INTRODUCTION:

Postoperative nausea and vomiting (PONV) occur in about 20–40% of adult patients following general anaesthesia in the absence of prophylactic antiemetic therapy. These symptoms cause significant discomfort, anxiety, and sleep disturbance for patients and create challenges for clinicians. Among modern antiemetic agents, 5-HT₃ receptor antagonists have gained attention due to their high efficacy and fewer side effects.

Ondansetron hydrochloride (OSH) is a selective 5-HT₃ receptor antagonist widely used for the prevention and treatment of nausea and vomiting induced by chemotherapy, radiotherapy, and anaesthesia. It exerts its antiemetic effect by blocking serotonin receptors both peripherally at the vagal nerve terminals and centrally at the chemoreceptor trigger zone, thereby inhibiting the vomiting reflex¹.

Ondansetron hydrochloride belongs to BCS Class II, characterized by high permeability but low and pH-dependent solubility¹. Although it exhibits moderate solubility in acidic conditions, its limited solubility at neutral pH can affect dissolution and bioavailability. After oral administration of an 8 mg tablet, its bioavailability is approximately 56%, as it undergoes partial first-pass metabolism. Common side effects include headache and constipation, but the drug is generally well tolerated².

Since poor aqueous solubility limits drug absorption³, various solubility enhancement techniques such as solid dispersions and co-crystallization have been explored. Solid dispersions improve dissolution by reducing particle size, increasing wettability, and enhancing porosity. These can be prepared using methods such as fusion, solvent evaporation, hot melt extrusion, and co-grinding⁴.

Co-crystallization is an emerging and effective technique for solubility enhancement. It involves the formation of a crystalline complex between the drug (API) and a suitable co-former in a fixed stoichiometric ratio through non-covalent interactions³. This approach can modify physicochemical properties such as solubility, stability, and dissolution rate without altering the drug’s pharmacological activity.

Common co-crystallization techniques include solvent evaporation, grinding, slurry crystallization, solvent drop grinding, high-throughput crystallization, hot melt extrusion, and Sonocrystallization³.

MATERIALS AND METHODS:

Materials:

Ondansetron Hydrochloride was obtained as a gift sample from Aurore Pharmaceuticals private Ltd. Hyderabad, Telangana, India.

Chemicals:

Ethanol, Co-formers, (Citric acid, Oxalic acid, Adipic acid, Tartaric acid) Polymers, (PEG 4000, PVP-K30, Eudragit), and for the preparation of buccal patch of ondansetron Hydrochloride materials like chitosan, poly vinyl pyrrolidone, propylene glycol, triethanolamine and acetic acid were obtained from central store of KLE college of pharmacy, Nipani.

Methodology:

Preformulation Study:

Characterization of Pure Drug:

Studies on various physico-chemical properties of drug substance were done along with chemical authentication by physical appearance, melting point determination, solubility analysis, and UV spectra.

Physical Appearance:

The physical appearance of the drug sample was characterized on the basis of color, Odor and taste. All these parameters were recorded and compared with standard.

Melting point determination:

Melting point of drug sample was determined by using capillary tube method by filling small amount of sample drug in capillary. The sample was heated slowly and observed continuously for most accurate results. The melting range was recorded with begins when the sample start to melt and ends when the sample is completely melted, then the readings were taken.

Solubility Analysis:

An excess amount of sample was mixed with 10ml water in volumetric flask. Then the flask was shaken for 48 hrs at 37±1ºC. The resulting solution was passed through a filter paper. The absorbance was measured using a UV- visible spectrophotometer at λmax of 310nm².

Analytical Method Adoption by UV Spectrophotometer:

For the analysis of Ondansetron Hydrochloride concentration in formulation, the UV spectrophotometer was used and for method adopting following steps were performed.

Determination of λmax of Ondansetron Hydrochloride:

The stock solution of Ondansetron Hydrochloride (10µg/ml) was prepared in distilled water. This sample was scanned in the range 200-400nm using UV spectrophotometer to determine λmax.

