CELLETS® 1000

(1000-1400 µm)

CELLETS® 1000 is a subtype of pellets made of microcrystalline cellulose. The size ranges from 1000 µm to 1400 µm. Find more product information and technical specifications.

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titelbild - Hydrodynamic behavior of MCC Spheres in a spouted bedingredientpharm
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Hydrodynamic behavior of MCC Spheres in a spouted bed

Abstract

This case study is a short abstract on spouted bed characteristics, following closely findings in the publication by J. Vanamu and A. Sahoo [1].

Spouted bed systems are of highest importance for all powder processing industries, and more specific in pharmaceutical industry for coating and drying in pellet technologies [2]. These systems offer manufacturing particularly fine and temperature-sensitive particles from small to large scale: laboratory systems are capable of processing product volumes of very few grams, while production systems can handle capacities of several tons [3].

But how to control conditions in spouted beds for efficient process applications, like mixing, coating, or drying?

There might be certain reasons, that the hydrodynamic behavior of the spouted bed in the pharmaceutical industries is less investigated. The referred publication shed some light on the hydrodynamic characteristics of a spouted bed where the MCC Spheres (CELLETS®) are adopted as the bed material. These starter cores are ideal model systems due to their perfect sphericity and zero-level friability. At the same time, smooth and defined surface structure initiate perfect modelling conditions in the spouted bed dynamics.

Material

CELLETS®, made of 100% Microcrystalline Cellulose, have been used as bed material. The physical properties of the CELLETS® are shown in Table 1. The CELLETS® particle morphology is represented in Figure 1.

Parameter Value
CELLETS® 700 and CELLETS® 1000
Size distribution 700-1000 µm (CELLETS® 700)

1000-1400 µm (CELLETS® 1000)
Bulk density 800 kg/m3
Particle sphericity > 0.9
Void fraction 0.42
Geldart classification B

Table 1: Physical properties of the CELLETS®.

SEM micrographs of CELLETS® 700

Figure 1: SEM micrographs of CELLETS® 700, found in [1].

Spouted bed: experiment setup

There are some international players on the market of spouted bed technologies, such as Glatt which seems to be the major one (Figure 2). In this framework, a self-made setup is used for experiments. The experiments that have been carried out in a column, which is fabricated from a Perspex sheet. This column consists of a cylindrical section of height 0.53 m and a diameter of the cylinder of 0.135 m. The column further converged the diameter of the cylinder to 0.05 m as a conical bottom having a length of 0.47 m. The spouting air is supplied by a compressed air line is controlled by a gas regulator. The airflow is controlled by a gate valve and a mesh plate having a mesh size less than the size of the bed material is employed as a separator preventing the backflow of the bed material. Images are captured using a high-speed video camera to gain more details of the hydrodynamic characteristics of the flow pattern inside the spouted bed geometry.

Spouted bed

Figure 2: Scheme of a spouted bed (Glatt, Germany).

Experiments & spouted bed results

Experiments are carried out with three different static bed heights of shallow depth wherein the bed height is in the range of factor 2-3 of the Inlet diameter using two different particle distribution classes at 500-710 µm and 700-1000 µm, respectively. Analyzed parameters are the pressure drop across the bed, the bed expansion ratio, and the clusters concerning the superficial gas velocity are focused in the following.

J. Vanamu et al. found that the “bed expansion ratio increases with increasing superficial gas velocity until the onset of external spouting, further increase in the superficial gas velocity, the bed expansion ratio decreases. With increasing the volume of bed, the bed expansion ratio decreases. In a larger volume of bed, the particles tend to spout into the freeboard region rather than expanding with higher superficial gas velocity”. Initial spouting is symmetric, but with increasing superficial gas velocity spouting becomes asymmetric, and asymmetry is more pronounced or starts at lower superficial gas velocities for smaller particles. This agrees with existing theories of hydrodynamic behavior in a fluidized environment. Respecting the necessarity of a proper flow behavior for mixing, coating or drying applications in drug processing, symmetric spouting is essential. In turn, the superficial gas velocity may be kept low.

In case that high superficial gas velocity regimes are required for the operations a draft tube may be installed within the column to achieve the symmetric spout formation.

Summary

This case study highlights the Hydrodynamic behavior of MCC spheres in a spouted bed using image processing method. MCC spheres in the range between 500-710 µm and 700-1000 µm had been employed. All spheres showed a symmetric and asymmetric spouting in the spouted bed. With increasing superficial gas velocity, the fully suspended particles are limited to a certain height in the freeboard region due to the gas-solid crossflow. A change from symmetric to asymmetric spouting is observed with increasing superficial gas velocity.

