Design, Optimization and Characterization of a Prebiotic-Integrated Albendazole Mouth Dissolving Film Utilizing Mixed Hydrotropy for Enhanced Drug Solubility and Gastrointestinal Absorption

Albendazole is a benzimidazole derivative widely used as a broad-spectrum anthelmintic agent for the treatment of intestinal helminthic infections. Despite its therapeutic importance, albendazole belongs to Biopharmaceutical Classification System (BCS) Class II, characterized by low aqueous solubility and high permeability. Poor solubility results in limited dissolution in gastrointestinal fluids, leading to reduced oral bioavailability. Conventional tablet formulations of albendazole exhibit delayed onset of action and inconsistent absorption. Therefore, novel drug delivery systems are required to improve dissolution and absorption characteristics. Mouth dissolving films (MDFs) are thin polymeric strips that rapidly disintegrate in the oral cavity without the need for water. These films improve patient compliance, particularly in paediatric and geriatric populations. Mixed hydrotropy is an emerging solubility enhancement technique that utilizes combinations of hydrotropic agents such as sodium benzoate, urea, and sodium citrate to enhance drug solubility. This method reduces the need for organic solvents and surfactants. Prebiotics such as inulin and fructooligosaccharides improve gastrointestinal microflora and enhance nutrient and drug absorption. Incorporation of prebiotics into mouth dissolving films may improve gastrointestinal uptake of albendazole. This review discusses formulation strategies, optimization techniques, and characterization methods for developing prebiotic-integrated albendazole mouth dissolving films using mixed Hydrotropy.

Table: Formulation of Mouth Dissolving Film Using HPMC

Method of Preparation:

Preparation of Albendazole Mouth Dissolving Film

The mouth dissolving films were prepared by solvent casting method, which is widely used for oral film preparation.

Preparation of Hydrotropic Drug Solution

Piperazine was first dissolved in 5–10 ml of distilled water to prepare a hydrotropic solution. Then, Albendazole (100 mg) was slowly added to this solution with continuous stirring. After that, 1.5 ml of ethanol was added to enhance the solubility of the drug. The mixture was further stirred using a magnetic stirrer until a clear solution was obtained.

Preparation of Polymer Solution: HPMC (38 mg) and sodium alginate (6 mg) were dispersed in distilled water and stirred continuously to obtain a homogeneous viscous solution. PEG-400 (6 mg) was then added as a plasticizer and mixed thoroughly.

Addition of Additives: Citric acid (2.5 mg) was added as a saliva-stimulating agent, followed by stevia (1.5 mg) as a sweetening agent and inulin (2 mg) as a prebiotic. The mixture was then stirred until a uniform dispersion was achieved.

Mixing of Drug and Polymer Solution: The hydrotropic drug solution was slowly added to the polymer solution and stirred for 30–40 minutes to obtain a uniform casting solution. The mixture was then kept undisturbed for 15 minutes to remove air bubbles.

Casting of Film: The prepared solution was poured into a clean glass petri dish and spread uniformly to form a thin film.

Drying of Film: The films were dried either at room temperature or in a hot air oven at 40–45°C for 24 hours, after which they were carefully peeled off from the petri plate.

Cutting and Storage: The dried films were cut into uniform-sized strips, wrapped in aluminium foil, and stored in a desiccator until further evaluation.

Formulation-Optimization Formulation Table (F1–F5)

Table No: Albendazole Mouth Dissolving Film

Fig: Mouth Dissolving Film

Evaluation Parameters:

Physical Appearance:

Method- The prepared films were visually inspected for:

Table: Physical Appearance

Thickness:

Table: Thickness calculates by vernier calliper

Average Thickness: 0.142mm

Fig: Thickness calculates by vernier calliper

Weight Variation:

Table: Weight Variation calculate by (Electronic weighing machine): -

Fig. Weight Variation

Folding Endurance:

Table no: Folding Endurance calculate by (Use Hand): -

Average folding Endurance calculate by: 282

Fig. Folding Endurance

Surface pH

Measured value:pH=6.7 Suitable for oral cavity.

