Prospects for multivariate classification of a pharmaceutical intermediate with near-infrared spectroscopy as a process analytical technology (PAT) production control supplement.

NIR spectroscopy was applied to develop a fast and reliable quality control system for a pharmaceutical substance to support information obtained through PAT surveillance of its manufacturing process. After calculating different quantitative calibrations of the substance's key quality parameters, a general classification model has been derived to capture the over-all product grade. The final spectral quality conformity model consisting of 96 representative batches - covering high process variability - was sensibilized toward five important quality parameters by their incorporation as PLS responses.

Online process control of a pharmaceutical intermediate in a fluidized-bed drier environment using near-infrared spectroscopy.

In the production plant of an antibiotic substance, a new fluidized-bed drier has been installed. For online process control of the drying progress and determination of the ideal drying end point, a continuous near-infrared spectroscopic (NIRS) measuring setup was implemented to rapidly and simultaneously gain all essential product information. A bypass system outside the drier combined with a robust process probe proved to provide the best sampling system geometry.

Ionic liquids as superior solvents for headspace gas chromatography of residual solvents with very low vapor pressure, relevant for pharmaceutical final dosage forms.

1-n-Butyl-3-methylimidazolium dimethyl phosphate (BMIM DMP) was identified as the most suitable ionic liquid as solvent for the headspace gas chromatographic analysis of solvents with very low vapor pressure such as dimethylsulfoxide, N-methylpyrrolidone, sulfolane, tetralin, and ethylene glycol in a realistic matrix of commonly used excipients (carboxymethylcellulose, magnesium stearate, guar flour, and corn starch) in pharmaceutical products. Limits of quantification and limits of detection were in the low microgram per gram range. The detection of traces of sulfolane in a real sample of tablets containing the drug cefpodoxim proxetil demonstrated the applicability of the method.

Multivariate analysis and classification of the chemical quality of 7-aminocephalosporanic acid using near-infrared reflectance spectroscopy.

The capability of near-infrared (NIR) spectroscopy in comparison to conventional chemical testing to control the chemical quality of a pharmaceutical intermediate has been investigated. Multivariate projection methods including principal component analysis, partial least-squares discriminant analysis and soft independent modeling of class analogy have been evaluated. 7-Aminocephalosporanic acid has been chosen as an example providing a large variation of quality due to its relative chemical instability.