Iva

Figure 15 Photograph of the (A) Inhalator, (B) Handihaler, and (C) Foradil Aerolizer.

Figure 15 Photograph of the (A) Inhalator, (B) Handihaler, and (C) Foradil Aerolizer.

Figure 16 (A) Schematic (with permission of Lancet) and (B) photograph of prototype vertical spinning device (Nebulet).

[188] and hygroscopicity [48,189]. Such approaches may reduce the need for traditional excipients, such as lactose.

Dry powder aerosols must begin as a reservoir of free-flowing powder that can be dispersed in the airstream of the patient's inspiratory breath. To achieve a free-flowing powder, an excipient, lactose, is added as a carrier for the drug particles [190,191].

In dry powder delivery to the lung, recognizing the uniqueness of the complete system of formulation and generator is important. Certain design characteristics in the generators facilitate dispersion of the powder and capture of large particles that will not reach the lung. Thus, the success of the dry powder formulation depends to a large extent on the development of appropriate generators. Most methods have used a passive liberation of the powder into the patient's inhaled airflow. A prototype device has been described that employs a vertical spinning disk to project the aerosol in the airstream [192]. The device is shown in Fig. 16. This device has been used to produce dry powder aerosols but requires a large reservoir of drug to deliver a reproducible dose [48,193,194].

ADMINISTRATION ACCESSORIES Baffles

Most aerosol delivery systems have surfaces that are designed to collect or disperse particles. Jet nebulizers have spheres, as shown in Fig. 4, or plates placed immediately in front of the jet to collector break up large droplets. Metered-dose inhalers do not traditionally have baffles; however, the surface of the actuator collects aerosol particles as they pass through the mouthpiece. Dry powder aerosol generators deliver aerosols by tortuous channels that collect or deaggregate large particles.

Spacer Devices

Metered-dose inhalers dispense a plume of aerosol that may extend as much as 40 cm beyond the outlet of the actuator [160,195]. It is known that propellants with lower vapor pressures require some time to evaporate. A spacer placed between the patient and the MDI gives large droplets time to evaporate to respirable sizes while allowing collection of large particles or aggregates, which slow down as they move further from the jet, thus losing inertia and sedimentation properties under the influence of gravity [196-198]. Thus, less material is deposited in the mouth and more in the lungs of individuals than is deposited by the conventional MDI alone. The therapeutic advantage of depositing more drug in the lungs is multifaceted. Oral candidiasis has been reported in patients using inhaled corticosteroids to treat their asthma. This results from deposition in the mouth and throat. Reducing drug deposition in areas outside the target organ is always desirable, especially when toxic side effects are known to occur. Thus, a spacer device may reduce toxicity [199,200]. In some devices, the flowrate for inhalation can be monitored and adjusted by the patient by means of an airflow-actuated whistle in the spacer device [201,202]. This produces a sound at airflow rates known to result in optimal deposition in the lung. The simplest spacer device can consist of a reservoir bag [203-205], which is a bag into which the aerosol is generated to allow sedimentation before administration to the patient. The InspirBase device, a collapsible reservoir bag, is shown in Fig. 17 [205 -207]. Figure 18 shows an extended actuator tube spacer. Figure 19 shows a large-volume tube spacer and a holding chamber. There is some speculation concerning the effectiveness of tube spacers. Those with a volume of 80 mL may not be sufficiently large in design to give the patients enough air to inhale according to their own breathing pattern. Also, some of the respirable aerosol particles are thought to be removed by deposition in the actuator in such a device. Cone spacers, as shown in Fig. 20, with the correct aerosol formulation may be useful because there is no deleterious effect on the production of fine particles and because a sufficient volume of air, 700 mL, is present for the patient to breathe slowly. The cone shape is intended, to some extent, to enclose the plume of aerosol and, thus, offer reduced opportunity for impaction of particles, compared with MDIs alone or with tube spacers [198]. Because respirable particles will sediment unless they are removed by inhalation, the time from firing into the spacer to inhalation must be controlled. One such system sprayed into a large-volume spacer requires that inhalation be completed within 20 sec of firing. Manufacturer's specifications should be

Figure 17 (A) Schematic (with permission of American Review of Respiratory Disease). (B) Photograph of reservoir bag spacer (InspirEase).

Figure 18 (A) Schematic (with permission of Drug Topics). (B) Photograph of an extended actuator tube spacer (Azmacort).

consulted for each device that is used, although this is probably a good estimate for cone devices. The most common cone spacer devices are the Nebuhaler [208-210] and the Aerochamber [211,212]. Studies using conical spacer devices occasionally result in contradictory results [213]. Thus, there have been reports of both reduced [208] and enhanced [209,210] efficacy of a

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The term vaginitis is one that is applied to any inflammation or infection of the vagina, and there are many different conditions that are categorized together under this ‘broad’ heading, including bacterial vaginosis, trichomoniasis and non-infectious vaginitis.

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