CELLETS® are pellets or spheres made of microcrystalline cellulose. The size ranges from 100 µm to 1400 µm. Being neutral starter cores, they can be used as carrier system for low-dosed APIs and allow diverse functional coating. See pellet technologies for a detailed description.

CS_sphericity_image_4

Electron microscopy yield perfect imaging data of the MCC pellets’ surfaces. Magnification: 250x, working distance 8.0 mm, voltage: 10 keV.

Available size classes are (click for more information):

  • CELLETS® 100
  • CELLETS® 200
  • CELLETS® 350
  • CELLETS® 500
  • CELLETS® 700
  • CELLETS® 1000

Any size class of CELLETS® have same striking advantages:

  • low friability and extreme hardness
  • insolubility in water
  • high spherictity
  • smooth surface
  • good monodispersity

See case studies to see these starter pellets in action!

nutritional table for CELLETS®

A nutritional table for CELLETS®

A nutritional table for CELLETS®, what is it about? CELLETS® are made of 100% microcrystalline cellulose (MCC), developed for state of the art oral dosage forms, such as MUPS, capsules, sachets, stick pack units. Anyway, some pharmaceutical applications move towards food products and vice versa. This field of nutraceutical applications are extending market share and we got more frequently asked about energy and nutritional levels of MCC. So, let’s shed some light on this.

MCC is a modified form of cellulose that is often used as a filler and stabilizer in the food and pharmaceutical industries. It consists of plant fibers and serves primarily as a dietary fiber, but contains practically no usable nutrients such as vitamins, minerals, proteins or fats. It is calorie-free as it is not digested in the human body.
As microcrystalline cellulose is not metabolized, it does not provide any usable macro- or micronutrients. A nutritional table for 100 g of microcrystalline cellulose would therefore look like this:

Substance quantity per 100 g
Energy 0 kcal
Protein 0 g
Fat 0 g
Carbohydrates 0 g
Dietary fiber 100 g
Sugar 0 g
Salt 0 g
Vitamins & minerals 0 mg

Microcrystalline cellulose is a pure dietary fiber with no nutritional value and is not broken down or absorbed in the human digestive tract [1]. It therefore has no calories and provides no nutrients to the body. This nutritional table also holds for CELLETS® but has rare importance in pharmaceutical formulations.

References

[1] N. Prabsangob, NFS Journal, 31 (2023) 39-49. doi:10.1016/j.nfs.2023.03.002

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colon delivery of vitamin B2
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In vitro validation of colon delivery of vitamin B2 through a food grade multi-unit particle system

Colon delivery of vitamin B2

This article “In vitro validation of colon delivery of vitamin B2 through a food grade multi-unit particle system” discusses a novel method for delivering active ingredients, particularly riboflavin, to the colon in a food-grade, environmentally friendly form using a double-layer coated multi-unit particle system (MUPS). The MUPS uses a shellac outer layer, alginate inner layer, and cellulose core, maintaining integrity through upper digestive processes. Tests showed it releases about 90% of riboflavin in the colon, enhancing gut health by promoting beneficial short-chain fatty acids. This sustainable approach addresses rising demand for effective colon-targeted health products and aligns with EU regulations limiting microplastic use in consumable goods.

The MUPS containing riboflavin, branded as Humiome® B2 by DSM-Firmenich, utilizes cellulose pellets known as CELLETS® as the core material. The manufacturing process involves a fluid bed layering method, where riboflavin and pectin are applied as a binder onto the Cellets. The MUPS is then coated with layers of sodium alginate and hardened with calcium chloride, followed by a shellac outer layer. This design ensures a controlled, colonic release, offering an efficient, food-grade delivery system for active nutrients.

The study demonstrates the efficacy of a shellac-alginate MUPS for targeted delivery of riboflavin to the colon, using food-grade materials that align with environmental standards. In vitro models validated its effectiveness, with around 90% of riboflavin reaching the colonic region. Results show promise for health benefits linked to microbiome modulation and short-chain fatty acid production. Future clinical studies will focus on the impact of this delivery system on microbiome and host health, supporting its potential in functional foods, supplements, and medical nutrition.

