Pharmaceutical Ointment Tubes: Material Migration Risks and Seal Integrity Verification Methods

Pharmaceutical ointment tubes are widely used for semi-solid formulations such as creams, gels, and ointments. As primary packaging materials, these tubes must not only ensure containment and protection but also comply with stringent regulatory standards regarding material compatibility and seal integrity. Two critical quality concerns in ointment tube selection and validation are material migration risks and sealing performance. This article discusses the causes and control of material migration, as well as the testing methods used to verify sealing integrity.

1. Material Migration Risks in Ointment Tubes

Material migration refers to the movement of substances from the tube’s inner layer into the pharmaceutical product. This can pose safety risks and affect the drug’s stability and efficacy.

Common Sources of Migration:

• Plasticizers or stabilizers in polyethylene (PE) or polypropylene (PP) tubes

• Residual monomers or catalysts from the manufacturing process

• Printing inks or adhesives migrating through the laminate layer in laminated tubes

Risk Implications:

• Toxicity: Migrated substances may exceed permissible daily intake (PDI) levels.

• Drug degradation: Interactions between migrants and the API or excipients.

• Organoleptic changes: Alteration of smell, taste, or color in dermatological preparations.

Control Strategies:

• Use of pharmaceutical-grade polymers certified by pharmacopeias (e.g., USP <661>, EP 3.1)

• Conducting migration studies according to ICH and EMA guidelines

• Selecting multi-layer laminated tubes with functional barrier layers such as EVOH

2. Seal Integrity Verification for Ointment Tubes

Proper sealing prevents microbial contamination, water loss, or air ingress, all of which can compromise product quality.

Key Sealing Areas:

• Tube tail sealing (heat-sealed or crimped)

• Cap-thread interface

• Tamper-evident closures (if applicable)

Common Seal Integrity Tests:

1. Vacuum Leak Test

   • Tubes are submerged in water under vacuum. Bubbles indicate leaks.

2. Dye Penetration Test

   • Tubes are filled with a colored solution; external dye appearance suggests a compromised seal.

3. Pressure Decay Test / Helium Leak Test

   • Measures pressure loss over time to detect micro-leaks in high-precision testing.

4. Torque Testing of Caps

   • Ensures that the screw cap maintains a seal during transportation and usage.

3. Regulatory and Quality Considerations

Regulatory bodies such as the FDA, EMA, and NMPA require that all primary packaging materials:

• Are non-reactive, non-leachable, and suitable for intended use

• Undergo extractables and leachables (E&L) studies

• Are validated for seal integrity under expected storage and transportation conditions

Proper Quality by Design (QbD) approaches during tube selection and sealing process development can help mitigate risks early in the product development cycle.

Conclusion

In the development of pharmaceutical ointments, the packaging tube is a critical component that must meet strict standards for safety, compatibility, and integrity. Controlling material migration and ensuring seal reliability are essential for maintaining product quality and patient safety. Through rigorous material selection, regulatory-compliant testing, and continuous quality assurance, manufacturers can confidently deliver stable and effective semi-solid formulations to the market.