DESC:FIELD OF THE INVENTION:
The present invention relates to a ready- to- use injectable formulation of potassium phosphate and a process for preparing the same. The invention particularly relates to a ready-to-use injectable formulation comprising monobasic potassium phosphate, dibasic potassium phosphate, water for injection and optionally containing a tonicity adjusting agent.
BACKGROUND OF THE INVENTION:
Phosphorus is a crucial mineral that is involved in the various metabolism processes, the composition of bone and cell membranes, and acid-base balance. A key component of 2,3-diphosphoglycerate (2,3-DPG), which is required for the release of oxygen from haemoglobin and the delivery of oxygen to the tissues, phosphorus also contributes energy-rich bonds in the synthesis of adenosine triphosphate (ATP), a compound that is required for all physiologic and metabolic processes that require energy. A large portion of the body's total phosphorus is found in bones, with the remainder found in skeletal muscle, viscera, and extracellular fluid.
Normal blood phosphorus levels are between 2.5 to 4.5 mg/dL. The deficiency of phosphorus mineral can cause hypophosphatemia. Hypophosphatemia is a clinical condition in which serum phosphate concentrations are less than 2.5 mg / dL (0.81 mmol/L). Causes for such conditions can include alcohol use disorder, burns, starvation, and diuretic use, and symptoms include muscle weakness, respiratory failure, heart failure, and seizures and coma can occur. Potassium Phosphates Injection is a phosphorus replacement product indicated as a source of phosphorus: in intravenous fluids to correct hypophosphatemia in adults and paediatric patients when oral or enteral replacement is not possible, insufficient, or contraindicated.
The approved marketed product of potassium phosphorus for IV administration contains a combination of potassium and phosphates in specific ratios that is 3 mmol/mL phosphorus and 4.4 mEq/mL potassium, typically monobasic potassium phosphate and dibasic potassium phosphate as the source of phosphorus and potassium. This product requires dilution with compatible intravenous fluid, such as dextrose or propylene glycol or TPN solutions and after dilution, the solution is stable only for a maximum of 4 hours at room temperature 20°C to 25°C (68°F to 77°F) or 14 days under refrigeration at 2°C to 8°C (36°F to 46°F). Following dilution, the approved marketed product composition can be administered through peripheral or central administration. Some of the possible risks of a central venous catheter may include discomfort during placement, bleeding, infection, blocking or kinking and collapsed lung etc. Furthering these risks, the currently approved potassium phosphorus products are supplied and stored as concentrate formulations, which need dilution before administration and therefore require aseptic compounding, thereby increasing the risk of error and contamination. While care may be taken to avoid errors in calculations, contamination, and adverse effects, preparing the diluted solutions, and programming the correct infusion rate for administration often takes time and additional attention.
Therefore, there is still a need for potassium phosphate injectable formulations where such injectable formulations are ready-to-use, which eliminates the need for dilution before administration to a subject in need thereof and where such formulation has sufficiently long storage stability.
The present invention addresses the need for a ready-to-use injectable formulation of potassium phosphate solution intended to help in better patient compliance with ease of administration, provide accurate dosing and prevent medication errors. Finally, since the formulations provided herein do not need the cumbersome procedure of dilution, they are easy to administer.

