Extended-release topiramate capsules

• US 10,172,878 B2
• Filed: 11/21/2016
• Issued: 01/08/2019
• Est. Priority Date: 03/15/2013
• Status: Active Grant

• Current Assignee: Upsher-Smith Laboratories, LLC (SAWAI GROUP HOLDINGS Co., Ltd.)
• Original Assignee: Upsher-Smith Laboratories, LLC (SAWAI GROUP HOLDINGS Co., Ltd.)
• Inventors: Betterman, Sarah Michelle, Tantry, Jaidev Srinivas, Patrick, Laura Marie
• Primary Examiner(s): Shomer, Isaac
• Application Number:
  US15/357,597
• Publication Number:
  US 20170119808A1
• Time in Patent Office: 778 Days
• Field of Search: None
• CPC Class Codes: A61K 31/357 having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61K 9/5042 Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/5047 Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose

Abstract

An extended-release topiramate capsule that includes a capsule shell containing a single population of coated particles; wherein each coated particle includes a core and a coating thereon; wherein each particle core includes a homogeneous mixture comprising topiramate throughout its core; and wherein the coating includes one or more release controlling agent(s).

Claims

1. A container comprising an extended-release topiramate capsule and desiccant, wherein the extended-release topiramate capsule comprises:

a capsule shell comprising a single population of coated particles;

wherein each coated particle comprises a core and a coating thereon;

wherein each particle core comprises a homogeneous mixture throughout its core, the mixture comprising;

topiramate;

one or more filler(s); and

one or more binder(s);

wherein the coating comprises;

one or more release controlling agent(s);

one or more pore former(s); and

one or more plasticizer(s);

wherein the components in the particle core and coating are present in amounts that provide extended release of topiramate; and

wherein, when a single dose is given to a healthy human subject, an AUC_0-inf of 170 to 210 h·

μ

g/mL within a 95% confidence interval, and a C_max of 2 to 4 μ

g/mL within a 95% confidence interval are achieved in the subject'"'"'s plasma.

2. The container of claim 1 wherein the ratio of weight of desiccant to weight of filled capsules is at least 0.01.

3. The container of claim 1 wherein the ratio of weight of desiccant to weight of filled capsules is up to 0.9.

4. The container of claim 1 wherein the desiccant is selected from silica gel, bentonite clay, molecular sieve, and combinations thereof.

5. A container comprising an extended-release topiramate capsule and desiccant, wherein the extended-release topiramate capsule comprises:

a capsule shell comprising a single population of coated particles;

wherein each coated particle comprises a core and a coating thereon;

wherein each particle core comprises a homogeneous mixture throughout its core, the mixture comprising;

40 wt-% to 50 wt-% of topiramate, based on the total weight of an uncoated particle core;

45 wt-% to 55 wt-% of one or more filler(s), based on the total weight of an uncoated particle core; and

3 wt-% to 7 wt-% of one or more binder(s), based on the total weight of an uncoated particle core;

wherein the coating comprises;

55 wt-% to 65 wt-% of one or more release control agent(s), based on the total weight of the coating;

20 wt-% to 25 wt-% of one or more pore former(s), based on the total weight of the coating; and

10 wt-% to 20 wt-% of one or more plasticizer(s), based on the total weight of the coating;

wherein the particles are coated in an amount sufficient to provide a weight gain of 8% to 14%.

6. The container of claim 5 wherein each particle core comprises a homogeneous mixture throughout its core, the mixture comprising:

40 wt-% to 50 wt-% of topiramate, based on the total weight of an uncoated particle core;

45 wt-% to 55 wt-% of one or more filler(s), based on the total weight of an uncoated particle core;

wherein the one or more filler(s) is selected from the group of microcrystalline cellulose, dibasic calcium phosphate, lactose, tribasic calcium phosphate, mannitol, and combinations thereof; and

3 wt-% to 7 wt-% of one or more binder(s), based on the total weight of an uncoated particle core;

wherein the one or more binder(s) is selected from the group of hydroxypropyl methylcellulose, methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, hydroxypropyl cellulose, hydroxyethylcellulose, polyvinyl pyrrolidine, starch, natural gum, and combinations thereof;

wherein the coating comprises;

55 wt-% to 65 wt-% of one or more release control agent(s), based on the total weight of the coating;

wherein the one or more release controlling agent(s) is selected from the group of ethylcellulose, polyvinyl acetate, polyacrylate and polymethacrylate, copolymers thereof, and combinations thereof;

20 wt-% to 25 wt-% of one or more pore former(s), based on the total weight of the coating;

wherein the one or more pore former(s) is selected from the group of hypromellose, hydroxypropyl cellulose, methylcellulose, hydroxyethylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, polyethylene glycol, guar gum, xanthan gum, sodium alginate, polyvinylpyrrolidone, crospovidone, sodium starch glycolate, croscarmellose sodium, starch, mannitol, glucose, sucrose, fructose, mannose, galactose, sorbitol, dextran, sodium chloride, potassium chloride, calcium chloride, and combinations thereof; and

10 wt-% to 20 wt-% of one or more plasticizer(s), based on the total weight of the coating;

wherein the one or more plasticizer(s) is selected from the group of diethyl phthalate, triethyl citrate, dibutyl sebacate, polyethylene glycol, triacetin, tributyl citrate, glycerol, propylene glycol, and combinations thereof;

wherein the particles are coated in an amount sufficient to provide a weight gain of 8% to 14%.

7. The container of claim 6 wherein each particle core comprises a homogeneous mixture throughout its core, the mixture comprising:

40-50 wt-% of topiramate, based on the total weight of an uncoated particle core;

45-55 wt-% of microcrystalline cellulose, based on the total weight of an uncoated particle core; and

3-7 wt-% of hydroxypropyl methylcellulose, based on the total weight of an uncoated particle core;

wherein the coating comprises;

55-65 wt-% of ethylcellulose, based on the total weight of the coating;

20-25 wt-% of hydroxypropyl methylcellulose, based on the total weight of the coating; and

10-20 wt-% of diethyl phthalate, based on the total weight of the coating;

wherein the particles are coated in an amount sufficient to provide a weight gain of 8% to 14%.

8. The container of claim 7 wherein each particle core comprises a homogeneous mixture throughout its core, the mixture comprising:

44-46 wt-% of topiramate, based on the total weight of an uncoated particle core;

48-52 wt-% of microcrystalline cellulose, based on the total weight of an uncoated particle core; and

4-6 wt-% of hydroxypropyl methylcellulose, based on the total weight of an uncoated particle core;

wherein the coating comprises;

60-62 wt-% of ethylcellulose, based on the total weight of the coating;

22-24 wt-% of hydroxypropyl methylcellulose, based on the total weight of the coating; and

15-18 wt-% of diethyl phthalate, based on the total weight of the coating;

wherein the particles are coated in an amount sufficient to provide a weight gain of 10-12%.

9. The container of claim 5 wherein the ratio of weight of desiccant to weight of filled capsules is at least 0.01.

10. The container of claim 5 wherein the ratio of weight of desiccant to weight of filled capsules is up to 0.9.

11. The container of claim 5 wherein the desiccant is selected from silica gel, bentonite clay, molecular sieve, and combinations thereof.