TY - JOUR

T1 - Formation and characterization of porous indomethacin-PVP coprecipitates prepared using solvent-free supercritical fluid processing

AU - Gong, K.

AU - Viboonkiat, R.

AU - Rehman, I.U.

AU - Buckton, G.

AU - Darr, J.A.

PY - 2005

Y1 - 2005

N2 - Supercritical carbon dioxide (sc-CO2) was used to prepare coprecipitates of indomethacin (IM) and poly(vinylpyrrolidone) (PVP) with the aim to improve the dissolution rate of IM. The coprecipitates of IM and PVP at various proportions were prepared using a stirred batch reactor containing SC-CO2 as a gas saturated solution (i.e., the compressible CO 2 is dissolved in the molten compound). Temperatures between 40 and 90°C and pressure of 150 or 200 bar were employed. The coprecipitates prepared at 75°C and 150 bar were characterized using differential scanning calorimetry (DSC), powder X-ray diffraction (PXD), scanning electron microscopy (SEM), and dissolution testing. The results suggested that IM was totally amorphous at PVP weight fraction of 0.80 and above (indeed, as a molecular composite in which the drug molecules interact with the polymer backbone). As the PVP weight fraction decreased, IM displayed an increasing amount of crystalline material. The SEM photographs of coprecipitates showed a foamed and porous structure. The dissolution rate of IM was increased by incorporation of PVP. IM and PVP at various weight fractions exhibited comparatively higher dissolution rates than that of crystalline IM alone. The Sc-CO2 based process produced a solvent free, completely amorphous porous IM solid dispersion with a rapid dissolution rate. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association.

AB - Supercritical carbon dioxide (sc-CO2) was used to prepare coprecipitates of indomethacin (IM) and poly(vinylpyrrolidone) (PVP) with the aim to improve the dissolution rate of IM. The coprecipitates of IM and PVP at various proportions were prepared using a stirred batch reactor containing SC-CO2 as a gas saturated solution (i.e., the compressible CO 2 is dissolved in the molten compound). Temperatures between 40 and 90°C and pressure of 150 or 200 bar were employed. The coprecipitates prepared at 75°C and 150 bar were characterized using differential scanning calorimetry (DSC), powder X-ray diffraction (PXD), scanning electron microscopy (SEM), and dissolution testing. The results suggested that IM was totally amorphous at PVP weight fraction of 0.80 and above (indeed, as a molecular composite in which the drug molecules interact with the polymer backbone). As the PVP weight fraction decreased, IM displayed an increasing amount of crystalline material. The SEM photographs of coprecipitates showed a foamed and porous structure. The dissolution rate of IM was increased by incorporation of PVP. IM and PVP at various weight fractions exhibited comparatively higher dissolution rates than that of crystalline IM alone. The Sc-CO2 based process produced a solvent free, completely amorphous porous IM solid dispersion with a rapid dissolution rate. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association.

KW - Amorphous

KW - Drug

KW - Indomethacin

KW - Poly(vinylpyrrolidone)

KW - Solid dispersion

KW - Supercritical CO2

KW - indometacin

KW - povidone

KW - solvent

KW - article

KW - crystallization

KW - differential scanning calorimetry

KW - dispersion

KW - drug solubility

KW - evaporation

KW - porosity

KW - precipitation

KW - scanning electron microscopy

KW - supercritical fluid

KW - thermal analysis

KW - X ray diffraction

U2 - 10.1002/jps.20474

DO - 10.1002/jps.20474

M3 - Journal article

VL - 94

SP - 2583

EP - 2590

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

SN - 0022-3549

IS - 12

ER -