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The development of an innovative method to improve the dissolution performance of rivaroxaban.

作者信息

Ozon Emma Adriana, Mati Erand, Karampelas Oana, Anuta Valentina, Sarbu Iulian, Musuc Adina Magdalena, Mitran Raul-Augustin, Culita Daniela C, Atkinson Irina, Anastasescu Mihai, Lupuliasa Dumitru, Mitu Mirela Adriana

机构信息

Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, "Carol Davila" University of Medicine and Pharmacy, 6 Traian Vuia Street, 020945, Bucharest, Romania.

"Titu Maiorescu" University, Faculty of Pharmacy, Department of Pharmaceutical Technology, 16 Sincai Boulevard, 040314, Bucharest, Romania.

出版信息

Heliyon. 2024 Jun 15;10(12):e33162. doi: 10.1016/j.heliyon.2024.e33162. eCollection 2024 Jun 30.


DOI:10.1016/j.heliyon.2024.e33162
PMID:39021978
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11253053/
Abstract

Recent advancements in the formulation of solid dosage forms involving active ingredient-cyclodextrin complexes have garnered considerable attention in pharmaceutical research. While previous studies predominantly focused on incorporating these complexes into solid states, issues regarding incomplete inclusion prompted the exploration of novel methods. In this study, we aimed to develop an innovative approach to integrate liquid-state drug-cyclodextrin inclusion complexes into solid dosage forms. Our investigation centered on rivaroxaban, a hydrophobic compound practically insoluble in water, included in hydroxypropyl-β-cyclodextrin at a 1:1 M ratio, and maintained in a liquid state. To enhance viscosity, hydroxypropyl-cellulose (2 % w/w) was introduced, and the resulting dispersion was sprayed onto the surface of cellulose pellets (CELLETS®780) using a Caleva Mini Coater. The process parameters were meticulously controlled, with atomization air pressure set at 1.1 atm and a fluidizing airflow maintained at 35-45 m/h. Characterization of the coated cellets, alongside raw materials, was conducted using Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC) analyses. Physicochemical evaluations affirmed the successful incorporation of rivaroxaban into hydroxypropyl-β-cyclodextrin, with the final cellets demonstrating excellent flowability, compressibility, and adequate hardness. Quantitative analysis the HPLC-DAD method confirmed a drug loading of 10 mg rivaroxaban/750 mg coated cellets. dissolution studies were performed in two distinct media: 0.022 M sodium acetate buffer pH 4.5 with 0.2 % sodium dodecyl sulfate (mirroring compendial conditions for 10 mg rivaroxaban tablets), and 0.05 M phosphate buffer pH 6.8 without surfactants, compared to reference capsules and conventional tablet formulations. The experimental capsules exhibited similar release profiles to the commercial product, Xarelto® 10 mg, with enhanced dissolution rates observed within the initial 10 min. This research presents a significant advancement in the development of solid dosage forms incorporating liquid-state drug-cyclodextrin inclusion complexes, offering a promising avenue for improving drug delivery and bioavailability.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dd/11253053/bb4adeca3720/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dd/11253053/6cbc0f6aa7f3/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dd/11253053/11321cb6ee8e/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dd/11253053/f88b045d2c9a/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dd/11253053/0c818089d640/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dd/11253053/76273755d49a/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dd/11253053/8a42973b9dee/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dd/11253053/baa15073a425/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dd/11253053/bb4adeca3720/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dd/11253053/6cbc0f6aa7f3/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dd/11253053/11321cb6ee8e/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dd/11253053/f88b045d2c9a/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dd/11253053/0c818089d640/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dd/11253053/76273755d49a/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dd/11253053/8a42973b9dee/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dd/11253053/baa15073a425/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dd/11253053/bb4adeca3720/gr8.jpg

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引用本文的文献

[1]
Enhancing the Drug Release and Physicochemical Properties of Rivaroxaban via Cyclodextrin Complexation: A Comprehensive Analytical Approach.

Pharmaceuticals (Basel). 2025-5-22

[2]
Cyclodextrins: Enhancing Drug Delivery, Solubility and Bioavailability for Modern Therapeutics.

Pharmaceutics. 2025-2-22

[3]
Cyclodextrins: Advances in Chemistry, Toxicology, and Multifaceted Applications.

Molecules. 2024-11-12

本文引用的文献

[1]
Direct electrospinning for producing multiple activity nanofibers consisting of aggregated luteolin/hydroxypropyl-gamma-cyclodextrin inclusion complex.

Int J Biol Macromol. 2024-6

[2]
Effect of hydrophilic polymers on the solubility and dissolution enhancement of rivaroxaban/beta-cyclodextrin inclusion complexes.

Heliyon. 2023-9-1

[3]
Cyclodextrin Inclusion Complexes for Improved Drug Bioavailability and Activity: Synthetic and Analytical Aspects.

Pharmaceutics. 2023-9-19

[4]
Cyclodextrins and Their Derivatives as Drug Stability Modifiers.

Pharmaceuticals (Basel). 2023-7-28

[5]
Anticancer Activity of Novel Difluorinated Curcumin Analog and Its Inclusion Complex with 2-Hydroxypropyl-β-Cyclodextrin against Pancreatic Cancer.

Int J Mol Sci. 2023-3-28

[6]
Design and Optimization of Rivaroxaban-Cyclodextrin-Polymer Triple Complex Formulation with Improved Solubility.

Drug Des Devel Ther. 2022

[7]
The Influence of the Polymer Type on the Quality of Newly Developed Oral Immediate-Release Tablets Containing Amiodarone Solid Dispersions Obtained by Hot-Melt Extrusion.

Molecules. 2022-10-5

[8]
Preparation of Spherical Cellulose Nanocrystals from Microcrystalline Cellulose by Mixed Acid Hydrolysis with Different Pretreatment Routes.

Int J Mol Sci. 2022-9-15

[9]
Formation and Physico-Chemical Evaluation of Nifedipine-hydroxypropyl-β-cyclodextrin and Nifedipine-methyl-β-cyclodextrin: The Development of Orodispersible Tablets.

Pharmaceuticals (Basel). 2022-8-12

[10]
Design and Evaluation of Orally Dispersible Tablets Containing Amlodipine Inclusion Complexes in Hydroxypropyl-β-cyclodextrin and Methyl-β-cyclodextrin.

Materials (Basel). 2022-7-28

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