Tilmicosin (TMS) is a semisynthetic macrolide antibiotic restricted to veterinary use but is only partially soluble in aqueous solutions, which limits its administration in treatments. We developed a strategy to enhance the supersaturated solubility of TMS using amorphous solid dispersion (SD). The dissolution profile shown that the dissolution rate of TMS-SD was obviously faster than TMS. The pharmacokinetics of tilmicosin (TMS) and tilmicosin solid dispersion (TMS-SD) in pigs after oral administration at a single dose of 50 mg/kg b.w were investigated. The t_max of TMS-SD (2.50 hr) was 1.80 times faster than TMS (4.50 hr) (p < .05). There were no significant differences in the other PK parameters (C_max, t_1/2β, V/F, CL/F, MRT, and AUC_0-inf) (p > .05). The mean relative bioavailability of TMS-SD compared with TMS was 140.39%, according to the AUC_0-inf values. These results demonstrated that the solid dispersion technique enhanced the bioavailability of TMS and the new formulation administered to animals via drinking water may be used as a therapeutic alternative for clinical treatments.

中文翻译：

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替米考星固体分散体制剂在猪体内的药代动力学和生物利用度

替米考星 (TMS) 是一种半合成的大环内酯类抗生素，仅限于兽用，但仅部分溶于水溶液，这限制了其在治疗中的给药。我们开发了一种使用无定形固体分散体 (SD) 提高 TMS 过饱和溶解度的策略。溶出曲线表明，TMS-SD 的溶出速率明显快于 TMS。研究了替米考星 (TMS) 和替米考星固体分散体 (TMS-SD) 在猪中以 50 毫克/千克体重单剂量口服给药后的药代动力学。TMS-SD（2.50 小时）的 t _max比 TMS（4.50 小时）快 1.80 倍（p  < .05）。其他 PK 参数 (C _max , t _1/2β、V/F、CL/F、MRT 和 AUC _0-inf ) ( p  > .05)。根据 AUC _0-inf值，与 TMS 相比，TMS-SD 的平均相对生物利用度为 140.39% 。这些结果表明，固体分散技术提高了 TMS 的生物利用度，并且通过饮用水给予动物的新制剂可用作临床治疗的治疗替代方案。