Design and Characterization of Naproxen Fast Dissolving Tablets Employing Coccinia grandis Leaf Mucilage as a Natural Binder and Disintegrant

The oral route is considered the most traditional and widely used method for administering medications. Tablets are among the most commonly prescribed dosage forms because they are easy to self-administer, stable, and simple to manufacture. However, many patients especially children and the elderly face difficulty swallowing standard tablets, a challenge that becomes more pronounced during travel when access to water may be limited. These limitations of conventional tablets can be overcome by formulating mouth-dissolving tablets. Such tablets rapidly disintegrate in the mouth, typically within 20–30 seconds, allowing the active ingredient to interact with saliva and exert its therapeutic effect. Compared with conventional tablets, mouth-dissolving tablets offer improved patient compliance and acceptance, along with enhanced bioavailability, efficacy, and overall biopharmaceutical performance^.1

The mouth-dissolving drug delivery approach is especially beneficial for patients suffering from life-threatening conditions such as neurological disorders, radiation therapy–related complications, Parkinson’s disease, and AIDS who commonly experience dysphagia. Alternative dosage forms like effervescent tablets or dry syrups often cause discomfort in such patients because they must be taken with water. In contrast, mouth-dissolving tablets eliminate the need for water, thereby significantly improving patient convenience and adherence. These tablets are also known by several other terms, including orally disintegrating tablets, fast-dissolving tablets, and fast-melting tablets. According to the European Pharmacopoeia, an “orodispersible” tablet is one that rapidly disintegrates in the mouth without requiring water. Mouth-dissolving tablets (MDTs) have therefore become increasingly popular in pharmaceutical development due to these distinct advantages.

Advantages of Mouth Dissolving Tablets (MDTs)^2-4

Mouth-dissolving tablets (MDTs) are convenient oral dosage forms that quickly disperse in the mouth without the need for water, making them ideal for children, elderly individuals, and patients with swallowing difficulties. They provide a faster therapeutic effect because the drug can be absorbed through the buccal mucosa, bypassing the gastrointestinal tract. This also enhances bioavailability by reducing first-pass metabolism, allowing more of the drug to reach systemic circulation compared to conventional tablets.

Mouth-dissolving tablets (MDTs) offer improved taste and acceptability through the use of flavors and sweeteners, making them especially suitable for pediatric patients. Their high portability allows easy administration without water, making them convenient for travel or outdoor use. MDTs also support adaptable dosing, which is useful for drugs requiring precise dose adjustments. These features, along with their ease of use, enhance patient compliance. Additionally, MDTs provide formulation flexibility, enabling the incorporation of a wide range of active pharmaceutical ingredients, including those with poor solubility or stability in conventional forms. Advanced formulation technologies have significantly improved the performance of mouth-dissolving tablets (MDTs). Methods like lyophilization create highly porous structures for rapid dissolution, while direct compression uses specialized excipients to ensure quick disintegration without losing strength. The addition of superdisintegrants such as croscarmellose sodium, crospovidone, and sodium starch glycolate further enhances their breakdown in the mouth. These innovations allow MDTs to be tailored for optimal disintegration, taste masking, and stability. Overall, MDTs represent a major advancement in oral drug delivery, offering fast action, improved bioavailability, and better patient compliance, especially for pediatric, geriatric, and dysphagic patients.^5-7

Figure 1: Disintegration of Fast Dissolving Tablet⁸

Ideal Properties of Drugs for Formulating Mouth-Dissolving Tablets^9-11

Selecting an appropriate drug candidate is crucial for the effective development of mouth-dissolving tablets (MDTs). Ideal drugs should dissolve quickly in the oral cavity for rapid action, have acceptable taste or be easily taste-masked, and require low doses to maintain small tablet size. They must also remain stable in saliva, exhibit good bioavailability, and preferably avoid extensive first-pass metabolism. Additionally, compatibility with excipients like superdisintegrants is important to ensure proper tablet strength and fast disintegration. Drugs that allow flexible formulation approaches are most suitable, as they enhance overall performance, patient acceptability, and therapeutic effectiveness.

