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A Uniform Ultra-Small Microsphere/SAIB Hybrid Depot with Low Burst Release for Long-Term Continuous Drug Release

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Abstract

Purpose

In the present study, a uniform ultra-small microsphere/sucrose acetate isobutyrate (SAIB) hybrid depot (m-SAIB depot) was designed to provide a long-term sustained release drug delivery system which not only reduced the burst release of an SAIB depot, but also eliminated the lag-time of PLGA microspheres.

Methods

Risperidone loaded m-SAIB depot (Ris-m-SAIB depot) was characterized by in vitro drug release, pharmacokinetics, in vivo degradation and biocompatibility, in comparison with risperidone loaded SAIB depot (Ris-SAIB depot).

Results

Ris-m-SAIB depot showed a low burst release (0.64%) and a reduced in vitro drug release rate due to the encapsulation of most drug in microspheres. After intramuscular administration, the in vivo burst release of Ris-m-SAIB was significantly decreased, as reflected by the low Cmax/Cs(4-td) (approximately 30-fold reduction), in comparison with Ris-SAIB depot. From 4 to 78 days, Ris-m-SAIB depot showed a higher plasma drug level (1.55 ~ 16.30 ng/ml) with a steadier drug release profile compared with Ris-SAIB depot. Ris-m-SAIB depot degraded gradually with a degradation t1/2 of 54.6 days and exhibited good biocompatibility in vivo.

Conclusion

These results demonstrate the potential application of a uniform ultra-small microsphere/SAIB hybrid depot for continuously delivering small drug molecules for long periods of time without burst release.

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Abbreviations

9-OH-Ris:

9-Hydroxyrisperidone

AUC:

Area under the curve

BA:

Benzyl alcohol

Cmax :

Maximum concentration

Cmin :

Minimum concentration

Cs :

Mean value of plasma concentration at steady-state

DAS:

Drug and statistics software

DCM:

Dichloromethane

EtOH:

Ethanol

HPLC:

High performance liquid chromatography

Mg(OH)2 :

Magnesium hydroxide

PBS:

Phosphate buffered saline

PLA:

Poly-lactide

PLGA:

Poly (lactide-coglycolide)

PVA:

Poly (vinyl alcohol)

Ris:

Risperidone

Ris-m-SAIB depot:

Risperidone loaded microsphere/SAIB hybrid depot

Ris-SAIB depot:

Risperidone loaded SAIB depot

SAIB:

Sucrose acetate isobutyrate

SEM:

Scanning electron microscopy

SPG:

membrane Shirasu porous glass membrane

t1/2 :

Half-life

UPLC–MS/MS:

Ultra performance liquid chromatography-tandem mass spectrometry

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ACKNOWLEDGMENTS AND DISCLOSURES

Dr. David B Jack is gratefully thanked for correcting English of the manuscript.

Author information

Authors and Affiliations

  1. School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, People’s Republic of China

    Xia Lin, Yuhong Xu & Jian Chen

  2. School of Pharmaceutical Science, Jiangnan University, 1800 Lihu Road, Wuxi, 214122, People’s Republic of China

    Xia Lin & Ziyi Yang

  3. Department of Pharmaceutics Science, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, People’s Republic of China

    Xing Tang, Yu Zhang & Haibing He

  4. Normal College, Shenyang University, Shenyang, 110044, People’s Republic of China

    Yan Zhang

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  1. Xia Lin
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  2. Yuhong Xu
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Correspondence to Xia Lin or Ziyi Yang.

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Lin, X., Xu, Y., Tang, X. et al. A Uniform Ultra-Small Microsphere/SAIB Hybrid Depot with Low Burst Release for Long-Term Continuous Drug Release. Pharm Res 32, 3708–3721 (2015). https://doi.org/10.1007/s11095-015-1731-1

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  • DOI: https://doi.org/10.1007/s11095-015-1731-1

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