# US 11,433,066 B2 · Abuse-resistant pharmaceutical composition for the treatment of opioid dependence

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- Number: US 11,433,066 B2
- Document ID: US11433066B2
- Status: Granted
- Kind: B2
- Application number: 17/032,882
- Filed: 2020-09-25
- Published: 2021-01-14
- Granted: 2022-09-06
- Earliest claimed: 2011-09-19
- Assignees: Orexo AB
- Applicants: Orexo AB
- Inventors: Andreas Fischer
- Web page: https://patentgrep.com/patent/US11433066B2

## CPC

- A61K 31/485: Morphinan derivatives, e.g. morphine, codeine
- 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}
- A61K 9/006: {Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays}
- A61K 9/14: Particulate form, e.g. powders, {Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles (microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51)}
- A61K 9/20: Pills, tablets, {discs, rods (A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095)}
- A61K 9/2013: {Organic compounds, e.g. phospholipids, fats}
- A61K 9/2018: {Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates}
- 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 9/2095: {Tabletting processes}
- A61K 31/4748: forming part of bridged ring systems (strychnine A61K31/475; morphinan derivatives A61K31/485)
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/30: for treating abuse or dependence
- A61P 25/36: Opioid-abuse
- 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

## Abstract

There is provided pharmaceutical compositions for the treatment of e.g. opioid dependency comprising microparticles of a pharmacologically-effective amount of buprenorphine, or a pharmaceutically-acceptable salt thereof, in associative admixture with particles comprising a weak acid, or particles comprising weakly-acidic buffer forming materials. The composition may further comprise a disintegrant and/or particles of a pharmacologically-effective amount of naloxone, or a pharmaceutically-acceptable salt thereof. The compositions are useful in the treatment of opioid dependency/addiction and/or pain.

## Claims

### Claim 1

A method of treatment of opioid dependence in a subject, which method comprises:
providing a sublingual tablet comprising
(i) a dosage amount of buprenorphine or a pharmaceutically-acceptable salt thereof (calculated as the free base) that is 11.4 mg (±2%), 8.6 mg (±2%), 5.7 mg (±2%), 2.9 mg (±2%), or 1.4 mg (±2%);
(ii) a dosage amount of naloxone or a pharmaceutically-acceptable salt thereof (calculated as the free base) that is about ¼ of the above doses of buprenorphine or salt thereof; and
(iii) citric acid; and
(iv) a disintegrant,
which tablet is prepared according to a process comprising:
(a) associatively admixing microparticles of buprenorphine or pharmaceutically-acceptable salt thereof with particles of citric acid by a process of simple mixing and/or granulation, to form an associative admixture between the microparticles of buprenorphine or salt thereof and the particles of citric acid;
(b) mixing the associative admixture obtained in step (a) with particles comprising naloxone or pharmaceutically-acceptable salt thereof; and
(c) compressing the mixture obtained in step (b) to produce said tablet; and
sublingually administering the tablet to a subject in need of treatment of opioid dependence.

### Claim 2 (depends on 1)

The method as claimed in claim 1, wherein the disintegrant is selected from the group croscarmellose sodium, sodium starch glycolate, crosslinked polyvinylpyrrolidone, and mixtures thereof.

### Claim 3 (depends on 1)

The method as claimed in claim 1, wherein the tablet further comprises sodium citrate.

### Claim 4 (depends on 1)

The method as claimed in claim 1, wherein the tablet further comprises a binder, carrier particles, or both.

### Claim 5 (depends on 4)

The method as claimed in claim 4, wherein the binder is a cellulose gum or microcrystalline cellulose.

### Claim 6 (depends on 1)

The method as claimed in claim 1, wherein the associative admixture formed in step (a) is carried out by simple mixing.

### Claim 7 (depends on 1)

The method as claimed in claim 1, wherein the associative admixture formed in step (a) is carried out by granulation.

### Claim 8 (depends on 7)

The method as claimed in claim 7, wherein the granulation comprises dry granulation, wet granulation, melt granulation, thermoplastic pelletising, spray granulation or extrusion/spheronisation.

### Claim 9 (depends on 4)

The method as claimed in claim 4, wherein the binder, carrier particles, or both, are associatively admixed in step (a) by granulation.

### Claim 10 (depends on 3)

The method as claimed in claim 3, wherein the sodium citrate is in the form of particles, which are associatively admixed in step (a).

### Claim 11 (depends on 4)

The method as claimed in claim 4, wherein the carrier particles are present in the tablet, and the carrier particles are associatively admixed in step (a).