Hydroxyzine Hydrochloride Tablets

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

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

DOWNLOAD PDF HERE

1 DEFINITION

Hydroxyzine Hydrochloride Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of hydroxyzine hydrochloride (C₂₁H₂₇ClN₂O₂ · 2HCl).

2 IDENTIFICATION

A. The retention time of the main peak of the Sample solution corresponds to that of the hydroxyzine peak 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

Solution A: Trifluoroacetic acid and water (0.1:99.9)

Solution B: Trifluoroacetic acid and acetonitrile (0.05:99.95)

Mobile phase: See Table 1.

Diluent: Acetonitrile and water (30:70)

Standard solution: 0.05 mg/mL of USP Hydroxyzine Hydrochloride RS in Diluent

Sample stock solution: Nominally 0.5 mg/mL of hydroxyzine hydrochloride from Tablets in Diluent prepared as follows. Transfer a portion of finely powdered Tablets (NLT 10), equivalent to 50 mg of hydroxyzine hydrochloride, to a 100-mL volumetric flask and add 80 mL of Diluent. Sonicate for 30 min to dissolve and dilute with Diluent to volume. Centrifuge the solution and use the supernatant.

[Note—The use of a centrifuge speed of 3000 rpm for 10 min may be suitable.]

Sample solution: Nominally 0.05 mg/mL of hydroxyzine hydrochloride from the Sample stock solution in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm. For Identification B, use a diode array detector in the range of 200–400 nm.

Column: 2.1-mm × 15-cm; 1.8-µm packing L1

Flow rate: 0.3 mL/min

Injection volume: 2 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 1.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of hydroxyzine hydrochloride (C₂₁H₂₇ClN₂O₂ · 2HCl) in the portion of Tablets taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response from the Sample solution

rₛ = peak response from the Standard solution

Cₛ = concentration of USP Hydroxyzine Hydrochloride RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of hydroxyzine hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Change to read:

Dissolution 〈711〉

Test 1

Medium: Water; 900 mL

Apparatus 2: 50 rpm

Time: 45 min

Standard solution: USP Hydroxyzine Hydrochloride RS in Medium

Sample solution: Use a filtered portion of the solution under test. Dilute with Medium, if necessary.

Instrumental conditions

Mode: UV

Analytical wavelength: Maximum absorbance at about 230 nm

Analysis

Samples: Standard solution and Sample solution

Determine the percentage of the labeled amount of hydroxyzine hydrochloride (C₂₁H₂₇ClN₂O₂ · 2HCl) dissolved from the UV absorbances.

Tolerances: NLT 75% (Q) of the labeled amount of hydroxyzine hydrochloride (C₂₁H₂₇ClN₂O₂ · 2HCl) is dissolved.

Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.

Medium: Water; 250 mL

Apparatus 3: 30 dips/min

Time: 45 min

Standard solution: USP Hydroxyzine Hydrochloride RS in Medium

Sample solution: Use a filtered portion of the solution under test. Dilute with Medium, if necessary.

Instrumental conditions

Mode: UV

Analytical wavelength: Maximum absorbance at about 230 nm

Analysis

Samples: Standard solution and Sample solution

Determine the percentage of the labeled amount of hydroxyzine hydrochloride (C₂₁H₂₇ClN₂O₂ · 2HCl) dissolved from the UV absorbances.

Tolerances: NLT 75% (Q) of the labeled amount of hydroxyzine hydrochloride (C₂₁H₂₇ClN₂O₂ · 2HCl) is dissolved.

▲ Test 3: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.

Medium: 0.1 N hydrochloric acid; 500 mL

Apparatus 2: 50 rpm

Time: 30 min

Buffer: Dissolve 1.38 g of potassium phosphate, monobasic in 1 L of water. Adjust with phosphoric acid to a pH of 2.5.

Mobile phase: Acetonitrile and Buffer (40:60)

Standard solution: 0.02 mg/mL of USP Hydroxyzine Hydrochloride RS in Medium. Sonicate to dissolve, if necessary.

