Evaluating the Effectiveness of Papain and Bromelain as Dissolution Tier 2 Enzymes for Cross- Linked Soft Gelatin Capsules

Linked Soft Gelatin Capsules S. Tindal, K. Flood, J-E. Early, L. Covington, Z. Karjoo, E. Bailey Catalent Pharma Solutions Purpose USP <711> Dissolution is under revision to update the Tier 2 testing parameters for gelatin capsules where cross-linking of the gelatin has been observed and is impacting the dissolution results of the gelatin capsule. The revision introduces two new enzymes for use in Tier 2 testing over the pH ranges where the current enzymes are not effective in cleaving the cross-linked gelatin to enable rupture and disintegration of the cross-linked capsule. The new enzymes, papain and bromelain, are included for use in dissolution media with pH values ranging from 4.0 – 6.8. The revision also changes the pH range where pepsin is used from 1 – 6.8 to 1 – 4, increases the amount of pancreatin from 1750 UPS units / L to 2000 USP units / L and provides guidance for the use of an enzyme pre-soak for media where enzyme activity is inhibited (i.e., media containing some surfactants).