e.g. size of a particle, pellet, etc.



Cellets are inert starter cores made of microcrystalline cellulose (MCC). They play an important role in new formulations of solid dosage forms. As a carrier system for actives, the chemical inertness and surface smoothness are crucial parameters. Additionally, high level of robustness and sphericity simplify formulations and technical processes, such as fluidized bed technologies for coating and layering. In a joint study between the University of Hertfordshire and Freeman Technology (a Micromeritics company), the effect of pellets’ size on the behavior in a Wurster process is explained. Wurster fluid bed coating of Cellets with particle size larger than 400 µm is unproblematic. However, decreasing the particle size begins to complicate the coating process. So, powder rheology was used to compare Cellets with different particle sizes in terms of their effect on the powder flow in the Wurster fluid bed coater. For deeper knowledge, we strongly recommend reading investigations by V. Mohylyuk et al. [1]


Cellets® 90, 100, 200 and 350 (D50-size from 94 µm to 424 μm, Ingredientpharm, Switzerland). MCC powder Avicel® PH-102 (supplied by IMCD UK Ltd., UK) is included in the investigations, as it is widely used in industry and can be used by readers for comparison with other studies.

Wurster fluid-bed

Wurster process is a bottom-spray method, employed as a coating technology, for layering powder-like particles in a fluidized bed system (Figure 1). The process can be separated in different zones of mass flow, such as the down-flow zone or the horizontal transport zone. The flowability in these zones is crucial for homogeneous and efficient coating of the particles.


Figure 1: Wurster process is a bottom-spray method for layering powder-like particles in a fluidized bed system.

Hereby, the size of particles might play an important role. The narrow size distribution of MCC pellets is shown in Figure 2 and Figure 3. Measured data is presented in Table 1.


Volume weightened size distribution of Cellets 90 (red, diamonds), Cellets 100 (orange, triangles), Cellets 200 (blue, circles), Cellets 350 (green, squares).

The compact Cellets with fair sphericity, zero friability and a high level of surface smoothness show a fair mass flow rate which is almost independent of particle size at given experimental conditions and was determined by the gravitational funnel method. The reference MCC powder did not flow through the orifice.

Excipient PSD
Flow rate
Avicel PH-102 115a 1.85 No flow
Cellets 90 94b 0.44 1.76
Cellets 100 163b 0.27 2.06
Cellets 200 270b 0.34 1.89
Cellets 350 424b 0.22 1.83

Table 1: Particle size distribution (D50) value and span by laser diffraction (a) and digital microscopy (b), and the mass flow rate by gravitational funnel method (5 mm diameter orifice) for the investigated excipients.

Impact of the Cellets’ size

The impact of the Cellets’ size on bulk powder behavior can only be estimated by screening additional parameters. In addition to the mass flow rate, standard pharmacopoeia methods such as bulk/tapped density were initially employed for the characterization of the powder’s properties. This was extended to rotating drum measurements providing the dynamic angle of repose and dynamic cohesivity index. Via powder rheology the conditioned bulk density, basic flowability energy, specific energy, pressure drop, permeability and compressibility (Figure 4) were obtained [1].

By picking the compressibility of Cellets at an applied force of 10 kPa normal stress, two key points need to be mentioned: (a) smaller particle size induces a higher rate of compressibility; (b) Cellets are less compressible than the reference MCC powder.

These findings are part of the open question on powder flow in a Wurster process. It is expected, that Cellets with a lower compressibility will result in better flow behavior in the fluidized bed.


Microscopic imaging of Cellets 100 (top left), 200 (top right), 350 (bottom left) with 1 mm scale bar and 100x magnification. Bottom right: surface of Cellets 350 in 1000x magnification.


Compressibility at 10 kPa normal stress on Cellets with varying particle size (D50) and Avicel® PH-102.


The flow of Cellets’ through a Wurster fluid-bed coater is likely to show improved performance as the Cellets’ particle size increases. Among others, a lower compressibility demonstrates a rheological behavior which is superior to MCC.


