Stabilisation of amorphous furosemide increases the oral drug bioavailability in rats

Line Hagner Nielsen; Thomas Rades; Anette Müllertz

doi:10.1016/j.ijpharm.2015.05.063

Stabilisation of amorphous furosemide increases the oral drug bioavailability in rats

Line Hagner Nielsen, Thomas Rades, Anette Müllertz

18 Citationer (Scopus)

Abstract

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/cm2/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.

Originalsprog	Engelsk
Tidsskrift	International Journal of Pharmaceutics
Vol/bind	490
Udgave nummer	1-2
Sider (fra-til)	334-40
Antal sider	7
ISSN	0378-5173
DOI	https://doi.org/10.1016/j.ijpharm.2015.05.063
Status	Udgivet - 25 jul. 2015

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10.1016/j.ijpharm.2015.05.063

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title = "Stabilisation of amorphous furosemide increases the oral drug bioavailability in rats",

abstract = "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 ±0.6mg/cm2/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.",

keywords = "Administration, Oral, Animals, Biological Availability, Chemistry, Pharmaceutical, Crystallization, Drug Compounding, Drug Stability, Furosemide, Glass, Hydrogen-Ion Concentration, Male, Pharmaceutical Solutions, Povidone, Rats, Rats, Sprague-Dawley, Solubility, Transition Temperature",

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T1 - Stabilisation of amorphous furosemide increases the oral drug bioavailability in rats

AU - Nielsen, Line Hagner

AU - Rades, Thomas

AU - Müllertz, Anette

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 ±0.6mg/cm2/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 ±0.6mg/cm2/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

SN - 0378-5173

VL - 490

SP - 334

EP - 340

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

IS - 1-2

ER -

Stabilisation of amorphous furosemide increases the oral drug bioavailability in rats

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