Wax, White

Nonproprietary Names

BP: White beeswax JP: White beeswax PhEur: Cera alba USPNF: White wax

Synonyms

Bleached wax; E901.

Chemical Name and CAS Registry Number

White beeswax [8012-89-3]

Empirical Formula and Molecular Weight

White wax is the chemically bleached form of natural beeswax;

see Section 13.

Beeswax consists of 70–75% of a mixture of various esters of straight-chain monohydric alcohols with even-numbered carbon chains from C24 to C36 esterified with straight-chain acids. These straight-chain acids also have even numbers of carbon atoms up to C36 together with some C18 hydroxy acids. The chief ester is myricyl palmitate. Also present are free acids (about 14%) and carbohydrates (about 12%) as well as approximately 1% free wax alcohols and stearic esters of fatty acids.

Structural Formula

See Section 4.

Functional Category

Controlled-release vehicle; stabilizing agent; stiffening agent.

Applications in Pharmaceutical Formulation or Technology

White wax is a chemically bleached form of yellow wax and is used in similar applications: for example, to increase the consistency of creams and ointments, and to stabilize water-in- oil emulsions. White wax is used to polish sugar-coated tablets and to adjust the melting point of suppositories.

White wax is also used as a film coating in sustained-release tablets.(1)White beeswax microspheres may be used in oral dosage forms to retard the absorption of an active ingredient from the stomach, allowing the majority of absorption to occur in the intestinal tract. Wax coatings can also be used to affect the release of drug from ion-exchange resin beads.(2–4)

See also Yellow Wax.

Description

White wax consists of tasteless, white or slightly yellow-colored sheets or fine granules with some translucence. Its odor is similar to that of yellow wax but is less intense.

Pharmacopeial Specifications

See Table I.

Table I:  Pharmacopeial specifications for white wax.

 

Test JP 2001 PhEur 2005 USPNF 23    

Characters + + —    

Drop point 60–678C 61–668C 62–658C    

Acid value 5–9 or 17–22 17–24 17–24    

Ester value — 70–80 72–79    

Ester value : acid value — 3.3 : 4.3 —    

ratio    

Saponification value 80–100 87–104 +    

Ceresin, paraffins, and — + +    

certain other waxes    

Glycerols and other polyols — + +    

Saponification cloud test — — +    

Purity + — —    

Relative density — ≈0.960 —  

Typical Properties

Arsenic: 43 ppm

Density: 0.95–0.96 g/cm3 Flash point: 245–2588C Heavy metals: 40.004%

Iodine number: 8–11

Lead: 410 ppm Melting point: 61–658C Peroxide value: 48

Solubility: soluble in chloroform, ether, fixed oils, volatile oils, and warm carbon disulfide; sparingly soluble in ethanol (95%); practically insoluble in water.

Unsaponified matter: 52–55%

Stability and Storage Conditions

When the wax is heated above 1508C, esterification occurs with a consequent lowering of acid value and elevation of melting point. White wax is stable when stored in a well-closed container, protected from light.

Incompatibilities

Incompatible with oxidizing agents.

Method of Manufacture

Yellow wax (beeswax) is obtained from the honeycomb of the bee (Apis mellifera Linne´ (Fam. Apidae)); see Yellow Wax. Subsequent treatment with oxidizing agents bleaches the wax to yield white wax.

Safety

White wax is used in both topical and oral formulations, and is generally regarded as an essentially nontoxic and nonirritant

818 Wax, White

material. However, although rare, hypersensitivity reactions to beeswax (attributed to contaminants in the wax) have been reported.(5,6)

Handling Precautions

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

Regulatory Status

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

Related Substances

Yellow wax.

Comments

—

Specific References

Nughroho AK, Fudholi A. Comparison of mefenamic acid dissolution in sustained release tablets using hydroxypropyl

methylcellulose and cera alba as film coating. Indonesian J Pharm

1999; 10(2): 78–84.

Giannola L, Stefano V, Caro V. White beeswax microspheres: a comparative in vitro evaluation of cumulative release of the anticancer agents fluorouracil and ftorafur. Pharmazie 1993; 48: 123–126.

Giannola LI, De Caro V, Rizzo MC. Preparation of white beeswax microspheres loaded with valproic acid and kinetic study of drug release. Drug Dev Ind Pharm 1995; 21: 793–807.

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.

Cronin E. Contact dermatitis from cosmetics. J Soc Cosmet Chem

1967; 18: 681–691.

Rothenborg HW. Occupational dermatitis in beekeeper due to poplar resins in beeswax. Arch Dermatol 1967; 95: 381–384.

