Typical Properties

Antimicrobial activity: see Table III. Methylparaben exhibits antimicrobial activity of pH 4–8. Preservative efficacy decreases with increasing pH owing to the formation of the phenolate anion. Parabens are more active against yeasts and molds than against bacteria. They are also more active against Gram-positive bacteria than against Gram-negative bacteria.

Table III: Minimum inhibitory concentrations (MICs) of methylparaben in aqueous solution.(4)

 

Microorganism MIC (mg/mL)    

Aerobacter aerogenes ATCC 8308 2000    

Aspergillus oryzae 600    

Aspergillus niger ATCC 9642 1000    

Aspergillus niger ATCC 10254 1000    

Bacillus cereus var. mycoides ATCC 6462 2000    

Bacillus subtilis ATCC 6633 2000    

Candida albicans ATCC 10231 2000    

Enterobacter cloacae ATCC 23355 1000    

Escherichia coli ATCC 8739 1000    

Escherichia coli ATCC 9637 1000    

Klebsiella pneumoniae ATCC 8308 1000    

Penicillium chrysogenum ATCC 9480 500    

Penicillium digitatum ATCC 10030 500    

Proteus vulgaris ATCC 8427 2000    

Proteus vulgaris ATCC 13315 1000    

Pseudomonas aeruginosa ATCC 9027 4000    

Pseudomonas aeruginosa ATCC 15442 4000    

Pseudomonas stutzeri 2000    

Rhizopus nigricans ATCC 6227A 500    

Saccharomyces cerevisiae ATCC 9763 1000    

Salmonella typhosa ATCC 6539 1000    

Sarcina lutea 4000    

Serratia marcescens ATCC 8100 1000    

Staphylococcus aureus ATCC 6538P 2000    

Staphylococcus epidermidis ATCC 12228 2000    

Trichoderma lignorum ATCC 8678 250    

Trichoderma mentagrophytes 250  



Methylparaben is the least active of the parabens; antimicrobial activity increases with increasing chain length of the alkyl moiety. Activity may be improved by using combinations of parabens as synergistic effects occur. Therefore, combinations of methyl-, ethyl-, propyl-, and butylparaben are often used together. Activity has also been reported to be enhanced by the addition of other excipients such as: propylene glycol (2–5%);(2) phenylethyl alcohol;(3) and edetic acid.(4) Activity may also be enhanced owing to synergistic effects by using combinations of parabens with other antimicrobial preservatives such as imidurea.(5)

The hydrolysis product p-hydroxybenzoic acid has practically no antimicrobial activity.

See also Section 12.

Density (true): 1.352 g/cm3

Dissociation constant: pKa = 8.4 at 228C

Melting point: 125–1288C

Partition coefficients: values for different vegetable oils vary considerably and are affected by the purity of the oil; see Table IV.

Solubility: see Table V.

Table IV: Partition coefficients of methylparaben in vegetable oil and water.(6,7)

 

Solvent Partition coefficient oil : water    

Almond oil 7.5    

Castor oil 6.0    

Corn oil 4.1    

Diethyl adipate 200    

Isopropyl myristate 18.0    

Lanolin 7.0    

Mineral oil 0.1    

Peanut oil 4.2    

Soybean oil 6.1  

Table V: Solubility of methylparaben in various solvents.(4)

Solvent Solubility at 258C unless otherwise stated

Ethanol 1 in 2

Ethanol (95%) 1 in 3

Ethanol (50%) 1 in 6

Ether 1 in 10

Glycerin 1 in 60

Mineral oil Practically insoluble

Peanut oil 1 in 200

Propylene glycol 1 in 5

Water 1 in 400

1 in 50 at 508C 1 in 30 at 808C

Stability and Storage Conditions

Aqueous solutions of methylparaben at pH 3–6 may be sterilized by autoclaving at 1208C for 20 minutes, without decomposition.(8) Aqueous solutions at pH 3–6 are stable (less than 10% decomposition) for up to about 4 years at room temperature, while aqueous solutions at pH 8 or above are subject to rapid hydrolysis (10% or more after about 60 days storage at room temperature); see Tables VI and VII.(9)

468 Methylparaben

Methylparaben should be stored in a well-closed container in a cool, dry place.

Table VI: Predicted rate constants and half-lives for methylparaben dissolved in dilute hydrochloric acid solution, at 258C.

immune responses to enzymatically formed metabolites of the parabens in the skin.

