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Ikegami, Kazuhiko; Kawashima, Yasunaru; Takeuchi, Hirofumi; Yamamoto, Hiromitsu; Isshiki, Nobuyuki; Momose, Den-ichi; Ouchi, Kiyohisa

doi:10.1023/a:1020492213172

Cited by 53 publications

(17 citation statements)

References 4 publications

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“…10,37) Based on the strategy of increasing FPF by decreasing the drug-carrier interaction, various techniques have been studied in order to improve the inhalation properties of DPI. 22,[38][39][40][41][42] A schematic diagram of the estimated relation between the drug-carrier interaction and the inhalation properties is illustrated in Fig. 8.…”

Section: Discussionmentioning

confidence: 99%

Application and Mechanism of Inhalation Profile Improvement of DPI Formulations by Mechanofusion with Magnesium Stearate

et al. 2008

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Dry powder inhaler (DPI) formulations have been utilized in the treatment of respiratory disease [1][2][3] and for systemic administration.4 -7) They have become common in the inhalation therapy field because of various advantages, such as being free from anti-environmental propellants 8) and ease of use with portable small devices.DPI formulations with fine drug particles and coarse carrier particles have been widely used for a long time. Usually their components are simple and they can be manufactured with conventional equipment. Therefore, they appear to be a valuable option as the formulation for clinical trials, especially in the early stages of development. The carrier particles play the critical role in preventing the agglomeration of fine drug particles which possesses high surface energy due to their large specific surface area. On the other hand, it is necessary to achieve the high deposition in the deep lungs to satisfy the required bioavailability. Because only small particles (aerodynamic diameter below 5 mm) can reach the lungs, fine drug particles should be detached from the coarse carrier particles through the inhalation process. The percentage of small particles to the entire dose is defined as fine particle fraction (FPF). Therefore, FPF is an index of the extent of deposition in the lungs.Studies have been conducted to clarify the factors that control the inhalation properties of the carrier-based DPI formulations. [9][10][11][12][13][14] Many studies focused on the carrier surface properties especially rugosity and/or coverage of high energy binding sites. 10,[15][16][17][18][19][20][21] Surface energy of particles would be one of the major factors influencing the inhalation profile of DPI including FPF. 22,23) However the mechanism of FPF increase has not been fully clarified so far. This seems to be because the inhalation profile of DPI is affected by various factors including particle size, morphology electrostatic charge and inhalation condition. 10,12,[24][25][26] Therefore, there is a need for preparation and characterization of series of powder samples that are different in surface properties but similar in other properties and compare them under the same inhalation condition.Mechanofusion can modify the surface energy of lactose carrier particles without drastic change of the particle size and can make the particle shape round to lessen the differences.Inverse gas chromatography (IGC) has been utilized to examine the effect of surface energy on the inhalation behavior of DPI. We reported that mechanofusion on a lactose carrier changed the carrier's surface condition and the inhalation properties of DPI formulations containing the lactose carrier and Compound A.27) The Andersen cascade impactor (ACI) profile suggested that the increase of FPF was accompanied by the decrease of the interaction between Compound A and carrier particles. Begat et al. also reported that mechanofusion of lactose with Mg-St reduced the interaction between drug and lactose particles.28) Mg-St is known as lubri...

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Section: Discussionmentioning

confidence: 99%

Application and Mechanism of Inhalation Profile Improvement of DPI Formulations by Mechanofusion with Magnesium Stearate

et al. 2008

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“…The difference in the deposition profiles from different formulations could be attributed to the difference in the morphological features like elongation ratio and surface smoothness. This can be explained by the fact that elongated particles have aerodynamic diameters almost independent of their length and is governed by the shorter dimension of the particle (40,41). Such particles exhibit smaller aerodynamic diameters than spherical particles of similar mass or volume (42).…”

Section: In-vitro Aerosol Deposition Studiesmentioning

confidence: 99%