DESIGN AND EVALUATION OF AN OSMOTIC PUMP TABLET (OPT) FOR PREDNISOLONE, A POORLY WATER-SOLUBLE DRUG, USING (SBE)(7M)-BETA-CD

Purpose. The purpose of this study was to develop a controlled-porosit y osmotic pump tablet (OPT) for poorly water soluble drugs using a sul fobutyl ether-beta-cyclodextrin, (SBE)(7m)-beta-CD or Captisol(TM), wh ich acted as both a solubilizer and as an osmotic agent. Methods. Pred nisolone (PDL) was chosen as a model drug for this study. The release of PDL from osmotic pump devices and tablets was studied. In vivo abso rption of PDL from OPT was evaluated in male beagle dogs. Results. PDL release from the osmotic pump tablet with (SBE)(7m)-beta-CD was compl ete. Another cyclodextrin, hydroxypropyl-beta-cyclodextrin (HP-beta-CD ), and a sugar mixture of lactose and fructose resulted in incomplete release. Although PDL release from the OPT with (SBE)(7m)-beta-CD and the sugar formulation displayed mainly zero-order release characterist ics, the tablet utilizing HP-beta-CD showed apparent first-order relea se characteristics. An in vivo absorption study in dogs correlated ver y well with the in vitro release profiles using the Japanese Pharmacop oeia dissolution method. Conclusions. The present results confirm that (SBE)(7m)-beta-CD can serve as both the solubilizer and the osmotic a gent for OPT of PDL, and modify the input rate of PDL without compromi sing oral bioavailability.