Solid dispersions of atorvastatin with Kolliphor RH40: Enhanced supersaturation and improvement in a hyperlipidemic rat model.

Autor: Torrado-Salmerón C; Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain; Instituto Universitario de Farmacia Industrial (IUFI), Complutense University of Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain. Electronic address: ctorrado@ucm.es., Guarnizo-Herrero V; Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain. Electronic address: victor08@ucm.es., Torrado G; Department of Biomedical Science, Faculty of Pharmacy, University of Alcalá de Henares, Ctra Madrid-Barcelona Km 33,600, 28805 Madrid, Spain. Electronic address: guillermo.torrado@uah.es., Peña MÁ; Department of Biomedical Science, Faculty of Pharmacy, University of Alcalá de Henares, Ctra Madrid-Barcelona Km 33,600, 28805 Madrid, Spain. Electronic address: angeles.pena@uah.es., Torrado-Santiago S; Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain; Instituto Universitario de Farmacia Industrial (IUFI), Complutense University of Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain. Electronic address: torrado2@ucm.es., de la Torre-Iglesias PM; Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain; Instituto Universitario de Farmacia Industrial (IUFI), Complutense University of Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain. Electronic address: pmtorre@ucm.es.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2023 Jan 25; Vol. 631, pp. 122520. Date of Electronic Publication: 2022 Dec 26.
DOI: 10.1016/j.ijpharm.2022.122520
Abstrakt: Atorvastatin is a potent lipid-lowering drug with poor solubility and high presystemic clearance that limits its therapeutic efficacy. The aim of this study was to develop solid dispersions and micellar systems to obtain fast-dissolving atorvastatin systems that enhances their anti-hyperlipidemic effect. Solubility and wettability studies allow the development of solid dispersions with low proportions of croscarmellose sodium as hydrophilic carrier. Solid state characterization studies indicated that the addition of Kolliphor® RH40 surfactant to solid dispersions increases intermolecular hydrogen bonding between drug and polymer chains. Dissolution studies in biorelevant Fasted State Simulate Intestinal Fluid (FaSSIF pH 6.5) medium showed for atorvastatin solid dispersion a supersaturation peak of atorvastatin followed by an aggregation/precipitation process. Only the presence of a surfactant such as Kolliphor® RH40 in atorvastatin micellar system, promotes the presence of micelles that achieve delayed recrystallization. Efficacy studies were carried out using a hyperlipidemic model of rats fed with a high- fat diet. The atorvastatin micellar system at doses of 10 mg/kg, revealed a significant improvement in serum levels of total cholesterol, low-density lipoproteins, and triglycerides compared to atorvastatin raw material. This micellar system also exhibited more beneficial effects on liver steatosis, inflammation and ballooning injury.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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