Manufacturing of Mouth Dissolving Tablets^12-13

The production of mouth-dissolving tablets (MDTs) involves several carefully controlled steps to ensure rapid disintegration and effective drug release. It begins with formulation development, where a suitable drug and excipients such as superdisintegrants, diluents, binders, and flavoring agents are selected. The ingredients are then uniformly blended, followed by granulation (wet or dry) if needed to improve flow and compressibility. The prepared blend or granules are compressed into tablets using appropriate tooling and optimized pressure to balance strength and fast dissolution. In some cases, taste-masking coatings are applied to enhance palatability. The final tablets undergo quality control tests, including disintegration, dissolution, hardness, and friability, before being packaged in moisture-resistant materials to ensure stability and maintain product quality.

Evaluation of Fast Dissolving Tablets (FDTs)¹⁴

Fast dissolving tablets (FDTs) undergo various evaluation tests to ensure their quality, safety, and effectiveness. Key parameters include disintegration time (ideally under 30 seconds) to confirm rapid breakdown in saliva-like conditions, and dissolution testing to measure drug release using techniques like UV-Visible spectrophotometry or HPLC. Mechanical properties such as hardness and friability are assessed to ensure tablets are strong yet resistant to damage, with friability typically below 1%. Additional tests include weight variation and content uniformity to ensure consistent dosage, taste-masking evaluation for patient acceptability, and moisture content analysis for stability. In some cases, in-vivo studies are conducted to evaluate pharmacokinetics, bioavailability, and overall therapeutic performance.

Recent Developments in Fast Dissolving Tablets (FDTs)^15-16

Recent advancements in fast dissolving tablet (FDT) technology have significantly improved patient convenience, bioavailability, and manufacturing efficiency. Innovations such as advanced superdisintegrants and co-processed excipients enhance tablet strength, flow properties, and rapid disintegration. Modern techniques like 3D printing, freeze-drying, spray drying, and improved direct compression enable the production of highly porous and fast-acting tablets. The integration of nanotechnology improves solubility and drug release, while advanced taste-masking methods increase patient acceptability. Additionally, developments in orally disintegrating films (ODFs), moisture stability, and higher drug-loading capacity further expand the applicability of FDTs, making them a highly effective and patient-friendly drug delivery system.

Table 1: Marketed fast-dissolving/oro-dispersible tablet (FDT/ODT) product^17-18

OBJECTIVES OF STUDY

1. To extract and purify mucilage from Coccinia grandis leaves using a standardized extraction procedure.

2. To characterize the extracted mucilage for its physicochemical properties such as solubility, swelling index, viscosity, pH, moisture content, and micromeritic characteristics.

3. To formulate Naproxen fast dissolving tablets using Coccinia grandis mucilage in varying concentrations as a natural binder and disintegrant.

4. To evaluate the prepared FDTs for parameters like: Disintegration time, Wetting time, Hardness, Friability, Weight variation, Drug content uniformity, In-vitro dissolution studies

5. To compare the performance of mucilage-based tablets with tablets formulated using synthetic excipients (e.g., croscarmellose sodium or PVP).

6. To analyze drug excipient compatibility using FTIR or DSC studies.

7. To select the optimized formulation based on disintegration time, dissolution profile, and mechanical strength.

8. To establish the suitability of Coccinia grandis mucilage as a natural, safe, cost-effective, and efficient binder/disintegrant in FDT formulations.

RATIONALE OF THE STUDY

Fast dissolving tablets have emerged as a patient-friendly dosage form, offering advantages for pediatric, geriatric, bedridden, and dysphagic patients who experience difficulty swallowing conventional tablets. Naproxen, a widely used NSAID, suffers from delayed onset of action due to its poor aqueous solubility and slow dissolution rate. Formulating it into fast dissolving tablets can significantly enhance its onset of analgesic and anti-inflammatory effects. Coccinia grandis (ivy gourd) is a commonly available plant containing natural mucilage known for its swelling, binding, and disintegrating properties. Natural mucilages offer several advantages over synthetic excipients biodegradability, non-toxicity, low cost, biocompatibility, and environmental friendliness. However, its application as a binder and disintegrant in Naproxen fast dissolving tablets has not been extensively investigated. This study aims to explore the potential of Coccinia grandis leaf mucilage as a multifunctional excipient that can provide both rapid disintegration and sufficient mechanical strength to FDTs. The successful utilization of this natural mucilage may lead to the development of safer, more economical, and sustainable pharmaceutical formulation

EXPERIMENTAL WORK

MATERIALS:

The following materials collected for the experimental work done.

