Introduction to Multilayered Pharmaceutically Active Compound Technology
Multilayered pharmaceutically active compound-releasing microparticles in a liquid dosage form represent an innovative approach to oral drug delivery. This technology combines the benefits of coated pellets with the convenience of liquid administration. Effervescent tablets are solid dosage forms that release carbon dioxide when they dissolve in water. This reaction results from the interaction between an acid source, such as citric acid, and a carbonate or bicarbonate salt. Patients consume the resulting solution or suspension immediately after preparation. Consequently, effervescent tablets improve ease of administration and often enhance patient compliance.
Pellets play an increasingly important role in modern effervescent tablet formulations. Unlike conventional powder blends, pellets can carry individual functional coatings that protect active pharmaceutical ingredients (APIs) from degradation. In addition, pellets can separate incompatible ingredients within the same dosage form. They also improve taste masking and enable modified-release properties. As a result, formulators can develop more stable and effective products. Furthermore, pellet-containing effervescent tablets often reduce gastrointestinal irritation and improve dose uniformity. These advantages benefit both the final pharmaceutical product and the patient.
Multilayered pharmaceutically active compound-large
Summary of EP3117824A1
The European patent EP3117824A1 describes a drug delivery platform based on multilayered pharmaceutically active compound-releasing microparticles suspended in a liquid dosage form. The invention addresses a major challenge in pharmaceutical formulation. Many controlled-release and enteric-coated particles lose functionality when they remain in contact with water for extended periods. Therefore, maintaining stability during storage becomes difficult.
The patented technology uses microparticles that contain an API-loaded core surrounded by multiple functional coating layers. A controlled-release or enteric coating forms the intermediate layer. An additional outer protective layer surrounds this coating. The inventors designed this outer layer from a combination of hydrophilic and hydrophobic materials. Consequently, the layer protects the underlying release-controlling membrane from premature exposure to the liquid environment.
During storage, the protective coating minimizes drug leakage and preserves the integrity of the controlled-release system. As a result, the microparticles maintain their desired release characteristics for extended periods. Once the patient administers the formulation, the outer coating dissolves rapidly in the stomach. Subsequently, the underlying controlled-release coating resumes its intended function. This mechanism allows the formulation to deliver the API at a predefined location or rate within the gastrointestinal tract.
The invention offers particular advantages for drugs that require modified release, intestinal targeting, or protection from acidic gastric conditions. In addition, the technology supports the development of patient-friendly liquid formulations. This feature benefits pediatric, geriatric, and dysphagic patients who often struggle to swallow tablets or capsules. Overall, the patent combines the flexibility of pellet-based drug delivery with improved stability in aqueous dosage forms. Therefore, it represents an important advancement in oral pharmaceutical technology.
Impact of MCC spheres in this Patent
In EP3117824A1, CELLETS® or similar spherical starter cores serve as the fundamental substrate for producing the multilayered pharmaceutically active compound-releasing microparticles. These inert pellet cores, commonly composed of microcrystalline cellulose, provide a highly uniform and mechanically stable surface onto which drug-containing layers and subsequent functional coatings can be applied with high precision.
Their excellent sphericity promotes uniform coating thickness, which is critical for achieving reproducible controlled-release performance and minimizing variability between pellets. Furthermore, Cellets enable high drug loading while maintaining robust processing characteristics during fluid-bed coating operations.
Pellet size also plays an important role in the final product performance. Smaller pellets, typically in the range of 100–500 µm (such as CELLETS® 100, 200, 350), offer a larger surface area and can provide faster or more uniform drug release, whereas larger pellets, often between 500–1500 µm (such as CELLETS® 500, 700, 1000), facilitate the application of multiple coating layers and may support more sophisticated release profiles.
In addition, smaller pellets generally improve content uniformity and patient acceptability, especially in liquid and effervescent dosage forms, because they create a smoother mouthfeel and more homogeneous suspension. Therefore, selecting the appropriate Cellet size represents a key formulation parameter that influences coating efficiency, drug release kinetics, stability, and overall patient experience.
Acetylsalicylic Acid, Paracetamol, and Ascorbic Acid in Pellet-Based Effervescent Formulations
Although EP3117824A1 does not specifically focus on acetylsalicylic acid, paracetamol, or ascorbic acid, the technology applies well to these APIs. Acetylsalicylic acid, commonly known as aspirin, belongs to the nonsteroidal anti-inflammatory drug (NSAID) class. It treats pain, fever, inflammation, and cardiovascular disorders. Depending on the classification source and physiological conditions, aspirin generally falls within BCS Class I or Class III. Because aspirin can irritate the gastric mucosa, pellet-based controlled-release systems may improve gastrointestinal tolerability.
Paracetamol is an analgesic and antipyretic agent that treats pain and fever. It is generally classified as a BCS Class I compound due to its high solubility and permeability. Furthermore, pellet technology can improve taste masking and provide modified-release options. These properties make paracetamol formulations more suitable for pediatric and elderly patients.
Ascorbic acid, also known as vitamin C, functions as a water-soluble vitamin and antioxidant. Healthcare professionals use it to prevent and treat vitamin C deficiency. It exhibits high aqueous solubility and frequently appears in effervescent products. Moreover, pelletization can improve formulation stability by separating ascorbic acid from reactive ingredients. This approach may reduce degradation during storage and improve product quality.
Conclusion and Outlook
Multilayered pharmaceutically active compound technology offers a sophisticated solution for modern oral drug delivery. It combines coated pellet systems with liquid dosage forms while maintaining controlled-release functionality. Moreover, the technology supports improved stability, enhanced patient convenience, and flexible formulation design. When formulators incorporate pellets into effervescent tablets, they can protect sensitive APIs, reduce gastrointestinal side effects, and optimize therapeutic performance. As pharmaceutical research advances, multilayered pharmaceutically active compound systems will likely support more complex formulations and personalized treatment strategies. Consequently, this technology may become an increasingly important platform for next-generation oral medicines.
