Comments

In cosmetics, carnauba wax is mainly used to increase the stiffness of formulations, e.g. lipsticks and mascaras.

The EINECS number for carnauba wax is 232-399-4.

Specific References

Ema˚ s M, Nyqvist H. Methods of studying aging and stabilization of spray-congealed solid dispersions with carnauba wax. 1: microcalorimetric investigation. Int J Pharm 2000; 197: 117–127.

Marti-Mestres G, Nielland F, Rigal S, et al. Texture and sensory analysis in stick formulations. STP Pharma Sci 1999; 9(4): 371– 375.

Reza MS, Quadir MA, Haider SS. Comparative evaluation of plastic, hydrophobic and hydrophilic polymers as matrices for controlled-release drug delivery. J Pharm Pharm Sci 2003; 6(2): 282–291.

Gioannola LI, De Caro V, Severino A. Carnauba wax microspheres loaded with valproic acid: preparation and evaluation of drug release. Drug Dev Ind Pharm 1995; 21: 1563–1572.

Miyagawa Y, Okabe T, Yamaguchi Y, et al. Controlled-release of diclofenac sodium from wax matrix granule. Int J Pharm 1996; 138(2): 215–224.

Aritomi H, Yamasaki Y, Yamada K, et al. Development of sustained-release formulation of chlorpheniramie maleate using powder-coated microsponge prepared by dry impact blending method. J Pharm Sci Tech Yakukzaigaku 1996; 56(1): 49–56.

Huang HP, Mehta SC, Radebaugh GW, Fawzi MB. Mechanism of drug release from an acrylic polymer-wax matrix tablet. J Pharm Sci 1994; 83(6): 795–797.

Joseph I, Venkataram S. Indomethacin sustained release from alginate-gelatin or pectin-gelatin coacervates. Int J Pharm 1995; 126: 161–168.

Kumar K, Chakrabarti T, Srivastava GP. Sustained release tablet formulation of diethylcarbamazine citrate (Hetrazan). Indian J Pharm 1975; 37: 57–59.

Dave SC, Chakrabarti T, Srivastava GP. Sustained release tablet formulation of diphenhydramine hydrochloride (Benadryl) - part

II. Indian J Pharm 1974; 36: 94–96.

Rodriguez L, Albertini B, Passerin N, et al. Hot air coating technique as a novel method to produce microparticles. Drug Dev Ind Pharm 2004; 30(9): 913–923.

Parent RA, Cox GE, Babish JG, et al. Subchronic feeding study of carnauba wax in beagle dogs. Food Chem Toxicol 1983; 21(1): 85–87.

Parent RA, Re TA, Babish JG, et al. Reproductive and subchronic feeding study of carnauba wax in rats. Food Chem Toxicol 1983; 21(1): 89–93.

Rowland IR, Butterworth KR, Gaunt IF, et al. Short-term toxicity study of carnauba wax in rats. Food Chem Toxicol 1982; 20(4): 467–471.

Chowdhury MM. Allergic contact dermatitis from prime yellow carnauba wax and coathylene in mascara. Contact Dermatitis 2002; 46(6): 244.

FAO/WHO. Evaluation of certain food additives and naturally occurring toxicants. Thirty-ninth report of the joint FAO/WHO expert committee on food additives. World Health Organ Tech Rep Ser 1992; No. 828.

General References

—

Authors

PJ Weller.

Date of Revision

5 April 2005.

Wax, Cetyl Esters

Nonproprietary Names

USPNF: Cetyl esters wax

Synonyms

Cera cetyla; Crodamol SS; Cutina CP; Liponate SPS; Prota- chem MST; Ritaceti; Ritachol SS; spermaceti wax replacement; Starfol Wax CG; Synaceti 116; synthetic spermaceti.

Chemical Name and CAS Registry Number

Cetyl esters wax [977067-67-6]

Empirical Formula and Molecular Weight

CnH2nO2 where n = 26–38.≈470–490

The USPNF 23 describes cetyl esters wax as a mixture consisting primarily of esters of saturated fatty alcohols (C14– C18) and saturated fatty acids (C14–C18).