Parabens are nonmutagenic, nonteratogenic, and noncarci- nogenic. Sensitization to the parabens is rare, and these compounds do not exhibit significant levels of photocontact sensitization or phototoxicity.

Initial pH

of solution

Rate constant

k  s(a) (hour—1)

Half-life

t1/2  s(a) (day)

Hypersensitivity reactions to parabens, generally of the delayed type and appearing as contact dermatitis, have been reported. However, given the widespread use of parabens as preservatives, such reactions are relatively uncommon; the classification of parabens in some sources as high-rate sensitizers may be overstated.(22)

Immediate hypersensitivity reactions following injection of

(a) Indicates the standard error.

Table VII: Predicted remaining amount of methylparaben dissolved in dilute hydrocholoric acid solution, after autoclaving.

 

Initial pH of solution Rate constant

k  s(a) (hour—1) Predicted residual amount after autoclaving (%)    

1 (4.96  0.16) × 10—1 84.77  0.46    

2 (4.49  0.37) × 10—2 98.51  0.12    

3 (2.79  0.57) × 10—3 99.91  0.02    

4 (1.49  0.22) × 10—3 99.95  0.01  

(a) Indicates the standard error.

Incompatibilities

The antimicrobial activity of methylparaben and other para- bens is considerably reduced in the presence of nonionic surfactants, such as polysorbate 80, as a result of micelliza- tion.(10,11) However, propylene glycol (10%) has been shown to potentiate the antimicrobial activity of the parabens in the presence of nonionic surfactants and prevents the interaction between methylparaben and polysorbate 80.(12)

Incompatibilities with other substances, such as bento- nite,(13) magnesium trisilicate,(14) talc, tragacanth,(15) sodium alginate,(16) essential oils,(17) sorbitol,(18) and atropine,(19) have been reported. It also reacts with various sugars and related sugar alcohols.(20)

Absorption of methylparaben by plastics has also been reported; the amount absorbed is dependent upon the type of plastic and the vehicle. It has been claimed that low-density and high-density polyethylene bottles do not absorb methylpar- aben.(21)

Methylparaben is discolored in the presence of iron and is subject to hydrolysis by weak alkalis and strong acids.

Method of Manufacture

Methylparaben is prepared by the esterification of p-hydroxy- benzoic acid with methanol.

Safety

Methylparaben and other parabens are widely used as antimicrobial preservatives in cosmetics and oral and topical pharmaceutical formulations. Although parabens have also been used as preservatives in injections and ophthalmic preparations, they are now generally regarded as being unsuitable for these types of formulations owing to the irritant potential of the parabens. These experiences may depend on

preparations containing parabens have also been reported.(23–25) Delayed-contact dermatitis occurs more fre- quently when parabens are used topically, but has also been reported to occur after oral administration.(26–28)

Unexpectedly, preparations containing parabens may be used by patients who have reacted previously with contact dermatitis provided they are applied to another, unaffected, site. This has been termed the paraben paradox.(29)

Concern has been expressed over the use of methylparaben in infant parenteral products because bilirubin binding may be affected, which is potentially hazardous in hyperbilirubinemic neonates.(30)

The WHO has set an estimated total acceptable daily intake for methyl-, ethyl-, and propylparabens at up to 10 mg/kg body-weight.(31)

LD50 (dog, oral): 3.0 g/kg(32) LD50 (mouse, IP): 0.96 g/kg LD50 (mouse, SC): 1.20 g/kg

Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of material handled. Methylparaben may be irritant to the skin, eyes, and mucous membranes and should be handled in a well-ventilated environment. Eye protection, gloves, and a dust mask or respirator are recommended.

Regulatory Status

Methylparaben and propylparaben are affirmed GRAS Direct Food Substances in the USA at levels up to 0.1%. All esters except the benzyl ester are allowed for injection in Japan. In cosmetics, the EU and Brazil allow use of each paraben at 0.4%, but the total of all parabens may not exceed 0.8%. The upper limit in Japan is 1.0%.

Accepted for use as a food additive in Europe. Included in the FDA Inactive Ingredients Guide (IM, IV, and SC injections; inhalation preparations; ophthalmic preparations; oral cap- sules, tablets, solutions and suspensions; otic, rectal, topical, and vaginal preparations). Included in medicines licensed in the UK. Included in the Canadian List of Acceptable Non- medicinal Ingredients.