General References

Puleo SL. Beeswax. Cosmet Toilet 1987; 102(6): 57–58.

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, Yellow

Nonproprietary Names

BP: Yellow beeswax JP: Yellow beeswax PhEur: Cera flava USPNF: Yellow wax

Synonyms

Apifil; E901; refined wax.

Chemical Name and CAS Registry Number

Yellow beeswax [8012-89-3]

Empirical Formula and Molecular Weight

Yellow wax is naturally obtained beeswax; see Section 13.

The PhEur 2005 describes yellow wax as the wax obtained by melting the walls of the honeycomb made by the honeybee, Apis mellifera, with hot water and removing foreign matter.

Pharmacopeial Specifications

See Table I.

Table I: Pharmacopeial specifications for yellow wax.

Test JP 2001 PhEur 2005 USPNF 23

Characters + + —

Drop point 60–678C 61–668C 62–658C

Relative density — ≈0.960 —

Acid value 5–9 or 17–22  17–22 17–24

Ester value — 70–80 72–79

Beeswax consists of 70–75% of a mixture of various esters of straight-chain monohydric alcohols with even-numbered

Ester value : acid value ratio

— 3.3 : 4.3 —

carbon chains from C24 to C36 esterified with straight-chain

Saponification value 80–100 87–102 —

acids. These straight-chain acids also have even numbers of carbon atoms up to C36 together with some C18 hydroxy acids.

Ceresin, paraffins, and certain other waxes

— + +

The chief ester is myricyl palmitate. Also present are free acids Purity + — —

(about 14%) and carbohydrates (about 12%) as well as approximately 1% free wax alcohols and stearic esters of fatty

Glycerol and other polyols (as glycerol)

— 40.5% +

acids.

Structural Formula

See Section 4.

Functional Category

Controlled-release vehicle; polishing agent; stabilizing agent; stiffening agent.

Applications in Pharmaceutical Formulation or Technology

Yellow wax is used in food, cosmetics, and confectionery products. Its main use is in topical pharmaceutical formula- tions, where it is used at a concentration of 5–20%, as a stiffening agent in ointments and creams. Yellow wax is also employed in emulsions because it enables water to be incorporated into water-in-oil emulsions.

In some oral formulations yellow wax is used as a polishing agent for sugar-coated tablets. It is also used in sustained- release formulations. Yellow wax coatings can be used to affect the release rate of drug from ion-exchange resin beads,(1) and has also been used in multiparticulate controlled-release dosage forms of chlorphenamine maleate.(2)

Yellow wax forms a soap with borax.

Description

Yellow or light brown pieces or plates with a fine-grained matt, noncrystalline fracture and a faint characteristic odor. The wax becomes soft and pliable when warmed.

Saponification cloud test — — +

Typical Properties

Acid value: 20

Arsenic: 43 ppm

Density: 0.95–0.96 g/cm3 Flash point: 245–2588C Heavy metals: 40.004%

Iodine number: 8–11

Lead: 410 ppm Melting point: 61–658C Peroxide value: 48

Solubility: soluble in chloroform, ether, fixed oils, volatile oils, and warm carbon disulfide; sparingly soluble in ethanol (95%); practically insoluble in water.

Unsaponified matter: 52–55%

Viscosity (kinematic): 1470 mm2/s (1470 cSt) at 998C

Stability and Storage Conditions

When the wax is heated above 1508C esterification occurs with a consequent lowering of acid value and elevation of melting point. Yellow wax is stable when stored in a well-closed container, protected from light.

Incompatibilities

Incompatible with oxidizing agents.

820 Wax, Yellow

Method of Manufacture

Yellow wax is a natural secretion of bees (Apis mellifera Linne´ (Fam. Apidae)) and is obtained commercially from honey- combs. Honey is abstracted from combs either by draining or centrifugation and water is added to the remaining wax to remove soluble impurities. Hot water is then added to form a floating melt, which is strained to remove foreign matter. The wax is then poured into flat dishes or molds to cool and harden.

Safety

Yellow wax is generally regarded as an essentially nontoxic and nonirritant material, and is used in both topical and oral formulations. However, hypersensitivity reactions attributed to contaminants in the wax, although rare, have been reported.(3,4)

Handling Precautions

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

Regulatory Status

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

Related Substances

White wax.

Comments

Studies have shown that yellow wax, when added to suppository formulations, increased the melting point of the preparation significantly and decreased the rate of release of the active substance.(5)

Specific References

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.

