Effect of degradation of peg 600 on color fading and crosslinking in soft gelatin capsule shell

Abstract

Autoxidation of polyethylene glycol (PEG) 600, which is a hydrophilic liquid commonly filled in soft gelatin capsules, results in formaldehyde which is an oxidizing agent. The objectives of the present study were to study the effect of formaldehyde on fading of brilliant blue dye and crosslinking in the soft gelatin capsules; also to investigate possibility of inhibition of PEG 600 autoxidation by a selected antioxidant. Nine PEG 600 based fill formulations were prepared according to a full factorial design with 2 factors and 3 levels of water (0, 5, 10 %w/w) and an antioxidant, i.e. d-α-tocopherol (0, 0.001, 0.05 %w/w). They were encapsulated in non-colored and brilliant blue colored shells. The capsules were stored in ambler glass bottles under 30oC/75%RH for 90 days. Physicochemical properties of capsules were evaluated. The results showed that autoxidation of PEG 600 occurred and initial water content in the formulation had a significant effect on formaldehyde formation analyzed at 14 days (p-value = 0.001). The maximum level of d-α-tocopherol used in this study could not inhibit PEG 600 autoxidation. Color fading was not visually observed. However, delta E of capsule shells at 90 days was increased from that at first day and the total color content was reduced in some formulations. Brilliant blue in the shell was found to migrate into PEG 600 based liquid fill. Moreover, crosslinking of the gelatin shell could be detected by FT-IR spectroscopy and it was confirmed by dissolution results. Overall, it could be concluded that autoxidation of PEG 600 resulting in formaldehyde which could cause a problem of gelatin cross-linking, rather than fading of brilliant blue dye.