LAUSR

ABSTRACT 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 Cmax and prolonged Tmax 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.