Characterization during storage and dissolution of Solid dispersions containing furosemide and hydroxypropyl methylcellulose

TY - JOUR

T1 - Characterization during storage and dissolution of Solid dispersions containing furosemide and hydroxypropyl methylcellulose

AU - Nielsen, Line Hagner

AU - Rades, T.

AU - Müllertz, A.

PY - 2013/7/1

Y1 - 2013/7/1

N2 - Solid dispersions containing furosemide and various amounts of hydroxypropyl methylcellulose (HPMC) were prepared by spray drying to investigate if the physical stability of amorphous furosemide during storage and dissolution could be improved by formulating the drug as a solid dispersion. All solid dispersions, containing 20, 50, or 80 w/w % HPMC, were stable for 730 days when stored at 22 °C and 33 % relative humidity (RH), whereas under accelerated storage conditions of 40 °C and 75 % RH the amorphous furosemide in the solid dispersions with 20 and 50 % HPMC converted to a crystalline form within 30 days of storage. In contrast, furosemide in solid dispersions containing 80 % HPMC stayed amorphous for 30 days. Dissolution experiments in conjunction with XRPD and in-line Raman spectroscopy showed that the addition of 80 % HPMC was necessary for complete avoidance of solid state conversion of amorphous fiirosemide to a crystalline form during dissolution.

AB - Solid dispersions containing furosemide and various amounts of hydroxypropyl methylcellulose (HPMC) were prepared by spray drying to investigate if the physical stability of amorphous furosemide during storage and dissolution could be improved by formulating the drug as a solid dispersion. All solid dispersions, containing 20, 50, or 80 w/w % HPMC, were stable for 730 days when stored at 22 °C and 33 % relative humidity (RH), whereas under accelerated storage conditions of 40 °C and 75 % RH the amorphous furosemide in the solid dispersions with 20 and 50 % HPMC converted to a crystalline form within 30 days of storage. In contrast, furosemide in solid dispersions containing 80 % HPMC stayed amorphous for 30 days. Dissolution experiments in conjunction with XRPD and in-line Raman spectroscopy showed that the addition of 80 % HPMC was necessary for complete avoidance of solid state conversion of amorphous fiirosemide to a crystalline form during dissolution.

KW - Amorphous fiirosemide

KW - Biorelevant dissolution

KW - Hydroxypropyl methylcellulose

KW - Physical stability

KW - Solid dispersions

KW - Solid state characterisation

M3 - Journal article

AN - SCOPUS:84881607103

SN - 1773-2247

VL - 23

SP - 409

EP - 415

JO - Journal of Drug Delivery Science and Technology

JF - Journal of Drug Delivery Science and Technology

IS - 4

ER -