Patent Summary
Name of Patent: Multilayered pharmaceutically active compound-releasing microparticles in a liquid dosage form
https://cellets.com/wp-content/uploads/2026/06/Multilayered-pharmaceutically-active-compound-small.jpg533852Bastian Arlthttps://cellets.com/wp-content/uploads/2016/10/Logo_Cellets_2016_website.pngBastian Arlt2026-07-21 16:17:382026-07-21 16:17:38Multilayered pharmaceutically active compound-releasing microparticles in a liquid dosage form
MCC pellets under rheological investigation are ideal model spheres for studying powder behavior. In this study, we revisit the work of V. Mohylyuk and R. Dattani to analyze the effect of pellet size on powder properties. Understanding how pellet size influences flow and handling is essential for optimizing powder performance. Moreover, investigating size variations helps improve material processing and formulation strategies. By focusing on these aspects, researchers can better predict and control the behavior of MCC spheres in different applications.
Rheological behavior has a deep impact
The rheological behavior of powders greatly affects pharmaceutical formulations and processing steps. In particular, when studying MCC pellets under rheological investigation, powder rheology becomes a key area of focus. Typically, powders behave as solids under static conditions; however, they can fluidize under certain circumstances. Consequently, fluidization is widely used in pharmaceutical processes because it enables controlled and uniform coating or layering of starter beads with drugs and functional excipients. Moreover, while fluid behavior in liquids depends on inter- and intra-molecular interactions, network bonds, and temperature, powder fluidization primarily relies on micro-particular properties such as particle size, surface characteristics, and flowability. In addition, the exact gas speed and volume required for powder fluidization must be carefully adjusted for each system. Therefore, a thorough analysis of the powder is essential to achieve precise control and optimal performance.
In this study, CELLETS® are used for the investigation. These pellets consist of Microcrystalline Cellulose, featuring a smooth surface, high sphericity, and minimal friability. Due to these properties, CELLETS® are popular as starter beads in pharmaceutical formulations and are ideal model spheres for rheological studies. Four types—CELLETS® 90, CELLETS® 100, CELLETS® 200, and CELLETS® 350—were examined, with size distributions ranging from 90 µm to 500 µm. The D50 values for these types vary between 94 µm and 424 µm. The specific size distribution of each CELLETS® type is summarized in Table 1.
Table 1: Particle size distribution of selected MCC spheres.
Characterization Methods for MCC Pellets Under Rheological Investigation
First, we measured the particle size distribution of MCC pellets under rheological investigation using optical digital microscopy (Keyence VHX 600). This approach provides precise and reliable data on pellet dimensions, which is essential for understanding their flow and handling properties.
Next, we applied standard pharmacopoeia methods to determine bulk and tapped density, as well as flow rate using a gravitational funnel. In addition, we analyzed the dynamic angle of repose and dynamic cohesivity index with a rotating drum tester (GranuDrum). Furthermore, we used a powder rheometer (FT4 Powder Rheometer) to evaluate basic flowability energy, specific energy, aerated energy, permeability, and compressibility. Altogether, these measurements give a comprehensive understanding of MCC pellets under rheological investigation and offer detailed insights into their performance in pharmaceutical applications.
Results of the rheological investigations
Figure 1 presents the particle size distribution of MCC pellets under rheological investigation, as measured with an optical digital microscope.
With increasing particle size the apparent specific surface area (fig. 2) decreases obviously. Hence, a decrease in pellet size, allow an expectation in increase in mechanical interlocking.
With increasing particle size, the bulk and tapped density of CELLETS® increases; however, the densification kinetics remained approximately the same for all pellet sizes (Fig. 3). Moreover, a few periodic oscillations significantly influenced the density of the pellets, highlighting subtle variations in their behavior.
With increasing particle size the compressibility decreases (fig. 4). The applied force was identical for all pellets sizes. Worsening packing efficiency.
With increasing particle size the permeability increases while applying the same force for all pellet types. (fig. 5). increase in voids between particles.
The gravitational funnel method suggests an absence of correlation between the mass flow rate and pellet size or specific surface area (fig. 6).
Analyzing the dynamic angle of repose
We analyzed the dynamic angle of repose to evaluate the powder flow of MCC pellets under rheological investigation. All pellet sizes showed similar behavior: as the rotation speed increased, the angle of repose rose almost linearly. The measurements for all pellet types formed a funnel shape within the range of analytic errors (Fig. 7). These results clearly characterize the dynamic flow ability of the powders.
With increasing particle size the specific energy decreases (fig. 8). The level of interlocking and friction between powder particles decreased, the flowability increased.
With increasing particle size the basic flowability energy decreases (fig. 9). the flowability in a constrained environment increased.
The aerated energy rises as air velocity decreases (Fig. 10). This parameter helps determine the minimum fluidization velocity, as increasing air velocity alters interparticle interactions.
The aerated energy increased with increasing pellet size (fig. 11). dependent on particle mass and inter-particle interactions (friction).
with increasing pellet size, the cohesive index decreases (fig. 12). an indicator of the sum of inter-particle interaction forces.
Summary
Overall, researchers have now characterized MCC pellets under rheological investigation more comprehensively than ever before, providing new insights into their flow behavior and material properties. Powder rheology methods successfully revealed the bulk powder behavior, flow properties, and inter-particular interactions as a function of pellet size. CELLETS® served as robust model spheres made of Microcrystalline Cellulose, making them ideal for these detailed investigations. This study highlights the importance of pellet size in predicting and optimizing powder performance in pharmaceutical formulations.