OBJECT OF THE INVENTION:
An object of the present invention is to provide a ready-to-use injectable formulation comprising potassium phosphate and optionally containing a tonicity adjusting agent.
Another object of the present invention is to provide a process for preparing a ready-to-use injectable formulation comprising potassium phosphate and optionally containing a tonicity adjusting agent.
One another object of the present invention is to provide safe, efficacious and stable, ready-to-use injectable formulation comprising potassium phosphate and optionally containing a tonicity adjusting agent.
One further object of the present invention is to provide a ready-to-use injectable formulation comprising potassium phosphate which is easy to administer, easy to store and easy to transport.
Yet another object of the present invention is to provide a method for treating hypophosphatemia in adult and paediatric patient by administering a ready-to-use injectable formulation comprising potassium phosphate.
SUMMARY OF THE INVENTION
The present invention relates to a ready- to- use injectable formulation of potassium phosphate and a process for preparing the same. The invention particularly relates to a ready-to-use injectable formulation comprising monobasic potassium phosphate, dibasic potassium phosphate, water for injection and optionally containing a tonicity adjusting agent. Such formulations are suitable to be administered without any dilution or any other adjustment to a required phosphate and/or potassium concentration. The formulation of the present invention has a long shelf life and is easy to administer, easy to store and easy to transport.
The present invention relates to a ready to use injectable formulation comprising potassium phosphate in an amount of about 2 mg/ml to about 30 mg/ml. In one embodiment, the present invention relates to a ready to use injectable formulation comprising potassium phosphate in an amount of about 2 mg/ml to about 30 mg/ml, and optionally containing a tonicity agent.
In one embodiment, the ready to use injectable formulation comprises potassium phosphate in an amount of about 0.01 mmol/ml to about 0.2 mmol/ml of phosphorus. In another embodiment, the present invention relates to a ready to use injectable formulation comprises potassium phosphate in an amount of about 0.01 mmol/ml to about 0.2 mmol/ml of phosphorus, and optionally containing a tonicity agent.
In another embodiment, the ready to use injectable formulation comprises monobasic potassium phosphate in an amount of about 1 mg/ml to about 15 mg/ml.
In one more embodiment, the ready to use injectable formulation comprises dibasic potassium phosphate in an amount of about 1 mg/ml to about 15 mg/ml.
In an embodiment, the present invention relates to a ready to use injectable formulation comprising monobasic potassium phosphate in an amount of about 1 mg/ml to about 15 mg/ml and dibasic potassium phosphate in an amount of about 1 mg/ml to about 15 mg/ml, wherein the formulation optionally contains a tonicity agent.
In a further embodiment, the ready to use injectable formulation comprises monobasic potassium phosphate in an amount of about 0.01 mmol/ml to about 0.1 mmol/ml of phosphorus.
In one another embodiment, the ready to use injectable formulation comprises dibasic potassium phosphate in an amount of about 0.01 mmol/ml to about 0.1 mmol/ml of phosphorus.
In an embodiment, the present invention relates to a ready to use injectable formulation comprising monobasic potassium phosphate in an amount of about 0.01 mmol/ml to about 0.1 mmol/ml of phosphorus and dibasic potassium phosphate in an amount of about 0.01 mmol/ml to about 0.1 mmol/ml of phosphorus, wherein the formulation optionally contains a tonicity agent.
In an embodiment, the injectable formulation is free of any tonicity adjusting agent.
In one embodiment, the ready-to-use injectable formulation of the present invention comprises about 0.027 mmol/ml of phosphorus. In another embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 2.02 mg/ml or about 0.015 mmol/ml of phosphorus and (b) dibasic potassium phosphate in an amount of about 2.12 mg/ml or about 0.012 mmol/ml of phosphorus. In an embodiment, the injectable formulation further comprises propylene glycol as a tonicity adjusting agent. In a preferred embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.027 mmol/ml of phosphorus further contains about 17 mg/ml propylene glycol. In an embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.027 mmol/ml of phosphorus contains about 0.04 mEq/ml of potassium. In another embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.027 mmol/ml of phosphorus is an aqueous solution.
In a preferred embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 2.02 mg/ml or about 0.015 mmol/ml of phosphorus, (b) dibasic potassium phosphate in an amount of about 2.12 mg/ml or about 0.012 mmol/ml of phosphorus, (c) about 17 mg/ml propylene glycol and (d) water for injection. In one embodiment, such formulation contains about 0.04 mEq/ml of potassium.
In one embodiment, the ready-to-use injectable formulation of the present invention comprises about 0.055 mmol/ml of phosphorus. In another embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 4.11 mg/ml or about 0.030 mmol/ml of phosphorus and (b) dibasic potassium phosphate in an amount of about 4.33 mg/ml or about 0.025 mmol/ml of phosphorus. In an embodiment, the injectable formulation further comprises propylene glycol as a tonicity adjusting agent. In a preferred embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.055 mmol/ml of phosphorus further contains about 17.3 mg/ml propylene glycol. In an embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.055 mmol/ml of phosphorus contains about 0.08 mEq/ml of potassium. In another embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.055 mmol/ml of phosphorus is an aqueous solution.
In a preferred embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 4.11 mg/ml or about 0.030 mmol/ml of phosphorus, (b) dibasic potassium phosphate in an amount of about 4.33 mg/ml or about 0.025 mmol/ml of phosphorus, (c) about 17.3 mg/ml propylene glycol and (d) water for injection. In one embodiment, such formulation contains about 0.08 mEq/ml of potassium.
In one embodiment, the ready-to-use injectable formulation of the present invention comprises about 0.068 mmol/ml of phosphorus. In another embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 5.08 mg/ml or about 0.037 mmol/ml of phosphorus and (b) dibasic potassium phosphate in an amount of about 5.35 mg/ml or about 0.031 mmol/ml of phosphorus. In an embodiment, the injectable formulation further comprises propylene glycol as a tonicity adjusting agent. In a preferred embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.068 mmol/ml of phosphorus further contains about 11.65 mg/ml propylene glycol. In an embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.068 mmol/ml of phosphorus contains about 0.1 mEq/ml of potassium. In another embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.068 mmol/ml of phosphorus is an aqueous solution.
In a preferred embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 5.08 mg/ml or about 0.037 mmol/ml of phosphorus, (b) dibasic potassium phosphate in an amount of about 5.35 mg/ml or about 0.031 mmol/ml of phosphorus, (c) about 11.65 mg/ml propylene glycol and (d) water for injection. In one embodiment, such formulation contains about 0.1 mEq/ml of potassium.
In one embodiment, the ready-to-use injectable formulation of the present invention comprises about 0.18 mmol/ml of phosphorus. In another embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 13.44 mg/ml or about 0.099 mmol/ml of phosphorus and (b) dibasic potassium phosphate in an amount of about 14.16 mg/ml or about 0.081 mmol/ml of phosphorus. In an embodiment, the injectable formulation is free of any tonicity adjusting agent. In another embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.18 mmol/ml of phosphorus contains about 0.264 mEq/ml of potassium. In a further embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.18 mmol/ml of phosphorus is an aqueous solution.
In a preferred embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 13.44 mg/ml or about 0.099 mmol/ml of phosphorus, (b) dibasic potassium phosphate in an amount of about 14.16 mg/ml or about 0.081 mmol/ml of phosphorus, and (c) water for injection, wherein such formulation is free of any tonicity adjusting agent. In one embodiment, such formulation contains about 0.264 mEq/ml of potassium.
In one embodiment, the ready-to-use injectable formulation of the present invention comprises about 0.027 mmol/ml of phosphorus. In another embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 2.02 mg/ml or about 0.015 mmol/ml of phosphorus and (b) dibasic potassium phosphate in an amount of about 2.12 mg/ml or about 0.012 mmol/ml of phosphorus. In an embodiment, the injectable formulation further comprises sodium chloride as a tonicity adjusting agent. In a preferred embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.027 mmol/ml of phosphorus further contains about 7 mg/ml sodium chloride. In an embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.027 mmol/ml of phosphorus contains about 0.04 mEq/ml of potassium. In another embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.027 mmol/ml of phosphorus is an aqueous solution.
In a preferred embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 2.02 mg/ml or about 0.015 mmol/ml of phosphorus, (b) dibasic potassium phosphate in an amount of about 2.12 mg/ml or about 0.012 mmol/ml of phosphorus, (c) about 7 mg/ml sodium chloride and (d) water for injection. In one embodiment, such formulation contains about 0.04 mEq/ml of potassium.
In one embodiment, the ready-to-use injectable formulation of the present invention comprises about 0.055 mmol/ml of phosphorus. In another embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 4.11 mg/ml or about 0.030 mmol/ml of phosphorus and (b) dibasic potassium phosphate in an amount of about 4.33 mg/ml or about 0.025 mmol/ml of phosphorus. In an embodiment, the injectable formulation further comprises sodium chloride as a tonicity adjusting agent. In a preferred embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.055 mmol/ml of phosphorus further contains about 5.5 mg/ml sodium chloride. In an embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.055 mmol/ml of phosphorus contains about 0.08 mEq/ml of potassium. In another embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.055 mmol/ml of phosphorus is an aqueous solution.
In a preferred embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 4.11 mg/ml or about 0.030 mmol/ml of phosphorus, (b) dibasic potassium phosphate in an amount of about 4.33 mg/ml or about 0.025 mmol/ml of phosphorus, (c) about 5.5 mg/ml sodium chloride and (d) water for injection. In one embodiment, such formulation contains about 0.08 mEq/ml of potassium.
In one embodiment, the ready-to-use injectable formulation of the present invention comprises about 0.068 mmol/ml of phosphorus. In another embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 5.08 mg/ml or about 0.037 mmol/ml of phosphorus and (b) dibasic potassium phosphate in an amount of about 5.35 mg/ml or about 0.031 mmol/ml of phosphorus. In an embodiment, the injectable formulation further comprises sodium chloride as a tonicity adjusting agent. In a preferred embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.068 mmol/ml of phosphorus further contains about 5.2 mg/ml sodium chloride. In an embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.068 mmol/ml of phosphorus contains about 0.1 mEq/ml of potassium. In another embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.068 mmol/ml of phosphorus is an aqueous solution.
In a preferred embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 5.08 mg/ml or about 0.037 mmol/ml of phosphorus, (b) dibasic potassium phosphate in an amount of about 5.35 mg/ml or about 0.031 mmol/ml of phosphorus, (c) about 5.2 mg/ml sodium chloride and (d) water for injection. In one embodiment, such formulation contains about 0.1 mEq/ml of potassium.
In one embodiment, the ready-to-use injectable formulation of the present invention comprises about 0.18 mmol/ml of phosphorus. In another embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 13.44 mg/ml or about 0.099 mmol/ml of phosphorus and (b) dibasic potassium phosphate in an amount of about 14.16 mg/ml or about 0.081 mmol/ml of phosphorus. In an embodiment, the injectable formulation is free of any tonicity adjusting agent. In another embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.18 mmol/ml of phosphorus contains about 0.264 mEq/ml of potassium. In a further embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.18 mmol/ml of phosphorus is an aqueous solution.
In a preferred embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 13.44 mg/ml or about 0.099 mmol/ml of phosphorus, (b) dibasic potassium phosphate in an amount of about 14.16 mg/ml or about 0.081 mmol/ml of phosphorus, and (c) water for injection, wherein such formulation is free of any tonicity adjusting agent. In one embodiment, such formulation contains about 0.264 mEq/ml of potassium.
In one another embodiment, the ready-to-use injectable formulation of the present invention has a pH from about 5.5 to about 7.5. In a preferred embodiment, the ready-to-use injectable formulation of the present invention has a pH from about 6 to about 7.
In an embodiment, the ready-to-use injectable formulation of the present invention has a volume of about 10 ml.
In one embodiment, the ready-to-use injectable formulation of the present invention has a volume of about 100 ml.
In a further embodiment, the ready-to-use injectable formulation of the present invention has a volume of about 200 ml.
In another embodiment, the ready-to-use injectable formulation of the present invention has a volume of about 250 ml.
In one more embodiment, the ready-to-use injectable formulation of the present invention can be administered via peripheral vein.
In an embodiment, the present invention relates to a method of treating hypophosphatemia to a subject in need thereof by administering the ready-to-use injectable formulation comprising potassium phosphates.

DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to a ready- to- use injectable formulation of potassium phosphate and a process for preparing the same. The invention particularly relates to a ready-to-use injectable formulation comprising monobasic potassium phosphate, dibasic potassium phosphate, water for injection and optionally containing a tonicity adjusting agent. Such formulations are suitable to be administered without any dilution or any other adjustment to a required phosphate and/or potassium concentration. The formulation of the present invention has a long shelf life and is easy to administer, easy to store and easy to transport.
As used in the present specification, the following words, phrases and symbols are generally intended to have the meanings as set forth below, except to the extent that the context in which they are used indicates otherwise.
As used herein, the term "about" may be used to specify a value of a quantity or parameter (e.g. the length of an element) to within a continuous range of values in the neighborhood of (and including) a given (stated) value. For example, “about 100” means any value between 90 and 110, including 90 and 110 such as 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, and/or 110 and fractions in-between.
As used herein and unless otherwise stated, the term “concentration” refers to the weight per ml concentration. Also, the singular forms “a” and “the” include plural references unless the context clearly dictates otherwise.
The term "formulation" or "dosage form" or “composition” has been employed interchangeably for the purpose of the present invention and mean that it is a pharmaceutical formulation which is suitable for administration to a patient or subject. The subject can be an animal, preferably a mammal, more preferably a human.
The terms "comprises", "comprising", or any other variations thereof, are intended to cover a non-exclusive inclusion, such that a process or method that comprises a list of steps does not include only those steps but may include other steps not expressly listed or inherent to such process or method. Similarly, one or more devices or sub-systems or elements or structures or components proceeded by "comprises...a" does not, without more constraints, preclude the existence of other devices or other sub-systems or other elements or other structures or other components or additional devices or additional sub-systems or additional elements or additional structures or additional components.
As used herein, the word “injectable ” means suitable for insertion of liquid into the body via a hypodermic needle into one or more different locations that include, but are not limited to, intravenous through peripheral and central vein, intra-arterial, subcutaneous, intramuscular, intradermal, intracavernous, intracavitary, intravesical, interstitial, intra-articular, intradermal, intrafusal, intralesional, intratumor, intraperitoneal, intrapleural, intrasynovial, intrathecal, and intratracheal, or via infiltration, nerve block, IV infusion, or other route of injection.
Phosphorus in the form of organic and inorganic phosphate has a variety of important biochemical functions in the body and is involved in many significant metabolic and enzyme reactions in almost all organs and tissues. It exerts a modifying influence on the steady state of calcium levels, a buffering effect on acid-base equilibrium and a primary role in the renal excretion of hydrogen ion. Phosphorus is present in plasma and other extracellular fluid, in cell membranes and intracellular fluid, as well as in collagen and bone tissues. Phosphate in the extracellular fluid is primarily in inorganic form, and plasma levels may vary somewhat with age.
The term "ready - to - use” or “RTU” when used in conjunction with the solutions presented herein refers to a solution that does not require any dilution prior to administration and such solution can be directly administered to a patient. The terms "ready - to - use” and “RTU” can be said to be interchangeable. The term “phosphorus” is used synonymously with the term “phosphate” or “phosphates”.
Potassium phosphate is an inorganic potassium salt that is the potassium salt of phosphoric acid. It is an inorganic phosphate salt and an inorganic potassium salt. Potassium phosphate is a generic term for the salts of potassium and phosphate ions including monobasic potassium phosphate (KH2PO4) having a molar mass approximately 136 g/mol, dibasic potassium phosphate (K2HPO4) having a molar mass approximately 174 g/mol and tribasic potassium phosphate (K3PO4) having a molar mass approximately 212.27 g/mol.
KH2PO4 is the molecular structure of monobasic potassium phosphate, commonly known as potassium acid phosphate, which when dissolved in a liquid yields an acidic solution. A basic solution is created when dibasic potassium phosphate, which has the chemical structure K2HPO4.
In one embodiment, the present invention relates to a ready-to-use injectable formulation comprising potassium phosphate and optionally a tonicity adjusting agent.
In an embodiment, the ready-to-use injectable formulation of the present invention comprises potassium phosphate, wherein the potassium phosphate further comprises monobasic potassium phosphate (KH2PO4) and dibasic potassium phosphate (K2HPO4).
The present invention relates to a ready to use injectable formulation comprising potassium phosphate in an amount of about 2 mg/ml to about 30 mg/ml.
In one embodiment, the ready to use injectable formulation comprises potassium phosphate in an amount of about 0.01 mmol/ml to about 0.2 mmol/ml of phosphorus.
In another embodiment, the ready to use injectable formulation comprises monobasic potassium phosphate in an amount of about 1 mg/ml to about 15 mg/ml.
In one more embodiment, the ready to use injectable formulation comprises dibasic potassium phosphate in an amount of about 1 mg/ml to about 15 mg/ml.
In a further embodiment, the ready to use injectable formulation comprises monobasic potassium phosphate in an amount of about 0.01 mmol/ml to about 0.1 mmol/ml of phosphorus.
In one another embodiment, the ready to use injectable formulation comprises dibasic potassium phosphate in an amount of about 0.01 mmol/ml to about 0.1 mmol/ml of phosphorus.
In one another embodiment, the ready-to-use formulation of the present invention comprises monobasic potassium phosphate (KH2PO4) in amount of about 2.02 mg/ml, or about 4.11 mg/ml, or about 5.08 mg/ml, or about 13.44 mg/ml.
In one more embodiment, the ready-to-use formulation of potassium phosphate solution of present invention comprises dibasic potassium phosphate (K2HPO4) in amount of about 2.12 mg/ml or about 4.33 mg/ml, or about 5.35 mg/ml or about 14.16 mg/ml.
In one embodiment, the ready-to-use formulation of potassium phosphate solution of present invention comprising monobasic potassium phosphate (KH2PO4) in amount of about 0.015 mmol/ml, or about 0.030 mmol/ml, or about 0.037 mmol/ml, or about 0.099 mmol/ml of phosphorus.
In an embodiment, the ready-to-use formulation of potassium phosphate solution of present invention comprising dibasic potassium phosphate (K2HPO4) in amount of about 0.012 mmol/ml, or about 0.025 mmol/ml, or about 0.031 mmol/ml, or about 0.081 mmol/ml of phosphorus.
The ready-to-use injectable formulation of the present invention may optionally comprise a tonicity adjusting agent. Preferably, the injectable formulation of the present invention is isotonic. The term isotonic has the same salt concentration as cells and blood. The term isotonic is used interchangeably with isosmotic with reference to specific body fluids. Suitable tonicity adjusting agents include, per are not limited to propylene glycol, potassium chloride, dextrose, sucrose, mannitol, sorbitol, mannose, glycerin, sodium chloride, sodium carbonate and meglumine, sodium lactate, ringer’s solution, and lactate ringer’s solution. In a preferred embodiment, the tonicity adjusting agent is propylene glycol. In another preferred embodiment, the tonicity adjusting agent is sodium chloride.
The ready-to-use injectable formulation of the present invention may comprise a tonicity adjusting agent in an amount between about 0 mg/ml to about 50 mg/ml. In one embodiment, the ready-to-use injectable formulation of the present invention comprises about 0 mg/ml to about 50 mg/ml of a tonicity adjusting agent selected from propylene glycol and sodium chloride. In a embodiment, the ready-to-use injectable formulation of the present invention comprises about 0 mg/ml to about 50 mg/ml of propylene glycol. In one more embodiment, the ready-to-use injectable formulation of the present invention comprises about 0 mg/ml to about 50 mg/ml of sodium chloride. In a preferred embodiment, the ready-to-use injectable formulation of the present invention may contain about 0 mg/ml, or about 11.65 mg/ml or about 17.0 mg/ml, or about 17.3 mg/ml propylene glycol. In another preferred embodiment, the ready-to-use injectable formulation of the present invention may contain about 0 mg/ml, or about 5.2 mg/ml or about 5.5 mg/ml, or about 7 mg/ml sodium chloride.
The ready-to-use injectable formulation of the present invention also comprises a pharmaceutically acceptable vehicle. In one embodiment, the ready-to-use injectable formulation of the present invention is an aqueous formulation. In a preferred embodiment, the pharmaceutically acceptable vehicle is water for injection.
The ready-to-use injectable formulation of the present invention may comprise a pharmaceutically acceptable vehicle in an amount sufficient to make up the total volume of the formulation. In one embodiment, the volume of the ready-to-use injectable formulation of the present invention is about 10 ml. In one more embodiment, the volume of the ready-to-use injectable formulation of the present invention is about 100 ml. In another embodiment, the volume of the ready-to-use injectable formulation of the present invention is about 200 ml. In a further embodiment, the volume of the ready-to-use injectable formulation of the present invention is about 250 ml. In an embodiment, the volume of the ready-to-use injectable formulation of the present invention is about 1000 ml.
