title: Molecular Factors Governing the Liquid and Glassy States Recrystallization of Celecoxib in Binary Mixtures with Excipients of Different Molecular Weights.
abstract: Transformation of poorly water-soluble crystalline pharmaceuticals to the amorphous form is one of the most promising strategies to improve their oral bioavailability. Unfortunately, the amorphous drugs are usually thermodynamically unstable and may quickly return to their crystalline form. A very promising way to enhance the physical stability of amorphous drugs is to prepare amorphous compositions of APIs with certain excipients which can be characterized by significantly different molecular weights, such as polymers, acetate saccharides, and other APIs. By using different experimental techniques (broadband dielectric spectroscopy, differential scanning calorimetry, X-ray diffraction) we compare the effect of adding the large molecular weight polymer-polyvinylpyrrolidone (PVP K30)-and the small molecular weight excipient-octaacetylmaltose (acMAL)-on molecular dynamics as well as the tendency to recrystallization of the amorphous celecoxib (CEL) in the amorphous solid dispersions: CEL-PVP and CEL-acMAL. The physical stability investigations of the binary systems were performed in both the supercooled liquid and glassy states. We found that acMAL is a better inhibitor of recrystallization of amorphous CEL than PVP K30 deep in the glassy state (T < Tg). In contrast, PVP K30 is a better crystallization inhibitor of CEL than acMAL in the supercooled liquid state (at T > Tg). We discuss molecular factors governing the recrystallization of amorphous CEL in examined solid dispersions.
authors.affiliation: Institute of Physics, University of Silesia in Katowice , ul. Uniwersytecka 4, 40-007 Katowice, Poland.|Silesian Center for Education and Interdisciplinary Research , ul. 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.
authors.forename: K
authors.identifier: 0000-0002-0691-3631
authors.initials: K
authors.lastname: Grzybowska
authors.affiliation: Institute of Physics, University of Silesia in Katowice , ul. Uniwersytecka 4, 40-007 Katowice, Poland.|Silesian Center for Education and Interdisciplinary Research , ul. 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Chmiel
authors.affiliation: Institute of Physics, University of Silesia in Katowice , ul. Uniwersytecka 4, 40-007 Katowice, Poland.|Silesian Center for Education and Interdisciplinary Research , ul. 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Knapik-Kowalczuk
authors.affiliation: Institute of Physics, University of Silesia in Katowice , ul. Uniwersytecka 4, 40-007 Katowice, Poland.|Silesian Center for Education and Interdisciplinary Research , ul. 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Grzybowski
authors.affiliation: Institute of Physics, University of Silesia in Katowice , ul. Uniwersytecka 4, 40-007 Katowice, Poland.|Silesian Center for Education and Interdisciplinary Research , ul. 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Jurkiewicz
authors.affiliation: Institute of Physics, University of Silesia in Katowice , ul. Uniwersytecka 4, 40-007 Katowice, Poland.|Silesian Center for Education and Interdisciplinary Research , ul. 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Paluch
mesh_terms: D002152:Calorimetry, Differential Scanning / Q000379:methods; D000068579:Celecoxib / Q000737:chemistry*; D003460:Crystallization / Q000379:methods; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D008970:Molecular Weight; D011108:Polymers / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D013816:Thermodynamics; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D005079:Excipients; D011108:Polymers; D011205:Povidone; D000068579:Celecoxib
keywords: amorphous drug; celecoxib; crystallization; devitrification; glass transition; molecular dynamics; physical stability; solid dispersion