Coadministration of a water-soluble polymer increases the usefulness of cyclodextrins in solid oral dosage forms

The aim of this study was to investigate the effect of cyclodextrins (beta-CD, HP-beta-CD and (SBE)(7m)-beta-CD), and coadministration of water-soluble polymer (hydroxypropylmethylcellculose; HPMC) and cyclodextrins (CDs) on aqueous solubility and oral bioavailability of glibenclamide (GBA). GBA was administered orally and intravenously to dogs. GBA showed A(L)-type diagram for beta-CD and A(p)-type diagrams for both beta-CD derivatives studied. HPMC (0.05 %) enhanced the solubilizing effect of CDs but did not affect the type of phase-solubility diagram. Orally administered GBA and its physical mixture with HP-beta-CD showed poor absolute :boavailability while GBA/beta-CD, GBA/HP-beta-CD and GBA/(SBE)(7m)-beta-CD enhanced significantly the absolute bioavailability of GBA. Orally administered GBA/beta-CD/HPMC and GBA/(SBE)(7m)-beta-CD/HPMC showed similar absolute bioavailability compared to formulations not containing HPMC even though 80 % (in the case of (SBE)(7m)-beta-CD) or 40 % (in the case of beta-CD) less CD was used. In conclusion, the oral bioavailability of GBA was significantly increased by CD-complexation and the amount of CD needed was significantly reduced by co-administration of HPMC.