A new method to identify physically stable concentration of amorphous solid dispersions (I) : case of flutamide + kollidon VA64
PBN-AR
Instytucja
Wydział Matematyki, Fizyki i Chemii (Uniwersytet Śląski w Katowicach)
Informacje podstawowe
Główny język publikacji
angielski
Czasopismo
MOLECULAR PHARMACEUTICS (45pkt w roku publikacji)
ISSN
1543-8384
EISSN
Wydawca
AMER CHEMICAL SOC
DOI
URL
Rok publikacji
2017
Numer zeszytu
10
Strony od-do
3370-3380
Numer tomu
14
Liczba arkuszy
0,50
Autorzy
Pozostali autorzy
+ 2
Słowa kluczowe
angielski
amorphous solid dispersion;
dielectric spectroscopy;
flutamide; kollidon VA64;
molecular dynamics;
physical stability;
Streszczenia
Język
angielski
Treść
In this paper, a novel approach to determine stable concentration in API-polymer systems is presented. As a model, binary amorphous mixtures flutamide (FL) drug with a copolymer Kollidon VA64 (PVP/VA) have been used. It is worthwhile to note that finding an effective method to achieve this goal is a matter of great importance because physical stability of the amorphous pharmaceuticals is the key issue that is investigated worldwide. Due to the fact that molecular dynamics was found to be the crucial factor affecting physical stability of disordered pharmaceuticals, we examined it for both neat FL and its PVP/VA mixtures by means of broadband dielectric spectroscopy (BDS). Thorough investigation of the impact of polymeric additive on the molecular mobility of disordered FL reveals unusual, previously unreported behavior. Namely, simultaneously with the beginning of the recrystallization process, we observe some transformation from unstable supersaturated concentration of investigated mixture to the different, unknown concentration of FL-PVP/VA. Observed, during BDS experiment, transformation enables us to determine the limiting, highly physically stable concentration of FL in PVP/VA polymer (saturated solution), which is equivalent to FL + 41% wt. of PVP/VA. The described high physical stability of this unveiled system has been confirmed by means of long-term XRD measurements. According to our knowledge, this is the first time when such a behavior has been observed by means of BDS.
Cechy publikacji
original-article
Inne
System-identifier
3342800137767
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