Evaluation of physicochemical properties and in vivo efficiency of atorvastatin calcium/ezetimibe solid dispersions

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 t...

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Bibliographic Details
Published in:European journal of pharmaceutical sciences 2016-01, Vol.82, p.21-30
Main Authors: Jahangiri, Azin, Barzegar-Jalali, Mohammad, Garjani, Alireza, Javadzadeh, Yousef, Hamishehkar, Hamed, Asadpour-Zeynali, Karim, Adibkia, Khosro
Format: Article
Language:English
Subjects:
Animals
Atorvastatin
Atorvastatin Calcium - administration & dosage
Atorvastatin Calcium - chemistry
Atorvastatin Calcium - pharmacology
Atorvastatin Calcium - therapeutic use
Cholesterol - blood
Diet, High-Fat
Drug Combinations
Ezetimibe
Ezetimibe - administration & dosage
Ezetimibe - chemistry
Ezetimibe - pharmacology
Ezetimibe - therapeutic use
Fatty Liver - blood
Fatty Liver - drug therapy
Fatty Liver - pathology
Hyperlipidemias - blood
Hyperlipidemias - drug therapy
Hyperlipidemias - pathology
In vivo evaluation
Liver - drug effects
Liver - pathology
Liver steatosis
Male
Povidone - chemistry
Rats, Wistar
Solid dispersion
Solubility
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Summary: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
ISSN:0928-0987
1879-0720
DOI:10.1016/j.ejps.2015.11.007