(M0930-07-38) Evaluating Mucoadhesion of Polymer Films Using Wax Substrates with Mucin Coating

Purpose: Mucoadhesive oral thin films (OTF) represent an innovative drug delivery platform that ensures faster onset of action, improved patient compliance, and avoidance of first-pass metabolism. However, assessing their mucoadhesive and mechanical properties remains a challenge due to the lack of standardized methods [1]. The formulation of OTF involves polymers, plasticizers, surfactants, flavors and sweeting agents [2]. Among different polymers Hydroxypropyl methylcellulose, Carboxymethyl cellulose, Poly (vinyl alcohol), Pullulan and Sodium alginate are commonly used, each have its own properties. For instance, HPMC has moderate mucoadhesive properties whereas sodium alginate has high mucoadhesive properties [3]. In this study, we propose a universal protocol for evaluating mucoadhesion using three types of waxes (water-soluble, oil-soluble, and dual-soluble) as substrates. The main objectives of the research are to establish reliable assessment techniques for mucoadhesive properties and to investigate the interaction between polymers such as HPMC, Sodium alginate, Carbopol with these waxes.

Methods: A 1% w/v solution of each polymer (HPMC, Sodium alginate, and Carbopol) was prepared and the film was produced using the solvent casting method in 60 mm petri dishes, which were then kept at room temperature for 48 hours to form thin films and trimmed before study. Substrates were melted at 60-70°C and poured into 95 mm x 15 mm petri dishes, then allowed to solidify at room temperature for 24 hours. Another set of substrates was prepared using the same method and coated with a 4% w/v mucin solution. A texture analyzer (CT3-1000, Brookfield, MA, USA) was used to determine the adhesive force (AF), with parameters set to a target force of 0.96 N, a hold time of 15 seconds, and a speed of 0.1 mm/s [4]. The thin films were attached to the probe using double-sided tape. The wax substrates, both with and without mucin coating, were placed under the probe, and 200 µl of artificial saliva was applied for conditioning. The adhesive behavior of the OTFs against various substrates was then investigated [4]

Results: The research aims to establish reliable assessment techniques for mucoadhesive properties and to investigate the interaction between polymers (HPMC, Sodium Alginate, Carbopol) and various wax substrates. Using a texture analyzer, the adhesive force (AF) of oral thin films (OTFs) against substrates with and without mucin coating was measured. Results showed that mucin coating generally increased the adhesive force, indicating stronger interactions when mucin was present. For HPMC films, the AF significantly increased from 0.36 N to 1.14 N with mucin on cetostearyl alcohol, showing a pronounced enhancement. Similarly, Sodium Alginate films showed an increase from 0.77 N to 0.97 N on cetostearyl alcohol. However, the AF slightly decreased for Bees Wax when mucin was present (1.26 N to 1.19 N for Sodium Alginate). PEG 1450 showed reduction of mucoadhesion with mucin coating for all. Carbopol films demonstrated a consistent increase in AF with mucin on cetostearyl alcohol and a decrease on Bees Wax and PEG 1450. The variation in AF across different substrates suggests specific interactions between the polymers and waxes, influenced by the presence of mucin. These findings contribute to the understanding of mucoadhesive properties, highlighting the importance of mucin in enhancing adhesion.

Conclusion: The investigation revealed significant interactions between various polymers (HPMC, Sodium Alginate, Carbopol) and wax substrates in the presence of mucin. The results highlighted that mucin coating generally enhances adhesive force, indicating that mucin plays a critical role in mucoadhesion. HPMC films showed the most substantial increase in adhesion on cetostearyl alcohol with mucin, suggesting strong potential for applications requiring high mucoadhesive strength. Sodium Alginate and Carbopol films also demonstrated increased adhesion with mucin, though the degree of enhancement varied with the substrate type. These findings provide valuable insights into the selection of polymer-wax combinations for developing effective mucoadhesive drug delivery systems. Further research could explore the molecular mechanisms behind these interactions and optimize formulations for specific clinical needs.

References: [1] Alaei, S., & Omidian, H. (2021). Mucoadhesion and Mechanical Assessment of Oral Films. European Journal of Pharmaceutical Sciences, 159, 105727.
[2] Hithun,D., Venkatachalam. S, and Radhakrishnan, A. (2018) "A Review on Formulation of Oral Dissolving Film." Journal of Chemical and Pharmaceutical Research 10.4 151-159.
[3] Karki, Sandeep, et al. (2016) "Thin films as an emerging platform for drug delivery." Asian journal of pharmaceutical sciences 11.5, 559-574.
[4] Alaei, S., Omidi, Y., & Omidian, H. (2021). In vitro evaluation of adhesion and mechanical properties of oral thin films. European Journal of Pharmaceutical Sciences, 166, 105965.

Acknowledgements: We acknowledge Nova Southeastern University as facilities for the equipment and Brookfield for their kind donation of the Texture Analyzer. HO and SDC designed, analyzed, revised the data, and designed the poster. SDC conducted the experiments.
Disclaimer: The statements, opinions and data contained in this abstract are solely those of the individual author(s) and contributor(s) and not of the AAPS, or the reviewer/editor. AAPS and/or the reviewer/editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Funding: This research received no external funding.
Disclosure or conflict of interest statements: The authors declare no conflicts of interest.

Thin films and substrates with and without mucin coating and Texture analyzer. (A) Thin films of various polymers: (i) HPMC film, (ii) Sodium alginate film, and (iii) Carbopol film. (B) Substrates without mucin layer: (i) PEG 1450, (ii) Beeswax, and (iii) Cetostearyl alcohol. (C) Substrates with mucin layer: (i) PEG 1450, (ii) Beeswax, and (iii) Cetostearyl alcohol. (D) Image of texture analyzer during assessment of adhesive force of OTF against substrate.

Adhesive force of polymer films against different substrate.