Griffin EN, Niebergall PJ. Release kinetics of a controlled-release multiparticulate dosage form prepared using a hot-melt fluid bed coating method. Pharm Dev Technol 1999; 4(1): 117–124.

Cronin E. Contact dermatitis from cosmetics. J Soc Cosmet Chem

1967; 18: 681–691.

Rothenborg HW. Occupational dermatitis in beekeeper due to poplar resins in beeswax. Arch Dermatol 1967; 95: 381–384.

Murrukmihadi M. Effect of cera flava on the release of sodium salicylate from suppository dosage form. Indonesian J Pharm 1999; 10(3): 135–139.

General References

Puleo SL. Beeswax. Cosmet Toilet 1987; 102(6): 57–58.

Authors

AH Kibbe.

Date of Revision

5 April 2005.

Xanthan Gum

Nonproprietary Names

BP: Xanthan gum PhEur: Xanthani gummi USPNF: Xanthan gum

Synonyms

Corn sugar gum; E415; Keltrol; polysaccharide B-1459;

Rhodigel; Vanzan NF; Xantural.

Chemical Name and CAS Registry Number

Xanthan gum [11138-66-2]

Empirical Formula and Molecular Weight

(C35H49O29)n   Approximately 2 × 106

The USPNF 23 describes xanthan gum as a high molecular weight polysaccharide gum. It contains D-glucose and D- mannose as the dominant hexose units, along with D- glucuronic acid, and is prepared as the sodium, potassium, or calcium salt.

Structural Formula

Each xanthan gum repeat unit contains five sugar residues: two glucose, two mannose, and one glucuronic acid. The polymer backbone consists of four b-D-glucose units linked at the 1 and 4 positions, and is therefore identical in structure to cellulose. Trisaccharide side chains on alternating anhydroglucose units distinguish xanthan from cellulose. Each side chain comprises a glucuronic acid residue between two mannose units. At most of the terminal mannose units is a pyruvate moiety; the mannose nearest the main chain carries a single group at C-6. The resulting stiff polymer chain may exist in solution as a single, double, or triple helix that interacts with other xanthan gum molecules to form complex, loosely bound networks.(1,2)

Functional Category

Stabilizing agent; suspending agent; viscosity-increasing agent.

Applications in Pharmaceutical Formulation or Technology

Xanthan gum is widely used in oral and topical pharmaceutical formulations, cosmetics, and foods as a suspending and stabilizing agent.(3–5) It is also used as a thickening and emulsifying agent. It is nontoxic, compatible with most other pharmaceutical ingredients, and has good stability and viscosity properties over a wide pH and temperature range; see Section 11. Xanthan gum gels show pseudoplastic behavior, the shear thinning being directly proportional to the shear rate. The viscosity returns to normal immediately on release of shear stress.

When xanthan gum is mixed with certain inorganic suspending agents, such as magnesium aluminum silicate, or organic gums, synergistic rheological effects occur.(6) In general,

mixtures of xanthan gum and magnesium aluminum silicate in ratios between 1 : 2 and 1 : 9 produce the optimum properties. Similarly, optimum synergistic effects are obtained with xanthan gum : guar gum ratios between 3 : 7 and 1 : 9.

Although primarily used as a suspending agent, xanthan gum has also been used to prepare sustained-release matrix tablets.(7–10) Controlled-release tablets of diltiazem hydrochlor- ide prepared using xanthan gum have been reported to sustain the drug release in a predictable manner and the drug release profiles of these tablets were not affected by pH and agitation rate.(11)

Xanthan gum has been incorporated in an ophthalmic liquid dosage form, which interacts with mucin, thereby helping in the prolonged retention of the dosage form in the precorneal area.(12)

Recent studies have revealed that xanthan gum can also be used as an excipient for spray-drying and freeze-drying processes for better results.(13,14)

Xanthan gum can be used to increase the bioadhesive strength in vaginal formulations and as a binder in colon specific drug delivery systems.(15,16)

Xanthan gum is also used as a hydrocolloid in the food industry, and in cosmetics it has been used as a thickening agent in shampoo.(17)

Description

Xanthan gum occurs as a cream- or white-colored, odorless, free-flowing, fine powder.

Pharmacopeial Specifications

See Table I.

Table I:  Pharmacopeial specifications for xanthan gum.

