Compression-Induced Phase Transitions of Bicalutamide

Autor: Marian Paluch, Justyna Knapik-Kowalczuk, Renata Jachowicz, Krzysztof Niwiński, Agata Antosik-Rogóż, Joanna Szafraniec-Szczęsny, Mateusz Kurek, Sebastián Peralta, Karolina Gawlak, Ewa Szefer, Krzysztof Chmiel, Krzysztof Pielichowski
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Pharmaceutics
Volume 12
Issue 5
Pharmaceutics, Vol 12, Iss 438, p 438 (2020)
Digibug: Repositorio Institucional de la Universidad de Granada
Universidad de Granada (UGR)
Digibug. Repositorio Institucional de la Universidad de Granada
instname
ISSN: 1999-4923
DOI: 10.3390/pharmaceutics12050438
Popis: 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.
Polish National Science Centre 2015/16/W/NZ7/00404
Databáze: OpenAIRE
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