Sustained Release Solid Formulations and Methods of Manufacturing the Same

• US 20110008424A1
• Filed: 04/28/2008
• Published: 01/13/2011
• Est. Priority Date: 02/18/2008
• Status: Active Grant

• Current Assignee: Handa Pharmaceuticals LLC (Handa Pharmaceuticals, Inc.)
• Original Assignee: Handa Pharmaceuticals LLC (Handa Pharmaceuticals, Inc.)
• Inventors: Chang, Shajoung, Choi, Oak
• Granted Patent: US 8,951,557 B2
• Time in Patent Office: Days
• US Class Current: 424/452
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2068 Compounds of unknown constitution, e.g. material from plants or animals oils, fats, waxes, shellac A61K9/2013
• CPC Class Codes: A61K 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids

Abstract

Disclosed are a sustained release solid formulation comprising a drug, for example, oxycodone or its pharmaceutically acceptable salt, in a water-insoluble matrix, which comprises a wax type excipient and copovidone, and thus, has increased compressibility and fluidity and reduced adhesiveness, and a method of preparing the same.

Claims

1. A sustained release solid formulation comprising a drug in a water-insoluble matrix, wherein the water-insoluble matrix comprises a wax type excipient and copovidone, and has the void filled or the surface coated with the wax and a reduced porosity by the wax and the copovidone.

2. The sustained release solid formulation as set forth in claim 1, which is prepared by a method comprising:

i) mixing a drug with a wax type excipient to prepare a mixture or granules;

ii) heating the mixture or granules of step i) to a temperature at which the wax type excipient can be melted, and then cooling the heated mixture or granules; and

iii) compressing or filling in a capsule the mixture or granules of step ii),

wherein copovidone is added in any of steps i), ii) and iii).

3. The sustained release solid formulation as set forth in claim 1, wherein the drug is selected from the group consisting of an analgesic, an anti-allergic drug, a blood pressure depressant, an antibiotic, a bronchodilator or an antiasthmatic, an antiarrhythmic, a central nervous system drug, a cell growth inhibitor or a metastasis inhibitor, an antimigraine, a gastrointestinal drug, an oral antidiabetic, a urinary incontinence drug, pharmaceutically acceptable salts and esters thereof, and a combination thereof.

4. The formulation as set forth in claim 3, wherein the drug is oxycodone or its pharmaceutically acceptable salt.

5. The formulation as set forth in claim 1, wherein the wax type excipient is selected from the group consisting of glyceryl fatty acid ester, fatty acid ester, carnauba wax, beeswax, white beeswax, paraffin, microcrystalline wax, hydrogenated oil and a combination thereof.

6. The formulation as set forth in claim 5, wherein the glyceryl fatty acid ester or the fatty acid ester is selected from the group consisting of glyceryl palmitostearate, glyceryl behenate, glyceryl stearate, glyceryl oleate, glyceryl myristate, cetyl palmitate, cetyl caprate, stearyl palmitate, stearyl stearate and a mixture thereof.

7. The formulation as set forth in claim 2, wherein the wax type excipient is included at an amount of 10 to 50 parts by weight, based on 100 parts by weight of the mixture or granules.

8. The formulation as set forth in claim 2, wherein copovidone is included at an amount of 1 to 50 parts by weight, based on 100 parts by weight of the mixture or granules.

9. The formulation as set forth in claim 1, wherein the drug is coated with a hydrophobic carrier and adsorbed with an adsorbent.

10. The formulation as set forth in claim 9, wherein the hydrophobic carrier is selected from the group consisting of vegetable oil, mineral oil, synthetic oil, amphoteric surfactant having an HLB (hydrophilic-lipophilic balance) value less than 6, phospholipid lecithin and a mixture thereof, and the adsorbent is selected from the group consisting of colloidal silicon dioxide, talc and a mixture thereof.

11. The formulation as set forth in claim 9, wherein the hydrophobic carrier is used at an amount of 1 to 10 parts by weight based on 100 parts by weight of the drug, and the adsorbent is used at an amount of 50 to 150 parts by weight based on 100 parts by weight of the hydrophobic carrier.

12. The formulation as set forth in claim 1, which further comprises a release control agent selected from the group consisting of alkyl cellulose, polyvinyl acetate, polyoxyethylene-polyoxypropylene block copolymer, polyethylene oxide, hydroxypropylalkylcellulose, hydroxyalkylcellulose, sodium alginate, xanthan gum, locust bean gum, ammonio methacrylate copolymer, anionic copolymer of methacrylic acid and methacrylic acid methyl or ethyl ester, hydroxypropylmethylcellulose acetyl succinate, hydroxypropylmethylcellulose phthalate, carboxyvinyl polymer and a mixture thereof.

13. A method of preparing a sustained release solid formulation, which comprises:

i) mixing a drug with a wax type excipient to prepare a mixture or granules;

ii) heating the mixture or granules of step i) to a temperature at which the wax type excipient can be melted, and then cooling the heated mixture or granules; and

iii) compressing or filling in a capsule the mixture or granules of step ii),

wherein copovidone is added in any of steps i), ii) and iii).

14. The method as set forth in claim 13, wherein, in step ii), the heating is performed at a temperature higher than the melting point of the wax type excipient for 0.5 to 2 hours.

15. The method as set forth in claim 14, wherein, in step ii), the temperature is 1 to 10°

C. higher than the melting point of the wax type excipient.