Inhibitory effect of 2-hydroxypropyl-beta-cyclodextrin on crystal-growth of nifedipine during storage: superior dissolution and oral bioavailability compared with polyvinylpyrrolidone K-30

J Pharm Pharmacol. 1992 Feb;44(2):73-8. doi: 10.1111/j.2042-7158.1992.tb03564.x.

Abstract

To prevent the crystal-growth of nifedipine during storage, 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) was employed as a hydrophilic drug carrier and compared with polyvinylpyrrolidone K-30 (PVP). Amorphous nifedipine powders were prepared by spray-drying with HP-beta-CyD or PVP, and their crystal-growing behaviour at accelerated storage conditions were examined by X-ray diffraction analysis and microscopy. Although PVP initially retarded the crystallization of nifedipine, it failed to control the increase of crystal size after prolonged storage at 60 degrees C, 75% r.h., resulting in a remarkable decrease in dissolution rate in water. In sharp contrast, a relatively fine and uniform size of nifedipine crystals was maintained in the HP-beta-CyD system even after accelerated storage conditions. The enhanced dissolution observed for all the HP-beta-CyD systems in a dissolution medium containing 0.1% non-ionic surfactant HCO-60 were clearly reflected in the in-vivo absorption of nifedipine following oral administration to dogs. These results suggest that HP-beta-CyD is particularly useful in solving problems encountered on storage of amorphous nifedipine in solid dosage forms.

Publication types

  • Comparative Study

MeSH terms

  • 2-Hydroxypropyl-beta-cyclodextrin
  • Animals
  • Biological Availability
  • Crystallization
  • Cyclodextrins* / chemistry
  • Dogs
  • Drug Carriers
  • Microscopy, Electron
  • Nifedipine / chemistry*
  • Nifedipine / pharmacokinetics
  • Povidone / chemistry
  • Tablets
  • X-Ray Diffraction
  • beta-Cyclodextrins*

Substances

  • Cyclodextrins
  • Drug Carriers
  • Tablets
  • beta-Cyclodextrins
  • 2-Hydroxypropyl-beta-cyclodextrin
  • Povidone
  • Nifedipine