Structural Formula

See Section 4.

Functional Category

Emollient; stiffening agent.

Applications in Pharmaceutical Formulation or Technology

Cetyl esters wax is a stiffening agent and emollient used in creams and ointments as a replacement for naturally occurring spermaceti.

Cetyl esters wax is hydrophobic and has been proposed as a suitable component of an ophthalmic gelatin-based, controlled- release delivery matrix.(1)

The physical properties of cetyl esters wax vary greatly from manufacturer to manufacturer owing to differences between the mixtures of fatty acids and fatty alcohol esters that are used. Differences between products appear most obviously in the melting point, which can range from 43–478C (USPNF 23 range) to 51–558C, depending on the mixture. Materials with a high melting point tend to contain predominantly cetyl and stearyl palmitates. See Table I.

Table I: Uses of cetyl esters wax.

Use Concentration (%)

Cold cream 12.5

Rose water ointment 12.5

Spermaceti ointment 20.0

Topical creams and ointments 1–15

Description

Cetyl esters wax occurs as white to off-white, somewhat translucent flakes (typically in the range of 5 mm to several millimeters in the largest dimension), having a crystalline structure and a pearly luster when caked. It has a faint, aromatic odor and a bland, mild taste.

Pharmacopeial Specifications

See Table II.

Table II: Pharmacopeial specifications for cetyl esters wax.

Test USPNF 23

Melting range 43–478C

Acid value 45

Iodine value 41

Saponification value 109–120

Paraffin and free acids +

Typical Properties

Dielectric constant: 6–18 Flash point: >2408C Peroxide value: 40.5 Refractive index: n60 = 1.440

Solubility: high melting materials tend to be less soluble. See

Table III.

Table III: Solubility of cetyl esters wax.

Solvent Solubility at 208C

unless otherwise stated

Acetone 1 in 500

Chloroform 1 in 2.5

Dichloromethane 1 in 3

Ethanol 1 in 170

Ethanol (95%) Practically insoluble 1 in 2.5 at 788C

Ether Soluble

Ethyl acetate 1 in 80

Fixed and volatile oils Soluble

Hexane 1 in 8

Mineral oil 1 in 70

Water Practically insoluble

Specific gravity: 0.820–0.840 at 508C

Viscosity (dynamic): 6.7–7.4 mPa s (6.7–7.4 cP) at 1008C

Stability and Storage Conditions

Store in a well-closed container in a cool, dry place. Avoid exposure to excessive heat (above 408C).

812 Wax, Cetyl Esters

Incompatibilities

Incompatible with strong acids or bases.

Method of Manufacture

Cetyl esters wax is prepared by the direct esterification of the appropriate mixtures of fatty alcohols and fatty acids.

Safety

Cetyl esters wax is an innocuous material generally regarded as essentially nontoxic and nonirritant.

LD50 (rat, oral): >16 g/kg

Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of material handled.

Regulatory Status

Included in the FDA Inactive Ingredients Guide (topical preparations). Included in nonparenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non- medicinal Ingredients.

Related Substances

Spermaceti wax.

Spermaceti wax

CAS number: [8002-23-1]

Appearance: spermaceti is a waxy substance obtained from the head of the sperm whale. It consists of a mixture of the cetyl esters of fatty acids (C12–C18) with cetyl laurate, cetyl myristate, cetyl palmitate, and cetyl stearate comprising at least 85% of the total esters. It occurs as white, translucent, slightly unctuous masses with a faint odor and mild, bland taste.

Iodine value: 3.0–4.4

Melting point: 44–528C Refractive index: n80 = 1.4330 Saponification value: 120–136

Solubility: soluble in chloroform, boiling ethanol (95%), ether, and fixed or volatile oils; practically insoluble in ethanol (95%) and water.

Specific gravity: 0.938–0.944

Uses: spermaceti has been used in creams, ointments, and suppositories,(2) although it has largely been superseded in pharmaceutical and cosmetics formulation by the synthetic material, cetyl esters wax.

Comments: the EINECS number for spermaceti wax is 232- 302-5.

