Introduction to delayed release oral pharmaceutical compositions
Delayed release oral pharmaceutical compositions enable drug delivery at a defined time after oral administration. Unlike immediate release dosage forms, these systems control when the active pharmaceutical ingredient becomes available for absorption. As a result, they protect acid-sensitive drugs and allow targeted delivery to specific gastrointestinal regions. Moreover, delayed release forms can reduce gastric irritation and peak-related side effects. Therefore, they often improve patient tolerance and adherence. From a consumer compliance perspective, these formulations support simplified dosing schedules and more predictable therapeutic effects. Consequently, they play a key role in chronic therapies that demand long-term adherence and consistent drug exposure.
Summary of US12521351B1: delayed release oral pharmaceutical compositions
The patent US12521351B1 describes delayed release oral pharmaceutical compositions designed primarily for treating inflammatory bowel disease. Specifically, the invention focuses on multiparticulate systems containing mesalamine and hyaluronan within an oral capsule. These particles use an inert core that serves as a substrate for successive functional layers. First, a mesalamine-containing drug layer is applied. Next, a hyaluronan layer follows, which contributes both therapeutic and release-modifying functions. Finally, an outer coating controls the onset of drug release in the gastrointestinal tract.
Importantly, the patent emphasizes controlled release timing rather than simple gastro-resistance. The coating system delays drug exposure until the dosage form reaches intestinal regions associated with inflammation. As a result, the formulation minimizes drug loss in the stomach and improves local efficacy. Furthermore, the multiparticulate design allows uniform drug distribution throughout the intestine, which reduces variability in drug exposure.
In addition, the patent outlines manufacturing methods such as fluid-bed coating and encapsulation. These processes ensure reproducible layer thickness and particle size distribution. Consequently, the formulations achieve consistent dissolution behavior across batches. The patent also defines preferred ranges for core size, drug load, and coating thickness. Therefore, it provides a framework for scalable industrial production.
Overall, US12521351B1 demonstrates how delayed release oral pharmaceutical compositions can combine therapeutic targeting with patient-friendly oral delivery. By integrating functional excipients and structured layering, the invention advances existing mesalamine therapies toward improved clinical performance.
Technical considerations and formulation context
Delayed release oral drug forms differ fundamentally from uncontrolled release systems. While immediate release products dissolve rapidly after ingestion, delayed release formulations intentionally suppress early dissolution. Consequently, they reduce exposure in the stomach and shift drug availability to later intestinal segments. This distinction becomes critical for drugs that cause gastric irritation or degrade in acidic environments.
Dissolution profiles represent a central design parameter. Ideally, delayed release systems show minimal drug release under acidic conditions. Then, they exhibit a rapid and reproducible release once intestinal pH thresholds are reached. Therefore, formulators must carefully balance coating composition, thickness, and particle size. In addition, variability in gastrointestinal transit times must be considered during development.
However, delayed release formulations face several obstacles. Uniform coating of multiparticulates remains technically demanding. Moreover, small variations in process parameters can significantly affect release kinetics. Stability during storage also presents challenges, especially for moisture-sensitive coatings. As a result, robust process control and extensive dissolution testing are essential.
Within this patent context, CELLETS® 500 play a supportive yet important role. These microcrystalline cellulose starter cores provide a smooth, inert, and size-defined substrate. Consequently, they enable uniform drug layering and coating application. Their narrow particle size distribution improves batch reproducibility and dissolution consistency. Therefore, CELLETS® 500 contribute directly to the functional reliability of delayed release oral pharmaceutical compositions.
Conclusion and outlook
Delayed release oral pharmaceutical compositions continue to shape modern oral drug delivery. They align pharmacokinetics with disease physiology and patient needs. The US12521351B1 patent illustrates how structured multiparticulate systems can enhance intestinal targeting and therapeutic consistency. Looking ahead, advances in coating polymers, starter core technologies, and process analytics will further refine these formulations. Consequently, delayed release oral pharmaceutical compositions will remain central to improving efficacy, safety, and long-term patient compliance in oral therapies.
