Do softgel manufacturing or gastric conditions break down carrageenan into poligeenan?

Carrageenan (CGN) is a high molecular weight (typically 200-800 kDa) polysaccharide derived from red seaweed. It is used as a food additive and as a functional excipient in pharmaceutical and nutraceutical products. In softgels, CGN can offer advantages over gelatin, including pH tolerance up to 12, thermal stability during processing (70-90 °C), and resistance to cross-linking. However, under extreme conditions, such as prolonged exposure to strong acid and temperatures exceeding 100 °C, CGN may degrade into low-molecular-weight fragments (<20 kDa), known as poligeenan, which has been linked to toxicological effects. This study investigates whether conditions used in softgel manufacturing or simulated gastrointestinal digestion could cause CGN to degrade into poligeenan or similar low-molecular-weight species. Iota carrageenan from three different batches used in food, nutraceutical, and pharmaceutical products was subjected to controlled stress conditions, including high temperature and low pH. Molecular weight distributions were measured using gel permeation chromatography (GPC). Carrageenan exhibited excellent thermal stability at 95 °C and 105 °C without significant molecular weight reduction when not exposed to acid. Under gastric-simulating conditions (pH 1.2 at 37 °C), moderate hydrolysis occurred, but fragments remained above the 20 kDa threshold. In contrast, combined acid and high-temperature treatment induced substantial degradation, yielding fragments under 20 kDa. No low-molecular-weight fragments consistent with poligeenan (<20 kDa) were observed under relevant conditions, reinforcing carrageenan's safety profile for use as a functional excipient in controlled-release dosage forms and dietary supplements.