Multivariate figures of merit (FOM) investigation on the effect of instrument parameters on a Fourier transform-near infrared spectroscopy (FT-NIRS) based content uniformity method on core tablets.

Since near infrared spectroscopy (NIRS) was introduced to the pharmaceutical industry, efforts have been spent to leverage the power of chemometrics to extract out the best possible signal to correlate with the analyte of the interest. In contrast, only a few studies addressed the potential impact of instrument parameters, such as resolution and co-adds (i.e., the number of averaged replicate spectra), on the method performance of error statistics. In this study, a holistic approach was used to evaluate the effect of the instrument parameters of a FT-NIR spectrometer on the performance of a content uniformity method with respect to a list of figures of merit. The figures of merit included error statistics, signal-to-noise ratio (S/N), sensitivity, analytical sensitivity, effective resolution, selectivity, limit of detection (LOD), and noise. A Bruker MPA FT-NIR spectrometer was used for the investigation of an experimental design in terms of resolution (4 cm(-1) and 32 cm(-1)) and co-adds (256 and 16) plus a center point at 8 cm(-1) and 32 co-adds. Given the balance among underlying chemistry, instrument parameters, chemometrics, and measurement time, 8 cm(-1) and 32 co-adds in combination with appropriate 2nd derivative preprocessing was found to fit best for the intended purpose as a content uniformity method. The considerations for optimizing both instrument parameters and chemometrics were proposed and discussed in order to maximize the method performance for its intended purpose for future NIRS method development in R&D.

In vitro monitoring of dissolution of an immediate release tablet by focused beam reflectance measurement.

Changes in in vitro drug release profiles of oral dosage forms are commonly observed due to storage of drug product at elevated temperature and humidity. An example is presented of an immediate release drug product which underwent changes to both release profile and crystal form on storage at elevated humidity. The dissolution rate for unstressed tablets was comparable regardless of the crystal form present. Decreased release rate was only observed for stressed tablets that exhibited crystal form conversion. The cause of the dissolution change was determined by evaluating tablets manufactured with three drug substance crystal forms by fiber optic ultraviolet detection and focused beam reflectance measurement (FBRM). Tablets were also analyzed by near-infrared spectroscopy for crystal form determination. The observed change in dissolution rate correlated with detection of a greater number of larger particles by FBRM. FBRM results indicate increased aggregation of the tablet material due to crystal form conversion, resulting in the presence of slowly disintegrating and dissolving granules during the dissolution process. The improved understanding of the dissolution process allows evaluation of the potential in vivo impact of the stability changes.