3 78

Lanolin
15 Berggren J et al. Compression behaviour and tablet-forming ability of spray-dried amorphous composite particles. Eur J Pharm Sci 2004; 22: 191200.

inhalation application.(13,14) Amorphous spray-dried lactose has also been studied in composites with PVP.(15) See also Lactose, Anhydrous, Lactose, Inhalation and Lactose, Monohydrate. 19 Specific References

20

General References

1 Kibbe AH, ed. Handbook of Pharmaceutical Excipients, 3rd edn. London and Washington, DC: Pharmaceutical Press and American Pharmaceutical Association, 2000; 641643. 2 Blaug SM, Huang W. Interaction of dextro amphetamine sulfate with spray-dried lactose. J Pharm Sci 1972; 61: 17701775. 3 Castello RA, Mattocks AM. Discoloration of tablets containing amines and lactose. J Pharm Sci 1962; 51: 106108. 4 Wirth DD et al. Maillard reaction of lactose and fluoxetine hydrochloride: a secondary amine. J Pharm Sci 1998; 87: 3139. 5 Hutton JT et al. Lactose product and method. United States Patent No. 3,639,170; 1972. 6 Vromans H et al. Spray-dried lactose and process for preparing the same. United States Patent No. 4,802,926; 1989. 7 Vromans H et al. Studies on tableting properties of lactose. VII. The effect of variations in primary particle size and percentage of amorphous lactose in spray dried lactose products. Int J Pharm 1987; 35(12): 2937. 8 Elversson J et al. Droplet and particle size relationship and shell thickness of inhalable lactose particles during spray drying. J Pharm Sci 2003; 92(4): 900910. 9 Harjunen PI et al. Effects of ethanol to water ratio in feed solution on the crystallinity of spray dried lactose. Drug Dev Ind Pharm 2002; 28(8): 949955. 10 Bhattachar SN et al. Evaluation of the vibratory feeder method for assessment of powder flow properties. Int J Pharm 2004; 269: 385 392. 11 Corrigan DO et al. The effects of spray drying solutions of polyethylene glycol (PEG) and lactose/PEG on their physicochemical properties. Int J Pharm 2002; 235(12): 193205. 12 Takeuchi H et al. Spray dried lactose composite particles containing an ion complex of alginatechitosan for designing a dry coated tablet having a time controlled releasing function. Pharm Res 2000; 17: 94 99. 13 Kawashima Y et al. Effect of surface morphology of carrier lactose on dry powder inhalation property of pranlukast hydrate. Int J Pharm 1998; 172: 179188. 14 Harjunen P et al. Lactose modifications enhance its drug performance in the novel multiple dose Taifun (R) DPI. Eur J Pharm Sci 2002; 16(45): 313321.

Bolhuis GK, Armstrong NA. Excipients for direct compaction: an update. Pharm Dev Technol 2006; 11: 111124. Bolhuis GK, Chowhan ZT. Materials for direct compaction. Alderborn G, Nystrom C, eds. Pharmaceutical Powder Compaction Technology. New York: Marcel Dekker, 1996; 473476. Bolhuis G et al. New developments in spray-dried lactose. Pharm Tech 2004; June: 2631. DMV-Fonterra Excipients. Technical literature: SuperTab 11SD, SuperTab 14SD, 2008. http://www.dmv-fonterra-excipients.com (accessed 27 February 2009). Friesland Foods Domo. Technical literature: Lactopress Spray-Dried, Lactopress Spray-Dried 250, 2008. http://www.domo.nl/pharma (accessed 27 February 2009). Fell JT, Newton JM. The characterization of the form of lactose in spraydried lactose. Pharm Acta Helv 1970; 45: 520522. Fell JT, Newton JM. The production and properties of spray-dried lactose, part 1: the construction of an experimental spray drier and the production of spray-dried lactose under various conditions of operation. Pharm Acta Helv 1971; 46: 226235. Fell JT, Newton JM. The production and properties of spray-dried lactose, part 2: the physical properties of samples of spray-dried lactose produced on an experimental drier. Pharm Acta Helv 1971; 46: 425430. Meggle GmbH. Technical literature: FlowLac 90, FlowLac 100, 2008. http://www.meggle-pharma.de (accessed 27 February 2009). Price R, Young PM. Visualisation of the crystallisation of lactose from the amorphous state. J Pharm Sci 2004; 93: 155164. Sheffield Pharma Ingredients. Technical literature: NF Lactose-315, NF Lactose-316 Fast Flo, 2008. http://www.sheffield-products.com (accessed 27 February 2009).

21 Authors S Edge, AH Kibbe, J Shur. 22 Date of Revision 27 February 2009.

Lanolin
1 Nonproprietary Names BP: Wool Fat JP: Purified Lanolin PhEur: Wool Fat USP: Lanolin 2 Synonyms Adeps lanae; cera lanae; E913; lanolina; lanolin anhydrous; Protalan anhydrous; purified lanolin; refined wool fat. 3 Chemical Name and CAS Registry Number Anhydrous lanolin [8006-54-0] 4 Empirical Formula and Molecular Weight The USP 32 describes lanolin as the purified wax-like substance obtained from the wool of the sheep, Ovis aries Linne (Fam. Bovidae), that has been cleaned, decolorized, and deodorized. It contains not more than 0.25% w/w of water and may contain up to 0.02% w/w of a suitable antioxidant; the PhEur 6.0 specifies up to 200 ppm of butylated hydroxytoluene as an antioxidant. See also Section 18. 5 Structural Formula See Section 4. 6 Functional Category Emulsifying agent; ointment base.

