Multiple unit pellet system (MUPS) is a matrix consisting of more than one unit pellet system. It allows designing diverse drug release and compositions in pharmaceutical formulations.
Multiple-Unit Pellet System with Diclofenac Sodium represents a modern and flexible approach to oral drug delivery. This multiparticulate system divides the drug dose into many small pellets, each functioning as an individual unit. Because of this design, the formulation ensures more uniform gastrointestinal distribution and minimizes dose dumping. It also improves patient compliance and allows combination of different release profiles in a single dosage form.
Diclofenac Sodium, a potent nonsteroidal anti-inflammatory drug (NSAID), reduces pain, inflammation, and fever. However, it has low solubility and high permeability, which limits its absorption. Therefore, formulating it in a multiple-unit pellet system improves its bioavailability and controls its release rate. As a result, patients experience longer relief with fewer side effects, especially gastrointestinal irritation.
Summary of the Publication
The study “Development of a Biphasic-Release Multiple-Unit Pellet System with Diclofenac Sodium Using Novel Calcium Phosphate-Based Starter Pellets” focuses on creating a capsule with both rapid and sustained release. It combines two types of pellets: delayed-release (DR) pellets coated to resist stomach acid, and extended-release (XR) pellets designed for gradual release in the intestine. This structure allows a quick onset of action and a long-lasting therapeutic effect.
The researchers introduced dicalcium phosphate anhydrous (DCPA) as a new starter core. Unlike conventional cores such as microcrystalline cellulose (for example CELLETS® 500), sucrose, or isomalt, DCPA cores are dense and insoluble. They show excellent strength, low friability, and smooth flow. These qualities make them ideal for producing stable multiparticulate systems. Furthermore, the team used a fluid-bed coating process to ensure even layers of drug and polymer, verified by scanning electron and Raman microscopy.
Dissolution testing showed clear differences among core types. DCPA-based pellets released the drug steadily and predictably, even under variable pH and hydrodynamic conditions. In contrast, soluble cores like sucrose and isomalt caused uneven release and premature erosion. The biphasic MUPS capsules with DCPA pellets combined rapid and prolonged release successfully. Under simulated physiological conditions, they maintained consistent performance and outperformed commercial reference formulations.
The study highlights that the pellet core material strongly affects drug release and mechanical behavior. Insoluble DCPA cores provided stability and controlled release, while soluble ones failed to maintain coating integrity. Therefore, choosing the right core is essential for reliable performance in Multiple-Unit Pellet System with Diclofenac Sodium formulations.
Conclusion and Outlook
Multiple-Unit Pellet System with Diclofenac Sodium offers a strong platform for precise and predictable drug delivery. The use of calcium phosphate-based starter pellets supports biphasic release with high mechanical stability and consistent drug diffusion. As a result, patients benefit from immediate pain relief followed by sustained therapeutic action.
In the future, researchers can use UV imaging, Raman mapping, and other visualization techniques to monitor the release process in real time. These tools will deepen understanding of coating behavior and in vivo performance. Continued development of the Multiple-Unit Pellet System with Diclofenac Sodium will likely lead to safer, more effective, and patient-friendly oral therapies.
https://cellets.com/wp-content/uploads/2025/10/Anmerkung-2025-10-09-140557-1.jpeg8531294Bastian Arlthttps://cellets.com/wp-content/uploads/2016/10/Logo_Cellets_2016_website.pngBastian Arlt2025-10-09 15:14:062025-10-09 15:14:06Multiple-Unit Pellet System with Diclofenac Sodium
Research Advances in MCC Pellet Technology and Applications
Scientific literature on MCC pellets highlights the growing importance of CELLETS® in pharmaceutical and scientific research. These microcrystalline cellulose spheres play a key role in developing reliable multiparticulate drug delivery systems. Researchers have investigated improved rivaroxaban dissolution, efficient film coating kinetics, and their use in orally disintegrating films. In addition, studies focus on colon-targeted vitamin B₂ release and fluidized-bed coating performance. Moreover, academic theses explore uniform hot-melt coating techniques and detailed modeling of tablet disintegration. As a result, MCC pellets continue to prove their versatility across many dosage forms. Consequently, this expanding body of literature reinforces the value of CELLETS® in advancing modern drug delivery technologies.
Selected Scientific literature on MCC pellets
Please, find scientific literature on MCC pellets (CELLETS®), MCC spheres. This list is constantly updated and does not claim to be complete. If you are author, scientist or R&D specialist, please submit your present publication to us for improving the visibility.
