Near-infrared spectroscopy as a nondestructive alternative to conventional tablet hardness testing.

Abstract

Near-infrared reflectance spectroscopy (NIRS) was used to evaluate and quantify the effect of compression force on the NIR spectra of tablets. Flat, white tablets with no orientation (scoring, etc.) were manufactured on a Stokes Rotary Tablet Press. NIRS was used to predict tablet hardness on the following four formulations and one placebo matrix: hydrochlorothiazide (HCTZ) 15% and 20% in a placebo matrix (microcrystalline cellulose and magnesium stearate), and chlorpheniramine maleate (CTM) 2% and 6% in a placebo matrix. Five or six levels of tablet hardness from 2 to 12 kg were used for each formulation. Laboratory hardness data was compared to NIR reflectance data using a NIRSystems Rapid Content Analyzer. Multiple linear regression and partial least squares regression techniques were used to determine the relationship between tablet hardness and NIRS spectra. An increase in tablet hardness produced an upward shift (increase in absorbance) in the NIRS spectra. A series of equations was developed by calibrating tablet hardness data against NIR reflectance response for each formulation. The results of NIRS hardness prediction were at least as precise as the laboratory hardness test (SE = 0.32). A NIRS method is presented which has the potential as an alternative to conventional hardness testing of tablets.