Formultion And Evaluation of Mucoadhesive Buccal Films

The development of novel drug delivery systems for existing drug molecules improves drug

performance in terms of efficacy, safety, patient compliance, and overall therapeutic benefit. Buccal drug delivery is a method in which the drug is administered through the buccal mucosa, thereby bypassing the gastrointestinal tract and first-pass hepatic metabolism. This route enables the therapeutic agent to directly enter systemic circulation and provide rapid drug action. Among the different drug delivery systems, the buccal delivery system is considered highly promising because the buccal mucosa provides a protective barrier against toxins and microorganisms while allowing efficient drug absorption [1].

Mucoadhesive Buccal Films

Various mucoadhesive dosage forms have been developed, including tablets, patches, strips, ointments, gels, disks, and films. Among these, buccal films have gained significant attention because they overcome the limitations associated with oral gels, such as short residence time and easy removal by saliva. An ideal buccal film should be soft, flexible, strong, and expandable to withstand mechanical stress in the oral cavity. Additionally, it should possess adequate mucoadhesive strength to remain attached to the buccal mucosa for the desired period and ensure controlled drug release [2].

Manufacturing Methods of Buccal Films

The following methods are commonly used for the preparation of mouth dissolving and buccal films:

1. Solvent Casting Method
2. Semisolid Casting Method
3. Hot Melt Extrusion Method
4. Solid Dispersion Extrusion Method
5. Rolling Method[3]

1. Solvent Casting Method

In the solvent casting method, water-soluble polymers are dissolved in water. The drug and other excipients are dissolved separately in a suitable solvent. Both solutions are then mixed thoroughly to obtain a uniform solution, which is subsequently cast into a petri plate or mold and dried to form a thin film.[3]

2. Semisolid Casting Method

In this method, a solution of water-soluble film-forming polymer is first prepared. This solution is then added to a solution containing acid-insoluble polymers such as cellulose acetate phthalate or cellulose acetate butyrate prepared in ammonium or sodium hydroxide. A suitable plasticizer is added to obtain a gel mass. The gel mass is cast into films or ribbons using heat-controlled drums. The thickness of the prepared film ranges from 0.015 to 0.05 inches. Generally, the ratio of acid-insoluble polymer to film-forming polymer should be 1:4.[4]

3. Hot Melt Extrusion Method

In the hot melt extrusion method, the drug is mixed with solid carriers, and the mixture is introduced into an extruder. The heaters present in the extruder melt the mixture, and the molten mass is then shaped into films using dies. This method offers several advantages, including fewer processing steps, improved content uniformity, and an anhydrous manufacturing process.[5]

4. Solid Dispersion Extrusion Method

In this technique, immiscible components are mixed with the drug and extruded to prepare solid dispersions. The prepared solid dispersions are then shaped into films with the help of dies.[6]

5. Rolling Method

In the rolling method, a drug-containing solution or suspension is rolled onto a carrier surface. Water and alcohol are commonly used as solvents. The formed film is dried using rollers and cut into the desired shape and size. Other ingredients, including active pharmaceutical agents, are dissolved in a small quantity of aqueous solvent using a high-shear processor to obtain a homogeneous viscous solution before film formation [7].

MATERIALS AND METHODS

Materials

The materials used in the preparation of mucoadhesive buccal films included Tramadol Hydrochloride, which was obtained from Lupin Limited, Mumbai. Hydroxypropyl methylcellulose (HPMC) was procured from Colorcon Asia Pvt Ltd, Goa, while polyvinyl alcohol (PVA) and citric acid were obtained from Merck Life Science / Rankem. Carbopol 934, glycerol/PEG 400, and sodium saccharin were purchased from S. D. Fine Chemicals. All chemicals and reagents used in the study were of analytical grade and used without further purification.

Preparation of Tramadol HCl Mucoadhesive Buccal Films

Mucoadhesive buccal films of Tramadol Hydrochloride were prepared by the solvent casting method. PVA was dissolved in distilled water, followed by the addition of Carbopol 934 with continuous stirring. Tramadol HCl was dissolved separately and mixed with the polymeric solution. Sodium saccharin, citric acid, and glycerol/PEG 400 were added as sweetener, saliva-stimulating agent, and plasticizer, respectively. The final solution was poured into a Petri dish, dried at room temperature or in a hot air oven, and cut into 2 × 2 cm² films for evaluation.[13]

Calculation for Buccal Film

The total area of a 9 cm Petri dish was calculated using:

A=πr2=3.14×(4.5)2=63.6 cm2

 

Approximately 16 films of size 2 × 2 cm² were prepared from one Petri dish. Each film contained 50 mg of Tramadol HCl.

