Novel Approach to DPI Carrier Lactose with Mechanofusion Process with Additives and Evaluation by IGC

Kumon, Michiko; Suzuki, Masahiko; Kusai, Akira; Yonemochi, Etsuo; Terada, Katsuhide

doi:10.1248/cpb.54.1508

Cited by 60 publications

(41 citation statements)

References 32 publications

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“…1 and Table 3 were cited from our previous report. 27) For all four drugs, the lactose mechanofusion-processed with Mg-St showed higher FPF compared to the intact lactose. Namely, mechanofusion with Mg-St decreased the deposition of drugs on the upper part, especially on the pre-separator, and increased it on the lower stages compared to intact lactose (Fig.…”

Section: Resultsmentioning

confidence: 86%

“…27) In brief, the formulated powder was filled in a capsule and inhaled with Jethaler at the flow rate of 30 l/min. The amount of the drug deposited on each part of the ACI was measured by HPLC or UV absorption analysis.…”

Section: Methodsmentioning

confidence: 99%

“…Regarding the analysis of Compound A, the details have already been reported. 27) TNRA was analyzed with an HPLC system employing a mixture of acetonitrile and 0.01 mol/l sodium phosphate buffer (pH 7.0) (43 : 57%, v/v) as the mobile phase running at a flow rate of ca. 1 ml/min and UV detection at 254 nm.…”

Section: Methodsmentioning

confidence: 99%

“…The basic method has already been reported elsewhere. 27) Briefly, samples were packed into a silanised glass column. Methane was used for the inert reference; n-decane, n-nonane, n-octane and n-heptane were used to determine the alkane line.…”

Section: Methodsmentioning

confidence: 99%

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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: Resultsmentioning

confidence: 86%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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

et al. 2008

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“…Iida et al used several methods for effective surface treatment of excipient by dissolving surface asperities in aqueous ethanol solution (4), covering lactose particles with antistatic properties owning sucrose tristearate (J-1803F) (5) and magnesium stearate (6), applying shear stress in a high-speed powder mixer (7), and covering with hydroxypropyl methylcellulose in a Wurster fluidized bed (8). Kumon et al applied a novel mechanofusion approach in the presence of additives to modify the shape and the surface texture of lactose (9). The smoothing procedure, based on the wetting in water-ethanol mixture with or without ternary component (magnesium stearate) and drying of lactose powder in high-shear mixer, was successfully carried out by other workers (10,11).…”

Section: Introductionmentioning

confidence: 99%

Effective Modification of Particle Surface Properties Using Ultrasonic Water Mist

et al. 2009

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Abstract. The goal of the present study was to design a new technique to modify particle surface properties and, through that, to improve flowability of poorly flowing drug thiamine hydrochloride and pharmaceutical sugar lactose monohydrate of two different grades. The powdered particles were supplied by a vibratory feeder and exposed to an instantaneous effect of water mist generated from an ultrasound nebulizer. The processed and original powders were evaluated with respect to morphology (scanning electron microscopy, atomic force microscopy, and spatial filtering technique), flow, and solid state properties. It was found that rapid exposition of pharmaceutical materials by water mist resulted in the improvement of powder technical properties. The evident changes in flowability of coarser lactose were obviously due to smoothing of particle surface and decreasing in the level of fines with very slight increment in particle size. The changes in thiamine powder flow were mainly due to narrowing in particle size distribution where the tendency for better flow of finer lactose was related to surface and size modifications. The aqueous mist application did not cause any alteration of the crystal structures of the studied materials. The proposed water mist treatment technique appears to be a robust, rapid, and promising tool for the improvement of the technological properties of pharmaceutical powders.

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Formulation of Inhalation Medicines

Traini

Young

2013

Inhalation Drug Delivery

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Novel Approach to DPI Carrier Lactose with Mechanofusion Process with Additives and Evaluation by IGC

Cited by 60 publications

References 32 publications

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

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

Effective Modification of Particle Surface Properties Using Ultrasonic Water Mist

Formulation of Inhalation Medicines

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