Related Substances

Butylparaben; ethylparaben; methylparaben potassium; methylparaben sodium; propylparaben.

Methylparaben potassium Empirical formula: C8H7KO3 Molecular weight: 190.25

CAS number: [26112-07-2]

Methylparaben 469

Synonyms: methyl 4-hydroxybenzoate potassium salt; potas- sium methyl hydroxybenzoate.

Comments: methylparaben potassium may be used instead of methylparaben because of its greater aqueous solubility.

Methylparaben sodium Empirical formula: C8H7NaO3 Molecular weight: 174.14

CAS number: [5026-62-0]

Synonyms: E219; methyl 4-hydroxybenzoate sodium salt; sodium methyl hydroxybenzoate; soluble methyl hydroxy- benzoate.

Appearance: a white, odorless or almost odorless, hygroscopic crystalline powder.

Acidity/alkalinity: pH = 9.5–10.5 (0.1% w/v aqueous solution)

Solubility: 1 in 50 of ethanol (95%); 1 in 2 of water; practically insoluble in fixed oils.

Comments: methylparaben sodium may be used instead of methylparaben because of its greater aqueous solubility. However, it may cause the pH of a formulation to become more alkaline.

Comments

The EINECS number for methylparaben is 202-785-7. In addition to the most commonly used paraben esters, some other less-common esters have also been used; see Table VIII. A specification for methylparaben is contained in the Food Chemicals Codex (FCC).

Table VIII:  CAS numbers of less common paraben esters.

 

Name CAS Number    

Benzylparaben 94-18-8    

Isobutylparaben 4247-02-3    

Isopropylparaben 4191-73-5  

Specific References

Decker RL, Wenninger JA. Frequency of preservative use in cosmetic formulas as disclosed to FDA—1987. Cosmet Toilet 1987; 102(12): 21–24.

Prickett PS, Murray HL, Mercer NH. Potentiation of preservatives (parabens) in pharmaceutical formulations by low concentrations of propylene glycol. J Pharm Sci 1961; 50: 316–320.

Richards RME, McBride RJ. Phenylethanol enhancement of preservatives used in ophthalmic preparations. J Pharm Pharmacol 1971; 23: 141S–146S.

Haag TE, Loncrini DF. Esters of para-hydroxybenzoic acid. In: Kabara JJ, ed. Cosmetic and Drug Preservation. New York: Marcel Dekker, 1984: 63–77.

Rosen WE, Berke PA, Matzin T, Peterson AF. Preservation of cosmetic lotions with imidazolidinyl urea plus parabens. J Soc Cosmet Chem 1977; 28: 83–87.

Hibbott HW, Monks J. Preservation of emulsions—p-hydroxy- benzoic ester partition coefficient. J Soc Cosmet Chem 1961; 12: 2–10.

Wan LSC, Kurup TRR, Chan LW. Partition of preservatives in oil/ water systems. Pharm Acta Helv 1986; 61: 308–313.

Aalto TR, Firman MC, Rigler NE. p-Hydroxybenzoic acid esters as preservatives I: uses, antibacterial and antifungal studies, properties and determination. J Am Pharm Assoc (Sci) 1953; 42: 449–457.



Kamada A, Yata N, Kubo K, Arakawa M. Stability of p- hydroxybenzoic acid esters in acidic medium. Chem Pharm Bull 1973; 21: 2073–2076.

Aoki M, Kameta A, Yoshioka I, Matsuzaki T. Application of surface active agents to pharmaceutical preparations I: effect of Tween 20 upon the antifungal activities of p-hydroxybenzoic acid esters in solubilized preparations [in Japanese]. J Pharm Soc Jpn 1956; 76: 939–943.

Patel N, Kostenbauder HB. Interaction of preservatives with macromolecules I: binding of parahydroxybenzoic acid esters by polyoxyethylene 20 sorbitan monooleate (Tween 80). J Am Pharm Assoc (Sci) 1958; 47: 289–293.

Poprzan J, deNavarre MG. The interference of nonionic emulsi- fiers with preservatives VIII. J Soc Cosmet Chem 1959; 10: 81–87.

Yousef RT, El-Nakeeb MA, Salama S. Effect of some pharmaceu- tical materials on the bactericidal activities of preservatives. Can J Pharm Sci 1973; 8: 54–56.

