Juang R H, Storey D E
Department of Pharmaceutical Research & Development, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
Pharm Res. 1998 Nov;15(11):1714-20. doi: 10.1023/a:1011956612000.
The purpose of this study was to develop an analytical method for the quantitative determination of the extent of neutralization of the carboxylic acid function in Carbopol 974P NF using Diffuse Reflectance Fourier Transform Infrared Spectroscopy (DRIFT) with Kubelka-Munk function analysis.
Carbopol 974P NF is a high molecular weight, chemically crosslinked polymer of acrylic acid, that has the C=O stretching band of the unionized carboxylic acid function at 1695 cm(-1). The quantitative determination of the extent of neutralization of the carboxylic acid function in Carbopol 974P NF is based upon the asymmetrical C=O stretching of the carboxylate anion at 1570 cm(-1) measured by DRIFT spectroscopy.
To overcome spectral differences arising from sample preparation (powders, granules and tablets) and in an effort to increase the precision of the analytical method, the following approaches were used: (1) an internal standard, (2) first derivative of the spectrum to eliminate the effect of baseline drift and (3) the ratio of the first derivative of the C=O stretch of the carboxylate anion peak (1570 cm(-1)) in the neutralized Carbopol 974P NF to that of the peak of the internal standard (866 cm(-1)). The above data treatment techniques proved to be superior to the usual methods of peak height or peak area. The calibration curve of the ratio of the first derivative (1570 cm(-1)/866 cm(-1)) was a linear function of the mass of sodium carboxylate over the range from 0.0% to 100.0% neutralization of the carboxylic acid function in Carbopol 974P NF (Fig. 1a). No particle size or sample preparation effects were noted within the experimental error.
DRIFT spectroscopy using the Kubelka-Munk function is a powerful tool for the routine determination of the extent of neutralization of the carboxylic acid function in Carbopol 974P NF in complex pharmaceutical formulations.
本研究的目的是开发一种分析方法，用于使用漫反射傅里叶变换红外光谱（DRIFT）结合库贝尔卡-蒙克函数分析来定量测定卡波姆974P NF中羧酸官能团的中和程度。
卡波姆974P NF是一种高分子量的丙烯酸化学交联聚合物，其未离解羧酸官能团的C=O伸缩带位于1695 cm(-1)处。卡波姆974P NF中羧酸官能团中和程度的定量测定基于通过DRIFT光谱在1570 cm(-1)处测量的羧酸根阴离子的不对称C=O伸缩。
为了克服因样品制备（粉末、颗粒和片剂）产生的光谱差异，并努力提高分析方法的精度，采用了以下方法：（1）内标；（2）光谱的一阶导数以消除基线漂移的影响；（3）中和后的卡波姆974P NF中羧酸根阴离子峰（1570 cm(-1)）的C=O伸缩一阶导数与内标峰（866 cm(-1)）的一阶导数之比。上述数据处理技术被证明优于通常的峰高或峰面积方法。一阶导数之比（1570 cm(-1)/866 cm(-1)）的校准曲线是卡波姆974P NF中羧酸官能团中和度从0.0%到100.0%范围内羧酸钠质量的线性函数（图1a）。在实验误差范围内未观察到粒度或样品制备的影响。
使用库贝尔卡-蒙克函数分析的DRIFT光谱是用于常规测定复杂药物制剂中卡波姆974P NF中羧酸官能团中和程度的有力工具。
