Crocetin esters (crocins) are a series of glycosides of a C20-dicarboxylic acid, called crocetin. They are responsible for the coloring properties of Crocus sativus L. dry stigmas (saffron) that comprise the most expensive spice in the world.
Crocins are freely water-soluble in contrast to most carotenoids and are highly valued in the food industry. In addition to their known applications in the food industry, an increasing number of studies indicates a variety of pharmacological actions for crocetin and crocins.
Kyriakoudi and colleagues found that the exposure of saffron aqueous extracts to the conditions mimicking the human gastrointestinal tract resulted in 50% loss of crocetin esters.
Monitoring changes in the extracts at oral, gastric, or intestinal phases, separately, verified this view pointing out the critical effect of pH, temperature, and duration of process but not of digestive enzymes .
: A. Kyriakoudi, et al., Changes in Total and Individual Crocetin Esters upon in Vitro Gastrointestinal Digestion of Saffron Aqueous Extracts, Journal of Agricultural and Food Chemistry, 2013, 61 (22), pp. 5318-5327
Changes in Crocetin Esters upon in Vitro Gastrointestinal Digestion of Saffron Aqueous Extract, adapted from reference .
Unlike the aforementioned digestion procedure, at NextHerbal Labs:
- The chemical stability as well as the release rate of four major saffron phytochemicals viz. Picrocrocin, Safranal, Crocin 1, and Crocin 2 were measured by means of dissolution testing. Dissolution is an official technique in the pharmaceutical and nutraceutical analyses. Currently, dissolution testing is routinely used to provide critical in vitro drug release information for quality control (QC) purposes, can be a promising tool for predicting in vivo drug release, and plays an essential role in the Biopharmaceutics Classification System (BCS)–based biowaiver approach . - Instead of saffron aqueous extract, Safr'Inside™ - a standardized saffron solid/powder extract was used in our studies. 30 mg of this powder was encapsulated in hard gelatin capsule (Vcaps Plus, Capsugel) and each capsule was put in a vessel containing dissolution medium (e.g., 0.1 N HCl, Phosphate buffer solution pH 6.8, Acidified water pH 2.0, and Acidified water pH 3.0). - At different time intervals, an aliquot was sampled from Dissolution Tester (Labindia) assisted with USP Apparatus # 2 (Paddle) and rotated at 100 rpm. - At the end, the sample was filtered through a 0.45 μm syringe filter and transferred into amber 2-mL vials for HPLC−UV analysis. : S. Klein, Advancements in Dissolution Testing of Oral and Non-oral Formulations, AAPS PharmSciTech, 2019, 20 (266), DOI: 10.1208/s12249-019-1479-8
Dissolution tester (model: DS 8000,Labindia Analytical HPLC (model: 1100, Agilent Technologies, CA, USA) Instruments, India)
According to the Picrocrocin and Safranal plots, the concentration profiles between four media/pHs show very small differences. It means that the dissolution and stability of mentioned markers are pH-independent.
The slope of concentration decline for Safranal is higher than that for Picrocrocin. In other words, Picrocrocin is more stable than Safranal. As Safranal is a volatile molecule, it can escape from the medium at dissolution temperature of 37 ºC.
As expected, the rank of two crocins' concentrations in four pHs is: pH 6.8 > pH 3.0 > 0.1N HCl ≈ pH 2.0. Crocins are most stable in neutral aqueous medium (e.g., at pH 6.8) but degrade quickly at pH ≤ 2 within 10 min.
This study shows that dissolution could be considered as a powerful technique for in vitro characterization and quality control of herbal dietary supplements like saffron. Moreover, crocins which their pharmacological activities are well documented are very prone to degradation in acidic medium (gastric fluid). Therefore, everysaffron-based nutraceuticals for oral administration should be protected against acidby using an enteric coat(ed)/EC or acid/gastric resistant encapsulation.
We evaluated three types of delayed release empty capsules for encapsulation of Safr'Inside™ powder: AR-Caps (CapsCanada), DRcaps (Capsugel), and Bio-VXR (BioCaps Enterprises Inc.). Regarding two criteria: a) suitability for dietary supplement or nutraceutical application and b) proper dissolution attributes in both acidic and buffer stages, only one type capsule among three ones was chosen.
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