Patents US20240350437A1 and US20240350438A1 – Gamma-hydroxybutyrate compositions having improved pharmacokinetics in the fed state – Google Patents relates to pharmaceutical compositions and systems designed to provide controlled and consistent drug release for oral administration. The invention addresses challenges associated with delayed or multi-stage drug delivery, particularly for active pharmaceutical ingredients (APIs) with complex absorption profiles or sensitivity to environmental factors like pH. More specifically, gamma-hydroxybutyrate (GHB) is employed as API. GHB is a drug from the group of sedatives that is approved for the treatment of narcolepsy with cataplexy in adults.
The core of the patent involves multiparticulate formulations, in which small spherical particles or granules are coated with APIs and polymers. These coatings are designed to modulate drug release rates, enabling gradual, sustained, or targeted delivery in the gastrointestinal tract. This technology is particularly useful for achieving precise therapeutic effects, minimizing dosing frequency, and reducing potential side effects caused by rapid drug release.
The document highlights advancements in coating techniques and the use of stabilizing agents to improve the integrity and functionality of the drug delivery system. It also discusses scalability and manufacturing efficiency, making these formulations suitable for large-scale production while maintaining consistency in dosage and performance.
Potential applications include treatments for chronic conditions or drugs that require precise dosing regimens. The invention provides flexibility in formulating for a range of APIs, allowing for customization to meet specific therapeutic needs. By enabling controlled drug release, the technology enhances medication adherence and efficacy, benefiting both patients and healthcare providers.
What is the role of MCC pellets as drug carrier of gamma-hydroxybutyrate compositions?
This patent US20240350437A1 focuses on an innovative approach to creating multiparticulate pharmaceutical formulations designed for oral administration. The patent introduces CELLETS® which are a key component of the drug delivery system. CELLETS® are small, uniform spherical particles made of inert microcrystalline cellulose (MCC), that act as carriers for active pharmaceutical ingredients (APIs). These particles provide an optimal surface for drug layering, facilitating precise drug release profiles. In this patent, these types of CELLETS® are applicable:
CELLETS® 90
CELLETS® 100
CELLETS® 127
The invention addresses challenges in achieving controlled drug release, particularly for APIs requiring multi-step or delayed absorption. By coating these MCC carriers with specific polymers and APIs, the system allows for tailored drug release at targeted points in the gastrointestinal tract. This is especially beneficial for drugs with narrow therapeutic windows or those sensitive to pH levels.
The patent emphasizes advancements in coating techniques and formulation stability, ensuring high reproducibility and efficient manufacturing processes. The resulting multiparticulate system supports dosage flexibility, reduced side effects, and improved patient adherence compared to conventional tablet or capsule forms.
The invention has implications for developing treatments for chronic conditions, where consistent and predictable drug release is critical. The application of CELLETS® in this context highlights their versatility and potential to enhance the efficacy and safety of oral drug delivery systems.
Document information
Document Type and Numbers:
(“Gamma-hydroxybutyrate compositions having improved pharmacokinetics in the fed state”).
US20240350438A1 (“Gamma-hydroxybutyrate compositions having improved pharmacokinetics in the fed state”).
Kind Code: A1
Inventors:
Julien Grassot, Cendrine Grangeon, Jordan Dubow
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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Please, find scientific literature on 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 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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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:
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.
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).
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.
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.
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.
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”)
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”)
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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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This case study on Atomoxetine HCl pellets is a short abstract of the publication by Y.D. Priya et al. [1].
Atomoxetine is a medication used to treat attention deficit hyperactivity disorder (ADHD) [2]. The API is marketed under the trade names Atomoxetine, Atomoxe, Agakalin, and Strattera (initially launched) [3]. Atomoxetine is an extremely bitter API. As being initially launched for children as capsules or tablets, the paediatric compliance by improved taste-masking and the simplified administration to paediatrics are in focus of this study.
A multi-unit particulate pellet coating (MUPS) was selected as oral dosage form. The fluidized bed technology (with Wurster column) was employed for coating and layering processes. This is a well-known technology, which Is for instance offered by Glatt. Starter cores were coated with the API, followed by layering with a polymeric coating for which realized the taste-masking.
