Introduction to Different Pelletization Techniques and Their Functionality in Drug Formulations
Different pelletization techniques form a core part of pharmaceutical manufacturing for solid dosage forms that deliver active pharmaceutical ingredients (APIs) with enhanced performance. Pelletization, a process that generates small, uniform spherical particles, improves flow properties, enables controlled or delayed release, and reduces local irritation in the gastrointestinal tract compared with conventional tablets and capsules. These techniques include direct pelletization, layering pelletization, extrusion-spheronization, spray drying, and other advanced methods, each offering specific functional benefits. Direct pelletization allows quick single-step formation with minimal equipment and lower cost. Layering pelletization deposits drug onto inert cores to improve drug loading and modify release profiles. More complex methods like extrusion-spheronization yield highly uniform pellets but require more processing time. Across all approaches, the choice of technique affects drug dissolution, stability, and manufacturability, and each technique opens opportunities to tailor drug release, enhance bioavailability, and optimize patient compliance through multiparticulate delivery systems.
Summary of the Thesis
The PhD thesis [1] “Application of High-Shear Granulator in Different Pelletization Techniques” by Azza Asim Khalid Mahmoud explores high-shear granulator applications. Furthermore, it demonstrates how these granulators improve different pelletization techniques to produce optimized drug delivery pellets. Consequently, different pelletization techniques become essential for solid dosage forms, enhancing flow properties and ensuring uniform size distribution. Moreover, the study highlights how these techniques enable precise control over drug release while equipment choice reduces cost and streamlines production. In addition, both direct pelletization and layering pelletization are analyzed within a high-shear granulator framework. Therefore, Quality by Design (QbD) principles guide the definition of process parameters that impact pellet quality. Through risk assessments, design of experiments (DoE), and optimization strategies, critical parameters are identified. These include impeller speed, chopper speed, binder volume, and granulating liquid, which strongly affect pellet size, yield, hardness, and dissolution. Overall, the research confirms that mastering different pelletization techniques enhances pharmaceutical pellet formulation efficiency and performance.
Direct pelletization with high-shear granulation
The thesis demonstrates that direct pelletization with high-shear granulation can produce pellets with desirable physical attributes and consistent drug distribution through careful experimental design. By applying a full factorial design and central composite design, the author constructs an optimal design space. The study also incorporates active pharmaceutical ingredients—amlodipine besylate and hydrochlorothiazide—showing how optimized pellets retain good content uniformity and dissolution performance when loaded. On the layering pelletization front, MCC cores serve as a base for drug deposition, with micro-computed tomography and thermal analysis confirming structural features that contribute to improved drug release. The research highlights how the high-shear granulator facilitates physical transformations such as partial amorphization of loaded drugs, which can enhance dissolution rates.
The thesis underscores the advantages of integrating QbD concepts into pelletization, improving reproducibility and understanding of how process variables interact. Overall, the study provides a comprehensive view of how different pelletization techniques benefit from high-shear granulation to produce robust pellet formulations with desirable critical quality attributes.
Use of CELLETS® in the Study
Within the thesis, CELLETS®—spherical microcrystalline cellulose cores—play a key role in the layering pelletization process. These inert cores are typically defined in uniform sizes of approximately 100 µm to 1400 µm. They provide a stable and consistent substrate onto which drug combinations (hydrochlorothiazide and amlodipine besylate) are deposited under high-shear conditions. The application of CELLETS® enhances layering efficiency, facilitates uniform drug distribution, and contributes to improved pellet morphology and mechanical integrity. Their use is integral to investigating how high-shear granulation affects drug layering and the resulting pharmacotechnical properties of the pellets.
Conclusion and Outlook
This thesis confirms that different pelletization techniques, particularly direct and layering methods, gain substantial functional advantages when implemented with high-shear granulation and QbD strategies. The research shows that such integration leads to pellets with optimized size, mechanical strength, and drug release characteristics. Moreover, the use of CELLETS® strengthens drug layering approaches and helps maintain uniformity in multiparticulate systems. Future research may expand on scaling these methods for commercial production, exploring additional API combinations. They are employing real-time monitoring technologies to further enhance control over pellet quality. By advancing the understanding of how process parameters affect critical quality attributes, this work positions high-shear granulation. This technology is a versatile tool for modern drug formulation technologies.
