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hydroxynorketamine modified-release dosage form ChatGPT Image 11. Juli 2025, 13_57_57
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Patent on hydroxynorketamine modified‑release dosage form for the use in the treatment of depression

Introduction

The development of a hydroxynorketamine modified-release dosage form marks an important advance in neuropsychiatric therapy. Hydroxynorketamine (HNK), a ketamine metabolite, shows rapid antidepressant activity through mechanisms different from ketamine itself. It works mainly by modulating α7-nicotinic acetylcholine receptors and activating mTOR pathways.

This targeted action makes HNK a strong candidate as an active pharmaceutical ingredient with a favorable safety profile. Unlike ketamine, it avoids dissociative and addictive side effects. A modified-release form built with CELLETS®—uniform spherical pellets—offers tighter therapeutic control. It sustains plasma concentration, reduces peak-to-trough swings, and helps patients stay consistent with treatment.

In addition, the inert cores often range between 100 and 500 μm in size. A more refined range of 200 to 400 μm improves precision. About 90% of particles fall within this window, confirmed by sieve analysis. One example is CELLETS® 200, which demonstrates this particle size distribution effectively.

API Function and Patient Benefits

Hydroxynorketamine mainly acts by inhibiting α7-nicotinic receptors. This lowers intracellular Ca²⁺ and D-serine levels and reduces NMDA receptor excitotoxicity. At the same time, it boosts mTOR signaling and strengthens AMPA receptor function.

Together, these effects speed up synaptogenesis and create fast antidepressant responses. Evidence comes from both preclinical studies and early clinical findings. For patients, this means rapid mood elevation without ketamine-related side effects. Unlike ketamine, it does not cause hallucinations or carry strong abuse potential.

From a pharmacokinetic view, a modified-release dosage form improves consistency in therapy. It also simplifies dosing schedules and increases tolerability.

Modified‑release dosage Formulation with CELLETS®

The incorporation of CELLETS® into the modified‑release formulation provides several benefits. Their uniform size and high sphericity ensure consistent drug coating and predictable release. CELLETS® also enable multiparticulate dosing, which reduces variability and allows tailored release profiles.

For hydroxynorketamine (HNK), CELLETS® can carry specific polymer coatings such as ethylcellulose or Eudragit. These coatings dissolve or erode at controlled rates, releasing the API steadily over time. This method lowers peak systemic concentrations, which reduces side effects while maintaining efficacy.

Additionally, CELLETS® support monolithic layering or reservoir systems. This setup allows complex release patterns, such as an initial burst followed by sustained delivery. Such profiles are ideal for achieving a rapid onset and maintaining antidepressant effects in depression treatment.

Key Findings on Hydroxynorketamine modified‑release dosage form

In the disclosed patent (US 2025 0177325 A1), researchers describe a multiparticulate modified‑release system for hydroxynorketamine. They use CELLETS® as the core substrate. The CELLETS® carry successive polymer layers that control drug release. This design produces an initial release phase followed by prolonged delivery.

Pharmacokinetic modeling shows a flattened plasma-concentration profile, lower maximum concentration (Cmax), longer time to peak (Tmax), and higher area under the curve (AUC). Together, these factors maintain therapeutic HNK levels over time. This steady exposure may reduce rebound symptoms and cut dosing frequency. As a result, patient adherence improves, and treatment regimens may shift to once-daily or even less frequent dosing.

Conclusion and Outlook

In conclusion, the hydroxynorketamine modified‑release dosage form using CELLETS® offers a promising pharmaceutical approach. It leverages HNK’s unique mechanism as a non-dissociative antidepressant. Controlled release maximizes its clinical potential.

Cellet-based formulations improve pharmacokinetics, enhance tolerability, and increase convenience. These benefits could significantly help patients with treatment-resistant depression. Further work is needed, including in vitro−in vivo correlation studies, polymer selection optimization, and confirmatory clinical trials.

Looking ahead, this technology may expand HNK applications to other neuropsychiatric or neurodegenerative disorders. It provides a refined dosage form that meets both patient needs and therapeutic goals.

