Abstract：
Herein, we aimed to formulate a novel oral disintegrating tablet (ODT) of aripiprazole (ARP) capable of rapid disintegration using a direct compression technique. Different ODTs were fabricated with directly compressible excipients, and their disintegration time, wettability (water absorption ratio and wetting time), and mechanical properties (hardness and friability) were evaluated. The optimized ODT comprised F-Melt® type C, Prosolv® SMCC HD90, and Na croscarmellose (10 mg of ARP in a 130 mg tablet). The ODT with 3.1-5.2 kp hardness exhibited rapid disintegration (14.1-17.2 sec), along with appropriate mechanical strength (friability < 0.24%). In a bioequivalent study in Korean healthy subjects (randomized, single-dose, two-period crossover design, n = 37), the novel ODT offered the equivalent pharmacokinetic profile to that of a conventional immediate release tablet (Otsuka, Abilify®, Japan), despite different disintegration and dissolution profiles. The 90% confidence intervals of the geometric mean test to reference ratios considering the area-under-the-curve and maximum plasma drug concentrations were 1.0306-11051 and 0.9448-1.1063, respectively, satisfying FDA regulatory criteria for bioequivalence. The novel ART ODT was physicochemically stable under the accelerated storage condition (40 °C, RH75%) for 24 weeks. Therefore, the novel ARP-loaded ODT is expected to be an alternative to oral ARP therapy, providing improved patient adherence.
摘要：
在这里，我们的目标是配制一种新型的阿立哌唑（ARP）口腔崩解片（ODT），该片剂能够使用直接压缩技术快速崩解。用直接可压缩的赋形剂制造不同的ODT，和它们的崩解时间，润湿性（吸水率和润湿时间），和机械性能（硬度和脆性）进行评估。优化的ODT包括F-Melt®C型，Prosolv®SMCCHD90和交联羧甲基纤维素钠(130mg片剂中10mg的ARP)。具有3.1-5.2kp硬度的ODT表现出快速崩解（14.1-17.2秒），以及适当的机械强度(脆性<0.24%)。在韩国健康受试者的生物等效性研究中（随机，单剂量,两周期交叉设计，n=37),新型ODT提供了与常规速释片剂相当的药代动力学曲线(Otsuka，Abilify®,Japan),尽管不同的崩解和溶出曲线。考虑到曲线下面积和最大血浆药物浓度的几何平均测试与参考比率的90％置信区间分别为1.0306-11051和0.9448-1.1063，满足FDA生物等效性监管标准。新型ARTODT在加速储存条件下（40°C，RH75%)持续24周。因此,新型ARP负载ODT有望成为口服ARP治疗的替代方案，提供改善的患者依从性。
