Physical stability and resistance to peroxidation of a range of liquid-fill hard gelatin capsule products on extreme long-term storage

Abstract

Background: The industrial take-up of liquid-fill hard capsule technology is limited in part by lack of published long-term physical and chemical stability data which demonstrate the robustness of the system.

Objective: To assess the effects of extreme long-term storage on liquid-fill capsule product quality and integrity, with respect to both the capsules per se and a standard blister-pack type (foil–film blister).

Materials and methods: Fourteen sets of stored peroxidation-sensitive liquid-fill hard gelatin capsule product samples, originating ~20 years from the current study, were examined with respect to physical and selected chemical properties, together with microbiological evaluation.

Results and discussion: All sets retained physical integrity of capsules and blister-packs. Capsules were free of leaks, gelatin cross-linking, and microbiological growth. Eight samples met a limit (anisidine value, 20) commonly used as an index of peroxidation for lipid-based products with shelf lives of 2–3 years. Foil–film blister-packs using PVC or PVC–PVdC as the thermoforming film were well-suited packaging components for the liquid-fill capsule format.

Conclusion: The study confirms the long-term physical robustness of the liquid-fill hard capsule format, together with its manufacturing and banding processes. It also indicates that various peroxidation-sensitive products using the capsule format may be maintained satisfactorily over very prolonged storage periods.

Keywords::

• Long-term
• disintegration
• cross-linking
• leak
• blister
• microbiological
• lipid
• pharmaceutical
• nutraceutical

Acknowledgement

The authors gratefully acknowledge helpful discussions with Dr. Stephen Brown and Dr. Jane Fraser of Encap Drug Delivery in preparing this article.

Declaration of interest

The authors report no declarations of interest.