Floating drug delivery systems have been reported for different active pharmaceutical ingredients as single-unit tablets with gas-generating agents. In this present research, the formulation of floating multiple-unit minitablets of Nimodipine without using gas-generating agent was attempted with an objective of increased residence time, sustain-release and improved oral bioavailability. Solid dispersion with different ratios (1:0.5, 1:1, 1:1.5, 1:2, 1:2.5) of drug with the lipophilic carrier such as Compritol ATO 888, Gelucire 43/01, G39/01 and Precirol ATO 05 was formulated using melt granulation technique. The adsorbent Sylysia 350 to lipophilic carrier is maintained at 1:1. The granules were compressed into minitablets weighing 15 mg and were filled into a ‘0’ size capsule. Differential scanning calorimetry study justified no interaction of the drug with excipients. The formulations which exhibited desirable flow property, floating lag time less than 1 min and floating time of 12 h were further characterized for various post-compression parameters. The optimized single-dose (capsule) of floating multiple-unit minitablets of Nimodipine consisting of 60 mg of drug, 120 mg of G43/01 and 120 mg of Sylysia 350 showed an average of floating lag time within 24.48 s, floating time of 14.32 h and sustained-release up to 12 h. Pharmacokinetic study of the optimized formulation (F9) showed nearly 2.5 times increase in area under the curve with increased residence time in comparison to aqueous suspension of Nimodipine. The stability study revealed no significant change in various parameters before and after storage. Hence, gelucire 43/01-based multiple-unit minitablets of Nimodipine can be considered a promising approach for sustaining the drug release with gastric retention for 12 h without using gas-generating agent.

中文翻译：

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不使用产气剂的尼莫地平漂浮多单位微型片剂的配制和开发：体外和体内表征

浮动药物输送系统已被报道为具有气体发生剂的单一单位片剂的不同活性药物成分。在本研究中，以增加滞留时间，缓释和改善口服生物利用度为目的，尝试了不使用产气剂的尼莫地平多单位漂浮微型片剂的配方。具有亲脂性载体的药物与不同比例（1：0.5、1：1、1：1.5、1：2、1：2.5）的固体分散体，例如Compritol ATO 888，Gelucire 43/01，G39 / 01和Precirol ATO 05使用熔融造粒技术配制。Sylysia 350对亲脂性载体的吸附保持在1：1。将颗粒压制成重量为15mg的小片，​​并装入“ 0”号胶囊中。差示扫描量热法研究证明该药物与赋形剂没有相互作用。对于各种压缩后参数，进一步表征了表现出所需流动性，小于1分钟的漂浮滞后时间和12小时的漂浮时间的制剂。由60毫克药物，120毫克G43 / 01和120毫克Sylysia 350组成的尼莫地平漂浮多单位微型片剂的优化单剂量（胶囊）显示平均漂浮滞后时间为24.48 s，漂浮时间为14.32小时和持续释放长达12小时。优化的制剂（F9）的药代动力学研究表明，与尼莫地平的水悬浮液相比，曲线下面积增加了近2.5倍，停留时间增加了。稳定性研究表明，储存前后各种参数没有明显变化。因此，