Oropharyngeal deposition

Direct airway administration of asthma medications through inhalation is most efficient and minimizes systemic adverse effects. Poor inhaler technique can result in increased oropharyngeal deposition of the drug with decreased efficacy and increased adverse effects. Figure 11-1 provides... 

Low oropharyngeal deposition Low device retention Low exhaled loss Multi-dose system. 

A further advantage is the potential for reduced systemic side effects of the HFA-BDP as a result of both reduced oropharyngeal deposition and thus less gastrointestinal absorption from swallowed BDP and the lower total ex-actuator dose needed to achieve comparable efficacy. 

Spacer devices, also known as holding chambers, are used with MDIs to overcome problems in coordinating inhalation with actuation, especially in children, and minimize oropharyngeal deposition of drug particles.Essentially, a spacer serves as a reservoir to hold the aerosol cloud for the patient to inhale through a one-way valve at a natural pace. 

Minimal extrapulmonary loss of drug, with low oropharyngeal deposition, low device retention, and low exhaled loss ... 

Steed, K.P. Towse, L.J. Freund, B. Newman, S.P. Lung and oropharyngeal depositions of fenoterol hydrobromide delivered from the prototype HI hand-held multidose respi-mat nebuliser. Eur. J. Pharm. Sci. 1997, 5, 55-61. 

The probability of oropharyngeal deposition is determined more by droplet size than by velocity and density because the particle inertia is proportional to the density, velocity, and the square of the diameter. It, therefore, follows that oropharyngeal drug deposition is reduced and the respirable drug delivery is increased when MDI sprays are finely atomized and evaporate rapidly. Such MDI sprays are generally promoted by increasing the propellant vapor pressure and reducing the actuator spray nozzle diameter.f ... 

The spray droplet size distribution has a major influence on the amount of oropharyngeal deposition and the amount of drug delivered to the lungs and the regions of lung deposition. Methods for spray droplet particle sizing from MDIs " have been reviewed. 

The deposition in the mouth is largely due to impaction (except for ultrafine aerosols). This mode of deposition therefore increases with particle size and velocity. The reduction of oropharyngeal deposition is desirable both to improve the efficiency of lung deposition and to reduce its variability [26]. To accomplish this, the velocity of the particles must be sufficiently low. The lower bound for the particle velocity is dictated by the inspiratory flow carrying the aerosol cloud. But some aerosol generators impart high velocity to the particles in the course of formation of the aerosol cloud. 

Clark AR, Newman SP, Dasovich N. Mouth and oropharyngeal deposition of pharmaceutical aerosols. J Aerosol Med 1998 ll(suppl. 1) 116—121. 

Dolovich M, Rhem R. Impact of oropharyngeal deposition on inhaled dose. J Aerosol Med 1998 ll(suppl 1) S112-S115. 

Lung deposition of fenoterol with the use of Respimat, a MDI, and a MDI plus Aerochamber in healthy volunteers was found to be 39, 11 and 10%, respectively. The use of Respimat resulted in uniform deposition of drugs throughout the peripheral, intermediate, and central lung zones. On the other hand, oropharyngeal deposition of fenoterol from Respimat was lower than that from the MDI (37% vs 72%). 

Local adverse effects from ICSs include oropharyngeal candidiasis and dysphonia that are dose-dependent. The dysphonia appears to be due to a local corticosteroid-induced myopathy of the vocal cords. The use of a spacer device can decrease oropharyngeal deposition and thus decrease the incidence and severity of local side effects. In infants who require delivery through a facemask, the parent should clean the nasal-perioral area with a damp cloth following each treatment to prevent topical candidal infections. 

Steed, K. P., L. J. Towse, B. Freund, and S. P. Newman. 1997. Lung and oropharyngeal depositions of fenoterol hydrobromide delivered from the prototype III hand-held multidose Respimat nebuliser. Eur.. Pharmaceut. Sci. 5 55-61. 

It is possible to evaluate the balance between pulmonary bioavailabiUty and systemic bioavailability if the following data are known retention of the drug in the inhaler, the percentage pulmonary and oropharyngeal deposition of the drug, the degree of Gl absorption, and the inactivation by the first-pass metaboUsm. From these data the L/T ratio (L = local bioavailability T = systemic bioavailabiUty) can be derived. 

The patient s inspiratory flow rate also affects impaction of aerosol particles in the oral cavity. Data from a study by Anderson et al. show the effect of increasing inspiratory flow rate on oropharyngeal deposition of an aerosol with 3.0-pm MM AD (6). In that study, the authors increased flow rate from 0.4 to 1.2 L/s in a group of normal subjects. The aerosol was generated by nebulizer, so there was no additional effect of pressurized propellant. As inspiratory flow rate increased, average deposition in the oral cavity increased from 20 to 38%. 

In another experiment, the investigators instructed volunteers to inhale histamine aerosol that was generated by jet nebulizer at 0.6 and 0.055 L/s. They reported that airway resistance was increased after the slower inhalation maneuver (i.e., 2.83 X baseline) compared to that recorded after the faster inhalation (i.e., 2.23 X baseline) (p <0.05). Based on their first experiment, the investigators concluded that the enhanced potency in histamine aerosol, observed during the slower inhalation maneuver, could be due to reduced oropharyngeal deposition and increased penetration of drug into the lungs (70). 

Dolovich et al. reported that oropharyngeal deposition was reduced from 65% of the emitted dose to 6.5% in a group of patients with varying degrees of airflow obstruction who inhaled aerosol from an MDI alone and an MDI used in combination with the small volume Aerochamber spacer, respectively. Total and regional lung deposition fractions were unaltered by the addition of the spacer (76). 

Newman studied the effect of using a larger-volume spacer (Nebuhaler) in combination with an MDI. In nine patients with obstractive lung disease, they found that oropharyngeal deposition decreased from 80.9% with the MDI alone to 16.5% with the MDI/spacer. Lung deposition increased from 8.7 to 20.9% (77). 

The reduction in oropharyngeal deposition by using a spacer with an MDI is especially important in the case of inhaled steroids because it also reduces the incidence of candidiasis. Thus, using a spacer with an inhaled steroid is a good example of how the therapeutic index of this class of drug can be enhanced. Nevertheless, there is little evidence to suggest that spacers improve the clinical outcome of inhaled medications. For more details about spacers, we refer the reader to Chap. 12. 

Newman and colleagues (78), found lung deposition was improved over the metered-dose inhaler alone at both slow (25 L/min) and fast (100 L/min) inhalation rates, with the slower inhalation rate achieving the highest total and peripheral lung delivery. Oropharyngeal deposition was halved. 

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