Combination of 3D printing technologies and compressed tablets for preparation of riboflavin floating tablet-in-device (TiD) systems
Combination of 3D printing technologies and compressed tablets for preparation of riboflavin floating tablet-in-device (TiD) systems
复制标题
结合 3D 打印技术和压缩片剂制备核黄素漂浮片装置 (TiD) 系统
DOI：
10.1016/j.ijpharm.2018.08.011
复制
发表时间：
2018-10-05
影响因子：
5.8
通讯作者：
Sheng, Fugeng
中科院分区：
文献类型：
--
作者：
Fu, Junhui;Yin, Hui;Sheng, Fugeng
胃漂浮片是一种多功能剂型，具有长期胃潴留、缓释和提高生物利用度等优点，但通常不能满足漂浮时间和缓释要求。我们将压缩片剂与3D打印装置相结合，设计了一种新型的胃漂浮系统，将核黄素片填充到装置中。表格填充的设备可以称为平板设备（TiD）系统。商用聚乳酸长丝用于熔融沉积建模（FDM） 3D打印装置的主体和帽。制备了四种类型的TiD体系。其基本结构包括无网、中心对称双网（包括外围密封充气室和中心双侧网室）、单网（包括上侧密封充气室和下侧单侧网室）和偏心双网（包括偏心双侧网室和充气室）。它们是根据浮力原理对每个腔室参数进行精确计算后精心设计的。它们都表现出良好的漂浮能力，但由于药物释放合适，只选择了后两种TiD体系。采用直接压实法制备了由核黄素、乳糖、羟丙基甲基纤维素（HPMC）和硬脂酸镁组成的压缩核黄素片。所有片剂均表现出快速的药物释放，但由于装置的屏障作用和片剂浆液的形成，药物释放受到装置的高度阻碍。单网和双网TiD系统在72 h时的累计释放量分别为41%和62%，同时进行井浮。在家兔模型上，通过CT检查进一步证实了TiD系统在体内长期（> 72 h）胃漂浮功能。TiD系统适用于超长期漂浮和胃路控释药物的口服给药。
Gastric floating tablets are a multifunctional dosage form with the merits of long-term gastric retention, sustained release and improved bioavailability though floating time and sustained release are usually not satisfied. Here we designed a novel gastric floating system by combining compressed tablets with 3D printed devices, wherein a riboflavin tablet was filled into a device. The table-filled device can be called a tablet-in-device (TiD) system. Commercial poly(lactic acid) filaments were used for fused deposition modeling (FDM) 3D printing of the body and cap of the device. Four types of TiD systems were prepared. The basic structures of them involved non-net, centrally symmetric double-net (including a peripheral sealed air-filled chamber and a centric net-on-both-sides chamber), single-net (including a sealed air-filled chamber on the top side and a net-on-one-side chamber on the bottom side), and eccentric double-net (including an eccentric net-on-both-sides chamber and an air-filled chamber). They were exquisitely designed after precise calculations of every chamber parameters according to the buoyant principle. All of them showed good floating ability, although only the latter two TiD systems were selected due to appropriate drug release. Compressed riboflavin tablets, consisting of riboflavin, lactose, hydroxypropyl methylcellulose (HPMC) and magnesium stearate, were prepared with the direct compaction method. All the tablets showed rapid drug release though the release was highly hindered by the devices in the TiD systems due to the barrier effect of devices and the tablet slurry formation. The single-net and double-net TiD systems achieved the cumulative release of 41% and 62% at 72 h, respectively, along with simultaneously well floating. In vivo long-term ( > 72 h) gastric floating function of TiD systems was further demonstrated on the rabbit models by the CT investigation. TiD systems are appropriate for oral administration of drugs with super long-term floating and controlled release in the gastric route.