Pudipeddi Madhu, Zannou Erika A, Vasanthavada Madhav, Dontabhaktuni Aruna, Royce Alan E, Joshi Yatindra M, Serajuddin Abu T M
Novartis Healthcare Pvt. Ltd., 8th Floor, D Wing, I Labs, Hitech City, Hyderabad 500081, India.
J Pharm Sci. 2008 May;97(5):1831-42. doi: 10.1002/jps.21052.
Two methods for the measurement of surface pH of pharmaceutical solids, namely, the dye-sorption method and the slurry pH method, were compared. High purity drug substances, instead of excipients, were used as model solids, because acidic or basic impurities present in excipients could influence slurry pH. Solid test samples were prepared by sorption of methanol-water solutions of several indicator dyes, and their diffuse reflectance UV-visible spectra were measured. The solid surface pH values were estimated by comparing base-to-acid peak ratios of the diffuse reflectance UV-visible spectra of solid samples to the calibration plots of dye solutions in aqueous standard buffers of known pH. In the slurry pH method, pH values of concentrated slurries of the compounds in water were considered to represent solid surface pH. The agreement between the two methods was mixed and depended on the compound or the indicator used. It was concluded that in many cases calibration plots of indicator dye spectra in aqueous buffers were not applicable to the solid state, and, as a result, the reliability of the method was low. The slurry method provided a simple and reliable measurement of surface pH indicating that concentrated slurry may closely represent solid surface pH.
比较了两种测量药物固体表面pH值的方法，即染料吸附法和浆液pH值法。使用高纯度原料药而非辅料作为模型固体，因为辅料中存在的酸性或碱性杂质可能会影响浆液pH值。通过吸附几种指示剂染料的甲醇-水溶液制备固体测试样品，并测量其漫反射紫外-可见光谱。通过将固体样品漫反射紫外-可见光谱的碱峰与酸峰之比与已知pH值的水性标准缓冲液中染料溶液的校准曲线进行比较，估算固体表面pH值。在浆液pH值法中，化合物在水中的浓浆液的pH值被视为代表固体表面pH值。两种方法之间的一致性参差不齐，取决于所使用的化合物或指示剂。得出的结论是，在许多情况下，水性缓冲液中指示剂染料光谱的校准曲线不适用于固态，因此该方法的可靠性较低。浆液法提供了一种简单可靠的表面pH值测量方法，表明浓浆液可能与固体表面pH值密切相关。
