(19d) Influence of Physical Factors and Powder Properties On the Accuracy and Precision of Multivariate Calibration Models Using NIR Spectroscopy

During the last decade the study and implementation of NIR spectroscopy has increased exponentially giving a valuable advance to the science especially in the study of powder behavior. The pharmaceutical industry is moving toward the use of continuous production enabling the use of continuous powder mixing. This last step involves the use of important sensors to measure homogeneity of mixing online which has been a great challenge. NIR spectrometer plays an important role in this matter and that is why a continuous deep study is necessary in order to be completely sure of the degree of prediction that can be achieved under different physical conditions. Considering this subject different calibration models were made in a complete range of concentration from 0 to 100% w/w for Naproxen as API. The excipient used was Lactose Monohydrate with Magnesium Stearate 1%. The mixtures were prepared with intervals of 1 % from 0 to 30% and with intervals of 5 % from 30% to 100%. These powders have different properties making the mixture a challenge for the NIR. The powder mixing was done initially in a V-blender and the mixing time for all the mixtures were the same. Then the powders were introduced in the continuous mixer rotated at different RPM and NIR spectra were taken with two different NIR spectrophotometers at the output stream and samples were taken to be analyzed and compared with UV spectrophotometer. Precision and exactitude results had variability that depends on the cohesion of the mixtures, average particle size and type of NIR.