TY - JOUR

T1 - Real-time dissolution behavior of furosemide in biorelevant media as determined by UV imaging

AU - Gordon, Sarah

AU - Naelapää, Kaisa

AU - Rantanen, Jukka

AU - Selen, Arzu

AU - Müllertz, Anette

AU - Østergaard, Jesper

PY - 2013

Y1 - 2013

N2 - The potential of UV imaging as a new small scale flow-through dissolution testing platform and its ability to incorporate biorelevant media was tested. Furosemide was utilized as a model poorly soluble drug, and dissolution media simulating conditions in the small intestine (5/1.25 mM and 40/10 mM bile salt/phospholipid, pH 6.5) together with corresponding blank buffer were employed. Dissolution rates as a function of flow rate (0.2-1.0 mL/min) were determined directly from UV images, and by analysis of collected effluent using UV spectrophotometry. A good agreement in dissolution rates was observed, however repeatability of data based on measurement of collected effluent was superior to that obtained by UV imaging in the utilized prototypic flow cell. Both methods indicated that biorelevant media did not markedly increase the dissolution rate of furosemide as compared to buffer. Qualitatively, UV images indicated that uncontrolled swelling/precipitation of furosemide on the compact surface was occurring in some samples. In situ Raman spectroscopy together with X-ray diffraction analysis confirmed that the observations were not due to a solid form transformation of furosemide. The presented results highlight the complementary features of the utilized techniques and, in particular, the detailed information related to dissolution behavior which can be achieved by UV imaging.

AB - The potential of UV imaging as a new small scale flow-through dissolution testing platform and its ability to incorporate biorelevant media was tested. Furosemide was utilized as a model poorly soluble drug, and dissolution media simulating conditions in the small intestine (5/1.25 mM and 40/10 mM bile salt/phospholipid, pH 6.5) together with corresponding blank buffer were employed. Dissolution rates as a function of flow rate (0.2-1.0 mL/min) were determined directly from UV images, and by analysis of collected effluent using UV spectrophotometry. A good agreement in dissolution rates was observed, however repeatability of data based on measurement of collected effluent was superior to that obtained by UV imaging in the utilized prototypic flow cell. Both methods indicated that biorelevant media did not markedly increase the dissolution rate of furosemide as compared to buffer. Qualitatively, UV images indicated that uncontrolled swelling/precipitation of furosemide on the compact surface was occurring in some samples. In situ Raman spectroscopy together with X-ray diffraction analysis confirmed that the observations were not due to a solid form transformation of furosemide. The presented results highlight the complementary features of the utilized techniques and, in particular, the detailed information related to dissolution behavior which can be achieved by UV imaging.

KW - Buffers

KW - Furosemide

KW - Solubility

KW - Spectrophotometry, Ultraviolet

KW - Spectrum Analysis, Raman

KW - Technology, Pharmaceutical

KW - X-Ray Diffraction

U2 - 10.3109/10837450.2012.737808

DO - 10.3109/10837450.2012.737808

M3 - Journal article

C2 - 23136844

VL - 18

SP - 1407

EP - 1416

JO - Pharmaceutical Development and Technology

JF - Pharmaceutical Development and Technology

SN - 1083-7450

IS - 6

ER -