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

Abstract

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.

Keywords: GERD; epithelial barrier effect; film-forming capacity; mucoadhesion; rheology; viscosity.

Figure 1

Experimental results of mucoadhesion studies: the bars show the percent of the applied formulation that remains attached to the mucin film after tilting at 90° for 6 min (mean ± S.D. of ten replicates).

Figure 2

Amount of formulation per surface area unit that remains attached to the mucin film after tilting at 90° and after the subsequent washing in beakers and repositioning at 90° (mean ± S.D. of ten replicates).

Figure 3

Flow curves (viscosity) of Esoxx One and AL2106 formulations.

Figure 4

Amplitude Sweep of Esoxx One and AL2106 formulations. G′ and G″ are the elastic and viscous moduli, respectively. The G′ storage modulus for Esoxx One was not measurable.

Figure 5

Viscosity of Esoxx One, pure mucin, the sum of the formulation/mucin viscosities, and the viscosity of Esoxx One/mucin 1:1 mixture.

Figure 6

Viscosity of the AL2106 formulation, pure mucin, the sum of the formulation/mucin viscosities, and the viscosity of AL2106/mucin 1:1 (w/w) mixture.

Figure 7

Esoxx One/mucin interaction: G′ and G″ values of diluted Esoxx One, 6% mucin, theoretical G′ and G″ values of the sum of the two formulations and mucin moduli, G′ and G″ values of the Esoxx One/mucin 1:1 (w/w) mixture.

Figure 8

AL2106/mucin interaction: G′ and G″ values of diluted AL2106 formulation, 6% mucin, theoretical G′ and G″ values of the sum of the two formulations and mucin moduli, G′ and G″ values of AL2106/mucin 1:1 (w/w) mixture.

Figure 9

Relationship between the pH of the AL2106 solution and the amount of acid added.

Figure 10

Diffusion of caffeine in the basolateral receptor fluid after 4, 5, and 6 h from the application of the test formulations, expressed as the percentage of the caffeine amount (mean ± S.D. of six replicates) found after the application of saline (negative control). Statistical significance was set at * p < 0.005 and ** p < 0.0005 vs. saline, and *** p < 0.00005 for AL2106 vs. Esoxx One).

Figure 11

Transepithelial electrical resistance (TEER) expressed in Ohm cm² at baseline (T = 0 h) and after 6 h of treatment (T = 6 h) (mean ± S.D.). Statistical significance was set at * p < 0.1, ** p < 0.05, or *** p < 0.005 vs. saline, and at § p < 0.1 for AL2106 vs. Esoxx One.

Figure 12

Flow of Lucifer Yellow (mean ± S.D.) after 6 h of treatment followed by washing of the products. Each analysis was carried out on three samples for each batch in triplicate (n = 9) (* p < 0.005 for both batches vs. saline and for AL2106 vs. Esoxx One).