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 coated immediate release bilayer tablet for orally delivering a fixed dose of olanzapine and 10 mg of samidorphan, wherein the bilayer tablet comprises:
a first tablet layer comprising:
10 mg samidorphan or a pharmaceutically acceptable salt of samidorphan in an amount to deliver 10 mg samidorphan;
about 35-43 wt % microcrystalline cellulose, based on the weight of the first tablet layer;
about 37-43 wt % lactose or a hydrate thereof, based on the weight of the first tablet layer; and
about 1.5 to about 2 wt % magnesium stearate;
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 38-42 wt % microcrystalline cellulose, based on the weight of the second tablet layer;
about 46-49 wt % lactose or a hydrate thereof, based on the weight of the second tablet layer; and
about 1.0 wt % magnesium stearate;
and
a film coating over the first and second tablet layer.
2. The pharmaceutically acceptable coated immediate release bilayer 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 1.0 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 coated immediate release bilayer 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.
4. The pharmaceutically acceptable coated immediate release bilayer tablet of claim 1 , wherein the pharmaceutically acceptable salt of samidorphan in amount to deliver 10 mg samidorphan is 13.6 mg samidorphan L-malate.
5. The pharmaceutically acceptable coated immediate release bilayer tablet of claim 1 , 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.
6. The pharmaceutically acceptable coated immediate release bilayer tablet of claim 1 , wherein the first tablet layer further comprises about 2.0 wt % crospovidone and the second tablet layer further comprises about 1.0 wt % crospovidone.
7. The pharmaceutically acceptable coated immediate release bilayer tablet of claim 1 , wherein the dose of olanzapine is 5 mg.
8. The pharmaceutically acceptable coated immediate release bilayer tablet of claim 1 , wherein the dose of olanzapine is 10 mg.
9. The pharmaceutically acceptable coated immediate release bilayer tablet of claim 1 , wherein the dose of olanzapine is 15 mg.
10. The pharmaceutically acceptable coated immediate release bilayer tablet of claim 1 , wherein the dose of olanzapine is 20 mg.
11. A pharmaceutically acceptable coated immediate release bilayer tablet for orally delivering a fixed dose of olanzapine and 10 mg of samidorphan, wherein the bilayer tablet comprises:
a first tablet layer comprising:
13.6 mg samidorphan L-malate;
about 40 wt % microcrystalline cellulose, based on the weight of the first tablet layer;
about 42 wt % lactose monohydrate, based on the weight of the first tablet layer; and
about 1.75 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 40 wt % microcrystalline cellulose, based on the weight of the second tablet layer;
about 47 wt % lactose or a hydrate thereof, based on the weight of the second tablet layer; and
about 1.0 wt % magnesium stearate;
and
a film coating over the first and second tablet layer.
12. The pharmaceutically acceptable coated immediate release bilayer tablet of claim 11 , wherein the samidorphan L-malate has a particle size distribution (D10) of about 10 μm to about 80 μm, a particle size distribution (D50) of about 40 μm to about 200 μm, and a particle size distribution (D90) of about 100 μm to about 300 μm.
13. The pharmaceutically acceptable coated immediate release bilayer tablet of claim 12 , 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 1.0 using a USP Apparatus II (Paddle Method) at 37° C., with a paddle speed of 75 rpm.
14. A pharmaceutically acceptable coated immediate release bilayer 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;
about 35-43 wt % microcrystalline cellulose, based on the weight of the first tablet layer; and
about 37-43 wt % lactose or a hydrate thereof, based on the weight of the first tablet layer;
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 38-42 wt % microcrystalline cellulose, based on the weight of the second tablet layer;
about 46-49 wt % lactose or a hydrate thereof, based on the weight of the second tablet layer;
and
a film coating over the first and second tablet layer; wherein the bi-layer tablet releases at least 85% of olazanpine and at least 85% of the samidorphan after 15 minutes when the bi-layer 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.
15. A pharmaceutically acceptable coated immediate release bilayer tablet for orally delivering, as a fixed dose, olanzapine and 10 mg of samidorphan wherein the bilayer tablet, comprises:
a first tablet layer comprising:
10 mg samidorphan or a pharmaceutically acceptable salt of samidorphan in an amount to deliver 10 mg samidorphan;
about 30-45 wt % microcrystalline cellulose, based on the weight of the first tablet layer;
about 35-50 wt % lactose or a hydrate thereof, based on the weight of the first tablet layer;
a second tablet layer comprising:
a dose of olanzapine selected from the group consisting of 2.5 mg, 5 mg, 10 mg, 15 mg and 20 mg of the olanzapine;
about 35-45 wt % microcrystalline cellulose, based on the weight of the second tablet layer;
about 45-55 wt % lactose or a hydrate thereof, based on the weight of the second tablet layer; and
a film coating over the first and second tablet layer.