INTRODUCTION:

Drug distribution via the buccal mucosal membrane—the mouth cavity's lining—is known as buccal delivery. Due to its great bioavailability, the medication bypasses the hepatic first pass metabolism and enters the systemic circulation straight through the jugular vein on the inside¹. To be kept in the mouth cavity for the necessary amount of time, an effective buccal drug delivery system has to be flexible and possess strong bioadhesive properties. To increase the bioavailability of medications that have significant first-pass hepatic effects and to control drug release at a steady pace, bioadhesive preparations have been created².

In order to provide the necessary therapeutic response, it should also release the medication in a controlled and predictable way. For oral administration, a number of buccal mucosal dose forms have been suggested, such as buccal tablets, buccal patches, and buccal gels³.

Hyperglycemia, or consistently elevated blood sugar, is a symptom of diabetes mellitus, a chronic metabolic disease. The hormone insulin, which controls blood sugar levels, is either not produced in sufficient amounts by the body or is resisted by the cells. High blood sugar is caused by disruptions in glucose metabolism brought on by the reduction of insulin action. In type 2 diabetes, body cells develop insulin resistance, and the pancreas is unable to generate enough insulin to combat the insulin resistance condition. In type 1 diabetes, the immune system targets the pancreatic cells that create insulin4.

A vital source of energy for the cells in the body, glucose levels in the blood is controlled by several hormones, the most significant of which is insulin. After consuming carbs, the pancreas produces insulin, which helps the body absorb glucose into cells, particularly muscle and fat cells. If glucose is not utilized right away for energy production, it is transformed into glycogen and stored in the muscles and liver for later use. In order to keep blood sugar levels steady between meals, the pancreas produces glucagon, which tells the liver to turn glycogen again to glucose ⁵.

When this sensitive regulatory mechanism is disrupted, diabetes develops. The degeneration of pancreatic beta cells that secrete insulin, results in creating minimal or no insulin, serving the cause for type 1 diabetes. Type 2 diabetes is characterized by insulin resistance, which raises blood sugar levels because the pancreas is unable to produce enough insulin to compensate. Chronic uncontrolled hyperglycemia can lead to serious long-term issues with the cardiovascular system, kidneys, eyes, and nerves ^6,7.

Blood glucose monitoring, medication, and lifestyle modifications are all part of managing diabetes. In order to control blood sugar, medications like metformin and repaglinide are essential. Repaglinide addresses postprandial glucose levels, whereas metformin primarily affects fasting blood glucose levels. Repaglinide employs meal timing to account for glucose rises in cases of chronically disturbed eating patterns. Drug therapy, lifestyle modifications, and routine monitoring can all help manage diabetes and reduce complications ⁸.

There are an estimated 828 million people with diabetes worldwide, including 212 million in India. The nation with the greatest number of diabetes sufferers worldwide is India, where one in four individuals (26%) have the disease. In November 2024, India's population was expected to be 17.78% of the world's total population^9,10.

MATERIALS AND METHOD:

Authorized local vendors provided the API Repaglinide, additional excipients, and reagents utilized in this investigation. All of these were of analytical quality. Before the experiment began, every instrument was thoroughly inspected and calibrated.

Preformulation Study:

Electrical melting point equipment was used to determine the point at which Repaglinide melted in a capillary tube approach.

Using the shake flask technique, the distribution coefficient of Repaglinide between the n-octanol-water system was ascertained.

Repaglinide's dissolution in phosphate buffer solutions with pH values of 6.8 and 7.4 was assessed using the phase equilibrium technique.

Using a Fourier Transform Infrared spectrometer, drug-excipient compatibility investigations were conducted. Compatibility experiments were conducted on both pure Repaglinide and Repaglinide with physical mixtures i.e. including excipients.

Formulation of Repaglinide incorporated buccal film:

Repaglinide-containing films were made with varying proportions of carbopol, chitosan, plus hydroxypropyl methyl cellulose. To get a transparent solution (0.1% w/v), chitosan was dissolved and agitated in a 1% glacial acetic acid solution. An hour was spent soaking carbopol in water to prepare a 0.1% w/v dispersion. 95% ethanol was used to soak HPMC K4M in order to achieve a 0.5% w/v dispersion. To achieve a bubble-free dispersion, the mixed polymeric dispersions were progressively combined in the amounts indicated in Table 1 for an hour in 95% ethanol. The weighed amount of Repaglinide was then gradually added to the polymeric solution and agitated using a magnetic stirrer to ensure that the medication was distributed evenly over the petridish's surface. As a plasticizer, glycerol was applied.

