Center for Research Development and Evolution of Pharmaceutical Excipients and Generic Drugs, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
Center for Research Development and Evolution of Pharmaceutical Excipients and Generic Drugs, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China.
Int J Pharm. 2018 Jul 10;545(1-2):37-44. doi: 10.1016/j.ijpharm.2018.04.011. Epub 2018 Apr 9.
Pregabalin is a promising drug for the treatment of neuropathic pain, a chronic disease affecting a large population needing long-term treatment. However, due to its short half-life, the commercial tablet has to be administered 2-3 times per day, with inconvenience for patient and fluctuations of plasma concentration. In this study, a gastro-floating drug delivery system of pregabalin was developed to prolong the gastric retention of drugs absorbed or act in stomach or upper gastrointestinal tract. First of all, it was proved that the drug was mainly absorbed in stomach and upper gastrointestinal tract. The final formulation was optimized in consideration of buoyancy and drug release profile. The gastro-floating tablet was prepared with hydroxypropyl methylcellulose (HPMC) as sustained-release matrix, lipophilic cetyl alcohol as floating-assistance agent and other excipients to achieve satisfying buoyancy and sustained release performance with mechanisms of diffusion and matrix erosion. Food exhibited significant effect on the pharmacokinetics of gastro-floating tablet and conventional capsule. Compared with conventional capsules, the relative bioavailability of gastro-floating tablet in fasted conditions or in fed conditions was only 62.47 ± 10.80% and 100.98 ± 17.25% respectively, even though the gastro-floating tablet obtained decreased C and prolonged T in fasted and fed conditions. Besides, good in vivo-in vitro correlation of the gastro-floating tablet was established. In summary, a gastro-floating tablet of pregabalin exhibiting desired buoyancy and release profiles was designed, and the tablet expressed significantly sustained-release behavior in fed conditions with good in vivo-in vitro correlation. The designed gastro-floating system is a promising choice for the patients to relieve neuropathic pain.
普瑞巴林是一种有前途的治疗神经病理性疼痛的药物，这种慢性病影响着大量需要长期治疗的人群。然而，由于其半衰期短，商业片剂必须每天服用 2-3 次，这给患者带来不便，并导致血浆浓度波动。在这项研究中，开发了一种普瑞巴林胃漂浮药物递送系统，以延长在胃中吸收或作用的药物的胃滞留时间。首先，证明药物主要在胃和上胃肠道中被吸收。最终的配方是在考虑浮力和药物释放特性的情况下进行优化的。胃漂浮片是用羟丙基甲基纤维素（HPMC）作为缓控释基质、亲脂性鲸蜡醇作为漂浮助剂和其他辅料制备的，以实现令人满意的漂浮和持续释放性能，其机制为扩散和基质侵蚀。食物对胃漂浮片和普通胶囊的药代动力学有显著影响。与普通胶囊相比，空腹和进食条件下胃漂浮片的相对生物利用度分别仅为 62.47±10.80%和 100.98±17.25%，尽管胃漂浮片在空腹和进食条件下降低了 C 和延长了 T。此外，还建立了胃漂浮片的良好体内-体外相关性。总之，设计了一种具有理想的漂浮和释放特性的普瑞巴林胃漂浮片，该片在进食条件下表现出明显的持续释放行为，并具有良好的体内-体外相关性。所设计的胃漂浮系统是缓解神经病理性疼痛患者的一个有前途的选择。