Atomoxetine layering
Starter cores are made of Microcrystalline Cellulose (MCC) in sizes comparable to CELLETS® 200, while a fair efficiency of drug layering was observed with the combination of HPMC (Hydroxypropyl methyl cellulose) and HPC (Hydroxypropyl cellulose) as binders. The composition of API layering is presented in Table 1. The drug dispersion was sprayed onto the MCC pellets with an inlet temperature between 50 °C and 55 °C and a fluidized bed temperature between 35 °C and 40 °C.
API layering material
Composition
Starter core
MCC pellets
58.00
API layering
Atomoxetine HCl
25.00
Hydroxypropyl methylcellulose
3.50
Hydroxypropyl Cellulose
3.50
Low-Substituted Hydroxypropyl Cellulose
5.00
Talc
5.00
Purified Water
Qs
Total weight (mg)
100.00
Table 1: Formulation of API layered pellets.
Taste-masking coating
The polymeric taste-masking layer is made of a methacrylate co-polymer (Eudragit EPO) providing an excellent coating with taste masking properties for fine particles and tablets. The composition of the taste-masking suspension is shown in Table 2. The inlet temperature is between 40 °C and 45 °C, and fluidized bed temperature is between 25 °C and 30 °C.
Polymeric coating material
Composition
Drug Layered pellets
100.00
Eudragit EPO
25.00
Sodium Lauryl Sulfate
2.500
Stearic acid
3.750
Talc
6.25
FD&C Yellow No. 6
0.50
FD&C Red No. 3
0.05
Purified Water
Qs
Total weight (mg)
138.050
Table 2: Formulation of polymeric coating suspension.
The efficiency of taste-masking was benchmarked by a bitterness rating on human volunteers. Figure 1 shows, that the taste sensitivity identifies a bitterness at 6 µg/ml API concentration and an extreme bitterness at 7 µg/ml API and higher concentration. Thus, the threshold bitterness of Atomoxetine HCl is 6 µg/ml.
Figure 1: Concentration of drug solution (µg/ ml). Bitter intensity ratings from no bitterness (green), bitterness (blue), extremely bitter (red).
All the volunteers felt bitter taste when the drug layered pellets were coated with 6.25 mg of Eudragit EPO. Whereas in the pellets coated with 12.5 mg and 18.75 mg of Eudragit EPO, bitter taste was masked up to 15 seconds after keeping the tablet in the mouth, and later all the human volunteers felt bitter taste. When the concentration of Eudragit EPO was increased to 25 mg, the bitter taste of Atomoxetine HCl was completely taste-masked and no volunteer was felt bitter taste.
Figure 2: In-Vivo Taste evaluation in healthy human volunteers.
Figure 3 depicts the entire particle size of a taste-masked MCC pellet coated with the Atomoxetine drug layer and 25 mg of Eudragit EPO. The average particle size of the taste-masked pellets is between 180 µm and 250 µm, assuming, that no gritty feeling of particles in patient’s mouth will appear. It should be said, that a micronization of Atomoxetine HCl was deemed to be necessary for the drug layering process. Micronization minimized the surface roughness of the API layered pellet so that an efficient taste-masking coating can be applied.
Figure 3: SEM picture of cross section of a Taste masked pellets coated with 25 mg Eudragit EPO.
Summary
MCC pellets in the size of about 200 µm were layered with Atomoxetine. HPMC and HPC were used as binders, realizing a precise surface definition for a subsequent taste-masking coating. The taste-masking was most efficient at a polymeric concentration of 25 mg. Keeping the size of the coated pellets below 300 µm avoids a gritty feeling and thus increase the patient’s compliance.
This study by Priya et al. indicated that the fluidized bed process produced the most appropriate taste masked pellets of Atomoxetine HCl for oral disintegrating tablets.
[2] “Atomoxetine Hydrochloride Monograph for Professionals”. Drugs.com. American Society of Health-System Pharmacists. Archived from the original on 4 April 2019. Retrieved 22 March 2019.
