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

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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.

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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

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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.

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  1. Weili Heng and Yuanfeng Wei contributed equally to this work.

Authors and Affiliations

  1. School of Pharmacy, China Pharmaceutical University, Nanjing, 211198, People’s Republic of China

    Weili Heng & Jianjun Zhang

  2. School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198,, People’s Republic of China

    Yuanfeng Wei, Shengyan Zhou, Di Ma, Yuan Gao & Shuai Qian

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  1. Weili Heng
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  2. Yuanfeng Wei
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Correspondence to Jianjun Zhang or Shuai Qian.

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Heng, W., Wei, Y., Zhou, S. et al. Effects of Temperature and Ionic Strength of Dissolution Medium on the Gelation of Amorphous Lurasidone Hydrochloride. Pharm Res 36, 72 (2019). https://doi.org/10.1007/s11095-019-2611-x

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