title: Molecular Dynamics, Recrystallization Behavior, and Water Solubility of the Amorphous Anticancer Agent Bicalutamide and Its Polyvinylpyrrolidone Mixtures.
abstract: In this paper, we investigated the molecular mobility and physical stability of amorphous bicalutamide, a poorly water-soluble drug widely used in prostate cancer treatment. Our broadband dielectric spectroscopy measurements and differential scanning calorimetry studies revealed that amorphous BIC is a moderately fragile material with a strong tendency to recrystallize from the amorphous state. However, mixing the drug with polymer polyvinylpyrrolidone results in a substantial improvement of physical stability attributed to the antiplasticizing effect governed by the polymer additive. Furthermore, IR study demonstrated the existence of specific interactions between the drug and excipient. We found out that preparation of bicalutamide-polyvinylpyrrolidone mixture in a 2-1 weight ratio completely hinder material recrystallization. Moreover, we determined the time-scale of structural relaxation in the glassy state for investigated materials. Because molecular mobility is considered an important factor governing crystallization behavior, such information was used to approximate the long-term physical stability of an amorphous drug and drug-polymer systems upon their storage at room temperature. Moreover, we found that such systems have distinctly higher water solubility and dissolution rate in comparison to the pure amorphous form, indicating the genuine formulation potential of the proposed approach.
authors.affiliation: Institute of Physics, University of Silesia , Uniwersytecka 4, 40-007 Katowice, Poland.|Silesian Center for Education and Interdisciplinary Research , 75 Pulku Piechoty 1A, 41-500 Chorzow, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Szczurek
authors.affiliation: Institute of Physics, University of Silesia , Uniwersytecka 4, 40-007 Katowice, Poland.|Silesian Center for Education and Interdisciplinary Research , 75 Pulku Piechoty 1A, 41-500 Chorzow, Poland.
authors.forename: Marzena
authors.identifier: 0000-0001-8808-8067
authors.initials: M
authors.lastname: Rams-Baron
authors.affiliation: Institute of Physics, University of Silesia , Uniwersytecka 4, 40-007 Katowice, Poland.|Silesian Center for Education and Interdisciplinary Research , 75 Pulku Piechoty 1A, 41-500 Chorzow, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Knapik-Kowalczuk
authors.affiliation: Jagiellonian University , Faculty of Pharmacy, Department of Pharmaceutical Technology and Biopharmaceutics, Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Antosik
authors.affiliation: Jagiellonian University , Faculty of Pharmacy, Department of Pharmaceutical Technology and Biopharmaceutics, Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Szafraniec
authors.affiliation: Jagiellonian University , Faculty of Pharmacy, Department of Pharmaceutical Technology and Biopharmaceutics, Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Witold
authors.initials: W
authors.lastname: Jamróz
authors.affiliation: Silesian Center for Education and Interdisciplinary Research , 75 Pulku Piechoty 1A, 41-500 Chorzow, Poland.|Institute of Materials Science, University of Silesia , 75 Pulku Piechoty 1A, 41-500 Chorzow, Poland.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Dulski
authors.affiliation: Jagiellonian University , Faculty of Pharmacy, Department of Pharmaceutical Technology and Biopharmaceutics, Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Renata
authors.initials: R
authors.lastname: Jachowicz
authors.affiliation: Institute of Physics, University of Silesia , Uniwersytecka 4, 40-007 Katowice, Poland.|Silesian Center for Education and Interdisciplinary Research , 75 Pulku Piechoty 1A, 41-500 Chorzow, Poland.
authors.forename: Marian
authors.initials: M
authors.lastname: Paluch
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization / Q000379:methods; D004339:Drug Compounding / Q000379:methods; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D011108:Polymers / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry; D012995:Solubility
chemical_list: D000970:Antineoplastic Agents; D005079:Excipients; D011108:Polymers; D011205:Povidone
keywords: amorphous bicalutamide; crystallization; glass transition; molecular dynamic; physical stability; polyvinylpyrrolidone