Studies on Hydrophobic Drug-Soluble Carrier Coprecipitates(1)

In order to increase the dissolution rate of furosemide(4-choro-N-furfury1-5-sulfamoy1 anthranilic acid_, various ratio coprecipitates with water-soluble polymers, such as polyvinylpyrrolidone and polythylene glycol, of different molecular weight, were prepared and quantitatively studied by comparing their dissolution characteristics of furosemide at powder state and at nondisintegrating disk state containing constant surface area at various temperatures and rotating velocities. The dissolution characteristics of furosemide from pure furosemide disks and 1:2(w/w) furosemide-PVP coprecipitate disks were in accordance with Noyes-Nernst equation and the rate constant of dissolution was proportional to the square root of rotating velocity of the disks. The intrinsic rate of dissoluton at 150 rpm, 37.deg.C was $2.21{\times}10^{-7}$ for the PVP 10, 000 COPRECIPITATE, $1.64{\times}10^{-7}$ for the PVP 40, 000 coprecipitate, and$ 1.44 {\times} 10^{-7}$for the PVP 360, 000 corprecipitate, while the rate was $1.27{\times}10^{-8}M/cm^{2} min$ for pure furosemide, repectively. The activation energy of dissolution was about 17, 000 for furosemide and about 7, 300 cal/mole for the 1:2 furosemide PVP 40, 000 coprecipitate, respectively.