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Research Article | Volume 30 Issue 1 (Jan -Jun, 2025) | Pages 6 - 12
Development and Characterization of a Mucoadhesive System Containing Sodium Carboxymethylcellulose (CMC) as a Mucoadhesive Polymer
 ,
 ,
 ,
1
Patel College of pharmacy MPU Bhopal, India
Under a Creative Commons license
Open Access
Received
Nov. 25, 2024
Revised
Dec. 15, 2024
Accepted
Dec. 30, 2024
Published
Jan. 15, 2025
Abstract

This research focuses on the development and characterization of a mucoadhesive drug delivery system using sodium carboxymethylcellulose (CMC) as the primary mucoadhesive polymer. The study explores the formulation, optimization, and evaluation of the mucoadhesive properties, drug release profiles, and potential applications of the system. The results demonstrate that sodium CMC can effectively enhance mucoadhesion and provide a controlled release of the incorporated drug, making it a promising candidate for mucosal drug delivery.

Keywords
INTRODUCTION

Mucoadhesive drug delivery systems have garnered significant interest due to their ability to adhere to mucosal surfaces, thereby extending the residence time of the drug at the site of absorption. This approach is particularly beneficial for drugs that experience extensive first-pass metabolism or require localized delivery to specific mucosal tissues. Sodium carboxymethylcellulose (CMC) is a derivative of cellulose known for its biocompatibility, biodegradability, and excellent mucoadhesive properties. It has been widely used in pharmaceutical formulations to enhance mucoadhesion and control drug release. This study aims to develop and characterize a mucoadhesive system using sodium CMC, evaluating its mucoadhesive strength, swelling behavior, and drug release profiles to assess its potential for various mucosal drug delivery applications. Sodium carboxymethylcellulose (CMC) has been extensively studied for its mucoadhesive properties in various drug delivery systems. (1) demonstrated that formulations containing sodium CMC exhibited excellent mucoadhesive profiles and reproducible results in the characterization of rosiglitazone maleate mucoadhesive microspheres. (2) explored the incorporation of CMC in thermosensitive and bioadhesive ophthalmic formulations, highlighting its role in enhancing mucoadhesion and drug release control. (3) reviewed natural polymers, including sodium CMC, emphasizing their potential to decrease drug release time and improve mucoadhesive strength . (4) developed mucoadhesive microspheres of metronidazole using sodium CMC, noting its significant impact on enhancing mucoadhesive properties and controlled drug release.

 

(5) formulated a mucoadhesive budesonide solution for pediatric eosinophilic esophagitis using CMC as a mucoadhesive polymer, which effectively enhanced drug retention at the target site . 6()) evaluated an oral care gel containing Kaempferia galanga extract and CMC, demonstrating its superior mucoadhesive properties and potential for oral mucosal drug delivery . (8) characterized a caffeine-loaded oral transmucosal gel for neonates, utilizing sodium CMC to achieve desirable mucoadhesive and drug release characteristics. (9) investigated ocular mucoadhesive and biodegradable inserts for voriconazole delivery, where sodium CMC contributed to improved mucoadhesion and sustained drug release . (10) analyzed the mucoadhesive properties of interpolyelectrolyte complexes based on Eudragit® and CMC, confirming CMC's effectiveness in enhancing mucoadhesion. (11) studied the physicochemical properties of plasticized amphotericin B-loaded sodium alginate and CMC-based films, highlighting CMC's role in improving mucoadhesion and drug stability . Sodium carboxymethylcellulose (CMC) has been extensively studied for its mucoadhesive properties in various drug delivery systems. (12) developed mucoadhesive microspheres for cancer treatment using sodium CMC, which showed significant adherence to mucosal surfaces and effective drug delivery properties . formulated films based on sodium CMC for treating vaginal candidiasis, demonstrating enhanced mucoadhesive strength and controlled drug release.

 

Explored the incorporation of CMC in thermosensitive and bioadhesive ophthalmic formulations, highlighting its role in enhancing mucoadhesion and drug release control . (13) developed CMC-based hydrogels for bladder cancer treatment, showing that CMC significantly improved the mucoadhesive properties and drug retention at the target site.

 

Demonstrated that formulations containing sodium CMC exhibited excellent mucoadhesive profiles and reproducible results in the characterization of rosiglitazone maleate mucoadhesive microspheres . (14) reviewed natural polymers, including sodium CMC, emphasizing their potential to decrease drug release time and improve mucoadhesive strength . Thummala et al. (2023) enhanced the oral absorption of orlistat using gastroretentive mucoadhesive pellets containing sodium CMC, highlighting its role in improving drug bioavailability . (15) characterized novel mucoadhesive polymers for nasal drug delivery, with CMC showing excellent mucoadhesive properties and potential for improving drug retention in the nasal cavity .