Comments

—

Specific References

Nadkarni SR, Yalkowsky SH. Controlled delivery of pilocarpine 1: in vitro characterization of Gelfoam matrices. Pharm Res 1993; 10: 109–112.

Baichwal MR, Lohit TV. Medicament release from fatty suppo- sitory bases. J Pharm Pharmacol 1970; 22: 427–432.

General References

Egan RR, Portwood O. Higher alcohols in skin lotions. Cosmet Perfum 1974; 89(3): 39–42.

Holloway PJ. The chromatographic analysis of spermaceti. J Pharm Pharmacol 1968; 20: 775–779.

Spencer GF, Kleiman R. Detection of spermaceti in a hand cream. J Am Oil Chem Soc 1978; 55: 837–838.

Authors

PJ Weller.

Date of Revision

18 February 2005.

Wax, Microcrystalline

Nonproprietary Names

USPNF: Microcrystalline wax

Synonyms

Amorphous wax; E907; petroleum ceresin; petroleum wax (microcrystalline).

Chemical Name and CAS Registry Number

Microcrystalline wax [63231-60-7]

Empirical Formula and Molecular Weight

Microcrystalline wax is composed of a mixture of straight- chain and randomly branched saturated alkanes obtained from petroleum. The carbon chain lengths range from C41 to C57; cyclic hydrocarbons are also present.

Structural Formula

See Section 4.

Functional Category

Coating agent; controlled-release vehicle; stiffening agent.

Applications in Pharmaceutical Formulation or Technology

Microcrystalline wax is used mainly as a stiffening agent in topical creams and ointments.

The wax is used to modify the crystal structure of other waxes (particularly paraffin wax) present in a mixture so that changes in crystal structure, usually exhibited over a period of time, do not occur. Microcrystalline wax also minimizes the sweating or bleeding of oils from blends of oils and waxes. Microcrystalline wax generally has a higher melting point than paraffin wax, and higher viscosity when molten, thereby increasing the consistency of creams and ointments when incorporated into such formulations.

Microcrystalline wax is also used in oral controlled-release matrix pellet formulations for various active compounds(1–3) and as a tablet- and capsule-coating agent. In controlled-release systems, microcrystalline wax coatings can also be used to affect the release of drug from ion-exchange resin beads.(4)

Microcrystalline wax is also used in confectionery, cos- metics, and food products.

Description

Microcrystalline wax occurs as odorless and tasteless waxy lumps or flakes containing small irregularly shaped crystals. It may vary in color from white to yellow, amber, brown, or black depending on the grade of material; pharmaceutical grades are usually white or yellow.

The USPNF 23 describes microcrystalline wax as a mixture of straight-chain, branched-chain, and cyclic hydrocarbons,

obtained by solvent fractionation of the still-bottom fraction of petroleum by suitable means of dewaxing or de-oiling.

Pharmacopeial Specifications

See Table I.

Table I: Pharmacopeial specifications for microcrystalline wax.

Test USPNF 23

Color +

Melting range 54–1028C

Consistency 3–100

Acidity +

Alkalinity +

Residue on ignition 40.1%

Organic acids +

Fixed oils, fats, and rosin +

Organic volatile impurities +

Typical Properties

Acid value: 1.0

Density: 0. 928–0.941 g/cm3

Freezing point: 60.0–75.08C Refractive index: n100 = 1.435–1.445 Saponification value: 0.05–0.10

Solubility: soluble in benzene, chloroform, and ether; slightly soluble in ethanol; practically insoluble in water. When melted, microcrystalline wax is miscible with volatile oils and most warm fixed oils.

Viscosity (dynamic): 10.0–30.0 mPa s (10.0–30.0 cP) at 1008C.

Stability and Storage Conditions

Microcrystalline wax is stable in the presence of acids, alkalis, light, and air. The bulk material should be stored in a well- closed container in a cool, dry place.

Incompatibilities

—

Method of Manufacture

Microcrystalline wax is obtained by solvent fractionation of the still-bottom fraction of petroleum by suitable dewaxing or de- oiling.