https://cellets.com/wp-content/uploads/2025/12/Different-Pelletization-Techniques-Functionality-and-Key-Insights.jpg10171529Bastian Arlthttps://cellets.com/wp-content/uploads/2016/10/Logo_Cellets_2016_website.pngBastian Arlt2025-12-11 14:57:222025-12-11 15:02:32Different pelletization techniques: Introduction and Summary of the Thesis by Azza A. K. Mahmoud
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
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®
Hot-melt coating materials improve efficiency and product quality in pharmaceutical and industrial manufacturing. They melt when heated and solidify quickly, forming strong, uniform coatings on various surfaces. As a result, manufacturers reduce production time, lower costs, and avoid using solvents. Furthermore, understanding wetting behavior and delamination is critical to optimize coating performance. For example, CELLETS® 1000 microcrystalline cellulose pellets serve as excellent starter cores, promoting uniform wetting and consistent coating thickness. Consequently, hot-melt coating materials have become a reliable solution for modern manufacturing needs.
Enhancing pharmaceutical and industrial applications by hot-melt coating materials
In the study titled Delamination and Wetting Behavior of Natural Hot-Melt Coating Materials, published in Powder Technology [1], the authors investigated the delamination and wetting behaviors of various natural materials.The research aimed to understand how these materials interact with substrates during the coating process, which is crucial for applications in the pharmaceutical industry.The study utilized laboratory coating experiments and micro-computed tomographic measurements to assess delamination frequency, and a drop shape analyzer to evaluate wetting behavior.Interestingly, the study found no correlation between delamination and wetting behavior, suggesting that other factors may influence delamination in hot-melt coatings.
Among the materials tested, CELLETS® 1000, a type of microcrystalline cellulose (MCC) pellet with a size range between 1000 and 1400 µm, was highlighted for its suitability in hot-melt coating applications.These spherical pellets are known for their chemical inertness, low friability, high sphericity, and smooth surface, making them ideal as starter cores for multiparticulate drug delivery systems.In the context of the study, CELLETS® 1000 demonstrated excellent wetting properties with contact angles ranging from 10° to 18°, which is favorable for uniform coating.However, the study did not find a direct correlation between wetting behavior and delamination, indicating that other factors may play a more significant role in delamination during hot-melt coating processes. Researchers assume that delamination may have resulted from the different thermal expansion coefficients of the carrier particle and the coating material [2]. A change in temperature may have led to thermal stresses and may have promoted spalling or delamination. Subsequent swelling of a hygroscopic carrier material due to moisture could also lead to structural
changes in the coating structure and might cause delamination.
Use of CELLETS® in hot-melt coating processes
The use of CELLETS® in hot-melt coating processes offers several advantages.Their uniform size distribution and smooth surface contribute to consistent coating thickness and quality.Additionally, the chemical inertness of CELLETS® ensures compatibility with a wide range of coating materials, reducing the risk of undesirable interactions.These characteristics make CELLETS® a reliable choice for developing controlled-release formulations and enteric coatings in pharmaceutical applications.
In summary, the study underscores the importance of understanding the delamination and wetting behaviors of natural hot-melt coating materials.While CELLETS® 1000 exhibited favorable wetting properties, the lack of correlation between wetting behavior and delamination suggests that other factors should be considered when selecting materials for hot-melt coating processes.Further research is needed to identify these factors and optimize coating processes for improved product performance.
[2] S. Ebnesajjad, A.H. Landrock, Introduction and adhesion theories, Adhesives Technology, Handbook, 38, Elsevier 2015, pp. 1–18; doi: 10.1016/B978-0-323-35595-7.00001-2.
Understanding Hot-Melt Coating Materials
Hot-melt coating materials are thermoplastic substances that bond effectively to substrates when melted. Their melting point, adhesion properties, and chemical compatibility directly influence coating uniformity and durability. Therefore, selecting the correct material is crucial for minimizing delamination and ensuring product quality. Additionally, their solvent-free nature makes them environmentally friendly and cost-efficient.
Optimizing Coating with CELLETS®
CELLETS® offer significant advantages as starter cores in hot-melt coating processes. Their spherical shape and smooth surface promote uniform wetting and consistent coating thickness. Furthermore, their chemical inertness ensures compatibility with diverse coating materials, reducing the risk of unwanted interactions. Consequently, these MCC spheres support reliable and high-quality coating outcomes in both pharmaceutical and industrial applications.