Allwood MC. The adsorption of esters of p-hydroxybenzoic acid by magnesium trisilicate. Int J Pharm 1982; 11: 101–107.

Eisman PC, Cooper J, Jaconia D. Influence of gum tragacanth on the bactericidal activity of preservatives. J Am Pharm Assoc (Sci) 1957; 46: 144–147.

Myburgh JA, McCarthy TJ. The influence of suspending agents on preservative activity in aqueous solid/liquid dispersions. Pharm Weekbl (Sci) 1980; 2: 143–148.

Chemburkar PB, Joslin RS. Effect of flavoring oils on preservative concentrations in oral liquid dosage forms. J Pharm Sci 1975; 64: 414–417.

Runesson B, Gustavii K. Stability of parabens in the presence of polyols. Acta Pharm Suec 1986; 23: 151–162.

Deeks T. Oral atropine sulfate mixtures. Pharm J 1983; 230: 481.

Ma M, Lee T, Kwong E. Interaction of methylparaben preservative with selected sugars and sugar alcohols. J Pharm Sci 2002; 91(7): 1715–1723.

Kakemi K, Sezaki H, Arakawa E, et al. Interactions of parabens and other pharmaceutical adjuvants with plastic containers. Chem Pharm Bull 1971; 19: 2523–2529.

Weiner M, Bernstein IL. Adverse Reactions to Drug Formulation Agents: A Handbook of Excipients. New York: Marcel Dekker, 1989: 298–300.

Aldrete JA, Johnson DA. Allergy to local anesthetics. J Am Med Assoc 1969; 207: 356–357.

Latronica RJ, Goldberg AF, Wightman JR. Local anesthetic sensitivity: report of a case. Oral Surg 1969; 28: 439–441.

Nagel JE, Fuscaldo JT, Fireman P. Paraben allergy. J Am Med Assoc 1977; 237: 1594–1595.

Micha¨ elsson G, Juhlin L. Urticaria induced by preservatives and dye additives in food and drugs. Br J Dermatol 1973; 88: 525–532.

Warin RP, Smith RJ. Challenge test battery in chronic urticaria. Br J Dermatol 1976; 94: 401–406.

Kaminer Y, Apter A, Tyano S, et al. Delayed hypersensitivity reaction to orally administered methylparaben. Clin Pharm 1982; 1(5): 469–470.

Fisher AA. Cortaid cream dermatitis and the ‘‘paraben paradox’’ [letter]. J Am Acad Dermatol 1982; 6: 116–117.

Loria CJ, Escheverria P, Smith AL. Effect of antibiotic formulations in serum protein: bilirubin interaction of newborn infants. J Pediatr 1976; 89(3): 479–482.

FAO/WHO. Toxicological evaluation of certain food additives with a review of general principles and of specifications. Seventeenth report of the joint FAO/WHO expert committee on food additives. World Health Organ Tech Rep Ser 1974: No. 539.

Lewis RJ, ed. Sax’s Dangerous Properties of Industrial Materials, 11th edn. New York: Wiley, 2004: 2004.

General References

Bando H, Mohri S, Yamashita F, et al. Effects of skin metabolism on percutaneous penetration of lipophilic drugs. J Pharm Sci 1997; 86(6): 759–761.

Forster S, Buckton G, Beezer AE. The importance of chain length on the wettability and solubility of organic homologs. Int J Pharm 1991; 72: 29–34.

470 Methylparaben

Golightly LK, Smolinske SS, Bennett ML, et al. Pharmaceutical excipients: adverse effects associated with inactive ingredients in drug products (part I). Med Toxicol 1988; 3: 128–165.

Grant DJW, Mehdizadeh M, Chow AH-L, Fairbrother JE. Non-linear van’t Hoff solubility–temperature plots and their pharmaceutical interpretation. Int J Pharm 1984; 18: 25–38.

Jian L, Li Wan Po A. Ciliotoxicity of methyl- and propyl-p- hydroxybenzoates: a dose-response and surface-response study. J Pharm Pharmacol 1993; 45: 925–927.

Jones PS, Thigpen D, Morrison JL, Richardson AP. p-Hydroxybenzoic acid esters as preservatives III: the physiological disposition of p- hydroxybenzoic acid and its esters. J Am Pharm Assoc (Sci) 1956; 45: 268–273.

Kostenbauder HB. Physical chemical aspects of preservative selection for pharmaceutical and cosmetic emulsions. Dev Ind Microbiol 1962; 1: 286–296.

