(T1130-05-27) Development of a Delayed Release Softgel Dosage Form

Purpose: Pectin, a naturally derived polysaccharide, is a versatile tool for oral drug delivery applications. Softgel capsules formed by the combination of pectin and gelatin can be used as a delayed-release delivery technology for pharmaceutical and nutraceutical applications. Delayed-release dosage forms provide benefits such as enteric protection of sensitive API from the stomach's acidic environment, releasing the drug at the preferred site of absorption, and preventing unpleasant side effects from the release of the API in the stomach. This project is aimed at developing a delayed release softgel dosage form by incorporating an enteric polymer directly into the capsule shell. This innovative method of softgel manufacturing eliminates the need for an additional pan-coating step.

Methods: Pectin was incorporated into the gelatin shell during softgel manufacture without the need for a typical coating step. In order to evaluate the robustness of the enteric functionality of delayed-release softgel, two-stage dissolution tests were conducted using Pion's fiber-optic probes. Drug release was measured in different dissolution media (e.g., FaSSGF, intermediate pH [pH 3.0 – 5.0] medium, enzymatic medium, and alcohol-containing medium). In addition, two-stage disintegration tests were performed in FaSSGF and standard buffer for quantitative rupture testing of the softgels.

Results: The softgel capsules filled with refined fish oil or acetaminophen had a regular clear appearance and robust physical properties indicated by high seam and burst strength which were measured by texture analyzer. The softgels stayed intact in acidic pH 1.2 medium with and without enzyme for 120 minutes. In addition, the softgels stayed intact in a pH 5.0 medium for up to 60 minutes. They then ruptured and released the fill material within 45 minutes in pH 6.8 ~ 7.6 buffer medium with or without enzyme during dissolution and disintegration tests. Additionally, the enteric softgels have excellent thermal stability, and good physical and chemical stability for up to 24 months.

Conclusion: A delayed release softgel has been successfully developed to provide an alternative softgel platform where enteric release is desirable, without needing the additional functional coating step. The softgels have been demonstrated to meet pharmacopeia standards for in-vitro performance with robust enteric performance in acidic and intermediate pH environments. The enteric softgels also have good physical and chemical stability. This innovative technology provides a dosage form that can deliver nutraceutical ingredients or active pharmaceutical ingredients that require protection from an acidic stomach environment or enhance absorption by delivering the drugs to the lower gastrointestinal tract.


Figure 1 Delayed Release Acetaminophen capsule 2 stage dissolution


Table 1 Physical stability Results of two stage dissolution of delayed release fish oil capsules


Table 2 Chemical stability results of delayed release fish oil capsules