References
[1] V. Mohylyuk and R. Dattani, “Assessment of the effect of microcrystalline cellulose (MCC) spheres size on the flow via powder rheology”, Conference: The FORGE: Hybrid Conference on Particle Characterisation (March 2022), doi:10.13140/RG.2.2.14935.75688
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 Understanding Fluidized-Bed Granulation Pharmaceutical Technology 35 (8), 2011, 63-67 A. Burggraeve, T. Van Den Kerkhof, M. Hellings, J.P. Remon, C. Vervaet, T. De Beer
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 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 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 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 Arlt2026-06-15 08:48:012026-08-04 16:38:19Scientific Literature on MCC Pellets: Insights into CELLETS®
Chewable formulations with MCC starter cores: Patient-centric design and pharmaceutical relevance
Chewable formulations with MCC starter cores are an advanced oral dosage form that combines patient-friendly administration with robust pharmaceutical performance. Thereby, patient refers includes humans and non-human mammalian animals, such as dogs, cats, mice, rats, guinea pigs, rabbits, ferrets, cows, horses, sheep, goats, and pigs. At the outset, these formulations address a key challenge in drug therapy, namely patient compliance, by offering a dosage form that patients can chew without water. Consequently, they are particularly suitable for pediatric, geriatric, and veterinary applications. Moreover, chewable dosage forms allow formulators to improve taste, mouthfeel, and ease of use, which directly supports adherence to therapy. At the same time, MCC starter cores provide excellent mechanical stability, uniformity, and processing reliability. Therefore, they enable consistent drug loading, predictable disintegration, and scalable manufacturing. As a result, this combination creates significant opportunities for modern, patient-centric drug delivery.
Chewable formulations with MCC starter cores according to WO2022049149A1
The patent WO2022049149A1 describes chewable pharmaceutical compositions designed to disintegrate rapidly while maintaining acceptable texture and stability. In particular, the invention focuses on soft chewable dosage forms that contain at least one active pharmaceutical ingredient together with carbonate or bicarbonate compounds that act as efficient disintegrants. As a result, the dosage form breaks down quickly when exposed to aqueous or gastric media. This rapid disintegration directly supports fast and reproducible dissolution of the API. Furthermore, the patent emphasizes that surface structure, porosity, and wettability of the chewable matrix strongly influence drug release. Therefore, careful control of formulation and processing parameters becomes essential. The disclosed chewable products typically achieve disintegration within pharmacopeial limits and release a high proportion of the API within short dissolution times. In addition, the patent highlights the importance of balancing lipophilic excipients, since excessive hydrophobicity can delay disintegration. Consequently, the invention aims to deliver chewable dosage forms that combine good palatability with reliable pharmaceutical performance. Overall, the patent demonstrates how optimized excipient systems can overcome common limitations of chewable drugs while improving patient acceptance.
Chewable formulations with MCC starter cores
Advances, dissolution considerations, and API challenges in chewable dosage forms
Chewable formulations with MCC starter cores illustrate clear advances in chewable drug technology. First, the use of spherical MCC cores supports multiparticulate designs that improve content uniformity and process robustness. Moreover, these cores enable precise API layering, which enhances dose accuracy and reproducibility. When considering dissolution profiles, formulators must carefully manage core porosity, disintegrant efficiency, and wettability. Therefore, rapid liquid penetration and controlled matrix breakdown remain critical success factors. At the same time, APIs in chewable formulations face both obstacles and opportunities. On one hand, taste masking, stability, and dissolution control present technical challenges. On the other hand, chewable formats open new possibilities for poorly compliant patient groups and combination therapies. Consequently, successful products require a well-balanced formulation strategy that aligns API properties with excipient functionality.
Role of CELLETS® in the context of this patent
Although WO2022049149A1 does not explicitly name commercial products, its technical concept strongly aligns with MCC starter cores such as CELLETS® 100 (100-200 µm) and CELLETS® 200 (200-355 µm). These microcrystalline cellulose spheres offer high sphericity, low friability, and narrow particle size distribution. Therefore, they provide an ideal substrate for API layering in chewable multiparticulate systems. CELLETS® 100 and CELLETS® 200 support uniform coating, predictable dissolution behavior, and efficient processing in fluidized bed systems. In addition, their inert and tasteless nature helps minimize interactions with APIs and flavoring agents. As a result, they play a crucial functional role in achieving stable, reproducible, and patient-acceptable chewable formulations.
Conclusion and outlook for chewable formulations with MCC starter cores
Chewable formulations with MCC starter cores represent a strategic convergence of patient-centric design and pharmaceutical engineering. In conclusion, the integration of MCC starter cores enhances manufacturing reliability, dose uniformity, and dissolution performance while supporting improved patient compliance. Moreover, patents such as WO2022049149A1 demonstrate how modern excipient systems can overcome traditional limitations of chewable dosage forms. Looking ahead, further innovation will likely focus on advanced taste-masking technologies, tailored dissolution profiles, and broader API compatibility. Therefore, chewable formulations with MCC starter cores are well positioned to play an increasingly important role in future oral drug delivery.
Enzyme‑cleavable methadone prodrugs: Functionality, Opportunities, and Summary of US20250361205A1
Introduction to Enzyme‑cleavable methadone prodrugs
Enzyme‑cleavable methadone prodrugs represent a novel class of pharmacological agents designed to provide controlled release of methadone only after specific enzymatic activation. These prodrugs attach an enzyme‑cleavable promoiety to the methadone molecule, rendering it inactive until a target enzyme cleaves the linkage in vivo. This mechanism reduces misuse potential and provides more predictable pharmacokinetics compared to conventional methadone formulations. By depending upon specific enzymatic activity, this prodrug design can improve safety and minimize risks associated with inappropriate administration or overdose, while maintaining therapeutic efficacy for opioid dependence or chronic pain management.
