Cetirizine Hydrochloride Orally Disintegrating Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION 

Cetirizine Hydrochloride Orally Disintegrating Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of cetirizine hydrochloride (C₂₁H₂₅ClN₂O₃.2HCl). 

2 IDENTIFICATION 

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. 

3 ASSAY 

Procedure 

Buffer A: Dissolve 13.2 g of sodium 1-decanesulfonate in 2760 mL of water. Add 5.5 g of monobasic sodium phosphate and 1.2 mL of phosphoric acid. Pass through a suitable filter. 

Buffer B: Dissolve 13.2 g of sodium 1-decanesulfonate in 2000 mL of water. Add 5.5 g of monobasic sodium phosphate and 1.2 mL of phosphoric acid. Pass through a suitable filter. Solution A: Acetonitrile and Buffer A (31:69) Solution B: Acetonitrile and Buffer B (50:50) Mobile phase: See Table 1. 

Table 1

Diluent: Acetonitrile and 0.01 N hydrochloric acid (20:80) 

System suitability stock solution: 0.04 mg/mL of USP Meclizine Related Compound A RS, prepared as follows. Transfer a quantity of the compound into a suitable volumetric flask. Add 5% of the flask volume of acetonitrile to dissolve the components. Sonicate if needed. Dilute with Diluent to volume. 

System suitability solution: 0.4 mg/mL of USP Cetirizine Hydrochloride RS and 1.2 µg/mL of USP Meclizine Related Compound A RS, prepared as follows. In a 100-mL volumetric flask, dissolve 40 mg of USP Cetirizine Hydrochloride RS in Diluent, and then pipet 3.0 mL of the System suitability stock solution. Dilute with Diluent to volume. 

Standard solution: 0.4 mg/mL of USP Cetirizine Hydrochloride RS in Diluent 

Sample solution: Nominally 0.4 mg/mL of cetirizine hydrochloride, prepared as follows. Transfer 20 Tablets into a 500-mL volumetric flask, add 375 mL of Diluent, and stir for at least 30 min. Dilute with Diluent to volume and pass a portion of this solution through a suitable filter (GHP or PVDF), discarding the first 1 mL of filtrate. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 230 nm. For Identification test B, use a diode array detector in the range of 210–300 nm. 

Column: 4.6-mm × 15-cm; 3.5-µm packing L1 

Column temperature: 30° 

Flow rate: 1.5 mL/min 

Injection volume: 20 µL 

System suitability 

Samples: System suitability solution and Standard solution 

[Note—Identify the components on the basis of their relative retention times, as shown in Table 2.] 

Suitability requirements 

Resolution: NLT 1.5 between cetirizine and meclizine related compound A, System suitability solution 

Relative standard deviation: NMT 2.0%, Standard solution 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of cetirizine hydrochloride (C₂₁H₂₅ClN₂O₃.2HCl) in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × 100 

r_U = peak response from the Sample solution 

r_S = peak response from the Standard solution 

C_S = concentration of USP Cetirizine Hydrochloride RS in the Standard solution (mg/mL) 

C_U = nominal concentration of cetirizine hydrochloride in the Sample solution (mg/mL) 

Acceptance criteria: 90.0%–110.0% 

4 PERFORMANCE TESTS 

Disintegration 〈701〉: NMT 30 s 

Dissolution 〈711〉 

Medium: pH 6.5 phosphate buffer (4.77 g/L monobasic potassium phosphate and 2.62 g/L of dibasic potassium phosphate); 900 mL, degassed by USP procedure 

Apparatus 2: 50 rpm Time: 15 min 

Buffer: 2.7 g/L of monobasic potassium phosphate in water. Add 0.6 mL/L of phosphoric acid. 

Mobile phase: Acetonitrile and Buffer (33:67) 

Diluent: Acetonitrile and 0.01 N hydrochloric acid (20:80) 

Standard stock solution: 0.1 mg/mL of USP Cetirizine Hydrochloride RS in Diluent 

Standard solution: 0.01 mg/mL of USP Cetirizine Hydrochloride RS from Standard stock solution, in Medium Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size, discarding the first 1–2 mL. Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 230 nm 

Column: 4.6-mm × 7.5-cm; 3.5-µm packing L1 

Column temperature: 40° 

Flow rate: 2.5 mL/min 

Injection volume: 100 µL 

Run time: 2.7 times the retention time of cetirizine 

System suitability 

Sample: Standard solution 

Suitability requirements 

Tailing factor: NMT 2.0 

Relative standard deviation: NMT 2.0% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of cetirizine hydrochloride (C₂₁H₂₅ClN₂O₃.2HCl) dissolved: 

Result = (r_U/r_S) × C_S  x 1/L × V × 100 

r_U = peak response from the Sample solution 

r_S = peak response from the Standard solution 

C_S = concentration of cetirizine hydrochloride in the Standard solution (mg/mL) 

L = label claim (mg/Tablet) 

V = volume of Medium, 900 mL 

Tolerances: NLT 80% (Q) of the labeled amount of cetirizine hydrochloride (C₂₁H₂₅ClN₂O₃.2HCl) is dissolved. 21 

Uniformity of Dosage Units 〈905〉: Meet the requirements 

5 IMPURITIES 

Organic Impurities 

Buffer A, Buffer B, Solution A, Solution B, Mobile phase, and Diluent: Proceed as directed in the Assay. 