Marouchoc SR. Cosmetic preservation. Cosmet Technol 1980; 2(10): 38–44.

Matthews C, Davidson J, Bauer E, et al. p-Hydroxybenzoic acid esters as preservatives II: acute and chronic toxicity in dogs, rats and mice. J Am Pharm Assoc (Sci) 1956; 45: 260–267.

Sakamoto T, Yanagi M, Fukushima S, Mitsui T. Effects of some cosmetic pigments on the bactericidal activities of preservatives. J Soc Cosmet Chem 1987; 38: 83–98.

Sokol H. Recent developments in the preservation of pharmaceuticals.

Drug Standards 1952; 20: 89–106.

Authors

R Johnson, R Steer.

Date of Revision

23 August 2005.

Mineral Oil

Nonproprietary Names

BP: Liquid paraffin JP: Liquid paraffin

PhEur: Paraffinum liquidum USP: Mineral oil

Synonyms

Avatech; Drakeol; heavy mineral oil; heavy liquid petrolatum; liquid petrolatum; paraffin oil; Sirius; white mineral oil.

Chemical Name and CAS Registry Number

Mineral oil [8012-95-1]

Empirical Formula and Molecular Weight

Mineral oil is a mixture of refined liquid saturated aliphatic (C14–C18) and cyclic hydrocarbons obtained from petroleum.

Structural Formula

See Section 4.

Functional Category

Emollient; lubricant; oleaginous vehicle; solvent.

Applications in Pharmaceutical Formulation or Technology

Mineral oil is used primarily as an excipient in topical pharmaceutical formulations, where its emollient properties are exploited as an ingredient in ointment bases; see Table I. It is additionally used in oil-in-water emulsions,(1–5) as a solvent, and as a lubricant in capsule and tablet formulations, and to a limited extent as a mold-release agent for cocoa butter suppositories. It has also been used in the preparation of microspheres.(6–8)

Therapeutically, mineral oil has been used as a laxative, see Section 14. It is indigestible and thus has limited absorption. Mineral oil is used in ophthalmic formulations for its lubricant properties. It is also used in cosmetics and some food products.(9)

 

Table I: Uses of mineral oil.    

Use Concentration (%)    

Ophthalmic ointments 3.0–60.0    

Otic preparations 0.5–3.0    

Topical emulsions 1.0–32.0    

Topical lotions 1.0–20.0    

Topical ointments 0.1–95.0  

Description

Mineral oil is a transparent, colorless, viscous oily liquid, without fluorescence in daylight. It is practically tasteless and odorless when cold, and has a faint odor of petroleum when heated.

Pharmacopeial Specifications

See Table II.

Table II:  Pharmacopeial specifications for mineral oil.

 

Test JP 2001 PhEur 2005 USP 28    

Identification + + —    

Specific gravity 0.860–0.890 0.827–0.890 0.845–0.905    

Viscosity 537 mm2/s(a) 110–230 mPa s(b) 534.5 mm2/s(c)    

Odor + — —    

Acidity or alkalinity + + +    

Heavy metals 410 ppm — —    

Arsenic 42 ppm — —    

Solid paraffin + + +    

Sulfur compounds + — —    

Polycyclic aromatic + + —    

compounds    

Limit of polynuclear + — +    

compounds    

Readily carbonizable + + +    

substances  

(a) At 37.88C.

(b) At 208C.

(c) At 408C.

Typical Properties

Boiling point: >3608C

Flash point: 210–2248C

Pour point: —12.2 to —9.48C Refractive index: n20 = 1.4756–1.4800 Surface tension: ≈35 mN/m at 258C.

Solubility: practically insoluble in ethanol (95%), glycerin, and water; soluble in acetone, benzene, chloroform, carbon disulfide, ether, and petroleum ether. Miscible with volatile oils and fixed oils, with the exception of castor oil.

Viscosity (dynamic): 110–230 mPa s at 208C.

Stability and Storage Conditions

Mineral oil undergoes oxidation when exposed to heat and light. Oxidation begins with the formation of peroxides, exhibiting an ‘induction period’. Under ordinary conditions, the induction period may take months or years. However, once a trace of peroxide is formed, further oxidation is autocatalytic and proceeds very rapidly. Oxidation results in the formation of aldehydes and organic acids, which impart taste and odor. Stabilizers may be added to retard oxidation; butylated hydroxyanisole, butylated hydroxytoluene, and alpha toco- pherol are the most commonly used antioxidants.