Sample solution: Pass a portion of the solution under test through a suitable filter of 10-µm pore size. Dilute with Medium to a concentration similar to that of the Standard solution, if necessary. Pass through a suitable filter of 0.45-µm pore size, discarding an appropriate volume of filtrate so that a consistent result can be obtained.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm

Column: 4.6-mm × 15-cm; 5-µm packing L1

Column temperature: 45°

Flow rate: 1 mL/min

Injection volume: 10 µL

Run time: NLT 2.7 times the retention time of hydroxyzine

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

Determine the percentage of the labeled amount of hydroxyzine hydrochloride (C₂₁H₂₇ClN₂O₂ · 2HCl) dissolved.

Result = (rᵤ / rₛ) × Cₛ × V × D × (1/L) × 100

rᵤ = peak response of hydroxyzine from the Sample solution

rₛ = peak response of hydroxyzine from the Standard solution

Cₛ = concentration of USP Hydroxyzine Hydrochloride RS in the Standard solution (mg/mL)

V = volume of the Medium, 500 mL

D = dilution factor of the Sample solution, if necessary

L = label claim (mg/tablet)

Tolerances: NLT 80% (Q) of the labeled amount of hydroxyzine hydrochloride (C₂₁H₂₇ClN₂O₂ · 2HCl) is dissolved ▲ (RB 1-Apr-2024)

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Organic Impurities

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

Standard stock solution: 25.0 µg/mL each of USP Hydroxyzine Hydrochloride RS, USP Hydroxyzine Related Compound A RS, and USP 4-Chlorobenzophenone RS in Diluent

Standard solution: 1.0 µg/mL each of USP Hydroxyzine Hydrochloride RS, USP Hydroxyzine Related Compound A RS, and USP 4-Chlorobenzophenone RS from the Standard stock solution in Diluent

Sample solution: Nominally 500 µg/mL of hydroxyzine hydrochloride from Tablets prepared as follows. Transfer a portion of finely powdered Tablets (NLT 10), equivalent to 50 mg of hydroxyzine hydrochloride, to a 100-mL volumetric flask. Add 80 mL of Diluent. Sonicate 30 min to dissolve and dilute with Diluent to volume. Centrifuge the solution and use the supernatant.

[Note—The use of a centrifuge speed of 3000 rpm for 10 min may be suitable.]

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detectors

Hydroxyzine and hydroxyzine related compound A: UV 230 nm

4-Chlorobenzophenone: UV 254 nm

Column: 2.1-mm × 15-cm; 1.8-µm packing L1

Flow rate: 0.3 mL/min

Injection volume: 2 µL

System suitability

Sample: Standard solution

[Note—See Table 2 for the relative retention times.]

Suitability requirements

Resolution: NLT 5.0 between hydroxyzine related compound A and hydroxyzine

Relative standard deviation: NMT 3.0% each for hydroxyzine related compound A, hydroxyzine, and 4-chlorobenzophenone

Analysis

Samples: Standard solution and Sample solution

For degradation products detected at UV 230 nm

Calculate the percentage of any individual unspecified degradation product in the portion of Tablets taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response of each unspecified degradation product from the Sample solution

rₛ = peak response of hydroxyzine from the Standard solution

Cₛ = concentration of USP Hydroxyzine Hydrochloride RS in the Standard solution (µg/mL)

Cᵤ = nominal concentration of hydroxyzine hydrochloride in the Sample solution (µg/mL)

For 4-chlorobenzophenone detected at UV 254 nm

Calculate the percentage of 4-chlorobenzophenone in the portion of Tablets taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response of 4-chlorobenzophenone from the Sample solution

rₛ = peak response of 4-chlorobenzophenone from the Standard solution

Cₛ = concentration of USP 4-Chlorobenzophenone RS in the Standard solution (µg/mL)

Cᵤ = nominal concentration of hydroxyzine hydrochloride in the Sample solution (µg/mL)

Acceptance criteria: See Table 2. Disregard any peak below 0.03%.

Table 2

ᵃ These are process impurities that are controlled in the drug substance. They are not to be reported or included in the total degradation products.

6 ADDITIONAL REQUIREMENTS

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

Labeling: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.

USP Reference Standards 〈11〉

USP 4-Chlorobenzophenone RS

4-Chlorobenzophenone.

C₁₃H₉ClO 216.66

USP Hydroxyzine Hydrochloride RS

USP Hydroxyzine Related Compound A RS

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

Also known as p-Chlorobenzhydrylpiperazine.

C₁₇H₁₉ClN₂ 286.80