Controlled and complete release of a model poorly water-soluble drug, prednisolone, from hydroxypropyl methylcellulose matrix tablets using (SBE)(7m)-beta-cyclodextrin as a solubilizing agent.
Sustained-release formulations such as hydroxypropyl methylcellulose (HPMC)-based hydrophilic matrix tablets of poorly water-soluble drugs often result in incomplete release because of the poor solubility and dissolution rate of the drug in the hydrophilic matrix. Sulfobutylether-beta-cyclodextrins ((SBE)(7M)-beta-CDs) have been known to improve the solubility of such drugs by forming inclusion complexes. The present paper deals with the modification of drug release from an HPMC-based matrix tablet of a sparingly water-soluble drug, prednisolone (PDL), using (SBE)(7M)-beta-CD as a solubilizing agent. Tablets were prepared by direct compression of a physically mixed PDL, (SBE)(7M)-beta-CD, and polymer. On exposure to water, an in situ PDL:(SBE)(7M)-beta-CD complex was formed in the gel layer, and enhanced drug release relative to a control formulation was observed (lactose used as the excipient instead of (SBE)(7M)-beta-CD ). Other possible changes due to the incorporation of (SBE)(7M)-beta-CD in the formulation were also probed. Incorporation of (SBE)(7M)-beta-CD lead to a higher water uptake relative to the control (lactose) formulation. For a fixed total tablet weight, polymer type, and loading, the drug release rate appeared to depend on the molar ratio of (SBE)(7M)-beta-CD to PDL and not the absolute amount of (SBE)(7M)-beta-CD present in the matrix tablet. This work shows that incorporation of (SBE)(7M)-beta-CD into the matrix tablets could be considered in designing a sustained-release tablet of poorly water-soluble drugs.
Rao
V M
VM
The Department of Pharmaceutical Chemistry, 2095 Constant Avenue, The University of Kansas, Lawrence, Kansas 66047, USA.
Haslam
J L
JL
Stella
V J
VJ
D003505:Cyclodextrins / Q000008:administration & dosage*; D007785:Lactose / Q000008:administration & dosage* / Q000031:analogs & derivatives; D008747:Methylcellulose / Q000008:administration & dosage* / Q000031:analogs & derivatives; D010078:Oxazines; D011239:Prednisolone / Q000008:administration & dosage* / Q000737:chemistry; D012995:Solubility; D013607:Tablets; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D010078:Oxazines; C103513:SBE7-beta-cyclodextrin; D013607:Tablets; D047392:beta-Cyclodextrins; D008747:Methylcellulose; C071191:MK 458; D011239:Prednisolone; D007785:Lactose