Patent Summary
Name of Patent: Delayed release oral pharmaceutical composition
Introduction to Particle Size Distributions of Inert Spheres and Their Role in Pelletized Pharmaceutical Products
In pharmaceutical formulation science, Particle Size Distributions of Inert Spheres represent a fundamental quality attribute for multiparticulate dosage forms. Inert spheres, such as microcrystalline cellulose pellets, act as neutral carriers for active pharmaceutical ingredients. They enable precise drug layering, predictable dissolution, and uniform content distribution in capsules or tablets. A narrow and well-characterized PSD improves processability and coating uniformity. It also supports reproducible drug delivery performance in multiparticulate systems. Inert spheres such as CELLETS® offer tight PSD and high sphericity. Therefore, they provide robust cores for dosage forms ranging from low-dose products to extended-release multiparticulates.
A Publication Worth Reading: computerized image analysis
The publication by Heinicke and Schwartz [1] evaluates computerized image analysis for measuring PSD in pharmaceutical spheres and pellets. The study covers particle size ranges from approximately 425 to 1400 micrometers. Traditional sizing methods, such as sieve analysis, provide limited resolution and statistical detail. In contrast, image analysis demonstrated high repeatability and sensitivity. It quantified size differences that traditional methods could not detect. The authors compared two inert sphere lots before drug layering in a fluid-bed rotor granulator. Differences in starting PSD appeared clearly in the resulting granulated products. This result highlights the importance of core PSD for downstream performance. Furthermore, image analysis detected coating thickness increments as small as four micrometers.
The authors also investigated sampling strategies and sample sizes necessary for reliable measurements, recognizing that an appropriate representativeness of sample draws is critical for statistically meaningful PSD outcomes. Importantly, image analysis captured not only size distribution but also provided visual and morphological data for each particle, thereby enriching the dataset beyond mere dimensional statistics. The technique’s effectiveness was tested in both laboratory and commercial scale contexts, including measuring polymer-coated nonpareils during continuous fluid-bed processing. The similarity between in-situ samples (collected via process sampling ports) and whole batch samples suggested that fluid-bed processes in these systems provide sufficiently homogeneous conditions for representative PSD capture by image analysis.
Beyond the direct findings, the work situates PSD measurement via image analysis within a broader pharmaceutical quality landscape. Historically, PSD has been a critical parameter because it influences particle flow, coating behavior, drug layering uniformity, content uniformity, and ultimately drug release characteristics. The continuous development of in-line and at-line image analysis methods positions this approach as part of process analytical technology (PAT), enabling more dynamic control and monitoring of multiparticulate manufacturing.
Advances in Image Analysis for Determining Particle Size Distributions of Inert Spheres
Image analysis has evolved rapidly as a high-resolution method for determining PSD in pharmaceutical spheres. It directly measures individual particle dimensions and morphologies with high precision. Unlike sieve analysis or laser diffraction, image analysis provides particle-by-particle size and shape data. Therefore, it improves PSD accuracy, reproducibility, and visualization during development and quality control. Dynamic image analysis platforms process thousands of particles within minutes. As a result, they generate robust PSD and shape statistics correlated with functional performance criteria.
Important facts include the distinction between number-based and volume-based PSD measures. Metrics such as D10, D50, and D90 describe the spread and balance of the size distribution. In addition, image analysis extracts shape parameters such as sphericity and aspect ratio. These parameters strongly influence flow properties and coating behavior. Moreover, image analysis enables rapid in-process feedback for monitoring and control. This capability supports coating thickness control and ensures batch-to-batch consistency.
Persisting Obstacles
Despite these advances, obstacles persist. Adequate sample preparation is essential to avoid overlapping particles and bias, especially when using static imaging methods. Agglomeration, depth-of-field effects, and segmentation challenges in image processing can introduce measurement uncertainty if not properly managed. Opportunities exist to integrate enhanced machine vision, artificial intelligence (AI), and real-time imaging to improve discrimination of individual particles in complex mixtures or in high-throughput manufacturing environments. In-line imaging systems with real-time analytics can transform PSD from a static quality attribute to a dynamic process performance indicator.
CELLETS® exemplify the concept of narrow PSD and high surface homogeneity in inert spheres. These microcrystalline cellulose pellets exhibit tight particle size distributions within specified fractions (e.g., 100–200 µm, 150–300 µm, up to 1000-1400 µm) with high sphericity, low friability, and consistent surface characteristics that enhance coating uniformity and enable predictable performance in multiparticulate dosage forms. The narrow PSD and uniform surface enable reproducible drug layering, optimized flow properties, and controlled release profiles, making them ideal cores in fluid bed and Wurster coating operations.
Conclusion and Outlook
The study by Heinicke and Schwartz underscores the value of image analysis for PSD determination. They compared traditional sizing methods with image analysis for inert spheres and coated pharmaceutical pellets. The detection of fine particle diameter differences and detailed morphology supports formulation design, process control, and quality assurance. Future image analysis developments, including AI and in-line PAT integration, will further enhance PSD measurement capabilities. These advances will enable real-time adjustments and closed-loop control in pellet manufacturing. As multiparticulate drug delivery advances, precise characterization of Particle Size Distributions of Inert Spheres remains essential. This precision supports consistent therapeutic outcomes, regulatory compliance, and manufacturing efficiency. Ongoing innovations in imaging hardware, software, and data analytics will strengthen real-time quality control and predictive modeling.
References
[1] G. Heinicke, J. B. Schwartz, Pharmaceutical Development and Technology 2005 (9) 4, 359-367, doi:10.1081/PDT-200032996
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
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Cellulose-derived spherical activated carbon offers a sustainable and efficient solution for adsorbing harmful compounds such as uremic toxins [1]. This carbon material is made from renewable cellulose, which is transformed into spherical particles and then activated to increase surface area and porosity. The spherical shape improves flow properties and reduces dust, making it ideal for pharmaceutical and biomedical applications. Moreover, it combines eco-friendly production with strong adsorption performance, providing a safer and more manageable alternative to traditional powdered carbon.
Uremic toxins are metabolic waste compounds that accumulate in the body when kidney function declines. These toxins interfere with biological processes and contribute to various health issues. Drugs and adsorbent therapies aim to remove them effectively, but such interventions must be selective to avoid removing essential molecules. Therefore, understanding both the functionality and potential toxicity of uremic toxins is crucial for designing safe and effective treatments. While adsorption therapies can improve toxin clearance, they also carry risks such as unintended drug adsorption or gut irritation, which must be minimized through precise material engineering.
Summary of the Publication
Shin et al. (2025) present a study on sustainable cellulose-derived spherical activated carbon designed for efficient uremic toxin removal. The research focuses on transforming cellulose into spherical carbon precursors and activating them to achieve high porosity and surface area. The resulting material combines uniform shape, hierarchical pore structure, and strong mechanical integrity. These properties make it ideal for biomedical use, particularly for toxin adsorption under gastrointestinal conditions. The authors report that the spheres maintain their shape across different pH levels and perform well even in dynamic or competitive adsorption environments.
Furthermore, the adsorption kinetics show that these spherical carbons quickly capture uremic toxin molecules such as indole derivatives. The authors compare the material with conventional activated carbon powders and find significant improvements in handling and biocompatibility. Importantly, the spheres demonstrate low cytotoxicity, which supports their suitability for oral or extracorporeal use. Because of their uniform size and reduced dusting, they minimize irritation risks and can be easily integrated into medical formulations or devices. In addition, the study discusses the environmental and economic benefits of using cellulose feedstocks, showing that this process supports circular material use and low-cost production.
A key part of the research involves CELLETS® 100 and CELLETS® 500. These cellulose microspheres act as templates during synthesis. CELLETS® 100, having a smaller diameter, produces finer activated carbon spheres, while CELLETS® 500 leads to larger ones. This variation allows the authors to tune pore structure, surface area, and mechanical properties. Consequently, CELLETS® 100-derived carbons show faster adsorption kinetics, whereas CELLETS® 500-derived carbons offer better durability. The study highlights that choosing the right CELLETS® grade directly influences the final adsorption performance and application potential of the spherical carbon.
