Claims for Patent: 10,456,354

Summary for Patent: 10,456,354

Title:	Ready-to-use injectable pharmaceutical compositions comprising neostigmine and glycopyrrolate
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.
Inventor(s):	Rahul Dhulaji Bhise, Ajay Kumar Singh, Mahadeo Vasant Mahadik, Ashish Anilrao DUBEWAR, Molugu Prashanth Reddy
Assignee:	Azurity Pharmaceuticals Inc
Application Number:	US16/176,866
Patent Claims:	1. A ready-to-use injectable pharmaceutical composition comprising (i) neostigmine or a pharmaceutically acceptable salt, solvate or hydrate thereof, (ii) glycopyrrolate or a pharmaceutically acceptable salt, solvate or hydrate thereof, (iii) one or more aminopolycarboxylic acids, and (iv) a pharmaceutically acceptable liquid vehicle, wherein the pharmaceutical composition is stable for at least 3 months at 25° C. and 60% relative humidity. 2. 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. 3. The pharmaceutical composition according to claim 1, wherein the composition is in the form of a solution, suspension, or emulsion. 4. The pharmaceutical composition according to claim 1, wherein the composition is suitable for subcutaneous, intravenous or intramuscular administration. 5. The pharmaceutical composition according to claim 1, comprising neostigmine methylsulfate and glycopyrronium bromide. 6. The pharmaceutical composition according to claim 1, wherein the one or more aminopolycarboxylic acids are selected from the group consisting of ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA). 7. The pharmaceutical composition according to claim 6, wherein the aminopolycarboxylic acid is EDTA. 8. The pharmaceutical composition according to claim 1, comprising: (i) neostigmine or a pharmaceutically acceptable salt thereof, (ii) glycopyrrolate or a pharmaceutically acceptable salt thereof, and (iii) a pharmaceutically acceptable liquid vehicle; wherein the one or more aminopolycarboxylic acids comprise a stabilizing amount of ethylenediaminetetraacetic acid (EDTA). 9. The pharmaceutical composition according to claim 8, wherein the composition has a pH ranging from about 3.0 to about 4.0. 10. The pharmaceutical composition according to claim 8, wherein the composition is provided in a sealed container selected from the group consisting of ampoules, vials and pre-filled syringes. 11. The pharmaceutical composition according to claim 8, wherein the composition is a solution, suspension, or emulsion. 12. The pharmaceutical composition of claim 8, wherein the composition is suitable for subcutaneous, intravenous or intramuscular administration. 13. The pharmaceutical composition according to claim 8, comprising neostigmine methylsulfate and glycopyrronium bromide. 14. The pharmaceutical composition according to claim 8, wherein the neostigmine concentration is from about 0.5 mg/mL to about 5 mg/mL. 15. The pharmaceutical composition according to claim 8, wherein the glycopyrrolate concentration is from about 0.1 mg/mL to about 1 mg/mL. 16. The pharmaceutical composition according to claim 8, wherein ethylenediaminetetraacetic acid (EDTA) is present from about 0.1 mg/mL to about 5 mg/mL of the composition. 17. The pharmaceutical composition of claim 8 comprising: (i) from about 0.5 mg/mL to about 5 mg/mL of neostigmine methylsulfate; (ii) from about 0.1 mg/mL to about 1 mg/mL of glycopyrrolate bromide; and (iii) about 0.5 mg/mL of EDTA. 18. The pharmaceutical composition of claim 17 comprising: (i) from about 1 mg/mL to about 3 mg/mL of neostigmine methylsulfate; (ii) from about 0.2 mg/mL to about 0.7 mg/mL of glycopyrrolate bromide; and (iii) about 0.5 mg/mL of EDTA. 19. The pharmaceutical composition of claim 18, comprising about 1 mg/mL of neostigmine methylsulfate, about 0.2 mg/mL of glycopyrronium bromide and about 0.5 mg/mL of ethylenediaminetetraacetic acid (EDTA). 20. The pharmaceutical composition of claim 18, comprising about 2.5 mg/mL of neostigmine methylsulfate, about 0.5 mg/mL of glycopyrronium bromide and about 0.5 mg/mL of ethylenediaminetetraacetic acid (EDTA). 21. The pharmaceutical composition of claim 1, wherein the level of Glycopyrrolate Impurity C is less than 1% (w/w) as measured by HPLC.