System suitability stock solution: 0.04 mg/mL each of USP Cetirizine Related Compound G RS, USP Cetirizine Related Compound B RS, USP 4-Chlorobenzophenone RS, USP Meclizine Related Compound A RS, and USP Cetirizine Related Compound A RS, and 0.06 mg/mL each of USP Hydroxyzine Related Compound A RS and USP Cetirizine Related Compound C RS, prepared as follows. Transfer a quantity of each compound into a suitable volumetric flask. Add 5% of the flask volume of acetonitrile to dissolve the compounds. Sonicate as needed. Dilute with Diluent to volume. 

System suitability solution: 0.4 mg/mL of USP Cetirizine Hydrochloride RS; 1.2 µg/mL each of USP Cetirizine Related Compound G RS, USP Cetirizine Related Compound B RS, USP 4-Chlorobenzophenone RS, USP Meclizine Related Compound A RS, and USP Cetirizine Related Compound A RS; and 1.8 µg/mL each of USP Hydroxyzine Related Compound A RS and USP Cetirizine Related Compound C RS, prepared as follows. In a 100-mL volumetric flask, dissolve 40 mg of USP Cetirizine Hydrochloride RS in Diluent, and then pipet 3.0 mL of the System suitability stock solution. Dilute with Diluent to volume. 

Standard stock solution: 0.04 mg/mL each of USP Cetirizine Hydrochloride RS, USP Cetirizine Related Compound G RS, USP Hydroxyzine Related Compound A RS, and USP 4-Chlorobenzophenone RS, prepared as follows. Transfer a quantity of each compound into a suitable volumetric flask. Add 5% of the flask volume of acetonitrile to dissolve the compounds. Sonicate if needed. Dilute with Diluent to volume. 

Standard solution: 0.8 µg/mL each of USP Cetirizine Hydrochloride RS, USP Cetirizine Related Compound G RS, USP Hydroxyzine Related Compound A RS, and USP 4-Chlorobenzophenone RS from Standard stock solution, in Diluent 

Sample solution: Nominally 400 µg/mL of cetirizine hydrochloride, prepared as follows. Transfer 20 Tablets into a 500-mL volumetric flask, add 375 mL of Diluent, and stir for at least 30 min. Dilute with Diluent to volume and pass a portion of this solution through a suitable filter (GHP or PVDF), discarding the first 1 mL of filtrate. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 230 nm and 260 nm 

Column: 4.6-mm × 15-cm; 3.5-µm packing L1 

Column temperature: 30° 

Flow rate: 1.5 mL/min 

Injection volume: 50 µL 

System suitability 

Samples: System suitability solution and Standard solution 

Suitability requirements 

Resolution: NLT 1.5 between cetirizine and meclizine related compound A, System suitability solution 

Relative standard deviation: NMT 10.0% for each component, Standard solution 

Analysis 

Samples: Standard solution and Sample solution 

Chromatograph the System suitability solution, and identify the components on the basis of their relative retention times, as shown in Table 2. Use the peak response at 260 nm for 4-chlorobenzophenone. Use 230 nm for all other degradation products. Calculate the percentage of cetirizine related compound G, hydroxyzine related compound A, and 4-chlorobenzophenone in the portion of Tablets taken: 

Result = (r_U/r_S) × (C_S/C_U) × 100 

r_U = peak response of cetirizine related compound G, hydroxyzine related compound A, or 4-chlorobenzophenone from the Sample solution

r_S = peak response of the appropriate USP Reference Standard from the Standard solution

C_S = concentration of the appropriate USP Reference Standard in the Standard solution (μg/mL)

C_U = nominal concentration of cetirizine hydrochloride in the Sample solution (mg/mL) 

Calculate the percentage of all other degradation products in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × 100 

r_U = peak response of any other degradation product from the Sample solution

r_S = peak response of cetirizine from the Standard solution 

C_S = concentration of USP Cetirizine Hydrochloride RS in the Standard solution (mg/mL) 

C_U = nominal concentration of cetirizine hydrochloride in the Sample solution (mg/mL) 

Table 2 

^a Process impurity included in the table for Identification only. Process impurities are controlled in the drug substance, and are not to be reported or included in the total impurities for the drug product. 

6 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in tight containers. Store at controlled room temperature. 

Change to read: 

USP Reference Standards 〈11〉 

USP Cetirizine Hydrochloride RS 

USP Cetirizine Related Compound A RS 

(RS)-2-[2-[4-[(4-Chlorophenyl)phenylmethyl]piperazin-1-yl]ethoxy]acetic acid ethyl ester oxalate. 

C₂₃H₂₉ClN₂O₃.C₂H₂O₄    506.97

USP Cetirizine Related Compound B RS 

2-(4-Benzhydrylpiperazin-1-yl)ethan-1-ol. 

C₁₉H₂₄N₂O      296.41  

USP Cetirizine Related Compound C RS 

2-(2-{4-[(4-Chlorophenyl)phenylmethyl]piperazin-1-yl}ethoxy)acetamide. 

C₂₁H₂₆ClN₂O₃      387.90 

USP Cetirizine Related Compound G RS 

2-{4-[(4-Chlorophenyl)phenylmethyl)piperazin-1-yl}ethanol. 

C₁₉H₂₃ClN₂O₃    330.85 

USP 4-Chlorobenzophenone RS 

(4-Chlorophenyl)phenylmethanone. 

C₁₃H₁₉ClN₂    216.66 

USP Hydroxyzine Related Compound A RS 

1-[(4-Chlorophenyl)phenylmethyl]piperazine. 

C₁₇H₁₉ClN₂    286.80 

s USP Meclizine Related Compound A RS 

4-Chlorobenzhydrol. 

C₁₃H₁₁ClO      218.68