Table 2 : List of materials

Table 3: Natural Polymer List

Table 4: List of Equipments

EXTRACTION OF MUCILAGES^19-21

The mucilage can be extracted through the following steps:

1. Collection: Collect ~500 g fresh leaves of Coccinia grandis.
2. Preparation: Wash thoroughly → (optional) blanch briefly → chop into small pieces.
3. Extraction (Maceration): Soak leaves in distilled water (1:10 ratio) for 24 hrs with occasional stirring.
4. Filtration: Filter using muslin cloth/filter paper to obtain aqueous extract.
5. Concentration: Evaporate at ≤50 °C to reduce volume to ~100–150 mL.
6. Precipitation: Add 2–3 volumes of chilled ethanol → keep at 4 °C for 24 hrs.
7. Separation: Centrifuge (5000 rpm, 15–20 min) → collect precipitate → wash with cold ethanol.
8. Drying: Dry at ≤40 °C (or freeze dry) until constant weight.
9. Yield: From 500 g leaves → ~48 g dried mucilage.

IDENTIFICATION OF DRUG^22-24

1. Organoleptic Properties : Observe and record color, odor and taste of the drug.

2. Melting Point : Take a small amount of powder in a fusion tube. Place in melting point apparatus (with castor oil). Heat gradually and Note the Temperature when melting starts Temperature when completely melted

3. Solubility Study (UV Method using Naproxen)

Stock Solution: Weigh 10 mg drug and Dissolve in 10 mL methanol → 1 mg/mL solution

Working Solutions: Dilute stock to get 2–10 µg/mL concentrations

Λ max Determination: Scan in UV range (200–400 nm), λmax ≈ 231 nm

Absorbance Measurement: Set instrument at 231 nm , Measure absorbance of all solutions

Calibration Curve: Plot Absorbance vs Concentration , Get equation (e.g., Y = 0.045X + 0.002) and Check linearity (r² ≈ 0.999)

4. Sample Analysis : Powder tablets and take amount = 10 mg drug  ,Dissolve, filter, dilute and Measure absorbance at λmax , Compare with standard to confirm identity & content

RESULTS & DISCUSSIONS

Physicochemical Characterization of Coccinia grandis Mucilage

The isolated mucilage of Coccinia grandis was evaluated for its physicochemical properties to determine its suitability as a natural superdisintegrant.

The mucilage appeared as a white, amorphous, tasteless powder with a characteristic odor, making it acceptable for oral dosage forms. It exhibited slight solubility in hot water and formed a viscous colloidal solution in cold water, indicating strong hydration and swelling ability key requirements for a superdisintegrant.

A swelling index of 46.3% confirms excellent swelling capacity, which promotes rapid tablet disintegration. The pH of 6.7 indicates near neutrality, ensuring compatibility with most drugs and minimizing irritation.^25-28

However, micromeritic properties revealed poor flow characteristics, as indicated by:

• Low bulk density (0.083 g/cm³)
• High Carr’s index (33.6%)
• Hausner’s ratio (1.50)
• Angle of repose (39.5°)

These findings suggest the need for flow enhancers during formulation.

Thermal analysis showed stability up to ~200°C, indicating suitability for pharmaceutical processing. Overall, the mucilage demonstrates good swelling ability but poor flow, making it effective when combined with other excipients.7

Calibration Curve of Naproxen

The UV spectrophotometric analysis of Naproxen was carried out at λmax = 231 nm, and a calibration curve was prepared.

