Pharmaceutical Research Institute, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing 210009, China.
AAPS PharmSciTech. 2013 Jun;14(2):861-9. doi: 10.1208/s12249-013-9975-8. Epub 2013 May 7.
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.
本研究旨在开发和评估一种新型的多单位片剂，该片剂将微丸与缓控释包衣和具有时控包衣的片剂相结合，用于治疗昼夜节律疾病。模型药物单硝酸异山梨酯（ISMN）被喷涂在微晶纤维素（MCC）基微丸上，并包衣以 Eudragit（®）NE30D，作为缓控释层。包衣微丸与缓冲剂（MCC PH-200/MCC KG-802/PC-10 的混合物，比例为 40:40:20）以 4:6 的比例使用单冲压片机进行压缩。采用常规盘式包衣工艺，施加 OpadryII 隔离层、HPMC E5 溶胀层和 Surelease（®）可破裂层。采用中心复合设计响应面法研究这些涂层对 4 小时时间段内释放时间差异的平方的影响。对制剂微丸和片剂进行药物释放研究，以研究释放行为，并使用扫描电子显微镜（SEM）监测微丸和片剂及其横截面形态。实验结果表明，该系统具有脉冲溶解曲线，包括 4 小时的滞后期和 4 小时的缓释时间。与目前市售制剂相比，这种片剂可为昼夜节律疾病提供更好的治疗选择。