Conclusion and Outlook
The development of cellulose-derived spherical activated carbon marks a major step toward safer and more sustainable toxin removal technologies. By merging green chemistry with advanced nanoengineering, these materials achieve both environmental and therapeutic goals. Their customizable size, stability, and porosity enable versatile use in pharmaceutical formulations and medical devices. Looking ahead, researchers must explore long-term biocompatibility, selective adsorption behavior, and performance in complex biological fluids. Moreover, scaling up production under pharmaceutical standards will determine clinical viability. With further optimization, cellulose-derived spherical activated carbon could revolutionize uremic toxin management and open new paths for eco-friendly therapeutic materials.
References
[1] Kyungmin Shin, Su-Bin Kim, Yong-Han Kim, Dae-Duk Kim, Seul-Yi Lee, Soo-Jin Park, Materials & Design,a available online 10 October 2025, 114892. doi:10.1016/j.matdes.2025.114892
Multiple-Unit Pellet System with Diclofenac Sodium represents a modern and flexible approach to oral drug delivery. This multiparticulate system divides the drug dose into many small pellets, each functioning as an individual unit. Because of this design, the formulation ensures more uniform gastrointestinal distribution and minimizes dose dumping. It also improves patient compliance and allows combination of different release profiles in a single dosage form.
Diclofenac Sodium, a potent nonsteroidal anti-inflammatory drug (NSAID), reduces pain, inflammation, and fever. However, it has low solubility and high permeability, which limits its absorption. Therefore, formulating it in a multiple-unit pellet system improves its bioavailability and controls its release rate. As a result, patients experience longer relief with fewer side effects, especially gastrointestinal irritation.
Summary of the Publication
The study “Development of a Biphasic-Release Multiple-Unit Pellet System with Diclofenac Sodium Using Novel Calcium Phosphate-Based Starter Pellets” focuses on creating a capsule with both rapid and sustained release. It combines two types of pellets: delayed-release (DR) pellets coated to resist stomach acid, and extended-release (XR) pellets designed for gradual release in the intestine. This structure allows a quick onset of action and a long-lasting therapeutic effect.
The researchers introduced dicalcium phosphate anhydrous (DCPA) as a new starter core. Unlike conventional cores such as microcrystalline cellulose (for example CELLETS® 500), sucrose, or isomalt, DCPA cores are dense and insoluble. They show excellent strength, low friability, and smooth flow. These qualities make them ideal for producing stable multiparticulate systems. Furthermore, the team used a fluid-bed coating process to ensure even layers of drug and polymer, verified by scanning electron and Raman microscopy.
Dissolution testing showed clear differences among core types. DCPA-based pellets released the drug steadily and predictably, even under variable pH and hydrodynamic conditions. In contrast, soluble cores like sucrose and isomalt caused uneven release and premature erosion. The biphasic MUPS capsules with DCPA pellets combined rapid and prolonged release successfully. Under simulated physiological conditions, they maintained consistent performance and outperformed commercial reference formulations.
The study highlights that the pellet core material strongly affects drug release and mechanical behavior. Insoluble DCPA cores provided stability and controlled release, while soluble ones failed to maintain coating integrity. Therefore, choosing the right core is essential for reliable performance in Multiple-Unit Pellet System with Diclofenac Sodium formulations.
Conclusion and Outlook
Multiple-Unit Pellet System with Diclofenac Sodium offers a strong platform for precise and predictable drug delivery. The use of calcium phosphate-based starter pellets supports biphasic release with high mechanical stability and consistent drug diffusion. As a result, patients benefit from immediate pain relief followed by sustained therapeutic action.
In the future, researchers can use UV imaging, Raman mapping, and other visualization techniques to monitor the release process in real time. These tools will deepen understanding of coating behavior and in vivo performance. Continued development of the Multiple-Unit Pellet System with Diclofenac Sodium will likely lead to safer, more effective, and patient-friendly oral therapies.
