Info

particles, most notably a-lactose monohydrate (28,53,54). Other approaches include developing particles to overcome the forces of interaction, which include van der Waals forces, capillary forces, electrostatic forces, and mechanical interlocking (53,54). Spherical porous particles that exhibit unique properties of dispersion and aerodynamic behavior have been produced. These particles disperse readily since their van der Waals forces are smaller. However, capillary forces are enhanced in porous structures, hence, capillary condensation can occur at relatively lower relative humidities (10-50% RH), which can adversely affect particle deaggregation and enhance agglomeration. This is especially true for respirable aerosol particles in the solid state. Irregularly shaped porous particles can experience decreased or increased structural cohesion (mechanical interlocking) and surface electrostatics depending on whether the number of contact points between particles is decreased or increased and on the extent of surface asperities (52,53). Once airborne, these particles, which may be geometrically large, behave as aerodynamically small particles, following equation (2).

The metering of DPIs is closely linked to the device itself and may be divided into three common systems (27): capsules, multidose blister packs, and powder reservoir systems. The considerations that go into these metering systems include convenience to the patients, stability on storage, compatibility with product, and ease of filling.

The components of a DPI are the formulation, the metering system, and the device. The device may involve various dispersion mechanisms, pressure drops/shear stress/ resistance levels. The performance of a DPI involves evaluation of component compatibility and influence on device performance. The performance of commercial passive inhaler devices is influenced by the pressure drop (i.e., shear stress or resistance) (55) generated by a patient during an inspiratory flow cycle (56). Recently, it has been suggested that particle size and emitted dose determinations should be conducted as a function of pressure drop/shear stress/device resistance. For powder reservoir devices (27), such as the Turbuhaler (57), evaluation throughout the life of the device is required as part of a stability program. For unit-dose systems (27), such as the Spinhaler (58), barrier integrity must be evaluated for the unit-dose packaging.

Several successful DPI products are currently on the U.S. market (27). Figure 7 shows examples of two DPIs, the Turbuhaler and the Diskus, currently marketed in the United States for the delivery of the steroids budesonide and fluticasone, respectively. Table 6 shows the major elements of a number of passive DPIs. In addition to the

Dessicani store storage unit

Inhalation chamber Bypass air inlet

Aerosol

Figure 7 Examples of two dry powder inhalers: (A) the Turbuhaler™ and (B) the Diskus™.

Dfitg exit Ron mouthpiece

Strip IkJ peeled

Maniftjid

Index wheel

Empty strip

Contrasting wneet Lever

Thumbgrip

Inhalation chamber Bypass air inlet

Dessicani store storage unit

Dfitg exit Ron mouthpiece

Aerosol

Strip IkJ peeled

Maniftjid

Contrasting wneet Lever

Thumbgrip

Index wheel

Empty strip

Coiled sinp Pockets containing drug

Figure 7 Examples of two dry powder inhalers: (A) the Turbuhaler™ and (B) the Diskus™.

Table 6 Characteristics of Select Passive Dry Powder Inhalers
0 0

Post a comment