摘要：为了找寻2批缬沙坦原料制备的缬沙坦氨氯地平片溶出存在显著差异的原因,以p H=4. 5的磷酸盐缓冲液作为溶出介质,测定缬沙坦氨氯地平片的溶出;以粉末X射线衍射测定缬沙坦原料晶型,以激光粒度法测定缬沙坦原料粒径,以光学显微镜观察缬沙坦原料及其在预混料中粒子的形貌,对比批间差异,探究导致溶出差异的原因。结果显示:2批缬沙坦原料晶型均为无定形;在质量分数为1%的十二烷基硫酸钠(SDS)和液体石蜡中测定的粒径相同;但2批缬沙坦原料在粉末形态、预混料中的颗粒形貌存在明显差异,缬沙坦原料颗粒形貌分别为树枝状和球团状。在晶型和粒径相同的情况下,原料颗粒形貌可能影响制剂的溶出,球团状原料在片剂制备过程中物料间接触面小,难以粘结成大团块,片剂崩解后溶出较快;树枝状原料则相反。并且当原料的晶型和粒径相同时,仅采用粒径数据无法区分原料的批间差异,应增加对原料颗粒形貌的控制。

Abstract: In order to find the reasons for the significant difference in dissolution rate of valsartan amlodipine tablets prepared from two batches of valsartan raw materials，dissolution rate of valsartan amlodipine tablets was determined in the dissolution medium of PBS ( pH = 4． 5) ．The crystal form of valsartan was determined by powder X-ray diffraction，the particle size of valsartan was determined by laser particle size analysis method，particle morphology of valsartan and premixer were observed by optical microscope，and the differences between batches were compared to explore the causes of differences in dissolution rate．The results showed that the crystal forms of the two batches of valsartan were amorphous，and the particle sizes measured in 1% SDS and liquid paraffin were also the same，but there were significant differences in the particle shape of the two batches of valsartan in the powder form and premix．The first batch and the second batch of valsartan raw materials were dendritic and globular，respectively．Therefore，in the case of the same crystal form and particle size，the form of the raw material may affect the dissolution of the preparation．The globular raw material has a small contact surface between other materials during the preparation of the tablet，and it is difficult to bond into a large agglomerate，and the tablet made by globular raw material dissolved faster than dendritic raw material．Moreover，when the crystal form and the particle diameter of the raw material were the same，the particle size cannot be used to distinguish the difference between the raw material batches，and the control of the grain shape of the raw material should be emphasized．

Keywords: valsartan; particle size; dissolution