Abstract

Colon target delivery of active ingredients is frequently applied in pharmaceutical products. However, in functional food and beverage applications, dietary supplements, and medical nutrition, formats targeting colonic delivery to improve human health are rare. Nevertheless, there is emerging evidence for beneficial effects of colonic delivered nutrients on gut microbiota and host health which increases the demand for sustainable food grade materials that are regulatory approved for application. In this paper, we describe a double layer coated multi-unit particle system (MUPS) with a diameter of approximately 730 microns consisting of food grade materials: shellac as outer layer, alginate as inner layer, cellulose as a core and riboflavin as active ingredient. The suitability of the MUPS for colonic delivery was tested in three well-established in vitro digestion and fermentation models: the USP Apparatus 3 and the TNO Intestinal Models 1 and 2 (TIM-1 and TIM-2). All systems confirmed the integrity of the MUPS under simulated upper gastrointestinal tract conditions with approximately 90% of the active ingredient being released under simulated ileal-colonic conditions. The TIM-2 model also showed the effects of riboflavin loaded MUPS on the microbiome composition with an increase in the production of short-chain fatty acids, acetate and butyrate. The results of these experiments provide a reliable basis for validation of this vitamin-loaded food grade MUPS in future human clinical trials. In addition, following the recent announcement of the European Commission to restrict intentionally added microplastics to products, the materials used in the described formulation offer an environmentally friendly alternative to often applied methyl acrylate based coatings.

Source of Abstract

In vitro validation of colon delivery of vitamin B2 through a food grade multi-unit particle system in: Beneficial Microbes- Vorabveröffentlichung

 

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Homogeneity and mechanical properties of orodispersible films loaded with pellets
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Homogeneity and mechanical properties of orodispersible films loaded with pellets

This article on homogeneity and mechanical properties of orodispersible films loaded with pellets was published on Oct 20 2024 on ScienceDirect.

Abstract

Orodispersible films (ODFs) have served as an emerging platform for the delivery of drugs in a convenient way. The production of ODFs with incorporated pellets may still be a challenging process due to problems to obtain proper homogeneity and deteriorating mechanical properties of the films with incorporated relatively big particles in high concentration. The goal of this work was to evaluate the possibility to achieve fast disintegrating ODFs with homogenously incorporated spherical granules without loss of required mechanical properties. Hypromellose films with incorporated placebo pellets (size 200 µm or 100 µm) in a content range of 20–45 % w/w were prepared by a solvent casting method. Planetary mixer (Thinky) was successfully applied for preparation of a homogeneous mass for casting. The suspended spherical solid particles caused dose and size dependent changes in the mechanical properties and disintegration behaviour of ODFs films, but only 100 µm pellets in concentration higher than 40 % reduced significantly the tear resistance. The films with the pellets disintegrated faster and the larger particles reduced the disintegration time by 60 %. Good homogeneity of pellets distribution, expressed as a number of the particles per unit area, was confirmed for films obtained with a gap height 500 or 800 µm.

Document information

Pellet materials

Pellets in two different sizes: CELLETS® 100 and CELLETS® 200, composed of 100% microcrystalline cellulose, were used as model spherical granules.

Authors

Katarzyna Centkowska, Martyna Szadkowska, Marta Basztura, Małgorzata Sznitowska

Source

published on Oct 20 2024 on ScienceDirect under CC BY 4.0 license.

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packaged modified release gamma-hydroxybutyrateadobe firefly
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Patent on packaged modified release gamma-hydroxybutyrate formulations having improved stability

The patent WO2019123269A1, titled “Packaged modified release gamma-hydroxybutyrate formulations having improved stability“ presents innovative formulations and packaging methods designed to enhance the dissolution and chemical stability of gamma-hydroxybutyrate (GHB), a treatment for narcolepsy. Current GHB treatments, like XYREM®, require patients to wake up mid-sleep for a second dose, making this method cumbersome. This patent aims to develop a once-nightly, modified-release GHB form that maintains stability through advanced packaging, which controls relative humidity to ensure long-term effectiveness and prevent chemical degradation of GHB into gamma-butyrolactone (GBL).

