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AAPS PharmSciTech

, Volume 14, Issue 2, pp 861–869 | Cite as

A Novel Multi-Unit Tablet for Treating Circadian Rhythm Diseases

  • Qi Liu
  • Yinhua Gong
  • Yun Shi
  • Liqun Jiang
  • Chunli Zheng
  • Liang Ge
  • Jianping Liu
  • Jiabi Zhu
Research Article

Abstract

This study aimed to develop and evaluate a novel multi-unit tablet that combined a pellet with a sustained-release coating and a tablet with a pulsatile coating for the treatment of circadian rhythm diseases. The model drug, isosorbide-5-mononitrate, was sprayed on microcrystalline cellulose (MCC)-based pellets and coated with Eudragit® NE30D, which served as a sustained-release layer. The coated pellets were compressed with cushion agents (a mixture of MCC PH-200/ MCC KG-802/PC-10 at a ratio of 40:40:20) at a ratio of 4:6 using a single-punch tablet machine. An isolation layer of OpadryII, swellable layer of HPMC E5, and rupturable layer of Surelease® were applied using a conventional pan-coating process. Central-composite design-response surface methodology was used to investigate the influence of these coatings on the square of the difference between release times over a 4 h time period. Drug release studies were carried out on formulated pellets and tablets to investigate the release behaviors, and scanning electron microscopy (SEM) was used to monitor the pellets and tablets and their cross-sectional morphology. The experimental results indicated that this system had a pulsatile dissolution profile that included a lag period of 4 h and a sustained-release time of 4 h. Compared to currently marketed preparations, this tablet may provide better treatment options for circadian rhythm diseases.

KEY WORDS

central composite design circadian rhythm diseases in vitro dissolution study multi-unit tablet sustained-release and pulsatile coating 

Abbreviations

5-ISMN

Isosorbide-5-mononitrate

MCC

Microcrystalline cellulose

PC

Pregelatinized starch

HPMC

Hydroxypropyl methyl cellulose

h

Hours

min

Minutes

rpm

Rotations per minute

ANOVA

Analysis of variance

GMS

Glyceryl monostearate

Notes

ACKNOWLEDGMENTS

This study was financially supported by a program supporting scientific research conducted by college graduates in Jangsu Province (No. CXLX12_0313). We would like to thank the Asahi Kasei, ISP, Evonik and Colorcon Corporations for providing the blank MCC pellets, excipients, and coating materials.

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Copyright information

© American Association of Pharmaceutical Scientists 2013

Authors and Affiliations

  1. 1.Pharmaceutical Research InstituteChina Pharmaceutical UniversityNanjingChina

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