Name: Calcium Phosphate, Dibasic Anhydrous
CAS No: Dibasic calcium phosphate [7757-93-9]
BP: Anhydrous Calcium Hydrogen Phosphate JP: Anhydrous Dibasic Calcium Phosphate PhEur: Calcium Hydrogen Phosphate, Anhydrous USP: Anhydrous Dibasic Calcium Phosphate
A-TAB; calcii hydrogenophosphas anhydricus; calcium monohydrogen phosphate; calcium orthophosphate; Di-Cafos AN; dicalcium orthophosphate; E341; Emcompress Anhydrous; Fujicalin; phosphoric acid calcium salt (1 : 1); secondary calcium phosphate.
Dibasic calcium phosphate [7757-93-9]
CaHPO4 136.06
See Section 4.
Anhydrous dibasic calcium phosphate is used both as an excipient and as a source of calcium in nutritional supplements. It is used particularly in the nutritional/health food sectors. It is also used in pharmaceutical products because of its compaction properties, and the good flow properties of the coarse-grade material.(1–5) The predominant deformation mechanism of anhydrous dibasic calcium phosphate coarse-grade is brittle fracture and this reduces the strain-rate sensitivity of the material, thus allowing easier transition from the laboratory to production scale. However, unlike the dihydrate, anhydrous dibasic calcium phosphate when compacted at higher pressures can exhibit lamination and capping. This phenomenon can be observed when the material represents a substantial proportion of the formulation, and is exacerbated by the use of deep concave tooling. This phenomenon also appears to be independent of rate of compaction. Anhydrous dibasic calcium phosphate is abrasive and a lubricant is required for tableting, for example 1% w/w magnesium stearate or 1% w/w sodium stearyl fumarate. Two particle-size grades of anhydrous dibasic calcium phosphate are used in the pharmaceutical industry. Milled material is typically used in wet-granulated or roller-compacted formulations. The ‘unmilled’ or coarse-grade material is typically used in directcompression formulations. Anhydrous dibasic calcium phosphate is nonhygroscopic and stable at room temperature. It does not hydrate to form the dihydrate. Anhydrous dibasic calcium phosphate is used in toothpaste and dentifrice formulations for its abrasive properties.
Anhydrous dibasic calcium phosphate is a white, odorless, tasteless powder or crystalline solid. It occurs as triclinic crystals.
See Table I. See also Section 18.
Acidity/alkalinity pH = 7.3 (20% slurry); pH = 5.1 (20% slurry of A-TAB); pH = 6.1–7.2 (5% slurry of Fujicalin). Angle of repose 328 (for Fujicalin) Density 2.89 g/cm3 Density (bulk) 0.78 g/cm3 for A-TAB; 0.45 g/cm3 for Fujicalin. Density (tapped) 0.82 g/cm3 for A-TAB; 0.46 g/cm3 for Fujicalin. Melting point Does not melt; decomposes at 4258C to form calcium pyrophosphate. SEM 1: Excipient: Emcompress Anhydrous; manufacturer: JRS Pharma LP; magnification: 50; voltage: 5 kV. SEM 2: Excipient: Emcompress Anhydrous; manufacturer: JRS Pharma LP; magnification: 200; voltage: 5 kV Moisture content Typically 0.1–0.2%. The anhydrous material contains only surface-adsorbed moisture and cannot be rehydrated to form the dihydrate. NIR spectra see Figure 1. Particle size distribution A-TAB: average particle diameter 180 mm; Emcompress Anhydrous: average particle diameter 136 mm; Fujicalin: average particle diameter 94 mm; Powder: average particle diameter: 15 mm. Solubility Practically insoluble in ether, ethanol, and water; soluble in dilute acids. Specific surface area 20–30 m2 /g for A-TAB; 35 m2 /g for Fujicalin.
Dibasic calcium phosphate anhydrous is a nonhygroscopic, relatively stable material. Under conditions of high humidity it does not hydrate to form the dihydrate. The bulk material should be stored in a well-closed container in a dry place.
Dibasic calcium phosphate should not be used to formulate tetracyline antibiotics.(6) The surface of milled anhydrous dibasic calcium phosphate is alkaline(2) and consequently it should not be used with drugs that are sensitive to alkaline pH. However, reports(7,8) suggest there are differences in the surface alkalinity/acidity between the milled and unmilled grades of anhydrous dibasic calcium phosphate; the unmilled form has an acidic surface environment. This difference has important implications for drug stability, particularly when reformulating from, e.g. roller compaction to direct compression, when the particle size of the anhydrous dibasic calcium phosphate might be expected to change. Dibasic calcium phosphate dihydrate has been reported to be incompatible with a number of drugs and excipients, and many of these incompatibilities are expected to occur with dibasic calcium phosphate, anhydrous; see Calcium phosphate, dibasic dihydrate.
Calcium phosphates are usually prepared by reacting very pure phosphoric acid with calcium hydroxide, Ca(OH)2 obtained from limestone, in stoichiometric ratio in aqueous suspension(2) followed by drying at a temperature that will allow the correct hydration state to be achieved. After drying, the coarse-grade material is obtained by means of a classification unit; the fine particle-size material is obtained by milling. Dibasic calcium phosphate, anhydrous, may also be prepared by spray-drying.(5,9)
Dibasic calcium phosphate anhydrous is widely used in oral pharmaceutical products, food products, and toothpastes, and is generally regarded as a relatively nontoxic and nonirritant material.
Observe normal precautions appropriate to the circumstances and quantity of material handled. The fine-milled grades can generate nuisance dusts and the use of a respirator or dust mask may be necessary.
GRAS listed. Accepted as a food additive in Europe. Included in the FDA Inactive Ingredients Database (oral capsules and tablets). Included in nonparenteral medicines licensed in Europe. Included in the Canadian List of Acceptable Non-medicinal Ingredients.
Calcium phosphate, dibasic dihydrate; calcium phosphate, tribasic; calcium sulfate
Anhydrous dibasic calcium phosphate is one of the materials that have been selected for harmonization by the Pharmacopeial Discussion Group. For further information see the General Information Chapter <1196> in the USP32–NF27, the General Chapter 5.8 in PhEur 6.0, along with the ‘State of Work’ document on the PhEur EDQM website, and also the General Information Chapter 8 in the JP XV. Grades of anhydrous dibasic calcium phosphate available for direct compression include A-TAB (Innophos), Di-Cafos AN (Chemische Fabrik Budenheim), Emcompress Anhydrous (JRS Pharma LP), and Fujicalin (Fuji Chemical Industry Co. Ltd.). A study has examined the use of calcium phosphate in reducing microbial contamination during direct compression in tableting.(10) The EINECS number for calcium phosphate is 231-837-1. The PubChem Compound ID (CID) for anhydrous dibasic calcium phosphate is 24441.