摘要
为提高氟苯尼考(FF)的溶解度和体内外释药性能,本试验以醋酸羟丙甲纤维素琥珀酸酯(HPMCAS-HF)为载体,利用基于溶剂-反溶剂原理的新型共沉淀法制备氟苯尼考无定形固体分散体(FF-HF ASD),采用粉末X-射线衍射(PXRD)、红外光谱扫描(FT-IR)和差示扫描量热(DSC)对FF-HF ASD进行表征,以体外溶出试验为指标进行FF-HF ASD制备方法的优化;通过扫描电子显微镜(SEM)测定FF-HF ASD的形态和粒径;对其稳定性进行考察;通过在肉鸡体内的药动学参数分析其体内释药规律。结果显示,制备的FF-HF ASD无FF晶体衍射峰,无FF的晶体熔点峰,FF以无定形态分散于载体中,形成了无定形固体分散体;当FF与载体在反溶剂中的搅拌时间为5 min、反溶剂温度为25℃时,制备出的固体分散体的体外溶出最佳;该固体分散体在(25±5)℃、相对湿度为(75±3)%的条件下1个月内稳定性良好;与FF原料药相比,FF-HF ASD在肉鸡体内的生物利用度提高了约30.6%。结果表明,利用共沉淀法可成功制备溶解性良好的氟苯尼考无定形固体分散体,该固体分散体稳定性良好,且可提高氟苯尼考在肉鸡体内的生物利用度。
In order to improve the solubility and drug release performance of florfenicol(FF)in vitro and in vivo,this study prepared florfenicol-HF amorphous solid dispersion(FF-HF ASD)by a new co-precipitation method on the principle of solvent-antisolvent with HPMCAS-HF as matrix.FF-HF ASD was characterized by power X-ray diffraction(PXRD),Fourier transform infrared spectroscopy(FT-IR),and differential scanning calorimetry(DSC).The preparation method of FF-HF ASD was optimized by in vitro dissolution test.The morphology and particle size of FF-HF ASD were determined by scanning electron microscopy(SEM),and its stability was investigated.Pharmacokinetic parameters in broilers were used to analyze the drug release in vivo.The results showed that no crystal diffraction peak of FF in PXRD and no specific melting point peak of FF in DSC were observed,indicating that FF was amorphous after being prepared into solid dispersion.The solid dispersion had the best in vitro dissolution when the mixing time of FF and polymer in the antisolvent was 5 min,and the temperature of antisolvent was 25℃.The solid dispersion was stable within 1 month at(25±5)℃and relative humidity of(75±3)%.Compared with FF,the bioavailability of FF-HF ASD in broilers was increased by about 30.6%.Thus,the FF-HF ASD prepared by co-precipitation method has good stability,solubility and bioavailability.
作者
张雨晴
刘连超
高建亭
赵兴华
何欣
ZHANG Yu-qing;LIU Lian-chao;GAO Jian-ting;ZHAO Xing-hua;HE Xin(College of Veterinary Medicine,Hebei Agricultural University,Baoding 071001,China;Hebei Shengxue Dacheng Pharmaceutical Co.,Ltd.,Shijiazhuang 051430,China)
出处
《中国兽医杂志》
CAS
北大核心
2023年第8期41-47,共7页
Chinese Journal of Veterinary Medicine
基金
河北省重点研发计划(20326626D)
河北省自然科学基金生物农业联合基金重点项目(C2022204215)。
