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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

Packaged modified release gamma-hydroxybutyrate formulations improve stability and simplify treatment. The patent WO2019123269A1, titled “Packaged modified release gamma-hydroxybutyrate formulations having improved stability,” introduces innovative formulations and packaging methods. These methods enhance both dissolution and chemical stability of gamma-hydroxybutyrate (GHB), a therapy for narcolepsy. Currently, treatments like XYREM® force patients to wake during the night for a second dose, which proves cumbersome. Therefore, this patent develops a once-nightly, modified-release GHB formulation. Moreover, advanced packaging controls relative humidity, ensuring long-term effectiveness and preventing chemical degradation of GHB into gamma-butyrolactone (GBL).

Key Innovations:

  1. Modified Release Formulation: The patent combines immediate and modified release components, both containing GHB or a pharmaceutically acceptable salt. The modified release component controls GHB release over time. As a result, it provides sustained therapeutic effects throughout the night. Therefore, patients do not need a second dose. Consequently, this formulation improves convenience and supports adherence to treatment.
  2. Stability Issues with GHB: GHB is highly hygroscopic and chemically unstable. Consequently, it degrades easily, especially in high-humidity environments. This degradation produces GBL, which reduces the drug’s effectiveness. Therefore, the patent develops a formulation with stable dissolution profiles and improved chemical stability. Moreover, it maintains stability even under stressful storage conditions, such as high temperature and humidity.
  3. Packaging Innovation: To enhance stability, the GHB formulations use packaging that maintains a specific relative humidity range (29% to 54%). This control of humidity is crucial because it prevents GHB from degrading into GBL. Moreover, the packaging material has a low water vapor transmission rate. As a result, it reduces moisture exposure and ensures the drug stays stable over time.
  4. Hydrophobic Coating: The patent applies a hydrophobic coating, such as glyceryl tristearate or hydrogenated vegetable oil, along with methacrylic acid copolymers. These coatings control the release rate of GHB. Moreover, they protect it from moisture. As a result, the formulation provides a steady release and prevents premature degradation.
  5. Pharmaceutical Composition: The GHB composition includes varying ratios of immediate and modified release components. These ratios ensure a sufficient therapeutic dose while maintaining stability. Moreover, particle size and formulation ratios (e.g., 40/60 to 60/40) play key roles in achieving the desired pharmacokinetics and release profiles.

Controlling the relative humidity within the packaging

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 development of modified release gamma-hydroxybutyrate represents a major advancement in narcolepsy therapy, aiming to improve both patient compliance and treatment effectiveness. Traditional formulations of gamma-hydroxybutyrate (GHB) require multiple nightly doses, which can disrupt sleep and reduce overall quality of life. The patented formulation described in US11896572B2 introduces a novel modified release system that extends the duration of action, making it possible to achieve 6 to 8 hours of therapeutic benefit with a single bedtime dose.

How Modified Release Gamma-Hydroxybutyrate Works

This formulation combines immediate-release and delayed-release mechanisms to provide both rapid onset and sustained therapeutic effects. The immediate-release portion allows GHB to take effect quickly, while the delayed-release portion maintains drug levels over time, reducing abrupt concentration peaks and minimizing side effects. This dual-action delivery is designed to improve pharmacokinetics and ensure more consistent symptom control.

The Role of CELLETS® in Modified Release Gamma-Hydroxybutyrate Drug Release

A central innovation in this patent involves the use of CELLETS®, spherical microcrystalline cellulose particles that provide a stable foundation for modified release drug delivery. In the immediate-release portion, CELLETS® carry a coating of sodium oxybate combined with a binder such as povidone. Meanwhile, the delayed-release portion relies on specialized polymers and hydrogenated vegetable oil, which work together to control pH-dependent release in the gastrointestinal tract. Furthermore, CELLETS® maintain consistent particle size and predictable dissolution rates, which in turn improve absorption and strengthen the overall pharmacokinetic profile of modified release gamma-hydroxybutyrate.

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. This specific patent, recommend the following MCC Sphere types: CELLETS® 90, CELLETS® 100 or CELLETS® 127.

Advantages for Narcolepsy Patients

The patented system combines immediate and delayed release. This design allows for a once-nightly dose, which improves adherence and convenience for patients. The innovation also ensures more restorative sleep. At the same time, it reduces the burden of frequent dosing. As a result, narcolepsy management becomes more reliable and patient-friendly.

By refining the pharmacokinetics of GHB, modified release gamma-hydroxybutyrate offers a significant improvement over traditional formulations.

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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Extended-release compositions comprising atomoxetine
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Patent on Extended-release compositions comprising atomoxetine

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

United States Patent Application 20240299307 focuses on an extended-release formulation of atomoxetine, commonly used for treating ADHD. The patent describes a unique pellet-based drug delivery system designed to control the release of atomoxetine over an extended period. This system aims to reduce the dosing frequency and maintain steady drug levels in the bloodstream, enhancing patient compliance and reducing the side effects associated with fluctuating drug levels.

Key Elements of the Invention:

  1. Pellets: The invention uses pellets as the core of the formulation, each containing atomoxetine or a pharmaceutically acceptable salt like atomoxetine hydrochloride. The pellets are coated with a functional layer that controls the rate and duration of drug release.
  2. Extended Release: The functional coating consists primarily of cellulose acetate-based polymers like cellulose acetate phthalate or cellulose acetate butyrate. This coating slows the drug’s release, allowing for less than 40% of the atomoxetine to be released within the first two hours, ensuring a sustained release for 8 to 20 hours, depending on the coating thickness.
  3. Patient Benefits: The extended-release design minimizes the need for multiple daily doses, improving patient adherence to the treatment. Additionally, it helps maintain consistent therapeutic levels of atomoxetine in the bloodstream, reducing the side effects from rapid peaks and valleys in drug concentration.
  4. Manufacturing Process: The pellets are made by applying a drug layer over a nonpareil seed (such as CELLETS®), followed by an optional sealing layer and a functional coating that dictates the extended-release profile. These pellets can be encapsulated or compressed into tablets.

Function of CELLETS®:

CELLETS® are microcrystalline cellulose spheres commonly used as a core in pellet-based formulations. In this patent, CELLETS® act as inert carriers that provide a solid foundation for the application of atomoxetine and subsequent coatings. Their uniform size and shape ensure consistent layering of the drug and functional coatings, which is crucial for achieving the desired release profile. CELLETS® facilitate the manufacturing of multi-particulate systems where each pellet provides a controlled dose of the active ingredient. By using CELLETS®, the formulation can be tailored for extended-release by controlling the thickness of the drug and polymer layers applied to the surface​.

In summary, this patent provides an effective method to enhance the therapeutic benefits of atomoxetine, focusing on an extended-release formulation that improves patient outcomes through consistent drug release and convenient dosing.

Document information

Document Type and Number:
Kind Code: A1

Inventors:

Tu, Yu-hsing (West Windsor, NJ, US)
Chalamuri, Shanmuka Harish (Plainsboro, NJ, US)
Kathala, Kalyan (Monroe, NJ, US)
Perumal, Ashok (Monmouth Junction, NJ, US)
Lee, James A. (West Windsor, 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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Firefly How to improve the dissolution performance of rivaroxaban. 18547 example image

How to improve the dissolution performance of rivaroxaban?

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