灰黄霉素固体分散体在比格犬上的药物代谢动力学分析  

Pharmacokinetic analysis of griseofulv in solid dispersion in Beagle dogs

作　　者：王灵灵 王令令 张雨晴 马宁[1] 何欣[1] WANG Lingling;WANG Lingling;ZHANG Yuqing;MA Ning;HE Xin(College of Veterinary Medicine,Hebei Agricultural University,Baoding,Hebei 071001,China)

机构地区：[1]河北农业大学动物医学院,河北保定071001

出　　处：《中国兽医学报》2022年第11期2223-2230,共8页Chinese Journal of Veterinary Science

基　　金：河北省重点研发计划资助项目(20326626D,19227505D);河北省自然科学基金重点资助项目(C202220-4215)。

摘　　要：为了提高灰黄霉素的溶解度,本研究选用醋酸羟丙基甲基纤维素琥珀酸酯(hydroxypropyl methyl cellulose succinate acetate, HPMCAS)的3种规格HF、MF、LF为载体,利用基于溶剂-反溶剂原理的新型共沉淀法制备灰黄霉素固体分散体(amorphous solid dispersion, ASD)。通过粉末X射线衍射、差示量热扫描、傅利叶红外扫描及扫描电子显微镜等对其进行表征,并通过体外溶出度测定和药物代谢动力学对其体内外释药进行研究。结果显示当灰黄霉素与3种载体的比例为1∶9时,均可形成灰黄霉素无定形固体分散体,且以HPMCAS-HF为载体时体外溶出效果最佳,使灰黄霉素的溶解度提高了8倍。另外,在比格犬的药动学研究显示,该固体分散体在体内最大血药浓度(Cmax)比灰黄霉素原料药提高了6.2倍。该固体分散体在4个月内稳定性良好。结果表明,利用新型共沉淀法制备的灰黄霉素固体分散体稳定性良好,能显著提高灰黄霉素的溶解度和生物利用度。In order to improve the solubility of griseofulvin, three kinds of HF,MF and LF of hydroxypropyl methyl cellulose succinate acetate(HPMCAS) were used as carriers in this study.A new type of amorphous solid dispersion(ASD) of griseofulvin was prepared by co-precipitation method based on solvent-antisolvent principle.It was characterized by powder X-ray diffraction(XRD),differential calorimetry(DSC),Fourier infrared(FTIR) and scanning electron microscope(SEM),and its dissolution in vitro and pharmacokinetics were used to study its drug release in vivo and in vitro.The results showed that when the ratio of griseofulvin to the three carriers was 1∶9,the amorphous solid dispersions of griseofulvin could be formed, and hpMCAS-HF was used as the carrier for the best dissolution in vitro,which increased the solubility of griseofulvin by 8 times.In addition, pharmacokinetic studies in beagles showed that the maximum plasma concentration(Cmax) of the solid dispersion in vivo was 6.2 times higher than that of griseofulvin.The solid dispersion was stable in 4 months.The results showed that the solid dispersions of griseofulvin prepared by the new coprecipitation method had good stability and could significantly improve the solubility and bioavailability of griseofulvin.

关 键 词：灰黄霉素 无定形固体分散体 共沉淀法 溶解度 比格犬 

分 类 号：S859.1[农业科学—临床兽医学]