Aerosols inhalation properties

Battelle Pacific Northwest Labs. 1975. Effect of physico-chemical properties on metabolism of transuranium oxide aerosols inhaled by beagle dogs. Richland, WA Battelle Pacific Northwest Labs. BNWLSA5430. 

SABAs, such as albuterol, are hydrophilic and have onset of action within 5 to 15 minutes after aerosol inhalation, reach peak response within 0.5 to 2 hours, and have a response that is sustained for 4 to 6 hours. Men have a greater volume of distribution for albuterol than women, but African Americans and European Americans have no difference in albuterol pharmacokinetics [9]. In comparison, the onset of bronchodilation is 30 to 50 minutes for LABAs such as salmeterol because of their lipophilicity, a property resulting from the addition of a long side chain. Peak response... 

Isoetharine, a sympathomimetic agent with bronchodilating properties (aerosol inhaler 340 mcg/metered spray), is indicated in the treatment of bronchial asthma and reversible bronchospasm that may occur with bronchitis and emphysema (see also Figure 94). 

The two main determinants for medicine deposition in the respiratory tract are the aerodynamic size distribution of the aerosol and the manoeuvre with which the aerosol is inhaled. They govern the mechanisms that are respraisible for particle deposition in the lungs. By varying the inhalation manoeuvre, not only the distribution in the airways for the same aerosol is changed in many cases also the amount and properties of the delivered fine particle dose are affected. The complex interplay between inhalation manoeuvre, aerosol properties and site of deposition has led to many misconceptions regarding the best inhaler choice for individual patients and the way these inhalers need to be operated to achieve optimal therapy for the patient. In this chapter the medicine deposition mechanisms for inhaled aerosols are explained as functions of the variables involved. In addition, the working principles of different inhaler types are described and it is discussed how their performance depends on many inhalation variables. Finally, some persistent misconceptions in the literature about the most preferable dry powder inhaler properties and performance are umaveUed. 

In the United States, use of CEC propeUants, designated as PropeUants 11, 12, and 114, is strictly limited to specialized medicinal aerosol products such as metered-dose inhalers. The physical properties and chemical names of these propeUents are given in Table 2. 

Propagated outbreaks of infection relate to the direct transmission of an infective agent from a diseased individual to a healthy, susceptible one. Mechanisms of such transmission were described in Chapter 4 and include inhalation of infective aerosols (measles, mumps, diphtheria), direct physical contact (syphilis, herpes virus) and, where sanitation standards are poor, through the introduction of infected faecal material into drinking water (cholera, typhoid). The ease oftransmission, and hence the rate of onset of an epidemic (Fig. 16.3) relates not only to the susceptibility status, and general state of health of the individuals but also to the virulence properties of the organism, the route oftransmission, the duration of the infective period associated with the disease. 

Dry powders must be able to flow readily in order to leave the capsule or powder reservoir, but must also generate a fine aerosol enabling the patient to inhale a proper dose. These two requirements are often difficult to achieve simultaneously. Fine powders tend to be eohesive and have poor flow properties. Blending with a carrier phase, pelletization, and other approaches have been used to overcome these limitations. The featmes of blends and homogeneous powders are compared in Table 4 from a DPI device perspective ... 

Adhesive mixtures require large carrier crystals to improve the handhng properties of the powders. Dispersion of the small drng particles over the larger carrier material should assure dose uniformity. However, the small dmg particles shonld be removed from the carrier material dnring inhalation, to render an aerosol clond of respirable particles. If the particles remain on the carrier, month or throat deposition of the drng will occur, which might decrease therapeutic efficacy or cause serious side-effects. 

The potential for liquid aerosols or finely divided powders to be inhaled will be determined by their particle size. Deposition patterns for dusts will depend not only on the particle size of the dust but also the hygroscopicity, electrostatic properties and shape of the particles, and the respiratory dynamics of the individual. Thus, it is only possible to make very general statements about sites of... 

Even when the appropriate inhaler is chosen, the influence of the disease state cannot be ignored. Disease states can influence the dimension and properties of the airways and hence the disposition of any inhaled drug. Thus, great care must be taken when extrapolating the findings based on intratracheal administration to different animal species in order to predict deposition profiles after inhalation of aerosol formulations by patients suffering from airway disease. DPIs are not appropriate in many diseases when the ability to have sufficient airflow is hindered. Since many diseases that we would like to treat via pulmonary administration of biomolecules cause a decrease in airflow, we must be careful in the decision of which type of inhalation mechanism to choose. 

Fujitani, Y., Kobayashi, T., Arashidani, K., Kunugita, N. and Suemura, K. (2008) Measurement of the physical properties of aerosols in a fullerene factory for inhalation exposure assessment /. Occup. Environ. Hyg., 5 (6), 380-389. 

At present, dry powder inhalers (DPIs) are not used as commonly in the United States as are pMDIs. DPIs have been the last pharmaceutical inhalation aerosol system developed. Although the concept of operation is readily envisioned for these devices, the development of an efficient dry powder dispersion device intended for lung delivery has been notoriously difficult. Most of these devices function by using interactive mixtures of fine drug particles (1-5 pm diameter) and carrier excipient particles (usually 75 200 pm). Some evidence suggests that DPI performance is dictated largely by the physicochemical properties of the excipients used (5). However, as will be discussed, the availability of different choices of excipients is very limited, particularly in the United States. 

Podczeck F. The influence of particle size distribution and surface roughness of carrier particles on the in vitro properties of dry powder inhalations. Aerosol Sci Technol 1999 31 (4) 301 321. 

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