Effect of grinding with hydroxypropyl cellulose on the dissolution and particle size of a poorly water-soluble drug.
A new benzofuroquinoline derivative, 3,9-bis(N,N-dimethylcarbamoyloxy)-5H-benzofuro[3,2-c]quinoli ne-6-one (KCA-098), shows poor oral absorption due to practical insolubility in water. In this study, a co-grinding technique employing a water-soluble polymer was used for improvement of the dissolution rate of KCA-098. Powder X-ray diffraction patterns and IR spectra of KCA-098 showed the conversion of the drug from a crystal state to an amorphous state by grinding with a polymer such as hydroxypropyl cellulose (HPC-SL) or polyvinylpyrrolidone (PVP K30). The particle size of KCA-098 was remarkably reduced to a submicron size by grinding with HPC-SL. The co-ground mixture with HPC-SL showed a rapid dissolution rate and maintained supersaturation for more than 1 h. On the other hand, the co-ground mixture with PVP K30 showed rapid dissolution and supersaturation for a shorter period. These data suggest that the rapid dissolution rate was obtained by the conversion of the drug particles from a crystal to amorphous state by grinding with water-soluble polymers and that a reduction in particle size to the submicron level led to the maintenance of supersaturation due to good dispersion.
Yamada
T
T
Pharmaceutical Laboratories, Kissei Pharmaceutical Co., Ltd., Nagano, Japan.
Saito
N
N
Imai
T
T
Otagiri
M
M
D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D003375:Coumestrol / Q000031:analogs & derivatives* / Q000737:chemistry; D004339:Drug Compounding; D010316:Particle Size; D011205:Povidone; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
C088191:KCA 098; D002482:Cellulose; C008079:hydroxypropylcellulose; D011205:Povidone; D003375:Coumestrol