348 Isopropyl Myristate 6 Schick JB, Milstein JM. Burn hazard of isopropyl alcohol in the 20 General References neonate. 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 serum isopropanol and acetone concentrations. Pharmacotherapy 1993; 13(1): 60–63. 21 Author 9 Lewis RJ, ed. Sax’s Dangerous Properties of Industrial Materials, 11th CP McCoy. edn. 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). 22 Date of Revision 11 Food Chemicals Codex, 6th edn. Bethesda, MD: United States Pharmacopeia, 2008; 511. 5 February 2009. Isopropyl Myristate I 1 Nonproprietary Names actives; it is also used cosmetically in stable mixtures of water and (2) BP: Isopropyl Myristate glycerol. Isopropyl myristate is used as a penetration enhancer for PhEur: Isopropyl Myristate transdermal formulations, and has been used in conjunction with USP-NF: Isopropyl Myristate therapeutic ultrasound and iontophoresis.(3) It has been used in a water-oil gel prolonged-release emulsion and in various microemul- 2 Synonyms sions. Such microemulsions may increase bioavailability in topical (4) Estol IPM; HallStar IPM-NF; isopropyl ester of myristic acid; and transdermal applications. Isopropyl myristate has also been used in microspheres, and significantly increased the release of drug Isopropylmyristat; isopropylis myristas; Kessco IPM 95; Lexol (5) IPM-NF; myristic acid isopropyl ester; Rita IPM; Stepan IPM; from etoposide-loaded microspheres. Isopropyl myristate is used in soft adhesives for pressure- Super Refined Crodamol IPM; Tegosoft M; tetradecanoic acid, 1- (6) methylethyl ester; Waglinol 6014. sensitive adhesive tapes. Table I: 3 Chemical Name and CAS Registry Number Uses of isopropyl myristate. 1-Methylethyl tetradecanoate [110-27-0] Use Concentration (%) Detergent 0.003–0.03 4 Empirical Formula and Molecular Weight Otic suspension 0.024 C H O 270.5 Perfumes 0.5–2.0 17 34 2 Microemulsions <50 Soap 0.03–0.3 5 Structural Formula Topical aerosols 2.0–98.0 Topical creams and lotions 1.0–10.0 8 Description Isopropyl myristate is a clear, colorless, practically odorless liquid of low viscosity that congeals at about 58C. It consists of esters of propan-2-ol and saturated high molecular weight fatty acids, 6 Functional Category principally myristic acid. Emollient; oleaginous vehicle; skin penetrant; solvent. 9 Pharmacopeial Specifications 7 Applications in Pharmaceutical Formulation or See Table II. Technology Isopropyl myristate is a nongreasy emollient that is absorbed readily 10 Typical Properties by the skin. It is used as a component of semisolid bases and as a Boiling point 140.28C at 266 Pa (2 mmHg) solvent for many substances applied topically. Applications in Flash point 153.58C (closed cup) topical pharmaceutical and cosmetic formulations include bath oils; Freezing point 58C make-up; hair and nail care products; creams; lotions; lip products; Solubility Soluble in acetone, chloroform, ethanol (95%), ethyl shaving products; skin lubricants; deodorants; otic suspensions; and acetate, fats, fatty alcohols, fixed oils, liquid hydrocarbons, vaginal creams; see Table I. For example, isopropyl myristate is a toluene, and waxes. Dissolves many waxes, cholesterol, or self-emulsifying component of a proposed cold cream formula,(1) lanolin. Practically insoluble in glycerin, glycols, and water. which is suitable for use as a vehicle for drugs or dermatological Viscosity (dynamic) 5–7 mPa s (5–7 cP) at 258C Isopropyl Myristate 349 Table II: Pharmacopeial specifications for isopropyl myristate. 18 Comments Isopropyl myristate has been used in microemulsion templates to Test PhEur 6.0 USP32–NF27 produce nanoparticles as potential drug delivery vehicles for Identification þþ proteins and peptides.