Key Innovations:

  1. Modified Release Formulation: The patent includes an immediate and modified release component, both containing GHB or a pharmaceutically acceptable salt. The modified release form is designed to control the release of GHB over time, providing sustained therapeutic effects throughout the night without the need for a second dose. This formulation helps improve patient convenience and adherence to treatment.
  2. Stability Issues with GHB: GHB is highly hygroscopic and chemically unstable, which leads to degradation, especially in high humidity environments. Its instability results in the formation of GBL, a degradation product that reduces the drug’s effectiveness. The patent addresses these challenges by creating a formulation with stable dissolution profiles and chemical stability, even under stressful storage conditions (e.g., high temperature and humidity).
  3. Packaging Innovation: To further enhance the stability, the GHB formulations are packaged in a way that maintains a specific relative humidity range (29% to 54%) within the package. This careful control of humidity is crucial to prevent GHB from degrading into GBL. The packaging material has a low water vapor transmission rate, reducing moisture exposure and ensuring the drug remains stable over time.
  4. Hydrophobic Coating: The patent uses a hydrophobic coating (e.g., glyceryl tristearate, hydrogenated vegetable oil) and methacrylic acid copolymers for the modified release component. These coatings help control the release rate of GHB and protect it from moisture, ensuring a steady release and preventing premature degradation.
  5. Pharmaceutical Composition: The GHB composition in the patent includes varying ratios of immediate and modified release components. These compositions are tailored to provide a sufficient therapeutic dose while maintaining stability. The sizes of the particles and the specific formulation ratios (e.g., 40/60 to 60/40) are key factors in achieving the desired pharmacokinetics and release profiles.

The primary innovation lies in controlling the relative humidity within the packaging, alongside a modified release formulation with hydrophobic coatings to maintain the drug’s chemical stability and effectiveness. These advancements make GHB therapy more convenient by eliminating the need for a second nightly dose and addressing the stability challenges that have plagued previous formulations.

In this patent, CELLETS® play a crucial role as inert cores used in the formulation of modified release or the active or salts thereof. These starter spheres serve as carriers for the active ingredient by providing a surface for multi-layer drug layering. Their primary function is to ensure uniform drug distribution and control the release profile of GHB. The benefits include enhancing dissolution stability, maintaining the integrity of the dosage form over time, and helping to modulate the release rate of the drug for once-nightly dosing convenience. For these aspects, MCC starter sphere types where employed: CELLETS® 90, CELLETS® 100, CELLETS® 127. Glatt ProCell™ technique is used for spraying molten API.

Document information

Document Type and Number: (“Packaged modified release gamma-hydroxybutyrate formulations having improved stability”).
Kind Code: A1

Inventors:

Hervé GUILLARD

Disclaimer

This text was partly generated by chatGPT engine version GPT‑4o, on Oct 21, 2024. Image was generated with Adobe Firefly.

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pulsatile release caffeine formulationadobe firefly

Patent on pulsatile release caffeine formulation

The patent application 20240316057 focuses on a pulsatile release formulation for caffeine, designed to control its release profile over a specific time frame. The formulation is targeted at therapeutic and non-therapeutic uses — enhancing mental alertness and addressing conditions like morning grogginess or fatigue. By using a release-controlling polymeric system, the caffeine release can be delayed, achieving a time-controlled vitalization of the body.

The key component in this formulation is CELLETS®, which act as a neutral core upon which the active ingredient (caffeine) and various release-controlling polymers are layered. CELLETS®, made from microcrystalline cellulose, serve as an ideal platform due to their uniform size and consistent performance. These attributes are essential for ensuring the precise, staggered release of caffeine at different stages of the gastrointestinal tract.

The use of CELLETS® in this pulsatile system enables a multi-phase release profile. Initially, the formulation allows for a delayed release, where the caffeine remains largely intact through the acidic environment of the stomach. Once the formulation passes into more neutral areas of the gastrointestinal tract, the polymers dissolve, leading to rapid caffeine release. This method ensures that caffeine is absorbed in a controlled manner over a period of 4 to 8 hours after ingestion, thus avoiding sudden spikes in caffeine levels that can cause jitters or other side effects.

This approach also has the benefit of tailoring the release pattern to the body’s needs over time, with an initial delay followed by a burst of caffeine when it is most needed—such as during the morning hours after a night of sleep. The polymeric coatings, including methacrylate-based polymers (e.g., Eudragit®), allow for precise control of this delayed release profile.

