Characterization of layered pellets forms the basis of advanced pharmaceutical pellet design. These pellets consist of inert cores coated with active drug layers. Their detailed analysis ensures uniformity, strength, and consistent drug release. Layered systems offer precise dosing, extended or modified release, and taste masking. When the solid-state properties of the drug are modified through amorphization, the pellets can show faster dissolution and better bioavailability. In this study, researchers examined how a high-shear granulator can produce pellets that combine amorphized amlodipine besylate and hydrochlorothiazide, focusing on structure, performance, and stability.
Amlodipine besylate normally appears in a crystalline form with high solubility and a melting point near 200 °C. In contrast, hydrochlorothiazide is poorly soluble and melts near 270 °C. Turning them into an amorphous or co-amorphous form breaks down the crystal lattice, improving solubility and dissolution rate. In co-amorphous systems, the two drugs interact through hydrogen bonding, which stabilizes the amorphous state and prevents recrystallization. This interaction increases the dissolution of both drugs and enhances their bioavailability. The study found that partially amorphized drug mixtures in layered pellets improved release rates while maintaining physical stability.
A high-shear granulator creates these layered systems efficiently. Its strong mechanical forces and controlled heat allow uniform coating and induce amorphization at the same time. Because it works without solvents, this process is clean, fast, and suitable for sensitive compounds.
Summary of the Publication
In the study The Development and Characterization of Layered Pellets Containing a Combination of Amorphized Amlodipine Besylate and Hydrochlorothiazide Using a High-Shear Granulator, Mahmoud et al. [1] developed layered pellets by coating microcrystalline cellulose cores (CELLETS®) with drug mixtures in different molar ratios (2:1, 1:1, 1:2). The high-shear granulator (ProCepT 4M8) operated at 1,500 rpm and 60 °C for three hours. The goal was to achieve partial amorphization and study its impact on dissolution and stability. After preparation, the pellets were stored at –20 °C before testing.
Differential scanning calorimetry showed that amlodipine lost its sharp melting peak, confirming full amorphization. Hydrochlorothiazide retained a broad, weaker peak, meaning it was only partly amorphous. X-ray diffraction supported this: the 2:1 mixture had the lowest crystallinity (26.8 %), while the 1:2 mixture showed the highest (53.6 %). Micro-CT imaging revealed that the drug formed an even layer around the CELLETS® cores. Although some pores appeared, they were inherent to the cores rather than defects from coating.
Texture analysis indicated a small increase in hardness—from 19.8 N for plain CELLETS® to around 21 N for layered pellets—showing the coating slightly strengthened the structure. Dissolution testing showed moderate improvement for amlodipine and a strong improvement for hydrochlorothiazide, with release rates increasing up to 2.6 times. The faster release resulted from reduced crystallinity, improved wettability, and closer contact between drug and medium. FTIR spectra revealed broadening and merging of N–H peaks, confirming new hydrogen bonding and lattice disruption. Stability testing over one month showed that 2:1 and 1:1 ratios stayed mostly amorphous, while the 1:2 mixture recrystallized heavily.
Use of CELLETS® in This Study
The authors used CELLETS®, spherical microcrystalline cellulose cores about 1 mm in size, as the foundation for layering. Their smooth and strong surfaces ensured even coating under high shear. Micro-CT confirmed complete drug coverage and consistent thickness. Moreover, the CELLETS® provided the mechanical strength needed to prevent pellet fracture during processing. Their stable core structure helped maintain uniform shape and resistance to deformation.
Conclusion and Outlook
The study proves that solvent-free high-shear granulation can produce layered pellets with amorphized drug mixtures. The characterization of layered pellets showed lower crystallinity, faster release, and stable structure. Using CELLETS® as cores provided excellent mechanical support. The co-amorphous state of amlodipine and hydrochlorothiazide improved dissolution, especially for the poorly soluble hydrochlorothiazide.
Looking ahead, future research should test long-term stability under stress and evaluate in vivo bioavailability. Scaling the high-shear process could make it viable for industrial use. Furthermore, exploring multi-layer systems or combining more drugs could expand the possibilities of characterization of layered pellets in modern pharmaceutical development.
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Cellulose-derived spherical activated carbon offers a sustainable and efficient solution for adsorbing harmful compounds such as uremic toxins [1]. This carbon material is made from renewable cellulose, which is transformed into spherical particles and then activated to increase surface area and porosity. The spherical shape improves flow properties and reduces dust, making it ideal for pharmaceutical and biomedical applications. Moreover, it combines eco-friendly production with strong adsorption performance, providing a safer and more manageable alternative to traditional powdered carbon.
Uremic toxins are metabolic waste compounds that accumulate in the body when kidney function declines. These toxins interfere with biological processes and contribute to various health issues. Drugs and adsorbent therapies aim to remove them effectively, but such interventions must be selective to avoid removing essential molecules. Therefore, understanding both the functionality and potential toxicity of uremic toxins is crucial for designing safe and effective treatments. While adsorption therapies can improve toxin clearance, they also carry risks such as unintended drug adsorption or gut irritation, which must be minimized through precise material engineering.
