When medications are administered or stored in the buccal region (the cheek), they diffuse through the oral mucosa (the tissues lining the mouth) and enter the bloodstream directly. This is known as buccal administration. Because buccal administration circumvents first-pass metabolism by avoiding the digestive tract, it may offer some medications greater bioavailability and a quicker onset of action than oral administration. Thin films and tablets are two drug formulations that are administered buccally. Commercially available in buccal forms were the following medications: nicotine as a smoking cessation aid; the opioid drugs buprenorphine, naloxone, and fentanyl; the cardiovascular drug nitroglycerin; the hormone replacement therapy testosterone; the nausea medication prochlorperazine; and the psychiatric drug asenapine ^[1] an anticonvulsant, used to treat acute epileptic seizures.^[2]

        
           
       
Fig No: 01 Structure of Clotrimazole

METHODOLOGY

Preformulation Studies:

Pre-formulation studies are meant to provide formulators with knowledge that will help them create stable and bioavailable dosage forms. Using pre-formulation parameters increases the likelihood of creating a product that is stable, safe, effective, and acceptable. It also serves as a foundation for improving the drug product's quality ^6,7.

Solubility Profile of Clotrimazole

The formulation and efficacy of the antifungal drug clotrimazole can be affected by certain solubility properties. Because of its weak water solubility, clotrimazole may not be as bioavailable when taken orally. It dissolves better in organic solvents such as methanol, ethanol, and chloroform. Clotrimazole's solubility may change with pH; it dissolves better in acidic settings than in neutral or alkaline ones.

pH 6.8 Phosphate Buffer Preparation:

Weighted 11.45 gm of potassium Dihydrogen phosphate and 28.80 gm of disodium hydrogen phosphate and made up to 1000 ml with distilled water.

Calibration Curve of Clotrimazole:

Calibration curve for clotrimazole involves preparing a series of standard solutions of known concentrations and measuring their absorbance using a suitable analytical technique, typically UV-Vis spectrophotometry. Following a step-by-step guide as: After measuring 100 mg of Clotrimazole, it was placed into a 100 ml volumetric flask and dissolved in a pH 6.8 phosphate buffer solution. The volume was then adjusted to 100 ml to achieve a concentration of 1000 µg/ml. From this solution, 10 ml was taken and further diluted to 100 ml with pH 6.8 phosphate buffer solution, resulting in a concentration of 100 µg/ml. From this standard stock solution, aliquots of 0.2 ml, 0.4 ml, 0.6 ml, 0.8 ml, and 1 ml were taken and diluted with pH 6.5 phosphate buffer solution to obtain concentrations of 2, 4, 6, 8, and 10 µg/ml. The absorbance of these solutions was measured at 255 nm against a blank of pH 6.8 phosphate buffer solution.

Compatibility Studies of Drug & Excipients

FTIR can help determine if there is any significant interaction between clotrimazole and excipients used in buccal tablets, such as polymers (e.g., hydroxypropyl methylcellulose, micro crystalline cellulose), fillers, or stabilizers. Changes in peak positions or intensities compared to the pure drug spectra could indicate interactions.

Characteristic Peaks of Clotrimazole:

C–Cl stretching: Clotrimazole contains a chlorinated aromatic ring, showing peaks in the range of 600-800 cm??1;. C=N stretching (imidazole ring): Clotrimazole has an imidazole ring, which shows a characteristic peak around 1600-1700 cm??1;. Aromatic C–H bending: Peaks typically appear in the region of 1450-1600 cm??1;. Aromatic C=C stretching: Peaks in the range of 1500-1600 cm??1; may be observed. The region between 600-1500 cm??1; serves as the fingerprint region, unique to clotrimazole, and helps confirm its presence. Deviations here might indicate formulation issues or degradation. Shifts in peaks, such as broadening or intensity changes in the O–H or N–H regions (if present due to excipients or moisture), may suggest hydrogen bonding. This can provide insights into the drug release profile and stability in the buccal environment.

Method of Formulation of Clotrimazole Buccal Tablet:

Manufacturing clotrimazole buccal tablets involves formulating the active ingredient, clotrimazole, with specific excipients to create a tablet that adheres to the buccal mucosa for prolonged drug release. This method improves the local therapeutic effect, especially for oral fungal infections. Below is a step-by-step outline of a typical manufacturing method

Formulation of Clotrimazole Buccal Tablets:

Bioadhesive Polymers carrageenan, Locust bean gum, were selected to act as thickening agent or Emulsifier. Microcrystalline cellulose used with the Bio Polymers to improve tablet structure which can act as good suspending agent. Xanthum Gum is selected to add to the bulk mixture which act as a binder. Magnesium stearate, talc added to aid in tablet ejection from the mould. The clotrimazole and selected excipients were weighed accurately. The active ingredient and excipients got mixed uniformly using a blender or V-blender to ensure even distribution. Proper mixing is crucial to ensure consistent drug release from each tablet. The formulation can be done in two ways by using wet granulation method and direct compression method. In wet granulation process, If clotrimazole and excipients require binding for a more cohesive mix, wet granulation can be employed using a binding solution which is made with binder mixed with methanol or water. Mix until the powder becomes uniformly wet and forms a dough-like consistency then pass it through the sieve number 16. The obtained granules were dried in an oven or fluidized bed dryer ensuring the granules are free-flowing and stable. The dried granules through a screened to achieve uniform granule size. Add lubricants magnesium stearate and talc. Mix lightly to avoid breaking the granules. Then they got compressed using tableting tool. In the second method which is direct compression method, If the powder blend flows well, it can be directly compressed into tablets without granulation.

RESULTS AND DISCUSSIONS:

Pre formulation Studies:

Solubility Profile of Clotrimazole

Solubility studies were carried out to select a suitable solvent to dissolve the drug and to select the dissolution medium.

Table1: Solubility studies

Development of Calibration Curve of Clotrimazole:

In the validation studies, it was found that the estimation of Clotrimazole by spectrophotometric method at 255 nm has good reproducibility, at the concentration between 2-10 µg/ml.  Correlation between concentration and absorbance was found to be 0.9976 which is closer to 1.

Table. 2 Calibration curve of Clotrimazole

       
           
       
Fig. 2 Calibration curve of Clotrimazole                                               

Compatibility Studies of Drug & Excipients

In the present study, physical mixture of Clotrimazole solid form along with different polymers were prepared and analyzed by FTIR to find out the compatibility between the drug and polymers. The IR spectra of Clotrimazole along with the physical mixture of Clotrimazole with different polymers are shown from the graph which showed that the drug and excipients.

Formulation of Clotrimazole buccal Tablets:

The clotrimazole and selected excipients were weighed accurately. The active ingredient and excipients got mixed uniformly using a blender or V-blender to ensure even distribution. Proper mixing is crucial to ensure consistent drug release from each tablet. wet granulation can be employed using a binding solution which is made with binder mixed with methanol or water. Mix until the powder becomes uniformly wet and forms a dough-like consistency then pass it through the sieve number 16. The obtained granules were dried in an oven or fluidized bed dryer ensuring the granules are free-flowing and stable. The dried granules through a screened to achieve uniform granule size. Add lubricants magnesium stearate and talc. Mix lightly to avoid breaking the granules. Then they got compressed using tableting tool. Using this method 9 different preparations were done by named CZL1, CZL2, CZL3, CZL4, CZL5, CZL6, CZL7, CZL8, CZL 9 using different proportions of excipients as shown in the below table.