Effect of Formaldehyde on the Physicochemical Properties of Soft Gelatin Capsule Shells

The effect of formaldehyde (FA) on three physicochemical properties of soft gelatin capsule shells was studied to interpret a change in the internal structure of those capsule shells whose disintegration time was remarkably prolonged by long-term storage at 40°C or more. Shells with different degrees of crosslinking were prepared by immersing the shells in 0-3% FA solutions for 10 min. These shells were evaluated by measuring the following three physicochemical properties : equilibrium swelling ratio (Seq), the gel strength of the swollen shells, and the percent of gelatin dissolved after 10 min (D10) from the shells.When the soft gelatin capsule shells were crosslinked by the treatment with FA, Seq determined by second-order kinetics in the swelling of the shells decreased linearly with an increase in the amount of FA. The gel strength of the swollen shells increased with an increasing amount of FA, whereas the D10 of gelatin from the shells was diminished drastically at a given small amount of FA. From these findings, we confirmed that a three-dimensional network was formed tightly by interchain covalent crosslinking in the shells by treatment with FA.These results were, on the whole, closely similar to the phenomenon observed in the disintegration test for the soft gelatin capsules stored long-term at 40°C or more. Therefore, it was suggested that the evaluations of these physicochemical properties were available also for capsule shells treated by heating to clarify a mechanism for the prolongation of the disintegration time of the soft gelatin capsules.