Ready-to-use potassium phosphates in sodium chloride solutions

11925,661

18/460941

September 05, 2023

Ready-to-use (RTU) potassium phosphates solutions for phosphorus replacement therapy are presented that include potassium phosphate and sodium chloride at a fixed volume with 1.5 to 15 mmol/100 mL phosphorus, no more than 22 mEq/100 mL potassium and less than 50 mcg/L aluminum.

Nivagen Pharmaceuticals, Inc. (Sacramento, CA, US)

Nivagen Pharmaceuticals, Inc. (Sacramento, CA, US)

1. A sterile ready-to-use aqueous potassium solution, comprising potassium phosphates and sodium chloride, wherein the solution comprises between 1.5 mmol/100 mL and 15 mmol/100 ml phosphorous and equal or less than 50 mcg/L aluminum, and wherein the solution has a pH of between 2 and 6.

2. The solution of claim 1 , wherein the potassium phosphates comprise potassium dihydrogen phosphate and potassium hydrogen phosphate at a molar ratio of about 0.7 to 1.3.

3. The solution of claim 2 , wherein the potassium dihydrogen phosphate is present in the solution an amount of between about 112 mg/100 ml and about 1,120 mg/100 ml and wherein the potassium hydrogen phosphate is present in the solution in an amount of between about 118 mg/100 ml and about 1,180 mg/100 ml.

4. The solution of claim 1 , wherein the potassium is present in the solution in an amount of no more than 22 mEq/100 mL.

5. The solution of claim 1 , wherein the sodium chloride is present in the solution in an amount of up to 900 mg/100 ml.

6. The solution of claim 1 , wherein the solution has, after autoclaving and storage of at least 3 months at 25° C. and 40% relative humidity, a total liquid particle count of no more than 360 and no more than 30 for particles having a size of equal to or greater than 15 and equal to or greater 25 micrometer size, respectively.

7. The solution of claim 1 , wherein the solution has, after autoclaving and storage of at least 3 months at 25° C. and 40% relative humidity, a change in phosphorus of no more than 1% absolute.

8. The solution of claim 1 , wherein the solution has, after autoclaving and storage of at least 3 months at 25° C. and 40% relative humidity, a change in potassium of no more than 2% absolute.

9. The solution of claim 1 , wherein the solution is packaged in a flexible polyolefin container, optionally at a volume of between 100 mL and 1,000 mL, and optionally wherein the flexible polyolefin container is a flexible multilayer bag.

10. The solution of claim, 9 wherein the flexible polyolefin container is further contained in a secondary metallized overwrap.

11. A sterile ready-to-use premixed pharmaceutical product stored in a flexible polymeric container, wherein the pharmaceutical product comprises a potassium phosphates in an aqueous sodium chloride solution containing (a) less than 50 mcg/L aluminum, (b) between about 1.5 mmol 100 ml and 15 mmol/100 ml phosphorus, and (c) no more than about 22 mEq/100 mL potassium.

12. The pharmaceutical product of claim 11 , wherein the potassium phosphates comprise potassium dihydrogen phosphate and potassium hydrogen phosphate at a molar ratio of about 0.7 to 1.3, and/or wherein the potassium dihydrogen phosphate is present in the solution an amount of between about 112 mg/100 ml and about 1,120 mg/100 ml and wherein the potassium hydrogen phosphate is present in the solution in an amount of between about 118 mg/100 ml and about 1,180 mg/100 ml.

13. The pharmaceutical product of claim 12 , wherein the sodium chloride is present in the aqueous solution in an amount of up to 900 mg/100 ml.

14. The pharmaceutical product of claim 11 , wherein the premixed pharmaceutical product in the flexible polymeric container has a volume of between 100 mL and 1,000 mL.

15. The pharmaceutical product of claim 14 , wherein the flexible polyolefin container is a flexible multilayer bag.

16. The pharmaceutical product of claim 11 , wherein the flexible polymeric container is enclosed in a secondary metallized overwrap.

17. A method of administering phosphates to a patient in need of phosphorus replacement therapy, comprising: administering, without prior dilution, a sterile, and ready-to-use solution comprising potassium phosphates and sodium chloride solution from a flexible container to the patient at a rate of infusion and by a route of administration corresponding to the patient's age and degree of need of phosphorus replacement; wherein the solution comprises between 1.5 mmol/100 mL and 15 mmol/100 ml phosphorus, no more than about 22 mEq/100 mL potassium, and less than 50 mcg/L aluminum.

18. The method of claim 17 , wherein the rate of infusion is 6.8 mmol phosphates per hour or 15 mmol phosphates per hour.

19. The method of claim 17 , wherein the route of administration is a central venous catheter or peripheral venous catheter.

20. The method of claim 17 , wherein the solution is administered after storage of at least 3 months at 25° C. and 40% relative humidity.

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edspgr.11925661