Research article Optimising the in vitro and in vivo performance of oral cocrystal formulations via spray coating European Journal of Pharmaceutics and Biopharmaceutics, Volume 124, March 2018, Pages 13-27
Dolores R. Serrano, David Walsh, Peter O’Connell, Naila A. Mugheirbi, Zelalem Ayenew Worku, Francisco Bolas-Fernandez, Carolina Galiana, Maria Auxiliadora Dea-Ayuela, Anne Marie Healy
Conference abstract Multiple-unit orodispersible mini-tablets International Journal of Pharmaceutics, Volume 511, Issue 2, 25 September 2016, Page 1128
Anna Kira Adam, Christian Zimmer, Stefan Rauscher, Jörg Breitkreutz
Research article Asymmetric distribution in twin screw granulation European Journal of Pharmaceutics and Biopharmaceutics, Volume 106, September 2016, Pages 50-58
Tim Chan Seem, Neil A. Rowson, Ian Gabbott, Marcelde Matas, Gavin K. Reynolds, AndyIngram
Research article Physical properties of pharmaceutical pellets Chemical Engineering Science, Volume 86, 4 February 2013, Pages 50-60
Rok Šibanc, Teja Kitak, Biljana Govedarica, StankoSrčič Rok Dreu
Research article Labscale fluidized bed granulator instrumented with non-invasive process monitoring devices Chemical Engineering Journal, Volume 164, Issues 2–3, 1 November 2010, Pages 268-274
Jari T. T. Leskinen, Matti-Antero H. Okkonen, Maunu M. Toiviainen, Sami Poutiainen, Mari Tenhunen, Pekka Teppola, Reijo Lappalainen, Jarkko Ketolainen, Kristiina Järvinen
Research article Granule size distribution of tablets Journal of Pharmaceutical Sciences, Volume 99, Issue 4, April 2010, Pages 2061-2069
Satu Virtanen, Osmo Antikainen, Heikki Räikkönen, Jouko Yliruusi
Research article New insights into segregation during tabletting International Journal of Pharmaceutics, Volume 397, Issues 1–2, 15 September 2010, Pages 19-26
S. Lakio, S. Siiriä, H. Räikkönen, S. Airaksinen, T. Närvänen, O. Antikainen, J.Yliruusi
Research article In vivo evaluation of the vaginal distribution and retention of a multi-particulate pellet formulation European Journal of Pharmaceutics and Biopharmaceutics, Volume 73, Issue 2, October 2009, Pages 280-284
Nele Poelvoorde, Hans Verstraelen, Rita Verhelst, Bart Saerens, Ellen De Backer, Guido Lopes dos Santos Santiago, Chris Vervaet, Mario Vaneechoutte, Fabienne De Boeck, Luc Van Borteld, Marleen Temmerman, Jean-Paul Remon
List – Publications with MCC spheres, 2008 and earlier
Research article Attrition strength of different coated agglomerates Chemical Engineering Science, Volume 63, Issue 5, March 2008, Pages 1361-1369
B. van Laarhoven, S.C.A. Wiers, S.H. Schaafsma, G.M.H. Meesters
https://cellets.com/wp-content/uploads/2021/03/books-2463779_1920-small.jpg601854Bastian Arlthttps://cellets.com/wp-content/uploads/2016/10/Logo_Cellets_2016_website.pngBastian Arlt2025-10-07 08:48:012025-11-10 16:26:03Scientific Literature on MCC Pellets: Insights into CELLETS®
The renaissance of micropellets is promoting innovative technologies
In recent years, formulations based on pellets and micropellets have been the trend. New technologies make it possible to circumvent property rights for active ingredients and are therefore very popular with pharmaceutical customers. But which technologies are the most important?
Pellets are the jack-of-alltrades of solid dosage forms. Positioned somewhere between powder and granulate, they make bitter medicine more palatable and can even awaken a child’s instinct to play when the dosage forms are imaginative enough. One well-known example is the Xstraw, a plastic tube shaped like a drinking straw which is filled with pellets of active ingredient, through which children or elderly people can take in the medicine with water. Pellets in tablets are also making a splash – hybrids which combine all the advantages of both dosage forms. The pioneers in the development of these formulations, known as Multiple Unit Pellet Systems (or MUPS for short), was Astra Zeneca in 1999. Their move to embed the proton pump inhibitor Omeprazole in micropellets and then compress these pellets into immediate release tablets was an award-winning one at the time. The development of MUPS and Xstraw symbolizes the impetus pellets have fueled in recent years.
Klaus N. Möller, Head of Business Development at Glatt in Binzen / Germany, explains: “New excipients, coating materials and sophisticated processes allow us to extend the patent protection period and to make the dosage form more attractive.“
The number of patents registered yearly for pellet-based formulations has increased exponentially and is set to continue. According to research performed by IMS Health, the market for OSD (Oral Solid Dosage Forms) is growing by 6 to 8 percent every year. The number of drugs approved by the FDA also reflect this trend: in 2015, more than half were solid products.
