# US 11,110,054 B2 · Ready-to-use injectable pharmaceutical compositions comprising neostigmine and glycopyrrolate

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- Number: US 11,110,054 B2
- Document ID: US11110054B2
- Status: Granted
- Kind: B2
- Application number: 16/170,948
- Filed: 2018-10-25
- Published: 2019-12-12
- Granted: 2021-09-07
- Earliest claimed: 2018-10-25
- Assignees: Slayback Pharma LLC
- Applicants: Slayback Pharma LLC
- Inventors: Rahul Dhulaji Bhise; Ajay Kumar Singh; Mahadeo Vasant Mahadik; Ashish Anilrao Dubewar; Molugu Prashanth Reddy
- Web page: https://patentgrep.com/patent/US11110054B2

## 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 9/08: Solutions {(composition of solutions A61K47/00)}
- A61K 31/27: of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
- A61K 31/40: having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K 47/183: {Amino acids, e.g. glycine, EDTA or aspartame}
- 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

The present invention provides stable, ready-to-use injectable pharmaceutical compositions, comprising the combination of neostigmine, glycopyrrolate, a stabilizing amount of one or more aminopolycarboxylic acids, and a pharmaceutically acceptable liquid vehicle. Other aspects of the invention relate to methods for making such compositions and methods of using such compositions for reversing the effects of non-depolarizing neuromuscular blocking agents. Preferably, the composition comprises neostigmine methylsulfate, glycopyrronium bromide, ethylenediaminetetraacetic acid (EDTA) and a pharmaceutically acceptable liquid vehicle, and is provided in a pre-filled, ready-to-use sealed container, such as a pre-filled syringe, suitable for intravenous administration.

## Claims

### Claim 1

A stable ready-to-use injectable pharmaceutical composition for reversing the effects of non-depolarizing neuromuscular blocking agents in a patient in need thereof, comprising (i) about 1 mg/mL of neostigmine or a pharmaceutically acceptable salt, solvate or hydrate thereof, (ii) about 0.2 mg/mL of glycopyrrolate or a pharmaceutically acceptable salt, solvate or hydrate thereof, (iii) a pharmaceutically acceptable liquid vehicle, (iv) a tonicity modifier; and (v) a pH adjusting agent; wherein the level of Glycopyrrolate Impurity C in the composition is less than 1% when stored at 40° C. and 75% relative humidity for 3 months;
wherein the tonicity modifier is sodium chloride; and
wherein the pH adjusting agent is sodium hydroxide, hydrochloric acid or a mixture thereof.

### Claim 2 (depends on 1)

The pharmaceutical composition according to claim 1, wherein the composition is provided in a sealed container selected from the group consisting of ampoules, vials and pre-filled syringes.

### Claim 3 (depends on 1)

The pharmaceutical composition according to claim 1, wherein the composition is in the form of a solution, suspension, or emulsion.

### Claim 4 (depends on 1)

The pharmaceutical composition according to claim 1, wherein the composition is suitable for subcutaneous, intravenous or intramuscular administration.

### Claim 5 (depends on 1)

The pharmaceutical composition according to claim 1, comprising neostigmine methylsulfate and glycopyrronium bromide.

### Claim 6 (depends on 1)

The pharmaceutical composition according to claim 1, wherein the composition has a pH ranging from about 3.0 to about 4.0.

### Claim 7

A stable ready-to-use injectable pharmaceutical composition comprising (i) about 1 mg/mL of neostigmine methylsulfate, (ii) about 0.2 mg/mL of glycopyrronium bromide, (iii) a pharmaceutically acceptable liquid vehicle; (iv) a tonicity modifier; and (v) q.s. of a pH adjusting agent, wherein the level of Glycopyrrolate Impurity C in the composition is less than 1%, when stored at 40° C. and 75% relative humidity for 3 months;
wherein the tonicity modifier is sodium chloride; and
wherein the pH adjusting agent is sodium hydroxide, hydrochloric acid or a mixture thereof.

### Claim 8 (depends on 7)

The pharmaceutical composition according to claim 7, wherein the composition is provided in a sealed container selected from the group consisting of ampoules, vials and pre-filled syringes.

### Claim 9 (depends on 7)

The pharmaceutical composition according to claim 7, wherein the composition has a pH ranging from about 3.0 to about 4.0.

### Claim 10

A stable ready-to-use injectable pharmaceutical composition consisting of (i) about 1 mg/mL of neostigmine methylsulfate, (ii) about 0.2 mg/mL of glycopyrronium bromide, (iii) a pharmaceutically acceptable liquid vehicle; (iv) sodium chloride as tonicity modifier; and (v) sodium hydroxide, hydrochloric acid or mixture thereof as pH adjusting agent, wherein the level of Glycopyrrolate Impurity C in the composition is less than 1%, when stored at 40° C. and 75% relative humidity for 3 months.