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Research Advances in MCC Pellet Technology and Applications
Scientific literature on MCC pellets highlights the growing importance of CELLETS® in pharmaceutical and scientific research. These microcrystalline cellulose spheres play a key role in developing reliable multiparticulate drug delivery systems. Researchers have investigated improved rivaroxaban dissolution, efficient film coating kinetics, and their use in orally disintegrating films. In addition, studies focus on colon-targeted vitamin B₂ release and fluidized-bed coating performance. Moreover, academic theses explore uniform hot-melt coating techniques and detailed modeling of tablet disintegration. As a result, MCC pellets continue to prove their versatility across many dosage forms. Consequently, this expanding body of literature reinforces the value of CELLETS® in advancing modern drug delivery technologies.
Selected Scientific literature on MCC pellets
Please, find scientific literature on MCC pellets (CELLETS®), MCC spheres. This list is constantly updated and does not claim to be complete. If you are author, scientist or R&D specialist, please submit your present publication to us for improving the visibility.
Research article Optimising the in vitro and in vivo performance of oral cocrystal formulations via spray coating European Journal of Pharmaceutics and Biopharmaceutics, Volume 124, March 2018, Pages 13-27
Dolores R. Serrano, David Walsh, Peter O’Connell, Naila A. Mugheirbi, Zelalem Ayenew Worku, Francisco Bolas-Fernandez, Carolina Galiana, Maria Auxiliadora Dea-Ayuela, Anne Marie Healy
Conference abstract Multiple-unit orodispersible mini-tablets International Journal of Pharmaceutics, Volume 511, Issue 2, 25 September 2016, Page 1128
Anna Kira Adam, Christian Zimmer, Stefan Rauscher, Jörg Breitkreutz
Research article Asymmetric distribution in twin screw granulation European Journal of Pharmaceutics and Biopharmaceutics, Volume 106, September 2016, Pages 50-58
Tim Chan Seem, Neil A. Rowson, Ian Gabbott, Marcelde Matas, Gavin K. Reynolds, AndyIngram
Research article Physical properties of pharmaceutical pellets Chemical Engineering Science, Volume 86, 4 February 2013, Pages 50-60
Rok Šibanc, Teja Kitak, Biljana Govedarica, StankoSrčič Rok Dreu
Research article Labscale fluidized bed granulator instrumented with non-invasive process monitoring devices Chemical Engineering Journal, Volume 164, Issues 2–3, 1 November 2010, Pages 268-274
Jari T. T. Leskinen, Matti-Antero H. Okkonen, Maunu M. Toiviainen, Sami Poutiainen, Mari Tenhunen, Pekka Teppola, Reijo Lappalainen, Jarkko Ketolainen, Kristiina Järvinen
Research article Granule size distribution of tablets Journal of Pharmaceutical Sciences, Volume 99, Issue 4, April 2010, Pages 2061-2069
Satu Virtanen, Osmo Antikainen, Heikki Räikkönen, Jouko Yliruusi
Research article New insights into segregation during tabletting International Journal of Pharmaceutics, Volume 397, Issues 1–2, 15 September 2010, Pages 19-26
S. Lakio, S. Siiriä, H. Räikkönen, S. Airaksinen, T. Närvänen, O. Antikainen, J.Yliruusi
Research article In vivo evaluation of the vaginal distribution and retention of a multi-particulate pellet formulation European Journal of Pharmaceutics and Biopharmaceutics, Volume 73, Issue 2, October 2009, Pages 280-284
Nele Poelvoorde, Hans Verstraelen, Rita Verhelst, Bart Saerens, Ellen De Backer, Guido Lopes dos Santos Santiago, Chris Vervaet, Mario Vaneechoutte, Fabienne De Boeck, Luc Van Borteld, Marleen Temmerman, Jean-Paul Remon
List – Publications with MCC spheres, 2008 and earlier
Research article Attrition strength of different coated agglomerates Chemical Engineering Science, Volume 63, Issue 5, March 2008, Pages 1361-1369
B. van Laarhoven, S.C.A. Wiers, S.H. Schaafsma, G.M.H. Meesters
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This patent describes an oral formulation designed to deliver a drug (a Pyridinone derivative) specifically to the small intestine. The formulation contains coated granules, pellets, beads, minicapsules, or minitablets. Each particle includes a core material and an enteric coating polymer, which ensures targeted drug release. Moreover, the patent covers the preparation method and its medical use.
