Ndindayino F et al. Direct compression properties of melt-extruded isomalt.Int J Pharm 2002; 235(1–2): 149–157.

Ndindayino F et al. Bioavailability of hydrochlorothiazide from isomalt-based moulded tablets. Int J Pharm 2002; 246: 199–202.

O’Brien Nabors L, ed. Alternative Sweeteners: An Overview, 3rd edn. NewYork: Marcel Dekker, 2001; 553.

21 AuthorsB Fritzsching, O Luhn, A Schoch.

22 Date of Revision16 January 2009.

Isopropyl Alcohol

1 Nonproprietary NamesBP: Isopropyl AlcoholJP: IsopropanolPhEur: Isopropyl AlcoholUSP: Isopropyl Alcohol

2 SynonymsAlcohol isopropylicus; dimethyl carbinol; IPA; isopropanol; petro-hol; 2-propanol; sec-propyl alcohol; rubbing alcohol.

3 Chemical Name and CAS Registry NumberPropan-2-ol [67-63-0]

4 Empirical Formula and Molecular WeightC3H8O 60.1

5 Structural Formula

6 Functional CategoryDisinfectant; solvent.

7 Applications in Pharmaceutical Formulation orTechnology

Isopropyl alcohol (propan-2-ol) is used in cosmetics and pharma-ceutical formulations, primarily as a solvent in topical formula-tions.(1) It is not recommended for oral use owing to its toxicity; seeSection 14.

Although it is used in lotions, the marked degreasing propertiesof isopropyl alcohol may limit its usefulness in preparations usedrepeatedly. Isopropyl alcohol is also used as a solvent both for tabletfilm-coating and for tablet granulation,(2) where the isopropylalcohol is subsequently removed by evaporation. It has also beenshown to significantly increase the skin permeability of nimesulidefrom carbomer 934.(3)

Isopropyl alcohol has some antimicrobial activity (see Section10) and a 70% v/v aqueous solution is used as a topical disinfectant.Therapeutically, isopropyl alcohol has been investigated for thetreatment of postoperative nausea or vomiting.(4)

8 DescriptionIsopropyl alcohol is a clear, colorless, mobile, volatile, flammableliquid with a characteristic, spirituous odor resembling that of amixture of ethanol and acetone; it has a slightly bitter taste.

9 Pharmacopeial SpecificationsSee Table I.

Table I: Pharmacopeial specifications for isopropyl alcohol.

Test JP XV PhEur 6.0 USP 32

Identification þ þ þAppearance of

solutionþ þ —

Absorbance — þ —Characters — þ —Specific gravity 0.785–0.788 0.785–0.789 0.783–0.787Refractive index — 1.376–1.379 1.376–1.378Acidity or alkalinity þ þ þWater 40.75% 40.5% —Nonvolatile residue 41.0mg 420ppm 40.005%Distillation range 81–838C — —Benzene — þ —Peroxides — þ —Assay — — 599.0%

10 Typical PropertiesAntimicrobial activity Isopropyl alcohol is bactericidal; at con-

centrations greater than 70% v/v it is a more effectiveantibacterial preservative than ethanol (95%). The bactericidaleffect of aqueous solutions increases steadily as the concentra-tion approaches 100% v/v. Isopropyl alcohol is ineffectiveagainst bacterial spores.

Autoignition temperature 4258CBoiling point 82.48CDielectric constant D20 = 18.62Explosive limits 2.5–12.0% v/v in airFlammability Flammable.Flash point 11.78C (closed cup); 138C (open cup). The water

azeotrope has a flash point of 168C.Freezing point �89.58CMelting point �88.58CMoisture content 0.1–13%w/w for commercial grades (13%w/w

corresponds to the water azeotrope).Refractive index

nD20 = 1.3776;

nD25 = 1.3749.

Solubility Miscible with benzene, chloroform, ethanol (95%),ether, glycerin, and water. Soluble in acetone; insoluble in salt

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346 Isopropyl Alcohol

solutions. Forms an azeotrope with water, containing 87.4%w/w isopropyl alcohol (boiling point 80.378C).

Specific gravity 0.786Vapor density (relative) 2.07 (air = 1)Vapor pressure

133.3 Pa (1mmHg) at �26.18C;4.32 kPa (32.4mmHg) at 208C;5.33 kPa (40mmHg) at 23.88C;13.33 kPa (100mmHg) at 39.58C.

Viscosity (dynamic) 2.43mPa s (2.43 cP) at 208C

11 Stability and Storage ConditionsIsopropyl alcohol should be stored in an airtight container in a cool,dry place.

12 IncompatibilitiesIncompatible with oxidizing agents such as hydrogen peroxide andnitric acid, which cause decomposition. Isopropyl alcohol may besalted out from aqueous mixtures by the addition of sodiumchloride, sodium sulfate, and other salts, or by the addition ofsodium hydroxide.

