Printed from: Pharmaceutical Excipients. [online] London: Pharmaceutical Press.

Calcium Carbonate
1. Nonproprietary Names
BP: JP: PhEur: USP: Calcium Carbonate Precipitated Calcium Carbonate Calcium Carbonate Calcium Carbonate

2. Synonyms
Balcarb; Cal-Carb; calcii carbonas; calcii carbonas praecipitatus; calcium carbonate (1 : 1); Calopake; carbonic acid calcium salt (1 : 1); creta preparada; Destab; E170; MagGran CC; Pharma-Carb; precipitated calcium carbonate; precipitated carbonate of lime; precipitated chalk; Sturcal; Vicality; Vivapress; Witcarb.

3. Chemical Name and CAS Registry Number

Carbonic acid, calcium salt (1 : 1) 471-34-1

4. Empirical Formula and Molecular Weight

CaCO3 100.09

5. Structural Formula
See Section 4.

6. Functional Category
Buffering agent; coating agent; colorant; opacifier; tablet binder; tablet and capsule diluent; therapeutic agent.

7. Applications in Pharmaceutical Formulation or Technology

Calcium carbonate, employed as a pharmaceutical excipient, is mainly used in solid-dosage forms as a diluent.15 It is also used as a base for medicated dental preparations,6 as a buffering agent, and as a dissolution aid in dispersible tablets. Calcium carbonate is used as a bulking agent in tablet sugar-coating processes and as an opacifier in tablet film-coating. Calcium carbonate is also used as a food additive and therapeutically as an antacid and calcium supplement.

8. Description
Calcium carbonate occurs as an odorless and tasteless white powder or crystals.
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See SEM 1, SEM 2, SEM 3, SEM 4, SEM 5, SEM 6.

9. Pharmacopeial Specifications
See Table I. See also Section 18.

10. Typical Properties

Acidity/alkalinity pH = 9.0 (10% w/v aqueous dispersion) Density (bulk) 0.8 g/cm3 Density (tapped) 1.2 g/cm3 Flowability Cohesive. Melting point Decomposes at 825C. Moisture content see Figure 1. NIR spectra see Figure 2. Particle size see Figure 3. Refractive index 1.59 Solubility Practically insoluble in ethanol (95%) and water. Solubility in water is increased by the presence of ammonium salts or carbon dioxide. The presence of alkali hydroxides reduces solubility. Specific gravity 2.7 Specific surface area 6.216.47 m2/g

11. Stability and Storage Conditions

Calcium carbonate is stable and should be stored in a well-closed container in a cool, dry place.

12. Incompatibilities
Incompatible with acids and ammonium salts (see also Sections 10 and 18).

13. Method of Manufacture

Calcium carbonate is prepared by double decomposition of calcium chloride and sodium bicarbonate in aqueous solution. Density and fineness are governed by the concentrations of the solutions. Calcium carbonate is also obtained from the naturally occurring minerals aragonite, calcite, and vaterite.

14. Safety
Calcium carbonate is mainly used in oral pharmaceutical formulations and is generally regarded as a nontoxic material. However, calcium carbonate administered orally may cause constipation and flatulence. Consumption of large quantities (460 g daily) may also result in hypercalcemia
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or renal impairment.7 Therapeutically, oral doses of up to about 1.5 g are employed as an antacid. In the treatment of hyperphosphatemia in patients with chronic renal failure, oral daily doses of 2.517 g have been used. Calcium carbonate may interfere with the absorption of other drugs from the gastrointestinal tract if administered concomitantly. LD50 (rat, oral): 6.45 g/kg

15. Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of material handled. Calcium carbonate may be irritant to the eyes and on inhalation. Eye protection, gloves, and a dust mask are recommended. Calcium carbonate should be handled in a well-ventilated environment. In the UK, the long-term (8-hour TWA) workplace exposure limit for calcium carbonate is 10 mg/m3 for total inhalable dust and 4 mg/m3 for respirable dust.8

16. Regulatory Status

GRAS listed. Accepted for use as a food additive in Europe. Included in the FDA Inactive Ingredients Database (buccal chewing gum, oral capsules and tablets; otic solutions; respiratory inhalation solutions). Included in nonparenteral medicines licensed in the UK. Included in the Canadian Natural Health Products Ingredients Database.

17. Related Substances

18. Comments
Calcium carbonate 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 USP33NF28, the General Chapter 5.8 in PhEur 7.0, along with the 'State of Work' document on the PhEur EDQM website, and also the General Information Chapter 8 in the JP XV. When calcium carbonate is used in tablets containing aspirin and related substances, traces of iron may cause discoloration. This may be overcome by inclusion of a suitable chelating agent. Grades with reduced lead levels are commercially available for use in antacids and calcium supplements. Directly compressible grades containing only calcium carbonate are commercially available, such as MagGran CC (Magnesia GmbH). Barcroft CS90 (SPI Pharma) is a directly compressible grade containing 10% starch and Calci-Press MD (Particle Dynamics Inc.) is a directly compressible blend of calcium carbonate and maltodextrin. A specification for calcium carbonate is contained in the Food Chemicals Codex (FCC).8 The EINECS number for calcium carbonate is 207-439-9. The PubChem Compound ID (CID) for calcium carbonate includes 10112 and 516889.

19. Specific References

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1. Allen LV. Featured excipient: capsule and tablet diluents. Int J Pharm Compound 2000; 4(4): 306310, 324325. 2. Serra MD, Robles LV. Compaction of agglomerated mixtures of calcium carbonate and microcrystalline cellulose. Int J Pharm 2003; 258(12): 153164. (PubMed) 3. Gorecki DKJ et al. Dissolution rates in calcium carbonate tablets: a consideration in product selection. Can J Pharm 1989; 122: 484487, 508. 4. Bacher C et al. Improving the compaction properties of roller compacted calcium carbonate. Int J Pharm 2007; 342: 115123. (PubMed) 5. Bacher C et al. Compressibility and compactibility of granules produced by wet and dry granulation. Int J Pharm 2008; 358: 6974. (PubMed) 6. Carmargo IM et al. Abrasiveness evaluation of silica and calcium carbonate used in the production of dentifrices. J Cos Sci 2001; 52: 163167. (PubMed) 7. Orwoll ES. The milk-alkali syndrome: current concepts. Ann Intern Med 1982; 97: 242248. (PubMed) 8. Health and Safety Executive. EH40/2005: Workplace Exposure Limits. Sudbury: HSE Books, 2005 (updated 2007). http://0-www.hse.gov.uk.library.newcastle.edu.au/coshh /table1.pdf (accessed 2 December 2010). 9. Food Chemicals Codex, 7th edn. Bethesda, MD: United States Pharmacopeia, 2010: 133.

20. General References

Armstrong NA. Tablet manufacture. In: Swarbrick J, Boylan JC, eds. Encyclopedia of Pharmaceutical Technology, 2nd edn, 3. New York: Marcel Dekker, 2002: 27132732. Ciancio SG. Dental products. In: Swarbrick J, Boylan JC, eds. Encyclopedia of Pharmaceutical Technology, 2nd edn, 3. New York: Marcel Dekker, 2002: 691701. European Directorate for the Quality of Medicines and Healthcare (EDQM). European Pharmacopoeia State Of Work Of International Harmonisation. Pharmeuropa 2010; 22(4): 583584. http://www.edqm.eu/site/-614.html (accessed 2 December 2010). Specialty Minerals Inc. Technical data sheet: Sturcal, 1998.

21. Author
NA Armstrong.

22. Date of Revision

1 February 2011.
Pharmaceutical Press and American Pharmacists Association 2011

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