Combination Product Comprising Phentermine and Topiramate, and Preparation Method Thereof

• US 20150044295A1
• Filed: 03/20/2013
• Published: 02/12/2015
• Est. Priority Date: 03/23/2012
• Status: Active Grant

• Current Assignee: Institute of Pharmacology and Toxicology Academy of Military Medical Sciences PLA China
• Original Assignee: Institute of Pharmacology and Toxicology Academy of Military Medical Sciences PLA China
• Inventors: LI, Song, Zhong, Wu, Zhou, Xinbo, Zheng, Zhibing, Wang, Xiaokui, Gao, Chunseng, Wang, Yuli, Yang, Meiyan, Shan, Li
• Granted Patent: US 9,421,188 B2
• Time in Patent Office: Days
• US Class Current: 424/495
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• 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 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 9/5047 Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: A61K 9/5084 Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs tablets containing such a mixture A61K9/2077
• CPC Class Codes: A61K 9/5089 Processes
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 Antihypertensives

Abstract

The present invention provides a combination product, which comprises immediate release pellet of phentermine and sustained-release pellet of topiramate, wherein the pellet of topiramate includes: a) a blank pellet core; b) an active drug layer that contains topiramate and is free of binding agent, the layer being located on surface of the blank pellet core; c) a sustained-release coating layer containing ethyl cellulose and PVP K30, the sustained-release coating layer being located on external of the active drug layer. The present invention further discloses a method for preparing the combination product.

Claims

1. A combination product, which comprises phentermine or salt thereof, and sustained-release pellet of topiramate, wherein the sustained-release pellet of topiramate comprises a blank pellet core, a drug layer and a sustained-release coating layer, which is characterized in that the drug layer is free of binding agent.

2. The combination product of claim 1, wherein the binding agent is selected from starch slurry, syrup, polyvinylpyrrolidone (povidone, PVP, such as PVP K30), methyl cellulose (MC), ethyl cellulose (EC), highly-substituted hydroxypropyl cellulose (H-HPC), hydroxypropyl methyl cellulose (HPMC), sodium carboxymethyl cellulose, gelatin, Arabic gum, and a mixture thereof.

3. The combination product of claim 1, wherein the sustained-release coating layer comprises a sustained-release material selected from ethyl cellulose, Eudragit NE 30D, Eudragit RS 30D, Eudragit RL30D, and a mixture thereof.

4. The combination product of claim 1, wherein the sustained-release coating layer comprises ethyl cellulose and PVP K30.

5. The combination product of claim 4, wherein the weight ratio of ethyl cellulose and PVP K30 is (1:

0.20)-(1;

0.45), for example (1;

0.25)-(1;

0.40), for example (1;

0.30)-(1;

0.35).

6. The combination product of claim 1, wherein the weight gain from the sustained-release coating is 2%-30%, for example 3%-20%, for example 5%-15%, for example 5%-10%, for example 5%-8%, for example 6%-8%.

7. The combination product of claim 1, wherein the drug layer of sustained-release pellet of topiramate consists of topiramate.

8. The combination product of claim 1, wherein the blank pellet core has a particle size of 150 μ

m-1500 μ

m, for example 250-1000 μ

m, for example 300-900 μ

m, for example 400-850 μ

m, for example 610-750 μ

m.

9. The combination product of claim 1, wherein the dosage form of said phentermine or salt thereof is immediate release pellet.

10. The combination product according to any one of claims 1-9, which is a capsule or tablet.

11. A method for preparing the sustained-release pellet of topiramate in the combination product according to any one of claims 1-10, the method comprising:

a) dissolving ingredients of the drug layer with suitable amount of solvent, and coating a blank pellet core with the obtained drug solution to give a drug-loaded pellet;

b) coating the drug-loaded pellet obtained in step a) with ingredients of sustained-release coating layer.

12. The method according to claim 11, wherein the step b) comprises the following steps:

dissolving ingredients of the sustained-release coating layer in a solvent, and coating the drug-loaded pellet obtained in step a) with the resultant solution.

13. The preparation method of claim 11 or 12, wherein the solvent is water, ethanol, acetone, propylene glycol, chloroform or a mixture thereof, for example, the solvent is a mixture of water and ethanol.

14. A use of the combination product according to any one of claims 1-10 in manufacture of a medicament for reducing body weight, reducing blood fat, lowering blood pressure, and treatment of mental or nervous diseases, or in manufacture of a medicament for treatment of hyperlipidemia, hypertension, diabetes, or coronary heart disease.

15. A method for realizing weight loss, blood fat reduction, antihypertension and treatment of mental or nervous diseases in a subject, comprising a step of administering the subject in such need a therapeutically effective amount of the combination product according to any one of claims 1-10.