The pH of the ready-to-use injectable formulation of the present invention may be between about 5.5 to about 7.5. In a preferred embodiment, the pH of the ready-to-use injectable formulation of the present invention may be between about 6.0 to about 7.0. In another embodiment, the pH of the ready-to-use injectable formulation of the present invention may be about 6.0, about 6.1, about 6.2, about 6.3, about 6.4, about 6.5, about 6.6, about 6.7, about 6.8, about 6.9, or about 7.0.
The present invention relates to a ready to use injectable formulation comprising potassium phosphate in an amount of about 2 mg/ml to about 30 mg/ml. In one embodiment, the present invention relates to a ready to use injectable formulation comprising potassium phosphate in an amount of about 2 mg/ml to about 30 mg/ml, and optionally containing a tonicity agent.
In one embodiment, the ready to use injectable formulation comprises potassium phosphate in an amount of about 0.01 mmol/ml to about 0.2 mmol/ml of phosphorus. In another embodiment, the present invention relates to a ready to use injectable formulation comprises potassium phosphate in an amount of about 0.01 mmol/ml to about 0.2 mmol/ml of phosphorus, and optionally containing a tonicity agent.
In another embodiment, the ready to use injectable formulation comprises monobasic potassium phosphate in an amount of about 1 mg/ml to about 15 mg/ml.
In one more embodiment, the ready to use injectable formulation comprises dibasic potassium phosphate in an amount of about 1 mg/ml to about 15 mg/ml.
In an embodiment, the present invention relates to a ready to use injectable formulation comprising monobasic potassium phosphate in an amount of about 1 mg/ml to about 15 mg/ml and dibasic potassium phosphate in an amount of about 1 mg/ml to about 15 mg/ml, wherein the formulation optionally contains a tonicity agent.
In a further embodiment, the ready to use injectable formulation comprises monobasic potassium phosphate in an amount of about 0.01 mmol/ml to about 0.1 mmol/ml of phosphorus.
In one another embodiment, the ready to use injectable formulation comprises dibasic potassium phosphate in an amount of about 0.01 mmol/ml to about 0.1 mmol/ml of phosphorus.
In an embodiment, the present invention relates to a ready to use injectable formulation comprising monobasic potassium phosphate in an amount of about 0.01 mmol/ml to about 0.1 mmol/ml of phosphorus and dibasic potassium phosphate in an amount of about 0.01 mmol/ml to about 0.1 mmol/ml of phosphorus, wherein the formulation optionally contains a tonicity agent.
In an embodiment, the injectable formulation is free of any tonicity adjusting agent.
The present invention relates to a ready-to-use injectable formulation comprising about 0.027 mmol/ml of phosphorus. In one embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 2.02 mg/ml or about 0.015 mmol/ml of phosphorus and (b) dibasic potassium phosphate in an amount of about 2.12 mg/ml or about 0.012 mmol/ml of phosphorus. In an embodiment, the injectable formulation further comprises propylene glycol as a tonicity adjusting agent. In a preferred embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.027 mmol/ml of phosphorus further contains about 17.0 mg/ml propylene glycol. In an embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.027 mmol/ml of phosphorus contains about 0.04 mEq/ml of potassium. In another embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.027 mmol/ml of phosphorus is an aqueous solution.
In a preferred embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 2.02 mg/ml or about 0.015 mmol/ml of phosphorus, (b) dibasic potassium phosphate in an amount of about 2.12 mg/ml or about 0.012 mmol/ml of phosphorus, (c) about 17.0 mg/ml propylene glycol and (d) water for injection. In one embodiment, such formulation contains about 0.04 mEq/ml of potassium.
The present invention relates to a ready-to-use injectable formulation comprising about 0.055 mmol/ml of phosphorus. In one embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 4.11 mg/ml or about 0.030 mmol/ml of phosphorus and (b) dibasic potassium phosphate in an amount of about 4.33 mg/ml or about 0.025 mmol/ml of phosphorus. In an embodiment, the injectable formulation further comprises propylene glycol as a tonicity adjusting agent. In a preferred embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.055 mmol/ml of phosphorus further contains about 17.3 mg/ml propylene glycol. In an embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.055 mmol/ml of phosphorus contains about 0.08 mEq/ml of potassium. In another embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.055 mmol/ml of phosphorus is an aqueous solution.
In a preferred embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 4.11 mg/ml or about 0.030 mmol/ml of phosphorus, (b) dibasic potassium phosphate in an amount of about 4.33 mg/ml or about 0.025 mmol/ml of phosphorus, (c) about 17.3 mg/ml propylene glycol and (d) water for injection. In one embodiment, such formulation contains about 0.08 mEq/ml of potassium.
The present invention relates to a ready-to-use injectable formulation comprising about 0.068 mmol/ml of phosphorus. In one embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 5.08 mg/ml or about 0.037 mmol/ml of phosphorus and (b) dibasic potassium phosphate in an amount of about 5.35 mg/ml or about 0.031 mmol/ml of phosphorus. In an embodiment, the injectable formulation further comprises propylene glycol as a tonicity adjusting agent. In a preferred embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.068 mmol/ml of phosphorus further contains about 11.65 mg/ml propylene glycol. In an embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.068 mmol/ml of phosphorus contains about 0.1 mEq/ml of potassium. In another embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.068 mmol/ml of phosphorus is an aqueous solution.
In a preferred embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 5.08 mg/ml or about 0.037 mmol/ml of phosphorus, (b) dibasic potassium phosphate in an amount of about 5.33 mg/ml or about 0.031 mmol/ml of phosphorus, (c) about 11.65 mg/ml propylene glycol and (d) water for injection. In one embodiment, such formulation contains about 0.1 mEq/ml of potassium.
The present invention relates to a ready-to-use injectable formulation comprising about 0.18 mmol/ml of phosphorus. In one embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 13.44 mg/ml or about 0.099 mmol/ml of phosphorus and (b) dibasic potassium phosphate in an amount of about 14.16 mg/ml or about 0.081 mmol/ml of phosphorus. In an embodiment, the injectable formulation is free of any tonicity adjusting agent. In another embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.18 mmol/ml of phosphorus contains about 0.264 mEq/ml of potassium. In a further embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.18 mmol/ml of phosphorus is an aqueous solution.
In a preferred embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 13.44 mg/ml or about 0.099 mmol/ml of phosphorus, (b) dibasic potassium phosphate in an amount of about 14.16 mg/ml or about 0.081 mmol/ml of phosphorus, and (c) water for injection, wherein such formulation is free of any tonicity adjusting agent. In one embodiment, such formulation contains about 0.264 mEq/ml of potassium.
In one embodiment, the ready-to-use injectable formulation of the present invention comprises about 0.027 mmol/ml of phosphorus. In another embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 2.02 mg/ml or about 0.015 mmol/ml of phosphorus and (b) dibasic potassium phosphate in an amount of about 2.12 mg/ml or about 0.012 mmol/ml of phosphorus. In an embodiment, the injectable formulation further comprises sodium chloride as a tonicity adjusting agent. In a preferred embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.027 mmol/ml of phosphorus further contains about 7 mg/ml sodium chloride. In an embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.027 mmol/ml of phosphorus contains about 0.04 mEq/ml of potassium. In another embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.027 mmol/ml of phosphorus is an aqueous solution.
In a preferred embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 2.02 mg/ml or about 0.015 mmol/ml of phosphorus, (b) dibasic potassium phosphate in an amount of about 2.12 mg/ml or about 0.012 mmol/ml of phosphorus, (c) about 7 mg/ml sodium chloride and (d) water for injection. In one embodiment, such formulation contains about 0.04 mEq/ml of potassium.
In one embodiment, the ready-to-use injectable formulation of the present invention comprises about 0.055 mmol/ml of phosphorus. In another embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 4.11 mg/ml or about 0.030 mmol/ml of phosphorus and (b) dibasic potassium phosphate in an amount of about 4.33 mg/ml or about 0.025 mmol/ml of phosphorus. In an embodiment, the injectable formulation further comprises sodium chloride as a tonicity adjusting agent. In a preferred embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.055 mmol/ml of phosphorus further contains about 5.5 mg/ml sodium chloride. In an embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.055 mmol/ml of phosphorus contains about 0.08 mEq/ml of potassium. In another embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.055 mmol/ml of phosphorus is an aqueous solution.
In a preferred embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 4.11 mg/ml or about 0.030 mmol/ml of phosphorus, (b) dibasic potassium phosphate in an amount of about 4.33 mg/ml or about 0.025 mmol/ml of phosphorus, (c) about 5.5 mg/ml sodium chloride and (d) water for injection. In one embodiment, such formulation contains about 0.08 mEq/ml of potassium.
In one embodiment, the ready-to-use injectable formulation of the present invention comprises about 0.068 mmol/ml of phosphorus. In another embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 5.08 mg/ml or about 0.037 mmol/ml of phosphorus and (b) dibasic potassium phosphate in an amount of about 5.35 mg/ml or about 0.031 mmol/ml of phosphorus. In an embodiment, the injectable formulation further comprises sodium chloride as a tonicity adjusting agent. In a preferred embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.068 mmol/ml of phosphorus further contains about 5.2 mg/ml sodium chloride. In an embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.068 mmol/ml of phosphorus contains about 0.1 mEq/ml of potassium. In another embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.068 mmol/ml of phosphorus is an aqueous solution.