472 Mineral Oil

Mineral oil may be sterilized by dry heat.

Mineral oil should be stored in an airtight container, protected from light, in a cool, dry place.

Incompatibilities

Incompatible with strong oxidizing agents.

Method of Manufacture

Mineral oil is obtained by distillation of petroleum. The lighter hydrocarbons are first removed by distillation and the residue is then redistilled between 330–3908C. The distillate is chilled and the solid fractions are removed by filtration. The filtrate is then further purified and decolorized by high-pressure hydrogena- tion or sulfuric acid treatment; the purified filtrate is then filtered through adsorbents. The liquid portion obtained is distilled and the portion boiling below 3608C is discarded. A suitable stabilizer may be added to the mineral oil; see Section 11.

Safety

Mineral oil is used as an excipient in a wide variety of pharmaceutical formulations; see Section 16. It is also used in cosmetics and in some food products.

Therapeutically, mineral oil has been used in the treatment of constipation, as it acts as a lubricant and stool softener when taken orally. Daily doses of up to 45 mL have been administered orally, while doses of up to 120 mL have been used as an enema. However, excessive dosage of mineral oil, either orally or rectally, can result in anal seepage and irritation and its oral use as a laxative is not considered desirable.

Chronic oral consumption of mineral oil may impair the appetite and interfere with the absorption of fat-soluble vitamins. Prolonged use should be avoided. Mineral oil is absorbed to some extent when emulsified and can lead to granulomatous reactions. Similar reactions also occur upon injection of the oil;(10) injection may also cause vasospasm.

The most serious adverse reaction to mineral oil is lipoid pneumonia caused by aspiration of the oil.(11,12) Mineral oil can enter the bronchial tree without eliciting the cough reflex.(13) With the reduction in the use of mineral oil in nasal formulations, the incidence of lipoid pneumonia has been greatly reduced. However, lipoid pneumonia has also been associated with the use of mineral oil-containing cosmetics(14) and ophthalmic preparations.(15) It is recommended that products containing mineral oil not be used in very young children, the elderly, or persons with debilitating illnesses.

Given its widespread use in many topical products, mineral oil has been associated with few instances of allergic reactions. The WHO has not specified an acceptable daily intake of mineral oil given the low concentration consumed in foods.(16)

LD50 (mouse, oral): 22 g/kg(17)

Handling Precautions

Observe precautions appropriate to the circumstances and quantity of material handled. Avoid inhalation of vapors and wear protective clothing to prevent skin contact. Mineral oil is combustible.

Regulatory Status

GRAS listed. Accepted in the UK for use in certain food applications. Included in the FDA Inactive Ingredients Guide (dental preparations, IV injections, ophthalmic preparations, oral capsules and tablets, otic, topical, transdermal, and vaginal preparations). Included in nonparenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non- medicinal Ingredients.

Related Substances

Mineral oil and lanolin alcohols; light mineral oil; paraffin; petrolatum.

Comments

Mineral oil in completely filled soft plastic tubes showed bubbles of gas after gamma irradiation. The bubbles were larger at higher levels of radiation. The iodine value also increased after high and low levels of irradiation.

Specific References

Zatz JL. Effect of formulation additives on flocculation of dispersions stabilized by a non-ionic surfactant. Int J Pharm 1979; 4: 83–86.

Wepierre J, Adrangui M, Marty JP. Factors in the occlusivity of aqueous emulsions. J Soc Cosmet Chem 1982; 33: 157–167.

Fong-Spaven F, Hollenbeck RG. Thermal rheological analysis of triethanolamine-stearate stabilized mineral oil in water emulsions. Drug Dev Ind Pharm 1986; 12: 289–302.

Abd Elbary A, Nour SA, Ibrahim I. Physical stability and rheological properties of w/o/w emulsions as a function of electrolytes. Pharm Ind 1990; 52: 357–363.

Jayaraman SC, Ramachandran C, Weiner N. Topical delivery of erythromycin from various formulations: an in-vivo hairless mouse study. J Pharm Sci 1996; 85: 1082–1084.

Zinotti C, Kedzierewicz F, Hoffman M, Maincent P. Preparation and characterization of ethyl cellulose microspheres containing 5- fluorouracil. J Microencapsul 1994; 11: 555–563.