The overall innovation provides a tailored caffeine delivery system that improves both efficacy and user experience. It offers applications beyond general alertness, potentially being useful for managing specific sleep-wake disorders, fatigue, or as a stimulant for individuals with delayed sleep-phase syndromes​. In this specific patent, also Glatt process technologies are included: Glatt CML 10 Container Blender, Glatt GS 60 Rotor Sieve, Glatt TMG Vertical Granulator, Glatt Mini Fluid Bed, Glatt GC 1 Pan Coater.

Document information

Document Type and Number: (“pulsatile release caffeine formulation”) and elsewhere.
Kind Code: A1

Inventors:

Yerlikaya, Firat (Çankaya, TR)
Arslanç, Aslihan (Çankaya, TR)

Disclaimer

This text was generated by chatGPT engine version GPT‑4o, on Oct 21, 2024. Image was generated with Adobe Firefly.

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Modified release Gamma-Hydroxybutyrateadobe firefly
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Patent on modified-release Gamma-Hydroxybutyrate formulations having improved pharmacokinetics

The patent application titled “Modified Release Gamma-Hydroxybutyrate (GHB) Formulations Having Improved Pharmacokinetics” (US20240148685) focuses on improving the delivery of GHB, a substance used for treating sleep disorders like narcolepsy, through modified-release formulations. The goal is to optimize GHB’s absorption, enhancing patient convenience and compliance by reducing the need for multiple nightly doses.

The key innovation in the patent is the use of CELLETS®, microcrystalline spheres often employed as a neutral core for drug layering. In this application, CELLETS® act as carriers for the active ingredient, allowing precise control over the release profile of GHB. These small spherical particles, made from microcrystalline cellulose, offer uniform size and high mechanical strength, ensuring consistent drug loading and a controlled release rate.

In this patent, the CELLETS® are coated with various layers of GHB and release-modifying agents, enabling a predictable and sustained release of the active substance. This modified release profile allows GHB to be administered in a once-nightly dose rather than requiring the patient to wake up for a second dose, which was a limitation with previous immediate-release formulations. This extended-release mechanism helps maintain stable plasma concentrations of GHB over an 8-hour period, improving both the efficacy of the treatment and patient compliance.

The innovation emphasizes addressing the shortcomings of existing GHB formulations by ensuring a better pharmacokinetic profile—particularly regarding absorption, bioavailability, and minimizing drug levels in the bloodstream after the therapeutic effect has been achieved. In this specific patent, the following MCC Sphere types are recommended: CELLETS® 90, CELLETS® 100, CELLETS® 127.

Document information

Document Type and Number: (“Modified release Gamma-Hydroxybutyrate formulations having improved pharmacokinetics”)
Kind Code: A1

Inventors:

Dubow, Jordan (Lyon, FR)
Guillard, Hervé (Villeurbanne, FR)
Mégret, Claire (Lyon, FR)
Dubuisson, Jean-françois (Lyon, FR)

Disclaimer

This text was generated by chatGPT engine version GPT‑4o, on Oct 21, 2024. Image was generated with Adobe Firefly.

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highly lipophilic physiologically activeadobe firefly
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Patent on controlled release formulations of highly lipophilic physiologically active substances

The patent application US20240139215A1 focuses on the development of controlled release formulations for highly lipophilic physiologically active substances, such as cannabinoids. These substances tend to have high lipid solubility (log P of 4 or more), making them difficult to deliver in a controlled and effective manner. This patent addresses the need for efficient controlled release systems that can provide consistent therapeutic effects by utilizing a matrix-based approach.

The formulation includes a matrix that contains one or more highly lipophilic active substances and water-soluble binders like hydroxypropyl methyl cellulose (HPMC), methyl cellulose (MC), or similar polymers. The key challenge with such substances is their tendency to release slowly and incompletely when taken orally, which this patent solves by adjusting the proportion of water-soluble binders. The binder content is carefully selected to be between 0.1-10% of the total matrix weight, optimizing the release rate of the active substances over the gastrointestinal transit time.