In a preferred embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 5.08 mg/ml or about 0.037 mmol/ml of phosphorus, (b) dibasic potassium phosphate in an amount of about 5.35 mg/ml or about 0.031 mmol/ml of phosphorus, (c) about 5.2 mg/ml sodium chloride and (d) water for injection. In one embodiment, such formulation contains about 0.1 mEq/ml of potassium.
In one embodiment, the ready-to-use injectable formulation of the present invention comprises about 0.18 mmol/ml of phosphorus. In another embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 13.44 mg/ml or about 0.099 mmol/ml of phosphorus and (b) dibasic potassium phosphate in an amount of about 14.16 mg/ml or about 0.081 mmol/ml of phosphorus. In an embodiment, the injectable formulation is free of any tonicity adjusting agent. In another embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.18 mmol/ml of phosphorus contains about 0.264 mEq/ml of potassium. In a further embodiment, the ready-to-use injectable formulation of the present invention comprising about 0.18 mmol/ml of phosphorus is an aqueous solution.
In a preferred embodiment, the ready-to-use injectable formulation of the present invention comprises (a) monobasic potassium phosphate in an amount of about 13.44 mg/ml or about 0.099 mmol/ml of phosphorus, (b) dibasic potassium phosphate in an amount of about 14.16 mg/ml or about 0.081 mmol/ml of phosphorus, and (c) water for injection, wherein such formulation is free of any tonicity adjusting agent. In one embodiment, such formulation contains about 0.264 mEq/ml of potassium.
The ready-to-use injectable formulation of the present invention may have a pH from about 5.5 to about 7.5. In a preferred embodiment, the ready-to-use injectable formulation of the present invention has a pH from about 6 to about 7.
The ready-to-use injectable formulation of the present invention may have a volume of about 10 ml. The ready-to-use injectable formulation of the present invention may have a volume of about 100 ml. The ready-to-use injectable formulation of the present invention may have a volume of about 200 ml. The ready-to-use injectable formulation of the present invention may have a volume of about 250 ml. The ready-to-use injectable formulation of the present invention may have a volume of about 1000 ml.
In one more embodiment, the ready-to-use injectable formulation of the present invention can be administered via peripheral vein.
In an embodiment, the present invention relates to a method of treating hypophosphatemia to a subject in need thereof by administering the ready-to-use injectable formulation comprising potassium phosphates.
The term “sterile” formulation, as used herein, means a formulation that has been brought to state of sterility and has not been subsequently exposed to microbiological contamination, i.e., the container holding the sterile formulation has not been compromised. Sterile formulations are generally prepared by pharmaceutical manufacturers in accordance with current Good Manufacturing Practice (cGMP) regulations of the U.S. Food and Drug Administration.
The term "stable" refers to a formulation which is physically as well as chemically stable as demonstrated by compliance to acceptable specification when the formulation is stored at convenient temperature, such as between about 0°C and about 60°C, for a commercially reasonable period of time, such as at least about 1 day, at least about 1 week, at least about 1 month, at least about 3 months, at least about 6 months, at least about 1 year, or at least about 2 years.. Suitably, the ready-to-use injectable formulation of the present invention remains physically stable, with no precipitation or crystallization or color change upon storage and the shelf life period of 18-24 months when stored at 2-8° C and 20-25° C. Suitably, the ready-to-use injectable formulation of the present invention remains chemically stable, wherein various parameters such as the drug content (assay ) and content of related substances, i.e. known and unknown impurities remains within specified limits such as those specified according to ICH guidelines, upon storage for prolonged period of time such as for at least 12 months, preferably for 18 months, more preferably 24 months or longer.
The ready-to-use injectable formulation of the present invention is stable for long shelf life and is easy to administer, easy to store and easy to transport. In some preferred aspects of the invention, the time for which long term storage is contemplated such that the formulation is substantially free of impurities when stored at room temperature.
The ready-to-use injectable formulation of the present invention may be packaged in a suitable container. In one embodiment, the ready-to-use injectable formulation of the present invention is dispensed in a pharmaceutically acceptable container such as plastic intravenous bags, including pre-mix bags and admix bags. The containers are flexible plastic bags, such as are customary for injection-ready solutions. In an embodiment, the pharmaceutical formulation of present invention is stored in terminally sterilized flexible container and are optionally overwrapped by secondary packaging which helps to maintain predetermined concentration of all solutes. In some embodiments, the formulation of present invention can be aseptically filled and stored in commercially available intravenous bags such as, but not limited to: ADDEASE®, ADD-VANTAGE®, BFSTM, DUPLEXTM, EXCEL®, FIRST CHOICETM, GALAXY®, INTRAVIA®, PROPYFLEXTM, SOLOMIX®, STEDIM® 71, STEDIM®100, VIAFLEX®, VIAFLOTM and VISIV®.
With respect to suitable polymeric autoclavable containers, various materials are deemed suitable for use herein, and especially preferred polymeric materials include polysulfone, polycarbonate, polypropylene, polyethylene (LDPE or HDPE), ethylene / propylene copolymers, polyolefins, acrylic - imide copolymers, polyester ( e.g. , PET , PEN and the like ), Teflon, Nylon, acetal (Delrin), polymethyl pentene, PVDC, ethyl vinyl acetate, polyvinyl chloride, and polyolefins.
In another embodiment, ready-to-use injectable formulation of the present invention may be packaged in a glass container. In one embodiment, the glass container can be an internally coated glass container. In certain other embodiments, the glass container is internally coated with silicon dioxide.
The ready-to-use injectable formulation of the present invention may be sterilized using appropriate sterilization techniques known to a person skilled in the art.
Procedure for filling ready-to-use injectable formulation of the present invention in suitable containers and their subsequent processing should be done with care to destroy or eliminate any microorganisms that may be present in the formulation. According to an embodiment, ready-to-use injectable formulation of the present invention may be prepared using aseptic processing techniques. All the ingredients used for preparing the ready-to-use injectable formulation of the present invention may be sterile. Sterility is maintained by using sterile materials and a controlled working environment. All containers and apparatus are sterilized, preferably by heat sterilization in moist steam, prior to filling. The container is then filled under aseptic conditions. Aseptic sterilization is preferably carried out by passing the formulation through at least one sterile filter, for e.g 0.22 µm. Several sterilizing grade membrane filters are available for aseptic filtration of water-based dosage forms such as cellulose acetate, nylon, polyether sulfone (PES) polypropylene (PP), polyvinyl difluoride (PVDF) and the like.
In another embodiment, ready-to-use injectable formulation of the present invention may be terminally sterilized at a temperature of at least about 100 ° C to 121 ° C for 15 to 30 minutes via moist heat sterilization or autoclaving.
In one embodiment, the ready-to-use injectable formulation of the present invention can be prepared by process comprising
(a) dissolving dibasic potassium phosphate in water for injection under continuous stirring;
(b) dissolving monobasic potassium phosphate in water for injection and adding into step
(a);
(c) optionally adding tonicity adjusting agent into step (b);
(d) making up volume with water for injection; and
(e) sterilizing the solution of step (d) by appropriate sterilization methods.
In another embodiment, the ready-to-use injectable formulation of the present invention can be prepared by process comprising
(a) dissolving tonicity adjusting agent in water for injection under continuous stirring;
(b) dissolving dibasic potassium phosphate in water for injection and adding into step (a);
(c) dissolving monobasic potassium phosphate in water for injection and adding into step (b);
(d) making up volume with water for injection; and
(e) sterilizing the solution of step (e) by appropriate sterilization methods.
The term "ameliorating," with reference to a disease or pathological condition, refers to any observable beneficial effect of the treatment. The beneficial effect can be evidenced, for example, by a delayed onset of clinical symptoms of the disease in a susceptible subject, a reduction in severity of some or all clinical symptoms of the disease, an improvement in the overall health or well-being of the subject, or by other parameters well known in the art that are specific to the disease.
The terms "treating," "treatment," or "therapy," as used herein refer to partially or completely alleviating, ameliorating, improving, relieving, delaying onset of, inhibiting progression of, reducing severity of, reducing incidence of, attenuating one or more of the electrolyte disorder or symptoms, in which there is low level of minerals found in body.
In another embodiment, the present invention relates to a method for treating hypophosphatemia in a subject in need thereof by administering the ready-to-use injectable formulation of the present invention.
The present invention provides a method of administering phosphates to a subject in need of phosphorus replacement therapy, and contemplated methods include a step of administering, without prior dilution, a ready-to-use injectable formulation comprising potassium phosphates at a rate of infusion and by a route of administration corresponding to the patient's age and degree of need of phosphorus. In a preferred embodiment, the ready-to-use injectable formulation of potassium phosphate solution is administered via peripheral vein.