O’Donnell PB, Iwata M, McGinty JW. Properties of multiphase microspheres of poly(D, 2-lactic-co-glycolic acid) prepared by a potentiometric dispersion technique. J Microencapsul 1995; 12: 155–163.

Bachtsi AR, Kiparissides C. An experimental investigation of enzyme release from poly(vinyl alcohol) crosslinked microspheres. J Microencapsul 1995; 12: 23–35.

Anonymous. Mineral hydrocarbons to be banned from foods.

Pharm J 1989; 242: 187.

Bloem JJ, van der Waal I. Paraffinoma of the face: a diagnostic and therapeutic problem. Oral Surg 1974; 38: 675–680.

Volk BW, Nathanson L, Losner S, et al. Incidence of lipoid pneumonia in a survey of 389 chronically ill patients. Am J Med 1951; 10: 316–324.

Smolinske SC. Handbook of Food, Drug, and Cosmetic Excipi- ents. Boca Raton, FL: CRC Press, 1992: 231–234.

Bennet JC, Plum F, eds. Textbook of Medicine. Philadelphia: WB Saunders, 1996: 407–408, 1016.

Becton DL, Lowe JE, Falleta JM. Lipoid pneumonia in an adolescent girl secondary to use of lip gloss. J Pediatr 1984; 105: 421–423.

Prakash UBS, Rosenow EC. Pulmonary complications from ophthalmic preparations. Mayo Clin Proc 1990; 65: 521.

FAO/WHO. Evaluation of certain food additives and contami- nants. Thirty-seventh report of the joint FAO/WHO expert committee on food additives. World Health Organ Tech Rep Ser 1991: No. 806.

Lewis RJ, ed. Sax’s Dangerous Properties of Industrial Materials, 11th edn. New York: Wiley, 2004: 2554–2555.

Mineral Oil 473

General References

Davis SS, Khanderia MS. Rheological characterization of Plastibases and the effect of formulation variables on the consistency of these vehicles part 3: oscillatory testing. Int J Pharm Technol Prod Manuf 1981; 2(Apr): 13–18.

Deasy PB, Gouldson MP. In-vitro evaluation of pellets containing enteric coprecipitates of nifedipine formed by non-aqueous spher- onization. Int J Pharm 1996; 132: 131–141.

Gosselin RE, Smith RP, Hodge HC, eds. Clinical Toxicology of Commercial Products, 5th edn. Baltimore: Williams & Wilkins, 1984: II-156–157.



Rhodes RK. Highly refined petroleum products in skin lotions. Cosmet Perfum 1974; 89(3): 53–56.

Authors

SC Owen.

Date of Revision

17 August 2005.

Mineral Oil, Light

Nonproprietary Names

BP: Light liquid paraffin JP: Light liquid paraffin

PhEur: Paraffinum perliquidum USPNF: Light mineral oil

Synonyms

905 (mineral hydrocarbons); Citation; light liquid petrolatum; light white mineral oil.

Chemical Name and CAS Registry Number

Light mineral oil [8012-95-1]

Empirical Formula and Molecular Weight

Light mineral oil is a mixture of refined liquid saturated hydrocarbons obtained from petroleum. It is less viscous and has a lower specific gravity than mineral oil.

Description

Light mineral oil is a transparent, colorless liquid, without fluorescence in daylight. It is practically tasteless and odorless when cold, and has a faint odor when heated. The USPNF 23 specifies that light mineral oil may contain a suitable stabilizer.

Pharmacopeial Specifications

See Table II.

Table II: Pharmacopeial specifications for light mineral oil.

Test JP 2001 PhEur 2005 USPNF 23

Identification + + —

Specific gravity 0.830–0.870  0.810–0.875  0.818–0.880

Viscosity 437 mm2/s(a) 25–80 mPa s 433.5 mm2/s(b)

Acidity or alkalinity  + + —

Heavy metals 410 ppm — —

Arsenic 42 ppm — —

Sulfur compounds + — —

Structural Formula

A mixture of refined liquid hydrocarbons, essentially paraffins and naphthenic in nature, obtained from petroleum.

Functional Category

Emollient; oleaginous vehicle; solvent; tablet and capsule lubricant; therapeutic agent.

Readily

carbonizable substances

Polycyclic aromatic compounds

Limit of polynuclear compounds

+ + +

+ + —

— — +