| 1. |
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| 2. |
- Mollmann, SH, et al.
(author)
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The stability of insulin in solid formulations containing melezitose and starch. Effects of processing and excipients
- 2006
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In: Drug Development and Industrial Pharmacy. - 0363-9045 .- 1520-5762. ; 32:6, s. 765-778
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Journal article (peer-reviewed)abstract
- Solid insulin formulations obtained by different methods of preparation were compared with respect to chemical stability and morphology. Spray- and freeze-drying, solution enhanced dispersion by supercritical fluids (SEDS) and precipitation into starch microspheres were the methods used for preparation of solid powders. The excipients applied were melezitose, starch and sodium taurocholate. The stability of the samples was evaluated after storage in open containers at 25°C and 30% RH for 6 months. All samples were amorphous after processing and storage as detected by XRD, except for the starch microspheres which were semi-crystalline. The spray- and freeze-dried samples containing melezitose and sodium taurocholate experienced a significant water uptake during storage, resulting in changes in morphology and disappearance of Tg. However, the chemical stability of these samples did not seem to be affected by the water uptake. Changes in morphology were not observed for the SEDS powders and the starch microspheres. The chemical stability of the samples was assessed by HPLC. In general, conventional spray and freeze drying resulted in samples with higher chemical stability compared to SEDS powders and starch microspheres. Nevertheless, the excipients applied were observed to be of major importance, and further optimization of the formulation as well as processing conditions may lead to slightly different conclusions.
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| 3. |
- Nguyen, Duy, 1986, et al.
(author)
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A breakage and adhesion regime map for the normal impact of loose agglomerates with a spherical target
- 2015
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In: AICHE Journal. - : Wiley. - 1547-5905 .- 0001-1541. ; 61:12, s. 4059-4068
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Journal article (peer-reviewed)abstract
- Discrete element method-based analysis is conducted to investigate the effects of interface energy between particles on the breakage and adhesion of loose agglomerates upon impact with a spherical target. A mechanistic approach is tested to find a relationship between particle properties, kinetic energy, and the agglomerate structure after the impact, which resulted in a new dimensionless number, the ratio of the two interface energies. In combination with Δ, a dimensionless number relating incident kinetic energy to agglomerate strength (Moreno-Atanasio and Ghadiri M, Chem Eng Sci. 2006;61(8):2476-2481), a good description of the agglomerate impact is obtained. The agglomerate structure after impact is mapped using the two dimensionless numbers and is in good agreement with experimental observations. The constructed regime map can serve as a guide for selecting preliminary process parameters in adhesive particle mixing.
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| 4. |
- Nguyen, Duy, 1986, et al.
(author)
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A study of the redistribution of fines between carriers in adhesive particle mixing using image analysis with coloured tracers
- 2016
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In: Powder Technology. - : Elsevier BV. - 1873-328X .- 0032-5910. ; 299, s. 71-76
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Journal article (peer-reviewed)abstract
- Understanding the dynamics and kinetics of mixing mechanisms, i.e. random mixing, de-agglomeration, adhesion, and redistribution, is critical in order to achieve a structure of interest in adhesive particle mixing. In this work, the redistribution of fines between carrier particles, one of the key mechanisms in establishing a homogeneous mixture, was investigated. Coloured carriers (tracers) and image analysis utilizing CIELCH colour space are used as a tool to assess the dynamics of such a mechanism via the evolution of the colour of blends. It is found that, in a high shear mixer, redistribution quickly reaches a pseudo-steady state within a time scale that is of the same order of magnitude as that of random mixing. Considering all the governing mechanisms necessary to achieve an adhesive mixture, it is concluded that the de-agglomeration of fine-particle agglomerates is the rate-limiting step. This work also demonstrates that the redistribution of fines is influenced by the structure of fines on carrier surfaces resulting from processing conditions. This finding supports the fact that beside material properties, blending conditions, e.g. mixing speed and time, are crucial as regards the structure of adhesive mixtures for inhalation. (C) 2016 Elsevier B.V. All rights reserved.
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| 5. |
- Nguyen, Duy, 1986, et al.
