ORAL DISINTEGRATING TABLETS OF CILOSTAZOL-HP-β-CD INCLUSION COMPLEX

Low solubility and biovariability associated with cilostazol (CLZ) pose serious formulation problems despite several advancements in dosage form design. The present research work amalgamates two different solubility enhancement techniques, viz. spray drying and cyclodextrin inclusion complexation to produce amorphous composites of CLZ with increased solubility and dissolution characteristics. FTIR studies unveiled inclusion/ interaction of cyclohexane ring and tetrazole moiety of CLZ in the hydroxypropyl-beta-cyclodextrin (HP-β-CD) cavity. Thermal analysis by DSC showed a decrease in melting points of CLZ and HP-β-CD, indicating favorable complex formation. P-XRD studies revealed reduction in crystallinity and amorphization of CLZ in the complex. SEM indicated a drastic change in surface morphology compared to pure CLZ. These complexes were compressed into oral disintegrating tablets (ODTs) using direct compression technique. The ODTs were characterized for disintegration time, wetting time and in vitro dissolution. Remarkable improvement in solubility and in vitro dissolution characteristics was observed for ODTs in water and compendial dissolution media. Inclusion complexation with HP-β-CD, amorphous composites produced by spray drying technique and the use of multi-functional co-processed excipients like Pearlitol SD-200, Kollidon CL and MCC-200 are responsible for increased solubility and dissolution of CLZ