混合水平多指标正交设计优选灰黄霉素溶液处方及稳定性考察

目的:筛选灰黄霉素溶液处方,建立质量控制标准,并对pH、含量稳定性进行考察。方法:采用紫外分光光度法测定灰黄霉素含量,利用单因素试验初步考察灰黄霉素溶液处方中各成分对pH的影响,再运用混合水平的正交表,以pH、含量为指标,对试验结果进行极差和方差分析。结果:灰黄霉素在2.5～20.0μg·ml^-1浓度范围内呈良好的线性关系,r=0.999 9;灰黄霉素溶液pH不稳定受各因素综合影响所致,影响大小为:贮存温度>N,N-二甲基甲酰胺（DMF）>包装材料。有效期内灰黄霉素含量稳定。灰黄霉素溶液处方引入缓冲体系后,6月内溶液pH控制在4.0～5.0。结论:筛选所得灰黄霉素溶液处方的含量、pH稳定,生产工艺简便,含量测定法准确可靠,适于质控。

Study on Stability and Formulation Screening of Griseofulvin Solution by Orthogonal Trial with Mixed Levels and Multi-index

Objective： To screen formulation of griseofulvin solution, establish its quality control method and study its pH and content stability. Method： The content of griseofulvin solution was determined by ultraviolet spectrophotometry. Single factor experiments were made to observe the effect of every component on pH stability. The method of orthogonal trial with mixed levels and multi-index was employed with range analysis and variance analysis. Result： The calibration curve was linear within the range of 2.5-20. 0ug.ml-1 for griseofulvin （ r = 0. 999 9）. The instability of pH was due to several factors, which was mostly influenced by storage temperature, then the amount of DMF and the packaging material. The content of griseofulvin was stable before the expiration date. The pH of griseofulvin solution could be stable between 4.0 and 5.0 with the help of the buffer solution. Conclusion： The formulation of griseofulvin solution which has been screened is stable, and the preparation process is simple. The assay method is accurate and reliable for the quality control of this preparation.