Preparation of Stock Solution:

For the preparation of stock solution 10mg of the pure drug was accurately weighed and dissolved in 100ml volumetric flask and then volume was made up to 100ml with water to give solution of 100µg/ml.

Preparation of Sample Solution:

Calibration sample were prepared from the stock solution I (100µg/ml) from this 0.4, 0.8, 1.2, 1.6, 2ml of withdrawn and volume is made up to 10 ml with water to get dilution of 4, 8, 12, 16, 20µg/ml.

Preparation of Calibration Curve for Ondansetron Hydrochloride:

To prepare calibration curve the serial dilution of Ondansetron Hydrochloride in concentration range 4, 8, 12, 16 20µg/ml were prepared in water and the absorbance of these dilutions were determined on UV spectrophotometer at λmax 310nm using water as blank. The absorbance values corresponding to each concentration were then statistically evaluated and plotted as a standard graph between absorbance on y-axis and concentration on x-axis.

Methods to Enhhance the Solubility of Ondansetron Hydrochloride:

1. Solid dispersion by Solvent Evaporation Method-

Preparation of Ondansetron Hydrochloride Solid dispersion:

The calculated amount of drug and the employed polymers like PEG 400, PVP-K 30 and Eudragit are weighed and mixed together in porcelain dish in weight ratio of 1:1 The mixture was dissolved in least amount of methanol (10ml) as a common solvent then solvent is evaporated on magnetic stirrer at room temperature till complete evaporation .The solid dispersion were prepared and kept for drying for 24hours⁴.

Table 1: Screening of Polymers.

Sr. No.	Name of Polymer	Quantity of Polymer (mg)	Quantity of Drug (mg)	Quantity of Solvent (ml)
1.	PEG 400	500	500	10
2.	PVP-K30	10	500	10
3.	Eudragit RS-100	10	500	10

2. Co-crystallization by solvent evaporation method: Ondansetron Hydrochloride co-crystals were prepared by solvent evaporation method. The drug and co-former were mixed in equimolar ratio 1:1(2mmol) in 10mL of ethanol and heated with constant stirring in a closed container for 2 h. The solution was then filtered through filter paper to remove insoluble. The filtered solution was then allowed to evaporate slowly at room temperature. The four co-formers were screened Citric acid, tartaric acid, oxalic acid and adipic acid⁵.

Table 2: Screening of co-formers.

Sr. No	Coformers	Quantity of coformer taken (mg)	Quantity of drug taken (mg)	Quantity of ethanol (ml)
1	Adipic acid	850	650	10
2	Oxalic acid	830	650	10
3	Citric acid	300	650	10
4	Tartaric acid	380	650	10

Formulation of Mucoadhesive Buccal Patch:

Method of Preparation of Buccal Patch:

The preparation of buccal film, the formula weights of chitosan [bioadhesive polymer] and PVP [film forming polymer] were dispersed in 21ml of an aqueous solution containing 1.5ml acetic acid. The polymeric dispersion was stirred slowly using a magnetic stirrer until a clear viscous solution was formed. The formula weight of ondansetron hydrochloride was dissolved in 10ml of aqueous solution containing 1.5ml acetic acid, 1.25ml propylene glycol⁸. Absolute ethanol and 4-5 drops of triethanolamine were added to solubilize ondansetron HCl to form clear film. The drug solution was added to the polymeric solution and mixed gently. The dispersion was left overnight to allow the removal of air bubbles. Film was cast into Teflon plate and dried in an oven at 40ºC for 12h. The dried buccal film was cut into 1×1 cm pieces, packed in an aluminum foil, and stored in a desiccator for further evaluation⁶.

Table 3: Formulation of Buccal Patch

Sr. No.	Ingredients	Quantity
1	Ondansetron Hydrochloride Co-crystals (equivalent to 8 mg drug)	12.67mg
2	PVP	1g
3	Chitosan	1.5g
4	Propylene Glycol	2.5ml
5	Acetic Acid	1.5ml
6	Ethanol: Water	QS (Quantity Sufficient)

RESULT:

Pre formulation studies:

1. Melting point:

Melting point of the ondansetron Hydrochloride was found to be 179°C (178 179ºC) by capillary method.