(11,12) Characters þ — Isopropyl myristate 50% has been shown to be an effective Appearance of solution þ — (13) pediculicide for the control of head lice. Relative density 0.853 0.846–0.854 The EINECS number for isopropyl myristate is 203-751-4. The Refractive index 1.434–1.437 1.432–1.436 Residue on ignition 40.1% 40.1% PubChem Compound ID (CID) for isopropyl myristate is 8042. Acid value 41.0 41.0 Saponification value 202–212 202–212 19 Specific References Iodine value 41.0 41.0 Viscosity 5–6 mPa s — 1 Jimenez SMM et al. Proposal and pharmacotechnical study of a modern Water 40.1% — dermo-pharmaceutical formulation for cold cream. Boll Chim Farm 5 5 1996; 135: 364–373. Assay (as C17H34O2) 90.0% 90.0% 2 Ayannides CA, Ktistis G. Stability estimation of emulsions of isopropyl myristate in mixtures of water and glycerol. J Cosmet Sci 2002; 53(3): 11 Stability and Storage Conditions 165–173. 3 Fang JY et al. Transdermal iontopheresis of sodium nonivaride acetate Isopropyl myristate is resistant to oxidation and hydrolysis, and III: combined effect of pretreatment by penetration enhancers. Int J does not become rancid. It should be stored in a well-closed Pharm 1997; 149: 183–195. container in a cool, dry place and protected from light. 4 Kogan A, Garti N. Microemulsions as transdermal delivery vehicles. Adv Colloid Interface Sci 2006; 123–126: 369–385. 12 Incompatibilities 5 Schaefer MJ, Singh J. Effect of isopropyl myristic acid ester on the I When isopropyl myristate comes into contact with rubber, there is a physical characteristics and in vitro release of etoposide from PLGA drop in viscosity with concomitant swelling and partial dissolution microspheres. AAPS Pharm Sci Tech 2000; 1(4): 32. of the rubber; contact with plastics, e.g. nylon and polyethylene, 6 Tokumura F et al. Properties of pressure-sensitive adhesive tapes with soft adhesives to human skin and their mechanism. Skin Res Technol results in swelling. Isopropyl myristate is incompatible with hard 2007; 13(2): 211–216. paraffin, producing a granular mixture. It is also incompatible with 7 Stenba¨ck F, Shubik P. Lack of toxicity and carcinogenicity of some strong oxidizing agents. commonly used cutaneous agents. Toxicol Appl Pharmacol 1974; 30: 7–13. 13 Method of Manufacture 8 Opdyke DL. Monographs on fragrance raw materials. Food Cosmet Isopropyl myristate may be prepared either by the esterification of Toxicol 1976; 14(4): 307–338. myristic acid with propan-2-ol or by the reaction of myristoyl 9 Guillot JP et al. Safety evaluation of cosmetic raw materials. J Soc chloride and propan-2-ol with the aid of a suitable dehydrochlor- Cosmet Chem 1977; 28: 377–393. inating agent. A high-purity material is also commercially available, 10 Lewis RJ, ed. Sax’s Dangerous Properties of Industrial Materials, 11th produced by enzymatic esterification at low temperature. edn. New York: Wiley, 2004; 2164. 11 Graf A et al. Protein delivery using nanoparticles based on microemul- sions with different structure types. Eur J Pharm Sci 2008; 33(4–5): 14 Safety 434–444. Isopropyl myristate is widely used in cosmetics and topical 12 Graf A et al. Microemulsions containing lecithin and sugar-based pharmaceutical formulations, and is generally regarded as a surfactant: nonparticle templates for delivery of proteins and peptides. nontoxic and nonirritant material.(7–9) Int J Pharm 2008; 350(1–2): 351–360. 13 Kaul N et al. North American efficacy and safety of a novel pediculicide (10) LD50 (mouse, oral): 49.7 g/kg rinse, isopropyl myristate 50% (results). J Cutan Med Surg 2007; 11(5): LD50 (rabbit, skin): 5 g/kg 161–167. 15 Handling Precautions 20 General References Observe normal precautions appropriate to the circumstances and Fitzgerald JE et al. Cutaneous and parenteral studies with vehicles quantity of material handled. containing isopropyl myristate and peanut oil. Toxicol Appl Pharmacol 1968; 13: 448–453. 16 Regulatory Status Nakhare S, Vyas SP. Prolonged release of rifampicin from internal phase of multiple w/o/w emulsion systems. IndianJ Pharm Sci 1995; 57: 71–77. Included in the FDA Inactive Ingredients Database (otic, topical, transdermal, and vaginal preparations). Used in nonparenteral 21 Author medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients. AK Taylor. 17 Related Substances 22 Date of Revision Isopropyl palmitate. 28 January 2009..