 

Test PhEur 2005 USPNF 23    

Identification + +    

Characters + —    

pH 6.0–8.0 —    

Viscosity 5600 mPas 5600 mPas    

Propan-2-ol 4750 ppm 40.075%    

Other polysaccharides + —    

Loss on drying 415.0% 415.0%    

Total ash 6.5–16.0% 6.5–16.0%    

Microbial contamination + +    

Bacteria 4103/g —    

Fungi 4102/g —    

Pyruvic acid — 41.5%    

Arsenic — 43 mg/g    

Lead — 45 mg/g    

Heavy metals — 40.003%    

Organic volatile impurities — +    

Assay — 91.0–108.0%  

822 Xanthan Gum

Typical Properties

Acidity/alkalinity: pH = 6.0–8.0 for a 1% w/v aqueous solution.

Freezing point: 08C for a 1% w/v aqueous solution.

Heat of combustion: 14.6 J/g (3.5 cal/g)

Melting point: chars at 2708C.

Particle size distribution: various grades with different particle sizes are available; for example, 100% less than 180 mm in size for Keltrol CG; 100% less than 75 mm in size for Keltrol CGF; 100% less than 250 mm, 95% less than 177 mm in size for Rhodigel; 100% less than 177 mm, 92% less than 74 mm in size for Rhodigel 200.

Refractive index: n20 = 1.333 for a 1% w/v aqueous solution.

Solubility: practically insoluble in ethanol and ether; soluble in cold or warm water.

Specific gravity: 1.600 at 258C

Viscosity (dynamic): 1200–1600 mPa s (1200–1600 cP) for a 1% w/v aqueous solution at 258C.

Stability and Storage Conditions

Xanthan gum is a stable material. Aqueous solutions are stable over a wide pH range (pH 3–12), although they demonstrate maximum stability at pH 4–10 and temperatures of 10–608C. Xanthan gum solutions of less than 1% w/v concentration may be adversely affected by higher than ambient temperatures: for example, viscosity is reduced. Solutions are also stable in the presence of enzymes, salts, acids, and bases.

The bulk material should be stored in a well-closed container in a cool, dry place.

Incompatibilities

Xanthan gum is an anionic material and is not usually compatible with cationic surfactants, polymers, or preserva- tives as precipitation occurs. Anionic and amphoteric surfac- tants at concentrations above 15% w/v cause precipitation of xanthan gum from a solution.

Under highly alkaline conditions, polyvalent metal ions such as calcium cause gelation or precipitation; this may be inhibited by the addition of a glucoheptonate sequestrant. The presence of low levels of borates (<300 ppm) can also cause gelation. This may be avoided by increasing the boron ion concentration

or by lowering the pH of a formulation to less than pH 5. The addition of ethylene glycol, sorbitol, or mannitol may also prevent this gelation.

Xanthan gum is compatible with most synthetic and natural viscosity-increasing agents. If it is to be combined with cellulose derivatives, then xanthan gum free of cellulase should be used to prevent depolymerization of the cellulose derivative.

The viscosity of xanthan gum solutions is considerably increased, or gelation occurs, in the presence of some materials such as ceratonia, guar gum, and magnesium aluminum silicate.(6) This effect is most pronounced in deionized water and is reduced by the presence of salt. This interaction may be desirable in some instances and can be exploited to reduce the amount of xanthan gum used in a formulation; see Section 7.

Xanthan gum solutions are stable in the presence of up to 60% water-miscible organic solvents such as acetone, metha- nol, ethanol, or propan-2-ol. However, above this concentra- tion precipitation or gelation occurs.

Xanthan gum is incompatible with oxidizing agents, some tablet film-coatings,(4) carboxymethylcellulose sodium,(18) dried aluminum hydroxide gel,(19) and some active ingredients such as amitriptyline, tamoxifen, and verapamil.(3)

Method of Manufacture

Xanthan gum is a polysaccharide produced by a pure-culture aerobic fermentation of a carbohydrate with Xanthomonas campestris. The polysaccharide is then purified by recovery with propan-2-ol, dried, and milled.(20,21)

Safety

Xanthan gum is widely used in oral and topical pharmaceutical formulations, cosmetics, and food products and is generally regarded as nontoxic and nonirritant at the levels employed as a pharmaceutical excipient.

The estimated acceptable daily intake for xanthan gum has been set by the WHO at up to 10 mg/kg body-weight.(22)

LD50 (dog, oral): >20 g/kg(22) LD50 (rat, oral): >45 g/kg

LD50 (mouse, oral): >1 g/kg(23) LD50 (mouse, IP): >50 mg/kg(23) LD50 (mouse, IV): 100–250 mg/kg

Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of material handled. Eye protection and gloves are recommended.

Regulatory Status

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

Related Substances

Ceratonia; guar gum.