Bussemer T, Dashevsky A, Bodmeier R
College of Pharmacy, Freie Universität Berlin, Kelchstr. 31, 12169 Berlin, Germany.
J Control Release. 2003 Dec 12;93(3):331-9. doi: 10.1016/j.jconrel.2003.08.012.
The objective of this study was to develop and evaluate a pulsatile drug delivery system based on drug-containing hard gelatin capsules, which were coated with a swelling layer and an outer insoluble, water-permeable polymeric coating. An inner pressure developed by the swelling layer resulted in the rupture of the outer coating. Preliminary studies with a simulated rupture test demonstrated the dependence of the lag time prior to rupture on the properties of the coating, such as its water permeability and mechanical strength. The lag time increased with a higher coating level, but decreased with the addition of the hydrophilic pore former, hydroxypropyl methylcellulose. Increasing the amount of the swelling layer decreased the lag time. The coated capsules took up release medium at a nearly constant rate until a critical maximum was reached, where the swelling pressure was sufficient to rupture the outer coating. The rate of medium uptake decreased with increasing coating level, while the extent of medium uptake was almost the same for the different coating levels. A hydrophobic particulate material, magnesium stearate, was added to the coating layer to reduce the mechanical strength and therefore the lag time. The test conditions, such as surfactant addition to the release medium or floating vs. complete immersion of capsules in the medium, affected the lag time.
本研究的目的是开发并评估一种基于含药硬明胶胶囊的脉冲式给药系统，该胶囊涂覆有溶胀层和外部不溶性、水可渗透的聚合物涂层。溶胀层产生的内部压力导致外部涂层破裂。模拟破裂试验的初步研究表明，破裂前的滞后时间取决于涂层的性质，如透水性和机械强度。滞后时间随着涂层水平的提高而增加，但随着亲水性成孔剂羟丙基甲基纤维素的添加而减少。增加溶胀层的量会缩短滞后时间。包衣胶囊以几乎恒定的速率吸收释放介质，直到达到临界最大值，此时溶胀压力足以使外部涂层破裂。介质吸收速率随着涂层水平的增加而降低，而不同涂层水平的介质吸收程度几乎相同。向涂层中添加疏水性颗粒材料硬脂酸镁以降低机械强度，从而缩短滞后时间。试验条件，如向释放介质中添加表面活性剂或胶囊在介质中漂浮与完全浸没，会影响滞后时间。