Fig. Surface pH

Drug Content:

Table no:Measured using UV Spectrophotometer

Average: 6.5mg

Drug content uniformity = 99%

Disintegration Time:

Table no: Disintegration Time

Average: 42.8

Fig: Disintegration Time

Fig: Disintegration Time

Medium:

• Phosphate buffer pH 6.8
• 37°C

Table no: Dissolution Study

UV drug absorption spectrum: Identification of drug by UV:

Standard curve in methanol 290 nm.

Fig: UV drug absorption spectrum (Albendazole)

Fig: UV Dilution Protocol

Melting Point Determination by Capillary Method:

The capillary method is a simple and accurate technique used to determine the melting point of a solid drug. The melting point is the temperature at which a substance changes from solid to liquid state. A sharp melting point range indicates purity of the drug, while a broad range indicates impurities. Albendazole melting point determination helps in drug identification and purity confirmation before formulation of mouth dissolving films.

Apparatus Required

• Melting point apparatus
• Capillary tube (sealed at one end)
• Thermometer or digital temperature display
• Mortar and pestle
• Albendazole sample

Procedure

1. Albendazole was finely powdered using mortar and pestle.
2. A clean capillary tube sealed at one end was taken.
3. The powdered drug was filled into the capillary tube up to 2–3 mm height.
4. The capillary tube was gently tapped to pack the powder.
5. The capillary tube was attached to the thermometer and placed inside the melting point apparatus.
6. The temperature was increased slowly at a rate of 1–2°C per minute.
7. The temperature at which the drug started melting and completely melted was recorded.

Table no: Melting Point Determination

Result: The melting point of Albendazole was found to be:

208∘C-210∘C
The observed melting point is within the reported range of 208–210°C, indicating that the drug sample is pure and suitable for formulation.

Qualitative Solubility Study:

Qualitative solubility study is performed to determine whether the drug is freely soluble, soluble, sparingly soluble, slightly soluble, or insoluble in different solvents by visual observation.

Procedure:

1. About 10 mg of Albendazole was taken in separate test tubes.
2. 10 ml of different solvents were added individually.
3. The mixtures were shaken for 10–15 minutes.
4. Solubility was observed visually.

Table no: Qualitative Solubility Study

Result: Albendazole was found to be:

• Practically insoluble in water
• Slightly soluble in ethanol
• Slightly soluble in phosphate buffer
• Freely soluble in hydrotropic solution
• This confirms that mixed Hydrotropy improves solubility of Albendazole.

Quantitative Solubility Study:

Quantitative solubility study determines the exact amount of drug dissolved per ml of solvent at room temperature.

Procedure

1. Excess amount of Albendazole was added to 10 ml solvent in stoppered vials.
2. The vials were shaken for 24 hours using a mechanical shaker at 25°C.
3. The solution was filtered using Whatman filter paper.
4. The filtrate was diluted suitably.
5. Absorbance was measured using UV Spectrophotometer at 295 nm.
6. Drug concentration was calculated using calibration curve.

Calibration Curve Data:

Table no: Calibration Curve Data

Calibration equation:y=0.056x+0.001

Fig: Quantitative Solubility Study

Quantitative Solubility Results:

Table no: Quantitative Solubility Results

Result:

Qualitative solubility study showed Albendazole is poorly soluble in water and slightly soluble in organic solvents.

Quantitative solubility study showed:

• Water = 0.0003 mg/ml
• Ethanol = 0.0016 mg/ml
• Buffer pH 6.8 = 0.0011 mg/ml
• Hydrotropic solution = 0.01 mg/ml

Hydrotropic solution increased solubility by approximately:0.01/0.0003- 33 times Therefore, mixed hydrotropy significantly enhanced Albendazole solubility.

Fig: Quantitative Solubility Stud

Fig: Quantitative Solubility Study