title: A novel multi-unit tablet for treating circadian rhythm diseases.
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.
authors: Pharmaceutical Research Institute, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing 210009, China.
authors: Qi
authors: Q
authors: Liu
authors: Yinhua
authors: Y
authors: Gong
authors: Yun
authors: Y
authors: Shi
authors: Liqun
authors: L
authors: Jiang
authors: Chunli
authors: C
authors: Zheng
authors: Liang
authors: L
authors: Ge
authors: Jianping
authors: J
authors: Liu
authors: Jiabi
authors: J
authors: Zhu
mesh_terms: D000284:Administration, Oral; D000787:Angina Pectoris / Q000188:drug therapy*; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000737:chemistry*; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D021081:Chronobiology Disorders / Q000188:drug therapy*; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005079:Excipients / Q000737:chemistry; D065347:Hypromellose Derivatives; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D007700:Kinetics; D008689:Methacrylates / Q000737:chemistry; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D011108:Polymers / Q000737:chemistry; D012995:Solubility; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D002317:Cardiovascular Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; C477853:Eudragit NE 30-D; D005079:Excipients; D008689:Methacrylates; D011108:Polymers; D013607:Tablets; D065347:Hypromellose Derivatives; C013517:ethyl cellulose; D002482:Cellulose; D008747:Methylcellulose; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate; C109691:microcrystalline cellulose
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