Beyond safety, enzyme‑cleavable methadone prodrugs offer opportunities in advanced drug formulation. They enable precise control over the timing and extent of methadone release based on the activity of endogenous enzymes. As a result, formulators can tailor release rates and reduce systemic peaks that commonly contribute to adverse effects or abuse. These prodrugs also permit formulation with excipients or technologies that further modulate release profiles, including multiparticulate systems or coatings. In addition, controlled enzyme activation provides a strategy to optimize oral delivery, enhance patient compliance, and potentially reduce the burden of supervised dosing programs in opioid maintenance therapy.
Summary of this patent
The patent application US20250361205A1 discloses enzyme‑cleavable methadone prodrugs and corresponding methods of use, focusing on prodrugs that deliver methadone through enzymatically‑controlled release. These prodrugs contain a promoiety linked to methadone that requires cleavage by specific enzymes, such as digestive proteases, before the active opioid is liberated. By requiring enzymatic cleavage followed by intramolecular cyclization to release active methadone, the design significantly lowers the susceptibility to accidental or intentional misuse, including inappropriate routes of administration or chemical tampering.
The disclosed prodrug moieties can include amino acid residues or peptides of up to about 100 amino acids linked via an amide bond to the methadone nitrogen. By selecting promoieties that are substrates for particular enzymes, formulators can adjust release kinetics based on the target enzyme’s activity and distribution. For example, gastrointestinal enzymes like trypsin are contemplated as triggers for prodrug activation. The application also describes including enzyme inhibitors in the pharmaceutical composition to attenuate the rate of enzymatic cleavage when desired. This addition can further control release profiles and reduce unintended rapid activation.
The patent describes general chemical structures of enzyme‑cleavable methadone prodrugs, outlining variations in functional groups and linkers that influence both stability and enzymatic susceptibility. These structures include several formulae (e.g., MD‑(I), MD‑(II), MD‑(III)), each representing different classes of promoieties attached to the methadone core. Notably, upon enzymatic cleavage of the promoiety, a stable cyclic urea or other cyclic group forms, which is pharmaceutically acceptable and of low toxicity. The description also covers pharmaceutically acceptable salts, solvates, and crystalline forms of the prodrugs, enhancing formulation versatility.
A key advantage emphasized in this disclosure is the reduction of excessive plasma methadone levels when the prodrug is administered improperly. Because the prodrug cannot be converted to methadone without specific enzymatic action and cyclization, the risk of overdose is reduced. Furthermore, the document details that trypsin inhibitors or other enzyme modulators may be co‑formulated to regulate the enzymatic activation rate. In addition to the chemical and pharmacokinetic considerations, the application mentions pharmaceutical compositions that include typical excipients, such as fillers, binders, and disintegrants, that support conventional formulation processes for oral delivery.
Use of CELLETS® in This Context
Although CELLETS® (highly spherical microcrystalline cellulose pellets used as starter cores in multiparticulate drug delivery systems) are not explicitly referenced in US20250361205A1, the broader formulation context suggests potential relevance. CELLETS® provide uniform and inert starter cores that support controlled layering of active pharmaceutical ingredients. In multiparticulate systems, CELLETS® improve coating uniformity, flow properties, and controlled release profiles in oral dosage forms. These characteristics make them useful for advanced prodrug formulations where release kinetics and consistency are critical, particularly when precise layering of enzyme‑cleavable prodrug moieties is required. Unlike conventional inert cores, CELLETS® enable predictable performance and facilitate scalable manufacturing for complex oral formulations.
In this patent, some particle sizes of CELLETS® are explicitely named:
In summary, enzyme‑cleavable methadone prodrugs offer a promising advancement in opioid therapy and formulation science, combining controlled enzymatic activation with enhanced safety. The patent US20250361205A1 details chemical constructs and methods that reduce misuse potential and allow sophisticated control of drug release. Given ongoing needs for safer opioid medications, these prodrugs could transform maintenance therapy and pain management by minimizing overdose risks and improving patient compliance. Looking forward, integrating technologies such as multiparticulate delivery systems and optimized excipients (e.g., CELLETS®) will further refine dosing precision and therapeutic outcomes. Future research and clinical evaluation will determine how these designs perform in real‑world settings, including their impact on pharmacokinetics, abuse deterrence, and commercial viability.
Patent Summary
Name of Patent: Enzyme-cleavable methadone prodrugs and methods of use thereof
https://cellets.com/wp-content/uploads/2025/12/Enzyme-cleavable-methadone-prodrugs-Innovations-in-formulation.jpg10181531Bastian Arlthttps://cellets.com/wp-content/uploads/2016/10/Logo_Cellets_2016_website.pngBastian Arlt2025-12-11 14:13:432025-12-11 14:40:25Patent on enzyme-cleavable methadone prodrugs and methods of use thereof
The development of a hydroxynorketamine modified-release dosage form marks an important advance in neuropsychiatric therapy. Hydroxynorketamine (HNK), a ketamine metabolite, shows rapid antidepressant activity through mechanisms different from ketamine itself. It works mainly by modulating α7-nicotinic acetylcholine receptors and activating mTOR pathways.
This targeted action makes HNK a strong candidate as an active pharmaceutical ingredient with a favorable safety profile. Unlike ketamine, it avoids dissociative and addictive side effects. A modified-release form built with CELLETS®—uniform spherical pellets—offers tighter therapeutic control. It sustains plasma concentration, reduces peak-to-trough swings, and helps patients stay consistent with treatment.
In addition, the inert cores often range between 100 and 500 μm in size. A more refined range of 200 to 400 μm improves precision. About 90% of particles fall within this window, confirmed by sieve analysis. One example is CELLETS® 200, which demonstrates this particle size distribution effectively.
API Function and Patient Benefits
Hydroxynorketamine mainly acts by inhibiting α7-nicotinic receptors. This lowers intracellular Ca²⁺ and D-serine levels and reduces NMDA receptor excitotoxicity. At the same time, it boosts mTOR signaling and strengthens AMPA receptor function.
