Molecular Disorder of Bicalutamide—Amorphous Solid Dispersions Obtained by Solvent Methods

Pharmaceutics

Renata Jachowicz¹  Witold Jamróz¹  Agata Antosik¹  Joanna Szafraniec¹  Mateusz Kurek¹  Jakub Szlęk¹  Karolina Gawlak²  Marian Paluch³  Justyna Knapik-Kowalczuk³ 

[1] 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, Gronostajowa 2, 30-387 Krakow, Poland;Division of Biophysics and Molecular Physics, Institute of Physics, University of Silesia, Uniwersytecka 4, 40-007 Katowice, Poland;

关键词: bicalutamide;    PVP;    solid dispersion;    spray drying;    evaporation;    dissolution;    amorphization;   

DOI  :  10.3390/pharmaceutics10040194

来源: DOAJ

【 摘 要 】

The effect of solvent removal techniques on phase transition, physical stability and dissolution of bicalutamide from solid dispersions containing polyvinylpyrrolidone (PVP) as a carrier was investigated. A spray dryer and a rotavapor were applied to obtain binary systems containing either 50% or 66% of the drug. Applied techniques led to the formation of amorphous solid dispersions as confirmed by X-ray powder diffractometry and differential scanning calorimetry. Moreover, solid–solid transition from polymorphic form I to form II was observed for bicalutamide spray dried without a carrier. The presence of intermolecular interactions between the drug and polymer molecules, which provides the stabilization of molecularly disordered bicalutamide, was analyzed using infrared spectroscopy. Spectral changes within the region characteristic for amide vibrations suggested that the amide form of crystalline bicalutamide was replaced by a less stable imidic one, characteristic of an amorphous drug. Applied processes also resulted in changes of particle geometry and size as confirmed by scanning electron microscopy and laser diffraction measurements, however they did not affect the dissolution significantly as confirmed by intrinsic dissolution study. The enhancement of apparent solubility and dissolution were assigned mostly to the loss of molecular arrangement by drug molecules. Performed statistical analysis indicated that the presence of PVP reduces the mean dissolution time and improve the dissolution efficiency. Although the dissolution was equally affected by both applied methods of solid dispersion manufacturing, spray drying provides better control of particle size and morphology as well as a lower tendency for recrystallization of amorphous solid dispersions.

【 授权许可】

Unknown