title: Stabilization of the Amorphous Ezetimibe Drug by Confining Its Dimension.
abstract: The purpose of this paper is to investigate the influence of nanoconfinement on the molecular mobility, as well as on the physical stability, of amorphous ezetimibe drug. Two guest/host systems, ezetimibe-Aeroperl 300 and ezetimibe-Neusilin US2, were prepared and studied using various experimental techniques, such as X-ray diffraction (XRD), differential scanning calorimetry (DSC), and broadband dielectric spectroscopy (BDS). Our investigation has shown that the molecular mobility of the examined anticholesterol agent incorporated into nanopore matrices strongly depends on the pore size of the host system. Moreover, it was found that the amorphous ezetimibe confined in 30 nm pores of Aeroperl 300 has a tendency to recrystallize, while the drug incorporated into the smaller--5 nm--pores of Neusilin US2 is not able to crystallize. It has been shown that this significant stabilization of ezetimibe drug can be achieved by an interplay of three factors: changes in molecular dynamics of the confined amorphous drug, the immobilization effect of pore walls on a part of ezetimibe molecules, and the use of host materials with pores that are smaller than the critical size of the drug crystal nuclei.
authors.affiliation: Institute of Physics, University of Silesia , ul. Uniwersytecka 4, 40-007 Katowice, Poland.|SMCEBI , ul. 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Knapik
authors.affiliation: Institute of Physics, University of Silesia , ul. Uniwersytecka 4, 40-007 Katowice, Poland.|SMCEBI , ul. 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.
authors.forename: Z
authors.initials: Z
authors.lastname: Wojnarowska
authors.affiliation: Institute of Physics, University of Silesia , ul. Uniwersytecka 4, 40-007 Katowice, Poland.|SMCEBI , ul. 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Grzybowska
authors.affiliation: Institute of Physics, University of Silesia , ul. Uniwersytecka 4, 40-007 Katowice, Poland.|SMCEBI , ul. 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Jurkiewicz
authors.affiliation: F1 Pharma sp. z o.o. , ul. Bobrzyńskiego 14, 30-348 Kraków, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Stankiewicz
authors.affiliation: Institute of Physics, University of Silesia , ul. Uniwersytecka 4, 40-007 Katowice, Poland.|SMCEBI , ul. 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Paluch
mesh_terms: D017607:Aluminum Compounds / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D000069438:Ezetimibe / Q000737:chemistry*; D017616:Magnesium Compounds / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D058608:Nanopores; D017640:Silicates / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D017607:Aluminum Compounds; D017616:Magnesium Compounds; D017640:Silicates; C033065:aluminum magnesium silicate; D000069438:Ezetimibe
keywords: Aeroperl 300; Neusilin US2; confinement; ezetimibe; glass transition; host/guest system; molecular dynamics; nanopores; physical stability