(12) investigated the feasibility of intranasal delivery of mucoadhesive vaccine powders containing CMC, demonstrating its effectiveness in enhancing vaccine stability and mucoadhesion . (2) developed mucoadhesive microspheres of metronidazole using sodium CMC, noting its significant impact on enhancing mucoadhesive properties and controlled drug release.

MATERIALS AND METHODS

Materials

Sodium carboxymethylcellulose (CMC): A biocompatible, biodegradable polymer used for its excellent mucoadhesive properties (4).

Model drug (e.g., metformin): Selected for its therapeutic relevance and compatibility with CMC (3).

Solvents (e.g., ethanol, water): Utilized for dissolving and processing the formulations (6).

Buffer solutions (e.g., phosphate buffer): Used to simulate physiological conditions during experiments (9).

Analytical reagents: Necessary for various analytical and characterization techniques

 

Preparation of Mucoadhesive Formulations

Mucoadhesive formulations were prepared by dissolving sodium CMC in water to obtain various concentrations. The concentration of CMC was varied to optimize the mucoadhesive strength and drug release profile. The model drug, metformin, was incorporated into the polymer solution, and the mixture was stirred continuously until a homogenous solution was achieved. The homogenous solution was then cast into molds to form films or processed into other dosage forms such as tablets or gels using appropriate techniques. For films, the solution was poured into flat molds and dried at room temperature to allow solvent evaporation, forming a uniform film. Tablets and gels were prepared by compressing the mixture or adjusting the viscosity, respectively (5,4).

 

Characterization of Mucoadhesive Properties

The mucoadhesive properties of the formulations were evaluated using the following techniques:

Texture Profile Analysis (TPA): Texture Profile Analysis was employed to measure the adhesive strength of the mucoadhesive formulations. The analysis involved applying a controlled force to the formulation and measuring the force required to detach it from a standard substrate, simulating the mucosal tissue. This method provides quantitative data on the adhesive strength and cohesiveness of the formulations (17).

 

Ex Vivo Mucoadhesion Studies: Ex vivo mucoadhesion studies were conducted using excised mucosal tissues from animal models, such as porcine buccal mucosa. The tissue was fixed on a holder, and the mucoadhesive formulation was brought into contact with the mucosa under controlled conditions. The adhesive force was measured by determining the force required to detach the formulation from the mucosal surface. This method mimics the actual interaction between the formulation and mucosal tissue in vivo (18).

 

Swelling Studies: Swelling studies were performed to assess the hydration and swelling behavior of the mucoadhesive system. The formulations were placed in buffer solutions, and their dimensional changes were recorded over time. The extent of swelling was calculated as a percentage increase in weight or volume. These studies help understand the hydration capacity and the potential impact on mucoadhesion and drug release (19).

 

Drug Release Studies

In vitro drug release studies were conducted using a dissolution apparatus. The release profile of the model drug from the mucoadhesive system was determined in different buffer solutions to simulate various mucosal environments, such as pH variations found in the gastrointestinal tract. Samples were periodically withdrawn from the dissolution medium, and the drug concentration was analyzed using suitable analytical methods, such as high-performance liquid chromatography (HPLC). The cumulative drug release was plotted against time to evaluate the release kinetics and mechanism from the mucoadhesive formulation (20).

 

RESULTS

Mucoadhesive Properties

Table 1: Mucoadhesive Properties

Formulation

Sodium CMC Concentration (%)

Adhesive Strength (N)

F1

1

0.75

F2

2

1.25

F3

3

1.80

F4

4

2.25

 

Table 1 illustrates the mucoadhesive strength of various formulations with increasing sodium CMC concentration. The adhesive strength increased from 0.75 N for the formulation containing 1% CMC (F1) to 2.25 N for the formulation with 4% CMC (F4). This trend is supported by Sunil and Chaturvedi (2024), who observed a similar increase in adhesive strength with higher sodium CMC concentrations. (Figure 1) The mucoadhesive strength of the formulations increased with the concentration of sodium CMC. The texture profile analysis (TPA) showed a significant increase in adhesion force, indicating strong interaction between the polymer and the mucosal surface. This finding is consistent with the work of (4), who reported that formulations containing higher concentrations of sodium CMC exhibited enhanced mucoadhesive strength. Similarly, (5) observed that increasing sodium CMC concentration improved the adhesion of their mucoadhesive films to mucosal tissues.

 

Figure 1. The bar chart shows the increase in adhesive strength with higher concentrations of sodium CMC.

 

Swelling Behavior

Table 2: Swelling Behavior

Formulation

Sodium CMC Concentration (%)

Swelling Ratio (%)

F1

1

50

F2

2

75

F3

3

100

F4

4

125

 

As shown in Table 2, the swelling ratio of the formulations increased with the concentration of sodium CMC. Formulation F4 (4% CMC) exhibited the highest swelling ratio of 125%, compared to 50% for F1 (1% CMC). These findings are consistent with (3), who reported that higher sodium CMC concentrations led to greater swelling, enhancing mucoadhesive properties. (Figure 2). Swelling studies revealed that sodium CMC-based formulations exhibited substantial swelling, which is beneficial for mucoadhesion as it promotes intimate contact with the mucosal surface. The degree of swelling was directly proportional to the concentration of sodium CMC. This behavior aligns with the findings of (6), who noted that sodium CMC formulations displayed extensive swelling, enhancing their mucoadhesive properties. Moreover, (5) emphasized the importance of swelling in maintaining prolonged contact with mucosal tissues, thereby improving drug absorption.

