Inhibitory effect of 2-hydroxypropyl-beta-cyclodextrin on crystal-growth of nifedipine during storage: superior dissolution and oral bioavailability compared with polyvinylpyrrolidone K-30.
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.
Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
K
K
Uekama
K
K
Ikegami
Z
Z
Wang
Y
Y
Horiuchi
F
F
Hirayama
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D001682:Biological Availability; D003460:Crystallization; D003505:Cyclodextrins / Q000737:chemistry; D004285:Dogs; D004337:Drug Carriers; D008854:Microscopy, Electron; D009543:Nifedipine / Q000737:chemistry* / Q000493:pharmacokinetics; D011205:Povidone / Q000737:chemistry; D013607:Tablets; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D004337:Drug Carriers; D013607:Tablets; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D011205:Povidone; D009543:Nifedipine