# US 2008/0187584 A1 · Stable pharmaceutical formulation of paroxetine hydrochloride and a process for preparation thereof

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2008/0187584 A1
- Document ID: US20080187584A1
- Status: Published application
- Kind: A1
- Application number: 12/077,458
- Filed: 2008-03-18
- Published: 2008-08-07
- Earliest claimed: 2001-12-28
- Assignees: Teva Pharmaceuticals USA, Inc.
- Inventors: Rakefet Cohen; Michael Fox
- Web page: https://patentgrep.com/patent/US20080187584A1

## CPC

- A61K 9/2886: {having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer (of the type active core-drug layer-inactive layer A61K9/209)}
- A61K 9/2009: {Inorganic compounds}
- A61K 9/2027: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates}
- A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 9/2077: {Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets}
- A61K 9/2866: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 31/4525: containing a five-membered ring with oxygen as a ring hetero atom
- A61K 9/2059: {Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin}
- A61K 9/2095: {Tabletting processes}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

Provided are formulations of a stable paroxetine hydrochloride tablet comprising paroxetine hydrochloride, povidone or copovidone as a binder, and an HCl free/non-hygroscopic filler, prepared by the wet granulation method. Preferably, the paroxetine hydrochloride is paroxetine hydrochloride hemihydrate.

## Claims

### Claim 1

An oral pharmaceutical dosage form comprising paroxetine hydrochloride, a binder selected from the group consisting of povidone and copovidone, and a filler that is HCl free or non-hygroscopic, wherein the pharmaceutical dosage form is prepared by wet granulating paroxetine hydrochloride in the presence of a binder grade of povidone or copovidone, and the filler, to obtain an intra-granular portion of a granulate, and converting the granulate to the oral pharmaceutical dosage form.

### Claim 2 (depends on 1)

The oral pharmaceutical dosage form of claim 1, wherein the filler is non-hygroscopic.

### Claim 3 (depends on 1)

The oral pharmaceutical dosage for of claim 1, wherein the filler is HCl free.

### Claim 4 (depends on 3)

The oral pharmaceutical dosage for of claim 3, wherein the filler is non-hygroscopic.

### Claim 5 (depends on 4)

The oral pharmaceutical dosage form of claim 4, wherein the filler is a sugar.

### Claim 6 (depends on 5)

The oral pharmaceutical dosage form of claim 5, wherein the sugar is mannitol.

### Claim 7 (depends on 4)

The oral pharmaceutical dosage form of claim 4, wherein the filler is dibasic calcium phosphate anhydrous.

### Claim 8 (depends on 1)

The oral pharmaceutical dosage form of claim 1, wherein the paroxetine hydrochloride is paroxetine hydrochloride hemihydrate.

### Claim 9 (depends on 1)

The oral pharmaceutical dosage form of claim 1, wherein the binder is povidone.

### Claim 10 (depends on 1)

The oral pharmaceutical dosage form of claim 1, wherein the binder is co-povidone.

### Claim 11 (depends on 1)

The oral pharmaceutical dosage form of claim 1, wherein the ratio of povidone or copovidone to paroxetine hydrochloride is from about 20% to about 60% weight to weight of povidone or copovidone to paroxetine hydrochloride.

### Claim 12 (depends on 11)

The oral pharmaceutical dosage form of claim 11, wherein the ratio is from about 30% to about 40%.

### Claim 13 (depends on 12)

The oral pharmaceutical dosage form of claim 12, wherein the ratio is from about 35% to about 40%.

### Claim 14 (depends on 1)

The oral pharmaceutical dosage form of claim 1, wherein the ratio of povidone or copovidone to intra-granular portion is about 2% to about 9% weight to weight of povidone or copovidone to intra-granular portion, the intra-granular weight including the weight of povidone or copovidone.

### Claim 15 (depends on 14)

The oral pharmaceutical dosage form of claim 14, wherein the ratio is about 3% to about 7%.

### Claim 16 (depends on 15)

The oral pharmaceutical dosage form of claim 15, wherein the ratio is about 4% to about 7%.

### Claim 17 (depends on 1)

The oral pharmaceutical dosage form of claim 1, wherein the wet granulating is carried out with water as a processing solvent.

### Claim 18 (depends on 1)

The oral pharmaceutical dosage form of claim 1, wherein the wet granulating is carried out with a mixture of water and a water miscible ketone or alcohol, or mixtures thereof as a processing solvent.

### Claim 19 (depends on 1)

The oral pharmaceutical dosage form of claim 1, wherein the dosage form is selected from the group consisting of tablets, capsules, sachets, granules, suspension, effervescent tablets, chewable tablets and geltabs.

### Claim 20 (depends on 19)

The oral pharmaceutical dosage form of claim 19, wherein the dosage form is a tablet.

### Claim 21 (depends on 1)

A method of reducing serotonin re-uptake comprising administering the oral pharmaceutical dosage form of claim 1 to a mammal.

### Claim 22

A process for preparing an oral pharmaceutical dosage form comprising the steps of:
a) wet granulating paroxetine hydrochloride in the presence of a binder grade of a binder selected from the group consisting of povidone and copovidone, and a filler that is HCl free or non-hygroscopic, to obtain an intra-granular portion of a granulate;
b) preparing a final blend from the granulate; and
c) converting the final blend to an oral pharmaceutical dosage form.

### Claim 23 (depends on 22)

The process of claim 22, wherein the filler is HCl free.

### Claim 24 (depends on 22)

The process of claim 22, wherein the filler is non-hygroscopic.

### Claim 25 (depends on 24)

The process of claim 24, wherein the filler is HCl free.

