Development of a sustained release dosage form for α-lipoic acid.: II.: Evaluation in human volunteers
Development of a sustained release dosage form for α-lipoic acid.: II.: Evaluation in human volunteers
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DOI：
10.1081/ddc-120027509
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发表时间：
2004-01-01
影响因子：
3.4
通讯作者：
Kratzel, M
中科院分区：
文献类型：
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作者：
Bernkop-Schnürch, A;Reich-Rohrwig, E;Kratzel, M
在本研究中，已在健康志愿者中生成并评估了α -硫辛酸（硫辛酸）的口服缓释剂型。将含有56.8% α -硫辛酸和43.2%壳聚糖乙酸酯的颗粒压缩成片剂（重量0.45 g，直径10.0 mm，厚度4 mm）。每名志愿者一次口服三片这种药片。在给药前和12小时内每小时从前臂静脉抽取血样。采用柱前衍生化和反相高效液相色谱法测定血浆α -硫辛酸浓度。结果表明，血浆α -硫辛酸水平的增加可以通过该配方实现至少12小时。在这段时间内，至少达到了两次最高血浆浓度。第一个最大值是基于α -硫辛酸的释放，它不是离子的，因此只松散地与壳聚糖结合，而第二个最大值是基于结肠中壳聚糖基质酶降解过程中药物的释放。AUC（0—bbb12）测定为183.8+/-101.4马克杯x min/mL（平均值+/-SD； n=8）。由于α -硫辛酸的脉冲持续释放，此处描述的剂型似乎对刺激II型糖尿病患者的葡萄糖摄取非常有益。
Within this study an oral sustained release dosage form of alpha-lipoic acid (thioctic acid) has been generated and evaluated in healthy volunteers. A granulate comprising 56.8% alpha-lipoic acid and 43.2% chitosan acetate was compressed to tablets (weight: 0.45 g; diameter: 10.0 mm; thickness: 4 mm). Three of these tablets were administered at once orally to each volunteer. Prior to administration and then every hour for 12 hours blood samples were taken from the antebrachial vein. alpha-Lipoic acid concentrations in plasma were quantified via precolumn derivatization and reversed-phase high-performance liquid chromatography (HPLC). Results demonstrated that an increased plasma level of alpha-lipoic acid can be achieved by this formulation for at least 12 hours. Within this time period at least two maximum plasma concentrations were reached. The first one is based on the release of alpha-lipoic acid, which is not ionically and therefore only loosely bound to chitosan, whereas a second maximum is based on the release of the drug during the enzymatic degradation of the chitosan matrix in the colon. The AUC(0-->12) was determined to be 183.8+/-101.4 mug x min/mL (mean+/-SD; n=8). Because of the pulsed sustained release of alpha-lipoic acid, the dosage form described here seems to be highly beneficial in order to stimulate the glucose uptake in the case of diabetes type II.