(W1230-06-37) Comparative Evaluation of Mucoadhesive Polymers Performance in Topical, Nasal, and Buccal Gel Formulations: Impact on Drug Product Physical Property, Behavior, and Patient Acceptability

Purpose: Mucoadhesive drug delivery systems (MDDS) are designed to adhere to mucosal surfaces like the oral, nasal, or vaginal mucosa, allowing for prolonged drug release and localized or systemic effects. These systems leverage the interaction between the formulation and the mucus layer epithelial cells, increasing the drug's residence time and potentially enhancing absorption and bioavailability. The objective is to investigate the influence of polymer characteristics used in topical, nasal, and buccal gel formulations on behavior, drug permeation profiles, and patient-centered parameters. Key physicochemical properties, such as rheological behavior, mucoadhesive strength, and retention on mucosal tissues, are systematically assessed. Comparative analysis highlights formulation-dependent performance trends and identifies route-specific polymer advantages [1]. This research provides insights into rational polymer selection, such as Gels prepared using Hydroxyethyl cellulose and hydroxypropyl cellulose for enhanced mucosal drug delivery [2]. In the current study, our strategy is to prepare topical, buccal, and nasal gel formulations using the same excipients but at different levels. It is hypothesized that the interplay between polymer type, concentration, and mucosal environment (topical, buccal, or nasal) critically influences gel performance, including residence time, permeability enhancement, and drug bioavailability. Thus, a rational, concentration-dependent polymer design can yield multifunctional delivery systems optimized for each mucosal surface's physicochemical and biological demands.

Methods: The gel formulation process began with the preparation of a polymer phase by dispersing purified water into a pre-weighed glass beaker, followed by continuous mixing using an overhead stirrer equipped with a shaft and impeller at a controlled speed. Natrosol 250M Pharma (Hydroxyethyl cellulose) and Klucel MF (Hydroxyproyl cellulose) at the level of 0.25% to 7.5% were selected as mucoadhesive and rheological modifiers. The polymers were gradually incorporated into the aqueous phase under constant stirring at 700 RPM, continuing until a uniform, clear gel base was achieved. Diclofenac Sodium is an NSAID and helpful in managing the pain. It is a BCS class II drug, and solubility studies proved that it is soluble in a hydroalcoholic solution. Therefore, the API phase was prepared by dissolving Diclofenac Sodium (1% w/w) at 500 RPM in another beaker containing a mixture of purified water (Q.S), Propylene Glycol (10% w/w), Glycerin (10% w/w), Phenoxyethanol (0.5% w/w), and Ethanol (10% w/w). Each component was added under continuous mixing, allowing complete solubilization. Upon achieving a clear API solution, it was slowly introduced into the polymeric gel matrix under homogenization with Silverson^® L5M-A homogenizer at 3000 RPM and mixing at 700 to 1000 RPM at room temperature to ensure uniform drug distribution. The speed was varied as per the gel thickness observation during processing. Throughout the process, critical mixing parameters, durations, and visual observations were recorded to monitor gel clarity, homogeneity, and phase compatibility, ensuring the reproducibility and stability of the final gel formulations.

Results: Diclofenac sodium formulation batches were successfully manufactured by following the standard manufacturing method for preparing topical, buccal, and nasal gels. The assay values were within 95% to 100%, and the degradation level was less than 0.05%. In Figure 2, the data presented confirms the stable gel formulation with no degradation. The pH of the finished formulation was found to be between 7.0 to 8.0. The prepared topical solution was stable at room temperature storage conditions for 1 month, and no precipitation was observed. Figure 3, Brookfield Texture analyzer CT3 4500 data represent the various texture analysis properties such as adhesiveness, cohesiveness, springiness, gumminess, and tension.

Conclusion: The polymer concentration and type significantly influenced the gel's mucoadhesive strength, as demonstrated by texture profile analysis using the Brookfield Texture Analyzer CT3 4500, indicating enhanced adhesiveness suited for mucosal retention. Rheological characterization via Brookfield DV3T confirmed that the gels exhibited shear-thinning behavior, desirable for ease of application and mucosal spreadability. HPLC analysis confirmed the chemical stability of Diclofenac sodium, with minimal degradation and consistent assay values across formulations. The formulations maintained a physiologically acceptable pH range (7.0–8.0), with no visible precipitation or phase separation observed over one month of storage at room temperature. This study demonstrates that strategic selection and concentration adjustment of cellulose-based polymers can be used to tailor mucoadhesive properties and rheological behavior, enabling the development of stable, versatile gel formulations suitable for multiple mucosal delivery routes—topical, buccal, and nasal—using a unified manufacturing approach.

References: [1] Aylla Mesquita Pestana et al. (2024) Analysis of Key Factors for Evaluating Mucosal Adhesion Using Swine Buccal Tissue. Journal of Pharmaceutical Sciences, ISSN: 0022-3549, Vol: 113, Issue: 8, Page: 2413-2419
[2] S. Roy, K. Pal, A. Anis, K. Pramanik & B. Prabhakar (2009) Polymers in Mucoadhesive Drug-Delivery Systems: A Brief Note, Designed Monomers and Polymers, 12:6, 483-495.


Composition


Fig 2 :Analytical Data


Fig 3: Texture analysis