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



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Torrado Salmerón, Carlos Félix and Guarnizo Herrero, Victor and Torrado Durán, Guillermo and Peña Fernandez, M. Ángeles and Torrado Durán, Santiago and Torre Iglesias, Paloma (2023) Solid dispersions of atorvastatin with Kolliphor RH40: enhanced supersaturation and improvement in a hyperlipidemic rat model. International journal of pharmaceutics, 631 . p. 122520. ISSN 0378-5173 (In Press)

[thumbnail of IJPHARM-122520- Pre-proofs.pdf] PDF - Accepted Version
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Official URL: https://doi.org/10.1016/j.ijpharm.2022.122520


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 fastdissolving 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.

Item Type:Article
Uncontrolled Keywords:Atorvastatin; Solid dispersion; Micellar system; Supersaturation; Hyperlipidemia; Liver steatosis
Subjects:Medical sciences > Pharmacy > Pharmacology
Medical sciences > Pharmacy > Drugs
Medical sciences > Pharmacy > Pharmaceutical technology
ID Code:76112
Deposited On:08 Feb 2023 09:35
Last Modified:09 Feb 2023 11:18

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