Designing an effective dissolution test for bilayer tablets tailored for optimal melatonin release in sleep disorder management.

This project aims to investigate the release performance of bilayer tablet (BL-Tablet) designed with both fast and slow-release technology, targeting sleep disorders. The tablet incorporates Melatonin, extracts of Eschscholzia californica and Melissa officinalis. In order to validate the effectiveness of the extended-release profile, an advanced dissolution test was herein proposed. This new method utilizes biorelevant intestinal fluid media and incorporates a stomach-to-intestine fluid changing (SIFC) system. To demonstrate the advantages of employing this method for assessing the controlled release profile of active ingredients, the dissolution results were compared with those obtained using the conventional EU Pharmacopoeia approach. Furthermore, the comparative analysis was extended to include a monolayer tablet version (ML-Tablet) lacking the slow-release technology. Technological characterization and bioaccessibility studies, including intestinal permeability test, were conducted as well to assess the pharmacological performance and bioavailability of active ingredients. The dissolution data recovered revealed that the two dissolution methods did not exhibit any significant differences in the release of ML-Tablet's. However, the dissolution profile of the BL-Tablet exhibited notable differences between the two methods particularly when assessing the behavior of the slow-release layer. In this scenario, both methods initially exhibited a similar release pattern within the first approximately 0.5 h, driven by the fast-release layer of the tablet. Following this, distinct gradual and sustained releases were observed, spanning 2.5 h for the EU Pharmacopoeia method and 8 h for the new SIFC-biorelevant dissolution method, respectively. Overall, the novel method demonstrated a substantial improvement compared to conventional EU Pharmacopoeia test in evaluating the performance of a controlled slow-release technology. Remarkably, the prolonged release technology did not have an adverse impact on melatonin intestinal absorption, and, consequently, maintaining its potential bioavailability of around 78%. Concluding, this research provides valuable insights into how the innovative dissolution test can assist formulators in developing controlled release formulations.

Barrier effect and wound healing activity of the medical device REF-FTP78 in the treatment of gastroesophageal reflux disease.

REF-FTP78 is a class IIb medical device present on the market with different trade names and developed for the treatment of gastroesophageal reflux disease (GERD). This medical device is based on polysaccharides from Aloe Barbadensis and fucoidans from brown seaweeds, such as Undaria pinnatifida and Fucus vesiculosus, and aims to exert a protective effect on the esophageal mucosa against the noxious components of refluxate. The present study reports on the efficacy of REF-FTP78 devoting a particular attention to the barrier effect and wound healing properties, combined with antioxidant and anti-inflammatory activities. Film-forming properties and barrier effect were investigated on in vitro reconstructed human esophageal epithelium, through TEER measurement and evaluation of caffeine and Lucifer yellow permeability, and in an ex vivo swine model of esophageal mucosa damage. Antioxidant and anti-inflammatory properties were evaluated in terms of scavenging activity towards DPPH, ABTS and NO radicals and a wound healing assay was carried out to study the influence of the product on cell migration. The obtained results highlighted a significant barrier effect, with a reduction in caffeine penetration equal to 65.3%, the ability to both repair and prevent the damage caused by an acid insult, confirmed by a good transepithelial resistance for the tissue treated with the tested item, and the capacity to promote wound healing. Furthermore, the tested product showed good antioxidant and anti-inflammatory properties in the performed radical scavenging assays. These findings support the use of REF-FTP78 in the treatment of GERD.

Rheological Behavior of a New Mucoadhesive Oral Formulation Based on Sodium Chondroitin Sulfate, Xyloglucan and Glycerol.

Background: The study aimed at assessing the mucoadhesive properties and the barrier effect of a formulation, labelled as AL2106, containing sodium chondroitin sulfate (ChS), xyloglucan from tamarind seed extract, and glycerol, by evaluating the capacity to adhere to a layer of mucin, the rheological synergism and the barrier effect in comparison to the marketed Esoxx One medical device. AL2106 is a medical device distributed by Alfasigma SpA, Italy with REF FTP57 (Manufacturer: Labomar SpA); it is analogous to Esoxx One medical device: the two products are drinkable solutions that, after swallowing, adhere to the esophageal mucosa, protecting it from the corrosive effect of the gastric acid reflux. AL2106 has been conceived to be better performing in terms of duration of the barrier effect compared to Esoxx One. Methods: The mucoadhesive properties, rheological behavior, buffering capacity against acidity, and film-forming ability with the resultant protecting effect on esophagus mucosa (caffeine permeation test) was compared between the two products. Results: The mucoadhesivity of the formulations was shown in vitro: both remained adherent to a mucin layer, also when the support was rotated by 90°, and when the film layer was washed with water, intended to simulate the washout due to swallowing. AL2106 showed a good buffering efficacy, being able to absorb at least 50% of its weight of 0.03 M HCl while maintaining the pH above 4. The film-forming effect and barrier properties of AL2106 and Esoxx One were confirmed by an in vitro study on reconstructed human esophageal epithelium. A greater film-forming efficacy of AL2106, lasting for at least 5 h, than Esoxx One was observed. Noteworthy, the barrier function of esophageal tissues was shown to be preserved after the application of both formulations. Conclusions: The combination of ChS with the mucoadhesive glycerol-xyloglucan complex and other excipients, which contribute to the barrier effect and to mucoadhesion, contained in AL2106, allowed a longer-lasting protective effect than Esoxx One, proving its effectivity and safety for oral use.