THE EFFECT OF COMPRESSION FORCE ON THE NEAR-INFRARED SPECTRA OFT ABLET DOSAGE FORMS

Abstract

The United States Pharmacopoeia/National Formulary (USP/NF) sets the standards and maintains monographs for the evaluation of tablets. These include Official Tests for uniformity of dosage units and disintegration testing, and Unofficial Tests for mechanical strength (hardness, crushing strength) and resistance to abrasion (friability). Current methods of analyzing tablet hardness involve the indirect measurement of the mechanical strength of a tablet through destructive and time-consuming procedures. Near-infrared reflectance spectroscopy (NIRS) is gaining acceptance in the pharmaceutical industry as a non-invasive and non-destructive method for the analysis of finished dosage forms and raw materials. This investigation outlines methods used to evaluate various tablet parameters using NIRS and the achievement of successful predictions of those parameters. NIR models for tablet hardness and density were developed for 15% and 20% hydrochlorothiazide and 2% and 6% chlorphenirarnine maleate in a 0.5% magnesium stearate and rnicrocrystalline cellulose matrix. NIR calibration models for tablet hardness were developed for flat-faced and convex round tablets containing 6% chlorphenirarnine maleate and 0.5% magnesium stearate, with either rnicrocrystalline cellulose or dibasic calcium phosphate dihydrate. Although the NIR response to changing hardness was the same regardless of the drug, separate models were required for tablets of different geometries. Scored tablets also required formulation specific calibrations for NIR hardness determination. Models for upper and lower compression forces were developed for flatfaced round tablets containing 6% chlorphenirarnine maleate and 0.5% magnesium stearate, with either rnicrocrystalline cellulose or dibasic calcium phosphate dihydrate. NIRS prediction of these parameters was at least as precise as the reference hardness test. Calibration of compression forces was successful for rnicrocrystalline cellulose-based tablets, but not for the more variable dibasic calcium phosphate dihydrate systems. The methods described in this investigation may serve as a model for the future acceptance of NIRS as an alternative to current compendia! methods for tablet hardness.