Immediate release multilayer tablet

Patent metadata

Field	Value
Publication number	US-2024091237-A1
Application number	US-202318510590-A
Country	US
Kind code	A1
Filing date	Nov 15, 2023
Priority date	Nov 12, 2020
Publication date	Mar 21, 2024
Grant date	—

Abstract

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.

First claim

What is claimed is:

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:
10 mg samidorphan or a pharmaceutically acceptable salt of samidorphan in an amount to deliver 10 mg samidorphan;
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 1.5 to about 2 wt % of 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 75-90 wt % of 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; based on the weight of the first tablet layer; and
about 1.0 wt % magnesium stearate;
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.

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 , wherein the pharmaceutically acceptable salt of samidorphan in amount to deliver 10 mg samidorphan is 13.6 mg samidorphan L-malate.

4 . The pharmaceutically acceptable tablet of claim 1 , further comprising a film coating over the tablet layers.

5 . The pharmaceutically acceptable tablet of claim 1 , wherein less than 1 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 40° C. and 75% relative humidity.

6 . The pharmaceutically acceptable 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 tablet of claim 1 , wherein the dose of olanzapine is 5 mg.

8 . The pharmaceutically acceptable tablet of claim 1 , wherein the dose of olanzapine is 10 mg.

9 . The pharmaceutically acceptable tablet of claim 1 , wherein the dose of olanzapine is 15 mg.

10 . The pharmaceutically acceptable tablet of claim 1 , wherein the dose of olanzapine is 20 mg.

11 . 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 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 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;
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 months in a closed container containing 250 g silica gel desiccant at 25° C. and 60% relative humidity.

12 . The pharmaceutically acceptable immediate release tablet of claim 11 , 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.

13 . The pharmaceutically acceptable immediate release tablet of claim 11 , 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.

14 . 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 1.0 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.

15 . A pharmaceutically acceptable immediate release tablet for orally delivering, as a fixed dose, olanzapine and 10 mg of samidorphan wherein the 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 75-90 wt % of a first diluent, based on the weight of the first tablet layer; and
a first disintegrant selected from the group consisting of polyvinylpyrrolidone, crosslinked sodium carboxymethyl cellulose, sodium starch glycolate and combinations thereof;
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 75-90 wt % of a second diluent; and
a second disintegrant selected from the group consisting of polyvinylpyrrolidone, crosslinked sodium carboxymethyl cellulose, sodium starch glycolate and combinations thereof, wherein less than 1.0 wt % impurities from olanzapine degradation are detected, using HPLC, after the tablet is stored for 3 months in a closed container containing 250 g silica gel desiccant at 25° C. and 60% relative humidity.

16 . The pharmaceutically acceptable tablet of claim 15 , 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.

Assignees

• Alkermes Pharma Ireland Ltd

Inventors

• Chiarella Renato A
• Guzman Hector
• Hurley Paul
• Manser David
• Perkin Kristopher

Classifications

• A61K31/5513 Primary

  1,4-Benzodiazepines, e.g. diazepam {or clozapine} · CPC title

• A61K9/2013

  Organic compounds, e.g. phospholipids, fats · CPC title

• A61K9/2018

  Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates · CPC title

• A61K9/2027

  obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates · CPC title

• A61K9/2054

  Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose · CPC title