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Effects of Temperature and Ionic Strength of Dissolution Medium on the Gelation of Amorphous Lurasidone Hydrochloride

  • Weili Heng
  • Yuanfeng Wei
  • Shengyan Zhou
  • Di Ma
  • Yuan Gao
  • Jianjun ZhangEmail author
  • Shuai QianEmail author
Research Paper
  • 229 Downloads

Abstract

Purpose

Amorphous lurasidone hydrochloride (LH) showed decreased dissolution behavior in comparison to crystalline LH owing to gelation during dissolution as reported in our previous study. The current study aims to investigate external factors including temperature and ionic strength on the gelation and hence the dissolution of amorphous LH.

Methods

Dissolution tests of amorphous LH were performed under different temperatures and buffer ionic strengths. The formed gels were characterized by rheology study, texture analysis, PLM, SEM, DSC, XRPD and FTIR.

Results

With the increase of temperature and ionic strength of medium, the dissolution of amorphous LH decreased, while the strength, hardness and adhesiveness of in situ formed gel enhanced. Amorphous LH converted into its crystalline state during dissolution and the crystallization rate was affected by medium conditions. With medium temperature increasing from 30°C to 45°C, the gel microstructure changed from interconnecting fibrillar network to spherical particle aggregate. On the other hand, the formed spherulitic gel aggregate exhibited increased particle size when increasing the ionic strength of medium.

Conclusions

With increase of temperature and ionic strength, the gel strength of in situ formed gel from amorphous LH enhanced with more compact microstructure, subsequently leading to decreased dissolution profiles.

Keywords

Lurasidone hydrochloride Amorphous gelation temperature ionic strength 

Abbreviations

BCS

Biopharmaceutics Classification System

DSC

Differential scanning calorimetry

FTIR

Fourier transform infrared spectroscopy

HPMC

Hydroxypropyl methylcellulose

LH

Lurasidone hydrochloride

PLM

Polarized light microscopy

SEM

Scanning electron microscopy

XRPD

X-ray powder diffraction

Notes

ACKNOWLEDGMENTS AND DISCLOSURES

This research was supported by National Natural Science Foundation of China (81,703,712, 81,773,675, 81,873,012), “Double First-Class” University Project (CPU2018GY11, CPU2018GY27), Top-notch Academic Programs Project of Jiangsu Higher Education Institutions (TAPP), Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), Jiangsu Province Double Innovation Talent Program (2015), Postgraduate Research & Practice Innovation Program of Jiangsu Province. The authors declare no competing financial interest.

Supplementary material

11095_2019_2611_MOESM1_ESM.docx (606 kb)
ESM 1 (DOCX 606 kb)

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.School of PharmacyChina Pharmaceutical UniversityNanjingPeople’s Republic of China
  2. 2.School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjingPeople’s Republic of China

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