title: Evaluation of physicochemical properties and in vivo efficiency of atorvastatin calcium/ezetimibe solid dispersions.
abstract: Fixed-dose combination of atorvastatin calcium (ATV) and ezetimibe (EZT) provides a considerable advantage in the management of hyperlipidemia. However, both ATV and EZT suffer from the poor aqueous solubility, which can limit their oral bioavailability. The aim of the present study was to improve the in vitro performance and evaluate the in vivo efficiency of the improved (ATV/EZT) fixed-dose combination. The formulation was prepared through solid dispersion (SD)technique, using Polyvinylpyrrolidone K30 via solvent method. Solid-state analysis and the in vitro drug release of the prepared formulations were also assessed. In order to estimate the therapeutic efficiency of the prepared SDs, in vivo studies including measurement of serum lipid levels, liver index and histological analysis of the liver tissue in hyperlipidemic rats were conducted. Differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD) showed that the drugs crystallinity was notably decreased during the preparation process. All SDs showed enhanced release for both drugs compared to their binary mixture, drugs: polymer physical mixtures (PMs) and marketed product. Administration of ATV/EZT SD led to a remarkable decrease (P<0.05) in the serum levels of total cholesterol (TC) and LDL-C in the high fat diet-induced hyperlipidemic rats compared to the PM. Additionally, the histopathological examination of the liver tissue revealed the improved efficiency of the SDs on the liver steatosis. According to the obtained results, ATV/EZT SD with improved physicochemical characteristics, showed favorable effects on the serum lipid levels and liver steatosis.
authors.affiliation: Drug Applied Research Center, and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; Students Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Azin
authors.initials: A
authors.lastname: Jahangiri
authors.affiliation: Drug Applied Research Center, and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Barzegar-Jalali
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Garjani
authors.affiliation: Biotechnology Research Center, and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Yousef
authors.initials: Y
authors.lastname: Javadzadeh
authors.affiliation: Drug Applied Research Center, and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Hamed
authors.initials: H
authors.lastname: Hamishehkar
authors.affiliation: Department of Analytical Chemistry, Faculty of Chemistry, University of Tabriz, Tabriz, Iran.
authors.forename: Karim
authors.initials: K
authors.lastname: Asadpour-Zeynali
authors.affiliation: Drug Applied Research Center, and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: adibkia@tbzmed.ac.ir.
authors.forename: Khosro
authors.initials: K
authors.lastname: Adibkia
mesh_terms: D000818:Animals; D000069059:Atorvastatin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat; D004338:Drug Combinations; D000069438:Ezetimibe / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D005234:Fatty Liver / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D011205:Povidone / Q000737:chemistry; D017208:Rats, Wistar; D012995:Solubility
chemical_list: D004338:Drug Combinations; D002784:Cholesterol; D000069059:Atorvastatin; D000069438:Ezetimibe; D011205:Povidone
keywords: Atorvastatin; Ezetimibe; In vivo evaluation; Liver steatosis; Solid dispersion