Osmotic pump tablets with solid dispersions synergized by hydrophilic polymers and mesoporous silica improve in vitro/in vivo performance of cilostazol.

ABSTRACT

The purpose of this study is to improve in vitro dissolution and in vivo bioavailability of the poorly soluble drug cilostazol (CLT) through amorphous solid dispersion technology, and this study prepared a stable supersaturated drug-loaded system to improve the problem of high free energy and instability of traditional solid dispersions. The optimized formulation of the solid dispersion is CLT Syloid®244FP Kolliphor®P188 = 11.51.5 (CLT-SD), where the co-loading of Syloid®244FP and Kolliphor®P188 has the synergistic effect. Drug polymers interactions and drug morphology were estimated by the physicochemical characterization, including DSC XRD, SEM, TEM, FT-IR, and Specific area analysis. Optimized formulation kept most drug in an amorphous state without significant change in dissolution, which could be maintained for at least 1 year. The solid dispersion was further prepared into osmotic pump tablets for the purpose of the controlled-release of drugs. The bioavailability of the three preparations (CLT, CLT-SD, osmotic pump tablets) was evaluated in Beagle dogs, which results clarified that the oral bioavailability of CLT-SD improved as compared with the CLT powder and osmotic pump tablets achieved controlled-release of drugs. In conclusion, co-loading drugs with mesoporous silica and hydrophilic polymer compounds can be a guiding future modification method for delivering supersaturated drug loading systems.