Examples of ready to use injectable formulation containing propylene glycol as tonicity adjusting agent.
Example 1: Ready-to-use injectable potassium phosphate formulation comprising 0.027 mmol/ml phosphorus
Ingredients Unit Quantity
Monobasic Potassium Phosphate mg/ml 2.02
mmol/ml 0.015
Dibasic Potassium Phosphate mg/ml 2.12
mmol/ml 0.012
Propylene glycol mg/ml 17.0
Water for Injection ml q.s to 1 ml
Potassium content mEq/ml 0.04
pH - 6.7
Osmolality mOsm/kg 285
The below table is representative of the stability data for the formulation as provided in Example 1.

Condition Initial 25 °C/60%RH 40 °C/20%RH
Time Interval 1M 3M 1M 3M
Description * * * * *
pH 6.67 6.91 6.89 6.92 6.85
Osmolality (mOsmol/Kg) 288 299 298 298 297
Weight per mL (g/mL) 1.003 1.002 1.002 1.003 1.002
Colour index (AU) 0.0001 -0.0006 0.0076 0.0024 0.0012
Particulate matter
Particulate matter (>10 µm ) (NMT-6000) 33 120 NP 140 NP
Particulate matter (>25 µm) (NMT-600) 67 0 NP 3 NP
Monobasic potassium phosphate (mg/mL) 5.1 5.2 5.1 5.1 5.2
Assay of Monobasic potassium phosphate (%) 101.0 101.5 101.3 101.0 101.5
Dibasic potassium phosphate (mg/mL) 5.4 5.4 5.4 5.4 5.4
Assay of Dibasic potassium phosphate (%) 101.4 100.6 101.1 100.0 101.7
Total Mmoles of 'P' from Monobasic Potassium phosphate and Dibasic Potassium phosphate 0.069 0.069 0.069 0.069 0.069
Total mEq of 'K' from Monobasic Potassium phosphate and Dibasic Potassium phosphate 0.100 0.100 0.100 0.100 0.100
*- Clear colourless solution free from visible particulates, NP- Not performed