One of the innovative aspects of the invention is the use of matrix pellets, which are small particles with a size range of 30 µm to 1800 µm. These pellets may be administered in various forms, such as capsules, tablets, or sachets. The flexibility of the dosage forms makes it easier to control and adjust the release kinetics of the active ingredients.

The CELLETS® play a crucial role in this formulation. They are used as neutral cores for the deposition of the active substances and their binders. CELLETS® are microcrystalline cellulose spheres that provide an ideal substrate for layering the active substance and polymers, ensuring uniform distribution and controlled release. By using these CELLETS®, the formulation can achieve a more predictable and consistent release profile, crucial for substances like cannabinoids that require precise dosing to avoid psychoactive side effects while maintaining therapeutic efficacy.

Additionally, these pellets can be coated with other materials to further control the release rate if desired, though this is optional. In many embodiments, the matrix pellets themselves are sufficient to achieve the desired controlled release without the need for additional coatings.

In conclusion, the US20240139215A1 patent introduces a novel approach to the controlled release of highly lipophilic substances, leveraging matrix technology with carefully chosen water-soluble binders and neutral cores like CELLETS®. This method ensures effective delivery and consistent release, addressing the challenges posed by the lipophilic nature of substances like cannabinoids. In this specific patent, the following MCC Sphere types are recommended: CELLETS® 500.

Document information

Document Type and Number: (“Controlled release formulations of highly lipophilic physiologically active substances”)
Kind Code: A1

Inventors:

Mirko Nowak
Jay Jesko Nowak
Annette Grave
Monika Wentzlaff
Sarah Barthold
Christian Geugelin

Disclaimer

This text was generated by chatGPT engine version GPT‑4o, on Oct 21, 2024. Image was generated with Adobe Firefly.

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methods of administering gamma-hydroxybutyrateadobe firefly
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Patent on methods of administering gamma-hydroxybutyrate compositions with divalproex sodium

The United States Patent Application US20240024263 focuses on methods of administering gamma-hydroxybutyrate (GHB) in combination with divalproex sodium (DVP), particularly for treating conditions like narcolepsy. The aim is to co-administer these drugs without altering their dosage or efficacy. The patent emphasizes how DVP affects GHB’s pharmacokinetics, allowing adjustments to minimize side effects while ensuring therapeutic benefits.

The role of CELLETS® in this patent is critical. CELLETS® are microcrystalline cellulose spheres used in drug formulations. They provide a stable, controlled-release matrix for GHB, ensuring consistent drug delivery over time. This controlled release minimizes fluctuations in drug concentrations, improving safety and efficacy. These MCC starter beads also help prevent interaction between GHB and DVP, ensuring that neither drug’s therapeutic effects are compromised.

By using CELLETS®, the formulation enhances the pharmacokinetic profile of GHB, ensuring a smoother and more predictable drug release. This innovation is crucial when GHB is administered alongside DVP, as it allows for better management of conditions like excessive daytime sleepiness or cataplexy, without significantly altering either drug’s profile.

In summary, this patent introduces an optimized co-administration strategy for GHB and DVP, with Cellets playing a pivotal role in achieving steady, controlled drug release and mitigating adverse drug interactions. This approach aims to improve the overall effectiveness and safety of treatment for sleep-related disorders. In this specific patent, the following MCC Sphere types are recommended: CELLETS® 90, CELLETS® 100 or CELLETS® 127. United States Patent Application US20240024263 seems as well to be a patent following the patent US11896572B2 wherein modified-release formulations are described.

Document information

Document Type and Number: (“Methods of administering gamma-hydroxybutyrate compositions with divalproex sodium”)
Kind Code: A1

Inventors:

Baek, Bong-Sook, Flamel Ireland Limited (Dublin, IE)

Disclaimer

This text was generated by chatGPT engine version GPT‑4o, on Oct 21, 2024. Image was generated with Adobe Firefly.

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Modified release gamma-hydroxybutyrateadobe firefly
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Patent on modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics

The patent US11896572B2, titled “Modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics,” outlines a pharmaceutical formulation aimed at optimizing the release and therapeutic effectiveness of gamma-hydroxybutyrate (GHB), a drug used for narcolepsy treatment. The patent focuses on improving GHB’s pharmacokinetics by creating a modified release system that extends its action, reducing the need for frequent dosing and improving patient compliance.