13 Method of ManufactureIsopropyl alcohol may be prepared from propylene; by thecatalytic reduction of acetone, or by fermentation of certaincarbohydrates.

14 SafetyIsopropyl alcohol is widely used in cosmetics and topicalpharmaceutical formulations. It is readily absorbed from thegastrointestinal tract and may be slowly absorbed through intactskin. Prolonged direct exposure of isopropyl alcohol to the skin mayresult in cardiac and neurological deficits.(5) In neonates, isopropylalcohol has been reported to cause chemical burns following topicalapplication.(6,7)

Isopropyl alcohol is metabolized more slowly than ethanol,primarily to acetone. Metabolites and unchanged isopropyl alcoholare mainly excreted in the urine.

Isopropyl alcohol is about twice as toxic as ethanol and shouldtherefore not be administered orally; isopropyl alcohol also has anunpleasant taste. Symptoms of isopropyl alcohol toxicity are similarto those for ethanol except that isopropyl alcohol has no initialeuphoric action, and gastritis and vomiting are more prominent; seeAlcohol. Delta osmolality may be useful as rapid screen test toidentify patients at risk of complications from ingestion of isopropylalcohol.(8) The lethal oral dose is estimated to be about 120–250mLalthough toxic symptoms may be produced by 20mL.

Adverse effects following parenteral administration of up to20mL of isopropyl alcohol diluted with water have included only asensation of heat and a slight lowering of blood pressure. However,isopropyl alcohol is not commonly used in parenteral products.

Although inhalation can cause irritation and coma, the inhala-tion of isopropyl alcohol has been investigated in therapeuticapplications.(3)

Isopropyl alcohol is most frequently used in topical pharmaceu-tical formulations where it may act as a local irritant.(9) Whenapplied to the eye it can cause corneal burns and eye damage.

LD50 (dog, oral): 4.80 g/kg(9)

LD50 (mouse, oral): 3.6 g/kgLD50 (mouse, IP): 4.48 g/kgLD50 (mouse, IV): 1.51 g/kgLD50 (rabbit, oral): 6.41 g/kgLD50 (rabbit, skin): 12.8 g/kgLD50 (rat, IP): 2.74 g/kg

LD50 (rat, IV): 1.09 g/kgLD50 (rat, oral): 5.05 g/kg

15 Handling PrecautionsObserve normal precautions appropriate to the circumstances andquantity of material handled. Isopropyl alcohol may be irritant tothe skin, eyes, and mucous membranes upon inhalation. Eyeprotection and gloves are recommended. Isopropyl alcohol shouldbe handled in a well-ventilated environment. In the UK, the long-term (8-hour TWA) workplace exposure limit for isopropyl alcoholis 999mg/m3 (400 ppm); the short-term (15-minute) workplaceexposure limit is 1250mg/m3 (500 ppm).(10) OSHA standards statethat IPA 8-hour time weighted average airborne level in theworkplace cannot exceed 400 ppm. Isopropyl alcohol is flammableand produces toxic fumes on combustion.

16 Regulatory StatusIncluded in the FDA Inactive Ingredients Database (oral capsules,tablets, and topical preparations). Included in nonparenteralmedicines licensed in the UK. Included in the Canadian List ofAcceptable Non-medicinal Ingredients.

17 Related SubstancesPropan-1-ol.

Propan-1-olEmpirical formula C3H8OMolecular weight 60.1CAS number [71-23-8]Synonyms Propanol; n-propanol; propyl alcohol; propylic alco-

hol.Autoignition temperature 5408CBoiling point 97.28CDielectric constant D 25 = 22.20Explosive limits 2.15–13.15% v/v in airFlash point 158C (closed cup)Melting point –1278CRefractive index n D

20 = 1.3862Solubility Miscible with ethanol (95%), ether, and water.Specific gravity 0.8053 at 208CViscosity (dynamic) 2.3mPa s (2.3 cP) at 208CComments Propan-1-ol is more toxic than isopropyl alcohol. In

the UK, the long-term (8-hour TWA) exposure limit for propan-1-ol is 500mg/m3 (200 ppm); the short-term (15-minute)exposure limit is 625mg/m3 (250 ppm).(10)

18 CommentsA specification for isopropyl alcohol is contained in the FoodChemicals Codex (FCC).(11)

The EINECS number for isopropyl alcohol is 200-661-7. ThePubChem Compound ID (CID) for isopropyl alcohol is 3776.

19 Specific References1 Rafiee Tehrani H, Mehramizi A. In vitro release studies of piroxicam

from oil-in-water creams and hydroalcoholic gel topical formulations.Drug Dev Ind Pharm 2000; 26(4): 409–414.