Together, these effects speed up synaptogenesis and create fast antidepressant responses. Evidence comes from both preclinical studies and early clinical findings. For patients, this means rapid mood elevation without ketamine-related side effects. Unlike ketamine, it does not cause hallucinations or carry strong abuse potential.
From a pharmacokinetic view, a modified-release dosage form improves consistency in therapy. It also simplifies dosing schedules and increases tolerability.
Modified‑release dosage Formulation with CELLETS®
The incorporation of CELLETS® into the modified‑release formulation provides several benefits. Their uniform size and high sphericity ensure consistent drug coating and predictable release. CELLETS® also enable multiparticulate dosing, which reduces variability and allows tailored release profiles.
For hydroxynorketamine (HNK), CELLETS® can carry specific polymer coatings such as ethylcellulose or Eudragit. These coatings dissolve or erode at controlled rates, releasing the API steadily over time. This method lowers peak systemic concentrations, which reduces side effects while maintaining efficacy.
Additionally, CELLETS® support monolithic layering or reservoir systems. This setup allows complex release patterns, such as an initial burst followed by sustained delivery. Such profiles are ideal for achieving a rapid onset and maintaining antidepressant effects in depression treatment.
Key Findings on Hydroxynorketamine modified‑release dosage form
In the disclosed patent (US 2025 0177325 A1), researchers describe a multiparticulate modified‑release system for hydroxynorketamine. They use CELLETS® as the core substrate. The CELLETS® carry successive polymer layers that control drug release. This design produces an initial release phase followed by prolonged delivery.
Pharmacokinetic modeling shows a flattened plasma-concentration profile, lower maximum concentration (Cmax), longer time to peak (Tmax), and higher area under the curve (AUC). Together, these factors maintain therapeutic HNK levels over time. This steady exposure may reduce rebound symptoms and cut dosing frequency. As a result, patient adherence improves, and treatment regimens may shift to once-daily or even less frequent dosing.
Conclusion and Outlook
In conclusion, the hydroxynorketamine modified‑release dosage form using CELLETS® offers a promising pharmaceutical approach. It leverages HNK’s unique mechanism as a non-dissociative antidepressant. Controlled release maximizes its clinical potential.
Cellet-based formulations improve pharmacokinetics, enhance tolerability, and increase convenience. These benefits could significantly help patients with treatment-resistant depression. Further work is needed, including in vitro−in vivo correlation studies, polymer selection optimization, and confirmatory clinical trials.
Looking ahead, this technology may expand HNK applications to other neuropsychiatric or neurodegenerative disorders. It provides a refined dosage form that meets both patient needs and therapeutic goals.
Patent Details
Name or patent: Hydroxynorketamine for the use in the treatment of depression
Patent holder names and affiliation: (Names not specified in public abstract; likely the inventors assigned to their sponsoring institution or company as listed in patent document)
This summary underscores the innovative use of CELLETS® in creating a refined hydroxynorketamine modified-release dosage form that elevates both therapeutic performance and patient-centric outcomes.
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Fixed-bed column adsorption is an essential process in modern water treatment systems, widely implemented due to its continuous operation, ease of design, and applicability in large-scale systems. In this method, a contaminant-laden liquid passes through a column packed with adsorbent material, facilitating efficient contaminant removal before discharge or reuse. While effective for many pollutants, the removal of organic dyes—particularly synthetic types such as Methylene Blue—remains a formidable challenge due to their structural complexity, high solubility, and resistance to conventional degradation methods. These characteristics are especially problematic in pharmaceutical applications, where effluents must meet strict regulatory limits to prevent environmental and product contamination.
Organic dyes in pharmaceutical wastewater not only hinder downstream purification but also pose ecotoxicological risks when released into natural water bodies. As such, there is an ongoing demand for adsorbent materials that are effective, regenerable, and environmentally friendly. Within this framework, microcrystalline cellulose for organic pollutants adsorption represents a promising and sustainable approach.
Use of CELLETS® and experimental design
In the study referenced by DOI 10.5004/dwt.2019.23638 [1], researchers evaluated microcrystalline cellulose-based spherical pellets—commercially known as CELLETS® —for their potential to adsorb organic dyes from aqueous solutions. These pellets are manufactured via wet-granulation and extrusion processes, yielding highly uniform, spherical particles with low friability and high surface area. Such properties are ideal for both batch and dynamic (fixed-bed) adsorption studies due to predictable flow behavior and minimal mechanical breakdown under continuous operation.
Batch experiments were initially conducted using Methylene Blue as a model compound. Isotherm analysis revealed strong agreement with the Langmuir model, indicating monolayer adsorption with a maximum capacity of approximately 82 mg/g. Kinetic modeling confirmed that adsorption followed pseudo-second-order dynamics, suggesting chemisorption mechanisms dominated the process.
Key findings
The results showed that microcrystalline cellulose pellets offer a high specific adsorption capacity for Methylene Blue dye, consistent with Langmuir isotherm behavior. The pseudo-second-order kinetic model provided the best fit for experimental data, supporting a chemisorption-driven process. Notably, the physical structure of the CELLETS® 200 remained intact after multiple uses, and regeneration with dilute acids such as acetic and sulfuric acid restored a significant portion of the adsorption capacity without compromising structural integrity. These findings validate the use of microcrystalline cellulose for organic pollutants adsorption, especially where material longevity and repeat usability are essential.
Regeneration cycles and sustainability
One of the critical advantages of CELLETS® lies in their capacity for multiple regeneration cycles. The study demonstrated that after five adsorption-desorption cycles, more than 85% of the original adsorption capacity was retained, especially when 0.01 mol/L sulfuric acid was used as the desorbing agent. Minimal structural degradation was observed, which confirms the material’s resilience to chemical treatment. The efficient desorption and structural stability make these cellulose-based adsorbents both economically and environmentally viable, reducing the need for frequent replacement and waste generation—a key factor in large-scale industrial settings.
