PMID- 32311456
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240227
IS  - 1879-0720 (Electronic)
IS  - 0928-0987 (Linking)
VI  - 149
DP  - 2020 Apr 18
TI  - Static and dynamic structural features of single pellets determine the release 
      behaviors of metoprolol succinate sustained-release tablets.
PG  - 105324
LID - S0928-0987(20)30113-5 [pii]
LID - 10.1016/j.ejps.2020.105324 [doi]
AB  - The multiple-unit sustained-release (MUSR) dosage forms containing numerous 
      sustained-release subunits present a reliable choice for oral formulation of 
      controlled release systems. As a typical MUSR, the metoprolol succinate 
      sustained-release tablet is an advanced system with limited researches devoted to 
      relating its structure to the drug release phase other than the preparation 
      process and modulation to the release behaviors. This research details a 
      three-dimension method to image the internal structure and detail drug release 
      features of commercial metoprolol succinate sustained-release tablets and 
      component individual single pellets. As such, a new perspective for MUSR dosage 
      form is provided. Using high energy synchrotron radiation X-ray microcomputed 
      tomography (SR-muCT), the in-situ structure parameters were obtained 
      nondestructively. It was demonstrated that the average number of spherical 
      pellets in a tablet was 853 +/- 12 (n = 3). The average volume of the pellets was 
      0.09 +/- 0.01 mm(3), the diameter was 0.55 +/- 0.03 mm, and the sphericity was 0.87 +/- 
      0.06. These data reflected the numerical features of pellets in MUSR tablets, 
      which were helpful for reverse engineering to MUSR. Based on the three 
      dimensional model generated by image processing and analysis software, the pellet 
      structures were divided into three layers of typical depot sustained release 
      system: pellet core, drug-containing layer and outer film. The dynamic structural 
      features determined refer to the changes of structures in pellets during in vitro 
      drug release, with evidence that the coating layer on the pellets maintained a 
      spherical morphology whilst numerous valleys appeared on the surface. The 
      material constitution and distribution in coating layer were evaluated by 
      synchrotron radiation-based Fourier transform infrared mapping and results 
      indicated a composition of hydroxypropyl methylcellulose dispersed in ethyl 
      cellulose. Knowledge of these structural characteristics confirmed that the 
      mechanism of sustained drug release was membrane controlled and consistent with 
      the drug release profiles. In conclusion, the structural investigation provided 
      knowledge of the intrinsic quality of metoprolol succinate sustained-release 
      tablets and offers guidance for reverse engineering of MUSR.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Sun, Xian
AU  - Sun X
AD  - Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese 
      Academy of Sciences, Shanghai 201210, China; University of Chinese Academy of 
      Sciences, Beijing 100049, China.
FAU - Wu, Li
AU  - Wu L
AD  - Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese 
      Academy of Sciences, Shanghai 201210, China.
FAU - Maharjan, Abi
AU  - Maharjan A
AD  - Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese 
      Academy of Sciences, Shanghai 201210, China; University of Chinese Academy of 
      Sciences, Beijing 100049, China.
FAU - Sun, Hongyu
AU  - Sun H
AD  - Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese 
      Academy of Sciences, Shanghai 201210, China.
FAU - Hu, Xiaoxiao
AU  - Hu X
AD  - Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese 
      Academy of Sciences, Shanghai 201210, China.
FAU - York, Peter
AU  - York P
AD  - Institute of Pharmaceutical Innovation, University of Bradford, Bradford, West 
      Yorkshire BD7 1DP, United Kingdom.
FAU - Sun, Huimin
AU  - Sun H
AD  - NMPA, Key Laboratory of Excipient Quality Research and Evaluation, Beijing 
      100050, China. Electronic address: sunhm@126.com.
FAU - Zhang, Jiwen
AU  - Zhang J
AD  - Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese 
      Academy of Sciences, Shanghai 201210, China; University of Chinese Academy of 
      Sciences, Beijing 100049, China; NMPA, Key Laboratory of Excipient Quality 
      Research and Evaluation, Beijing 100050, China. Electronic address: 
      jwzhang@simm.ac.cn.
FAU - Yin, Xianzhen
AU  - Yin X
AD  - Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese 
      Academy of Sciences, Shanghai 201210, China; NMPA, Key Laboratory of Excipient 
      Quality Research and Evaluation, Beijing 100050, China. Electronic address: 
      xzyin@mail.shcnc.ac.cn.
LA  - eng
PT  - Journal Article
DEP - 20200418
PL  - Netherlands
TA  - Eur J Pharm Sci
JT  - European journal of pharmaceutical sciences : official journal of the European 
      Federation for Pharmaceutical Sciences
JID - 9317982
SB  - IM
OTO - NOTNLM
OT  - Metoprolol succinate
OT  - Multiple-unit pellet system
OT  - Sustained release
OT  - Synchrotron radiation X-ray micro-computed tomography
EDAT- 2020/04/21 06:00
MHDA- 2020/04/21 06:01
CRDT- 2020/04/21 06:00
PHST- 2019/12/06 00:00 [received]
PHST- 2020/03/24 00:00 [revised]
PHST- 2020/03/24 00:00 [accepted]
PHST- 2020/04/21 06:01 [medline]
PHST- 2020/04/21 06:00 [pubmed]
PHST- 2020/04/21 06:00 [entrez]
AID - S0928-0987(20)30113-5 [pii]
AID - 10.1016/j.ejps.2020.105324 [doi]
PST - aheadofprint
SO  - Eur J Pharm Sci. 2020 Apr 18;149:105324. doi: 10.1016/j.ejps.2020.105324.