Hydroxyzine Pamoate Capsules

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

Hydroxyzine Pamoate Capsules contain hydroxyzine pamoate (C₂₁H₂₇ClN₂O₂ · C₂₃H₁₆O₆) equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of hydroxyzine hydrochloride (C₂₁H₂₇ClN₂O₂ · 2HCl).

2 IDENTIFICATION

A. The retention time of the hydroxyzine peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

B. The UV spectrum of the hydroxyzine peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Change to read:

Procedure

Solution A: To each L of water, add 1.0 mL of stronger ammonia water.

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and Solution A (80:20)

System suitability solution: 1 µg/mL of USP Hydroxyzine Pamoate RS (equivalent to 0.6 µg/mL of hydroxyzine hydrochloride), 3 µg/mL of USP Hydroxyzine Related Compound A RS, and 1 µg/mL of USP 4-Chlorobenzophenone RS in Diluent

Standard solution: 0.1 mg/mL of USP Hydroxyzine Pamoate RS (equivalent to 0.06 mg/mL of hydroxyzine hydrochloride) in Diluent

Sample stock solution: Nominally 1.0 mg/mL of hydroxyzine pamoate from Capsules (equivalent to 0.6 mg/mL of hydroxyzine hydrochloride) prepared as follows. Transfer a portion of the powder from NLT 10 Capsules to a suitable volumetric flask. Add 75% of the flask volume of Diluent, sonicate for NLT 15 min, and shake by mechanical means for NLT 30 min. Dilute with Diluent to volume. Centrifuge a portion of 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 0.1 mg/mL of hydroxyzine pamoate (equivalent to 0.06 mg/mL of hydroxyzine hydrochloride) from 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: 4.6-mm × 15-cm; 3.5-µm packing L1.

[Note—Rinse the column with a solution of acetonitrile and water (20:80) and then with a solution of acetonitrile and water (80:20) after each analysis.]

Column temperature: 45°

Flow rate: 1 mL/min

Injection volume: 10 µL

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for decloxizine and 4-chlorobenzophenone are 0.90 and 1.1, respectively. See Table 2 for the relative retention times for other compounds.]

Suitability requirements

Resolution: NLT 1.5 between hydroxyzine and hydroxyzine related compound A; NLT 1.5 between hydroxyzine related compound A and ▲4-chlorobenzophenone▲ (ERR 1-Jun-2021), System suitability solution

Tailing factor: NMT 1.5 for hydroxyzine, Standard solution

Relative standard deviation: NMT 0.73% for hydroxyzine, Standard solution

Analysis

Samples: Standard solution and Sample solution

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

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × (Mₛ / Mᵤ) × 100

rᵤ = peak response of hydroxyzine from the Sample solution

rₛ = peak response of hydroxyzine from the Standard solution

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

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

Mₛ = molecular weight of hydroxyzine hydrochloride, 447.83

Mᵤ = molecular weight of hydroxyzine pamoate, 763.27

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

Time: 60 min

Mobile phase: Methanol and 0.05 M monobasic sodium phosphate (60:40)

Standard solution: USP Hydroxyzine Hydrochloride RS in Medium

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

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 232 nm

Column: 4.6-mm × 25-cm; 10-µm packing L9

Flow rate: 1.9 mL/min

Injection volume: 50 µL

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of hydroxyzine hydrochloride (C₂₁H₂₇ClN₂O₂ · 2HCl) dissolved:

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

rᵤ = peak response of hydroxyzine from the Sample solution

rₛ = peak response of hydroxyzine from the Standard solution

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

D = dilution factor for the Sample solution, if needed

V = volume of the Medium, 900 mL

L = label claim (mg/Capsule)

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

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Organic Impurities

Mobile phase, Diluent, and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 1 µg/mL of USP Hydroxyzine Pamoate RS (equivalent to 0.6 µg/mL of hydroxyzine hydrochloride), 3 µg/mL of USP Hydroxyzine Related Compound A RS, and 1 µg/mL of USP 4-Chlorobenzophenone RS in Diluent

Sample solution: Nominally 1000 µg/mL of hydroxyzine pamoate from Capsules (equivalent to 600 µg/mL of hydroxyzine hydrochloride) prepared as follows. Transfer a portion of the powder from NLT 10 Capsules to a suitable volumetric flask. Add 75% of the flask volume of Diluent, sonicate for NLT 15 min, and shake by mechanical means for NLT 30 min. Dilute with Diluent to volume. Centrifuge a portion of the solution and use the supernatant.

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

System suitability

Sample: Standard solution

[Note—The relative retention times for decloxizine and 4-chlorobenzophenone are 0.90 and 1.1, respectively. See Table 2 for the relative retention times for other compounds.]

Suitability requirements

Resolution: NLT 1.5 between hydroxyzine and hydroxyzine related compound A; NLT 1.5 between hydroxyzine related compound A and 4-chlorobenzophenone

Relative standard deviation: NMT 5.0% each for hydroxyzine and hydroxyzine related compound A

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of hydroxyzine related compound A in the portion of Capsules taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response of hydroxyzine related compound A from the Sample solution

rₛ = peak response of hydroxyzine related compound A from the Standard solution

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

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

Calculate the percentage of each unspecified degradation product in the portion of Capsules taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × (Mₛ / Mᵤ) × 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 Pamoate RS in the Standard solution (µg/mL)

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

Mₛ = molecular weight of hydroxyzine hydrochloride, 447.83

Mᵤ = molecular weight of hydroxyzine pamoate, 763.27

Acceptance criteria: See Table 2. The reporting threshold is 0.05%.

Table 2

ᵃ This peak is due to the pamoate counterion; hence it is not an impurity and should not be included in the total degradation products.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers. Store at controlled room temperature.

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.

C₁₇H₁₉ClN₂ 286.80

USP Hydroxyzine Pamoate RS