Sustained Release Ziprasidone Microparticles Prepared by Spray Drying with Soluplus® and Ethyl Cellulose to Eliminate Food Effect and Enhance Bioavailability

Abstract

The purpose of this study was to develop and evaluate a new formulation of ziprasidone (ZIP) for improved fasted state absorption and sustained drug release. ZIP solid dispersions were produced via spray drying using Soluplus®, an amphiphilic polymer, as the solubility enhancer. Physicochemical analysis proved that ZIP presented at amorphous state in the spray-dried microparticles and the dissolution rate of ZIP from the Soluplus®-ZIP composite microparticles was significantly increased compared with that of the physical mixtures. Commonly used encapsulation materials including Eudragit® RL, Eudragit® S100 and Ethyl Cellulose were incorporated into the solid dispersions to regulate the drug release kinetics. The formulation containing ethyl cellulose provided the most sustained release behaviors. Pharmacokinetic studies in beagle dogs confirmed that there was no significant difference in oral bioavailability of the microparticles under fasted and fed states, and a prolonged Tmax value was simultaneously achieved compared with the commercial ZIP capsules.

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Abbreviations

AUC:

Area under the curve

ZIP:

Ziprasidone

SEM:

Scanning electron microscopy

XRD:

X-ray diffraction

FTIR:

Fourier-transform infrared spectroscopy

HPLC:

High-performance liquid chromatography

SOL:

Soluplus®

RL:

Eudragit® RL

S100:

Eudragit® S100

EC:

Ethyl cellulose

PM-1:

Physical mixture of Soluplus® and Ziprasidone (4:1)

PM-2:

Physical mixture of Soluplus®, Ziprasidone and Ethyl Cellulose (6:1:4)

SZ-1:

Soluplus®: Ziprasidone = 4:1

SZEC-5:

Soluplus®: Ziprasidone: Ethyl Cellulose = 6:1:4

MRT:

Mean residence time

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Acknowledgements

The authors would like to acknowledge financial support from National Natural Science Foundation of China (Grant No. 81503023).

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Correspondence to Wenjie Liu or Niyanhan Jiang.

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Liu, W., Wang, S., Lu, W. et al. Sustained Release Ziprasidone Microparticles Prepared by Spray Drying with Soluplus® and Ethyl Cellulose to Eliminate Food Effect and Enhance Bioavailability. AAPS PharmSciTech 21, 27 (2020). https://doi.org/10.1208/s12249-019-1592-8

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KEY WORDS

  • ziprasidone
  • solid dispersion
  • spray drying
  • food effect
  • sustained release