Pellets, as defined by pharmacy guru Prof. Peter Kleinebudde are “an isometric agglomerate of powder particles in an approximate spherical or cylindrical form”, and are a task for perfectionists. The smoother and rounder the pellets, the better they are at fulfilling their purpose. The equipment manufacturer Glatt and their specialists from Pharmaceutical Services have been actively ursuing the subject for years.
There are two fundamental ways of making active ingredient pellets: direct pelletization, in which the powdered active ingredient and excipient combine in a matrix, and active ingredient layering, in which uses side spray or Wurster technology to apply the active ingredient to a starter core of sugar or microcrystalline cellulose.
A case for the specialists
One interesting process variant for matrix pellets is the extrusion of wet granulate in a basket extruder and subsequent rounding in a spheronizer. Möller elucidates: “Continuous wet granulation, followed by extrusion, spheronization and drying now make it possible to perform continuous processes”. Active ingredient pellets made like this can then be covered with a functional coating, be continuously mixed with excipients and be directly compressed into a MUPS tablet. The challenge is to avoid separation of the ingredients and destruction of the tablets during pressing.
Glatt, whose portfolio comprises all granulation and pellet manufacturing techniques, has spent recent years developing additional ways of “fine tuning” the pellet process and has opened up a range of new, interesting possibilities for the lifecycle management of active ingredients.
Pellets and micropellets can be further processed into a wide range
Applying the final touches
But what differentiates the manufacturing of granulates from the manufacturing of pellets? From a pharmaceutical point of view, both processes are closely related and are only separated by the form of the particle, since the ideal shape for pellets is a sphere. There are also definite commonalities in procedure. As Möller explains: “The fluidized bed can be used for both granulation and pelletization. This is why we configure fluidized bed machines on request to be multipurpose installations which then allow the continuous manufacturing of pellets. The individual process modules for direct pelletization with rotor technology, for layering active ingredient and for pellet coating with Wurster technology or the simple drying of wet granulates can be added as necessary. Wurster technology has been used in practice for many years: it is a fluidized bed technique in which starter cores or active ingredient pellets are sprayed with a insists. Möller says: “This method is robust and, because the process is so stable, it’s generally the most popular way to process pellets.”
Depending on the composition of the tablets, processing can last anywhere between eight and ten hours. The knack is knowing how to optimize the efficiency and times of the production process. Additionally, Möller recommends timely expert assistance during the development of the pellet formulation and the production process: “Right from the beginning, it will help to avoid mistakes and to keep an eye on process times and manufacturing costs”.
Micropellets and more
Glatt’s development team demonstrated how to refine an established process with the fluidized bed agglomeration technique known as MicroPx. The trick is to use the Conti process, which was conceived in Pharmaceutical Services’ laboratories in Binzen: first, the active ingredient/excipient liquid is spray-dried to a very fine product dust in a fluidized bed and agglomerated into tiny primary particles. The micropellets then build up, layer by layer, until the desired size is reached. The heart of this technology is a zigzag classifier which continuously ejects particles of sufficient size from the process, while simultaneously allowing smaller particles to reenter the process chamber where they continue to grow. Möller explains that the result of this method are high dosage active ingredient pellets in the size range of 100 to 400 μm with a narrow particle size distribution and content uniformity of a consistent 90 to 95 percent. This means that one significant limitation of former times is now no longer an issue: for many years, the volume of a pellet- filled capsule was larger — and therefore much harder to swallow — than the equivalent tablet with the same dose and composition. The use of microencapsulation, which changes bitter-tasting active ingredients into tasteless microparticles, means the taste is much improved now, too. Micropellets can be also pressed into tablets or MUPS tablets which already begin disintegration in the mouth. But the reason pharmaceutical companies find the MicroPx process so exciting is that it makes completely new formulations possible and therefore allows the legal circumvention of property rights. The technology experts have long known the secret to the perfect pellet, too, an answer provided by Complex Perfect Spheres Technology (CPS). CPS is a souped-up rotor process for fluidized bed machines that uses direct pelletization to yield functionalized pellets and micropellets which are perfectly round and smooth. Unlike classic rotor technology, the modified technique uses a tapered rotating disc which allows the movement of particles to be directed and pelletization to be performed to a defined endpoint. The results are perfectly spherical pellets of exactly defined sizes of between 100 and 1500 μm and extremely narrow size distribution. This is how Glatt’s own Cellets of microcrystalline cellulose are created, which are used as starter cores for pellets and in the Wurster process, for example — thus completing the formulation cycle.
