Division of Pharmaceutical Sciences, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0NR, UK.
J Pharm Sci. 2009 Nov;98(11):4251-63. doi: 10.1002/jps.21739.
Three time-delayed capsule (TDC) formulations were investigated in a pharmacoscintigraphic study, using a three-way crossover design in eight healthy male volunteers. Additionally, the pulsed release of a TDC was investigated with time-lapse photography, using a nondisintegrating riboflavin tablet. The photographic study indicated how the release characteristics of the TDC relied on the erosion of a tablet containing hypromellose (HPMC). Each TDC was duel radio labelled with indium-111 and technetium-99 m DTPA complexes, to observe drug release scintigraphically (theophylline was a marker compound). Three formulations, having in vitro dissolution release times of 1.8, 2.9 or 4.0 h were shown to compare favourably with mean in vivo scintigraphic release times of 2.7, 3.0 and 4.0 h for each formulation containing 20, 24 or 35% (w/w) HPMC concentrations respectively. An increase in HPMC concentration was associated with a delayed technetium release time, and followed the same rank order as the in vitro dissolution study. Observed radiolabel dispersion always occurred in the small intestine. In conclusion, the study established that the TDC performs and demonstrates an in vitro-in vivo correlation. Additionally, time and site of release were accurately visualized by gamma scintigraphy, and confirmed with determination of theophylline absorption.
在一项采用三交叉设计的 8 名健康男性志愿者的药物闪烁照相研究中，考察了三种时滞胶囊（TDC）制剂。此外，还通过使用不崩解的核黄素片剂的延时摄影研究了 TDC 的脉冲释放。摄影研究表明，TDC 的释放特性如何依赖于含有羟丙甲纤维素（HPMC）的片剂的侵蚀。每个 TDC 均用铟-111 和锝-99m DTPA 复合物双重放射性标记，以通过闪烁扫描观察药物释放（茶碱是一种标记化合物）。三种制剂的体外溶解释放时间分别为 1.8、2.9 或 4.0 小时，与每种制剂的平均体内闪烁释放时间 2.7、3.0 和 4.0 小时相比表现良好，每个制剂分别含有 20%、24%或 35%（w/w）的 HPMC 浓度。HPMC 浓度的增加与锝释放时间的延迟有关，并且与体外溶解研究的顺序相同。观察到的放射性标记弥散总是发生在小肠中。总之，该研究表明 TDC 具有良好的性能并表现出体内-体外相关性。此外，通过伽马闪烁扫描可以准确地可视化释放时间和部位，并通过茶碱吸收的测定进行确认。