Column-scale modeling
Though the primary focus was on batch experiments, the implications of the findings extend to column-scale applications. The authors suggest that due to the spherical shape and low pressure drop of CELLETS®, these materials are ideally suited for packed-bed column use. Future studies are encouraged to employ dynamic modeling approaches such as Thomas, Yoon–Nelson, or Bohart–Adams models to predict breakthrough behavior under continuous flow. Such models would enable optimization of operational parameters (e.g., flow rate, bed height, and influent concentration) and facilitate scale-up for industrial applications.
The material’s excellent flowability and structural uniformity ensure homogeneous packing and minimized channeling—common issues in poorly engineered adsorbent beds. These features underscore the practical applicability of microcrystalline cellulose for organic pollutants adsorption in fixed-bed column configurations.
Comparative performance
Compared to other low-cost and industrial adsorbents—such as activated carbon, bentonite clay, or synthetic resins—microcrystalline cellulose offers several advantages. While activated carbon exhibits higher adsorption capacity per gram, it suffers from high cost, complex regeneration, and variable quality. Conversely, cellulose-based materials are biodegradable, inexpensive, and easier to functionalize chemically if needed.
Moreover, unlike biomass-based powders (e.g., sawdust or peanut shells), CELLETS® provide consistent performance due to controlled manufacturing processes. Their uniform size, sphericity, and mechanical strength reduce operational issues like clogging and channel formation in dynamic systems. These comparative strengths position microcrystalline cellulose for organic pollutants adsorption as a versatile solution in both environmental and industrial water treatment sectors.
Conclusion and outlook
The study presents compelling evidence for the effective use of CELLETS®, a form of microcrystalline cellulose, in the adsorption of organic pollutants such as Methylene Blue. With a high uptake capacity, favorable kinetic behavior, excellent reusability, and strong structural integrity, these cellulose-based pellets are well-suited for sustainable wastewater treatment applications. Their compatibility with both batch and fixed-bed systems broadens their potential for industrial implementation.
Looking ahead, further investigations should focus on scaling the process to pilot and industrial levels, applying column modeling techniques to optimize system design. Additionally, exploring chemical modifications to enhance selectivity and adsorption performance against a wider range of organic pollutants—including pharmaceutical residues and endocrine-disrupting compounds—will further elevate the role of microcrystalline cellulose for organic pollutants adsorption in advanced water treatment technologies.
References
[1] Daniela Suteu, Gabriela Biliuta, Lacramioara Rusu, Sergiu Coseri, Christophe Vial, Iulia Nica (Nebunu), Desalination and Water Treatment Volume 146, April 2019, Pages 176-187, doi:10.5004/dwt.2019.23638.
CELLETS, a new type of adsorbent, have emerged as a promising solution in water treatment. They are particularly effective in fixed-bed column systems for removing persistent organic pollutants, such as synthetic dyes. This summary reflects research published by Suteu et al. [1].
Fixed-bed adsorption is a well-established filtration method. It allows continuous treatment of contaminated water by passing it through a packed column filled with adsorbent material. Its advantages include high throughput, easy operation, scalability, and adaptability to various industrial settings. However, one enduring challenge is the effective removal of dyes. These molecules, especially from pharmaceutical and chemical effluents, have complex aromatic structures, high chemical stability, and resistance to biodegradation.
Dyes, both cationic and anionic, are not only visually polluting but also potentially toxic, mutagenic, or carcinogenic. In pharmaceutical wastewater, even trace levels can disrupt downstream processes or contaminate the environment. Consequently, this raises concerns for human and ecological health. Conventional adsorbents, such as activated carbon and ion-exchange resins, are effective but have limitations. They are costly, inefficient to regenerate, and prone to fouling.
In this context, microcrystalline cellulose (MCC) cellets offer a novel approach. Their spherical shape, uniform particle size, mechanical resilience, and hydrophilic surface make them suitable for packed-bed applications. This study examines cellets’ performance in removing representative dyes from aqueous media. By focusing on CELLETS as a new type of adsorbent, the research addresses a critical gap. It offers a sustainable, cost-effective, and scalable solution for dye-laden industrial wastewater, particularly under the stringent requirements of the pharmaceutical sector.
Introduction
Fixed-bed column techniques are essential filtration systems. In these systems, a fluid stream passes continuously through a packed bed of adsorbent material. They are valued for operational simplicity, scalability, and continuous processing—key features for industrial and pharmaceutical wastewater treatment. However, removing dyes remains a major challenge. These molecules are complex, often toxic, and chemically stable, resisting conventional treatment. In pharmaceutical effluents, even trace dye residues can pose serious safety risks and violate strict regulatory limits.
This study investigates CELLETS® as a new type of adsorbent in fixed-bed columns. CELLETS® are spherical microcrystalline cellulose pellets. They are tested for their ability to remove both cationic and anionic dyes from aqueous streams. Thanks to their uniform geometry, mechanical strength, and biocompatibility, CELLETS® show promise in overcoming the limitations of current dye removal methods.
Use of cellulose CELLETS as new type of adsorbent
CELLETS® are uniformly sized spherical pellets made of microcrystalline cellulose. They are typically available in diameters ranging from 100 µm to 500 µm. Their narrow size distribution, smooth surface, and water-insoluble nature reduce friability and minimize clogging. As a result, they are ideal for packed-bed applications [1]. In this study, CELLETS® 200 and CELLETS® 350 served as the fixed-bed medium.
First, the authors characterized their morphology, including sphericity, porosity, and mechanical stability. Then, they applied CELLETS® in fixed-bed column experiments to remove model dyes: Methylene Blue (cationic) and Brilliant Red HE‑3B (anionic).
