Ezetimibe

Lestari, Maria Lucia Ardhani Dwi; Ardiana, Febry; Indrayanto, Gunawan

doi:10.1016/b978-0-12-387667-6.00016-6

Cited by 19 publications

(5 citation statements)

References 39 publications

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“…Most of the active pharmaceutical ingredients (APIs) used in treatment of lipid disorders like simvastatin, lovastatin and fenofibrate are characterized by low water solubility and, as a result of slow release, have limited oral bioavailability. Ezetimibe, due to low solubility and high permeability, also belongs to II class of BCS (Biopharmaceutics Classification System) [11]. It is the first known hypolipidemic drug that selectively inhibits absorption of dietary and biliary cholesterol in the small intestine [12,13].…”

Section: Introductionmentioning

confidence: 99%

Physicochemical and dissolution properties of ezetimibe–aspirin binary system in development of fixed-dose combinations

Gòrniak

Czapor-Irzabek

Złocińska

et al. 2020

J Therm Anal Calorim

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The objective of this work was to investigate binary pharmaceutical mixtures of ezetimibe (EZT) and aspirin (ASA) in order to identify whether the occurrence of eutectic in this system has an effect on EZT dissolution improvement. Ezetimibeaspirin (EZT-ASA) solid dispersions prepared by grinding in the whole range of compositions were characterized using differential scanning calorimetry (DSC) for purpose to describe solid-liquid phase equilibrium diagram. The occurrence of interactions between ingredients was excluded by Fourier transform infrared spectroscopy and X-ray powder diffractometry. Dissolution studies have shown that the mixtures containing from 10 to 60 mass% of EZT (53.5 mass% of EZT in eutectic composition) have released ezetimibe faster than a sample of pure drug. Moreover, ASA is released more quickly from all obtained dispersions than from powder alone. Our studies have shown that obtained mixtures are useful to obtain the fixeddose combinations, capable to deliver these two APIs together in a single system with enhanced dissolution of EZT and ASA.

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Section: Introductionmentioning

confidence: 99%

Physicochemical and dissolution properties of ezetimibe–aspirin binary system in development of fixed-dose combinations

Gòrniak

Czapor-Irzabek

Złocińska

et al. 2020

J Therm Anal Calorim

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“…EZT is practically insoluble in water. The aqueous solubility of EZT hydrated forms is estimated to be 0.008 mg/mL, whereas EZT anhydrous forms reach a solubility level of 0.012 mg/mL [ 33 ]. The dissolution profiles were evaluated for the APIs released from prepared SDs and presented in Figure 8 and Figure 9 .…”

Section: Resultsmentioning

confidence: 99%

“…The Biopharmaceutical Classification System (BCS) classifies both EZT and SIM as class II drugs [ 33 , 34 ]. EZT is practically insoluble in aqueous media and the solubility of anhydrous and hydrated forms of the substance is approximately 12 µg/mL and 8 µg/mL, respectively [ 33 ]. The solubility of SIM in water is twice as high at approximately 30 µg/mL [ 35 ].…”

Section: Introductionmentioning

confidence: 99%

Preformulation Studies of Ezetimibe-Simvastatin Solid Dispersions in the Development of Fixed-Dose Combinations

et al. 2022

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Two active pharmaceutical ingredients (APIs) with limited solubility, simvastatin and ezetimibe, prepared as a drug-drug solid dispersion (SD) was evaluated for physicochemical, microstructural, and aqueous dissolution properties. The simvastatin-ezetimibe SD was prepared using the co-grinding method in a wide range of weight fractions and differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) were used to perform the phase composition analysis. DSC studies confirmed that simvastatin and ezetimibe form a simple eutectic phase equilibrium diagram. Analysis of Fourier transform infrared spectroscopy (FTIR) studies excluded strong interactions between the APIs. Our investigations have revealed that all studied dispersions are characterized by substantially improved ezetimibe dissolution regardless of simvastatin content, and are best when the composition oscillates near the eutectic point. Data obtained in our studies provide an opportunity for the development of well-formulated, ezetimibe-simvastatin fixed-dose combinations (for hypercholesterolemia treatment) with reduced ezetimibe dosages based on its dissolution improvement.

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“…It was worth noting that EZE was starting to have a slig weight loss at 45 to 90 °C. It has been reported that the mass loss of hydrate EZE belo 100 °C was due to the loss of water molecules in the EZE [31][32][33]. SIM was thermally stab below its melting point from the TGA trace (Figure 1).…”

Section: Thermal Analysismentioning

confidence: 93%

Co-Amorphous Formation of Simvastatin-Ezetimibe: Enhanced Physical Stability, Bioavailability and Cholesterol-Lowering Effects in LDLr−/−Mice

et al. 2022

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Hypercholesterolemia is one of the independent risk factors for the development of cardiovascular diseases such as atherosclerosis. The treatment of hypercholesterolemia is of great significance to reduce clinical cardiovascular events and patient mortality. Simvastatin (SIM) and ezetimibe (EZE) are commonly used clinically as cholesterol-lowering drugs; however, their treatment efficacy is severely affected by their poor water solubility and low bioavailability. In this study, SIM and EZE were made into a co-amorphous system to improve their dissolution, oral bioavailability, storage stability, and cholesterol-lowering effects. The SIM-EZE co-amorphous solids (CO) were prepared successfully using the melt-quenched technique, and the physicochemical properties of CO were characterized accordingly, which exhibited improved physical stability and faster dissolution release profiles than their physical mixture (PM). In the pharmacokinetic study, the SIM-EZE CO or PM was given once by oral gavage, and mouse blood samples were collected retro-orbitally at multiple time points to determine the plasma drug concentrations. In the pharmacodynamic study, low-density lipoprotein receptor-deficient (LDLr−/−) mice were fed with a high-fat diet (HFD) for two weeks to establish a mouse model of hypercholesterolemia. Using PM as a control, we investigated the regulation of CO on plasma lipid levels in mice. Furthermore, the mice feces were collected to determine the cholesterol contents. Besides, the effect of EZE on the NPC1L1 mRNA expression level in the mouse intestines was also investigated. The pharmacokinetics results showed that the SIM-EZE CO has improved bioavailability compared to the PM. The pharmacodynamic studies showed that SIM-EZE CO significantly increased the cholesterol-lowering effects of the drugs compared to their PM. The total cholesterol excretion in the mouse feces and inhibitory effect on NCP1L1 gene expression in the mouse intestines after being given the SIM-EZE CO were more dramatic than the PM. Our study shows that the SIM-EZE CO prepared by the melt-quenched method can significantly improve the stability, bioavailability, and cholesterol-lowering efficacy with excellent development potential as a new drug formulation.

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Ezetimibe

Cited by 19 publications

References 39 publications

Physicochemical and dissolution properties of ezetimibe–aspirin binary system in development of fixed-dose combinations

Physicochemical and dissolution properties of ezetimibe–aspirin binary system in development of fixed-dose combinations

Preformulation Studies of Ezetimibe-Simvastatin Solid Dispersions in the Development of Fixed-Dose Combinations

Co-Amorphous Formation of Simvastatin-Ezetimibe: Enhanced Physical Stability, Bioavailability and Cholesterol-Lowering Effects in LDLr−/−Mice

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