Brittle fracture index: 0.0362



(a)

Stability and Storage Conditions

Bonding index: 0.0049 (at compression pressure 177.8 MPa)

Density  (true):  1.589 g/cm3  for  anhydrous  b-lactose;

1.567 g/cm3 for Super-Tab Anhydrous.

Density (bulk): 0.68 g/cm3 for Pharmatose DCL 21; 0.67 g/cm3 for Pharmatose DCL 22; 0.65 g/cm3 for Super-Tab Anhy- drous.

Density (tapped): 0.88 g/cm3 for Pharmatose DCL 21;

0.79 g/cm3 for Pharmatose DCL 22; 0.87 g/cm3 for Super- Tab Anhydrous.

Mold growth may occur under humid conditions (80% RH and above). Lactose may develop a brown coloration on storage, the reaction being accelerated by warm, damp conditions; see Section 12. At 808C and 80% RH, tablets containing anhydrous lactose have been shown to expand 1.2 times after one day.(2)

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

Lactose, Anhydrous 387

Table II: Particle size distribution of selected commercially available lactoses.

Supplier/grade Percentage less than stated size

Incompatibilities

Lactose anhydrous is incompatible with strong oxidizers. When mixtures containing a hydrophobic leukotriene antagonist and anhydrous lactose or lactose monohydrate were stored for six weeks at 408C and 75% RH, the mixture containing anhydrous lactose showed greater moisture uptake and drug degrada- tion.(3)

Studies have also shown that in blends of roxifiban acetate (DMP-754) and lactose anhydrous, the presence of lactose anhydrous accelerated the hydrolysis of the ester and amidine groups.(4)

See Lactose, Monohydrate.

Method of Manufacture

There are two anhydrous forms of lactose: a-lactose and b- lactose. The anhydrous forms that are commercially available may exhibit hygroscopicity at high relative humidities. Anhy- drous lactose is produced by roller drying a solution of lactose above 93.58C. The resulting product is then milled and sieved. Two anhydrous a-lactoses can be prepared using special drying techniques: one is unstable and hygroscopic, the other exhibits good compaction properties.(5) However, these materials are not commercially available.

Safety

Lactose is widely used in pharmaceutical formulations as a diluent and filler-binder in oral capsule and tablet formulations. It may also be used in intravenous injections. Adverse reactions to lactose are largely due to lactose intolerance, which occurs in individuals with a deficiency of the intestinal enzyme lactase, and is associated with oral ingestion of amounts well over those in solid dosage forms.

See Lactose, Monohydrate.

Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of materials handled. Excessive generation of dust, or inhalation of dust, should be avoided.

Regulatory Status

Included in the FDA Inactive Ingredients Guide (IM, IV, and SC injections; oral capsules and tablets; inhalation preparations;



rectal, transdermal, and vaginal preparations). Included in nonparenteral and parenteral medicines licensed in the UK. Included in the Canadian List of Acceptable Non-medicinal Ingredients.

Related Substances

Lactose, monohydrate; lactose, spray-dried.

Comments

Lactose anhydrous has been used experimentally in hydrophilic matrix tablet formulations(6) and evaluated for dry powder inhalation applications.(7,8) Partial hydration of anhydrous lactose increases the specific surface area and reduces the flow properties of powders but has no effect on compactibility.(9) A specification for lactose is included in the Food Chemicals Codex (FCC); see Lactose, Monohydrate. The EINECS number for lactose anhydrous is 200-559-2.

Specific References

Kibbe AH, ed. Handbook of Pharmaceutical Excipients, 3rd edn. London and Washington, DC: Pharmaceutical Press and American Pharmaceutical Association, 2000: 642–643.

Du J, Hoag SW. The influence of excipients on the moisture senstitive drugs aspirin and niacinamide: comparison of tablets containing lactose monohydrate with tablets containing an- hydrous lactose. Pharm Dev Tech 2001; 6(2): 159–166.

Jain R, Railkar AS, Malick AW, et al. Stability of a hydrophobic drug in presence of hydrous and anhydrous lactose. Eur J Pharm Biopharm; 1998; 46(2): 177–182.

Badawy SI, Williams RC, Gilbert DC. Effect of different acids on solid state stability of an ester prodrug of a IIb/IIIa glycoprotein receptor antagonist. Pharm Dev Technol 1999; 4(3): 325–331.

Lerk CF, Andreae AC, de Boer AH, et al. Increased binding capacity and flowability of alpha-lactose monohydrate after dehydration. J Pharm Pharmacol 1983; 35(11): 747–748.

Heng PW, Chan LW, Easterbrook MG, Li X. Investigation of the influence of mean HPMC particle size and number of polymer particles on the release of aspirin from swellable hydrophilic matrix tablets. J Control Release 2001; 76(1–2): 39–49.

Larhrib H, Zeng XM, Martin GP, et al. The use of different grades of lactose as a carrier for aerosolized salbutamol sulphate. Int J Pharm 1999; 191(1): 1–14.

Vanderbist F, Wery B, Moyano-Pavon I, Moes AJ. Optimization of a dry powder inhaler formulation of nacystelyn, a new mucoactive agent. J Pharm Pharmacol 1999; 51(11): 1229–1234.

388 Lactose, Anhydrous

Cal S, Iglesias G, Souto C, et al. Effects of hydration on the properties of a roller-dried b-lactose for direct compression. Int J Pharm 1996; 129: 253–261.

General References

Bolhuis GK, Chowhan ZT. Materials for direct compaction. In: Alderborn G, Nystrom C, eds. Pharmaceutical Powder Compaction Technology. New York: Marcel Dekker, 1996: 469–473.

Borculo Domo Ingredients. Technical literature: Lactopress Anhydrous,

Lactopress Anhydrous 250, 2003.

DMV International. Technical literature: Pharmatose DCL 21, 2003. DMV International. Technical literature: Pharmatose DCL 22, 2004.

Lactose New Zealand. Technical literature: Super-Tab Anhydrous, 2004.

Quest International Inc. (Sheffield Products). Technical literature: Anhydrous Lactose NF Direct Tableting, Anhydrous Lactose NF 60M, 2004.

Authors

S Edge, A Kibbe, K Kussendrager.

Date of Revision

27 August 2005.