# US 10,307,417 B2 · Oral formulations and lipophilic salts of methylnaltrexone

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- Number: US 10,307,417 B2
- Document ID: US10307417B2
- Status: Granted
- Kind: B2
- Application number: 16/219,681
- Filed: 2018-12-13
- Published: 2019-04-25
- Granted: 2019-06-04
- Earliest claimed: 2010-03-11
- Assignees: Wyeth
- Applicants: Wyeth, LLC
- Inventors: Syed M. Shah; Christopher Richard Diorio; Eric C. Ehrnsperger; Xu Meng; Kadum A. Al Shareffi; Jonathan Marc Cohen
- Web page: https://patentgrep.com/patent/US10307417B2

## CPC

- A61K 31/485: Morphinan derivatives, e.g. morphine, codeine
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/2009: {Inorganic compounds}
- A61K 9/2013: {Organic compounds, e.g. phospholipids, fats}
- 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 9/28: Dragees; Coated pills or tablets {, e.g. with film or compression coating (A61K9/2072 takes precedence, e.g. partially coated tablets A61K9/2072, coated multilayer tablets A61K9/2086, tablets with drug-coated core A61K9/209)}
- A61K 47/12: Carboxylic acids; Salts or anhydrides thereof
- A61K 47/20: containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/08: for nausea, cinetosis or vertigo; Antiemetics
- A61P 1/10: Laxatives
- A61P 1/14: Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- C07D 489/08: Oxygen atom
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The present invention provides compositions comprising methylnaltrexone or a salt thereof, and compositions and formulations thereof, for oral administration.

## Claims

### Claim 1

A pharmaceutical composition for oral administration comprising a solid dosage of (i) methylnaltrexone bromide, and (ii) sodium dodecyl sulfate (SDS), wherein the composition is a tablet, wherein methylnaltrexone bromide is the sole active agent, wherein the tablet is not enterically coated, and wherein at least 50% of the composition dissolves in a dissolution apparatus with paddles at 100 rpm in 900 mL of 0.1 N HCl at 37° C. within about 15 minutes.

### Claim 2 (depends on 1)

The pharmaceutical composition of claim 1, further comprising a rapid-acting disintegrant.

### Claim 3 (depends on 2)

The pharmaceutical composition of claim 2, wherein the rapid-acting disintegrant is an effervescent disintegrant.

### Claim 4 (depends on 2)

The pharmaceutical composition of claim 2, wherein the rapid-acting disintegrant is sodium bicarbonate.

### Claim 5 (depends on 1)

The pharmaceutical composition of claim 1, wherein at least 75% of the composition dissolves in a dissolution apparatus with paddles at 100 rpm in 900 mL of 0.1 N HCl at 37° C. within about 15 minutes.

### Claim 6 (depends on 5)

The pharmaceutical composition of claim 5, wherein at least 90% of the composition dissolves in a dissolution apparatus with paddles at 100 rpm in 900 mL of 0.1 N HCl at 37° C. within about 15 minutes.

### Claim 7 (depends on 1)

The pharmaceutical composition of claim 1, wherein an ion pair forms when the methylnaltrexone bromide and sodium dodecyl sulfate (SDS) are dissolved in solution.

### Claim 8 (depends on 7)

The pharmaceutical composition of claim 7, wherein the solution is at a pH of about 1 to about 4.

### Claim 9 (depends on 2)

The pharmaceutical composition of claim 2, wherein an ion pair forms when the methylnaltrexone bromide and sodium dodecyl sulfate (SDS) are dissolved in solution.

### Claim 10 (depends on 9)

The pharmaceutical composition of claim 9, wherein the solution is at a pH of about 1 to about 4.

### Claim 11 (depends on 1)

The pharmaceutical composition of claim 1, wherein the composition in solution has an apparent octanol/water partition coefficient for methylnaltrexone of at least 0.25 at a pH between 1 and 4.

### Claim 12 (depends on 11)

The pharmaceutical composition of claim 11, wherein the apparent octanol/water partition coefficient for methylnaltrexone is at least 0.5.

### Claim 13 (depends on 11)

The pharmaceutical composition of claim 11, wherein the apparent octanol/water partition coefficient for methylnaltrexone is at least 1.

### Claim 14 (depends on 1)

The pharmaceutical composition of claim 1, wherein the ratio of methylnaltrexone bromide to sodium dodecyl sulfate in the tablet is about 3:1 by weight.

### Claim 15 (depends on 14)

The pharmaceutical composition of claim 14, wherein at least 75% of the composition dissolves in a dissolution apparatus with paddles at 100 rpm in 900 mL of 0.1 N HCl at 37° C. within about 15 minutes.

### Claim 16 (depends on 15)

The pharmaceutical composition of claim 15, wherein at least 90% of the composition dissolves in a dissolution apparatus with paddles at 100 rpm in 900 mL of 0.1 N HCl at 37° C. within about 15 minutes.

### Claim 17 (depends on 14)

The pharmaceutical composition of claim 14, wherein an ion pair forms when the methylnaltrexone bromide and sodium dodecyl sulfate (SDS) are dissolved in solution.

### Claim 18 (depends on 17)

The pharmaceutical composition of claim 17, wherein the solution is at a pH of about 1 to about 4.

### Claim 19 (depends on 1)

The pharmaceutical composition of claim 1 made with methylnaltrexone bromide and sodium dodecyl sulfate in a ratio of about 3:1 by weight.

### Claim 20 (depends on 1)

The pharmaceutical composition of claim 1, further comprising a chelating agent.

### Claim 21 (depends on 20)

The pharmaceutical composition of claim 20, wherein the chelating agent is calcium EDTA disodium.

### Claim 22 (depends on 14)

The pharmaceutical composition of claim 14, further comprising a chelating agent.

### Claim 23 (depends on 22)

The pharmaceutical composition of claim 22, wherein the chelating agent is calcium EDTA disodium.

### Claim 24 (depends on 14)

The pharmaceutical composition of claim 14, wherein the amount of methylnaltrexone bromide is about 150 mg.

### Claim 25 (depends on 24)

The pharmaceutical composition of claim 24, wherein the amount of methylnaltrexone bromide is 150 mg and the amount of sodium dodecyl sulfate (SDS) is 50 mg.

### Claim 26 (depends on 17)

The pharmaceutical composition of claim 17, wherein the amount of methylnaltrexone bromide is about 150 mg.

### Claim 27 (depends on 26)

The pharmaceutical composition of claim 26, wherein the amount of methylnaltrexone bromide is 150 mg and the amount of sodium dodecyl sulfate (SDS) is 50 mg.

### Claim 28 (depends on 19)

The pharmaceutical composition of claim 19, wherein the amount of methylnaltrexone bromide is about 150 mg.

### Claim 29 (depends on 28)

The pharmaceutical composition of claim 28, wherein the amount of methylnaltrexone bromide is 150 mg and the amount of sodium dodecyl sulfate (SDS) is 50 mg.