Patent Details

  • Name or patent: Hydroxynorketamine for the use in the treatment of depression
  • Patent number: US 20250177325 A1
  • Year of patent: 2025
  • Patent holder names and affiliation: (Names not specified in public abstract; likely the inventors assigned to their sponsoring institution or company as listed in patent document)

This summary underscores the innovative use of CELLETS® in creating a refined hydroxynorketamine modified-release dosage form that elevates both therapeutic performance and patient-centric outcomes.

hydroxynorketamine modified-release dosage form
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US20250186377A1 cellet‑based modified‑release gamma‑hydroxybutyrate formulation ChatGPT Image 11. Juli 2025, 13_12_09
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Patent on methods of administering gamma-hydroxybutyrate compositions with divalproex sodium

Introduction

Gamma‑hydroxybutyrate (GHB) is an endogenous neurotransmitter also used pharmaceutically—usually as sodium oxybate—for treating narcolepsy and related disorders. It exerts its therapeutic effects by modulating GABA_B receptors and promoting slow-wave sleep, alleviating cataplexy, and reducing excessive daytime sleepiness. Despite its efficacy, current twice-nightly dosing regimens present challenges: dose‑dumping in the presence of alcohol, variable pharmacokinetics depending on food intake, and patient inconvenience. To address these issues, modern formulations—and especially the innovative use of CELLETS® —pursue once-nightly controlled release.

API Benefits and Patient Advantages

Administering gamma‑hydroxybutyrate compositions in a modified‑release format brings multiple patient-centric benefits. A single nightly dose minimizes repeated nighttime awakenings and improves adherence. These formulations exhibit lower peak concentrations (C_max) with sustained therapeutic exposure (AUC)—achieving similar or better efficacy while reducing adverse events such as dizziness or nausea. This consistency is especially meaningful when dosing less than two hours after eating, which often is more convenient for patients; the controlled formulations are more forgiving of fed-state PK variability and less prone to alcohol-induced dose-dumping.

Use of CELLETS® in methods of administering gamma-hydroxybutyrate compositions

CELLETS® — spherical microcores used in multiparticulate drug delivery—are central to these modern GHB formulations. The patent US 20250186377 A1 introduces coated cellet-based microparticles that incorporate immediate-release (IR) and modified-release (MR) segments within a single unit dose. The MR portion involves CELLETS® (e.g. CELLETS® 90, CELLETS® 100 or CELLETS® 127, and other MCC beads) coated with polymers carrying free carboxyl groups combined with hydrophobic materials (e.g., high melting point waxes), engineered to delay GHB release until intestinal transit. CELLETS® enable precise layering, efficient coating, and reproducible drug release profiles while resisting pH- and alcohol-triggered dose dumping.

This multiparticulate approach achieves desired PK: IR CELLETS® ensure rapid onset while MR CELLETS® sustain plasma GHB levels up to 8 hours. In contrast to IR liquid sodium oxybate, the coated cellet formulation shows dose‑proportional C_max and AUC across doses of 4.5 g, 7.5 g, and 9 g, with most AEs clustering near C_max but at overall milder intensity. Remarkably, cellet-based formulations maintain comparable therapeutic exposure even with postprandial dosing, offering flexibility not seen in immediate-release forms.

Key Findings

The inventive cellet-based GHB composition delivers both immediate and controlled drug release in one unit, offering dose‑proportional pharmacokinetics and sustained therapeutic levels for 8 hours, under single-nightly dosing. It improves safety by reducing peak‑induced adverse events, lowers risk of alcohol‑related dose-dumping, and allows dosing within two hours after meals. Studies show comparable efficacy to twice-nightly IR sodium oxybate on sleep quality and daytime alertness, with better convenience and adherence.

Conclusion & Outlook

The patented cellet‑based modified-release formulation of GHB marks a significant advancement in administering gamma‑hydroxybutyrate compositions. By incorporating coated CELLETS® that combine IR and MR elements, this approach mitigates common limitations—meal dependency, alcohol interactions, multiple nightly doses—while preserving therapeutic efficacy. For patients with narcolepsy or cataplexy, this translates into improved sleep continuity, reduced daytime symptoms, and enhanced quality of life.

Looking ahead, further clinical evaluation could extend the CELLETS® platform to other formulations of gamma‑hydroxybutyrate salts or co‑therapies (e.g., with sodium valproate), further broadening the therapeutic utility. This modular, multiparticulate delivery system could set a new standard for nightly dosing regimens where controlled pharmacokinetics and patient preferences align.

Patent Details

  • Name/Title: cellet‑based modified‑release gamma‑hydroxybutyrate formulation

  • Patent Number: US 20250186377 A1

  • Year of Patent: 2025

  • Patent Holder(s): Not explicitly indicated in the publicly listed data, but associated inventors likely affiliated with pharmaceutical firms focusing on CNS therapeutics (e.g., Jazz Pharmaceuticals or Flamel Ireland).
US20250186377A1 cellet‑based modified‑release gamma‑hydroxybutyrate formulation ChatGPT Image 11. Juli 2025, 13_12_09
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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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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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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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