Author
Klaus Möller, Head of Business Development Glatt Process Technology Pharma
https://cellets.com/wp-content/uploads/2021/03/Pellets-and-micropellets-can-be-further-processed-into-a-wide-range.jpg5571257Bastian Arlthttps://cellets.com/wp-content/uploads/2016/10/Logo_Cellets_2016_website.pngBastian Arlt2021-03-22 10:39:542022-07-27 13:25:59The path to the perfect sphere
Several drug substances are known to be extremely bitter. In special for paediatric and geriatric applications, costumer compliance by means of taste acceptance is a highly sensitive topic. Taste masking is therefore an important issue in pharmaceutical industry of oral dosage forms not only to improve the compliance, but it is also used to define a unique taste identification by the costumer (competition advantages). This case study will focus on taste-masking of an API and on the optimization of release in the absorption window of the API.
Modifying the taste
Several methods are available to actively influence, hide or modify taste, such as the initial activation of the active pharmaceutical ingredient (API) by biotransformation [1], the complexation into the cavity of a complexing agent [2] or layering with coating substances [3] and other methods.
Among all these solutions, coating seems to be one of the best understood and most flexible methods. In terms of the API bitterness, mild and extreme bitter APIs are applicable. Additionally, coating [4] is well suited for high dosed API formulations. There are two main approaches: (1) direct coating of the bitter API particles in multiple unit pellet system (MUPS) tablets, or (2) global coating of the tablet which contains the bitter API.
In this case study, we focus on the direct coating of API in a formulation based on starter cores as the unit pellet system. CELLETS® 200 are used as starter cores. They are pellets made of microcrystalline cellulose in size ranges from 100 µm to 1400 µm. In this specific case study, the core size ranges between 100 µm and 200 µm with a defined size distribution. The main advantages of CELLETS® are high sphericity, low friability and optimum in hardness. An API is coated onto the starter cores with a drug load of 5-20 %. The taste-masking coating is performed with Eudragit EPO® so that the resulting particle size remains below 500 µm (Figure 1). Eudragit is the polymer of choice as it ideally prevents API release in oral cavity and allows its release in the absorption window of the API. The final dosage form is a MUPS tablet (Figure 2).
Sketch of a coated pellet starter core (green) with API (blue) and taste masking Eudragit EPO® (yellow) coating. The API drug load is between 5 % to 20 %. The resulting particle size remains below 500 µm.
Compaction is an issue during production, which requires mechanically stable pellets. Coated CELLETS® 200 after compaction still represent as “hard” core pellets. The coated pellets show only little deformation, a reversible compaction behavior and an intact coating.
Sketch of a MUPS tablet. Coated starter cores (yellow) and filling excipient formulation (white).
Here, the MUPS formulation defines a content uniformity with an excellent taste masking at pH 7 (as a measure for the oral cavity) and fast dissolution at pH 1 (representing conditions in the stomach). Figure 3 shows the evaluation of taste masking and dissolution efficiency tests, where the dissolution at pH 7 remains less than 10 % after 10 minutes, and a desired dissolution at pH 1 with a drug release better than 85 % after 30 minutes.
Drug release versus time for coated CELLETS® 200 starter cores. Blue line: in vitro dissolution testing at pH 1 (stomach). Red line: taste masking evaluation at pH 7 (oral cavity).
Summary
Taste masking and modification is crucial for costumer compliance in paediatric and geriatric applications. Several methods are available, such as direct API coating. CELLETS® are perfect starter cores for a successful formulation and simplify taste masking of extreme bitter APIs. CELLETS® properties allow perfect coating abilities due to a high degree of sphericity. CELLETS® of small sizes and narrow size distribution are applicable in MUPS tablets thanks to their low friability and excellent hardness.
[4] Hazzah, H.A., EL-Massik, M.A., Abdallah, O.Y. et al. Preparation and characterization of controlled-release doxazosin mesylate pellets using a simple drug layering-aquacoating technique. Journal of Pharmaceutical Investigation 43 (2013) 333–342. https://doi.org/10.1007/s40005-013-0077-0
https://cellets.com/wp-content/uploads/2021/03/CS_taste_image_1.png6681093Bastian Arlthttps://cellets.com/wp-content/uploads/2016/10/Logo_Cellets_2016_website.pngBastian Arlt2021-03-01 15:03:082022-07-27 12:21:43Taste-masked cellulose based pellets for compaction
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.
Size
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
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.
Summary
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.
Acknowledgement
We acknowledge Fraunhofer IFAM (Dresden, Germany) for providing electron microscopic images.
References
[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
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