Disintegration of weak lactose agglomerates for inhalation applications

Inhalation is a convenient and effective method of drug delivery for a number of common illnesses, many of which affect the respiratory system, such as asthma. Lactose is a commonly used material in the pharmaceutical industry as a carrier of drugs. The use of weak lactose agglomerates in dry powder inhalers depends very much on the way the agglomerates disintegrate. The disintegration of weak agglomerates depends on the bonding mechanism and the agglomerate structure, both of which are to date poorly understood. An experimental study of the disintegration of weak lactose agglomerates is reported here. The effects of agglomerate size and ambient humidity level on the extent and mechanism of breakage are investigated using a single agglomerate impact testing technique. The extent of disintegration is shown to scale with the square of the impact velocity. The dry-kept agglomerates are shown to fail in a mode similar to the ductile failure mode of solid materials, with large overall deformation and internal shearing, without the development of a clear crack plane. Agglomerates which have been kept in a humid environment exhibit a classical semi-brittle failure mode. The experimental results of impact tests with dry-kept agglomerates compare well to the results of numerical simulations using distinct element analysis (DEA). The impact test appears to be a useful tool for the determination of the influence of material properties and structure and process conditions on the breakage behaviour. (C) 1998 Elsevier Science B.V. All rights reserved.