Figure 2: Calibration curve of Naproxen in pH 6.8 phosphate buffer

The calibration curve showed a linear relationship between concentration and absorbance with equation:

y=0.0454x-0.001

This confirms that the method is reliable for quantitative estimation of Naproxen in formulations.²⁹

Drug–Excipient Compatibility (FTIR Study)

FTIR analysis was performed to evaluate possible interactions between Naproxen and mucilage.³⁰

Figure 3: FTIR study of of Naproxen

Figure 4: FTIR study of of Naproxen + polymer mixture

The FTIR spectrum of pure Naproxen showed characteristic peaks: ~3196 cm?¹ (O–H stretching), ~1730 cm?¹ (C=O group) ,1600–1500 cm?¹ (aromatic C=C)

In the drug–polymer mixture, all peaks were retained with only minor shifts, indicating: No chemical interaction, Good compatibility between drug and mucilage

Thus, the mucilage is suitable for formulation.

Precompression Parameters^31-33

The powder blends (F1–F12) were evaluated for flow properties :

Angle of repose range to 33.8° to 27.8°, indicating improved flow , Bulk density range from 0.44 to 0.52 g/cm³ and Carr’s index shows 18.5% to 13%

This improvement is due to the addition of synthetic superdisintegrants such as: Croscarmellose sodium (CCS), Sodium starch glycolate (SSG), Crospovidone. Formulations F11–F12 showed the best flow properties, making them ideal for compression.

Post-Compression Evaluation^31-34

All formulations met pharmacopeial limits for: Weight variation, Hardness (3.2–3.7 kg/cm²) and Friability and  disintegration test

• F1–F4 (Natural mucilage only): Slow disintegration due to gel formation
• F5–F8 (with CCS): Faster disintegration due to swelling + wicking
• F9–F10 (with SSG): Moderate improvement
• F11–F12 (with Crospovidone): Fastest disintegration

F12 showed:

• Wetting time: 34 sec
• Disintegration time: 38 sec

Thus, Crospovidone-based formulations performed best.

In-Vitro Dissolution Studies^31-34

Dissolution studies showed significant variation in drug release.

(a) Natural Polymer (F1–F4)

Figure 5: In-Vitro Dissolution Studies of FDT of Naproxen using Coccinia grandis mucilage (F1 to F4)

In their 80–90% release at 20 min and show slower due to viscous gel barrier

(b) With CCS (F5–F8)

Figure 6: In-Vitro Dissolution Studies of FDT of Naproxen using Coccinia grandis mucilage with Croscarmellose sodium (F5 to F8)

Shows Nearly 100% release within 20 min due to it Mechanism swelling + wicking .F8 showed optimal performance.

(c) With SSG (F9–F10)

Figure 7: In-Vitro Dissolution Studies of FDT of Naproxen using Coccinia grandis mucilage with Sodium Starch Glycolate, SSG (F9 to F10)

In their 97-98% release within 20 min, slightly promotes fast disintegration and drug release

(d) With Crospovidone (F11–F12)^35-39

Figure 8: In-Vitro Dissolution Studies of FDT of Naproxen using Coccinia grandis mucilage with Crospovidone (F11 to F12)

complete release within 15 minutes due to Mechanism: wicking without gel formation ,F12 was identified as the optimized formulation.

Conclusion

Drug release increased in the order: Coccinia grandis mucilage < SSG < CCS < crospovidone, reflecting differences in disintegration efficiency. Combining natural and synthetic polymers improved dissolution through synergistic effects. Formulation F12 showed the best performance, achieving complete drug release within 15 minutes. Overall, both the type and concentration of disintegrants significantly influence Naproxen release from FDTs.

Drug Release Kinetics analysis^40-43

Different kinetic models were applied to F12

Figure 9: Zero order plot for the Optimized formulation FDT of Naproxen (F12)

Figure 10: First order plot for the Optimized formulation FDT of Naproxen (F12)

Figure 11: Higuchi plot for the Optimized formulation FDT of Naproxen(F12)

Figure 12: Hixson Crowell plot for Optimized formulation FDT of Naproxenn (F12)