Inspiratory flow rate

Deposition experiments were carried out in replicate hollow casts of the upper airways or a human tracheobronchial tree using 0.2, 0.15 and 0.04 ym diameter particles and cyclic inspiratory flow rates of approximately 1 8 and 34 liters per minute (L/min) (see Table I). The replicates were produced from a single solid master airway cast prepared from the lungs of 34 year old male. The airway dimensions of the cast corresponded closely with the population mean of eight adult males as reported by Nikiforov and Schlesinger (1985). The airway diameters are somewhat larger and... 

Dry powder inhalers are generally described as breath actuated devices, because the inspiratory airstream releases the dose from the dose system and supplies the energy for the generation of fine drug particles from the powder formulation. Because the efficiency of dose release and powder disintegration increases with increasing inspiratory flow rate for most DPIs, these devices would be better described as breath controlled devices. In Section 3.9, the effect of resistance and clinical conditions on the flow curve and relevant flow parameters for DPIs are discussed. 

DPIs do not utilize Freon propellants, but use either with or without lactose as vehiculum. These devices have a clinical efficacy similar to standard metered-dose inhalers, but may be easier to use in selected patients, since a minimal inspiratory flow rate is necessary to inhale from a DPI. Therefore, the DPI may be difficult for patients with an insufficient inspiratory flow rate, which occurs in children, the elderly, people with severe COPD shared with diaphragm dysfunction, and during an exacerbation. The inspiratory flow rate is associated with the internal resistance of the device used. For instance the turbuhalor has a significant internal resistance and its delivered dose is dependent from the inspiratory flow rate. 

MDI delivery efficiency depends on the patient s inspiratory flow rate, breathing pattern and hand-mouth coordination. Increases in tidal volume and decreases in respiratory frequency enhance the peripheral deposition in the lung. Most patients need to be trained to use the MDI correctly, as up to 70% of patients fail to do so [26, 30]. 

Dolovich, M. A. (2000), Influence of inspiratory flow rate, particle size, and airway caliber on aerosolized drug delivery to the lung, Respir. Care, 45, 597-608. 

Pedersen, S., Hansen, O. R., and Fuglsang, G. (1990), Influence of inspiratory flow rate upon the effect of a turbuhaler, Arch. Dis. Child., 65,308-310. 

Inhalation at a low inspiratory flow rate (below 20L/min) to minimize upper airway and large airway deposition. 

The unit dose package contains the unit dose reservoir and an array of laser drilled nozzles, and the reservoir and nozzle array are connected with a heat seal that allows the formulation to flow from the reservoir to the nozzle after the seal is ruptured. The piston assembly consists of a motor, a piston, and a cam, which compresses the unit dose packet to extrude the drug under pressure through the nozzle array to produce aerosols suitable for inhalation. The AERx also has internal electronic monitoring, which measures the patient s inspiratory flow rate as a function of time of inspiration and triggers the dispensing of the dose at a predetermined inspiratory flow rate and time for... 

We have already discussed the impact of inspiratory flow rate on deposition the faster the subject inhales, the more material is deposited at bends and bifurcations in the upper and central airways, and the less material reaches the deep lung. Inspiratory flow rate may also affect the performance of inhalation systems this is particularly important in passive dry powder inhalers in which the energy of breathing is utilized to deagglomerate the formulation. Thus, for such systems, there is a contradictory requirement for the need to use high inspiratory flow rate to achieve fine particle size for deep lung delivery and yet to have sufficiently low inspiratory flow rate to avoid impaction before the drug entry to the absorptive surfaces devoid of mucociliary clearance. 

However, patients with low inspiratory flow rate (essentially children) have many difficulties to use them. Furthermore, when the particles are inhaled quickly, their inertia increases and there is an impaction in the throat. So, new devices are developed to improve the patient s compliance. They consist of a pump that compresses air in a special chamber so that the powder is expulsed as a cloud, owing to the pressure delivered by the compressed air. These systems are close to the old MDI. 

Oseltamivir is administered as an oral capsule and zanamivir by inhalation. Inhaled zanamivir has fewer adverse effects than oral oseltamivir, but there are concerns about its use in young and elderly patients, who are generally unable to achieve the inspiratory flow rate needed to ensure adequate lung deposition (2). Oral oseltamivir is more convenient and easier to administer, but needs to be given with food to lower the frequency of gastrointestinal adverse effects. 

Tiotropium is inhaled from the HandiHaler, a dry-powder, breath-activated inhaler system that delivers particles to the lung over a wide range of airflow limitations in patients with chronic obstructive pulmonary disease (COPD) it can be effectively delivered at inspiratory flow rates as low as 201/minute (2). Pharmacodynamic steady-state studies have shown that most of the bronchodUator activity is achieved with one to two doses within 48 hours, although a carryover effect on forced vital capacity was observed beyond 48 hours (3). 

When healthy volunteers were exposed by inhalation to 100 or 400 ppm tetrahydrofuran in air, the percentage of expired tetrahydrofuran was 25-35%. The elimination half-life of tetrahydrofuran was 30 min in individuals exposed to 200 ppm for 3h. Some tetrahydrofuran is absorbed in the nasal cavity due to its solubility and inspiratory flow rate. Tetrahydrofuran uptake in the nasal tissue is dependent on its reaction with tissue substrates. Some tetrahydrofuran can be metabolized in the nasal cavity. Tetrahydrofuran blood concentrations were higher at 1 h postexposure than immediately after cessation of exposure. In vitro studies indicated that tetrahydrofuran was first hydroxylated by microsomal enzymes. High concentrations (lO molH ) of tetrahydrofuran inhibited the in vitro activity of rat hepatic cytochrome P450 by 80%. Tetrahydrofuran has been noted to enhance the toxic action of a number of compounds and stimulate the rapid absorption of reactive metabolites. Some of the tetrahydrofuran is excreted in the exhaled breath, while the various metabolites of tetrahydrofuran are excreted in the urine. 

In particular, the propellant-driven metered-dose inhalers release the aerosol cloud at the very high velocity caused by the pressure of the propellant. The open-mouth technique of inhalation [79] helps to slow down the droplets (and to evaporate the volatile excipients). An even more effective solution is to use spacer devices [4,79-87], in which the aerosol cloud can slowed down, the volatile constituents can evaporate, and any large particles will sediment out. Moreover, the patient can then inhale the remaining aerosol under optimal conditions for pulmonary delivery [4,8,56,79], that is, with a slow inspiratory flow rate. 

For aerosols in which the particle velocity is determined by the inspiratory flow rate and the particle size is not sensitive to it, it is expected that the increase in flow rate increases the upper and central airway deposition. For example, Ryan et al. [90] found that fast vital capacity inhalation resulted in a greater proportion of nebulizer aerosol depositing in the central airways than when the aerosol was inhaled slowly. However, the dependence on the inspiratory flow rate becomes more subtle when the particles have intrinsic velocity (such as droplets generated by propellant-driven metered-dose inhalers that need to be entrained into the inhaled air) or the particle size is inspiratory flow dependent (as in the case of passive dry powder inhalers). 

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