The delayed-release oral formulation uses coated microcrystalline cellulose pellets (CELLETS®, CELLETS® 500) as the core material. These pellets range in size from 100 to 1,400 µm. In addition, the drug, a Pyridinone derivative for treating fibrostenotic Crohn’s disease, is protected by an enteric coating. This coating ensures that the drug releases in the intestine. Specifically, release occurs in a pH range of 6.2 to 6.8, which allows for topical availability in the ileum. Furthermore, the patent provides details on both the preparation process and medical applications.
Document information
Document Type and Number: (“ORAL FORMULATION OF A PYRIDINONE DERIVATE AND USE THEREOF IN PROPHYLAXIS AND/OR TREATMENT OF INTESTINAL FIBROSIS”)
Kind Code: A1
Inventors:
Wilhelm, Rudolf (Bischweier, DE)
Tewes, Bernhard (Vörstetten, DE)
Greinwald, Roland (Kenzingen, DE)
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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”)
The patent application US20240350420A1 focuses on pharmaceutical formulations and methods for treating conditions such as hyperhidrosis, which causes excessive sweating. It details the development of modified-release compositions using Pilocarpine HCl, a muscarinic agonist. These formulations aim to optimize drug delivery by using various release mechanisms, including immediate, delayed, or sustained release. Notably, the innovations include encapsulation techniques with polymer coatings. These coatings control dissolution rates under different conditions, ensuring stable and effective drug delivery over time.
Moreover, the application highlights formulations that combine Pilocarpine with other agents, such as Oxybutynin, to boost therapeutic efficacy. It also examines dissolution profiles under varying environmental conditions, emphasizing stability and performance consistency. Consequently, this approach seeks to improve patient outcomes by tailoring release profiles to specific medical needs. Additionally, it minimizes side effects through controlled drug exposure.
Why CELLETS® are important in these methods for treating hyperhidrosis
CELLETS® are microcrystalline cellulose spheres. They serve as an essential component in drug delivery systems designed for controlled and extended release of active pharmaceutical ingredients (API). These spheres act as inert core substrates, providing a uniform and stable base for layering active compounds and functional polymers. In addition, their consistent size and smooth surface allow precise and even distribution of coatings, which is critical for predictable drug release kinetics.
Cellets form the crucial base for formulations that rely on pellet technologies. These formulations improve the pharmacokinetic profile of APIs, especially highly lipophilic drugs, by controlling their release rate. By coating excipients and API, multi-layer systems on these cores enable gradual drug dissolution. This process reduces fluctuations in plasma drug levels and minimizes side effects. For example, in a Pilocarpine HCl formulation, coating CELLETS® with suitable excipients allows extended drug release. This maintains therapeutic concentrations longer and improves patient compliance by reducing dosing frequency.
Moreover, their flexibility allows use across various dosage forms, such as capsules, compressed tablets, or even gel-like forms. Additionally, the uniformity of these MCC starter beads ensures each pellet delivers a controlled dose of the active ingredient. Therefore, they are integral to achieving consistent therapeutic outcomes in complex drug delivery systems.
The function of Pilocarpine HCl
Pilocarpine HCl is a cholinergic agonist. It stimulates muscarinic receptors, increasing secretion production and smooth muscle contraction. Primarily, it treats glaucoma in ophthalmology by reducing intraocular pressure. This effect occurs through enhanced aqueous humor outflow. Additionally, it manages xerostomia (dry mouth) caused by conditions like Sjögren’s syndrome or radiation therapy for head and neck cancers. Its parasympathomimetic action stimulates saliva production and improves symptoms.
Document information
Document Type and Number: (“Pharmaceutical compositions and methods for treating hyperhidrosis”).