Lanolin
7 Applications in Pharmaceutical Formulation or Technology Lanolin is widely used in topical pharmaceutical formulations and cosmetics. Lanolin may be used as a hydrophobic vehicle and in the preparation of water-in-oil creams and ointments. When mixed with suitable vegetable oils or with soft paraffin, it produces emollient creams that penetrate the skin and hence facilitate the absorption of drugs. Lanolin mixes with about twice its own weight of water, without separation, to produce stable emulsions that do not readily become rancid on storage. See also Section 18. 8 Description

37 9

Lanolin should be stored in a well-filled, well-closed container protected from light, in a cool, dry place. Normal storage life is 2 years. 12 Incompatibilities

Lanolin may contain prooxidants, which may affect the stability of certain active drugs. 13 Method of Manufacture Lanolin is a naturally occurring wax-like material obtained from the wool of sheep, Ovis aries Linne (Fam. Bovidae). Crude lanolin is saponified with a weak alkali and the resultant saponified fat emulsion is centrifuged to remove the aqueous phase. The aqueous phase contains a soap solution from which, on standing, a layer of partially purified lanolin separates. This material is then further refined by treatment with calcium chloride, followed by fusion with unslaked lime to dehydrate the lanolin. The lanolin is finally extracted with acetone and the solvent is removed by distillation. 14 Safety

Lanolin is a pale yellow-colored, unctuous, waxy substance with a faint, characteristic odor. Melted lanolin is a clear or almost clear, yellow liquid. 9 Pharmacopeial Specifications

See Table I.
Table I: Pharmacopeial specifications for lanolin. Test Identification Characters Melting range Acidity and alkalinity Loss on drying Residue on ignition Sulfated ash Water-soluble acids and alkalis Water-soluble oxidizable substances Chloride Ammonia Acid value Iodine value Peroxide value Saponification value Water absorption capacity Paraffins Petrolatum Foreign substances (pesticide residues) Butylated hydroxytoluene JP XV 37438C 40.5% 40.1% 40.036% 41.0 1836 PhEur 6.0 38448C 40.5% 40.15% 4150 ppm 41.0 420 90105 41.0% 4200 ppm USP 32 38448C 40.25% 40.1% 40.035% 1836

Lanolin is widely used in cosmetics and a variety of topical pharmaceutical formulations. Although generally regarded as a nontoxic and nonirritant material, lanolin and lanolin derivatives are associated with skin hypersensitivity reactions, and the use of lanolin in subjects with known sensitivity should be avoided.(2,3) Other reports suggest that sensitivity arises from false positives in patch testing.(4) However, skin hypersensitivity is relatively uncommon;(5) the incidence of hypersensitivity to lanolin in the general population is estimated to be around 5 per million.(6) Sensitivity is thought to be associated with the content of free fatty alcohols present in lanolin products rather than the total alcohol content.(7) The safety of pesticide residues in lanolin products has also been of concern.(8,9) However, highly refined hypoallergenic grades of lanolin and grades with low pesticide residues are commercially available.(10) See also Section 18. 15 Handling Precautions Observe normal precautions appropriate to the circumstances and quantity of material handled. 16 Regulatory Status

10 Typical Properties Autoignition temperature 4458C Density 0.9320.945 g/cm3 at 158C Flash point 2388C Refractive index n40 = 1.4781.482 D Solubility Freely soluble in benzene, chloroform, ether, and petroleum spirit; sparingly soluble in cold ethanol (95%), more soluble in boiling ethanol (95%); practically insoluble in water. 11 Stability and Storage Conditions

Included in the FDA Inactive Ingredients Database (ophthalmic, otic, topical, and vaginal preparations). Included in nonparenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients. 17 Related Substances lanolin, hydrous; lanolin

Cholesterol; hydrogenated lanolin; alcohols; modified lanolin. See also Section 18.

