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Preparation and in vitro/in vivo evaluation of PLGA microspheres containing norquetiapine for long-acting injection

Authors Park CW, Lee HJ, Oh DW, Kang JH, Han CS, Kim DW

Received 12 September 2017

Accepted for publication 15 January 2018

Published 5 April 2018 Volume 2018:12 Pages 711—719

DOI https://doi.org/10.2147/DDDT.S151437

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Georgios D. Panos


Chun-Woong Park,1 Hyo-Jung Lee,1 Dong-Won Oh,1 Ji-Hyun Kang,1 Chang-Soo Han,1 Dong-Wook Kim2

1College of Pharmacy, Chungbuk National University, Cheongju, Republic of Korea; 2Department of Pharmaceutical Engineering, Cheongju University, Cheongju, Republic of Korea

Background: Norquetiapine (N-desalkyl quetiapine, NQ) is an active metabolite of quetiapine with stable pharmacokinetic and pharmacological properties. However, its short half-life is a drawback for clinical applications, and long-acting formulations are required.
Purpose: The objectives of this study were to prepare improved entrapment efficiency NQ freebase microspheres by the solvent evaporation method with poly(d,l-lactic-co-glycolic acid) (PLGA) as a release modulator and to evaluate their physicochemical and in vitro/in vivo release properties.
Methods: NQ freebase PLGA (1:5 w/w) formulations were prepared by the oil-in-water (o/w) emulsion–solvent evaporation method. A solution of the drug and PLGA in 9:1 v/v dichloromethane:ethanol was mixed with 0.2% polyvinyl alcohol and homogenized at 2,800 rpm. The emulsion was stirred for 3 h to dilute and evaporate the solvent. After that, the resulting product was freeze-dried. Drug-loading capacity was measured by the validated RP-HPLC method. The surface morphology of the microspheres was observed by scanning electron microscopy (SEM), and the physicochemical properties were evaluated by differential scanning calorimetry, powder X-ray diffraction, and Fourier-transform infrared spectroscopy particle size distribution. The in vitro dissolution test was performed using a rotary shaking bath at 37°C, with constant shaking at 50 rpm in sink condition.
Results: The NQ freebase microspheres prepared by o/w emulsion-solvent evaporation showed over 30 % efficiency. NQ was confirmed to be amorphous in the microspheres by powder X-ray diffraction and differential scanning calorimetry. Special chemical interaction in the microspheres was not observed by FT-IR. The in vitro dissolution test demonstrated that the prepared microspheres' release properties were maintained for more than 20 days. The in vivo test is also confirmed that the particles' long acting of the particle were maintained. Therefore, good in vitro–in vivo correlation was established.
Conclusion: In this study, NQ freebase-PLGA microspheres showed potential for the treatment of schizophrenia for long-periods.

Keywords: schizophrenia, freebase, o/w emulsion-solvent evaporation, freeze dry, active metabolite, IVIVC

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