title: Molecular Dynamics and Physical Stability of Coamorphous Ezetimib and Indapamide Mixtures.
abstract: Low physical stability is the main reason limiting the widespread use of amorphous pharmaceuticals. One approach to overcome this problem is to mix these drugs with various excipients. In this study coamorphous drug-drug compositions of different molar ratios of ezetimib and indapamid (i.e., EZB 10:1 IDP, EZB 5:1 IDP, EZB 2:1 IDP, EZB 1:1 IDP and EZB 1:2 IDP) were prepared and investigated using differential scanning calorimetry (DSC), broadband dielectric spectroscopy (BDS), and X-ray diffraction (XRD). Our studies have shown that the easily recrystallizing ezetimib drug can be significantly stabilized in its amorphous form by using even a small amount of indapamid (8.8 wt %). DSC experiments indicate that the glass transition temperature (Tg) of the tested mixtures changes with the drug concentration in accordance with the Gordon-Taylor equation. We also investigated the effect of indapamid on the molecular dynamics of the ezetimib. As a result it was found that, with increasing indapamid content, the molecular mobility of the binary drug-drug system is slowed down. Finally, using the XRD technique we examined the long-term physical stability of the investigated binary systems stored at room temperature. These measurements prove that low-molecular-weight compounds are able to significantly improve the physical stability of amorphous APIs.
authors: Institute of Physics, University of Silesia , ul. Uniwersytecka 4, 40-007 Katowice, Poland.|SMCEBI , ul. 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.
authors: J
authors: J
authors: Knapik
authors: Institute of Physics, University of Silesia , ul. Uniwersytecka 4, 40-007 Katowice, Poland.|SMCEBI , ul. 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.
authors: Z
authors: Z
authors: Wojnarowska
authors: Institute of Physics, University of Silesia , ul. Uniwersytecka 4, 40-007 Katowice, Poland.|SMCEBI , ul. 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.
authors: K
authors: K
authors: Grzybowska
authors: Institute of Physics, University of Silesia , ul. Uniwersytecka 4, 40-007 Katowice, Poland.|SMCEBI , ul. 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.
authors: K
authors: K
authors: Jurkiewicz
authors: School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin , College Green, Dublin 2, Ireland.
authors: L
authors: L
authors: Tajber
authors: Institute of Physics, University of Silesia , ul. Uniwersytecka 4, 40-007 Katowice, Poland.|SMCEBI , ul. 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.
authors: M
authors: M
authors: Paluch
mesh_terms: D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D058266:Dielectric Spectroscopy; D004338:Drug Combinations; D004355:Drug Stability; D000069438:Ezetimibe / Q000737:chemistry*; D007190:Indapamide / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
chemical_list: D004338:Drug Combinations; D000069438:Ezetimibe; D007190:Indapamide
keywords: coamorphous mixture; drug−drug mixture; ezetimibe; glass transition; indapamide; molecular dynamics; physical stability