Calcium Sulfate

Basic Information

Name: Calcium Sulfate

CAS No: Calcium sulfate [7778-18-9] Calcium sulfate dihydrate [10101-41-4]

Functional Categories

Desiccant Tablet and capsule diluent

1. Nonproprietary Names

BP: Calcium Sulphate Dihydrate PhEur: Calcium Sulphate Dihydrate USP-NF: Calcium Sulfate

2. Synonyms

Calcium sulfate anhydrous anhydrite; anhydrous gypsum; anhydrous sulfate of lime; Destab; Drierite; E516; karstenite; muriacite; Snow White. Calcium sulfate dihydrate alabaster; calcii sulfas dihydricus; CalTab; Compactrol; Destab; E516; gypsum; light spar; mineral white; native calcium sulfate; precipitated calcium sulfate; satinite; satin spar; selenite; terra alba; USG Terra Alba.

3. Chemical Name & CAS Registry

Calcium sulfate [7778-18-9] Calcium sulfate dihydrate [10101-41-4]

4. Empirical Formula & Molecular Weight

CaSO4 136.14 CaSO42H2O 172.17

5. Structural Formula

See Section 4.

6. Applications

Calcium sulfate dihydrate is used in the formulation of tablets and capsules. In granular form it has good compaction properties and moderate disintegration properties.(1,2) Calcium sulfate hemihydrate (see Section 17), is used in the preparation of plaster of Paris bandage, which is used for the immobilization of limbs and fractures; it should not be used in the formulation of tablets or capsules. Anhydrous calcium sulfate is hygroscopic and is used as a desiccant. The uptake of water can cause the tablets to become very hard and to fail to disintegrate on storage. Therefore, anhydrous calcium sulfate is not recommended for the formulation of tablets, capsules, or powders for oral administration. Therapeutically, calcium sulfate is used in dental and craniofacial surgical procedures.(3,4)

7. Description

Both calcium sulfate and calcium sulfate dihydrate are white or offwhite, fine, odorless, and tasteless powder or granules.

8. Pharmacopeial Specifications

See Table I.

9. Typical Properties

Acidity/alkalinity pH = 7.3 (10% slurry) for dihydrate; pH = 10.4 (10% slurry) for anhydrous material. Angle of repose 37.68 for Compactrol. (2) Compressibility see Figure 1. Density (bulk) 0.94 g/cm3 for Compactrol; (2) 0.67 g/cm3 for dihydrate; 0.70 g/cm3 for anhydrous material. Density (tapped) 1.10 g/cm3 for Compactrol; (2) 1.12 g/cm3 for dihydrate; 1.28 g/cm3 for anhydrous material. Density (true) 2.308 g/cm3 Flowability 48.4% (Carr compressibility index); 5.2 g/s for Compactrol. (2) Melting point 14508C for anhydrous material. NIR spectra see Figure 2. Particle size distribution 93% less than 45 mm in size for the dihydrate (USG Terra Alba); 97% less than 45 mm in size for the anhydrous material (Snow White). Average particle size is 17 mm for the dihydrate and 8 mm for the anhydrous material. For Compactrol, not less than 98% passes through a #40 screen (425 mm), and not less than 85% is retained in a #140 screen (100 mm). Solubility see Table II. Specific gravity 2.32 for dihydrate; 2.96 for anhydrous material. Specific surface area 3.15 m2 /g (Strohlein apparatus)

10. Stability & Storage

Calcium sulfate is chemically stable. Anhydrous calcium sulfate is hygroscopic and may cake on storage. Store in a well-closed container in a dry place, avoiding heat.

11. Incompatibilities

In the presence of moisture, calcium salts may be incompatible with amines, amino acids, peptides, and proteins, which may form complexes. Calcium salts will interfere with the bioavailability of tetracycline antibiotics.(5) It is also anticipated that calcium sulfate would be incompatible with indomethacin,(6) aspirin,(7) aspartame,(8) ampicillin,(9) cephalexin,(10) and erythromycin(11) since these materials are incompatible with other calcium salts. Calcium sulfate may react violently, at high temperatures, with phosphorus and aluminum powder; it can react violently with diazomethane

12. Method of Manufacture

Anhydrous calcium sulfate occurs naturally as the mineral anhydrite. The naturally occurring rock gypsum may be crushed and ground for use as the dihydrate or calcined at 1508C to produce the hemihydrate. A purer variety of calcium sulfate may also be obtained chemically by reacting calcium carbonate with sulfuric acid or by precipitation from calcium chloride and a soluble sulfate

13. Safety

Calcium sulfate dihydrate is used as an excipient in oral capsule and tablet formulations. At the levels at which it is used as an excipient, it is generally regarded as nontoxic. However, ingestion of a sufficiently large quantity can result in obstruction of the upper intestinal tract after absorption of moisture. Owing to the limited intestinal absorption of calcium from its salts, hypercalcemia cannot be induced even after the ingestion of massive oral doses. Calcium salts are soluble in bronchial fluid. Pure salts do not induce pneumoconiosis.

14. Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of material handled. The fine-milled grades can generate nuisance dusts that may be irritant to the eyes or on inhalation. The use of a respirator or dust mask is recommended to prevent excessive powder inhalation since excessive inhalation may saturate the bronchial fluid, leading to precipitation and thus blockage of the air passages.

15. Regulatory Status

GRAS listed. Accepted for use as a food additive in Europe. Included in the FDA Inactive Ingredients Database (oral capsules, sustained release, tablets). Included in nonparenteral medicines licensed in the UK and Europe. Included in the Canadian List of Acceptable Non-medicinal Ingredients.

16. Related Substances

Calcium phosphate, dibasic anhydrous; calcium phosphate, dibasic dihydrate; calcium phosphate, tribasic; calcium sulfate hemihydrate. Calcium sulfate hemihydrate Empirical formula CaSO4 1=2H2O Molecular weight 145.14 CAS number [26499-65-0] Synonyms annalin; calcii sulfas hemihydricus; calcined gypsum; dried calcium sulfate; dried gypsum; E516; exsiccated calcium sulfate; plaster of Paris; sulfate of lime; yeso blanco. Appearance A white or almost white, odorless, crystalline, hygroscopic powder. Solubility Practically insoluble in ethanol (95%); slightly soluble in water; more soluble in dilute mineral acids. Comments The BP 2009 defines dried calcium sulfate as predominantly the hemihydrate, produced by drying powdered gypsum (CaSO42H2O) at about 1508C, in a controlled manner, such that minimum quantities of the anhydrous material are produced. Dried calcium sulfate may also contain suitable setting accelerators or decelerators.

17. Comments

Calcium sulfate will absorb moisture and therefore should be used with caution in the formulation of products containing drugs that easily decompose in the presence of moisture. A specification for calcium sulfate is contained in the Food Chemicals Codex (FCC).(12) The EINECS number for calcium sulfate is 231-900-3. The PubChem Compound ID (CID) for cacium sulfate is 24497