2. Solubility analysis:

Inherent solubility of ondansetron Hydrochloride was determined in water. It was found to 47.4mg/ml Determination of λmax of Ondansetron Hydrochloride: A stock solution of 10µg/ml of Ondansetron Hydrochloride was prepared in water and scanned in UV range 200-400nm.The λmax of Ondansetron Hydrochloride was found to be 310nm⁷.

Fig 1: λmax of ondansetron Hydrochloride.

Standard curve of Ondansetron Hydrochloride:

Concentration from 4µg/ml - 20µg/ml of the drug were prepared from the stock I (100µg/ml) solution. The absorbance of the drug solution was taken at 310nm against reference. The variable absorbance was recorded against concentrations. The results were given in table no 5. A plot of concentration versus absorbance was found to be linear in concentration range 4ug/ml, 8ug/ml, 12ug/ml, 16ug/ml and 20ug/ml with R square value 0.997. The equation of the line was y= 0.0412x + 0.0217.

Table 4: Calibration curve of ondansetron Hydrochloride in water.

Sr. No.	Concentration (µg/ml)	Absorbance (nm)
1	4	0.179
2	8	0.368
3	12	0.500
4	16	0.691
5	20	0.841

Fig 2: Standard curve of ondansetron Hydrochloride.

Solubility Enhancement of Ondansetron Hydrochloride by using Solid Dispersion and Co- crystallization:

Solid Dispersion:

Ondansetron hydrochloride solid dispersion were prepared by using solvent evaporation method. The drug and polymers were mixed in weight ratio of 1:1.

Drug Content:

The percentage drug content of ondansetron Hydrochloride was determined by dissolving 50mg of co-crystals in 50ml of water. The solution was filtered and determined absorbance by using UV spectrophotomer. The percentage drug content was found to be 98.78%.

Solubility Analysis:

All the co-crystals of ondansetron hydrochloride have showed remarkable increased solubility but co-crystals of Ondansetron hydrochloride-tartaric acid have showed enhanced solubility by almost 13 times to that of original solubility of Ondansetron hydrochloride. Hence Tartaric acid was selected for further studies.

Evaluation of Mucoadhesive Buccal film:

1. Weight uniformity:

The weights of film were determined using digital balance and the average weight of all films were calculated, values were ranged from 53 to 91mg.

2. Thickness: Thickness of films were determined using a standard vernier caliper, The thickness of buccal patch was found to be 0.1mm.

3. Folding Endurance: The folding endurance study was carried out for determining flexibility of patch by repeatedly folding a small strip of the film at the same place till it broke. The folding endurance of patch was found to be 252±10. This revealed that the films have good mechanical strength and flexibility.

4. Surface pH: The surface pH of buccal film was found to be 6.5. The formulation has pH in the range of salivary pH (5 to 7). Hence may not produce any irritation to buccal mucosa.

5. Drug Content: The percent drug content from plain drug film and ondansetron hydrochloride co-crystals loaded film was found to be 99.38% and 98.07% respectively.

6. In-vitro drug release: In-vitro drug release studies were carried out for plain ondansetron hydrochloride buccal patch and ondansetron hydrochloride co-crystals loaded buccal patch in water. The study was performed for 10 minutes. and cumulative drug release was calculated at different time intervals. At the time of 10 minutes the drug release from ondansetron co-crystals loaded film was found to be 95.58% as compare to the plain drug.

Table 7: % drug release from formulations.

Sr. No.	Time (min)	Plain Drug Film (% CDR)	Co-Crystal Loaded Film (% CDR)
1	1	0.41	5.20
2	2	6.11	15.43
3	3	10.20	28.80
4	4	16.08	34.71
5	5	20.11	47.50
6	6	29.45	62.13
7	7	37.80	73.50
8	8	41.96	84.25
9	9	43.23	89.23
10	10	45.34	95.58

Fig 3. In-vitro drug release profile

7. Moisture loss: To determine the integrity of the film at dry conditions, they were evaluated for percentage moisture loss. The moisture loss of film was found to be 17.06±2.4%.

