Detection of formaldehyde-induced crosslinking in soft elastic gelatin capsules using near-infrared spectrophotometry.

The purpose of this research was to monitor the migration of formaldehyde from a polyethylene glycol (PEG) fill into the gelatin shell of a soft elastic gelatin capsule (SEGC) using near-infrared (NIR) spectrophotometry. SEGCs were filled with five solutions of aqueous formaldehyde in PEG (0, 0.05, 0.10, 0.20, and 0.40 v/v%), stored at ambient conditions for 48 hr, emptied, and scanned in NIR spectrophotometer. Principal component regression (PCR) was employed to analyze the spectra of the empty capsules. Good correlation was established (r2 = 0.988) when actual concentrations of formaldehyde in the PEG fill of the capsules were regressed against the principal component (PC) values from NIR spectra of the emptied and washed capsules. The loadings of the first PC describe a baseline shift in the spectra that arises from a change in water concentration. Lower PC loadings reveal the presence of signals at 1780 and 2200 nm that are not due to water absorbance, confirming the hypothesis that chemical bonds are formed during the formaldehyde-induced crosslinking of the gelatin in SEGCs. Gelatin crosslinking, initiated by formaldehyde migration from the PEG fill into the shell of an SEGC, was detected by NIR spectrophotometry. When NIR was coupled to principal component analysis, a linear relationship was found between the NIR spectra of empty SEGCs and the amount of crosslinking induced by concentrations of formaldehyde in the original fill material.