Keeping the conditions efficient for the mixing, coating or drying applications requires finally to suppress high superficial gas velocities, or changing the setup in such way, that symmetric spouting conditions are kept upright even at higher superficial gas velocities.

References

[1] J. Vanamu and A. Sahoo, Particuology 76 (2023) 101

[2] L. A. P. de Freitas, Particuology 42 (2019) 126

[3] Glatt GmbH, Binzen, Germany. Online on Nov 8, 2022: Spouted bed systems – Glatt – Integrated Process Solutions

Great thanks to Arihant Innochem Pvt. Ltd. who supplied and donated CELLETS® for this study.

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Coating uniformity of hot-melt coated particles Figure 2 (pure)

Coating uniformity of hot-melt coated particles

Abstract

Coating uniformity is a critical parameter in coating processes in novel pharmaceutical formulations. Speaking about pellet technology, coating and layering are the main methods for implementing drug functionalities, such as modified release of the active, taste-masking properties and further more. Coating uniformity guaranties not only upholding functionalities of the formulation, but also prevent risks such as dose dumping.

This application note is based on a publication of Wörthmann et al. [1] and focuses on selected aspects which are related to starter cores.

Cellets 1000, magnification 100x

Figure 1: Microscopic image of Cellets® 1000, magnification 100x.

Materials and techniques

Coating was applied on highly spherical starter cores Cellets® 1000 (Figure 1). The pellets have a relatively narrow size distribution with a mean particle size of d­­­­50 = 1197 μm, a standard deviation of σ = 113 μm, and particle density of 1.4 g/cm3. For analyzing the coating uniformity, stearin (54 % stearic acid and palmitic acid) and hydrogenated palm oil were used. For the hot-melt coating experiments a lab-scale Wurster fluidized bed was used. The overspray rate was estimated to 8 % (w/w). Processed particles were analyzed by image analysis (Figure 2) and micro-computed-tomography (μCT) (Figure 3). 2D and 3D software analysis were further conducted for the evaluation of the sphere dimension, layer thickness and coating uniformity.

Figure 2 shows a wax-coated particle, where the coating thickness varies and delamination is clearly visible (Figure 3). Small pores and fractions of the coating layer area are obvious.

Coating uniformity of hot-melt coated particles Figure 1

Figure 2: Images of coated pellets are used for a stepwise evaluation of the particle shell thickness. A: original image; B: segmented coating layer. Further software calculation steps are not shown here.

These undesired artefacts result from imperfect parameters, such as spreading mechanism, temperature fluctuations, viscosity, or drop size.

The coating layer thickness is analyzed for three particles of the same batch (Figure 4) using 5 % (w/w) stearin at a spraying rate of 1 g/min. The layer thickness varies between approximately 2 µm to 30 µm. A mean coating thickness is found between 12 µm and 16 µm.

Coating uniformity of hot-melt coated particles Figure 2

Figure 3: Portion of a micro-computed-tomography image of a wax-coated particle showing.

Coating uniformity of hot-melt coated particles Figure 3

Figure 4: Relative frequency of the coating layer-thickness of three particle shells from the same batch using 5 % (w/w) stearin at a spraying rate of 1 g/min. Mean thicknesses: particle I (blue): 15.5 μm, particle II (red): 12.4 μm, and particle III (grey): 15.6 μm.

In terms of customer safety and of compliance aspects, not only statistical information about the layer thickness are of interest. In case of inhomogeneous layers, taste-masking functionalities or even uncontrolled dose dumping might occur. In this context, a single-particle analysis is mandatory. 3D µCT is a powerful tool, which is complementary to existing methods, such as laser imaging methods, 2D analysis or thickness estimations. The analyzed mean thickness deviates by approximately 13 % among these methods (Figure 5).

Coating uniformity of hot-melt coated particles Figure 4

Figure 5: Mean layer-thicknesses measured using different methods. Relative standard deviation: 13 %.

Summary

Microcrystalline cellulose pellets (Cellets®) are used to study coating uniformity. 3D μCT can be a powerful tool to assess the quality of the final product coating and facilitates the selection of an appropriate combination of core particles and coating material. 3D visualization methods allow a critical single-particle analysis with a resolution of up to 2 µm. Furthermore, the determination of the particle’s uncoated surface area can be specified.

Acknowledgement

Prof. Heiko Briesen, Mario Wörthmann (Technical University Munich) and team are gratefully acknowledged for serving content for this note.

Research was financially supported by the Ministry of Economics and Energy (BMWi) and FEI (Germany) via project AiF 19970 N. Equipment funded by Deutsche Forschungsgemeinschaft (DFG, Germany) 198187031.

References

[1] B.M. Woerthmann, J.A. Lindner, T. Kovacevic, P. Pergam, F. Schmid, H. Briesen, Powder Technology 378 (2021) 51–59

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