Krögel I, Bodmeier R
College of Pharmacy, Freie Universität Berlin, Germany.
Pharm Res. 1998 Mar;15(3):474-81. doi: 10.1023/a:1011940718534.
The objective of this study was to develop and evaluate a pulsatile drug delivery system based on an impermeable capsule body filled with drug and an erodible plug placed in the opening of the capsule body.
The erodible plugs were either prepared by direct compression followed by placing the tablets in the capsule opening or by congealing a meltable plug material directly within the capsule opening. The disintegration/erosion properties of these plugs were determined and optimized for the final delivery system. In order to assure rapid drug release of the capsule content after erosion of the plug, various excipients (fillers, effervescent agents) and drugs with different solubilities were evaluated. The lag time prior to drug release and the subsequent drug release were investigated as function of capsule content, plug composition, plug preparation technique, plug hardness, weight, and thickness.
The erosion time of the compressed plugs increased with increasing molecular weight of the hydrophilic polymer (e.g. hydroxypropyl methylcellulose, polyethylene oxide), decreasing filler (lactose) content and decreased with congealable lipidic plugs with increasing HLB-value and inclusion on surfactants. For complete and rapid release of the drug from the capsule body, effervescent agents had to be included in the capsule content. The drug delivery system showed typical pulsatile release profiles with a lag time followed by a rapid release phase. The lag time prior to the pulsatile drug release correlated well with the erosion properties of the plugs and, besides the composition of the plug, could be controlled by the thickness (weight) of the plug.
A single-unit, capsular-shaped pulsatile drug delivery system was developed wherein the pulsatile release was controlled by the erosion properties of a compressed or congealed plug placed within the opening of the capsule opening.
本研究的目的是开发并评估一种基于不透性胶囊体（填充药物）和置于胶囊体开口处的可蚀塞的脉冲式药物递送系统。
可蚀塞通过直接压片制备，然后将片剂置于胶囊开口处，或者通过在胶囊开口内直接凝固可熔塞材料来制备。测定并优化这些塞子的崩解/侵蚀特性以用于最终的递送系统。为确保塞子侵蚀后胶囊内容物能快速释放药物，评估了各种辅料（填充剂、泡腾剂）以及不同溶解度的药物。研究了药物释放前的滞后时间以及随后的药物释放情况，作为胶囊内容物、塞子组成、塞子制备技术、塞子硬度、重量和厚度的函数。
压缩塞的侵蚀时间随着亲水性聚合物（如羟丙基甲基纤维素、聚环氧乙烷）分子量的增加而增加，随着填充剂（乳糖）含量的降低而增加，并且随着具有增加的HLB值和包含表面活性剂的可凝固脂质塞而降低。为使药物从胶囊体中完全且快速释放，胶囊内容物中必须包含泡腾剂。该药物递送系统呈现出典型的脉冲式释放曲线，先是有一个滞后时间，随后是快速释放阶段。脉冲式药物释放前的滞后时间与塞子的侵蚀特性密切相关，并且除了塞子的组成外，还可以通过塞子的厚度（重量）来控制。
开发了一种单单元的胶囊形脉冲式药物递送系统，其中脉冲式释放由置于胶囊开口处的压缩或凝固塞的侵蚀特性控制。