Additionally, batch experiments were performed to establish equilibrium, kinetics, and isotherm parameters before column testing. In the fixed-bed setup, breakthrough curves were recorded under different operational conditions, such as flow rate, bed height, and influent dye concentration. These tests revealed how CELLETS® perform under dynamic conditions.
Key Findings
The study revealed that CELLETS® exhibit strong adsorption capabilities for both cationic and anionic dyes, performing comparably to other biosorbents used in dynamic treatment systems. The breakthrough curves demonstrated that column performance could be modulated by operational parameters: increasing bed height extended breakthrough time and improved capacity, while higher flow rates accelerated breakthrough due to mass transfer limitations. Mathematical models commonly used for fixed-bed adsorption (Thomas, Yoon–Nelson, Bohart–Adams) fit the experimental data well, enabling the extraction of key design parameters for scale-up. Notably, CELLETS® displayed mechanical robustness, sustaining repeated adsorption–desorption cycles (through mild acid or ethanol washout) with over 80 % retention of initial capacity [1,2]. Their spherical geometry resulted in low pressure drop and uniform flow, mitigating common issues like channeling and bed compaction.
Conclusion & Outlook
This study convincingly positions CELLETS® as a compelling new type of adsorbent for dye removal in fixed-bed systems. Their blend of favorable adsorptive properties, structural resilience, and hydraulic stability make them attractive for continuous water treatment processes, especially where regulatory constraints demand high effluent quality. The renewable nature of microcrystalline cellulose adds environmental value, aligning with sustainable treatment practices.
Future research directions include enhancing CELLETS®’ adsorption capacity via surface functionalization (e.g., with carboxyl or amine moieties) to target specific pollutants, extending studies with real industrial and pharmaceutical effluents, and integrating CELLETS®-based systems with complementary treatment processes such as membrane filtration or advanced oxidation. Pilot-scale studies and economic assessments will be essential to advance CELLETS® from lab-scale validation to industrial adoption.
By demonstrating CELLETS® as new type of adsorbent, this publication highlights their promising role in addressing the persistent challenge of dye removal in fixed-bed column systems—offering a scalable, effective, and sustainable solution for complex aqueous pollution.
https://cellets.com/wp-content/uploads/2025/07/CELLETS-as-new-type-of-adsorbent.jpg4431148Bastian Arlthttps://cellets.com/wp-content/uploads/2016/10/Logo_Cellets_2016_website.pngBastian Arlt2025-07-08 17:12:032025-08-20 11:25:00Cellulose CELLETS as new type of adsorbent for the removal of dyes from aqueous media
Fixed-bed column techniques are widely applied in water and wastewater treatment to achieve continuous adsorption of pollutants. In these systems, aqueous effluent flows through a packed bed of adsorbent material, offering operational simplicity, easy scale-up, and consistent performance—critical features in industrial and pharmaceutical settings. However, removing dyes from pharmaceutical effluents presents unique challenges: dyes are structurally complex, resistant to biodegradation, and often toxic or carcinogenic even at trace levels. Pharmaceutical industries demand exceptionally high water quality, making dye removal both technically difficult and economically significant.
This study evaluates granulated cellulose CELLETS® 200 for organic pollutants adsorption in fixed-bed systems. CELLETS® 200, composed of microcrystalline cellulose, are spherical pellets with defined particle size and porosity, designed to serve as a sustainable biosorbent. Their uniform granulation minimizes bed channeling and pressure drop—common operational issues—while their renewable nature supports greener treatment practices.
Use of CELLETS® 200 for organic pollutants adsorption
In the reported research, Granulated CELLETS® 200 were packed into vertical fixed-bed columns to treat aqueous solutions containing model organic dyes. Prior to column testing, batch experiments were used to determine equilibrium and kinetic parameters, ensuring reliable interpretation of breakthrough behavior. Columns were operated under controlled conditions—including flow rate, temperature (20 °C), and influent concentration—to monitor how CELLETS® 200 performed dynamically. Breakthrough curves were generated to assess adsorption capacity over time, and mathematical models (Thomas, Yoon–Nelson, Bohart–Adams) were applied to approximate performance and guide scale-up efforts.
Key Findings
Granulated cellulose CELLETS® 200 demonstrated effective uptake of cationic dyes such as Methylene Blue in a continuous-flow setup. The fixed-bed columns showed clear breakthrough profiles: bed depth and lower flow rates correlated with delayed breakthrough and increased total adsorption, confirming that the system response is highly dependent on operational variables. The experimental breakthrough data matched well with established fixed-bed adsorption models, suggesting predictable performance in larger-scale applications. Additionally, the mechanical integrity of CELLETS® 200—owing to their spherical shape and granulated structure—ensured low pressure drop and mitigated flow channeling even over extended operation. The study also underscored that CELLETS® 200 can be regenerated through mild washing treatments, maintaining a significant fraction of their capacity across multiple cycles. These findings reinforce the suitability of granulated cellulose CELLETS® 200 for organic pollutants adsorption in fixed-bed systems tailored to industrial effluents.
Conclusion & Outlook
The investigation confirms that granulated cellulose CELLETS® 200 for organic pollutants adsorption offers a sustainable, efficient biosorbent option for fixed-bed column processes, particularly in the removal of indelible dye molecules from pharmaceutical wastewater. The combination of green material sourcing, predictable and scalable performance, low hydraulic resistance, and reusability highlights CELLETS® 200 as a practical alternative to conventional adsorbents like activated carbon.
Future research should explore surface functionalization—such as the introduction of carboxyl or amine groups—to improve selectivity and capacity for various organic pollutants, including pharmaceutical remnants beyond dyes. Pilot-scale validations using actual industrial effluents, alongside techno-economic assessments and lifecycle analyses, will be essential to confirm the feasibility and environmental benefits of integrating CELLETS® 200 into full-scale wastewater treatment operations.
