Pharmaceutical compositions for release control of methylphenidate

• US 8,465,768 B2
• Filed: 11/06/2009
• Issued: 06/18/2013
• Est. Priority Date: 11/07/2008
• Status: Active Grant

• Current Assignee: Samyang Holdings Corporation
• Original Assignee: Samyang Biopharmaceuticals Corporation (Samyang Holdings Corporation)
• Inventors: Park, Sang Yeob, Chung, Hojin, Pai, Chaul Min
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): Tcherkasskaya, Olga V
• Application Number:
  US13/126,855
• Publication Number:
  US 20110223247A1
• Time in Patent Office: 1,320 Days
• Field of Search: None
• US Class Current: 424/462
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/0095 Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006
• CPC Class Codes: A61K 9/5073 having two or more different coatings optionally including drug-containing subcoatings
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia

Abstract

Disclosed is a pharmaceutical composition for release control comprising a plurality of particles for release control. The plurality of particles for release control comprise a core material containing methylphenidate and a polymer coating layer for release control formed on the core material. The plurality of particles for release control are divided into two or more groups based on the average thickness of the polymer coating layer for release control. The particle groups are identical in terms of the composition of the polymer in the polymer coating layer, but are different in terms of the average thickness of the coated layer. The pharmaceutical composition for release control according to the present invention may control the release pattern of methylphenidate contained in the core material as desired, and can be used as an oral formulation in a variety of forms such as orally disintegrating tablets, etc.

Claims

1. A pharmaceutical composition for release control of methylphenidate comprising:

a plurality of particles comprising a core material containing methylphenidate and a polymer coating layer formed on the core material,

wherein the plurality of particles are identical in terms of the composition of the polymer in the polymer coating layer, but are divided into two or more particle groups based on the average thickness of the polymer coating layer, and

wherein the particle groups comprise a first particle group having an average coating layer thickness of 1 to 30 μ

m, and a second particle group having an average coating layer thickness of 45 to 250 μ

m.

2. The pharmaceutical composition according to claim 1, wherein the polymer coating layer comprises a single layer or two or more layers.

3. The pharmaceutical composition according to claim 2, wherein, in the polymer coating layer comprising two or more layers, each layer is identical or different in terms of the composition of the polymer.

4. The pharmaceutical composition according to claim 1, wherein the particles further comprise a coating selected from a sub-coating inside the polymer coating layer and an over-coating outside the polymer coating layer.

5. The pharmaceutical composition according to claim 1, wherein the polymer of the polymer coating layer is one or more selected from a group consisting of a water-insoluble polymer, a water-soluble polymer, an enteric polymer, and a gastric polymer.

6. The pharmaceutical composition according to claim 1, wherein the particles have an average diameter of 30 to 3500 μ

m.

7. The pharmaceutical composition according to a claim 1, wherein the particle groups further comprise a third particle group.

8. The pharmaceutical composition according to claim 1 7, wherein the first particle group has an average coating layer thickness of 2 to 30 μ

m, and the second particle group has an average coating layer thickness of 45 to 90 μ

m.

9. The pharmaceutical composition according to claim 7, wherein the weight ratio of the first particle group:

the second particle group;

the third particle group is 1;

0.1-10;

0.1-10.

10. The pharmaceutical composition according to claim 1, wherein the release profile of the pharmaceutical composition tested according to the method 2(paddle method) of “

36. release test method”

of the Korean Pharmacopoeia, 8th edition (KP VIII) in 500 mL of water at 50 rpm exhibits;

5 to 50% of the total drug is released within 1 hour,

10 to 65% of the total drug is released within 2 hours,

20 to 80% of the total drug is released within 4 hours,

30 to 95% of the total drug is released within 6 hours, and

50% or more of the total drug is released within 8 hours.

11. The pharmaceutical composition according to claim 10, wherein the release profile of the pharmaceutical composition tested according to the method 2 (paddle method) of “

36. release test method”

of KP VIII in 500 mL of water at 50 rpm exhibits;

10 to 40% of the total drug is released within 1 hour,

15 to 50% of the total drug is released within 2 hours,

30 to 75% of the total drug is released within 4 hours,

50 to 90% of the total drug is released within 6 hours, and

70% or more of the total drug is released within 8 hours.

12. The pharmaceutical composition according to claim 1, wherein the core material and the polymer coating layer further comprise one or more selected from a group consisting of a sugar, a sugar alcohol, a polymer material, a colorant, an aromatic, a sweetener, a surfactant, a lubricant, a stabilizer, an antioxidant, a foaming agent, paraffin, wax, and a plasticizer.

13. The pharmaceutical composition according to claim 12, wherein the plasticizer is one or more selected from a group consisting of acetyl triethyl citrate, dibutyl phthalate, tributyl citrate, triethyl citrate, acetyl triethyl citrate, propylene glycol, triacetin, polyethylene glycol, diethyl phthalate, dibutyl sebacate, diethyl sebacate, cetyl alcohol, stearyl alcohol, and cetostearyl alcohol.

14. The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition is an oral formulation.

15. The pharmaceutical composition according to claim 14, wherein the oral formulation is an orally disintegrating tablet, a chewable tablet, a capsule, a general tablet, a granule, or a syrup.

16. The pharmaceutical composition according to claim 7, wherein the difference between the average coating layer thickness of the second particle group and the third particle group is 10 to 80 μ

m.

17. The pharmaceutical composition according to claim 1, wherein the polymer of the polymer coating layer is water-insoluble ethyl acrylate-methyl methacrylate-chlorotrimethylammoniumethyl methacrylate copolymer.