Cd

Figure 3 Theoretical pulmonary deposition as a function of particle size for a range of distributions. (With permission of Journal of Pharmacy and Pharmacology.)

a result of their charge characteristics and become larger "particles," reduced in number, with the concomitant effect on deposition [25-27]. Second, the airways sometimes have charged areas at their surface that may influence charged particles to deposit [28]. Shape seriously influences deposition only when particles deviate significantly from sphericity. This is rarely the case with pharmaceutical inhalation aerosol particles or droplets. Hygroscopicity is the tendency of particles to associate with water in the atmosphere. Considerable effort has been expended in elucidating the behavior of hygroscopic environmental aerosols [29-37]. The airways of the lung have a relative humidity of 99.5% at a body temperature of 37°C [38-41].

Hygroscopic particles will grow in diameter as they associate with water [42,43]. Drugs that exhibit aqueous solubility will dissolve in the water, and this brings about further rapid association [6,17,42,44-46]. It has been suggested, for example, that cromolyn sodium and isoproterenol sulfate dihydrate grow to more than 2.5 times their original diameter in the lung [47]. Because this growth occurs rapidly, it influences deposition of particles in the respiratory tract [48-55].

This chapter is not concerned with specific formulation issues; however, referring to the prospect of controlled release of drugs from aerosols in the lung is worthwhile. The immediate benefit of this approach stems from the occurrence of nocturnal asthma and the need to treat this condition [56]. Several approaches have been taken to achieve this aim, ranging from reformulation [57] to the use of drug-carrier systems [58-64]. Although oral controlled-release theophylline

Figure 3 Theoretical pulmonary deposition as a function of particle size for a range of distributions. (With permission of Journal of Pharmacy and Pharmacology.)

exists, circadian pharmacokinetics may result in toxic systemic levels of the drug [65]. There would be great merit in developing a controlled-release inhaled product because this would target the site of action and present drug in small quantities, thus reducing the incidence of unwanted side effects. It has been suggested, however, that the maximum residence time of pharmaceutical aerosol particles in the lung is 12 hr [66]. This observation is based on lung deposition of particles and their removal by mucociliary clearance. Materials that prolong the residence time of drug in the lung should be viewed with some caution because they may pose a toxicity problem [67]. Therefore, some limitations to the effectiveness of a controlled-release delivery system may exist.

Coping with Asthma

Coping with Asthma

If you suffer with asthma, you will no doubt be familiar with the uncomfortable sensations as your bronchial tubes begin to narrow and your muscles around them start to tighten. A sticky mucus known as phlegm begins to produce and increase within your bronchial tubes and you begin to wheeze, cough and struggle to breathe.

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