title: Planetary ball milling and supercritical fluid technology as a way to enhance dissolution of bicalutamide.
abstract: Dissolution of bicalutamide processed with polyvinylpyrrolidone by either supercritical carbon dioxide or ball milling has been investigated. Various compositions as well as process parameters were used to obtain binary systems of the drug with the carrier. Thermal analysis and powder X-ray diffractometry confirmed amorphization of bicalutamide mechanically activated by ball milling and the decrease in crystallinity of the supercritical carbon dioxide-treated drug. Both methods led to reduction of particles size what was confirmed by scanning electron microscopy and laser diffraction measurements. Moreover, the effect of micronisation was found to depend on the parameters of applied process. Fourier transform infrared spectroscopy revealed the appearance of intermolecular interactions between drug and carrier molecules that play an important role in the stabilization of amorphous form of the active compound. Changes in crystal structure combined with reduced size of particles of bicalutamide dispersed within polymer matrix were found to improve dissolution of bicalutamide by 4 to 10-fold in comparison to untreated drug. It is of particular importance as poor dissolution profiles are considered to be the major limitation in bioavailability of the drug.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland; Department of Physical Chemistry and Electrochemistry, Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Krakow, Poland. Electronic address: joanna.szafraniec@uj.edu.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Szafraniec
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Antosik
authors.affiliation: Division of Biophysics and Molecular Physics, 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: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Kurek
authors.affiliation: Department of Physical Chemistry and Electrochemistry, Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Krakow, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Syrek
authors.affiliation: Division of Biophysics and Molecular Physics, 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: Krzysztof
authors.initials: K
authors.lastname: Chmiel
authors.affiliation: Division of Biophysics and Molecular Physics, 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
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland.
authors.forename: Renata
authors.initials: R
authors.lastname: Jachowicz
mesh_terms: D000726:Androgen Antagonists / Q000737:chemistry*; D000813:Anilides / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D004339:Drug Compounding / Q000379:methods*; D065546:Drug Liberation; D008855:Microscopy, Electron, Scanning; D009570:Nitriles / Q000737:chemistry*; D010316:Particle Size; D011205:Povidone / Q000737:chemistry; D033362:Powder Diffraction; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D014105:Tosyl Compounds / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D009570:Nitriles; D014105:Tosyl Compounds; C053541:bicalutamide; D011205:Povidone
keywords: Bicalutamide PVP; Dissolution; Planetary ball milling; Solid dispersion; Supercritical CO(2)