After pouring the solution onto a circular dish, the films were allowed to air dry for two hours at the ambient temperature followed by being dried in a hot air oven set at 40 °C for twenty-four hours. They were then placed in a vacuum desiccator to finish drying. Table 1 displays the several formulas that were made.

Table 1: Formulation of buccal film F1 to F6

Formulation code	Carbopol	Chitosan	HPMC	95 % ethanol	Repaglinide	Glycerol
Formulation code	(0.1 %w/v) (ml)	(0.1% w/v) (ml)	(0.5% w/v) (ml)	(ml)	(mg)	(ml)
F1	–	1	1	7.9	22	0.1
F2	–	2	2	5.9	22	0.1
F3	–	3	3	3.9	22	0.1
F4	1	–	1	7.9	22	0.1
F5	2	–	2	5.9	22	0.1
F6	3	–	3	3.9	22	0.1

Evaluation of Buccal Film:

A variety of metrics, including thickness, weight fluctuation, percentage of moisture uptake and loss, including drug content, folding endurance, tensile strength, percentage swelling index, and surface pH, were assessed for the prepared buccal films. Additionally, their stability over a prolonged period of time and in-vitro drug release characteristics were assessed.

RESULTS:

A substance's melting point is often employed to recognize it and determine the purity of it. The pure Repaglinide sample's melting point was determined to be 129.68±0.45°C, falling within the reporting range ¹¹.

Repaglinide is a very lipophilic medication, as evidenced by its distribution coefficient of 4.01 at ambient temperature in n-octanol and phosphate buffer pH7.4.

Repaglinide's saturation solubility in various buffers was investigated. The experiments' solubility revealed that the solubility of Repaglinide decreased in distilled water, at 22.59µg/mL, and increased from pH 6.8 to 7.4, or 88 µg/mL to 94µg/mL.

To verify the medications' compatibility with other formulation excipients, the FTIR spectra of the pure drug and the formulation including other substances were recorded. The FTIR spectra demonstrated that the medication and the chosen components did not physically interact to generate the buccal film (figure 1).

Evaluation of Mucoadhesive Buccal Film:

Based on the method proposed by Augusthy AR et al. for creating buccal films (12), the buccal films of Repaglinide utilizing a variety of polymers were formulated. These where then further assessed for a number of assessment characteristics, which are presented in Table 2.

In vitro drug release of films:

All formulations underwent an 8-hour in vitro drug release testing in phosphate buffer pH 6.8, and at different intervals, the cumulative drug release (CDR) was computed. The maximum drug release of almost 94.557%, was shown by formulation F2 (Figure 2 and table 3).

Table 2: Evaluation parameters of formulated films of Repaglinide

Parameters	F1	F2	F3	F4	F5	F6
Thickness (mm)	0.213 ± 0.03	0.148 ± 0.03	0.112 ± 0.04	0.235 ± 0.06	0.196 ± 0.05	0.138 ± 0.02
Weight (mg)	65.02 ± 8.73	48.44 ± 4.57	43.94 ± 5.69	68.45 ± 5.69	54.89 ± 4.16	46.74 ± 6.12
% moisture uptake	11.61 ± 2.32	9.633 ± 3.25	15.807 ± 6.85	12.89 ± 4.2	13.553 ± 3.9	12.6 ± 42
Surface pH	6.82 ± 0.03	6.38 ± 0.07	6.61 ± 0.03	6.29 ± 0.07	6.76 ± 0.07	6.82 ± 0.06
% Drug content	94.94 ± 0.17	96.86 ± 0.08	94.88 ± 0.14	93.15 ± 2.90	94.88 ± 0.12	96.88 ± 0.08
% moisture loss	11.3 ± 0.86	5.29 ± 1.47	4.76 ± 2.38	5.96 ± 2.63	3.74 ± 2.38	8.27 ± 3.81
Mucoadhesive strength (dyne/cm²)	5033 ± 530	4685 ± 450	3760 ± 273	5617 ± 636	5034 ± 563	4828 ± 452
% Swelling index	20.51 ± 1.58	14.33 ± 1.77	12.12 ± 1.24	23.04 ± 1.25	17.25 ± 1.43	16.77 ± 1.69
Folding endurance	290.10 ± 1.00	285.66 ± 2.08	256.33 ± 1.46	274.40 ± 2.00	296.66 ± 1.52	286.66 ± 2.56
Tensile strength (kg/cm²)	1.26 ± 0.01	1.57 ± 0.03	1.61 ± 0.01	1.26 ± 0.01	1.57 ± 0.031	1.61 ± 0.01

