Department of Pharmaceutical Engineering, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Department of Pharmaceutical Engineering, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan; Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
J Pharm Sci. 2018 Sep;107(9):2514-2518. doi: 10.1016/j.xphs.2018.05.014. Epub 2018 May 31.
Macrolide antibiotics are widely used at clinical sites. Clarithromycin (CAM), a 14-membered macrolide antibiotic, was reported to gelate under acidic conditions. Gelation allows oral administration of acid-sensitive CAM without enteric coating by hindering the penetration of gastric fluid into CAM tablets. However, it is unknown whether this phenomenon occurs in other macrolide antibiotics. In this study, we examined the gelation ability of 3 widely used macrolide antibiotics, roxithromycin (RXM), erythromycin A, and azithromycin. The results indicated that not only CAM but also RXM gelated under acidic conditions. Erythromycin A and azithromycin did not gelate under the same conditions. Gelation of RXM delayed the disintegration of the tablet and release of RXM from the tablet. Disintegration and release were also delayed in commercial RXM tablets containing disintegrants. This study showed that 2 of the 4 macrolides gelated, which affects tablet disintegration and dissolution and suggests that this phenomenon might also occur in other macrolides.
大环内酯类抗生素在临床中被广泛应用。克拉霉素（CAM），一种 14 元大环内酯类抗生素，据报道在酸性条件下会胶凝。胶凝作用可以阻止胃液渗透到 CAM 片剂中，从而使酸敏感的 CAM 能够不经肠溶包衣而口服给药。然而，目前尚不清楚这种现象是否也存在于其他大环内酯类抗生素中。在这项研究中，我们研究了 3 种常用的大环内酯类抗生素，罗红霉素（RXM）、红霉素 A 和阿奇霉素的胶凝能力。结果表明，不仅 CAM，而且 RXM 在酸性条件下也会胶凝。红霉素 A 和阿奇霉素在相同条件下不会胶凝。RXM 的胶凝作用会延迟片剂的崩解和 RXM 从片剂中的释放。含有崩解剂的市售 RXM 片剂的崩解和释放也会延迟。这项研究表明，4 种大环内酯类抗生素中有 2 种会胶凝，这会影响片剂的崩解和溶解，表明这种现象也可能发生在其他大环内酯类抗生素中。