[3] ROTE LISTE 2017, Verlag Rote Liste Service GmbH, Frankfurt am Main, ISBN 978-3-946057-10-9, (2017) 162.
Tamoxifen is widely used in transgenic research in mice to induce Cre recombinase activity and achieve conditional gene knockouts [1]. However administrating tamoxifen to mice is challenging The commonly used dosing methods are oral gavage or intraperitoneal injection [2] which require specialist staff training and can cause pain, distress and adverse effects to the animal. Tamoxifen containing rodent chow is commercially available however, the poor palatability of the diet leads to reduced food intake and weight loss of the mice. The addition of sweeteners improves palatability, but this can affect the metabolic balance of the mice.
In this application a study is described in which a palatable tamoxifen containing rodent chow is developed by mixing taste masking coated micropellets with powdered rodent food. This attempt shell improve:
Reduction of potential welfare concerns,
Reduction of dose variability,
and induce
a more consistent recombinase activity,
a decrease in the variability of phenotyping data from these experiments,
a reduction in the number of animals used
Methods
The API was spray layered onto microcrystalline cellulose substrates CELLETS® 100 and subsequently coated using Surelease®, both as aqueous formulations in a bench top fluidized bed coater (Mini Glatt®). Two taste masking coated tamoxifen citrate micropellet formulations were prepared and analyzed. One formulation has a coating levels of 5 % (F1) and the second formulation contains mannitol in the drug layer with a coating level of 10 % (F2). Sieve analysis of taste masking coated micropellets (Figure 2) shows that both formulations achieved yields of at least 99 % (proportion of pellets with size < 250 µm), see Fig. 1.
In USP II dissolution test the uncoated tamoxifen citrate (micronized and un-micronized particles) showed a fast dissolution at >80 % release within 45 minutes (Figure 3). The micronized particles dissolved slower than the un-micronized due to particle agglomeration during dissolution.
Drug release slowed down after applying the taste masking coating; with decreasing pore former concentration or increasing coating thickness, the drug release rate decreases. After 45 min, both formulations F1 and F2 showed >75 % drug release, successful as immediate release formulations (Fig. 2).
Figure 2: Drug release of Tamoxifen Citrate in USP II test. Graphs: F1 with coating Level 5 % and polymer ratio 75:25 (light green); F2 Mannitol with coating level 10 % polymer ratio 85:15 (light blue); Tamoxifen Citrate micronized (blue); Tamoxifen Citrate un-micronized (grey).
Taste masking effectiveness of Tamoxifen micropellets
The in vitro tests for evaluating the taste masking effectiveness of the formulations showed that after 30s, micropellets with both coating formulations are effective in providing a taste masking barrier with a tamoxifen citrate release of less than 0.5% (Fig. 3).
Figure 3: Inverted Vial test for taste masking effect evaluation. Graphs: F1 (green), F2 (blue) with % Release after 30s (light color) and Concentration (mg/ml) after 30s (dark color).
Summary
Taste masking of coated tamoxifen citrate micropellets were successfully manufactured in a fluidized bed applying the MicroCoat™ technology with > 99% yield and particle size < 250 µm. The coating provided effective protection to prevent tamoxifen citrate release in the mouth but immediate drug release in the stomach pH conditions of the mice. Additionally, the small particle size of the coated micropellets ensured effective mixing with the powder rodent feed with excellent recovery and uniformity. The product is flexible in dose adjustment and improves API handling safety in animal units, offering an innovative approach of doing tamoxifen to mice for Cre recombination research via voluntary food intake. The method has the potential to reduce suffering
and improve welfare of the mice, promoting 3Rs (replacement, reduction and refinement) in animal research.
Taste masked coated micropellets
Acknowledgement
The project is funded by the United Kingdom National Centre for the Replacement, Refinement and Reduction of Animals in Research (the NC3Rs) through the CRACK IT challenge Tat Fit project number NC/C020S02/1).
Dr. Fang Liu and her team are gratefully acknowledged for serving content for this note.
Fluid Pharma Ltd Contact: Dr. Fang LIU
College Lane, Hatfield, AL10 9AB, UK
Tel: +44 1707 28 4273
+44 796 3230 628 www.fluidpharma.com
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