of olanzapine selected from the group consisting of 5 mg, 10 mg, 15 mg and 20 mg of the olanzapine; and
about 75-90 wt % of the lactose monohydrate and microcrystalline cellulose.
2 . The pharmaceutically acceptable tablet of claim 1 , wherein the tablet releases at least 97% of the 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 table of claim 1 , wherein less than 0.5 wt % impurities from olanzapine degradation are detected, using HPLC, after the tablet is stored for 6 months in a closed container containing 250 g silica gel desiccant at 25° C. and 60% relative humidity.
4 . The pharmaceutically acceptable tablet of claim 1 , wherein the lubricant is magnesium stearate.
5 . The pharmaceutically acceptable tablet of claim 1 , wherein the pharmaceutically acceptable salt of samidorphan is samidorphan L-malate.
6 . The pharmaceutically acceptable tablet of claim 5 , wherein the particle size distribution (D10) of the samidorphan L-malate is about 10 μm to about 80 μm and the particle size distribution (D90) of the samidorphan L-malate is about 100 μm to about 300 μm.
7 . A pharmaceutically acceptable tablet for orally delivering a fixed dose of olanzapine and 10 mg of samidorphan, where the pharmaceutically acceptable tablet is prepared by a process comprising:
blending samidorphan L-malate with a composition comprising:
a first diluent independently selected from the group consisting of lactose or a hydrate thereof, microcrystalline cellulose, mannitol, sorbitol, xylitol, dicalcium phosphate, starch and combinations thereof; and
a first disintegrant selected from the group consisting of polyvinylpyrrolidone, crosslinked sodium carboxymethyl cellulose, sodium starch glycolate and combinations thereof, to form a samidorphan blend;
blending olanzapine with a composition comprising:
a second diluent selected from the group consisting of lactose or a hydrate thereof, microcrystalline cellulose, mannitol, sorbitol, xylitol, dicalcium phosphate, starch and combinations thereof; and
a second disintegrant selected from the group consisting of polyvinylpyrrolidone, crosslinked sodium carboxymethyl cellulose, sodium starch glycolate and combinations thereof, to form a olanzapine blend;
lubricating the olanzapine blend and the samidorphan blend with a lubricant selected from the group consisting of a stearate, stearic acid and combinations thereof, to form lubrication blends; and
compressing the lubrication blends to form the pharmaceutically acceptable tablet;
wherein the tablet comprises:
13.6 mg of the samidorphan L-malate;
a fixed dose of olanzapine selected from the group consisting of 5 mg, 10 mg, 15 mg and 20 mg of the olanzapine; and
about 75-90 wt % of the first and second diluent.
8 . A pharmaceutically acceptable immediate release tablet for orally delivering a fixed dose of olanzapine and 10 mg of samidorphan, wherein the tablet comprises:
13.6 mg samidorphan L-malate, wherein the particle size distribution (D50) of the samidorphan L-malate is about 40 μm to about 200 μm;
about 75-90 wt % of a diluent;
a lubricant selected from the group consisting of a stearate, stearic acid and combination thereof;
a fixed dose of olanzapine selected from the group consisting of 5 mg, 10 mg, 15 mg and 20 mg of the olanzapine; and
a disintegrant selected from the group consisting of polyvinylpyrrolidone, crosslinked sodium carboxymethyl cellulose, sodium starch glycolate and combinations thereof;
and a barrier layer to provide a physical distance between the samidorphan L-malate and the olanzapine.