(author)
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CFD simulation of transient particle mixing in a high shear mixer
- 2014
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In: Powder Technology. - : Elsevier BV. - 1873-328X .- 0032-5910. ; 258, s. 324-330
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Journal article (peer-reviewed)abstract
- Particle mixing is one of the key operations in pharmaceutical processing. In this work, an Eulerian-Eulerian multiphase framework has been employed to model and simulate particulate flow and mixing behaviour in the blending of dry powders for inhalation. The kinetic theory of granular flow and the frictional stress model are used to close the transport equations of dense particulate flow in a high shear mixer. The transient mixing dynamics, including start-up, within the mixer are captured by adding a scalar transport equation as a tracer. The solid velocity profile at the wall is experimentally determined by using a high speed camera and particle image velocimetry (PIV) evaluation. The evolution of a tracer movement is experimentally tracked using an imaging technique that is processed in the Matlab image toolbox to obtain the local particle concentration. The model can capture the main features in granular flow motion, e.g. bed height and the dominating flow direction. The mixing mechanism is found to be a combination of azimuthal, axial and radial mixing at the same order of magnitude. Rapid mixing is captured in the simulation and is in agreement with experimental data. Even though the continuum-based model can predict well some flow features and the transient mixing time, there is a need for further development of the continuum description of dense particulate flows.
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| 6. |
- Nguyen, Duy, 1986, et al.
(author)
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Mechanistic time scales in adhesive mixing investigated by dry particle sizing
- 2015
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In: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 69, s. 19-25
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Journal article (peer-reviewed)abstract
- This study exploits the mechanisms governing blending of adhesive mixtures, i.e. random mixing, deagglomeration and adhesion, and their relative importance to achieve mixing homogeneity. To this end, blending of micronized particles (fines) with carrier particles was carried out using a high shear mixer. Dry particle sizing using laser diffraction coupled with a strong powder dispersion unit was employed to measure the fines content in samples collected during mixing, and hence to assess blend homogeneity. The method was also employed to evaluate the relative strength of the agglomerates present in the fines. Particle sizing using a non-destructive imaging technique was used to monitor changes in particle size during blending. It could be shown that the de-agglomeration of the fine-particle agglomerates is the slowest mechanism and hence the rate-limiting step as regards achieving a homogeneous adhesive mixture. Consequently, a longer mixing time is needed for blending of larger agglomerates. Being fast, simple and reproducible, the laser diffraction technique was shown to be an efficient method for measurement of fine particle content and homogeneity of a mixture, while the non-destructive image analysis was able to give relevant information on the rate of de-agglomeration of the fine-particle agglomerates as well as on the size of the resulting carrier-fine particle assemblies.
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| 7. |
- Nguyen, Duy, 1986, et al.
(author)
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Numerical modelling of breakage and adhesion of loose fine-particle agglomerates
- 2014
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In: Chemical Engineering Science. - : Elsevier BV. - 0009-2509. ; 116, s. 91-98
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Journal article (peer-reviewed)abstract
- In this study, discrete element method (DEM) simulations are used to examine the breakage and capturing behaviour of loose fine-particle agglomerates on impact with a target particle. The model system is an agglomerate composed of 5 mu m fine particles and a 200 gm target particle. The cohesion between fine particles was modelled using the Johnson, Kendall and Roberts (JKR) theory. In contrast to the breakage of hard agglomerates which break in large fragments, as commonly investigated, loose agglomerates break in finer fragments. Impact velocity was found to be a significant parameter not only for the adhesion strength but also for the structure of the particles captured on the target. The capture ratio of the agglomerate as well as the thickness of the particle layer covering the target decreases with increasing impact velocity. High impact velocity results in finer fragments attached to the target with greater tensile strength due to the re-structuring mechanism that occurs during impact. Accordingly, impact velocity is one of the critical parameters governing the structure resulting after collision. However, the effect of material properties, e.g. surface energy, material hardness and plasticity, on adhesion behaviour should be investigated to obtain a full picture of the breakage-adhesion regime map.
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| 8. |
- Nguyen, Duy, 1986, et al.
