Info

Soluble drug

Transported on mucus escalator to pharynx

Dissolves ¡n lung fluids

Expectorated

Local effects: toxic, irritative pharmacological

Swallowed i

Local metabolism

Excreted in faeces

Absorbed from gastrointestinal tract, enters bloodstream

Enters blood

Systemic effect

Systemic effect

Excreted in urine

Excreted in urine

Figure 9.45 The fate of particles of (a) 5 ^m and (b, see opposite page) 2 ^m in diameter deposited in alveoli.

Reproduced from D. G. Clark, Proc. Eur. Soc. Study Drug Toxicity, 15, 252 (1974).

particles by uptake of water from the moist air in the respiratory system. Apart from its importance in determining the efficiency of an aerosol in reaching the alveoli, particle size may be critical in determining response, because of the influence of particle size on rate of solution.

The effect of particle size on the fate of particles inhaled from an aerosol is shown in Fig. 9.45.

When used by patients, the Spinhaler delivers about 25% by weight of sodium cro-moglicate, which is normally dispersed as particles below 6 ^m in diameter, about 5% being less than 2 ^m diameter. The mass medium diameter (and geometric standard deviation) of the sodium cromoglicate particle batches used were, respectively, 2 ± 1.2 and 11.7 ± 1.1 ^m. There is no doubt that the biological effect of the small particle material is dramatically greater than that of coarser material, hence the importance of storage conditions of the sodium cromoglicate cartridge capsules to prevent aggregation of the particles of drugs. Although the Spinhaler is designed to break up aggregates, its efficiency will be reduced if moisture uptake is increased by storage in humid conditions, either in the pharmacy or in the home. If aerosols of this drug with large (11 ^m diameter) size particles are administered, up to 66% of the dose will end up in the mouth.

An alternative dry powder aerosol device is illustrated in Fig. 9.46 and the mechanism of dispersion of powdered drug in a Ventodisk or Becodisk system is shown in Fig. 9.47

Types of pressurised aerosol

Typical pressurised aerosol systems are discussed in Chapter 7. In two-phase systems the

Insoluble drug

Engulfed by alveolar macrophages

Carried to ciliated epithelium

Transported by mucus escalator to pharynx

Expectorated

Swallowed

Absorbed in gastrointestinal tract

Systemic effect

Excreted in urine

2 mm PARTICLES

Excreted in faeces

Pulmonary deposition

Penetrates the alveolar membrane

Sequestered within tissue

Figure 9.45 (continued).

Reproduced from D. G. Clark, Proc. Eur. Soc. Study Drug Toxicity, 15, 252 (1974).

Soluble drug

Dissolves in

lung fluids

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