DETERMINATION OF EXTENT OF FORMALDEHYDE-INDUCE CROSS-LINKING IN HARD GELATIN CAPSULES BY NEAR-INFRARED SPECTROPHOTOMETRY

Purpose. To predict the degree of crosslinking from formaldehyde-stres sed hard gelatin capsules (HGCs) using near-infrared spectrophotometry (NIR). Methods. HGCs were exposed to a 150 ppb atmosphere of formalde hyde for 2.25, 4.60, 9.42, 16.0 and 24.0 hours. The capsules were fill ed with fresh amoxicillin, placed in a 90 degrees conical reflector co ne, and scanned in a NIR spectrophotometer. Principal component regres sion (PCR) was employed to analyze the spectra of the intact capsules. Dissolution profiles were then obtained for each experimental group. Results. The dissolution of amoxicillin from the capsules at pH 1.2 wa s found to decrease with increasing time of exposure to the formaldehy de atmosphere. A set of principal components (PCs) was farmed by a lin ear combination of the absorbance values at each wavelength scanned. A good correlation was established (r(2) = 0.963) when PC values from t he NIR spectra of the HGCs were regressed against percentage of amoxic illin dissolved at 45 minutes, at pH 1.2. Water content of the capsule s was found to be the largest determinant in the variation between HGC spectra at each exposure time. Conclusions. NIR spectrophotometry, co mbined with PCR, was successful at not only predicting dissolution of HGCs exposed to formaldehyde, but also at determining which wavelength s contributed most to spectral variation of these stressed HGCs.