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Physicochemical Characterization and Pharmacokinetics of Agomelatine-Loaded PLGA Microspheres for Intramuscular Injection

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Abstract

Purpose

The aim of this study was to design agomelatine loaded long acting injectable microspheres, with an eventual goal of reducing the frequency of administration and improving patient compliance in treatment of depression.

Methods

AGM-loaded microspheres were prepared by an O/W emulsion solvent evaporation method. The physicochemical properties and in vitro performance of the microspheres were characterized. The pharmacokinetics of different formulations with various particle sizes and drug loadings were evaluated.

Results

AGM-loaded microspheres with drug loading of 23.7% and particle size of 60.2 μm were obtained. The in vitro release profiles showed a small initial burst release (7.36%) followed by a fast release, a period of lag time and a second accelerated release. Pore formation and pore closure were observed in vitro, indicating that the release of drug from microspheres is dominated by water-filled pores. Pharmacokinetic studies showed that AGM microspheres could release up to 30 days in vivo at a steady plasma concentration. As well, particle size and drug loading could significantly influence the in vivo release of AGM microspheres.

Conclusions

AGM-loaded microspheres are a promising carrier for the treatment of major depressant disorder.

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Abbreviations

AGM:

Agomelatine

AUC:

Area under the curve

Cmax :

Maximum concentration

DALYs:

Disability adjusted life years

DAS:

Drug and statistics software

DSC:

Differential scanning calorimetry

EMA:

European Medicines Agency

FDA:

Food and drug administration

MDD:

Major depressive disorder

PLGA:

Poly (D,L-lactide- co-glycolide)

PXRD:

Powder X-ray diffraction

SD:

Standard deviation

SDS:

Sodium dodecyl sulfate

SEM:

Scanning electron microscopy

T1/2 :

Plasma half-life

Tmax:

Peak time

UPLC-MS/MS:

Ultra-performance liquid chromatography-tandem mass spectrometry

YLDs:

Years lived with disability

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Authors and Affiliations

  1. School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China

    Hongjuan Zhang, Chenguang Pu, Qiao Wang, Xinyi Tan, Jingxin Gou, Haibing He, Yu Zhang, Tian Yin, Yanjiao Wang & Xing Tang

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  1. Hongjuan Zhang
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  2. Chenguang Pu
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  3. Qiao Wang
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  7. Yu Zhang
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  9. Yanjiao Wang
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Correspondence to Yanjiao Wang.

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Zhang, H., Pu, C., Wang, Q. et al. Physicochemical Characterization and Pharmacokinetics of Agomelatine-Loaded PLGA Microspheres for Intramuscular Injection. Pharm Res 36, 9 (2019). https://doi.org/10.1007/s11095-018-2538-7

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  • DOI: https://doi.org/10.1007/s11095-018-2538-7

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