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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
  • 29 Downloads

Abstract

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.

KEY WORDS

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

Abbreviations

SNEDDS

Self-nanoemulsifying drug delivery system

HME

Hot-melt extrusion

ZH

Ziprasidone hydrochloride

BSC

Biopharmaceutical classification system

ZH-SD

Ziprasidone hydrochloride solid dispersion

ZH-PM

Ziprasidone hydrochloride physical mixture

CCD

Central composite design

NaAc-HAc

Acetate buffered

RH

Relative humidity

Q10

Cumulative dissolution of drugs in 10 min

DC

Drug content

Notes

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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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