PDF(Pubmed)
Abstract：
The bitter drug, warfarin, has a narrow therapeutic index (NTI) and is used in paediatrics and geriatrics. The aim of this feasibility study was to formulate the taste-masked warfarin-containing pellets to be applicable for dose personalisation and to improve patient compliance, as well as to investigate the effect of the core type (PharSQ® Spheres M, CELPHERE™ CP-507, and NaCl) on the warfarin release from the Kollicoat® Smartseal taste-masking-coated pellets. The cores were successfully drug-loaded and coated in a fluid-bed coater with a Wurster insert. An increase in particle size and particle size distribution was observed by optical microscopy. In saliva-simulated pH, at the Kollicoat® Smartseal level of 2 mg/cm2, none of the pellets demonstrated drug release, confirming their efficient taste-masking. However, in a stomach-simulated pH, a faster drug release was observed from PharSQ® Spheres M- and CELPHERE™ CP-507-coated pellets in comparison with NaCl cores. Additional experiments allowed us to explain the slower drug release from NaCl-containing pellets because of the salting-out effect. Despite the successful taste masking, the drug release from pellets was relatively slow (not more than 91% per 60 min), allowing for further formulation improvements.
摘要：
苦涩的药物，华法林,具有狭窄的治疗指数（NTI），用于儿科和老年病学。本可行性研究的目的是配制适用于剂量个性化的含华法林掩味颗粒，并提高患者的依从性。以及研究核心类型的影响(PharSQ®SpheresM，CELPHERE™CP-507和NaCl）对华法林从Kollicoat®Smartseal掩味包衣的小丸中的释放。将芯成功地装载药物并在具有Wurster插入物的流化床涂布机中涂覆。通过光学显微镜观察到粒度和粒度分布的增加。在唾液模拟的pH中，在Kollicoat®Smartseal水平为2mg/cm2时，无一微丸显示药物释放，确认他们有效的掩味。然而,在胃模拟的pH值，与NaCl核心相比,从PharSQ®SpheresM-和CELPHERE™CP-507包衣的小丸观察到更快的药物释放。其他实验使我们能够解释由于盐析效应而导致的含NaCl颗粒中药物释放较慢的现象。尽管成功了掩味，微丸的药物释放相对较慢（每60分钟不超过91％），允许进一步改进配方。