Safety

Microcrystalline wax is mainly used in topical pharmaceutical formulations but is also used in some oral products. It is generally regarded as a nontoxic and nonirritating material.

814 Wax, Microcrystalline

Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of material handled. Eye protection is recom- mended.

Regulatory Status

GRAS listed. Accepted for use as a food additive in Europe. Included in the FDA Inactive Ingredients Guide (oral capsules; topical and vaginal preparations). Included in nonparenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients.

Related Substances

Paraffin.

Comments

Rheological studies of a model ointment containing micro- crystalline wax, white petroleum, and mineral oil showed that while the latter two substances control the rheology of the ointment, microcrystalline wax incorporates itself into the existing white petroleum structure and builds up the structure of the ointment.(5)

Specific References

De Brabander C, Vervaet C, Gortz JP, et al. Bioavailability of ibuprofen from matrix minitablets based on a mixture of starch and microcrystalline wax. Int J Pharm 2000; 208: 81–86.

De Brabander C, Vervaet C, Fiermans L, Reman JP. Matrix minitablets based on starch/microcrystalline wax mixtures. Int J Pharm 2000; 199: 195–203.

Vergote GJ, Vervaet C, Van Driessche I, et al. Oral controlled release matrix pellet formulation containing nanocrystalline ketoprofen. Int J Pharm 2001; 219: 81–87.

Motycka S, Nairn J. Influence of wax coatings on release rate of anions from ion-exchange resin beads. J Pharm Sci 1978; 67: 500–

503.

Pena LE, Lee BL, Stearns JF. Structural rheology of a model ointment. Pharm Res 1994; 11: 875–881.

General References

Tennant DR. The usage, occurrences and dietary intakes of white mineral oils and waxes in Europe. Food Chem Toxicol 2004; 42: 481–492.

Authors

AH Kibbe.

Date of Revision

5 April 2005.

Wax, Nonionic Emulsifying

Nonproprietary Names

BP: Cetomacrogol emulsifying wax USPNF: Emulsifying wax

Synonyms

Collone NI; Crodex N; Emulgade 1000NI; Permulgin D; Polawax; Ritachol 2000; T-Wax.

Chemical Name and CAS Registry Number

Nonionic emulsifying wax [977069-99-0]

Empirical Formula and Molecular Weight

The USPNF 23 designates nonionic emulsifying wax as emulsifying wax that is prepared from cetostearyl alcohol and contains a polyoxyethylene derivative of a fatty acid ester of sorbitan. However, the BP 2004 describes nonionic emulsifying wax as cetomacrogol emulsifying wax prepared from ceto- stearyl alcohol and macrogol cetostearyl ether (22) (ceto- macrogol 1000). The UK and US materials are therefore constitutionally different. See also Section 18.

Structural Formula

See Section 4.

Functional Category

Emulsifying agent; stiffening agent.

Applications in Pharmaceutical Formulation or Technology

Nonionic emulsifying wax is used as an emulsifying agent in the production of oil-in-water emulsions that are unaffected by moderate concentrations of electrolytes and are stable over a wide pH range. The concentration of wax used alters the consistency of a product owing to its ‘self-bodying action’; at concentrations up to about 5% a product is pourable.

Concentrations of about 15% of nonionic emulsifying wax are commonly used in creams, but concentrations as high as 25% may be employed, e.g., in chlorhexidine cream BP. Nonionic emulsifying wax is particularly recommended for use with salts of polyvalent metals and medicaments based on nitrogenous compounds. Creams are susceptible to microbial spoilage and should be adequately preserved.

Nonionic emulsifying wax is also used in nonaqueous ointment bases, such as cetomacrogol emulsifying ointment BP, and in barrier creams.

Description

Nonionic emulsifying wax is a white or off-white waxy solid or flakes which melt when heated to give a clear, almost colorless liquid. Nonionic emulsifying wax has a faint odor characteristic of cetostearyl alcohol.

Pharmacopeial Specifications

See Table I.

Table I:  Pharmacopeial specifications for nonionic emulsifying wax.

