Compression-Induced Phase Transitions of Bicalutamide

Pharmaceutics

Ewa Szefer¹  Krzysztof Pielichowski¹  Renata Jachowicz²  Joanna Szafraniec-Szczęsny²  Agata Antosik-Rogóż²  Krzysztof Niwiński²  Mateusz Kurek²  Karolina Gawlak³  Marian Paluch⁴  Krzysztof Chmiel⁴  Justyna Knapik-Kowalczuk⁴  Sebastian Peralta⁵ 

[1] Department of Chemistry and Technology of Polymers, Cracow University of Technology, Warszawska 24, 31-155 Krakow, Poland;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;Faculty of Science and Technology, Institute of Physics, University of Silesia, SMCEBI, 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland;Pharmacy and Pharmaceutical Technology Department, School of Pharmacy, University of Granada, Campus de Cartuja s/n., 18071 Granada, Spain;

关键词: amorphous solid dispersions;    physical stability;    bicalutamide;    Kollidon^®VA64;    dissolution;    compression;   

DOI  :  10.3390/pharmaceutics12050438

来源: DOAJ

【 摘 要 】

The formation of solid dispersions with the amorphous drug dispersed in the polymeric matrix improves the dissolution characteristics of poorly soluble drugs. Although they provide an improved absorption after oral administration, the recrystallization, which can occur upon absorption of moisture or during solidification and other formulation stages, serves as a major challenge. This work aims at understanding the amorphization-recrystallization changes of bicalutamide. Amorphous solid dispersions with poly(vinylpyrrolidone-co-vinyl acetate) (PVP/VA) were obtained by either ball milling or spray drying. The applied processes led to drug amorphization as confirmed using X-ray diffraction and differential scanning calorimetry. Due to a high propensity towards mechanical activation, the changes of the crystal structure of physical blends of active pharmaceutical ingredient (API) and polymer upon pressure were also examined. The compression led to drug amorphization or transition from form I to form II polymorph, depending on the composition and applied force. The formation of hydrogen bonds confirmed using infrared spectroscopy and high miscibility of drug and polymer determined using non-isothermal dielectric measurements contributed to the high stability of amorphous solid dispersions. They exhibited improved wettability and dissolution enhanced by 2.5- to 11-fold in comparison with the crystalline drug. The drug remained amorphous upon compression when the content of PVP/VA in solid dispersions exceeded 20% or 33%, in the case of spray-dried and milled systems, respectively.

【 授权许可】

Unknown