Lee B J, Ryu S G, Cui J H
Biological Rhythm and Controlled Release Laboratory, College of Pharmacy, Kangwon National University, Chuncheon, South Korea.
Int J Pharm. 1999 Oct 15;188(1):71-80. doi: 10.1016/s0378-5173(99)00204-5.
A dual drug-loaded hydroxypropylmethylcellulose (HPMC) matrix tablet simultaneously containing drug in inner tablet core and outer coated layer was formulated using drug-containing aqueous-based polymeric Eudragit RS30D dispersions. Effects of coating levels, drug loadings in outer layers, amount and type of five plasticizers and talc concentration on the release characteristics were evaluated on the characteristics in simulated gastric fluid for 2 h followed by a study in intestinal fluids. Melatonin (MT) was selected as a model drug. The surface morphology of dual drug-loaded HPMC tablets using scanning electron microscope (SEM) was smooth, showing the distinct coated layer with about 75-microm coating thickness at the 15% coating level. Unlike the uncoated and conventionally coated HPMC tablet, the dual drug-loaded HPMC matrix tablet gave a biphasic linear release, showing a zero-order for 4 h (first) followed by another zero-order release when fitted using linear regression (r(2) = 0.99). As the coating levels (15, 25%) increased, the release rate was further decreased. The biphasic release profiles of dual drug-loaded HPMC matrix tablet was unchanged except when 25% coating level containing 0.5% drug concentration was applied. As the drug concentration in polymeric coating dispersion increased (0.25-1.0%), the amount of drug released increased. The time for the first linear release was also advanced. However, the biphasic release pattern was not changed. The biphasic release profiles of dual drug-loaded HPMC matrix tablet were highly modified, depending on the amount and type of five plasticizers. Talc (10-30%) in coating dispersion as an anti-sticking material did not affect the release profiles. The current dual drug-loaded HPMC matrix tablet, showing biphasic release profiles may provide an alternative to deliver drugs with circadian rhythmic behaviors in the body but needs to be further validated in future in human studies. The dual drug-loaded coating method is also interesting for the modified release of poorly water-soluble drugs because solubilizers and other additives can be added in drug-containing polymeric coating dispersions.
采用含药的水性聚合物Eudragit RS30D分散体，制备了一种双层载药羟丙基甲基纤维素（HPMC）骨架片，药物同时存在于片芯和外层包衣中。评估了包衣水平、外层药物载量、五种增塑剂的用量和类型以及滑石粉浓度对释放特性的影响，先在模拟胃液中考察2小时的特性，随后在肠液中进行研究。选择褪黑素（MT）作为模型药物。使用扫描电子显微镜（SEM）观察双层载药HPMC片的表面形态，其表面光滑，在15%包衣水平下显示出约75微米的明显包衣层厚度。与未包衣和传统包衣的HPMC片不同，双层载药HPMC骨架片呈现双相线性释放，线性回归拟合时显示4小时（第一阶段）为零级释放，随后是另一阶段的零级释放（r² = 0.99）。随着包衣水平（15%、25%）增加，释放速率进一步降低。双层载药HPMC骨架片的双相释放曲线保持不变，除了应用含0.5%药物浓度的25%包衣水平时。随着聚合物包衣分散体中药物浓度增加（0.25 - 1.0%），释放的药物量增加，第一阶段线性释放的时间也提前，但双相释放模式未改变。双层载药HPMC骨架片的双相释放曲线因五种增塑剂的用量和类型而发生显著改变。包衣分散体中作为抗粘材料的滑石粉（10 - 30%）不影响释放曲线。当前这种呈现双相释放曲线的双层载药HPMC骨架片可能为体内具有昼夜节律行为的药物递送提供一种替代方法，但未来需要在人体研究中进一步验证。双层载药包衣方法对于难溶性药物的缓释也很有意义，因为可以在含药聚合物包衣分散体中添加增溶剂和其他添加剂。
