(M1430-12-71) Evaluation on Stability of Plant Based Softgels (SeaGel® Technology) versus Gelatin Softgels

Purpose: Softgels continuously serve as a preferred dosage form for oral drugs and dietary supplements. As softgels can easily encapsulate a variety of liquid and semi-solid formulations, they have been used to deliver poorly soluble active ingredients and provide enhanced bioavailability. Gelatin softgels currently dominate the pharmaceutical industry, but there are numerous challenges with the material. For example, gelatin has the potential to crosslink with active ingredients leading to reduced solubility of the capsule shell. Gelatin is sensitive to high temperature and high/low humidity conditions, presenting challenges with storage and shipment of gelatin softgels. There is also a growing consumer preference for non-animal products to suit different dietary needs (vegan, halal, kosher, etc). In this study, a simple model fill formulation was used to encapsulate a poorly soluble active pharmaceutical ingredient (API), Ibuprofen (IB), using either gelatin as the shell forming material or a plant-based material based on IFF’s SeaGel® technology (noted as SeaGel® softgels). In this research, both USP I method and modified USPI/HPLC method was used to study the dissolution behavior of Ibuprofen from gelatin and SeaGel® soft capsules stored at both accelerated conditions (40 ⁰C, 75% RH) and long-term conditions (30 ⁰C, 65% RH) for more than 3 months.

Methods: Gel masses of gelatin or SeaGel® (carrageenan and starch) were prepared on a Ross CDA-4 mixer. The prepared gel masses were then transferred to a rotary die process using a Farmateck FTK55 encapsulator. Capsules were made using size 7.5 oval dies and filled with 400 mg of a 7.3 wt % IB in medium chain triglycerides (MCT). Capsule disintegration was tested using disintegration tester (model QC-21, Henson) as described in USP < 701 >. A modified USP I method was used for in vitro dissolution experiments with Agilent 708-DS and spectrophotometer Carey 60. HPLC analyses of IB were also conducted using an Agilent chromatograph consisting of G1311B pump, G1329B autosampler, G1316A oven, and G1314F UV detector. Capsule burst strength, elasticity, and hardness were measured using a texture analyzer with TA-4 probe and 1 mm/s compression speed.

Results: For freshly produced SeaGel® and gelatin softgels, it was observed that the plant based SeaGel® softgels have slightly slower disintegration and delivery at dissolution time less than 80 minutes. However, the f₂ similarity factor of SeaGel® to gelatin softgels was greater than 52 at all time points, which indicates an average difference of less than 10% between SeaGel® softgels and gelatin softgels. Additionally, when stored at accelerated or long-term storage condition for more than one month, SeaGel® softgels showed no change in disintegration or dissolution performance while gelatin softgels showed significantly slower disintegration and dissolution behavior than freshly produced gelatin softgels. As an example, Figure 1 shows a comparison of disintegration time as a function of storage time. Furthermore, the mechanical properties of gelatin softgels indicated possible cross-linking and migration of fill components and has higher variability than SeaGel® softgels as a function of aging time and aging conditions. This is consistent with similar findings of other scientists. ¹

Conclusion: Dissolution of an active in the dosage form is critical for absorption and bioavailability, and for product quality and consistency assessments during drug product life cycle. SeaGel® softgels showed approximately equivalent API dissolution behavior as that of gelatin capsules at the time of capsule production, but better stability than that of gelatin softgels.

References: 1. Chen, T. Humidity Influence to the Thermal and Mechanical Properties of Gelatin Capsules.

Acknowledgements: We would like to thank Kevin O’Donnell and Shrikant Khot for discussion and support of this report.


Figure 1. Comparison of disintegration time for gelatin soft gels and SeaGel® softgels in buffer dissolution medium (a) pH 1.2 and (b) pH 7.2 under accelerated storage condition 40 °C and 75% RH