Name: Calcium Phosphate, Dibasic Dihydrate
CAS No: Dibasic calcium phosphate dihydrate [7789-77-7]
BP: Calcium Hydrogen Phosphate JP: Dibasic Calcium Phosphate Hydrate PhEur: Calcium Hydrogen Phosphate Dihydrate USP: Dibasic Calcium Phosphate Dihydrate
Calcii hydrogenophosphas dihydricus; calcium hydrogen orthophosphate dihydrate; calcium monohydrogen phosphate dihydrate; DiCafos; dicalcium orthophosphate; DI-TAB; E341; Emcompress; phosphoric acid calcium salt (1 : 1) dihydrate; secondary calcium phosphate.
Dibasic calcium phosphate dihydrate [7789-77-7]
CaHPO42H2O 172.09
See Section 4.
Dibasic calcium phosphate dihydrate is widely used in tablet formulations both as an excipient and as a source of calcium and phosphorus in nutritional supplements.(1–8) It is one of the more widely used materials, 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 coarsegrade material. The predominant deformation mechanism of 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, dibasic calcium phosphate dihydrate is abrasive and a lubricant is required for tableting, for example about 1% w/w of magnesium stearate or about 1% w/w of sodium stearyl fumarate is commonly used. Two main particle-size grades of dibasic calcium phosphate dihydrate are used in the pharmaceutical industry. The milled material is typically used in wet-granulated, roller-compacted or slugged formulations. The ‘unmilled’ or coarse-grade material is typically used in direct-compression formulations. Dibasic calcium phosphate dihydrate is nonhygroscopic and stable at room temperature. However, under certain conditions of temperature and humidity, it can lose water of crystallization below 1008C. This has implications for certain types of packaging and aqueous film coating since the loss of water of crystallization appears to be initiated by high humidity and by implication high moisture vapor concentrations in the vicinity of the dibasic calcium phosphate dihydrate particles.(8) Dibasic calcium phosphate dihydrate is also used in toothpaste and dentifrice formulations for its abrasive properties
Dibasic calcium phosphate dihydrate is a white, odorless, tasteless powder or crystalline solid. It occurs as monoclinic crystals.
See Table I. See also Section 18.
Acidity/alkalinity pH = 7.4 (20% slurry of DI-TAB) Angle of repose 28.38 for Emcompress. (9) Density (bulk) 0.915 g/cm3 Density (tapped) 1.17 g/cm3 Density (true) 2.389 g/cm3 Flowability 27.3 g/s for DI-TAB;11.4 g/s for Emcompress. (9) Melting point Dehydrates below 1008C. Moisture content Dibasic calcium phosphate dihydrate contains two molecules of water of crystallization, which can be lost at temperatures well below 1008C. NIR spectra see Figure 1. Particle size distribution DI-TAB: average particle diameter 180 mm; fine powder: average particle diameter 9 mm. Solubility Practically insoluble in ethanol, ether, and water; soluble in dilute acids. Specific surface area 0.44–0.46 m2 /g for Emcompress.
Dibasic calcium phosphate dihydrate is a nonhygroscopic, relatively stable material. However, under certain conditions the dihydrate can lose water of crystallization. This has implications for both storage of the bulk material and coating and packaging of tablets containing dibasic calcium phosphate dihydrate. The bulk material should be stored in a well-closed container in a cool, dry place.
Dibasic calcium phosphate dihydrate should not be used to formulate tetracycline antibiotics.(10) Dibasic calcium phosphate dihydrate has been reported to be incompatible with indomethacin,(11) aspirin,(12) aspartame,(13) ampicillin,(14) cephalexin,(15) and erythromycin.(16) The surface of dibasic calcium phosphate dihydrate is alkaline(16) and consequently it should not be used with drugs that are sensitive to alkaline pH.
Calcium phosphates are usually manufactured by reacting very pure phosphoric acid with calcium hydroxide, Ca(OH)2 obtained from limestone, in stoichiometric ratio in aqueous suspension 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 dihydrate is widely used in oral pharmaceutical products, food products, and toothpastes, and is generally regarded as a nontoxic and nonirritant material. However, oral ingestion of large quantities may cause abdominal discomfort.
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 anhydrous; calcium phosphate, tribasic.
Dibasic calcium phosphate dihydrate 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 dibasic calcium phosphate dihydrate available for direct compression include Calstar (FMC Biopolymer), Di-Cafos (Chemische Fabrik Budenheim), DI-TAB (Innophos), and Emcompress (JRS Pharma LP). Accelerated stability studies carried out at elevated temperatures on formulations containing significant proportions of dibasic SEM 3: Excipient: dibasic calcium phosphate dihydrate; manufacturer: Innophos; lot no.: 16A-1 (89); magnification: 120. SEM 4: Excipient: dibasic calcium phosphate dihydrate, coarse grade; manufacturer: Innophos; lot no.: 16A-1 (89); magnification: 600. 1.5 0.0 1500 2300 1930 1956 1994 1969 1945 1911 1408 1514 1425 1475 1499 1300 1700 1900 2100 2500 1000 × [2nd deriv. log(1/R)] Wavelength/nm 1100 −3.0 0.8 log(1/R) −0.2 Figure 1: Near-infrared spectrum of dibasic calcium phosphate dihydrate measured by reflectance. C 98 Calcium Phosphate, Dibasic Dihydrate calcium phosphate dihydrate can give erroneous results owing to irreversible dehydration of the dihydrate to the anhydrous form. Depending on the type of packaging and whether or not the tablet is coated, the phenomenon can be observed at temperatures as low as 408C after 6 weeks of storage. As the amount of dibasic calcium phosphate dihydrate in the tablet is reduced, the effect is less easy to observe. The EINECS number for calcium phosphate is 231-837-1. The PubChem Compound ID (CID) for dibasic calcium phosphate dibydrate is 104805.