Lactose, Inhalation

Basic Information

Name: Lactose, Inhalation

CAS No: Inhalation lactose is lactose monohydrate, O-b-D-galactopyranosy, (1!4)-a-D-glucopyranose monohydrate [5989-81-1], [10039-26-6], [64044-51-5],

Functional Categories

Diluent Dry powder inhaler carrier

1. Nonproprietary Names

None adopted.

2. Synonyms

Inhalac; inhalation lactose; Lactohale; Respitose. For grades

3. Chemical Name & CAS Registry

Inhalation lactose is lactose monohydrate, O-b-D-galactopyranosy, (1!4)-a-D-glucopyranose monohydrate [5989-81-1], [10039-26-6], [64044-51-5],

4. Empirical Formula & Molecular Weight

C12H22O11 342.30 (for anhydrous) C12H22O11H2O 360.31 (for monohydrate)

5. Structural Formula

See Lactose, Anhydrous; Lactose, Monohydrate.

6. Applications

Inhalation lactose is widely used as a carrier, diluent, and flow aid in dry powder inhalation formulations. Inhalation lactose of suitable particle size can also be used to prepare soft pellets of dry powder inhaler formulations. See also Lactose, Anhydrous; Lactose, Monohydrate

7. Description

Lactose occurs as white to off-white crystalline particles or powder. It is odorless and slightly sweet-tasting.

8. Pharmacopeial Specifications

See Lactose, Anhydrous; Lactose, Monohydrate.

9. Typical Properties

Density (bulk) see Table I. Density (tapped) see Table I. Loss on drying see Table I. Particle size distribution see Table II. Surface area

10. Stability & Storage

Inhalation lactose should be stored in a well-closed container in a cool, dry place

11. Incompatibilities

Lactose is a reducing sugar. Typical reactions include the Maillard reaction with either primary(1) or secondary amines.(2) See also Lactose, Anhydrous; Lactose, Monohydrate.

12. Method of Manufacture

Inhalation lactose is manufactured by milling, sieving, air classifying, micronizing and/or blending pharmaceutical grade lactose, typically in dedicated facilities. Although off-the-shelf grades are available, the manufacturing processes can be tailored to produce lactose with properties for a specific application

13. Safety

Lactose is widely used in pharmaceutical formulations as a diluent in oral capsule and tablet formulations, and has a history of being used in dry powder inhaler formulations. Adverse reactions to lactose are largely due to lactose intolerance, which occurs in individuals with a deficiency of the enzyme lactase. Recently, the presence of milk proteins in lactose-containing dry powder inhalers, which can cause anaphylaxis in cases of severe allergy to cow’s milk, has been reported.(3,4) In view of the route of administration, inhalation lactose should be tested to additional micobiological specifications, for example, endotoxins, as requested by the regulatory authorities. Inhalation lactose is typically supplied with an increased range of microbiological tests. See also Lactose, Anhydrous; Lactose, Monohydrate.

14. Handling Precautions

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

15. Regulatory Status

GRAS listed. Included in the FDA Inactive Ingredients Database (inhalation preparations). Included in nonparenteral and parenteral medicines licensed in the UK, which refer to lactose monohydrate in general.

16. Related Substances

ee Lactose, Anhydrous; Lactose, Monohydrate.

17. Comments

Lactose is one of a very small number of excipients that are used in marketed dry powder inhaler products. Specific grades of inhalation lactose can be produced from the readily available wide range of pharmaceutical lactose grades using standard pharmaceutical manufacturing processes. Lactose is found in capsule, blister, and reservoir-based dry powder inhaler products. The relatively low mass per dose of lactose used means that, compared with conventional oral solid dosage forms, the levels of inhalation lactose ingested during inhalation are relatively small. In view of the importance of particle characteristics for powder blending and drug product performance(5–12), it has been suggested that pharmacopeial monograph acceptance criteria are not adequate for controlling key physicochemical characteristics for inhalation applications of this excipient. Accordingly, further material controls may be required to ensure consistent drug product pharmaceutical performance, such as control of surface properties. The effect of modifying the surfaces of lactose particles by particle smoothing, crystallization, and co-processing with other excipients on the aerosolization performance has been reported.(13–19) See also Lactose, Anhydrous; Lactose, Monohydrate.