Kind Code: A1
Inventors:
Stephen Wayne Andrews, Samuel Bruce Balik, John Edward Jett, Robert Michael LEMING
Disclaimer
This text was partly generated by chatGPT engine version GPT‑4o, on Nov 21, 2024. Image was generated with Adobe Firefly.
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Colon Delivery of Vitamin B2: A Novel Food-Grade Approach
Innovative Food-Grade Delivery Systems
This article, “In vitro validation of colon delivery of vitamin B2 through a food grade multi-unit particle system,” [1] presents a novel method for delivering active ingredients to the colon. Specifically, it focuses on riboflavin in a food-grade and environmentally friendly form. The system uses a double-layer coated multi-unit particle system (MUPS). The MUPS features a cellulose core, an alginate inner layer, and a shellac outer layer. This design protects the particles as they pass through the upper digestive tract.
Moreover, tests show that the system releases about 90% of riboflavin directly in the colon. This release promotes gut health by increasing beneficial short-chain fatty acids. In addition, this sustainable method responds to the growing demand for effective colon-targeted health products. It also complies with EU regulations that restrict microplastic use in consumable goods.
The MUPS containing riboflavin, branded as Humiome® B2 by DSM-Firmenich, uses cellulose pellets called CELLETS® as its core. During manufacturing, producers apply riboflavin and pectin as a binder onto the Cellets using a fluid bed layering method. Next, they coat the MUPS with layers of sodium alginate and harden them with calcium chloride. Finally, they add a shellac outer layer. This structure controls the release of riboflavin in the colon and provides an efficient, food-grade delivery system for active nutrients.
Furthermore, the study highlights the effectiveness of the shellac-alginate MUPS for targeted riboflavin delivery to the colon. Food-grade materials support environmental standards, making this approach sustainable. In vitro tests confirm that approximately 90% of riboflavin reaches the colonic region. The results also indicate potential health benefits, including microbiome modulation and increased short-chain fatty acid production. Looking ahead, clinical studies will examine how this delivery system affects the microbiome and overall host health. These findings support its use in functional foods, dietary supplements, and medical nutrition.
Abstract
Colon-targeted delivery of active ingredients is common in pharmaceutical products. However, such delivery systems are rare in functional foods, beverages, dietary supplements, and medical nutrition. Nevertheless, emerging evidence shows that nutrients delivered to the colon can benefit gut microbiota and overall host health. This trend increases the demand for sustainable, food-grade materials that are approved for regulatory use.
In this paper, we describe a double-layer coated multi-unit particle system (MUPS) with a diameter of approximately 730 microns. It consists of food-grade materials: shellac as the outer layer, alginate as the inner layer, cellulose as the core, and riboflavin as the active ingredient. We tested the MUPS for colonic delivery using three well-established in vitro digestion and fermentation models: USP Apparatus 3, TIM-1, and TIM-2. All models confirmed that the MUPS remained intact through simulated upper gastrointestinal conditions. Furthermore, approximately 90% of riboflavin was released under simulated ileal-colonic conditions.
The TIM-2 model also revealed effects on microbiome composition, showing increased production of short-chain fatty acids, including acetate and butyrate. These results provide a solid foundation for validating this vitamin-loaded food-grade MUPS in future human clinical trials. Additionally, following the European Commission’s recent decision to restrict intentionally added microplastics in products, the materials used in this formulation offer an environmentally friendly alternative to traditional methyl acrylate coatings.
Reference
[1] Steinert, R.E., Sybesma, W., Duss, R., Rehman, A., Watson, M., van den Ende, T.C., & Funda, E. (2024). In vitro validation of colon delivery of vitamin B2 through a food grade multi-unit particle system. Beneficial Microbes, 16(2), 253-269. doi:10.1163/18762891-bja00045
https://cellets.com/wp-content/uploads/2024/11/Titelbild-Steiner_2024.jpg6271200Bastian Arlthttps://cellets.com/wp-content/uploads/2016/10/Logo_Cellets_2016_website.pngBastian Arlt2024-11-12 14:54:572025-08-21 14:29:32In vitro validation of colon delivery of vitamin B2 through a food grade multi-unit particle system
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