AAPS PharmSciTech

, 20:37 | Cite as

A Combined Utilization of Plasdone-S630 and HPMCAS-HF in Ziprasidone Hydrochloride Solid Dispersion by Hot-Melt Extrusion to Enhance the Oral Bioavailability and No Food Effect

  • Xu Xue
  • Guoguang Chen
  • Xiaoqing Xu
  • Jin Wang
  • Jingjing Wang
  • Lili Ren
Research Article


The purpose of this study was to research a novel combination of Plasdone-S630 and HPMCAS-HF as hot-melt carrier used in ziprasidone hydrochloride for enhanced oral bioavailability and dismissed food effect. Ziprasidone hydrochloride solid dispersion (ZH-SD) was prepared by hot-melt extrusion technique, and its optimized formulation was selected by the central composite design (CCD), which was characterized for powder X-ray diffraction (PXRD), fourier transform infrared spectroscopy (FTIR), in vitro dissolution study, and stability study. Finally, the in vivo study in fasted/fed state was carried out in beagle dogs. Based on PXRD analysis, HME technique successfully dispersed ziprasidone with a low crystallinity hydrochloride form in the polymers. According to the analysis of FTIR, hydrogen bonds were formed between drug and polymers during the process of HME. Without any noticeable bulk, crystalline could be found from the micrograph of ZH-SD when analyzed the result of scanning electron microscope (SEM). Pharmacokinetics studies indicated that the bioavailability of ZH-SD formulation had no significant difference in fasted and fed state, and the Cmax and AUC of ZH-SD were two fold higher than Zeldox® in fasted state. This result indicated that ziprasidone has achieved a desired oral bioavailability in fasted state and no food effect.


hot-melt extrusion ziprasidone hydrochloride HPMCAS-HF oral bioavailability food effect 



Self-nanoemulsifying drug delivery system


Hot-melt extrusion


Ziprasidone hydrochloride


Biopharmaceutical classification system


Ziprasidone hydrochloride solid dispersion


Ziprasidone hydrochloride physical mixture


Central composite design


Acetate buffered


Relative humidity


Cumulative dissolution of drugs in 10 min


Drug content



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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Xu Xue
    • 1
  • Guoguang Chen
    • 1
  • Xiaoqing Xu
    • 1
  • Jin Wang
    • 1
  • Jingjing Wang
    • 1
  • Lili Ren
    • 1
  1. 1.Nanjing Tech UniversityNanjingChina

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