Isosorbide-5-mononitrate (5-ISMN) sustained-release pellets prepared by double layer coating for reducing 5-ISMN migration and sublimation.
The major aim of this study was to prepare isosorbide-5-mononitrate (5-ISMN) sustained-release pellets and evaluate their stability. The pellets were prepared by extrusion/spheronization, and then the core pellets were coated with ethylcellulose (EC 10cp) and Eudragit(®)NE30D. Here, EC was used as the subcoating agent while Eudragit(®)NE30D acted as the outer-coating agent. 5-ISMN sustained-release pellets as a novel drug delivery system contained the immediate-release portion in the outer-coating layer. Unexpectedly, 5-ISMN was found to migrate from the interior of the pellets to the surface forming needle crystals and exhibited the phenomenon of sublimation, which resulted in a tremendous increase in the release rate. Our research showed that the migration and sublimation of the active ingredient was related to the temperature and humidity. Polyvinylpyrrolidone (PVP K30) can affect the precipitation of 5-ISMN by forming a charge transfer complex between the drug and PVP, while hydroxypropyl methyl cellulose (HPMC E5) had no effect, and confirmed the correctness of this view through photographs and IR spectra. In the investigation of the stability, the results showed that there was no sublimation and migration while the pellets stored at 25°C/60%RH (ambient conditions) and 40°C/75% RH (stress conditions) during a 6-month period.
Li
Guofei
G
Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, China.
Han
Dandan
D
Guan
Tingting
T
Zhao
Xingna
X
He
Haibing
H
Tang
Xing
X
D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry; D006813:Humidity; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D012995:Solubility; D013678:Technology, Pharmaceutical; D013696:Temperature
D003692:Delayed-Action Preparations; D005079:Excipients; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; C013517:ethyl cellulose; D002482:Cellulose; D011205:Povidone; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate