Effect of grinding with hydroxypropyl cellulose on the dissolution and particle size of a poorly water-soluble drug

Chem Pharm Bull (Tokyo). 1999 Sep;47(9):1311-3. doi: 10.1248/cpb.47.1311.

Abstract

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.

MeSH terms

  • Cellulose / analogs & derivatives*
  • Cellulose / chemistry
  • Coumestrol / analogs & derivatives*
  • Coumestrol / chemistry
  • Drug Compounding*
  • Particle Size
  • Povidone
  • Solubility
  • Spectroscopy, Fourier Transform Infrared
  • X-Ray Diffraction

Substances

  • KCA 098
  • Cellulose
  • hydroxypropylcellulose
  • Povidone
  • Coumestrol