Lee B J, Choe J S, Kim C K
Biological Rhythm and Controlled Release Laboratory, College of Pharmacy, Kangwon National University, Chuncheon, Korea.
J Microencapsul. 1998 Nov-Dec;15(6):775-87. doi: 10.3109/02652049809008260.
A sustained release dosage form which delivers melatonin (MT), a pineal hormone, is of clinical value because of the short half-life of MT, for those who have a disordered circadian rhythm. The purpose of this study was to prepare MT-loaded microspheres by the emulsion melting/cooling method using stearyl alcohol (SA) and also dual walled chitosan and sodium alginate beads, and to evaluate the release characteristics in simulated gastric and intestinal fluid. The MT-loaded microspheres were spherical, ranging in diameter from about 250-750 microm. When polyethylene glycol 4000 (PEG), as a water-soluble or aluminium tristearate (AT), as a water-insoluble additive, was incorporated, the surface roughness was further reduced resulting in a smooth matrix structure. The dual walled chitosan and sodium alginate beads entrapping small MT-loaded microspheres were not spherical in structure. As the additives incorporated into SA microspheres increased, the drug content decreased. The release profiles of the MT-loaded microspheres were independent of pH. When the melted SA solution was cooled rapidly in 10 min to 25 degrees C, the drug content increased but the release rate of MT-loaded microspheres decreased. The release rate of drug decreased as the amount of SA increased but an increase of agitation speed and amount of AT and PEG resulted in increased release rates. The release rate of drug from dual walled chitosan beads increased slightly but was retarded in the case of dual walled alginate beads when compared to MT-loaded microspheres. The emulsion melting/cooling method used to prepare MT-loaded microspheres using SA is simple and inexpensive, and may provide an alternative for the preparation of an oral sustained release dosage form of MT without using harmful organic solvents. The dual walled chitosan and sodium alginate beads may also provide a convenient way to control the release of drugs.
褪黑素（MT）是一种松果体激素，由于其半衰期短，对于昼夜节律紊乱的患者而言，能够递送MT的缓释剂型具有临床价值。本研究的目的是采用硬脂醇（SA）通过乳液熔融/冷却法制备载MT的微球以及双壁壳聚糖和海藻酸钠珠，并评估其在模拟胃液和肠液中的释放特性。载MT的微球呈球形，直径约为250 - 750微米。当加入作为水溶性添加剂的聚乙二醇4000（PEG）或作为水不溶性添加剂的三硬脂酸铝（AT）时，表面粗糙度进一步降低，形成光滑的基质结构。包裹载MT小微球的双壁壳聚糖和海藻酸钠珠结构并非球形。随着加入SA微球中的添加剂增加，药物含量降低。载MT微球的释放曲线与pH无关。当将熔融的SA溶液在10分钟内快速冷却至25℃时，药物含量增加，但载MT微球的释放速率降低。药物释放速率随着SA用量的增加而降低，但搅拌速度、AT和PEG用量的增加会导致释放速率提高。与载MT微球相比，双壁壳聚糖珠中药物的释放速率略有增加，但双壁海藻酸钠珠中药物的释放则受到抑制。采用SA通过乳液熔融/冷却法制备载MT微球的方法简单且成本低廉，可能为制备MT口服缓释剂型提供一种无需使用有害有机溶剂的替代方法。双壁壳聚糖和海藻酸钠珠也可能为控制药物释放提供一种便捷方式。
