Stabilisation of amorphous furosemide increases the oral drug bioavailability in rats
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Stabilisation of amorphous furosemide increases the oral drug bioavailability in rats. / Nielsen, Line Hagner; Rades, Thomas; Müllertz, Anette.
In: International Journal of Pharmaceutics, Vol. 490, No. 1-2, 25.07.2015, p. 334-40.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Stabilisation of amorphous furosemide increases the oral drug bioavailability in rats
AU - Nielsen, Line Hagner
AU - Rades, Thomas
AU - Müllertz, Anette
N1 - Copyright © 2015 Elsevier B.V. All rights reserved.
PY - 2015/7/25
Y1 - 2015/7/25
N2 - A glass solution of the amorphous sodium salt of furosemide (ASSF) and polyvinylpyrrolidone (PVP) (80:20 w/w%) was prepared by spray drying. It was investigated if PVP was able to stabilise ASSF during storage and dissolution and whether this influenced the in vivo performance of the glass solution after oral dosing to rats. The glass solution had a glass transition temperature of 121.3 ± 0.5°C, which was significantly higher than that of the pure drug (101.2°C). ASSF in the glass solution was stable for at least 168 days when stored at 20°C and 0% relative humidity. The glass solution exhibited fast dissolution in simulated intestinal medium, pH 6.5; the intrinsic dissolution rate was found to be 10.1 ± 0.6 mg/cm(2)/min, which was significantly faster than the pure ASSF. When investigating the stability during dissolution in stimulated intestinal medium at pH 6.5, the ASSF in the glass solution showed signs of crystallinity after 1 min of dissolution, but crystallised to a lesser extent than pure ASSF. The stabilising effect of PVP on ASSF, led to improved relative oral bioavailability in rats of 263%, when compared to the pure ASSF.
AB - A glass solution of the amorphous sodium salt of furosemide (ASSF) and polyvinylpyrrolidone (PVP) (80:20 w/w%) was prepared by spray drying. It was investigated if PVP was able to stabilise ASSF during storage and dissolution and whether this influenced the in vivo performance of the glass solution after oral dosing to rats. The glass solution had a glass transition temperature of 121.3 ± 0.5°C, which was significantly higher than that of the pure drug (101.2°C). ASSF in the glass solution was stable for at least 168 days when stored at 20°C and 0% relative humidity. The glass solution exhibited fast dissolution in simulated intestinal medium, pH 6.5; the intrinsic dissolution rate was found to be 10.1 ± 0.6 mg/cm(2)/min, which was significantly faster than the pure ASSF. When investigating the stability during dissolution in stimulated intestinal medium at pH 6.5, the ASSF in the glass solution showed signs of crystallinity after 1 min of dissolution, but crystallised to a lesser extent than pure ASSF. The stabilising effect of PVP on ASSF, led to improved relative oral bioavailability in rats of 263%, when compared to the pure ASSF.
KW - Administration, Oral
KW - Animals
KW - Biological Availability
KW - Chemistry, Pharmaceutical
KW - Crystallization
KW - Drug Compounding
KW - Drug Stability
KW - Furosemide
KW - Glass
KW - Hydrogen-Ion Concentration
KW - Male
KW - Pharmaceutical Solutions
KW - Povidone
KW - Rats
KW - Rats, Sprague-Dawley
KW - Solubility
KW - Transition Temperature
U2 - 10.1016/j.ijpharm.2015.05.063
DO - 10.1016/j.ijpharm.2015.05.063
M3 - Journal article
C2 - 26026252
VL - 490
SP - 334
EP - 340
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
IS - 1-2
ER -
ID: 161624161