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Article

Improvement in the Oral Bioavailability and Efficacy of New Ezetimibe Formulations—Comparative Study of a Solid Dispersion and Different Micellar Systems

1
Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain
2
Department of Biomedical Science, Faculty of Pharmacy, University of Alcalá de Henares, Ctra Madrid-Barcelona Km 33,600, 28805 Madrid, Spain
3
Department of Science and Pharmaceutical Technology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santiago 8380494, Chile
4
Instituto Universitario de Farmacia Industrial, Complutense University, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain
*
Author to whom correspondence should be addressed.
Pharmaceutics 2020, 12(7), 617; https://doi.org/10.3390/pharmaceutics12070617
Received: 29 May 2020 / Revised: 27 June 2020 / Accepted: 1 July 2020 / Published: 2 July 2020
(This article belongs to the Section Pharmaceutical Technology, Manufacturing and Devices)
Ezetimibe (EZ) is a poorly water-soluble drug with low bioavailability. Strategies such as solid dispersions (SD) and micellar systems (MS) were developed to identify the most effective drug delivery formulations with the highest oral bioavailability, and to improve their lipid-lowering effect. The EZ formulations were prepared with different proportions of Kolliphor® RH40 as a surfactant (1:0.25, 1:0.5 and 1:0.75) and croscarmellose as a hydrophilic carrier. These excipients, and the addition of microcrystalline cellulose during the production process, led to significant improvements in the dissolution profiles of MS. Powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) revealed an amorphous form of ezetimibe with different semicrystalline states of microcrystalline cellulose for MS-I (1:0.75) and MS-II (1:0.75). Pharmacokinetic analysis after administration of MS-II (1:0.75) demonstrated a 173.86% increase in maximum plasma concentration (Cmax) and a 142.99% increase in oral bioavailability compared to EZ raw material (EZ-RM). Efficacy studies with the micellar system MS-II (1:0.75) in rats with hyperlipidemia showed that total cholesterol, triglycerides and high-density lipoprotein were reduced to normal levels and revealed improvements in low-density lipoprotein, aspartate and alanine aminotransferase. The improvement in the dissolution rate with micellar systems increases bioavailability and enhances the anti-hyperlipidemic effect of EZ. View Full-Text
Keywords: ezetimibe; solid dispersion; micellar systems; enhanced dissolution; oral bioavailability; antihyperlipidemic effect ezetimibe; solid dispersion; micellar systems; enhanced dissolution; oral bioavailability; antihyperlipidemic effect
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MDPI and ACS Style

Torrado-Salmerón, C.; Guarnizo-Herrero, V.; Gallego-Arranz, T.; del Val-Sabugo, Y.; Torrado, G.; Morales, J.; Torrado-Santiago, S. Improvement in the Oral Bioavailability and Efficacy of New Ezetimibe Formulations—Comparative Study of a Solid Dispersion and Different Micellar Systems. Pharmaceutics 2020, 12, 617. https://doi.org/10.3390/pharmaceutics12070617

AMA Style

Torrado-Salmerón C, Guarnizo-Herrero V, Gallego-Arranz T, del Val-Sabugo Y, Torrado G, Morales J, Torrado-Santiago S. Improvement in the Oral Bioavailability and Efficacy of New Ezetimibe Formulations—Comparative Study of a Solid Dispersion and Different Micellar Systems. Pharmaceutics. 2020; 12(7):617. https://doi.org/10.3390/pharmaceutics12070617

Chicago/Turabian Style

Torrado-Salmerón, Carlos, Víctor Guarnizo-Herrero, Teresa Gallego-Arranz, Yvonne del Val-Sabugo, Guillermo Torrado, Javier Morales, and Santiago Torrado-Santiago. 2020. "Improvement in the Oral Bioavailability and Efficacy of New Ezetimibe Formulations—Comparative Study of a Solid Dispersion and Different Micellar Systems" Pharmaceutics 12, no. 7: 617. https://doi.org/10.3390/pharmaceutics12070617

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