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• W4362575234 endingPage "122917" @default.
• W4362575234 startingPage "122917" @default.
• W4362575234 abstract "Atorvastatin calcium (AC), a cholesterol-lowering medication, has limited oral bioavailability (14 %) and adverse impacts on the gastrointestinal tract (GIT), liver, and muscle. So, in an effort to improve the poor availability and overcome the hepatotoxicity complications attendant to peroral AC administration, transdermal transfersomal gel (AC-TFG) was developed as a convenient alternative delivery technique. The impact of utilizing an edge activator (EA) and varying the phosphatidylcholine (PC): EA molar ratio on the physico-chemical characteristics of the vesicles was optimized through a Quality by Design (QbD) strategy. The optimal transdermal AC-TFG was tested in an ex-vivo permeation study employing full-thickness rat skin, Franz cell experiments, an in-vivo pharmacokinetics and pharmacodynamics (PK/PD) evaluation, and a comparison to oral AC using poloxamer-induced dyslipidemic Wister rats. The optimized AC-loaded TF nanovesicles predicted by the 23-factorial design strategy had a good correlation with the measured vesicle diameter of 71.72 ± 1.159 nm, encapsulation efficiency of 89.13 ± 0.125 %, and cumulative drug release of 88.92 ± 3.78 % over 24 h. Ex-vivo data revealed that AC-TF outperformed a free drug in terms of permeation. The pharmacokinetic parameters of optimized AC-TFG demonstrated 2.5- and 13.3-fold significant improvements in bioavailability in comparison to oral AC suspension (AC-OS) and traditional gel (AC-TG), respectively. The transdermal vesicular technique preserved the antihyperlipidemic activity of AC-OS without increasing hepatic markers. Such enhancement was proven histologically by preventing the hepatocellular harm inflicted by statins. The results showed that the transdermal vesicular system is a safe alternative way to treat dyslipidemia with AC, especially when given over a long period of time." @default.
• W4362575234 created "2023-04-06" @default.
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• W4362575234 date "2023-05-01" @default.
• W4362575234 modified "2023-10-16" @default.
• W4362575234 title "Formulation, and optimization of transdermal Atorvastatin Calcium-Loaded Ultra-flexible vesicles; ameliorates poloxamer 407-caused dyslipidemia" @default.
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• W4362575234 doi "https://doi.org/10.1016/j.ijpharm.2023.122917" @default.
• W4362575234 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37019321" @default.
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