Nonproprietary Names

USP:Acetone
PhEur:Acetone USP-NF: Acetone

Synonyms

Acetonum; dimethylformaldehyde; dimethyl ketone; b-ketopropane; pyroacetic ether.

Chemical Name and CAS Registry Number

2-Propanone [67-64-1]

Empirical Formula and Molecular Weight

C3H6O 58.08

Structural Formula

Functional Category

Solvent.

Applications in Pharmaceutical Formulation or Technology

Technology Acetone is used as a solvent or cosolvent in topical preparations, and as an aid in wet granulation.(1,2) It has also been used when formulating tablets with water-sensitive active ingredients, or to solvate poorly water-soluble binders in a wet granulation process. Acetone has also been used in the formulation of microspheres to enhance drug release.(3) Owing to its low boiling point, acetone has been used to extract thermolabile substances from crude drugs.(4)

Description

Acetone is a colorless volatile, flammable, transparent liquid, with a sweetish odor and pungent sweetish taste.

Pharmacopeial Specifications

See Table I. See also Section 18. Table I: Pharmacopeial specifications for acetone. Test PhEur 6.0 USP32–NF27 Identification Characters Appearance of solution Acidity or alkalinity Relative density þ þ þ þ 0.790–0.793 þ — — — 40.789 Related substances Matter insoluble in water Reducing substances Residue on evaporation þ þ þ450 ppm — — þ 40.004% Water Assay 43 g/L — þ599.0% 1100 1300 1500 1700 1900 2100 2300 2500 Wavelength/nm Figure 1: Near-infrared spectrum of acetone measured by transflectance (1 mm path-length).

Typical Properties

Boiling point 56.28C Flash point –208C Melting point 94.38C NIR spectra see Figure 1. Refractive index n 20D = 1.359 Solubility Soluble in water; freely soluble in ethanol (95%). Vapor pressure 185mmHg at 208C

Stability and Storage Conditions

Acetone should be stored in a cool, dry, well-ventilated place out of direct sunlight.

Incompatibilities

Acetone reacts violently with oxidizing agents, chlorinated solvents, and alkali mixtures. It reacts vigorously with sulfur dichloride, potassium t-butoxide, and hexachloromelamine. Acetone should not be used as a solvent for iodine, as it forms a volatile compound that is extremely irritating to the eyes.(4)

Method of Manufacture

Acetone is obtained by fermentation as a by-product of n-butyl alcohol manufacture, or by chemical synthesis from isopropyl alcohol; from cumene as a by-product in phenol manufacture; or from propane as a by-product of oxidation-cracking.

Safety

Acetone is considered moderately toxic, and is a skin irritant and severe eye irritant. Skin irritation has been reported due to its defatting action, and prolonged inhalation may result in headaches. Inhalation of acetone can produce systemic effects such as conjunctival irritation, respiratory system effects, nausea, and vomiting.(5) LD50 (mouse, oral): 3.0g/kg(5) LD50 (mouse, IP): 1.297g/kg LD50 (rabbit, oral): 5.340g/kg LD50 (rabbit, skin): 0.2g/kg 7 Acetyltributyl Citrate LD50 (rat, IV): 5.5g/kg LD50 (rat, oral): 5.8g/kg

Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of material handled. Acetone is a skin and eye irritant (see Section 14); therefore gloves, eye protection and a respirator are recommended. In the UK, the long-term (8-hour TWA) workplace exposure limit for acetone is 1210mg/m3 (500ppm). The shortterm (15-minute) exposure limit is 3620mg/m3 (1500ppm).(6)

Regulatory Status

Included in the FDA Inactive Ingredients Database (inhalation solution; oral tablets; topical preparations). Included in the Canadian List of Acceptable Non-medicinal Ingredients. Included in nonparenteral medicines licensed in the UK. 17 Related Substances —

Comments

A specification for acetone is included in the Japanese Pharmaceutical Excipients (JPE).(7) The EINECS number for acetone is 200-662-2. The PubChem Compound ID (CID) for acetone is 180. 19 Specific References 1 Ash M, Ash I. Handbook of Pharmaceutical Additives, 3rd edn. Endicott, NY: Synapse Information Resources, 2007; 430. 2 Tang ZG et al. Surface properties and biocompatibility of solvent-cast poly[e-caprolactone] films. Biomaterials 2004; 25(19): 4741–4748. 3 Ruan G, Feng SS. Preparation and characterization of poly(lactic acid)– poly(ethylene glycol)–poly(lactic acid) (PLA-PEG-PLA) microspheres for controlled release of paclitaxel. Biomaterials 2003; 24(27): 5037– 5044. 4 Todd RG, Wade A, eds. The Pharmaceutical Codex, 11th edn. London: Pharmaceutical Press, 1979; 6. 5 Lewis RJ, ed. Sax’s Dangerous Properties of Industrial Materials, 11th edn. New York: Wiley, 2004; 22–23. 6 Health and Safety Executive. EH40/2005: Workplace Exposure Limits. Sudbury: HSE Books, 2005 (updated 2007). http://www.hse.gov.uk/ coshh/table1.pdf (accessed 5 February 2009). 7 Japan Pharmaceutical Excipients Council. Japanese Pharmaceutical Excipients 2004. Tokyo: Yakuji Nippo, 2004; 35–36.

General References

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Author

AH Kibbe.

Date of Revision

5 February 2009.