Marchenko Victor A, Khalikov Salavat S, Vasilenko Yury A, Ilyin Mikhail M, Kravchenko Irina A
Department of Gorno-Altay Research Institute of Agriculture, Federal Altai Scientific Center of Agrobiotechnology, Barnaul, Russia.
Laboratory for Physiologically Active Organofluorine Compounds, Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Science, Moscow, Russia.
J Adv Vet Anim Res. 2020 Dec 3;7(4):718-725. doi: 10.5455/javar.2020.g473. eCollection 2020 Dec.
Solubility and bioavailability are crucial for maximizing the activity of an antiparasitic drug. This study aimed to develop a combined preparation for antiparasitic medicines using ivermectin (Iver), fenbendazole (FBZ), and triclabendazole (TBZ), considering their solubility, bioavailability, and activity.
Innovative preparations in solid dispersions (SD) were obtained using the joint mechanical processing of drug substances with polyvinylpyrrolidone (PVP) in an LE-101 roller mill. The preparations' efficacy was studied in 140 sheep spontaneously infected with gastrointestinal Strongylata, , , and . The preparations were given individually to the sheep in the form of an aqueous suspension orally. Their effectiveness was evaluated using intravital and postmortem parasitological examinations.
The results confirmed the increase in solubility of substances by 13-29 times. The experiments have shown the high efficacy of SD composition of FBZ/Iver/PVP (1/1/9) containing FBZ (at 3.0 mg/kg ) and Iver (at 0.2 mg/kg ) when used against gastrointestinal Strongylates and (95.8% and 100%, respectively), to a lesser extent against (38.5%). The SD composition of TBZ/Iver/PVP (1/1/9) of TBZ (at 3.0 mg/kg ) and Iver (at 0.2 mg/kg ) showed a high efficacy against gastrointestinal Strongylata and (96.8% and 100%, respectively) and less activity against (61.6%).
The high parasiticidal activity of SD based on FBZ, TBZ, and Iver in comparison with initial substances is explained by the formation of inclusion complexes of these substances with PVP when SD is dissolved in water and the synergistic effect of the active substances of the preparations. The resulting complexes have increased solubility in water and bioavailability. The use of such an SD suggests a significant reduction in the dosages of FBZ and TBZ without losing parasiticidal activity.
溶解度和生物利用度对于使抗寄生虫药物的活性最大化至关重要。本研究旨在考虑伊维菌素（Iver）、芬苯达唑（FBZ）和三氯苯达唑（TBZ）的溶解度、生物利用度和活性，开发一种用于抗寄生虫药物的复方制剂。
在LE - 101滚筒磨中，通过药物与聚乙烯吡咯烷酮（PVP）的联合机械加工，获得了固体分散体（SD）中的创新制剂。在140只自然感染胃肠道圆线虫的绵羊中研究了制剂的疗效。制剂以水悬浮液的形式口服单独给予绵羊。使用活体和死后寄生虫学检查评估其有效性。
结果证实物质的溶解度提高了13 - 29倍。实验表明，含FBZ（3.0 mg/kg）和Iver（0.2 mg/kg）的FBZ/Iver/PVP（1/1/9）的SD组合物在用于对抗胃肠道圆线虫和[此处原文缺失寄生虫名称]时具有高效性（分别为95.8%和100%），对[此处原文缺失寄生虫名称]的效果稍差（38.5%）。含TBZ（3.0 mg/kg）和Iver（0.2 mg/kg）的TBZ/Iver/PVP（1/1/9）的SD组合物对胃肠道圆线虫和[此处原文缺失寄生虫名称]具有高效性（分别为96.8%和100%），对[此处原文缺失寄生虫名称]的活性较低（61.6%）。
与初始物质相比，基于FBZ、TBZ和Iver的SD具有高杀寄生虫活性，这是由于当SD溶解于水时这些物质与PVP形成包合物以及制剂中活性物质的协同作用。所得的复合物在水中的溶解度和生物利用度有所提高。使用这种SD表明在不丧失杀寄生虫活性的情况下，FBZ和TBZ的剂量可显著降低。