Lanolin may gradually undergo autoxidation during storage. To inhibit this process, the inclusion of butylated hydroxytoluene is permitted as an antioxidant. Exposure to excessive or prolonged heating may cause anhydrous lanolin to darken in color and develop a strong rancidlike odor. However, lanolin may be sterilized by dry heat at 1508C. Ophthalmic ointments containing lanolin may be sterilized by filtration or by exposure to gamma irradiation.(1)

Hydrogenated lanolin Synonyms Adeps lanae hydrogenatus; hydrogenated wool fat. Acid value 41.0 Hydroxyl value 140180 Melting point 45558C Saponification value 48.0 Water 43.0% Comments Some pharmacopeias, such as the PhEur 6.0, contain a monograph for hydrogenated lanolin. This material is a mixture of higher aliphatic alcohols and sterols obtained from the direct, high-pressure, high-temperature hydrogenation of lanolin during which the esters and acids present are reduced to the corresponding alcohols. Hydrogenated lanolin may contain a

3 80

Lanolin, Hydrous
19 Specific References

suitable antioxidant; the PhEur 6.0 specifies not more than 200 ppm of butylated hydroxytoluene. Modified lanolin Comments Some pharmacopeias, such as the USP 32, contain a monograph for modified lanolin. This material is lanolin that has been processed to reduce the contents of free lanolin alcohols and detergent and pesticide residues. It contains not more than 0.25% w/w of water. The USP 32 specifies that it may contain not more than 0.02% w/w of a suitable antioxidant. 18 Comments Lanolin (the anhydrous material) may be confused in some instances with hydrous lanolin since the USP formerly contained monographs for lanolin and anhydrous lanolin in which the name lanolin referred to the material containing 2530% w/w of purified water. However, in the USP 32 the former lanolin monograph (hydrous lanolin) is deleted and the monograph for anhydrous lanolin is renamed lanolin. Since lanolin is a natural product obtained from various geographical sources, its physical characteristics such as color, consistency, iodine value, saponification value, and hydroxyl value may vary for the products from different sources. Consequently, formulations containing lanolin from different sources may also have different physical properties. A wide range of grades of lanolin are commercially available that have been refined to different extents in order to produce hypoallergenic grades or grades with low pesticide contents. Many lanolin derivatives are also commercially available that have properties similar to those of the parent material and include: acetylated lanolin; ethoxylated or polyoxyl lanolin ( water-soluble); hydrogenated lanolin; isopropyl lanolate; lanolin oil; lanolin wax; liquid lanolin; and water-soluble lanolin. A specification for anhydrous lanolin is contained in the Food Chemicals Codex (FCC),(11) where it is described as being used as a masticatory substance in chewing gum base. The EINECS number for lanolin is 232-348-6.

1 Smith GG et al. New process for the manufacture of sterile ophthalmic ointments. Bull Parenter Drug Assoc 1975; 29: 1825. 2 Anonymous. Lanolin allergy. Br Med J 1973; 2: 379380. 3 Breit J, Bandmann H-J. Dermatitis from lanolin. Br J Dermatol 1973; 88: 414416. 4 Kligman AM. The myth of lanolin allergy. Contact Dermatitis 1998; 39: 103107. 5 Wakelin SH et al. A retrospective analysis of contact allergy to lanolin. Br J Dermatol 2001; 145(1): 2831. 6 Clark EW. Estimation of the general incidence of specific lanolin allergy. J Soc Cosmet Chem 1975; 26: 323335. 7 Clark EW et al. Lanolin with reduced sensitizing potential: a preliminary note. Contact Dermatitis 1977; 3(2): 6974. 8 Copeland CA et al. Pesticide residue in lanolin [letter]. J Am Med Assoc 1989; 261: 242. 9 Cade PH. Pesticide residue in lanolin [letter]. J Am Med Assoc 1989; 262: 613. 10 Steel I. Pure lanolin in treating compromised skin. Manuf Chem 1999; 70(9): 1617. 11 Food Chemicals Codex, 6th edn. Bethesda, MD: United States Pharmacopeia, 2008; 526.

20

General References

Barnett G. Lanolin and derivatives. Cosmet Toilet 1986; 101(3): 2344. Osborne DW. Phase behavior characterization of ointments containing lanolin or a lanolin substitute. Drug Dev Ind Pharm 1993; 19: 1283 1302. Smolinske SC. Handbook of Food, Drug, and Cosmetic Excipients. Boca Raton, FL: CRC Press, 1992; 225229.

21 Author MC Bonner. 22 Date of Revision

18 February 2009.

Lanolin, Hydrous
1 Nonproprietary Names BP: Hydrous Wool Fat JP: Hydrous Lanolin PhEur: Wool Fat, Hydrous 2 Synonyms Adeps lanae cum aqua; Lipolan. 3 Chemical Name and CAS Registry Number Hydrous lanolin [8020-84-6] 4 Empirical Formula and Molecular Weight The JP XV describes hydrous lanolin as a mixture of lanolin and 2530% w/w purified water. The PhEur 6.0 describes hydrous lanolin as a mixture of lanolin and 25% w/w purified water; see also Section 18. The PhEur 6.0 additionally permits the inclusion of up to 150 ppm of butylated hydroxytoluene as an antioxidant. See also Lanolin. 5 Structural Formula See Section 4. 6 Functional Category Emulsifying agent; ointment base. 7 Applications in Pharmaceutical Formulation or Technology Hydrous lanolin is widely used in topical pharmaceutical formulations and cosmetics in applications similar to those for lanolin. Hydrous lanolin is commonly used in the preparation of waterin-oil creams and ointments. More water may be incorporated into hydrous lanolin than into lanolin. See also Section 18. 8 Description

Hydrous lanolin is a pale yellow-colored, unctuous substance with a faint characteristic odor. When melted by heating on a water bath,