化工进展2024，Vol.43Issue(8)：4230-4245,16.DOI:10.16085/j.issn.1000-6613.2023-1210
盐酸萘甲唑啉在甲醇-乙酸乙酯体系中的动力学及结晶工艺
Kinetics and crystallization process of naphazoline hydrochloride in methanol-ethyl acetate system
摘要
Abstract
Naphazoline hydrochloride(NPZ)is a vasoconstrictor drug that acts on the circulatory system.However,it has some poor crystal properties such as small average particle size and uneven distribution of particle size.Intermittent dynamic method was proposed to investigate the crystallization kinetics of NPZ in methanol-ethyl acetate system,and the influence of different technological conditions on the yield,particle size and variable coefficient were systematically investigated.The experimental results showed the nucleation mechanism of NPZ changed from heterogeneous nucleation to homogeneous nucleation with increase of supersaturation,and the crystal surface growth process followed a continuous growth mode.Growth kinetics model,nucleation rate and growth rate equations were:B0=9.591×104G2.10,B=2.031×1020 exp(-4.796×105/RT)M0.309T ΔC1.40ω1.37r and G=4.094×107 exp(-8.358×105/RT)ΔC1.36,respectively.The optimized conditions were as follows:crystal seed addition of 1.5%,crystallization temperature of 313.15K,stirring rate of 200r/min,supersaturation of 1.04,ethyl acetate addition rate of 7.037×10-4L/min,ethyl acetate to methanol mass ratio of 4∶1 and aging time of 2h.Crystals prepared under above conditions had a 30.49%increase in average particle size,a 32.30%reduction in variable coefficient,a 14.65%increase in bulk density,a 7.62%improvement in repose angle,a 30.76%improvement in Carr's index,and a 26.99%improvement in Hausner's ratio.The crystal size,particle size distribution and flowability were all improved.关键词
盐酸萘甲唑啉/结晶/动力学/粒度分布/优化Key words
naphazoline hydrochloride/crystallization/kinetics/particle size distribution/optimization分类
数理科学引用本文复制引用
何海霞,万亚萌,李帆帆,牛心雨,张静雯,李涛,任保增..盐酸萘甲唑啉在甲醇-乙酸乙酯体系中的动力学及结晶工艺[J].化工进展,2024,43(8):4230-4245,16.基金项目
河南省重大科技专项(201300310900) （201300310900）
河南省高等学校重点科研项目(19A530004) （19A530004）
2022年度河南工程学院一流本科课程项目(2022YLKCX02). （2022YLKCX02）
