Lactose, Monohydrate

Nonproprietary Names

BP: Lactose monohydrate

PhEur: Lactosum monohydricum JP: Lactose

USPNF: Lactose monohydrate

Synonyms

See Tables II and III.

Chemical Name and CAS Registry Number

O-b-D-Galactopyranosyl-(1→4)-a-D-glucopyranose mono- hydrate [64044-51-5]

Empirical Formula and Molecular Weight

C12H22O11·H2O 360.31

Structural Formula

 

The USPNF 23 describes lactose monohydrate as a natural disaccharide, obtained from milk, which consists of one galactose and one glucose moiety. The PhEur 2005 describes lactose monohydrate as the monohydrate of O-b-D-galactopyr- anosyl-(1→4)-a-D-glucopyranose. It is stated in the USPNF 23 that lactose monohydrate may be modified as to its physical characteristics, and may contain varying proportions of amorphous lactose.

Functional Category

Binding agent; diluent for dry-powder inhalers; tablet binder; tablet and capsule diluent.

Applications in Pharmaceutical Formulation or Technology

Lactose is widely used as a filler or diluent in tablets and capsules, and to a more limited extent in lyophilized products and infant formulas.(1–13) Lactose is also used as a diluent in dry-powder inhalation.(14–16) Various lactose grades are commercially available that have different physical properties such as particle size distribution and flow characteristics. This permits the selection of the most suitable material for a particular application; for example, the particle size range selected for capsules is often dependent on the type of

encapsulating machine used. Usually, fine grades of lactose are used in the preparation of tablets by the wet-granulation method or when milling during processing is carried out, since the fine size permits better mixing with other formulation ingredients and utilizes the binder more efficiently.

Other applications of lactose include use in lyophilized products, where lactose is added to freeze-dried solutions to increase plug size and aid cohesion. Lactose is also used in combination with sucrose (approximately 1 : 3) to prepare sugar-coating solutions.

Direct-compression grades of lactose monohydrate are available as granulated/agglomerated a-lactose monohydrate, containing small amounts of anhydrous lactose.

Direct-compression grades are often used to carry lower quantities of drug and this permits tablets to be made without granulation.

Other directly compressible lactoses are spray-dried lactose and anhydrous lactose. See Lactose, Spray-Dried, Lactose, Anhydrous.

Description

In the solid state, lactose appears as various isomeric forms, depending on the crystallization and drying conditions, i.e. a- lactose monohydrate, b-lactose anhydrous, and a-lactose anhydrous. The stable crystalline forms of lactose are a-lactose monohydrate, b-lactose anhydrous, and stable a-lactose anhydrous.

Lactose occurs as white to off-white crystalline particles or powder. Lactose is odorless and slightly sweet-tasting; a-lactose is approximately 20% as sweet as sucrose, while b-lactose is 40% as sweet.

SEM: 1

Excipient: Pharmatose 125M Manufacturer: DMV International Magnification: 100×

Voltage: 1.5 kV

 

390 Lactose, Monohydrate

SEM: 2

 Excipient: Pharmatose DCL 15 Manufacturer: DMV International

Pharmacopeial Specifications

See Table I.

Table I: Pharmacopeial specifications for lactose, monohydrate.

SEM: 3

Excipient: Wyndale Milled 100 Mesh Manufacturer: Lactose New Zealand



Water 4.5–5.5%(a) 4.5–5.5% 4.5–5.5%

Sulfated ash 40.1% 40.1% —

Magnification: 50×

Voltage: 10 kV

Microbial limit

Aerobic

4100/g 4102/g 4100/g

 SEM: 4

Excipient: Wyndale Sieved 80 Mesh Manufacturer: Lactose New Zealand Magnification: 50×

Voltage: 10 kV

 

(a) 4.0–5.5% for granulated powder.

(b) For the granulated powder, not more than 1.0%.

(c) Modified monohydrate form, not more than 1.0%.

Typical Properties

Angle of repose: 338 for Pharmatose DCL 15; 328 for

Tablettose 70 and Tablettose 80.

Brittle fracture index:

0.0749 (at compression pressure 189.5 MPa);

0.0883 (at compression pressure 191.0 MPa).(a)

Bonding index:

0.0081 (at compression pressure 189.5 MPa);

0.0052 (at compression pressure 191.0 MPa).(a) Compression pressure: 18.95–19.10 kN/cm2 Density (true): 1.545 g/cm3 (a-lactose monohydrate) Density (bulk): see Table II.

Density (tapped): see Table II.

Melting point: 201–2028C (for dehydrated a-lactose mono- hydrate)

Moisture content: lactose monohydrate contains approxi- mately 5% w/w water of crystallization and normally has a range of 4.5–5.5% w/w water content. See Table II.

Particle size distribution: see Table III.

Permanent deformation pressure:

370.0 MPa (at compression pressure 189.5 MPa);

485.0 MPa (at compression pressure 191.0 MPa).(a)

Reduced modulus of elasticity:

1472 (at compression pressure 189.5 MPa);

5155 (at compression pressure 191.0 MPas).(a)

Solubility: see Table IV.

Specific surface area: 0.08–0.14 m2/g for Lactochem Crystals and Lactochem Lactohale;(14) 0.23 m2/g for Pharmatose 200M.

Specific rotation [a]20: +54.48 to +55.98 as a 10% w/v solution. Lactose exhibits mutarotation and an equilibrium

Lactose, Monohydrate 391

Table II: Typical physical properties of selected commercially available lactose, monohydrate.

mixture containing 62% b-lactose and 38% a-lactose is obtained instantly on the addition of a trace of ammonia.

Tensile strength:

Supplier/grade Density (bulk)

(g/cm3)

Borculo Domo Ingredients

Crystals

Density

(tapped) (g/cm3)

Water

content (%)

2.987 MPa (at compression pressure 189.5 MPa);

2.517 MPa (at compression pressure 191.0 MPa).(a)

Water content: see Table II.

(a) Methods for characterizing the mechanical properties of compacts of pharmaceutical ingredients are specified in the Handbook of Pharmaceutical Excipients, 3rd edn.(17)