2 Ruckmani K et al. Eudragit matrices for sustained release of ketorolactromethamine: formulation and kinetics of release. Boll Chim Form2000; 139: 205–208.

3 Guengoer S, Bergisadi N. Effect of penetration enhancers on in vitropercutaneous penetration of nimesulide through rat skin. Pharmazie2004; 59: 39–41.

4 Merritt BA et al. Isopropyl alcohol inhalation: alternative treatment ofpostoperative nausea and vomiting. Nurs Res 2002; 51(2): 125–128.

5 Leeper SC et al. Topical absorption of isopropyl alcohol induced cardiacneurological deficits in an adult female with intact skin. Vet HumToxicol 2000; 42: 15–17.

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Isopropyl Alcohol 347

6 Schick JB, Milstein JM. Burn hazard of isopropyl alcohol in theneonate. Pediatrics 1981; 68: 587–588.

7 Weintraub Z, Iancu TC. Isopropyl alcohol burns. Pediatrics 1982; 69:506.

8 Monaghan MS et al. Use of delta osmolality to predict serumisopropanol and acetone concentrations. Pharmacotherapy 1993;13(1): 60–63.

9 Lewis RJ, ed. Sax’s Dangerous Properties of Industrial Materials, 11thedn. New York: Wiley, 2004; 2148–2149.

10 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).

11 Food Chemicals Codex, 6th edn. Bethesda, MD: United StatesPharmacopeia, 2008; 511.

20 General References—

21 AuthorCP McCoy.

22 Date of Revision5 February 2009.

Isopropyl Myristate

1 Nonproprietary NamesBP: Isopropyl MyristatePhEur: Isopropyl MyristateUSP-NF: Isopropyl Myristate

2 SynonymsEstol IPM; HallStar IPM-NF; isopropyl ester of myristic acid;Isopropylmyristat; isopropylis myristas; Kessco IPM 95; LexolIPM-NF; myristic acid isopropyl ester; Rita IPM; Stepan IPM;Super Refined Crodamol IPM; Tegosoft M; tetradecanoic acid, 1-methylethyl ester; Waglinol 6014.

3 Chemical Name and CAS Registry Number1-Methylethyl tetradecanoate [110-27-0]

4 Empirical Formula and Molecular WeightC17H34O2 270.5

5 Structural Formula

6 Functional CategoryEmollient; oleaginous vehicle; skin penetrant; solvent.

7 Applications in Pharmaceutical Formulation orTechnology

Isopropyl myristate is a nongreasy emollient that is absorbed readilyby the skin. It is used as a component of semisolid bases and as asolvent for many substances applied topically. Applications intopical pharmaceutical and cosmetic formulations include bath oils;make-up; hair and nail care products; creams; lotions; lip products;shaving products; skin lubricants; deodorants; otic suspensions; andvaginal creams; see Table I. For example, isopropyl myristate is aself-emulsifying component of a proposed cold cream formula,(1)

which is suitable for use as a vehicle for drugs or dermatological

actives; it is also used cosmetically in stable mixtures of water andglycerol.(2)

Isopropyl myristate is used as a penetration enhancer fortransdermal formulations, and has been used in conjunction withtherapeutic ultrasound and iontophoresis.(3) It has been used in awater-oil gel prolonged-release emulsion and in various microemul-sions. Such microemulsions may increase bioavailability in topicaland transdermal applications.(4) Isopropyl myristate has also beenused in microspheres, and significantly increased the release of drugfrom etoposide-loaded microspheres.(5)

Isopropyl myristate is used in soft adhesives for pressure-sensitive adhesive tapes.(6)

Table I: Uses of isopropyl myristate.

Use Concentration (%)

Detergent 0.003–0.03Otic suspension 0.024Perfumes 0.5–2.0Microemulsions <50Soap 0.03–0.3Topical aerosols 2.0–98.0Topical creams and lotions 1.0–10.0

8 DescriptionIsopropyl myristate is a clear, colorless, practically odorless liquid oflow viscosity that congeals at about 58C. It consists of esters ofpropan-2-ol and saturated high molecular weight fatty acids,principally myristic acid.

9 Pharmacopeial SpecificationsSee Table II.

10 Typical PropertiesBoiling point 140.28C at 266 Pa (2mmHg)Flash point 153.58C (closed cup)Freezing point �58CSolubility Soluble in acetone, chloroform, ethanol (95%), ethyl

acetate, fats, fatty alcohols, fixed oils, liquid hydrocarbons,toluene, and waxes. Dissolves many waxes, cholesterol, orlanolin. Practically insoluble in glycerin, glycols, and water.

Viscosity (dynamic) 5–7mPa s (5–7 cP) at 258C

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348 Isopropyl Myristate