The intention of this study was to compare the physicochemical properties, stability
and bioavailability of a clopidogrel napadisilate (CN)-loaded solid dispersion (SD)
and solid self-microemulsifying drug delivery system (solid SMEDDS). SD was prepared
by a surface attached method using different ratios of Cremophor RH60 (surfactant)
and HPMC (polymer), optimized based on their drug solubility. Liquid SMEDDS was composed
of oil (peceol), a surfactant (Cremophor RH60) and a co-surfactant (Transcutol HP).
A pseudo-ternary phase diagram was constructed to identify the emulsifying domain,
and the optimized liquid SMEDDS was spray dried with an inert solid carrier (silicon
dioxide), producing the solid SMEDDS. The physicochemical properties, solubility,
dissolution, stability and pharmacokinetics were assessed and compared to clopidogrel
napadisilate (CN) and bisulfate (CB) powders. In solid SMEDDS, liquid SMEDDS was absorbed
or coated inside the pores of silicon dioxide. In SD, hydrophilic polymer and surfactants
were adhered onto drug surface. The drug was in crystalline and molecularly dispersed
form in SD and solid SMEDDS, respectively. Solid SMEDDS and SD greatly increased the
solubility of CN but gave lower drug solubility compared to CB powder. These preparations
significantly improved the dissolution of CN, but the latter more increased than the
former. Stability under accelerated condition showed that they were more stable compared
to CB powder, and SD was more stable than solid SMEDDS. They significantly increased
the oral bioavailability of CN powder. Furthermore, SD showed significantly improved
oral bioavailability compared to solid SMEDDS and CB powder. Thus, SD with excellent
stability and bioavailability is recommended as an alternative for the clopidogrel-based
oral formulation.