8. Moisture uptake: To determine the physical stability of the patch at high humidity conditions, they were evaluated for percentage moisture uptake. The moisture uptake of film was found to be 4.74±2.42%.

CONCLUSION:

Ondansetron hydrochloride belongs to BCS class II drug (low solubility and high permeability). To enhance its solubility two different techniques (solid dispersion, co-crystallization) were used. Co-crystallization method showed enhanced solubility of ondansetron hydrochloride using tartaric acid as co-former by 13 times as compare to other studied method. Co-crystal loaded buccal film was prepared by using solvent casting method and evaluated for parameters such as thickness, weight variation folding endurance, moisture uptake and moisture loss, in-vitro drug release. Results showed that all the parameters were within acceptable limits. When prepared film is compared with plain drug-based film, the co-crystal-based film has shown better drug release profile. Thus, the present study concludes that co-crystallization is a promising approach in order to increase the solubility of BCS class 2 drug. Further buccal film of ondansetron hydrochloride is a safe and more effective drug delivery approach as compared to traditional approaches.

REFERENCE:

1. Praful R. Ingle, Prof. Ambika D. Nagarbhadiya, Dr. Ranjit D. A Review on Buccal Patches, International Journal of Novel Research and Development (IJNRD). 2023; 8.

2. Sahu GK Gupta C. Exploration of solubilization Strategies: Enhancing Bioavailability for Low Solubility Drugs, International Journal of Newgen Research in Pharmacy and Healthcare. 2023; 1(2).

3. Poonam K, Sameer R, et al Solubility Enhancement of Poorly Water-Soluble Drugs, International Journal of Pharmaceutical sciences And Research. 5(8).

4. Suthar RM, Narendra P, Hardik K. Patel, Sandip R. Patel. et al -In vitro Dissolution Enhancement of Ondansetron by Solid Dispersion in Super disintegrants. dx doI.org / 10.14227/ DT200413P34.

5. Wankhade A, Akolkar A, et al Solubility Enhancement Techniques by Co-Crystallization. International Journal of Creative Research Thoughts. 2023; 11.

6. Arushi Saxena, Formulation and Evaluation of Oral Dissolving Films of Ondansetron HCL World Journal Of Pharmaceutical Research. 9(7): 2019-2036.

7. Kalaichelvi R, Rao BM, Manikanta S, Gopinath G, Usha M, Ramana DV, Rao DS, Jayachandran E. UV spectrophotometric method for determination of ondansetron hydrochloride in pure and its formulation. Int J Pharm Pharm Sci. 2012; 4(4):151-2.

8. Shritika M, Asish Dev, Ganesh Deshmukh, S. Rathod. Current approaches in buccal drug delivery system, Pharmaceutical and Biological Evaluation, 2016; 3(2): 165-177.

Received on 16.02.2026 Revised on 19.03.2026

Accepted on 17.04.2026 Published on 04.07.2026

Available online from July 18, 2026

Asian J. Pharm. Tech. 2026; 16(3):241-245.

DOI: 10.52711/2231-5713.2026.00034

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.

Sr. No.	Method of Preparation	Polymer	Drug: Polymer Ratio	Intrinsic Solubility (mg/ml)	Enhanced Solubility (mg/ml)	Times Solubility Enhanced
1	Solvent Evaporation Method	PVP-K30	1:1	47.4	100.48	2.11
2	Solvent Evaporation Method	PEG-4000	1:1	47.4	67.3	1.41
3	Solvent Evaporation Method	Eudragit	1:1	47.4	52.33	1.10

Sr. No.	Method of Preparation	Coformer	Drug: Coformer Ratio	Intrinsic Solubility (mg/ml)	Enhanced Solubility (mg/ml)	Times Solubility Enhanced
1	Solvent Evaporation Method	Citric Acid	1:1	47.4	70.12	1.47
2	Solvent Evaporation Method	Tartaric Acid	1:1	47.4	631.01	13.31
3	Solvent Evaporation Method	Adipic Acid	1:1	47.4	64.10	1.35
4	Solvent Evaporation Method	Oxalic Acid	1:1	47.4	58.90	1.24