Example 2: Ready-to-use injectable potassium phosphate formulation comprising 0.055 mmol/ml phosphorus
Ingredients Unit Quantity
Monobasic Potassium Phosphate mg/ml 4.11
mmol/ml 0.030
Dibasic Potassium Phosphate mg/ml 4.33
mmol/ml 0.025
Propylene glycol mg/ml 17.3
Water for Injection ml q.s to 1 ml
Potassium content mEq/ml 0.08
pH - 6.7
Osmolality mOsm/kg 286

Example 3: Ready-to-use injectable potassium phosphate formulation comprising 0.068 mmol/ml phosphorus
Ingredients Unit Quantity
Monobasic Potassium Phosphate mg/ml 5.08
mmol/ml 0.037
Dibasic Potassium Phosphate mg/ml 5.35
mmol/ml 0.031
Propylene glycol mg/ml 11.65
Water for Injection ml q.s to 1 ml
Potassium content mEq/ml 0.1
pH - 6.7
Osmolality mOsm/kg 306
The below table is representative of the stability data for the formulation as provided in Example 3.
Condition Initial 25 °C/60%RH 40 °C/20%RH
Time Interval 1M 3M 1M 3M
Description * * * * *
pH 6.69 6.81 6.82 6.82 6.81
Osmolality (mOsmol/Kg) 289 310 312 310 308
Weight per mL (g/mL) 1.007 1.007 1.006 1.007 1.006
Colour index (AU) 0.0013 0.0028 0.0000 0.0020 0.0000
Particulate matter
Particulate matter (>10 µm ) (NMT-6000) 727 233 NP 263 NP
Particulate matter (>25 µm) (NMT-600) 67 0 NP 3 NP
Monobasic potassium phosphate (mg/mL) 5.1 5.2 5.1 5.1 5.2
Assay of Monobasic potassium phosphate (%) 101.0 101.5 101.3 101.0 101.5
Dibasic potassium phosphate (mg/mL) 5.4 5.4 5.4 5.4 5.4
Assay of Dibasic potassium phosphate (%) 101.4 100.6 101.1 100.0 101.7
Total Mmoles of 'P' from Monobasic Potassium phosphate and Dibasic Potassium phosphate 0.069 0.069 0.069 0.069 0.069
Total mEq of 'K' from Monobasic Potassium phosphate and Dibasic Potassium phosphate 0.100 0.100 0.100 0.100 0.100
*- Clear colourless solution free from visible particulates, NP- Not performed

Example 4: Ready-to-use injectable potassium phosphate formulation comprising 0.18 mmol/ml phosphorus
Ingredients Unit Quantity
Monobasic Potassium Phosphate mg/ml 13.44
mmol/ml 0.099
Dibasic Potassium Phosphate mg/ml 14.16
mmol/ml 0.081
Propylene glycol mg/ml 0
Water for Injection ml q.s to 1 ml
Potassium content mEq/ml 0.264
pH - 6.7
Osmolality mOsm/kg 353

The above exemplified formulations of the present invention were be prepared by the following process:
a) Propylene glycol was dissolved in water for injection under continuous stirring;
b) Dibasic potassium phosphate was dissolved in water for injection and added to solution of step (a);
c) Monobasic potassium phosphate was dissolved in water for injection and added to solution of step (b);
d) Volume was made up with water for injection; and
e) Solution of step (d) was sterilized by appropriate sterilization method.

Examples of ready to use injectable formulation containing sodium chloride as tonicity adjusting agent.
Example 5: Ready-to-use injectable potassium phosphate formulation comprising 0.027 mmol/ml phosphorus
Ingredients Unit Quantity
Monobasic Potassium Phosphate mg/ml 2.02
mmol/ml 0.015
Dibasic Potassium Phosphate mg/ml 2.12
mmol/ml 0.012
Sodium chloride mg/ml 7
Water for Injection ml q.s to 1 ml
Potassium content mEq/ml 0.04
pH - 6.7
Osmolality mOsm/kg 285
The below table is representative of the stability data for the formulation as provided in Example 5.
Condition 2-8 Degree C 25 °C/60%RH 40 °C/20%RH
Time Interval Initial 3M 6M 3M 6M 1M 3M 6M
Description * * * * * * * *
pH 6.75 6.76 6.72 6.77 6.72 6.75 6.77 6.72
Osmolality (mOsmol/Kg) 285 277 279 277 279 273 278 279
Weight per mL (g/mL) 1.005 NP 1.006 1.006 1.006 NP 1.006 1.006
Colour index (AU) NP 0.0152 0.0078 0.026 0.0078 NP 0.0006 0.0073
Particulate matter
Particulate matter (>10 µm ) (NMT-6000) 153 6 6 1 8 255 1 8
Particulate matter (>25 µm) (NMT-600) 10 0 0 0 0 13.3 0 0
Monobasic potassium phosphate (mg/mL) 2.0 2.1 2.0 2.1 2.0 2.1 2.0 2.0
Assay of Monobasic potassium phosphate (%) 99.2 104.2 99.2 104.2 99.2 104.2 99.2 99.2
Dibasic potassium phosphate (mg/mL) 2.1 2.2 2.2 2.2 2.2 2.2 2.2 2.2
Assay of Dibasic potassium phosphate (%) 98.9 103.6 98.9 103.6 98.9 103.6 103.6 98.9
Total Mmoles of 'P' from Monobasic Potassium phosphate and Dibasic Potassium phosphate 0.027 0.028 0.027 0.028 0.027 0.027 0.028 0.027
Total mEq of 'K' from Monobasic Potassium phosphate and Dibasic Potassium phosphate 0.04 0.04 0.04 0.04 0.04 0.04 0.04 0.04
*- Clear colourless solution free from visible particulates, NP- Not performed

Example 6: Ready-to-use injectable potassium phosphate formulation comprising 0.055 mmol/ml phosphorus
Ingredients Unit Quantity
Monobasic Potassium Phosphate mg/ml 4.11
mmol/ml 0.030
Dibasic Potassium Phosphate mg/ml 4.33
mmol/ml 0.025
Sodium chloride mg/ml 5.5
Water for Injection ml q.s to 1 ml
Potassium content mEq/ml 0.08
pH - 6.7
Osmolality mOsm/kg 286

Example 7: Ready-to-use injectable potassium phosphate formulation comprising 0.068 mmol/ml phosphorus
Ingredients Unit Quantity
Monobasic Potassium Phosphate mg/ml 5.08
mmol/ml 0.037
Dibasic Potassium Phosphate mg/ml 5.35
mmol/ml 0.031
Sodium chloride mg/ml 5.2
Water for Injection ml q.s to 1 ml
Potassium content mEq/ml 0.1
pH - 6.7
Osmolality mOsm/kg 306

The below table is representative of the stability data for the formulation as provided in Example 7.

Condition 2-8 Degree C 25 °C/60%RH 40 °C/20%RH
Time Interval Initial 3M 6M 3M 6M 1M 3M 6M
Description * * * * * * * *
pH 6.73 6.69 6.66 6.69 6.61 6.66 6.71 6.66
Osmolality (mOsmol/Kg) 306 294 304 295 304 301 294 302
Weight per mL (g/mL) 1.009 1.009 1.01 1.009 1.009 1.01 1.009 1.01
Colour index (AU) NP 0.0005 0.0031 0.0010 0.0015 0.0038 0.0016 0.0000
Particulate matter
Particulate matter (>10 µm ) (NMT-6000) NP 2 8 3 12 23.3 3 10
Particulate matter (>25 µm) (NMT-600) NP 0 0 0 0 0 0 0
Monobasic potassium phosphate (mg/mL) 5.1 5.1 5.1 5.1 5.1 5.1 5.1 5.1
Assay of Monobasic potassium phosphate (%) 100.5 100.5 100.5 100.5 100.5 100.5 100.5 100.5
Dibasic potassium phosphate (mg/mL) 5.4 5.4 5.4 5.4 5.4 5.4 5.4 5.4
Assay of Dibasic potassium phosphate (%) 101.0 101.0 101.0 101.0 101.0 101.0 101.0 101.0
Total Mmoles of 'P' from Monobasic Potassium phosphate and Dibasic Potassium phosphate 0.069 0.069 0.069 0.069 0.069 0.069 0.068 0.069
Total mEq of 'K' from Monobasic Potassium phosphate and Dibasic Potassium phosphate 0.099 0.099 0.100 0.100 0.100 0.100 0.100 0.100
*- Clear colourless solution free from visible particulates, NP- Not performed

