# US 11,077,050 B2 · Formulation for parenteral administration

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- Number: US 11,077,050 B2
- Document ID: US11077050B2
- Status: Granted
- Kind: B2
- Application number: 16/496,182
- Filed: 2018-03-19
- Published: 2020-09-17
- Granted: 2021-08-03
- Earliest claimed: 2017-03-24
- Assignees: Merck Sharp & Dohme Corp.
- Applicants: Merck Sharp & Dohme Corp.; Merck Sharp & Dohme B. V.; Sachin Mittal; Irina Kazakevich; Himanshu Bhattacharjee; Peter Bakker; Luke Schenck; David J. Goldfarb; Amitava Mitra; Donna Carroll; Nazia Khawaja
- Inventors: Sachin Mittal; Irina Kazakevich; Himanshu Bhattacharjee; Peter Bakker; Luke Schenck; David J. Goldfarb; Amitava Mitra; Donna Carroll; Nazia Khawaja
- Web page: https://patentgrep.com/patent/US11077050B2

## CPC

- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A61K 47/22: Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
- A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- A61K 47/38: Cellulose; Derivatives thereof
- A61K 9/10: Dispersions; Emulsions
- C07B 2200/13: Crystalline forms, e.g. polymorphs
- 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)
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

The instant invention provides pharmaceutical formulations for a long acting injectable drug product comprising a suspension of doravirine for parenteral administration via intramuscular or subcutaneous routes. The drug product can be used for the treatment or prophylaxis of infection by HIV or for the treatment, prophylaxis, or delay in the onset of AIDS (acquired immunodeficiency syndrome) or ARC (AIDS related complex).

## Claims

### Claim 1

A parenteral pharmaceutical composition for intramuscular or subcutaneous administration comprising a suspension of particles of crystalline Form II of doravirine (D-AHII) wherein the particles have a specific surface area within a range from 22.2 m2/g to 1.8 m2/g.

### Claim 2 (depends on 1)

The composition of claim 1 wherein the D-AHII has a particle size from about 100 nm (D10) to about 20 μm (D90).

### Claim 3 (depends on 1)

The composition of claim 1 wherein the D-AHII has a median particle size from about 200 nm to about 8 μm.

### Claim 4 (depends on 2)

The composition of claim 2 comprised of D-AHII at a concentration range from 1% to 30%.

### Claim 5 (depends on 2)

The composition of claim 2 comprised of D-AHII at a concentration range from 10% to 30%.

### Claim 6 (depends on 2)

The composition of claim 2 comprised of D-AHII at a concentration range from 20% to 30%.

### Claim 7 (depends on 4)

The composition of claim 4 further comprised of a surfactant which is one or more of polysorbate 80, polysorbate 20, poloxyamer 188, Vitamin E TPGS, docusate sodium or sodium deoxycholate.

### Claim 8 (depends on 7)

The composition of claim 7 wherein the surfactant is polysorbate 80 or Vitamin E TPGS or a combination of both.

### Claim 9 (depends on 4)

The composition of claim 4 wherein the D-AHII:surfactant weight ratio is from 150:1 to 1:1.

### Claim 10 (depends on 9)

The composition of claim 9 which is a microsuspension of D-AHII wherein the D-AHII:surfactant weight ratio is from 150:1 to 20:1.

### Claim 11 (depends on 9)

The composition of claim 9 which is a nanosuspension of D-AHII wherein the D-AHII:surfactant weight ratio is from 7.5:1 to 5:1.

### Claim 12 (depends on 1)

The composition of claim 1 further comprising a viscosity modifying agent which is PEG 3350 or sodium carboxymethylcellulose or a combination of both, wherein the concentration of the viscosity modifying agent is from 0.1 wt % to 3.0 wt % and the viscosity of the suspending vehicle is from 1.4 cP to 1220 cP.

### Claim 13 (depends on 1)

The composition of claim 1 wherein the pH of the composition is 7.

### Claim 14 (depends on 13)

The composition of claim 13 comprising a phosphate buffering agent.

### Claim 15 (depends on 1)

The composition of claim 1 further comprising a tonicity modifier which is one or more of dextrose, mannitol, sucrose, trehalose or sodium chloride.

### Claim 16 (depends on 15)

The composition of claim 15 wherein the tonicity modifier is:
(a) for a microsuspension, mannitol or sodium chloride or a combination of both; or
(b) for a nanosuspension, one or more of sucrose, trehalose or sodium chloride.

### Claim 17 (depends on 16)

The composition of claim 16 wherein the tonicity modifier is:
(a) for a microsuspension, sodium chloride; or
(b) for a nanosuspension, trehalose.

### Claim 18 (depends on 1)

The composition of claim 1 comprising:
Components
Quantity
D-AHII
30.0%
(w/v)
Polyethylene glycol 3350
3%
(w/v)
Polysorbate 80
0.2%
(w/v)
Phosphate buffer
10
mM
Water
QS to 100%
pH
7.0
Particle size distribution, micron
2.58/7.61/15.33
(D10/D50/D90)
Specific surface area (m2/g)
1.82.