The present invention generally relates to enteric-coated particles containing lactoferrin. More specifically, the present invention provides an enteric-coated particle comprising (or consisting essentially of): a) a core comprising (or consisting essentially of) an inert core-forming material selected from cellulose polymer, sugar, sugar alcohol, starch and carnauba wax; b) a first coating layer substantially covering the core and comprising (or consisting essentially of) b-1) lactoferrin, b-2) a pharmaceutically acceptable binder and optionally b-3) one or more other suitable excipients, such as a plasticizer; and c) a second coating layer substantially covering the first coating layer and comprising (or consisting essentially of) c-1) an enteric coating material, and optionally c-2) one or more suitable excipients, such as a plasticizer and/or an anti-tacking agent. The present invention further provides pharmaceutical compositions and oral dosage forms comprising one or more particles according to the present invention. [1]
Enteric-coated particles with CELLETS® and other starter beads
This formulations is based on starter beads, exemplary such as sugar, wax or microcrystalline cellulose (MCC). For the latter material MCC, specifically such as CELLETS® 100, CELLETS® 200, CELLETS® 350, CELLETS® 500, CELLETS® 700, or CELLETS® 1000 are mentioned. Through coating and layering of CELLETS® with excipients and the active, a modified release is obtained wherein at most 10% of lactoferrin is released from the particle within 120 minutes.
Document information
Document Type and Number: (“enteric-coated particles containing lactoferrin”)
https://cellets.com/wp-content/uploads/2024/04/Anmerkung-2024-04-25-155250.png838590Bastian Arlthttps://cellets.com/wp-content/uploads/2016/10/Logo_Cellets_2016_website.pngBastian Arlt2024-04-24 16:26:032024-04-25 16:31:42Modelling the disintegration of pharmaceutical tablets: integrating a single particle swelling model with the discrete element method
https://cellets.com/wp-content/uploads/2022/09/parameter-titelbild.png6271200Bastian Arlthttps://cellets.com/wp-content/uploads/2016/10/Logo_Cellets_2016_website.pngBastian Arlt2023-08-22 09:15:152023-08-23 08:21:33Critical aspects of starter spheres in oral pellet formulations one should consider
This article “Amorphous Solid Dispersions Layered onto Pellets – An Alternative to Spray Drying?” is an excerpt from the publication of Neuwirth et al., Pharmaceutics 2023, 15(3), 764; https://doi.org/10.3390/pharmaceutics15030764.
Abstract
Spray drying is one of the most frequently used solvent-based processes for manufacturing amorphous solid dispersions (ASDs). However, the resulting fine powders usually require further downstream processing when intended for solid oral dosage forms. In this study, we compare properties and performance of spray-dried ASDs with ASDs coated onto neutral starter pellets in mini-scale. We successfully prepared binary ASDs with a drug load of 20% Ketoconazole (KCZ) or Loratadine (LRD) as weakly basic model drugs and hydroxypropyl-methyl-cellulose acetate succinate or methacrylic acid ethacrylate copolymer as pH-dependent soluble polymers. All KCZ/ and LRD/polymer mixtures formed single-phased ASDs, as indicated by differential scanning calorimetry, X-ray powder diffraction and infrared spectroscopy. All ASDs showed physical stability for 6 months at 25 °C/65% rH and 40 °C/0% rH. Normalized to their initial surface area available to the dissolution medium, all ASDs showed a linear relationship of surface area and solubility enhancement, both in terms of supersaturation of solubility and initial dissolution rate, regardless of the manufacturing process. With similar performance and stability, processing of ASD pellets showed the advantages of a superior yield (>98%), ready to use for subsequent processing into multiple unit pellet systems. Therefore, ASD-layered pellets are an attractive alternative in ASD-formulation, especially in early formulation development at limited availability of drug substance.