[1] Mohylyuk V, Styliari ID, Novykov D, Pikett R, Dattani R. Assessment of the effect of Cellets’ particle size on the flow in a Wurster fluid-bed coater via powder rheology. J D Deliv Sci Tec. 2019; 54: 101320, doi: 10.1016/j.jddst.2019.101320.


Microcrystalline cellulose pellets (MCC) and sugar are well-known materials in pellet technology. Pellet technology describes the drug load onto starter pellets for controlled release formulations by Wurster process or others. Inert pellets are made of microcrystalline cellulose, while water soluble pellets are composed of sugar. Both material classes show desirable characteristics, such as a narrow particle size distribution, sphericity, surface smoothness. Also the batch-to-batch reproducibility and robustness of starter cores is high. A comparison does not seem to be that easy …

Starter cores in the micron range

Respecting the final application, the initial size of starter pellets defines the final size of the drug loaded pellet. In case of several layers of API and excipients, the initial size is factorized by the layering process. Pellet sizes in a range from 200 µm to 700 µm are frequently used (Table 1). We will focus on three size classes within this range and compare MCC pellets with those made of sugar.


Figure 1: MCC pellets (here: Cellets® 200) are shown with good sphericity and striking surface smoothness.

Small-sized pellets starting at 200 µm

Small-sized pellets with sizes starting at 200 µm and larger, exhibit a comparably large surface-to-volume ratio. This can be beneficial in some applications. For example, taste-masking of bitter API is accessible.


Figure 2: Sugar pellets (here: 50/70 mesh) are shown with moderate sphericity and reduced surface smoothness.

Figure 1 displays a microscopic image of MCC Cellets® 200 and Figure 2 displays the image of sugar pellets in 50/70 mesh, respectively. It is obvious, that for small-sized pellets, the sphericity and surface smoothness of MCC pellets is superior.

Size MCC Sugar
small Cellets® 200 50/70 mesh
Medium Cellets® 350 40/50 mesh
large Cellets® 500 25/30 mesh

Table 1: Size definition of MCC and sugar pellets.

Mid-sized pellets up to 500 µm

This class of pellets is frequently used for multi-layer coating technologies. Easy processing and reliable batch-to-batch control are positive aspects. Exemplary application is a hydrocortisone formulation for peadiatrics. Again, Figure 3 (MCC pellets) and Figure 4 (sugar pellets) show advantages in surface properties for the MCC material.


Figure 3: MCC pellets (Cellets® 350) are shown.


Figure 4: Sugar pellets (40/50 mesh) are shown

Large-sized pellets above 500 µm

In some applications, larger pellet sizes are requested. Let’s have short excurse into straws which can contain larger pellets in dry state. Upon use by sucking liquid through the straw, the API coating dissolves immediately while the pellet remains in the straw by simple filters.

In this size range the striking advantages of MCC pellets are not of immediate importance, but still visible.


Figure 5: MCC pellet above 500 µm (Cellets® 500).


Figure 6: Sugar pellet above 500 µm (25/30 mesh).


Microcrystalline cellulose pellets (Cellets®) show superior surface and sphericity properties compared to sugar pellets. In case of non-dissolving applications, MCC pellets are first choice. As sugar pellets exhibit strong dissolution in water, there is still a fair application range for them.



Starter beads such as pellets made of microcrystalline cellulose (MCC) are frequently used in the formulation of oral drug delivery systems, e.g. multiparticulates [1] or multi-unit pellet system (MUPS) tablets [2]. Certain properties are requested to MCC pellets. We shed some light on sphericity size and friability in this note.

Starter beads for MUPS tablets

MUPS tablets consist of pellets which are compressed – assisted by excipients such as disintegrants and fillers. The pellets used are usually functional coated to achieve desired drug release profiles.


Top: Inert Cellets® 100 (100-200 µm, left) in comparison with another MCC sphere (75-212 µm, right). Bottom: Inert Cellets® 200 (200-350 µm, left) in comparison with another MCC sphere (150-300 µm).