Example 8: Ready-to-use injectable potassium phosphate formulation comprising 0.18 mmol/ml phosphorus
Ingredients Unit Quantity
Monobasic Potassium Phosphate mg/ml 13.44
mmol/ml 0.099
Dibasic Potassium Phosphate mg/ml 14.16
mmol/ml 0.081
Sodium chloride mg/ml 0
Water for Injection ml q.s to 1 ml
Potassium content mEq/ml 0.264
pH - 6.7
Osmolality mOsm/kg 353

The above exemplified formulations of the present invention were be prepared by the following process:
a) Sodium chloride was dissolved in water for injection under continuous stirring;
b) Dibasic potassium phosphate was dissolved in water for injection and added to solution of step (a);
c) Monobasic potassium phosphate was dissolved in water for injection and added to solution of step (b);
d) Volume was made up with water for injection; and
e) Solution of step (d) was sterilized by appropriate sterilization method.

It will be readily apparent to one skilled in the art that varying substitutions and modifications may be made to the invention disclosed herein without departing from the spirit of the invention. Thus, it should be understood that although the present invention has been specifically disclosed by the preferred embodiments and optional features, modification and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and such modifications and variations are considered to be falling within the scope of the invention.
It is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The use of “including,” “comprising,” or “having” and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items.
It must be noted that, as used in this specification and the appended claims, the singular forms "a," "an" and "the" include plural references unless the context clearly dictates otherwise.
,CLAIMS:1. A ready-to-use injectable formulation comprising monobasic potassium phosphate, dibasic potassium phosphate, water for injection and optionally containing a tonicity adjusting agent.
2. The formulation according to claim 1, wherein the formulation comprises potassium phosphate in an amount of about 2 mg/ml to about 30 mg/ml.
3. The formulation according to claim 1, wherein the formulation comprises potassium phosphate in an amount of about 0.01 mmol/ml to about 0.2 mmol/ml of phosphorus.
4. The formulation according to claim 1, wherein the formulation contains a tonicity adjusting agent.
5. The formulation according to claim 1, wherein the formulation contains about 0 mg/ml to about 50 mg/ml of a tonicity adjusting agent.
6. The formulation according to claim 1, wherein the formulation contains about 0 mg/ml to about 50 mg/ml of tonicity adjusting agent selected from propylene glycol and sodium chloride.
7. The formulation according to claim 1, wherein the formulation is free of a tonicity adjusting agent.
8. The formulation according to claim 1, wherein the formulation comprises monobasic potassium phosphate in an amount of about 1 mg/ml to about 15 mg/ml.
9. The formulation according to claim 1, wherein the formulation comprises dibasic potassium phosphate in an amount of about 1 mg/ml to about 15 mg/ml.
10. The formulation according to claim 1, wherein the formulation comprises monobasic potassium phosphate in an amount of about 1 mg/ml to about 15 mg/ml and dibasic potassium phosphate in an amount of about 1 mg/ml to about 15 mg/ml, and wherein the formulation optionally contains a tonicity agent.
11. The formulation according to claim 1, wherein the formulation comprises monobasic potassium phosphate in an amount of about 0.01 mmol/ml to about 0.1 mmol/ml of phosphorus.
12. The formulation according to claim 1, wherein the formulation comprises dibasic potassium phosphate in an amount of about 0.01 mmol/ml to about 0.1 mmol/ml of phosphorus.
13. The formulation according to claim 1, wherein the formulation comprises monobasic potassium phosphate in an amount of about 0.01 mmol/ml to about 0.1 mmol/ml of phosphorus and dibasic potassium phosphate in an amount of about 0.01 mmol/ml to about 0.1 mmol/ml of phosphorus, and wherein the formulation optionally contains a tonicity agent.
14. The formulation according to claim 1, wherein the formulation comprises about 0.027 mmol/ml of phosphorus.
15. The formulation according to claim 14, wherein the formulation comprises (a) monobasic potassium phosphate in an amount of about 2.02 mg/ml or about 0.015 mmol/ml of phosphorus, (b) dibasic potassium phosphate in an amount of about 2.12 mg/ml or about 0.012 mmol/ml of phosphorus, (c) about 17 mg/ml propylene glycol and (d) water for injection.
16. The formulation according to claim 14, wherein the formulation comprises (a) monobasic potassium phosphate in an amount of about 2.02 mg/ml or about 0.015 mmol/ml of phosphorus, (b) dibasic potassium phosphate in an amount of about 2.12 mg/ml or about 0.012 mmol/ml of phosphorus, (c) about 7 mg/ml sodium chloride and (d) water for injection.
17. The formulation according to claim 1, wherein the formulation comprises about 0.055 mmol/ml of phosphorus.
18. The formulation according to claim 17, wherein the formulation comprises (a) monobasic potassium phosphate in an amount of about 4.11 mg/ml or about 0.030 mmol/ml of phosphorus, (b) dibasic potassium phosphate in an amount of about 4.33 mg/ml or about 0.025 mmol/ml of phosphorus, (c) about 17.3 mg/ml propylene glycol and (d) water for injection.
19. The formulation according to claim 17, wherein the formulation comprises comprises (a) monobasic potassium phosphate in an amount of about 4.11 mg/ml or about 0.030 mmol/ml of phosphorus, (b) dibasic potassium phosphate in an amount of about 4.33 mg/ml or about 0.025 mmol/ml of phosphorus, (c) about 5.5 mg/ml sodium chloride and (d) water for injection.
20. The formulation according to claim 1, wherein the formulation comprises about 0.068 mmol/ml of phosphorus.
21. The formulation according to claim 20, wherein the formulation comprises (a) monobasic potassium phosphate in an amount of about 5.08 mg/ml or about 0.037 mmol/ml of phosphorus, (b) dibasic potassium phosphate in an amount of about 5.35 mg/ml or about 0.031 mmol/ml of phosphorus, (c) about 11.65 mg/ml propylene glycol and (d) water for injection.
22. The formulation according to claim 20 wherein the formulation comprises (a) monobasic potassium phosphate in an amount of about 5.08 mg/ml or about 0.037 mmol/ml of phosphorus, (b) dibasic potassium phosphate in an amount of about 5.35 mg/ml or about 0.031 mmol/ml of phosphorus, (c) about 5.2 mg/ml sodium chloride and (d) water for injection.
23. The formulation according to claim 1, wherein the formulation comprises about 0.18 mmol/ml of phosphorus.
24. The formulation according to claim 23, wherein the formulation comprises (a) monobasic potassium phosphate in an amount of about 13.44 mg/ml or about 0.099 mmol/ml of phosphorus, (b) dibasic potassium phosphate in an amount of about 14.16 mg/ml or about 0.081 mmol/ml of phosphorus, and (c) water for injection, wherein such formulation is free of any tonicity adjusting agent.
25. The formulation of claim 1, wherein the formulation has a pH from about 5.5 to about 7.5.
26. A method of treating hypophosphatemia to a subject in need thereof by administering the ready-to-use injectable formulation according to claim 1.