Optimization of Formulation

Different batches (F1–F6) were prepared by varying polymer concentrations to study their effect on film properties. The optimized formulation was selected based on mechanical strength, mucoadhesive properties, flexibility, uniform drug distribution, and controlled drug release. F6 was considered the optimized batch due to its suitable film characteristics and satisfactory drug release profile.

Tramadol Hydrochloride was found to be a white crystalline, odourless, and bitter powder.

Solubility Study

Solvent	Observation	Interpretation
Water	Freely soluble	Supports rapid drug release
Methanol	Soluble	Good solubility in polar solvent
Ethanol	Slightly soluble	Moderate solubility
Chloroform/Ether	Practically insoluble	Poor solubility in non-polar solvents

Good aqueous solubility indicates suitability for buccal drug delivery.

Melting Point Determination

Parameter	Observation	Interpretation
Melting Point	180–184°C	Confirms purity and identity of drug

The observed melting point confirmed the purity of the drug sample.

pH Study

Parameter	Observation	Interpretation
pH (1% solution)	5.5–6.5	Suitable for buccal application

The pH range indicates minimal risk of mucosal irritation.

UV Spectroscopy (Determination of λmax)

The UV spectrum of Tramadol Hydrochloride showed maximum absorbance at:

λmax≈271 nm

 

 

 

The λmax value was used for calibration curve preparation and further drug analysis.

Standard Calibration Curve of Tramadol HCl

A standard calibration curve of Tramadol Hydrochloride was prepared in phosphate buffer pH 6.8 within the concentration range of 2–12 µg/mL. The absorbance increased linearly with concentration, confirming Beer–Lambert’s law.

Table  Standard Calibration Curve of Tramadol HCl in Phosphate Buffer pH 6.8

Concentration (µg/mL)	Absorbance
2	0.113
4	0.221
6	0.335
8	0.448
10	0.545
12	0.675

The regression equation obtained was:

y=0.1099x+0.0058

 

 

The correlation coefficient was found to be:

R2=0.9991

 

The developed UV spectrophotometric method showed excellent linearity, accuracy, and suitability for quantitative estimation of Tramadol HCl.

Drug–Excipient Compatibility Study (FTIR Analysis)

FTIR analysis of Tramadol Hydrochloride showed characteristic peaks at 3445 cm⁻¹ (O–H stretching), 3350 cm⁻¹ (N–H stretching), 1512 cm⁻¹ (aromatic C=C stretching), and 1110 cm⁻¹ (C–O–C stretching). Similar peaks with slight shifts were observed in the drug–excipient mixture, indicating absence of significant chemical interaction between the drug and excipients.

 

 

 

 

Figure: Combined graphical representation of physicochemical evaluation parameters of prepared mucoadhesive buccal films of Tramadol Hydrochloride including thickness, weight variation, folding endurance, surface pH, swelling index, mucoadhesive strength, drug content uniformity, and cumulative drug release.

Formulation F5 showed stable physicochemical properties under accelerated conditions, confirming good formulation stability.

CONCLUSION

The present study successfully developed and evaluated mucoadhesive buccal films of Tramadol hydrochloride to improve pain management by overcoming limitations of conventional oral dosage forms such as first-pass metabolism and delayed action. The buccal films were prepared using polymers like HPMC, PVA, and Carbopol 934 by the solvent casting method.All formulations (F1–F6) showed good physicochemical and mechanical properties, including uniform thickness, acceptable surface pH, and proper drug content uniformity. Mucoadhesive strength and swelling behavior increased with higher polymer concentration, especially Carbopol 934, which improved residence time and drug absorption.

In-vitro drug release studies showed that drug release was influenced by polymer concentration, with F1 showing faster release and F3 showing sustained release. The optimized formulation F5 provided the best balance of controlled drug release, mucoadhesion, and mechanical strength.Stability studies of F5 confirmed no significant changes in key parameters, indicating good formulation stability. Overall, the study concludes that mucoadhesive buccal films of Tramadol hydrochloride are a promising alternative drug delivery system, with further in-vivo and clinical studies recommended for future development.

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