Table 3: Results of in vitro % CDR, flux, and release kinetics

Formulations	Flux (mg/h/cm²)	% Cumulative drug release in 8h	Release kinetics R²(first order)
F1	1.380	86.707 ± 2.36	0.994
F2	1.441	94.557 ± 3.21	0.994
F3	1.363	85.628 ± 2.54	0.998
F4	1.277	80.211 ± 1.89	0.994
F5	1.404	88.197 ± 3.05	0.996
F6	1.353	85.007 ± 2.87	0.995

Figure 2: In vitro % cumulative drug release

Stability Studies:

The preparations were preserved for three months under 40°C±2°C along with % relative humidity being 75± 5%. After eight hours, the folding endurance, drug content, and percentage of drug release were assessed. After three months of storage, the findings showed only minor changes to the characteristics of F1 to F6.

DISCUSSION:

The API was added to mucoadhesive buccal films, which were made with a variety of described polymers. Every composition had a refined, silky look. It was discovered that the produced films' thickness and weight fluctuation fell within acceptable bounds. The percentages of moisture uptake and moisture loss showed that the films were sustainable across a range of moisture conditions.

The percentage of drugs in the movie ranged from 93.15±2.90 to 96.88±0.08. Tensile strength as well as folding endurance demonstrated the films' high mechanical strength along with flexibility¹³.

The surface pH ranged between 6.29±0.07 and 6.82± 0.06, which is closer to salivary pH (pH 6.8) and shows that the films are compatible with mucosa and cause less harm to it.

As the polymer concentrations rose, the compositions' mucoadhesive qualities improved. Compared to films merged with chitosan, those containing carbopol showed a higher mucoadhesive strength. With its many carboxylic acidic groups, carbopol is a cross-linked polyacrylate polymer that tends to form a hydrogen connection with the oligosaccharide chain in mucosal tissues. This may explain why carbopol films have a higher mucoadhesive strength.

The films' swelling indices were 12.12±1.24% and 23.04±1.25%, respectively, which are necessary for the medication to be released from the films.

With R2 values of 0.994 and 0.998, all of the formulations were found to have first-order release kinetics, indicating concentration-dependent drug release. According to the in vitro drug release investigation, the absorption of the medication is solubility limited rather than permeability limited because the F2 formulation contains chitosan, a well-known penetration booster.

A histopathological investigation is necessary to assess the formulations' safety for biological tissues. This might be viewed as a continuation of the work shown here.

The stability study has revealed that there is no any significant variation in studied parameters of the formulations after 3 months of storage at 40°C±2°C and 75±5% RH. These results suggest that the formulations are stable for long term storage.

CONCLUSION:

The buccal route of administration will surely enhance drug bioavailability, bypass first-pass metabolism, and offer rapid onset of action, which is crucial for controlling postprandial blood glucose levels. The stability study revealed that the parameters examined in the formulations did not significantly change after three months of storage at 40°C ± 2°C and 75 ± 5% RH. These findings show that the formulations hold up well over an extended period of storage. In order to control postprandial blood glucose levels, the buccal route may improve medication bioavailability, prevent first-pass metabolism, and offer a quick beginning of action. Thus, Repaglinide's mucoadhesive buccal films were effectively prepared and assessed in this investigation. It is clear from this investigation that the method under development is effective in increasing Repaglinide's solubility.

The mucoadhesive buccal films of Repaglinide could therefore be a safer and effective dosage formulation in the development of new therapies for reducing the dose and adverse effects of the drug.

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Received on 18.11.2025 Revised on 17.12.2025

Accepted on 12.01.2026 Published on 30.01.2026

Available online from February 05, 2026

Res. J. Pharma. Dosage Forms and Tech.2026; 18(1):47-51.

DOI: 10.52711/0975-4377.2026.00008

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