College of Pharmacy, Yeungnam University, Gyongsan 712-749, South Korea.
Biol Pharm Bull. 2010;33(8):1364-70. doi: 10.1248/bpb.33.1364.
The purpose of this research was to prepare and evaluate a non-bitter donepezil hydrochloride (DH) orally disintegrating tablet (ODT) for enhanced patient compliance. Taste masking was done by preparing microspheres with different ratios of drug and Eudragit EPO using spray drying method. The entrapment of the drug into microspheres was confirmed by scanning electron microscope (SEM) and X-ray powder diffraction. It was found that microspheres with a drug-polymer ratio of 1 : 2 could mask the taste obviously by inhibiting the release of DH in simulated salivary fluid. Microspheres-loaded tablets containing Polyplasdone NF and Low substituted Hydroxypropyl Cellulose (L-HPC) both at a 10% level showed rapid disintegration, in vitro (15.5 s) and in vivo (19.8 s), which were faster than that of marketed tablets (36.7, 41.3 s, respectively). Results from taste evaluation in human volunteers revealed that the ODTs with taste-masked microspheres had significantly enhanced palatability. Dissolution in vitro and pharmacokinetics in rats were evaluated for the tested ODTs compared to the donepezil hydrochloride commercial product (ARICEPT). Both tablets showed comparable dissolution patterns in vitro and similar area under curve from 0 to 24 h (AUC(0-24)), C(max) and T(max) of DH in vivo to each other, suggesting that the tested ODTs might give the similar drug efficacy in rats compared to that of ARICEPT. Thus, it was concluded that DH ODTs with masked taste were obtained by Eudragit EPO-based microspheres, drug loaded microspheres neither decreased the bioavailability nor delayed the release of DH.
本研究旨在制备和评价一种非苦味盐酸多奈哌齐（DH）口腔崩解片（ODT），以提高患者的顺应性。采用喷雾干燥法，用不同药物与 Eudragit EPO 比例的微球进行掩味处理。扫描电子显微镜（SEM）和 X 射线粉末衍射证实了药物被包埋在微球中。结果发现，药物-聚合物比为 1:2 的微球可以通过抑制 DH 在模拟唾液中的释放来明显掩味。载药微球的片剂，其中聚维酮 NF 和低取代羟丙基纤维素（L-HPC）的含量均为 10%，表现出快速崩解，体外（15.5s）和体内（19.8s），比市售片剂（分别为 36.7s 和 41.3s）更快。人体志愿者味觉评估结果表明，掩味微球的 ODT 具有显著改善的口感。与盐酸多奈哌齐商业产品（ARICEPT）相比，对测试的 ODT 进行了体外溶出度和大鼠药代动力学评估。两种片剂在体外均表现出相似的溶出模式，体内 DH 的 AUC(0-24)、C(max)和 T(max)相似，表明与 ARICEPT 相比，测试的 ODT 在大鼠中可能具有相似的药物疗效。因此，结论是，通过 Eudragit EPO 基微球获得了掩味的 DH ODT，载药微球既没有降低 DH 的生物利用度，也没有延迟其释放。