Figure 1: Top: Inert Cellets® 100 (100-200 µm, left) in comparison with another MCC sphere (75-212 µm, right). Bottom: Inert Cellets® 200 (200-350 µm, left) in comparison with another MCC sphere (150-300 µm).

The characteristics of the starter bead as a neutral carrier should therefore include high sphericity (Figure 1), constant particle size distribution and smooth surface. These aspects count especially for the formulation of low dosed highly active APIs.

For the application in MUPS tablets small size and high mechanical stability (low friability) are of interest to achieve desired drug loading and avoid film damage during compression.


Any question relating to optimized drug load and coating layers of pellets is a question of size and sphericity of the starter beads.

So, what is the main influence of size? Size needs to be considered for achieving desired drug load in relation to a total dimension of the pellet. While the total dimension of the pellet is mainly defined by the application – e.g. processing as a capsule, tablet or sachet –, the initial pellet size defines the maximum thickness of coating levels (Figure 2). Size might also be a matter of content uniformity with low dosed API and also needs to be mentioned by means of processability, which is in particular electrostatic loading or sticking. Particle size distribution influences the dissolution profile.


Figure 2: Sketch of a functionally coated pellet. The size of the initial pellet (green) defines the maximum thickness of all coating layers (blue) which may contain API and excipients, as well.

Figure 2: Sketch of a functionally coated pellet. The size of the initial pellet (green) defines the maximum thickness of all coating layers (blue) which may contain API and excipients, as well.


Sphericity is a strong parameter which influence depends on drug loading and coating levels. Also for the control of dissolution profile where specific surface area and content uniformity play important roles, the influence of sphericity needs to be understood (Figure 3). Please do not forget, that with decreasing sphericity, the flow probabilities of powders are decreasing (powder rheology), which might affect process properties such as powder transport.


Figure 3: Sketch of non-spherical starter beads (green) with coating layers (blue). Coating layer thickness and dissolution profiles are hard to control in this case.

Figure 3: Sketch of non-spherical starter beads (green) with coating layers (blue). Coating layer thickness and dissolution profiles are hard to control in this case.

Thus, starter beads of uniform size (distribution) and sphericity are the better solution for overcoming these issues by simplifying drug formulation and processing. Such starter beads can be pellets of MCC, sugar or tartaric acid. MCC pellets surely show perfect initial conditions as they exhibit chemical inertness and therefore can be combined with several APIs. In case of weakly basic APIs, tartaric acid pellets are advantageous.


Figure 4: A pellet inside a compressed MUPS tablet. The starter bead is surrounded by a coating layer of exemplarily excipient or API. A powdery excipients matrix surrounds the coated pellet. Friability is absolutely low.

Figure 4: A pellet inside a compressed MUPS tablet. The starter bead is surrounded by a coating layer of exemplarily excipient or API. A powdery excipients matrix surrounds the coated pellet. Friability is absolutely low.

Figure 4 shows a cross-section of a pellet in the matrix of a compressed MUPS tablet. It is mentionable, that due to low friability a high degree of sphericity as well as surface smoothness are kept after compression and film damage of coating layers is not identified.


Cellets® offer a perfect combination of chemical inertness towards the selection of the API and physical properties that allow optimized and stable processing in a fluid bed process for layering and coating of the starter beads. Main advantages are the low friability, smooth surface, sphericity and narrow size distributions.

Cellets® starter beads therefore provide excellent conditions for controlled drug dissolution profiles.


We acknowledge Fraunhofer IFAM (Dresden, Germany) for providing electron microscopic images.


[1] Pöllinger N, Drug Product Development for Older Adults—Multiparticulate Formulations. In: Stegemann S. (eds) Developing Drug Products in an Aging Society. AAPS Advances in the Pharmaceutical Sciences Series, vol 26 (2016). Springer, Cham. https://doi.org/10.1007/978-3-319-43099-7_16

[2] Bhad ME, Abdul S, Jaiswal SB, Chandewar AV, Jain JM, Sakarkar DM. MUPS tablets—a brief review. Int J Pharm Tech Res. 2010;2:847–55