甲芬那酸包合物和固体分散体的研究

目的　探索将甲芬那酸 (mefenamicacid ,MFA)制成包合物和固体分散体的工艺 ,以增加其溶解度和溶出速率。方法　采用环糊精 (β CD) ,聚乙二醇 40 0 0 (PEG 40 0 0 )为载体 ,以差示扫描量热图谱与甲芬那酸溶出度为指标 ,确定包合物和固体分散体的制备工艺。结果饱和溶液法制成了甲芬那酸 β CD包合物 ,熔融 冷冻法制成了甲芬那酸 PEG 40 0 0固体分散体 ,甲芬那酸包合物、固体分散体的溶解度分别增加 2 .3、3.1倍。正交试验 9组中以下 3组包合工艺为优 :A3 B3 C2 m(MFA)∶m(β CD) =1∶8,70℃搅拌 2h],A2 B2 C3 m(MFA)∶m(β CD) =1∶6 ,6 0℃搅拌 4h],A1B3 C3 m(MFA)∶m(β CD) =1∶4 ,70℃搅拌 4h]。考虑大规模生产宜选择 β CD用量小、包合效果较好的条件 ,又将A1B3 C3进行扩大试验 ,结果表明该工艺条件重复性好。熔融 冷冻法制备PEG 40 0 0 固体分散体可采用 1∶3～ 1∶4量比。结论　将甲芬那酸制成β CD包合物和PEG 40 0 0 固体分散体技术可行 ,均能显著增加其溶解度和溶出速率

Study on the inclusion compounds and solid dispersions of mefenamic acid

Objective To prepare β-CD(β-cyclodextrin) inclusion compounds and PEG- 4000poly-(ethylene glycol) 4000] solid dispersions of mefenamic acid (MFA)in order to improve its dissolution. Methods The inclusion compounds of MFA were prepared using saturated β-CD solution method by orthogonal test. The solid dispersions were prepared using melt-cool process with PEG- 4000 as a carrier. The inclusion compounds and solid dispersions were identified by differential scanning calorimetry (DSC) gram and their dissolution rates were tested in pH8.0 buffer solution. Results The suitable condition for preparing β-CD inclusion compounds of MFA industrially was the weight ratio of 1∶4 between MFA and β-CD, agitating for 4 h at 70 ℃. The suitable proportion for preparing solid dispersions of MFA was the weight ratio of 1∶4 between MFA and PEG- 4000. Conclusion Dissolution rates of MFA are apparently improved in inclusion compounds and PEG- 4000 solid dispersions, and the solubility of MFA is apparently increased by 2～3 times in inclusion compounds and PEG- 4000 solid dispersions.