The formulation includes both immediate-release and delayed-release particles, allowing for a controlled release of GHB. This combination ensures that a portion of the drug is rapidly released for quick onset, while the remaining is gradually released, providing sustained therapeutic effects over time. The goal is to provide 6 to 8 hours of sleep with just one bedtime dose.

A key aspect of the patent is the use of CELLETS® which are spherical microcrystalline cellulose particles that serve as a core for both immediate and delayed-release systems (pellet technologies). These CELLETS® are critical because they provide a stable, uniform platform for the drug’s release. For the immediate-release component, CELLETS® are coated with sodium oxybate and a binder (povidone). For the delayed-release part, CELLETS® are coated with additional polymers, such as methacrylic acid copolymers and hydrogenated vegetable oil, which control the release based on pH levels in the gastrointestinal tract. This dual-layer system ensures precise drug release timing, optimizing the treatment’s effectiveness and minimizing side effects like abrupt peaks in drug concentration.

The CELLETS® play a crucial role in maintaining particle size consistency, which is important for ensuring predictable dissolution and absorption rates, thereby enhancing the overall pharmacokinetic profile of the drug. This innovation represents an advancement over traditional formulations by offering more reliable and patient-friendly narcolepsy management. In this specific patent, the following MCC Sphere types are recommended: CELLETS® 90, CELLETS® 100 or CELLETS® 127.

By utilizing CELLETS® and other advanced components, the patent aims to reduce the frequency of administration (allowing for once-daily dosing) and improve patient compliance, which is especially important for MG patients who need consistent, long-term management of their symptoms.

Document information

Document Type and Number: (“modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics”)
Kind Code: B2

Inventors:

Jordan Dubow
Hervé Guillard
Claire Mégret
Jean-François DUBUISSON

Disclaimer

This text was generated by chatGPT engine version GPT‑4o, on Oct 21, 2024. Image was generated with Adobe Firefly.

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Extended release compositions comprising pyridostigmine

Patent on extended release compositions comprising pyridostigmine

The following patent on “Extended release compositions comprising pyridostigmine” employs CELLETS® as starter spheres made of Microcrystalline Cellulose. Please, read below a summary.

US Patent 20240299305 addresses an extended-release formulation of pyridostigmine, a drug primarily used to treat myasthenia gravis (MG). The goal of the patent is to create a dosage form that prolongs the drug’s therapeutic effects while minimizing side effects like dose dumping (a rapid release of the drug that can cause adverse effects). The patent describes a gastroretentive drug delivery system, designed to float and remain in the stomach for a longer time, thereby ensuring gradual release and absorption.

A key aspect of this patent is the use of CELLETS®, which are small, inert core particles used as carriers in pharmaceutical formulations. These CELLETS® serve as a starter sphere for the extended-release composition, being coated with layers of active ingredients like pyridostigmine and other substances that control the drug’s release rate. The formulation is intended to provide a controlled, steady release of pyridostigmine, improving patient outcomes by maintaining a stable plasma concentration of the drug for up to 24 hours.

The dosage form also incorporates components like a gas-generating agent, which enables the tablet to float in the stomach, and a water-soluble hydrophilic polymer that swells upon contact with gastric fluids, preventing the tablet from passing through the digestive system too quickly. This gastroretentive property is vital to ensure that the drug stays in the stomach long enough to achieve the desired extended release.

By utilizing CELLETS® and other advanced components, the patent aims to reduce the frequency of administration (allowing for once-daily dosing) and improve patient compliance, which is especially important for MG patients who need consistent, long-term management of their symptoms.

Document information

Document Type and Number:  (“Extended release compositions comprising pyridostigmine”)
Kind Code: A1

Inventors:

Vaka, Siva Ram Kiran (Piscataway, NJ, US)
Desai, Dipen (Basking Ridge, NJ, US)
Phuapradit, Wantanee (Lewes, DE, US)
Shah, Navnit H. (Monmouth Junction, NJ, US)
Shelke, Namdev B. (Hillsborough, NJ, US)

Disclaimer

This text was generated by chatGPT engine version GPT‑4o, on Oct 18, 2024. Image was generated with Adobe Firefly.

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