TY - JOUR
T1 - Polymeric microcontainers improve oral bioavailability of furosemide
AU - Nielsen, Line Hagner
AU - Melero, Ana
AU - Keller, Stephan Sylvest
AU - Jacobsen, Jette
AU - Garrigues, Teresa
AU - Rades, Thomas
AU - Müllertz, Anette
AU - Boisen, Anja
N1 - Copyright © 2016. Published by Elsevier B.V.
PY - 2016/5/17
Y1 - 2016/5/17
N2 - Microcontainers with an inner diameter of 223 μm are fabricated using the polymer SU-8, and evaluated in vitro, in situ and in vivo for their application as an advanced oral drug delivery system for the poorly water soluble drug furosemide. An amorphous sodium salt of furosemide (ASSF) is filled into the microcontainers followed by applying a lid using Eudragit L100. It is possible to control the drug release in vitro, and in vitro absorption studies show that the microcontainers are not a hindrance for absorption of ASSF. In situ perfusion studies in rats are performed with ASSF-filled microcontainers coated with Eudragit and compared to a furosemide solution. The absorption rate constant of ASSF confined in microcontainers is found to be significantly different from the solution, and by light microscopy, it is observed that the microcontainers are engulfed by the intestinal mucus. An oral bioavailability study in rats is performed with ASSF confined in microcontainers coated with Eudragit and a control group with ASSF in Eudragit-coated capsules. A relative bioavailability of 220% for the ASSF in microcontainers compared to ASSF in capsules is found. These studies indicate that the microcontainers could serve as a promising oral drug delivery system.
AB - Microcontainers with an inner diameter of 223 μm are fabricated using the polymer SU-8, and evaluated in vitro, in situ and in vivo for their application as an advanced oral drug delivery system for the poorly water soluble drug furosemide. An amorphous sodium salt of furosemide (ASSF) is filled into the microcontainers followed by applying a lid using Eudragit L100. It is possible to control the drug release in vitro, and in vitro absorption studies show that the microcontainers are not a hindrance for absorption of ASSF. In situ perfusion studies in rats are performed with ASSF-filled microcontainers coated with Eudragit and compared to a furosemide solution. The absorption rate constant of ASSF confined in microcontainers is found to be significantly different from the solution, and by light microscopy, it is observed that the microcontainers are engulfed by the intestinal mucus. An oral bioavailability study in rats is performed with ASSF confined in microcontainers coated with Eudragit and a control group with ASSF in Eudragit-coated capsules. A relative bioavailability of 220% for the ASSF in microcontainers compared to ASSF in capsules is found. These studies indicate that the microcontainers could serve as a promising oral drug delivery system.
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1016/j.ijpharm.2016.03.050
DO - 10.1016/j.ijpharm.2016.03.050
M3 - Journal article
C2 - 27033999
SN - 0378-5173
VL - 504
SP - 98
EP - 109
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -