Immediate release multilayer tablet

Patent metadata

Field	Value
Publication number	US-11951111-B2
Application number	US-202318327229-A
Country	US
Kind code	B2
Filing date	Jun 1, 2023
Priority date	Nov 12, 2020
Publication date	Apr 9, 2024
Grant date	Apr 9, 2024

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 method of treating schizophrenia or bipolar I disorder in a patient in need thereof, the method comprising orally administering to the patient, once daily, 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, 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 with a paddle speed of 75 rpm and using a three-prong sinker.

2. The method 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 method 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 method 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.

5. The method 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.

6. The method of claim 1 , wherein the dose of olanzapine is 5 mg.

7. The method of claim 1 , wherein the dose of olanzapine is 10 mg.

8. The method of claim 1 , wherein the dose of olanzapine is 15 mg.

9. The method of claim 1 , wherein the dose of olanzapine is 20 mg.

10. A method of treating schizophrenia or bipolar I disorder in a patient in need thereof, the method comprising orally administering to the patient, once daily, 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,
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 with a paddle speed of 75 rpm and using a three-prong sinker.

11. The method of claim 10 , 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.

12. A method of treating schizophrenia or bipolar I disorder in a patient in need thereof, the method comprising orally administering to the patient, once daily, 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.

13. A method of treating schizophrenia or bipolar I disorder in a patient in need thereof, the method comprising orally administering to the patient, once daily, 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,
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 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