(author)
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The exchange of fines between carriers in adhesive particle mixing: A study using DEM simulation
- 2016
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In: Powder Technology. - : Elsevier BV. - 1873-328X .- 0032-5910. ; 288, s. 266-278
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Journal article (peer-reviewed)abstract
- This study employs DEM simulations to investigate the transfer of fine particles between carrier particles, which is one of the important mechanisms governing adhesive particle mixing. Single collisions between a carrier coated with fines and a non-coated carrier were simulated, in which the interaction between particles was modelled using the JKR theory. Detailed post-impact analysis was carried out to characterise the transfer mechanism and the effects of interface energy between particles, impact velocity and impact angle on the transfer process. It was found that fines are transferred between carriers and are restructured with different patterns according to the relative magnitude of the kinetic energy and the interface energies of particles, both between fines and between fine-carrier. The impact angle, which is closely related to mixer type, has a significant influence on the transfer of fines when the kinetic energy is able to be dissipated into adhesive bonds between fines (which strength is characterised by the corresponding interface energy). The correlation of the particle properties (e.g. interface energies), the processing parameters (e.g. the impact velocity), and the type of mixer (e.g. the impact angle) in characterising the transfer mechanism is established.
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| 9. |
- Tamadondar, Mohammadreza, 1989, et al.
(author)
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Numerical modeling of adhesive particle mixing
- 2017
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In: AICHE Journal. - : Wiley. - 1547-5905 .- 0001-1541. ; 63:7, s. 2599-2609
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Journal article (peer-reviewed)abstract
- The discrete element method is used to investigate adhesive particle mixing in a system that includes large carrier particles and fine particle agglomerates in a Couette mixer. The simulation starts with 200 carriers and 10 agglomerates with 1000 fine particles each. During mixing, the agglomerates are broken, fractions adhere to the carriers, and there is continuous redistribution of fines between carriers. The focus is to obtain information on the quantity and quality of fine particles adhered to carriers by postprocessing the simulation data. Variation in the structure of agglomerates due to shearing is studied over mixing time. Findings indicate that major fraction of fine particles are dispersed evenly onto the surface of carriers and the rest are in form of free debris. A time-dependent index is introduced to predict the degree of mixing. Finally, the adhesion force between carriers and coated layers is observed to have a peak at 1 nN.
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| 10. |
- Tamadondar, Mohammadreza, 1989, et al.
(author)
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The influence of particle interfacial energies and mixing energy on the mixture quality of the dry-coating process
- 2018
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In: Powder Technology. - : Elsevier BV. - 1873-328X .- 0032-5910. ; 338, s. 313-324
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Journal article (peer-reviewed)abstract
- We investigate the effect of particle interface energies and mixing energy input on the macroscopic behavior of the dry-coating process by using the discrete element method (DEM). It is observed that the quality of the coating process is governed by two dimensionless numbers: the Stokes number St (mixing energy/strength of agglomerates) and the reduced intermixing coefficient Λ (cohesion /adhesion strength). Three unfavorable and one favorable process regimes were identified, and represented in a regime map as a function of St and Λ. For low St and Λ carriers are lumped and random mixing is fairly poor. For low St and high Λ the agglomerates are merged together and remain intact. At high St, the fine-carrier adhesion breaks and creates abundance of debris. Between these regions process conditions are favorable as is supported by experimental evidences. Results of this study can be used to establish guidelines for efficient operation of the dry-coating process in a high-shear mixer.
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| 11. |
- Thalberg, K, et al.
(author)
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Comparison of different flowability tests for powders for inhalation
- 2004
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In: Powder Technology. - : Elsevier BV. - 0032-5910. ; 146:3, s. 206-213
-
Journal article (peer-reviewed)abstract
- A series of placebo powders for inhalation was characterized regarding bulk density and powder flowability using different techniques. The powders were of the ordered mixture type and were prepared by mixing a pharmaceutical carrier grade of lactose with different fractions of intermediate sized and fine (i.e., micronized) lactose. A modified Hausner Ratio was obtained by measurement of the poured and the compressed bulk densities. Other tests investigated were the angle of repose, the avalanching behaviour using the AeroFlow, and the yield strength using the Uniaxial tester. Furthermore, the relation between ordered mixture composition and flowability was examined. Of the methods investigated, the modified Hausner Ratio discriminates well between the investigated powders and seems to have the widest measuring range. It was also found that the poured and compressed bulk densities provide information about the packing of the particles in the powders. A good correlation was obtained between the modified Hausner Ratio and the angle of repose. The AeroFlow was suitable for powders with a low percentage of fine particles, but could not discriminate between the more cohesive powders. The Uniaxial tester, on the other hand, seems to be better suited for more cohesive powders. Regarding the powder composition, addition of micronized particles has a strong influence on the flowability of ordered mixtures, while intermediate sized particles have little impact on the powder flow. (C) 2004 Elsevier B.V. All rights reserved.
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| 12. |
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