(W1230-06-36) Adhesive Insights: Evaluating Mucoadhesion Across Various Polymers in Gel Formulations

Purpose: Mucoadhesion refers to the interfacial interactions between a natural or synthetic polymer and the surface of a biological membrane and has gained considerable interest in pharmaceutical sciences over the last decades¹. Local drug delivery is a very challenging route of drug administration due to the short time exposure of the active pharmaceutical ingredient (API) at the site of action (e.g. nasal/oral cavity, vaginal/rectal tract) caused by factors like tongue movement, physiological washout, and the self-cleaning action of the vaginal tract^2,3. Mucoadhesive dosage forms have the potential to overcome these issues, therefore enhancing local and systemic drug delivery by retaining a dosage form for extended periods at the application site. This enables the actives to penetrate the biological barriers more effectively, providing a controlled rate of drug release that enhances bioavailability and therapeutic outcomes. Main driving factors that are influencing mucoadhesion are molecular weight, cross-linking, pH, and the concentration of the polymer^1,2 Well known polymers with mucoadhesion properties are polyacrylic acid, xanthan gum, carrageenan, alginates and hydroxypropyl methylcellulose⁴. In this study, various natural and synthetic polymers were combined in placebo gel formulations to identify potential synergistic effects. The aim was to develop a sprayable platform formulation with optimized in-vitro mucoadhesive properties, allowing feasible incorporation of model drugs.

Methods: Several placebo gel formulations were prepared and analysed. The formulations contain different polymer combinations of Carbopol® 971P NF, Noveon® AA-1 polycarbophil, Protanal® PH 1033, GRINDSTED® Xanthan Clear 80, Sodium hyaluronate (HA-E2.0), Gelcarin® PH 379, METHOCEL™ K4M Premium and METHOCEL™ E4M Premium (Table 1). Polymers concentration in all combinations did not exceed 0.8% w/w to ensure that the viscosities of all prepared samples remained within a similar range and were sufficiently low to obtain sprayable formulations. Mucoadhesion properties were evaluated using a method based on the in-vitro Oesophageal Retention Model (IVOR) that allowed mucoadhesion evaluation in a dynamic environment⁵ (Figure 1). Samples were spiked with a colorant, and the marker's percentage was quantified via UV-VIS spectroscopy after 2, 5 ,10, 15, 30 and 45 minutes in artificial saliva.

Results: During this study, the in-vitro mucoadhesive properties of different gel formulations were evaluated. The results indicated that the combination of 0.4% w/w GRINDSTED® Xanthan Clear 80 with either 0.4% w/w Carbopol 971P NF or 0.4% w/w Noveon® AA-1 polycarbophil achieved at nearly all timepoints the highest marker retention, suggesting the strongest molecule interactions between the polymers and the substrate. The combination of Carbopol 971P NF and Noveon® AA-1 polycarbophil also demonstrated a high marker retention rate of 27.5% (30 minutes) and 26.6% (45 minutes), particularly over the long term. Protanal® PH 1033 exhibit poor synergistic effects with either Carbopol polymer or Noveon® AA-1 polycarbophil (Figure 2).

Conclusion: Choosing the right polymer is fundamental to the successful development of a mucoadhesive formulation, as the process relies on a complex interplay of hydration, swelling, chain interpenetration, and hydrogen bonding. These mechanisms are crucial for ensuring strong and prolonged adhesion to the mucosal surface. Based on these principles, this study highlights the potential of using polymer combinations - Carbopol® 971P NF with Xanthan gum or Carbopol® 971P NF with Noveon® AA-1 polycarbophil, as a promising strategy. These combinations exhibited enhanced in-vitro mucoadhesive properties, making them ideal candidates for designing novel mucoadhesive drug delivery systems. Further studies are ongoing to evaluate different polymer combinations to optimize the mucoadhesive properties.

References: 1. Shaikh R, Raj Singh TR, Garland MJ, Woolfson AD, Donnelly RF. Mucoadhesive drug delivery systems. J Pharm Bioallied Sci. 2011 Jan;3(1):89-100. doi: 10.4103/0975-7406.76478. PMID: 21430958; PMCID: PMC3053525.
2. Mohamad Hamdi, N. A., Azmi, N. A., Mohd Sabari, N. H., Harun, A.F.& Haris, M. S. 2023; An insight into the use and advantages of Carbopol in topical mucoadhesive drug delivery system: A systematic review. Journal of Pharmacy, 3(1)., 53-65
3. Mennatullah M. Faisal, Shereen A. Sabry, Mahmoud A. Mahdy, Mohammed M. Waly and Amira M. El-Ganiny, 2016; Formulation and Evaluation of Fluconazole Mucoadhesive Gel for Vaginal Fungal Infection. International Journal of Trend in Research and Development, Volume 4(1), ISSN: 2394-9333
4. Boddupalli BM, Mohammed ZN, Nath RA, Banji D. Mucoadhesive drug delivery system: An overview. J Adv Pharm Technol Res. 2010 Oct;1(4):381-7. doi: 10.4103/0110-5558.76436. PMID: 22247877; PMCID: PMC3255397.
5. Young, S. A. and Smart, J. D. A novel in-vitro apparatus for evaluating the mucoadhesion of liquid and semi-solid formulations, J Pharm. Pharmacol. 50, 167 (1998)

Acknowledgements: The authors would like to thank International Flavors and Fragrances Inc. (IFF) for providing excipient support.


Table 1: Formulation Composition Overview


Figure 1: In-vitro Oesophageal Retention (IVOR) Model


Figure 2: Results From the Mucoadhesion Study