Optimized, sustainable and scalable strategy for producing disodium crocetinate from Crocus sativus L. stigmas

Introduction Saffron ( Crocus sativus L.), one of the world’s most valuable spices, has significant potential as a source of bioactive compounds for food, pharmaceutical, nutraceutical, and cosmetic applications. Among its constituents, crocetin has attracted increasing attention because its sodium salt, disodium crocetinate, exhibits much higher water solubility and is of interest in pharmaceutical sciences. This study aimed to develop and optimize a potentially scalable, non-chromatographic approach for the high-purity production of crocetin and its water-soluble disodium salt from saffron crocins, while simultaneously recovering safranal as a valuable co-product. Methods An integrated and sustainable process was developed for the production of disodium crocetinate through sequential conversion of saffron crocins by hydrolysis, purification, and crystallization. Hydrolysis of total crocin extracted from saffron stigmas was optimized using response surface methodology (RSM). In parallel, safranal was concentrated and isolated by liquid–liquid extraction. The crocetin produced after hydrolysis was purified using a non-chromatographic procedure consisting of aqueous extraction for carbohydrate removal, methanolic extraction of polyphenolic impurities, and recrystallization in dimethylformamide. In addition, the greenness parameters were calculated for the process of purification in terms of environmental and human safety effects. Discussion The optimized hydrolysis process achieved a conversion yield of 85.5% with 75% purity. During processing, safranal content increased 12-fold and was successfully recovered as a valuable co-product. Crocetin purification by the developed non-chromatographic approach yielded a highly pure product, with purity estimated at 99.3% based on HPLC-DAD and HPLC-MS analyses. ChlorTox was calculated for ethanol, DMF, and Diethyl ether as 617478, 2982, and 1412, respectively. AGREE prep was estimated at 0.52 in the overall process. Overall, the proposed process offers an economical, efficient, simple, environmentally friendly, and potentially scalable strategy for the valorization of saffron in different applications.