Case Study: Photostability Challenges in Soft Gelatin Capsules

Photostability Challenges in Soft Gelatin Capsules: A Formulation Case Study

Soft gelatin capsules (softgels) are widely used for oral delivery of lipophilic drugs and supplements due to their ease of administration and effective bioavailability. However, these dosage forms are also among the most vulnerable to photodegradation. Both the gelatin shell and the encapsulated fill can be impacted by exposure to light, particularly UV and visible radiation. This expert-level case study examines the photostability challenges encountered during the development of a light-sensitive softgel formulation and outlines solutions related to formulation optimization, packaging design, and compliance with ICH Q1B guidelines.

1. Photostability Risks in Soft Gelatin Capsules

Shell Sensitivity:

Gelatin and plasticizers like glycerin are prone to yellowing and oxidation under light
UV exposure can cause cross-linking or weakening of the shell, leading to brittleness or leakage

Fill Material Vulnerabilities:

Lipophilic solutions (e.g., oils, surfactants) can degrade or form radicals under light
Drug molecules suspended in oily bases may undergo photooxidation, particularly if unsaturated lipids are present

Additional Risk Factors:

Transparent or semi-transparent capsule shells transmit light to internal fill
Improperly selected capsule dyes may degrade or discolor under UV/visible light

2. Case Study Background: Omega-3 and Astaxanthin Softgel

Formulation Overview:

Softgel filled with a lipid-based mixture of omega-3 fatty acids and astaxanthin (a carotenoid antioxidant)
Intended for health supplements in tropical markets (Zone IVb)

Initial Observations:

Softgels developed brown discoloration after 5 days of storage under fluorescent light
HPLC analysis showed >10% degradation of astaxanthin content
Visible softening and capsule fusion observed at the contact points

3. Photostability Testing According to ICH Q1B

Study Design:

Softgel samples exposed in clear blister packs under xenon arc lamps
Total exposure: 1.5 million lux hours and 250 Wh/m² UV
Controls stored in dark under identical temperature and humidity conditions

Key Parameters Measured:

Visual appearance and color uniformity
Assay of astaxanthin and omega-3 fatty acids
Shell integrity (leakage, brittleness, fusion)
Impurity profile (oxidation byproducts and aldehyde formation)

Findings:

Astaxanthin degraded by 15% in light-exposed samples vs 3% in dark controls
Softgels lost elasticity and showed tackiness in light-exposed groups
Appearance changed from deep red to pale orange with blotching

4. Root Cause Analysis

Primary Contributors to Degradation:

Capsule shell: Light penetration and photoreactive gelatin constituents
Fill material: Highly unsaturated fatty acids prone to oxidation
Packaging: Clear blister offered insufficient light shielding

Additional Observations:

Dye used to color the softgel shell was not photostable under UV light
No light-protective agents (e.g., UV filters, antioxidants) included in shell or fill

5. Formulation and Packaging Interventions

Formulation Improvements:

Included tocopherol and ascorbyl palmitate as antioxidants in the fill
Switched gelatin source to one with lower UV-absorbing protein fractions
Increased fill viscosity to slow internal diffusion of reactive oxygen species

Shell Color Optimization:

Replaced unstable dye with a certified light-stable red iron oxide pigment
Tested multiple opacity levels by varying titanium dioxide concentration

Packaging Redesign:

Switched from clear PVC blister to foil-foil blister
Included a secondary carton with foil lining to block external light exposure
Modified label to read “Protect from light. Store in original package.”

6. Retesting and Regulatory Documentation

Post-Intervention Photostability Study:

Repeated ICH Q1B exposure with reformulated softgels
Degradation reduced to <5% for astaxanthin and <2% for omega-3s
Shell remained intact, with no visible tackiness or discoloration

Regulatory Documentation Prepared:

3.2.P.2.5: Justification for container-closure system and shell modifications
3.2.P.8.3: Photostability data comparing original and improved designs
3.2.P.7: Description of protective carton and foil blister combination

7. Best Practices for Managing Photostability in Softgels

Preventive Formulation Strategies:

Use light-stable colorants and UV absorbers in shell material
Include antioxidants in the fill to scavenge reactive oxygen species
Opt for gelatin alternatives like HPMC or pullulan in extreme cases

Packaging Guidelines:

Prefer foil-foil blisters or amber HDPE bottles for light-sensitive softgels
Use secondary packaging with verified light barrier properties
Print clear storage instructions for patients and distributors

8. Supporting SOPs and Templates

Available from Pharma SOP:

Photostability Testing SOP for Softgel Capsules
Softgel Shell Formulation Checklist for Light Sensitivity
Blister Packaging Comparison Template
Degradation Analysis and Visual Inspection Log Sheet

Additional photostability resources are available at Stability Studies.

Conclusion

Photostability challenges in soft gelatin capsules require a multidimensional approach—addressing not just the fill material but also the shell composition and the packaging system. This case study illustrates how understanding degradation mechanisms, optimizing formulation components, and using protective packaging can successfully mitigate light-induced risks. By aligning with ICH Q1B and WHO PQ standards, manufacturers can ensure product integrity, regulatory acceptance, and patient safety across global markets.