Sodium Phosphate, Monobasic

Basic Information

Name: Sodium Phosphate, Monobasic

CAS No: Anhydrous monobasic sodium phosphate [7558-80-7], Monobasic sodium phosphate monohydrate [10049-21-5], Monobasic sodium phosphate dihydrate [13472-35-0]

Functional Categories

Buffering agent Emulsifying agent Sequestering agent

1. Nonproprietary Names

BP: Anhydrous Sodium Dihydrogen Phosphate Sodium Dihydrogen Phosphate Monohydrate Sodium Dihydrogen Phosphate Dihydrate PhEur: Sodium Dihydrogen Phosphate Dihydrate USP: Monobasic Sodium Phosphate

2. Synonyms

Acid sodium phosphate; E339; Kalipol 32; monosodium orthophosphate; monosodium phosphate; natrii dihydrogenophosphas dihydricus; phosphoric acid, monosodium salt; primary sodium phosphate; sodium biphosphate; sodium dihydrogen orthophosphate; sodium dihydrogen phosphate.

3. Chemical Name & CAS Registry

Anhydrous monobasic sodium phosphate [7558-80-7], Monobasic sodium phosphate monohydrate [10049-21-5], Monobasic sodium phosphate dihydrate [13472-35-0]

4. Empirical Formula & Molecular Weight

NaH2PO4 119.98 NaH2PO4H2O 137.99 NaH2PO42H2O 156.01

5. Structural Formula

See Section 4.

6. Applications

Monobasic sodium phosphate is used in a wide variety of pharmaceutical formulations as a buffering agent and as a sequestering agent. Therapeutically, monobasic sodium phosphate is used as a mild saline laxative and in the treatment of hypophosphatemia.(1–3) Monobasic sodium phosphate is also used in food products, for example, in baking powders, and as a dry acidulant and sequestrant.

7. Description

The USP 32 states that monobasic sodium phosphate contains one or two molecules of water of hydration or is anhydrous. The hydrated forms of monobasic sodium phosphate occur as odorless, colorless or white, slightly deliquescent crystals. The anhydrous form occurs as a white crystalline powder or granules

8. Pharmacopeial Specifications

See Table I.

9. Typical Properties

Acidity/alkalinity pH = 4.1–4.5 for a 5% w/v aqueous solution of the monohydrate at 258C. Density 1.915 g/cm3 for the dihydrate. Dissociation constant pKa = 2.15 at 258C NIR spectra see Figures 1 and 2. Solubility Soluble 1 in 1 of water; very slightly soluble in ethanol (95%).

10. Stability & Storage

Monobasic sodium phosphate is chemically stable, although it is slightly deliquescent. On heating at 1008C, the dihydrate loses all of its water of crystallization. On further heating, it melts with decomposition at 2058C, forming sodium hydrogen pyrophosphate, Na2H2P2O7. At 2508C it leaves a final residue of sodium metaphosphate, NaPO3. Aqueous solutions are stable and may be sterilized by autoclaving. Monobasic sodium phosphate should be stored in an airtight container in a cool, dry place.

11. Incompatibilities

Monobasic sodium phosphate is an acid salt and is therefore generally incompatible with alkaline materials and carbonates; aqueous solutions of monobasic sodium phosphate are acidic and will cause carbonates to effervesce. Monobasic sodium phosphate should not be administered concomitantly with aluminum, calcium, or magnesium salts since they bind phosphate and could impair its absorption from the gastrointestinal tract. Interaction between calcium and phosphate, leading to the formation of insoluble calcium phosphate precipitates, is possible in parenteral admixtures.(4–6)

12. Method of Manufacture

Monobasic sodium phosphate is prepared by adding phosphoric acid to a hot, concentrated solution of disodium phosphate until the liquid ceases to form a precipitate with barium chloride. This solution is then concentrated and the monobasic sodium phosphate is crystallized

13. Safety

Monobasic sodium phosphate is widely used as an excipient in parenteral, oral, and topical pharmaceutical formulations. Phosphate occurs extensively in the body and is involved in many physiological processes since it is the principal anion of intracellular fluid. Most foods contain adequate amounts of phosphate, making hypophosphatemia(1) virtually unknown except in certain disease states(2) or in patients receiving total parenteral nutrition. Treatment is usually by the oral administration of up to 100 mmol of phosphate daily. Approximately two-thirds of ingested phosphate is absorbed from the gastrointestinal tract, virtually all of it being excreted in the urine, and the remainder is excreted in the feces. Excessive administration of phosphate, particularly intravenously, rectally, or in patients with renal failure, can cause hyperphosphatemia that may lead to hypocalcemia or other severe electrolyte imbalances.(7–9) Adverse effects occur less frequently following oral consumption, although phosphates act as mild saline laxatives when administered orally or rectally (2–4 g of monobasic sodium phosphate in an aqueous solution is used as a laxative). Consequently, gastrointestinal disturbances including diarrhea, nausea, and vomiting may occur following the use of monobasic sodium phosphate as an excipient in oral formulations. However, the level of monobasic sodium phosphate used as an excipient in a pharmaceutical formulation is not usually associated with adverse effects. LD50 (rat, IM): 0.25 g/kg(10) LD50 (rat, oral): 8.29 g/kg

14. Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of material handled. Monobasic sodium phosphate may be irritant to the skin, eyes, and mucous membranes. Eye protection and gloves are recommended.

15. Regulatory Status

GRAS listed. Accepted for use as a food additive in Europe. Included in the FDA Inactive Ingredients Database (injections; infusions; ophthalmic, oral, topical, and vaginal preparations). Included in nonparenteral and parenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients

16. Related Substances

Dibasic sodium phosphate; monobasic potassium phosphate. Monobasic potassium phosphate Empirical formula KH2PO4 Molecular weight 136.09 CAS number [7778-77-0] Synonyms E340; monopotassium phosphate; potassium acid phosphate; potassium biphosphate; potassium dihydrogen orthophosphate. Appearance Colorless crystals or a white, odorless, granular or crystalline powder. Acidity/alkalinity pH  4.5 for a 1% w/v aqueous solution at 258C. Solubility Freely soluble in water; practically insoluble in ethanol (95%). Comments 1 g of monobasic potassium phosphate represents approximately 7.3 mmol of potassium and of phosphate. The EINECS number for monobasic potassium phosphate is 231-913-4

17. Comments

One gram of anhydrous monobasic sodium phosphate represents approximately 8.3 mmol of sodium and of phosphate. One gram of monobasic sodium phosphate monohydrate represents approximately 7.2 mmol of sodium and of phosphate. One gram of monobasic sodium phosphate dihydrate represents approximately 6.4 mmol of sodium and of phosphate. A specification for sodium phosphate monobasic is contained in the Food Chemicals Codex (FCC).(11) The EINECS number for monobasic sodium phosphate is 231- 449-2. The PubChem Compound ID (CID) for monobasic sodium phosphate dihydrate is 23673460.