Materials
The model drugs ketoconazole (KCZ) and loratadine (LRD) were purchased from Sris Pharmaceuticals (Hyderabad, India). HPMCAS LG (hydroxypropyl-methylcellulose acetate succinate, wt%: methoxyl 20–24%, hydroxypropyl 5–9%, succinyl 14–18%; Mw = 18,000, HPMC-AS) was donated from Shin-Etsu Chemical (Tokyo, Japan). Eudragit L100-55 (methacrylic acid ethylacrylate copolymer, ratio 1:1, Mw = 320,000, EL100-55) was donated by Evonik (Darmstadt, Germany). Cellets 1000 (microcrystalline cellulose starter pellets, 1000–1400 µm) were provided by Glatt Pharmaceutical Services (Binzen, Germany). A detailed list of the pellets’ characteristics is shown in Table 1. Ethanol 96% (v/v) (technical grade) used in the sample preparation, and methanol (analytical grade) used for the HPLC analytics as well as the buffer salts disodium mono-hydrogen phosphate dodecahydrate (Na2HPO4·12H2O) and monosodium dihydrogen phosphate dodecahydrate (NaH2PO4·12H2O) were obtained from VWR Chemicals GmbH (Darmstadt, Germany).
Pellet Properties
d50 (xc min) [µm]
1123.44
(±7.36)
SPAN
0.166
(±0.002)
b/l
0.893
(±0.000)
SPHT
0.956
(±0.001)
Particle density [g/cm3]
1.452
(±0.016)
Sm [cm2/g]
36.41
(±0.29)
Table 1. Pellet properties of Cellets 1000. d50: mean particle diameter determined by the particle width; SPAN: width of the particle distribution; b/l: aspect ratio; SPHT: sphericity; Sm: specific surface area.
Pellet Coating (PC)
For pellet coating (PC) a laboratory scale fluid bed system Mini Glatt equipped with a Micro-Kit (Glatt GmbH, Binzen, Germany) was used. The coating was applied with a 0.5 mm two-fluid nozzle in bottom spray using the special bottom plate of the Micro-Kit to emulate a three-fluid nozzle with micro-climate. In the beginning, the machine was filled with 25.0 g of Cellets® 1000. The following process parameters were maintained throughout the process: Process gas flow 30 m3/h, product temperature 30.0 ± 1.0 °C (resulting inlet temperature 32–35 °C), spray pressure 1.5 bar and spray rate 1.0 ± 0.2 g/min. The final pellets had a theoretical drug-load of 10% (w/w) due to the fact that ASD and core pellets were used in a 1:1-ratio. […] To prepare the spraying solutions, the API and polymer were dissolved in ethanol 96% (v/v) under continuous stirring (solid content of 10% (w/w)). Prior to spraying, each solution was sonicated for 15 min to ensure complete dissolution of the components.
Subsequently, the coated pellets were manually sieved with a 2 mm mesh to eliminate multicore pellets. The pellets were dried under vacuum for 24 h at the same conditions as the SD powder.
Conclusions
In this study, we successfully prepared binary single phase ASDs of KCZ and LRD as weakly basic, slow crystallizing model APIs (drug load 20% (w/w)) using HPMC-AS or EL100-55 as pH-dependent soluble polymers via fluid bed pellet coating and spray drying. While the received ASD-pellets would not require further downstream processing other than capsule filling or tableting, the fine SD powder had to be transformed into dry granules. In combination with the slow crystallizers, KTZ and LOR, both manufacturing processes resulted in single-phased ASDs of high physical stability (up to 6 months) and similar dissolution performance when normalized to the total outer surface. The dissolution rate depends mainly on this total outer particle surface of the respective sample, independent of the manufacturing process, while the porosity of the sample had a minor impact on its dissolution behavior.
Especially for early formulation development, the high yield and ease of handling due to the pellet properties are strong advantages over the standard spray drying process. Nevertheless, the long process time in larger scale requires further process optimization in fluidized bed processing.
This case study is a short abstract on spouted bed characteristics, following closely findings in the publication by J. Vanamu and A. Sahoo [1].
Spouted bed systems are of highest importance for all powder processing industries, and more specific in pharmaceutical industry for coating and drying in pellet technologies [2]. These systems offer manufacturing particularly fine and temperature-sensitive particles from small to large scale: laboratory systems are capable of processing product volumes of very few grams, while production systems can handle capacities of several tons [3].
But how to control conditions in spouted beds for efficient process applications, like mixing, coating, or drying?
