Laboratory of Pharmaceutical Technology, Musashino University Graduate School of Pharmaceutical Sciences, Shinmachi, Nishi-Tokyo, Japan.
Drug Dev Ind Pharm. 2012 Apr;38(4):412-9. doi: 10.3109/03639045.2011.608679. Epub 2011 Sep 28.
The relationship between lubricant-mixing time and dissolution time was investigated, and we established a calibration model to predict dissolution time by near infrared (NIR) spectroscopy and the rationale of the prediction. The bulk powder consisted of theophylline, lactose, and potato starch were pre-mixed. After magnesium stearate (Mg-St) was added, the material was mixed for up to 180 min. The mixed powders were compressed to tablets and dissolution tests were performed. From each dissolution curve, 50% dissolution time (T50) was calculated. The NIR spectra of each tablet's upper surface was measured and a chemometric analysis was conducted. With the extension of mixing time, T50 was prolonged. The Mg-St widely covered the surface of each particle of the bulk powder after material mixing. This coating effect may decrease the wettability of the particles and cause the prolongation of dissolution time. The T50 was predicted by NIR spectroscopy with chemometrics and a calibration model was established. The regression vector showed typical peaks derived from -CH group of Mg-St, and it is suggested that those peaks, which were caused by the thin layer extension of Mg-St particles over the particle surfaces of other materials, contributed to the prediction of T50 prolongation. These studies show the usefulness of NIR measurements to control the effect of a lubricant in the process of raw powder material mixing.
考察了润滑剂混合时间与溶解时间的关系，并建立了近红外（NIR）光谱预测溶解时间的校准模型及其预测原理。将茶碱、乳糖和马铃薯淀粉的粗粉预混合，加入硬脂酸镁（Mg-St）后，将物料混合至多 180 分钟。将混合粉末压制成片剂并进行溶解试验。从每条溶解曲线中计算出 50%溶解时间（T50）。测量每个片剂上表面的 NIR 光谱并进行化学计量分析。随着混合时间的延长，T50 延长。物料混合后，Mg-St 广泛覆盖粗粉中每个颗粒的表面。这种覆盖效应可能会降低颗粒的润湿性，导致溶解时间延长。用化学计量学的 NIR 光谱预测 T50 并建立了校准模型。回归向量显示出典型的源于 Mg-St 的-CH 基团的峰，表明这些峰是由 Mg-St 颗粒在其他材料颗粒表面的薄层延伸引起的，有助于预测 T50 延长。这些研究表明，NIR 测量在控制原料药混合过程中润滑剂的效果方面非常有用。
