Name: Calcium Phosphate, Tribasic
CAS No: Calcium hydroxide phosphate [12167-74-7], Tricalcium orthophosphate [7758-87-4]
BP: Calcium Phosphate PhEur: Calcium Phosphate USP-NF: Tribasic Calcium Phosphate
Calcium orthophosphate; E341(iii); hydroxylapatite; phosphoric acid calcium salt (2 : 3); precipitated calcium phosphate; tertiary calcium phosphate; Tri-Cafos; tricalcii phosphas; tricalcium diorthophosphate; tricalcium orthophosphate; tricalcium phosphate; TRI-CAL WG; TRI-TAB.
Calcium hydroxide phosphate [12167-74-7], Tricalcium orthophosphate [7758-87-4]
Ca3(PO4)2 310.20 Ca5(OH)(PO4)3 502.32
See Sections 3 and 4.
Tribasic calcium phosphate is widely used as a capsule diluent and tablet filler/binder in either direct-compression or wet-granulation processes. The primary bonding mechanism in compaction is plastic deformation. As with dibasic calcium phosphate, a lubricant and a disintegrant should usually be incorporated in capsule or tablet formulations that include tribasic calcium phosphate. In some cases tribasic calcium phosphate has been used as a disintegrant.(1) It is most widely used in vitamin and mineral preparations(2) as a filler and as a binder. It is a source of both calcium and phosphorus, the two main osteogenic minerals for bone health. The bioavailability of the calcium is well known to be improved by the presence of cholecalciferol. Recent research reports that combinations of tribasic calcium phosphate and vitamin D3 are a cost-effective advance in bone fracture prevention.(3) In food applications, tribasic calcium phosphate powder is widely used as an anticaking agent. See Section 18. See also Calcium phosphate, dibasic dihydrate
The PhEur 6.4 states that tribasic calcium phosphate consists of a mixture of calcium phosphates. It contains not less than 35.0% and not more than the equivalent of 40.0% of calcium. The USP32– NF27 specifies that tribasic calcium phosphate consists of variable mixtures of calcium phosphates having the approximate composition 10CaO3P2O5H2O. This corresponds to a molecular formula of Ca5(OH)(PO4)3 or Ca10(OH)2(PO4)6. Tribasic calcium phosphate is a white, odorless and tasteless powder.
See Table I.
Acidity/alkalinity pH = 6.8 (20% slurry in water) Density 3.14 g/cm3 Density (bulk) 0.3–0.4 g/cm3 for powder form; 0.80 g/cm3 for granular TRI-TAB. (4) Density (tapped) 0.95 g/cm3 for granular TRI-TAB. (4) Flowability 25.0 g/s for granular TRI-TAB. (4) Melting point 16708C Moisture content Slightly hygroscopic. A well-defined crystalline hydrate is not formed, although surface moisture may be picked up or contained within small pores in the crystal structure. At relative humidities between about 15% and 65%, the equilibrium moisture content at 258C is about 2.0%. At relative humidities above about 75%, tribasic calcium phosphate may absorb small amounts of moisture. NIR spectra see Figure 1.Particle size distribution Tribasic calcium phosphate powder: typical particle diameter 5–10 mm; 98% of particles <44 mm. TRI-CAL WG: average particle diameter 180 mm; 99% of particles <420 mm, 46% <149 mm, and 15% <44 mm. TRI-TAB: average particle diameter 350 mm; 97% of particles <420 mm, and 2% <149 mm. Solubility Soluble in dilute mineral acids; very slightly soluble in water; practically insoluble in acetic acid and alcohols. Specific surface area 70–80 m2 /g(4)
Tribasic calcium phosphate is a chemically stable material, and is also not liable to cake during storage. The bulk material should be stored in a well-closed container in a cool, dry place.
All calcium salts are incompatible with tetracycline antibiotics. Tribasic calcium phosphate is incompatible with tocopheryl acetate (but not tocopheryl succinate). Tribasic calcium phosphate may form sparingly soluble phosphates with hormones.
Tribasic calcium phosphate occurs naturally as the minerals hydroxylapatite, voelicherite, and whitlockite. Commercially, it is prepared by treating phosphate-containing rock with sulfuric acid. Tribasic calcium phosphate powder is then precipitated by the addition of calcium hydroxide. Tribasic calcium phosphate is alternatively prepared by treating calcium hydroxide from limestone with purified phosphoric acid. It may also be obtained from calcined animal bones.(5) Some tribasic calcium phosphate products may be prepared in coarser, directly compressible forms by granulating the powder using roller compaction or spray drying.
Tribasic calcium phosphate is widely used in oral pharmaceutical formulations and food products, and is generally regarded as nontoxic and nonirritant at the levels employed as a pharmaceutical excipient. Ingestion or inhalation of excessive quantities may result in the deposition of tribasic calcium phosphate crystals in tissues. These crystals may lead to inflammation and cause tissue lesions in the areas of deposition. Oral ingestion of very large quantities of tribasic calcium phosphate may cause abdominal discomfort such as nausea and vomiting No teratogenic effects were found in chicken embryos exposed to a dose of 2.5 mg of tribasic calcium phosphate.(6) LD50 (rat, oral): >1 g/kg(4)
Observe normal precautions appropriate to the circumstances and quantity of material handled. Eye protection and gloves are recommended. Handle in a well-ventilated environment since dust inhalation may be an irritant. For processes generating large amounts of dust, the use of a respirator is recommended.
GRAS listed. Accepted for use as a food additive in Europe. Included in the FDA Inactive Ingredients Database (oral capsules and tablets). Included in nonparenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients.
Calcium phosphate, dibasic anhydrous; calcium phosphate, dibasic dihydrate.
One gram of tribasic calcium phosphate represents approximately 10.9 mmol of calcium and 6.4 mmol of phosphate; 38% calcium and 17.3% phosphorus by weight.(4) Tribasic calcium phosphate provides a higher calcium load than dibasic calcium phosphate and a higher Ca/P ratio. Granular and fine powder forms of tribasic calcium phosphate are available from various manufacturers. A specification for calcium phosphate tribasic is contained in the Food Chemicals Codex (FCC).(7) The EINECS number for calcium phosphate is 231-837-1. The PubChem Compound ID (CID) for tribasic calcium phosphate includes 24456 and 516943.