Evaluation of SCF-engineered particle-based lactose blends in passive dry powder inhalers

Schiavone, Helena; Srinivas, P.; Clark, Andrew R.; York, Peter; Tzannis, Stelios T.

doi:10.1016/j.ijpharm.2004.05.029

Cited by 79 publications

(48 citation statements)

References 29 publications

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“…This was consistent for all surface energy quantification parameters (enthalpy, entropy, and acid and base contributions). Similar observations have been made previously between fine particle fraction and surface energy (Schiavone et al, 2004). However, others have also reported a positive correlation between surface energy and fine particle fraction (Cline & Dalby, 2002).…”

Section: Discussionsupporting

confidence: 88%

“…As expected, for both budesonide and fluorescein, the milled lactose system provides significantly improved performance over the spray dried system ( Figure 5). This has been described previously and is thought to be related to the higher amorphous content in spray dried particles that may give rise to higher surface energies of spray dried particles (Louey, Van Oort, & Hickey, 2004;Newell et al, 2001a;Schiavone, Palakodaty, Clark, York, & Tzannis, 2004). It was also noted that fluorescein aerosol dispersion efficiencies were significantly higher than that observed for budesonide.…”

Section: Dispersion Studiesmentioning

confidence: 57%

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Prediction of Dry Powder Inhaler Formulation Performance From Surface Energetics and Blending Dynamics

Saleem

Smyth

Telko

2008

Drug Development and Industrial Pharmacy

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The Purpose of these studies was to investigate the ability of surface energy measurements and rates of mixing in dry powder inhaler formulations to predict aerosol dispersion performance. Two lactose carrier systems comprising either spray dried or milled particles were developed such that they had identical physical characteristics except for surface morphology and surface energies avoiding confounding variables common in other studies. Surface energy measurements confirmed significant differences between the powder systems. Spray dried lactose had a higher surface entropy (0.20 vs. 0.13 mJ/m2K) and surface enthalpy (103.2 vs. 79.2 mJ/m2) compared to milled lactose.Mixing rates of budesonide or fluorescein were assessed dynamically and significant differences in blending were observed between lactose systems for both drugs. Surface energies of the lactose carriers were inversely proportional to dispersion performance. In addition, the root mean square of blending rates correlated positively with aerosol dispersion performance. Both techniques have potential utility in routine screening dry powder inhaler formulations.3

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Section: Discussionsupporting

confidence: 88%

Section: Dispersion Studiesmentioning

confidence: 57%

Prediction of Dry Powder Inhaler Formulation Performance From Surface Energetics and Blending Dynamics

Saleem

Smyth

Telko

2008

Drug Development and Industrial Pharmacy

View full text Add to dashboard Cite

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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%

“…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.…”

mentioning

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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“…Drug adhesion to the carrier can be influenced by the surface of the drug and carrier, the drug to carrier ratio, the carrier particle size the mixing time and method, the amount of moisture and the electrostatic behavior (Schiavone et al, 2004;Beilmann et al, 2007). The median g-force was used to approximate the interaction between the co-spray dried powder and the sieved mannitol in the DPI formulations as shown in Figure 4.…”

Section: Determination Of the Drug-carrier Detachment Forcementioning

confidence: 99%

Budesonide dry powder for inhalation: effects of leucine and mannitol on the efficiency of delivery

Rattanupatam¹,

Srichana

2014

Drug Delivery

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Objective: The aim of this study was to develop a budesonide dry powder for inhalation using L-leucine and L-leucine -sieved mannitol as a carrier. Materials and methods: Budesonide and L-leucine were co-spray dried at a mass ratio of 1:50 then blended with various mass ratios of sieved mannitol in the range of 20-80. A 2 3 factorial study was applied to investigate the effects of the spray drying variables; feed rate, aspirator setting and airflow rate on the powder characteristics. The prepared dry powders were characterized using fourier transform-infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and ultracentrifugation. Drug contents and aerosolization properties were evaluated using high performance liquid chromatography (HPLC) and the Andersen cascade impactor (ACI), respectively. Results and discussion: There was no interaction between budesonide and L-leucine after co-spraying. The budesonide dry powders had a mass median aerodynamic diameter (MMAD) in the range of 1.9-2.2 mm at a flow rate of 60 L/min that was suitable for pulmonary delivery. Sieved mannitol as a coarse carrier decreased the interparticulate forces between fine particles of the co-spray dried budesonide-L-leucine and resulted in a high fine particle fraction (FPF) in the range of 64-68% while the co-spray dried powder of budesonide-L-leucine had an FPF of $49%. Conclusions: Blending of the co-spray dried powder with sieved mannitol significantly improved the delivery efficiency of the micronized budesonide better than the co-spray dried with L-leucine alone.

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Evaluation of SCF-engineered particle-based lactose blends in passive dry powder inhalers

Cited by 79 publications

References 29 publications

Prediction of Dry Powder Inhaler Formulation Performance From Surface Energetics and Blending Dynamics

Prediction of Dry Powder Inhaler Formulation Performance From Surface Energetics and Blending Dynamics

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

Budesonide dry powder for inhalation: effects of leucine and mannitol on the efficiency of delivery

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