 

Test BP 2004 USPNF 23    

Identification + —    

Characters + —    

Melting range — 50–548C    

Solidifying point 45–538C —    

pH (3% dispersion) — 5.5–7.0    

Alkalinity + —    

Acid value 40.5 —    

Hydroxyl value 175–192 178–192    

Iodine value — 43.5    

Refractive index (at 608C) 1.435–1.439 —    

Saponification value 42.0 414    

Sulfated ash 40.1% —  

Typical Properties

Density: 0.94 g/cm3

Flash point: >558C

Solubility: freely soluble in aerosol propellants, chloroform,

and hydrocarbons; moderately soluble in ethanol (96%); partly soluble in ether and insoluble in water (forms emulsions).

Stability and Storage Conditions

Nonionic emulsifying wax is stable and should be stored in a well-closed container in a cool, dry place.

Incompatibilities

Nonionic emulsifying wax is incompatible with tannin, phenol and phenolic materials, resorcinol, and benzocaine. It may reduce the antibacterial efficacy of quaternary ammonium compounds.

Method of Manufacture

The BP 2004 specifies that cetomacrogol emulsifying wax (nonionic emulsifying wax) may be prepared by melting and mixing together 800 g of cetostearyl alcohol and 200 g of macrogol cetostearyl ether (22) (cetomacrogol 1000). The mixture is then stirred until cold.

The USPNF 23 formula for nonionic emulsifying wax is a mixture of unstated proportions of cetostearyl alcohol and a polyoxyethylene derivative of a fatty acid ester of sorbitan.

Safety

Nonionic emulsifying wax is used in cosmetics and topical pharmaceutical formulations and is generally regarded as a nontoxic and nonirritant material.

816 Wax, Nonionic Emulsifying

Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of material handled. Eye protection is recom- mended.

Regulatory Status

Included in the FDA Inactive Ingredients Guide (topical aerosols, emulsions, lotions, and ointments). Included in nonparenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients.

Related Substances

Cationic emulsifying wax; cetostearyl alcohol; polyoxyethylene alkyl ethers; wax, anionic emulsifying.

It should be noted that there are many similar nonionic emulsifying waxes composed of different nonionic surfactants and fatty alcohols.

Cationic emulsifying wax

Synonyms: cetrimide emulsifying wax; Crodex C.

Method of manufacture: cetrimide emulsifying wax is prepared similarly to nonionic emulsifying wax and contains 90 g of cetostearyl alcohol and 10 g of cetrimide.

Comments: cationic emulsifying wax is claimed to be of particular value in cosmetic and pharmaceutical formula- tions when cationic characteristics are important. Thus it can be used in medicated creams, germicidal creams, ointments and lotions, hair conditioners, baby creams, and skin care products in which cationic compounds are included. Cationic emulsifying wax is compatible with cationic and nonionic materials, but is incompatible with anionic surfactants and drugs. Additional antimicrobial preservatives should be included in creams. Cetrimide may cause irritation to the eye; see Cetrimide.

Comments

The nomenclature for emulsifying wax is confused since there are three groups of emulsifying waxes with different titles in the UK and USA; see Table II.

Table II: Nomenclature for emulsifying wax.

UK USA

Nonionic Cetomacrogol emulsifying wax Emulsifying wax Anionic Emulsifying wax —

Cationic Cetrimide emulsifying wax —

The waxes have similar physical properties but vary in the type of surfactant used, which, in turn, affects the range of compatibilities. Emulsifying wax BP and emulsifying wax USP contain anionic and nonionic surfactants, respectively, and are therefore not interchangeable in formulations.

Specific References

—

General References

Eccleston GM. Properties of fatty alcohol mixed emulsifiers and emulsifying waxes. In: Florence AT, ed. Materials Used in Pharmaceutical Formulation: Critical Reports on Applied Chem- istry, vol. 6. Oxford: Blackwell Scientific, 1984: 124–156.

Hadgraft JW. The emulsifying properties of polyethyleneglycol ethers of cetostearyl alcohol. J Pharm Pharmacol 1954; 6: 816–829.

Authors

AJ Winfield.

Date of Revision

15 August 2005.