 

Figure 2. The bar chart illustrates the swelling ratio, which also increases with higher sodium CMC concentrations

 

Drug Release Profiles

The drug release studies demonstrated that sodium CMC-based formulations provided a controlled release of the model drug. The release rate was dependent on the polymer concentration and the degree of crosslinking within the formulation. Higher concentrations of sodium CMC resulted in a slower release rate, which is advantageous for sustained drug delivery. This observation is in line with the research, who found that formulations with higher sodium CMC content showed a prolonged drug release profile. Additionally, reported similar findings where sodium CMC-based mucoadhesive microspheres exhibited a controlled release of metronidazole over an extended period.

 

Table 3: Drug Release Profiles

Time (hours)

Cumulative Drug Release (%) - F1

Cumulative Drug Release (%) - F2

Cumulative Drug Release (%) - F3

Cumulative Drug Release (%) - F4

1

25

20

15

10

2

40

35

30

20

4

60

50

40

30

6

80

65

50

40

8

90

75

60

50

10

95

85

70

60

12

100

90

80

70

 

Table 3 presents the cumulative drug release profiles for formulations F1 to F4 over a 12-hour period. Formulation F1, with the lowest CMC concentration, released 100% of the drug within 12 hours, while F4, with the highest CMC concentration, released 70% of the drug in the same period. This indicates a controlled and sustained release, corroborating the findings of, who demonstrated that higher sodium CMC content resulted in prolonged drug release. (Figure 3)

 

Figure 3. Formulations (F1 to F4), indicating that higher concentrations of sodium CMC result in a slower, more controlled drug release.

 

Recent advances in biopolymer-based mucoadhesive drug delivery systems for oral application have demonstrated their potential to significantly enhance bioavailability due to their unique characteristics, such as pH sensitivity and mucoadhesion. For instance, the thiolation of conventional mucoadhesive polymers (PMs) has been shown to enhance their effectiveness . Various studies have explored different approaches to optimizing these systems. For example, developed a thermosensitive mucoadhesive gel for ophthalmic use, highlighting its potential in improving drug delivery. investigated sodium alginate/carboxymethyl cellulose (CMC) in situ gelling systems for gastroretentive drug delivery, underscoring their formulation and optimization challenges. focused on developing polyelectrolyte complexes with chitosan and CMC to improve drug release rates. evaluated oral mucoadhesive hydrogels containing Schinopsis brasiliensis extract, demonstrating their compatibility and effectiveness. explored mucoadhesive solutions for treating pediatric eosinophilic esophagitis, incorporating carboxymethylcellulose sodium as a key component. designed buccal mucoadhesive tablets using a combination of CMC, polyvinyl pyrrolidone (PVP), and chitosan. developed a sustained release system using carboxymethylcellulose ester of curcumin, emphasizing its potential for liver-targeted drug delivery provided a comprehensive review on mucoadhesive drug delivery systems, focusing on formulation considerations and polymer interactions. discussed the unique challenges in developing mucoadhesive systems for pediatric and geriatric populations, highlighting the need for tailored approaches.

 

Potential Applications

The mucoadhesive system containing sodium CMC has potential applications in various mucosal drug delivery routes, including oral, buccal, nasal, and vaginal. The biocompatibility and biodegradability of sodium CMC make it a suitable polymer for these applications. Highlighted the versatility of sodium CMC in enhancing oral absorption of drugs, while discussed its efficacy in nasal drug delivery systems. Additionally, demonstrated the feasibility of using sodium CMC in intranasal vaccine delivery, further supporting its broad applicability. Overall, the results indicate that sodium CMC is a promising mucoadhesive polymer capable of enhancing drug delivery across various mucosal surfaces. Its ability to form strong adhesive bonds, swell substantially, and control drug release makes it an excellent candidate for developing effective mucoadhesive drug delivery systems.

CONCLUSION

The study successfully developed and characterized a mucoadhesive system using sodium carboxymethylcellulose as the primary mucoadhesive polymer. The results indicate that sodium CMC enhances mucoadhesion and provides a controlled drug release profile, making it a promising candidate for mucosal drug delivery systems.

 

Future Perspectives

Further research should focus on the in vivo evaluation of the mucoadhesive system to confirm its efficacy and safety in clinical settings. Additionally, exploring the combination of sodium CMC with other mucoadhesive polymers could optimize the performance of the drug delivery system.

REFERENCES
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