Near-Infrared Assay and Content Uniformity of Tablets
Near-infrared (NIR) assay and content uniformity of tablets provide fast, accurate means of monitoring tablet production that are in step with FDA's process analytical technology initiative.The authors discuss the process for testing a newly released NIR tablet analyzer to determine instrument precision and accuracy using chlorpheniramine maleate tablets.The data show promising results that could relieve laboratory workload of high-performance liquid chromatography analysis and bring analysis closer to..
Near-infrared spectroscopy (NIRS) is an analytical technique based on absorption measured in the near-infrared region of the
electromagnetic spectrum that is between the visible and the mid-infrared (IR). The fundamental absorption bands of functional
groups occur in the mid-IR and are very strong. Usually, potassium bromide pellets, mulls, or dilutions are required to bring
the absorbances within the linear range of the mid-IR detector. The overtone absorptions of these fundamental bands occur
in the NIR spectral region and allow direct measurement without sample preparation because of the relative weakness of absorption.
The OH, CH, NH, and SH bonds have the strongest overtone absorbances in the NIR region (1).
There is considerable interest in the ability to test solid-dosage form samples more frequently than the 10 per batch specified
by the US Pharmacopeia monograph on content uniformity. Interest has increased in using NIR for tablet assay and content-uniformity testing because
of concerns of the European Union for better statistically based sampling and the US Food and Drug Administration's initiative
on process analytical technology (PAT) for better understanding and monitoring of production (2). NIR can be used as a rapid
at-line analysis method to obtain processing feedback in near real time during a tableting campaign. Transmission NIRS through
the tablet has been preferred to reflectance NIRS because of heterogeneity within tablets (3, 4). The reflection NIRS technique
may be used for coating analysis, but for bulk tablet analysis, the transmission NIRS technique may yield more consistent
Laboratory methods for tablet assay and content uniformity are usually time-consuming because they routinely are done by high-performance
liquid chromatography (HPLC), which requires lengthy calibration runs, the mixing of buffers, and the procurement and disposal
of volatile solvents. Analyzing 10 tablets for content uniformity may take hours, and the results may not be available to
tablet-press operators or for batch release for many days or even weeks after the tablets are compressed. Statistical process
control (SPC) techniques can be applied while measuring the tablets with NIR in real time during tableting so that assay and
content-uniformity problems can be detected before they go beyond acceptable limits.
Five batches of tablets (0.25-in. diameter and 100-mg weight) with 0 mg (placebo tablets), 0.1 mg, 0.5 mg, 1.0 mg, and 2.0
mg of chlorpheniramine maleate (CPM) per tablet were formulated and compressed on a tablet press (HT-AP 18 SS-U/I rotary tablet
press, Elizabeth Hata International, Inc., North Huntingdon, PA).