### Claim 26 (depends on 22)

The process of claim 22, wherein the filler is a sugar.

### Claim 27 (depends on 26)

The process of claim 26, wherein the sugar is mannitol.

### Claim 28 (depends on 22)

The process of claim 22, wherein the filler is dibasic calcium phosphate anhydrous.

### Claim 29 (depends on 22)

The process of claim 22, wherein the paroxetine hydrochloride is paroxetine hydrochloride hemihydrate.

### Claim 30 (depends on 22)

The process of claim 22, wherein the binder is povidone.

### Claim 31 (depends on 22)

The process of claim 22, wherein the binder is copovidone.

### Claim 32 (depends on 22)

The process of claim 22, wherein the ratio of povidone or copovidone to paroxetine hydrochloride is from about 20% to about 60% weight to weight of povidone or copovidone to paroxetine hydrochloride.

### Claim 33 (depends on 32)

The process of claim 32, wherein the ratio is from about 30% to about 40%.

### Claim 34 (depends on 33)

The process of claim 33, wherein the ratio is from about 35% to about 40%.

### Claim 35 (depends on 22)

The process of claim 22, wherein the ratio of povidone or copovidone to the intra-granular portion is about 2% to about 9% weight to weight of povidone or copovidone to the intra-granular portion, the intra-granular weight including the weight of povidone or copovidone.

### Claim 36 (depends on 35)

The process of claim 35, wherein the ratio is about 3% to about 7%.

### Claim 37 (depends on 36)

The process of claim 36, wherein the ratio is about 4% to about 7%.

### Claim 38 (depends on 22)

The process of claim 22, wherein the wet granulating is carried out with water as a processing solvent.

### Claim 39 (depends on 22)

The process of claim 22, wherein the wet granulating is carried out with a mixture of water and a water miscible ketone or alcohol, or mixtures thereof as a processing solvent.

### Claim 40 (depends on 22)

The process of claim 22, wherein the oral pharmaceutical dosage form is selected from the group consisting of tablets, capsules, sachets, granules, suspension, effervescent tablets, chewable tablets and geltabs.

### Claim 41 (depends on 40)

The process of claim 40, wherein the oral pharmaceutical dosage form is a tablet prepared by compressing the final blend.

### Claim 42 (depends on 41)

The process of claim 41, further comprising a step of coating the tablet.

### Claim 43 (depends on 42)

The process of claim 42, wherein the coating is carried out by using a composition of about 30% titanium dioxide, about 30% hydroxypropyl methylcellulose, about 8% polyethylene glycol and about 1% polysorbate, respective weight to weight.

### Claim 44

A tablet comprising of the following active ingredient and excipients, in weight to weight percentages:
a) about 10% to about 12.5% of paroxetine hydrochloride as an active ingredient;
b) about 70% to about 90% of dibasic calcium phosphate anhydrous;
c) about 1.5% to about 5% of sodium starch glycolate;
d) about 0.5% to about 3% of magnesium stearate; and
e) about 2.5% to about 7.5% of povidone,
wherein the tablet is prepared by wet granulating paroxetine hydrochloride in the presence of povidone, sodium starch glycolate and dibasic calcium phosphate anhydrous to obtain a granulate, and converting the granulate to a tablet.

### Claim 45 (depends on 44)

The tablet of claim 44, wherein the paroxetine hydrochloride is paroxetine hydrochloride hemihydrate.

### Claim 46 (depends on 44)

The tablet of claim 44, further comprising about 3 to about 12 mg of a coating composition of about 30% titanium dioxide, about 30% hydroxypropyl methylcellulose, about 8% polyethylene glycol and about 1% polysorbate, respective weight to weight.

### Claim 47 (depends on 44)

The tablet of claim 44, wherein the wet granulating is carried out with water as a processing solvent.

### Claim 48 (depends on 44)

The tablet of claim 44, wherein the wet granulating is carried out with a mixture of water and a water miscible ketone or alcohol, or mixtures thereof as a processing solvent.

### Claim 49 (depends on 44)

A method for inhibiting the re-uptake of serotonin comprising administering the tablet of claim 44 to a mammal.

### Claim 50

A process for preparing a paroxetine hydrochloride tablet comprising the steps of:
a) wet granulating with water as a processing solvent paroxetine hydrochloride in the presence of sodium starch glycolate, Grade 29 to Grade 32 povidone and dibasic calcium phosphate anhydrous;
b) milling the granulate;
c) mixing the granulate with an additional amount of sodium starch glycolate and calcium phosphate dibasic anhydrous;
d) adding magnesium stearate to obtain a final blend; and
e) compressing the final blend to obtain the tablet.

### Claim 51 (depends on 50)

The process of claim 50, wherein the paroxetine hydrochloride is paroxetine hydrochloride hemihydrate.

### Claim 52

A mechanically stable paroxetine hydrochloride tablet, wherein the tablet does not substantially lose its hardness after storage at a temperature of about 80° C. and a relative humidity of at least about 75% for at least about 24 hours.

### Claim 53 (depends on 52)

The tablet of claim 52, wherein the paroxetine hydrochloride is paroxetine hydrochloride hemihydrate.

### Claim 54 (depends on 52)

The tablet of claim 52, wherein the hardness is at least about 10 SCU after about 24 hours.

### Claim 55 (depends on 54)

The tablet of claim 54, wherein the hardness is at least about 14 SCU after about 24 hours.

### Claim 56 (depends on 55)

The tablet of claim 55, wherein the hardness is at least about 16 SCU after about 24 hours.

### Claim 57 (depends on 52)

A method of inhibiting serotonin re-uptake comprising administering the tablet of claim 52 to a mammal.