替米考星长效混悬剂的研制与质量评价

Preparation and Quality Evaluation of Tilmicosin Long-action Suspension

[目的]利用现代缓释技术,以替米考星为原料药,研制出溶解度较高、疗效强、可减少给药次数的替米考星长效混悬剂,并对其进行质量评价,为该药的批量生产提供可靠依据。[方法]通过正交优化法选择最优处方,并对最优处方进行含量测定试验、稳定性试验和药动学试验。[结果]替米考星长效混悬剂最佳处方为:替米考星原料药2.5g/100 mL,有机溶媒(1,2-丙二醇:乙醇=9:1)占比65%,润湿剂(吐温-80)0.3%,助悬剂(羟丙甲纤维素)5%,抗氧剂(无水亚硫酸钠)0.03%;含量测定结果为合格;影响因素试验发现替米考星长效混悬剂对高温和强光照敏感,对湿度不敏感;加速试验和长期试验发现替米考星长效混悬剂稳定性良好;药动学试验发现替米考星长效混悬剂和实验室自制替米考星溶液的AUC分别为43.164 9μg·h·mL^(-1)和26.206 5μg·h·mL^(-1),替米考星长效混悬剂的相对生物利用度为164.71%。[结论]本试验制得的替米考星长效混悬剂含量合格、稳定性良好、相对生物利用度高,可以批量生产,用于大型养殖场的大规模给药。

[Objective]In order to develop the Tilmicosin long-action suspension with characteristics of high solubility, good curative effect and low administration frequency by using modern slow-release technology and taking Tilmicosin ingredient as raw materials, so as to provide reliable basis for mass production on the basis of preliminary quality evaluation. [Methods]Choosing the optimal prescription through orthogonal optimization method, then content determination, stability and pharmacokinetic tests were conducted towards the optimized prescription. [Results]The proportions of the prescription for the Tilmicosin long-action suspension listed below Tilmicosin ingredients （2.5 g/100 mL）, Organic solvent （1,2-propylene glycol：ethanol = 9：1 ） accounting for 65%, Wetting agent （Twain-80） accounting for 0.3%, Suspended aid （Hydroxypropyl methyl cellulose） accounting for 5%, and Antioxidant （Anhydrous sodium sulfite） accounting for 0.03%. Results of content determination test manifested as qualified. Sensitivity test showed Tilmicosin long-action suspension was sensitive to high temperature and strong light, but it wasn＇ t humidity-sensitive. Accelerated test and long-term test indicated the long-action suspension had good stability. According to pharmacokinetic test result, the AUC of Tilmicosin long-action suspension and laboratory homemade Tilmicosin solution were 43.164 9μg· h· mL-1 and 26.206 5 μg ·h·mL-1, respectively. The relative bio-availability of the suspension was 164.71%. [Conclusions]The developed Tilmicosin long-action suspension was of qualified content determination, good stability and high relative bio-availability, it could be carried out mass production and applied in large-scale farms.