Summary of the Publication
Shin et al. (2025) present a study on sustainable cellulose-derived spherical activated carbon designed for efficient uremic toxin removal. The research focuses on transforming cellulose into spherical carbon precursors and activating them to achieve high porosity and surface area. The resulting material combines uniform shape, hierarchical pore structure, and strong mechanical integrity. These properties make it ideal for biomedical use, particularly for toxin adsorption under gastrointestinal conditions. The authors report that the spheres maintain their shape across different pH levels and perform well even in dynamic or competitive adsorption environments.
Furthermore, the adsorption kinetics show that these spherical carbons quickly capture uremic toxin molecules such as indole derivatives. The authors compare the material with conventional activated carbon powders and find significant improvements in handling and biocompatibility. Importantly, the spheres demonstrate low cytotoxicity, which supports their suitability for oral or extracorporeal use. Because of their uniform size and reduced dusting, they minimize irritation risks and can be easily integrated into medical formulations or devices. In addition, the study discusses the environmental and economic benefits of using cellulose feedstocks, showing that this process supports circular material use and low-cost production.
A key part of the research involves CELLETS® 100 and CELLETS® 500. These cellulose microspheres act as templates during synthesis. CELLETS® 100, having a smaller diameter, produces finer activated carbon spheres, while CELLETS® 500 leads to larger ones. This variation allows the authors to tune pore structure, surface area, and mechanical properties. Consequently, CELLETS® 100-derived carbons show faster adsorption kinetics, whereas CELLETS® 500-derived carbons offer better durability. The study highlights that choosing the right CELLETS® grade directly influences the final adsorption performance and application potential of the spherical carbon.
Conclusion and Outlook
The development of cellulose-derived spherical activated carbon marks a major step toward safer and more sustainable toxin removal technologies. By merging green chemistry with advanced nanoengineering, these materials achieve both environmental and therapeutic goals. Their customizable size, stability, and porosity enable versatile use in pharmaceutical formulations and medical devices. Looking ahead, researchers must explore long-term biocompatibility, selective adsorption behavior, and performance in complex biological fluids. Moreover, scaling up production under pharmaceutical standards will determine clinical viability. With further optimization, cellulose-derived spherical activated carbon could revolutionize uremic toxin management and open new paths for eco-friendly therapeutic materials.
References
[1] Kyungmin Shin, Su-Bin Kim, Yong-Han Kim, Dae-Duk Kim, Seul-Yi Lee, Soo-Jin Park, Materials & Design,a available online 10 October 2025, 114892. doi:10.1016/j.matdes.2025.114892
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
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Multiparticulate oral dosage form of tapentadol introduces a modern way to control drug release and improve pain management. The invention, described in patent US20250295596A1, replaces traditional monolithic extended-release tablets with numerous coated particles. This structure allows a smoother and more consistent release of tapentadol in the body. As a result, patients experience steadier pain relief, better compliance, and fewer side effects caused by fluctuating drug levels.
Key Findings of the Patent
The patent describes a system built from coated particles that contain tapentadol at the core. Each particle has a polymer and lubricant coating that controls how fast the drug is released. The combination of cellulose or acrylate polymers with magnesium stearate slows down the release effectively. In addition, the inventors found that high amounts of lubricant can support long-lasting release without affecting stability.
Unlike older tablet systems, this multiparticulate oral dosage form of tapentadol needs no extra subcoat between the drug and the coating layer. Therefore, manufacturing becomes easier and faster. Moreover, the system can include both immediate-release and extended-release particles. This design creates bimodal or multimodal kinetics, giving patients quick pain relief followed by prolonged action. The release rate can also be fine-tuned by adjusting coating thickness or lubricant particle size.
Importance for Human Health
This multiparticulate oral dosage form of tapentadol offers many advantages for patients. The small coated particles are easier to swallow than large tablets. Once in the body, they spread evenly through the digestive tract. This even distribution reduces irritation and ensures steady absorption. As a result, patients benefit from consistent pain control and fewer peaks or drops in drug concentration.
Furthermore, the formulation resists alcohol-induced dose dumping, which improves safety for opioid treatments. Because of its stability and flexibility, manufacturers can produce it reliably and at scale. This robust performance enhances both patient safety and production efficiency.
Role of CELLETS® 350 as Excipient
CELLETS® 350 serve as the excipient cores in this multiparticulate oral dosage form of tapentadol. These spherical microcrystalline cellulose pellets act as starter materials for layering the drug. They are uniform, strong, and chemically neutral. Thanks to their smooth surface and precise size, CELLETS® 350 allow a very even coating of tapentadol. This uniformity is crucial for predictable drug release. In addition, their good flow properties make manufacturing faster and more consistent. Therefore, Cellets 350 improve both the quality and efficiency of the formulation process.
Conclusion
The multiparticulate oral dosage form of tapentadol marks an important step forward in pain management. It combines precise control of drug release with easier swallowing and safer use. The use of CELLETS® 350 as excipient cores ensures reliable layering and coating, leading to consistent performance. Overall, this new dosage form provides a patient-friendly, safe, and scalable solution that improves therapeutic outcomes and production efficiency.
Patent Details
Name or patent: Multiparticulate oral dosage form providing prolonged release of tapentadol
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