Development of a calibration model for a five components pharmaceutical formulation by near infrared spectroscopy.

摘要

Pharmaceutical companies are required to perform blend uniformity analysis (BUA) during the validation of a new product. A sample thief is often used to obtain a sample of the powder mixture, which is analyzed by High Performance Liquid Chromatography (HPLC) or Ultraviolet-visible (UV-Vis) spectroscopy. In this project a 5% (w/w) active pharmaceutical ingredient (API) blend with five components was developed. Near infrared spectra of the samples were obtained after stream sampling from the V-blender and analyzed by UV-Vis for the API content to develop three different calibration model varying spectral regions. Chemometrics techniques as Partial Least Squares (PLS), and Principal Component Analysis (PCA) were used to develop calibration models. The calibration models were then used to determine ibuprofen content of samples from a validation blend. PCA was also used as a qualitative method to evaluate blend uniformity. A blending profile study was prepared using the standard deviation of the drug content and the near infrared spectra versus blending time having the same behavior. A comparison between sample thief and stream sampling techniques was also conducted. The root mean square errors of prediction for the three different calibration models were 2.239, 1.999, 2.697mg/g. The PCA technique was not a viable qualitative technique to evaluate blending uniformity. Segregation was observed in the sample thief analysis.