Dong Xinrui, Shu Xueye, Wang Yingnan, Niu Zhaohuan, Xu Shixia, Zhang Yue, Zhao Shuchun
School of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Yuhua East Road, Shijiazhuang 050018, China.
Hebei Research Center of Pharmaceutical and Chemical Engineering, Yuhua East Road, Shijiazhuang 050018, China.
J Vet Med Sci. 2018 Feb 2;80(1):173-180. doi: 10.1292/jvms.17-0434. Epub 2017 Nov 28.
Valnemulin, successfully developed by Sandoz in 1984, is a new generation derivative of pleuromutilin related to tiamulin. Valnemulin has low water-solubility, a short half-life period, low bioavailability, and instability. The application of valnemulin was restricted. Therefore, finding a more moderate delivery system is necessary to improve the shortcomings of valnemulin. The purpose of the study was to improve the strong stability and the irritation caused by of valnemulin hydrochloride power through pegylated-valnemulin prodrug mode. The prepared pegylated-valnemulin prodrug was characterized and evaluated by in vitro release performance under buffer solutions with pH levels of 7.4 and 3.6. The loading rate of valnemulin in PEG-succinic-valnemulin prodrug was determined by ultraviolet spectrophotometer and high performance liquid chromatography (HPLC). HPLC with evaporative light scattering detector was applied to determine the amount of PEG-succinic acid. The loading rate of valnemulin in PEG-succinic-valnemulin prodrug was 6.46%. PEG-succinic-valnemulin prodrug demonstrated a satisfactory solubility of valnemulin with 523 mg·ml and excellent stability verified by the stability experiment. The result of the in vitro release test showed that the prepared PEG-valnemulin prodrug has controlled release ability and the release rate of valnemulin from PEG-valnemulin prodrug with a pH of 7.4 was 64.98%, which was higher than that of pH3.6 with release rate of 31.90%. Therefore, the prepared PEG-succinic-valnemulin prodrug has great application potential.
1984年山德士公司成功研发出的沃尼妙林，是与替米考星相关的新一代截短侧耳素衍生物。沃尼妙林水溶性低、半衰期短、生物利用度低且不稳定，其应用受到限制。因此，有必要找到一种更合适的给药系统来改善沃尼妙林的这些缺点。本研究的目的是通过聚乙二醇化沃尼妙林前药模式来提高盐酸沃尼妙林原料药的稳定性并减轻其刺激性。制备的聚乙二醇化沃尼妙林前药在pH值为7.4和3.6的缓冲溶液中通过体外释放性能进行表征和评价。采用紫外分光光度计和高效液相色谱法（HPLC）测定聚乙二醇琥珀酸沃尼妙林前药中沃尼妙林的载药量。应用配备蒸发光散射检测器的HPLC测定聚乙二醇琥珀酸的含量。聚乙二醇琥珀酸沃尼妙林前药中沃尼妙林的载药量为6.46%。聚乙二醇琥珀酸沃尼妙林前药中沃尼妙林的溶解度为523 mg·ml，令人满意，稳定性实验验证了其具有优异的稳定性。体外释放试验结果表明，制备的聚乙二醇化沃尼妙林前药具有控释能力，pH值为7.4时沃尼妙林从聚乙二醇化沃尼妙林前药中的释放率为64.98%，高于pH值为3.6时的31.90%。因此，制备的聚乙二醇琥珀酸沃尼妙林前药具有很大的应用潜力。