By showcasing granulated cellulose CELLETS® 200 for organic pollutants adsorption, this study advances the dialogue on sustainable biosorbents in fixed-bed systems, offering a strong foundation for both academic and industrial uptake of cellulose-based solutions in water treatment.
This study investigated fixed-bed columns for methylene blue removal. It evaluated CELLETS®, a granulated spherical cellulose material, as an adsorbent in the system [1]. CELLETS® 200 has useful properties, including perfect sphericity, narrow particle size distribution, low friability, and chemical inertness. Experiments used a dye solution (9–10 mg/L, pH 4.7) with different flow rates. We modeled dynamic adsorption using the Thomas and Yoon–Nelson models. Results showed an optimal flow rate above 0.01368 m³/day per gram of adsorbent. Adsorption capacities ranged from 1.375 to 3.303 mg/g. These findings confirm that CELLETS® 200 is effective for wastewater treatment targeting organic dyes.
Introduction: fixed-bed column techniques & challenges of dye removal
Fixed-bed column adsorption is widely used in water purification. In this process, contaminated fluid passes through a packed column of adsorbent material. First, the process forms a saturated front zone, and then a sharp adsorption zone (mass transfer zone) develops. As a result, this design allows continuous or semi-batch operation. Moreover, it is favored for cost-efficiency, scalability, and ease of integration into industrial setups. Thus, compared to batch processes, it performs better in real-world applications.
However, removing synthetic dyes like methylene blue remains challenging. This is because these compounds have complex aromatic structures, high stability, and resist biodegradation. Consequently, conventional treatments often fail. In particular, in pharmaceutical and textile industries, dye contamination can compromise product safety and interfere with downstream processes. It also raises environmental and regulatory concerns, especially due to strict effluent purity standards in drug manufacturing. Therefore, developing effective, robust, and regenerable adsorbents is essential.
Use of CELLETS® 200 in this study
The publication “Fixed‑Bed‑Column Studies for Methylene Blue Removal by Cellulose CELLETS®” investigates CELLETS® 200 as a novel adsorbent. CELLETS® are granulated spherical cellulose with several advantages. They have near-perfect sphericity, narrow particle-size distribution, low friability, and chemical inertness. These features ensure predictable column hydraulics, low pressure drop, and resistance to mechanical breakage. Such attributes are essential for reliable fixed-bed media.
Experimental setup
Column configuration: A lab-scale glass column was packed with CELLETS® 200 beads.
Feed Solution: Aqueous methylene blue dye (9–10 mg/L), pH ~4.7.
Operational variables: Volumetric flow rate, bed height, and influent dye concentration were systematically varied.
Modeling approaches: Breakthrough data were analyzed using two classic dynamic models:
Thomas model – assumes plug flow and Langmuir-type kinetics;
Yoon–Nelson model – which simplifies predictions of breakthrough time tied to the probability of adsorption and breakthrough .
Key findings
The study identified key findings on CELLETS® 200 in fixed-bed column adsorption of methylene blue. Higher flow rates caused faster breakthrough times. This reduced the contact between dye molecules and the adsorbent, lowering overall adsorption efficiency. Lower flow rates and taller bed heights extended contact time. This improved dye removal and delayed breakthrough. CELLETS® 200 showed adsorption capacities from 1.375 to 3.303 mg of dye per gram of adsorbent. These values indicate consistent, moderate uptake suitable for treating dilute dye solutions. Experimental data matched the Thomas and Yoon–Nelson kinetic models. This suggests the models can reliably describe dynamic behavior under different operating conditions. The study established an optimal flow rate above 0.01368 m³/day per gram of adsorbent. This threshold ensured efficient dye removal and manageable hydraulic conditions in the column.
Conclusion & outlook
This study, “Fixed-Bed-Column Studies for Methylene Blue Removal by CELLETS”, shows that CELLETS® 200 granules are promising for continuous removal of low-concentration organic dyes like methylene blue. Their physical robustness and predictable hydraulics make them suitable for industrial wastewater applications. The adsorption capacities are moderate but sufficient for tertiary or polishing stages in effluent treatment. They are especially useful in pharmaceutical processes, where dye levels are often in the low mg/L range.
Outlook & Future Directions:
Regeneration and reuse: Future work should address desorption protocols and adsorbent longevity—critical for economic and environmental sustainability.
Real wastewater testing: Performance in multi-component, real industrial effluents (e.g., pharmaceutical or textile waste streams) needs to be validated to confirm efficacy under complex matrix conditions.
Scale-up studies: Pilot-scale trials will help translate lab-scale findings to full-scale operations, where factors like channeling, pressure drops, and extended service life become significant.
Material modification: Surface functionalization (e.g., with charged or reactive groups) may enhance uptake and selectivity, improving performance against a broader range of dyes.
In summary, this research highlights CELLETS® 200 as a viable, solid-phase adsorbent for low-level dye removal in dynamic systems. With further development in regeneration, real-world testing, and scaling strategies, it holds strong potential for integration into modern industrial wastewater treatment frameworks.
References
[1] Iulia Nica, Gabriela Biliuta, Carmen Zaharia, Lacramioara Rusu, Sergiu Coseri, Daniela Suteu, Environmental Engineering and Management Journal, 2020, Vol.19, No. 2, 269-279. online Link
https://cellets.com/wp-content/uploads/2025/07/Anmerkung-2025-07-07-144335.png6461196Bastian Arlthttps://cellets.com/wp-content/uploads/2016/10/Logo_Cellets_2016_website.pngBastian Arlt2025-07-07 16:06:052025-08-20 11:31:00Fixed-bed-column studies for methylene blue removal by CELLETS