There might be certain reasons, that the hydrodynamic behavior of the spouted bed in the pharmaceutical industries is less investigated. The referred publication shed some light on the hydrodynamic characteristics of a spouted bed where the MCC Spheres (CELLETS®) are adopted as the bed material. These starter cores are ideal model systems due to their perfect sphericity and zero-level friability. At the same time, smooth and defined surface structure initiate perfect modelling conditions in the spouted bed dynamics.
Material
CELLETS®, made of 100% Microcrystalline Cellulose, have been used as bed material. The physical properties of the CELLETS® are shown in Table 1. The CELLETS® particle morphology is represented in Figure 1.
Figure 1: SEM micrographs of CELLETS® 700, found in [1].
Spouted bed: experiment setup
There are some international players on the market of spouted bed technologies, such as Glatt which seems to be the major one (Figure 2). In this framework, a self-made setup is used for experiments. The experiments that have been carried out in a column, which is fabricated from a Perspex sheet. This column consists of a cylindrical section of height 0.53 m and a diameter of the cylinder of 0.135 m. The column further converged the diameter of the cylinder to 0.05 m as a conical bottom having a length of 0.47 m. The spouting air is supplied by a compressed air line is controlled by a gas regulator. The airflow is controlled by a gate valve and a mesh plate having a mesh size less than the size of the bed material is employed as a separator preventing the backflow of the bed material. Images are captured using a high-speed video camera to gain more details of the hydrodynamic characteristics of the flow pattern inside the spouted bed geometry.
Figure 2: Scheme of a spouted bed (Glatt, Germany).
Experiments & spouted bed results
Experiments are carried out with three different static bed heights of shallow depth wherein the bed height is in the range of factor 2-3 of the Inlet diameter using two different particle distribution classes at 500-710 µm and 700-1000 µm, respectively. Analyzed parameters are the pressure drop across the bed, the bed expansion ratio, and the clusters concerning the superficial gas velocity are focused in the following.
J. Vanamu et al. found that the “bed expansion ratio increases with increasing superficial gas velocity until the onset of external spouting, further increase in the superficial gas velocity, the bed expansion ratio decreases. With increasing the volume of bed, the bed expansion ratio decreases. In a larger volume of bed, the particles tend to spout into the freeboard region rather than expanding with higher superficial gas velocity”. Initial spouting is symmetric, but with increasing superficial gas velocity spouting becomes asymmetric, and asymmetry is more pronounced or starts at lower superficial gas velocities for smaller particles. This agrees with existing theories of hydrodynamic behavior in a fluidized environment. Respecting the necessarity of a proper flow behavior for mixing, coating or drying applications in drug processing, symmetric spouting is essential. In turn, the superficial gas velocity may be kept low.
In case that high superficial gas velocity regimes are required for the operations a draft tube may be installed within the column to achieve the symmetric spout formation.
Summary
This case study highlights the Hydrodynamic behavior of MCC spheres in a spouted bed using image processing method. MCC spheres in the range between 500-710 µm and 700-1000 µm had been employed. All spheres showed a symmetric and asymmetric spouting in the spouted bed. With increasing superficial gas velocity, the fully suspended particles are limited to a certain height in the freeboard region due to the gas-solid crossflow. A change from symmetric to asymmetric spouting is observed with increasing superficial gas velocity.
Keeping the conditions efficient for the mixing, coating or drying applications requires finally to suppress high superficial gas velocities, or changing the setup in such way, that symmetric spouting conditions are kept upright even at higher superficial gas velocities.
https://cellets.com/wp-content/uploads/2022/11/titelbild-Hydrodynamic-behavior-of-MCC-Spheres-in-a-spouted-bed.jpg6271200Bastian Arlthttps://cellets.com/wp-content/uploads/2016/10/Logo_Cellets_2016_website.pngBastian Arlt2022-11-21 12:32:382022-11-21 12:37:14Hydrodynamic behavior of MCC Spheres in a spouted bed
https://cellets.com/wp-content/uploads/2022/02/Cellets_BCS_class_I.png6621394Bastian Arlthttps://cellets.com/wp-content/uploads/2016/10/Logo_Cellets_2016_website.pngBastian Arlt2022-02-17 15:10:072022-07-19 11:27:16BSC Class I APIs in oral formulations
Adobe Firefly
ingredientpharm
ingredientpharm
ingredientpharm