Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China; Pharmaceutical College of Henan University, Kaifeng 475004, China.
Department of Radiology, 307 Hospital, PLA, 8 East Street, Beijing 100071, China; Department of Radiology, Clinical College of 307th Hospital of PLA, Anhui Medical University, Beijing 10071, China.
Int J Pharm. 2018 Oct 5;549(1-2):370-379. doi: 10.1016/j.ijpharm.2018.08.011. Epub 2018 Aug 11.
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.
胃漂浮片剂是一种多功能剂型，具有长期胃滞留、持续释放和提高生物利用度的优点，但其漂浮时间和持续释放通常不能令人满意。在这里，我们通过将压缩片剂与 3D 打印设备相结合，设计了一种新型胃漂浮系统，其中将核黄素片剂填充到设备中。填充片剂的设备可以称为片剂内设备（TiD）系统。商业聚乳酸（PLA）长丝用于 FDM 3D 打印设备的主体和盖子。制备了四种 TiD 系统。它们的基本结构涉及非网、中心对称双网（包括外围密封充气室和中心网两侧室）、单网（包括顶侧密封充气室和底侧单侧网室）和偏心双网（包括偏心网两侧室和充气室）。根据浮力原理，经过对每个腔室参数的精确计算，对它们进行了精巧的设计。尽管由于适当的药物释放，仅选择了后两种 TiD 系统，但它们都表现出良好的漂浮能力。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剂采用直接压缩法制备。所有片剂均表现出快速的药物释放，尽管由于设备的阻碍作用和片剂浆液的形成，TiD 系统中的设备对药物释放有很高的阻碍作用。单网和双网 TiD 系统在 72 小时时分别达到了 41%和 62%的累积释放，同时具有良好的漂浮性能。通过 CT 研究进一步在兔模型上证明了 TiD 系统在体内的长期（>72 小时）胃漂浮功能。TiD 系统适合于通过口服途径给予具有超长漂浮和控制释放时间的药物。
