Diphenhydramine and Phenylephrine Hydrochlorides 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

Diphenhydramine and Phenylephrine Hydrochlorides Tablets contain NLT 90.0% and NMT 110.0% of the labeled amounts of diphenhydramine hydrochloride (C₁₇H₂₁NO·HCl) and phenylephrine hydrochloride (C₉H₁₃NO₂·HCl).

2 IDENTIFICATION

A. The UV absorption spectra of the diphenhydramine and phenylephrine peaks of the Sample solutions and those of the Standard solution exhibit maxima and minima at the same wavelengths, as obtained in the Assay.

B. The retention times of the diphenhydramine and phenylephrine peaks of the Sample solution correspond to those of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 Procedure

It is suggested to use plastic vials for analysis.

Buffer: 3.45 g/L of monobasic ammonium phosphate in water. Adjust with phosphoric acid to a pH of 3.5 ± 0.05 if necessary.

Mobile phase: Acetonitrile and Buffer (25:75)

Solution A: Dilute 10 mL of glacial acetic acid with 1000 mL of water.

Diluent: Methanol and Solution A (30:70)

Standard solution: 0.25 mg/mL of USP Diphenhydramine Hydrochloride RS and 0.1 mg/mL of USP Phenylephrine Hydrochloride RS in Diluent

Sample solution: Nominally 0.25 mg/mL of diphenhydramine hydrochloride and 0.1 mg/mL of phenylephrine hydrochloride prepared as follows.

Transfer NLT 10 Tablets to a suitable volumetric flask, add 50% final volume of Solution A, and stir for NLT 30 min. Add 30% final volume of methanol, and stir additionally for NLT 90 min. To ensure that particles do not collect above the solvent level, periodically rinse particulate into solution with Solution A. Allow the resulting solution to cool to room temperature, and dilute with Solution A to volume. Pass a portion through a suitable filter of 0.45-µm pore size. Discard the first 2–3 mL of filtrate.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 214 nm. For Identification A, use a diode-array detector in the range of 200–350 nm.
• Column: 4.6-mm × 10-cm; 5-µm packing L9
• Flow rate: 2.0 mL/min
• Injection volume: 15 µL
• Run time: NLT 3 times the retention time of phenylephrine

System suitability

• Sample: Standard solution
• Suitability requirements
• Tailing factor: 0.5–3.0 for both phenylephrine and diphenhydramine
• Relative standard deviation: NMT 2.0% for both phenylephrine and diphenhydramine

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amounts of diphenhydramine hydrochloride (C₁₇H₂₁NO·HCl) and phenylephrine hydrochloride (C₉H₁₃NO₂·HCl) in the portion of Tablets taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of diphenhydramine or phenylephrine from the Sample solution

rₛ = peak response of diphenhydramine or phenylephrine from the Standard solution

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

Cᵤ = nominal concentration of diphenhydramine hydrochloride or phenylephrine hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

4.1 Dissolution 〈711〉

It is suggested to use plastic vials for analysis.

Medium: Simulated gastric fluid without pepsin; 900 mL

Apparatus 2: 50 rpm

Time: 45 min

Mobile phase: Proceed as directed in the Assay.

Standard solution: (L₁/900) mg/mL of USP Diphenhydramine Hydrochloride RS and (L₂/900) mg/mL of USP Phenylephrine Hydrochloride RS in Medium, where L₁ is the label claim of diphenhydramine hydrochloride in mg/Tablet; and L₂ is the label claim of phenylephrine hydrochloride in mg/Tablet.

Sample solution: Pass a portion of the solution under test through a suitable filter of 10–20 µm pore size.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 214 nm
• Column: 4.6-mm × 10-cm; 5-µm packing L9
• Flow rate: 2.0 mL/min
• Injection volume: 100 µL
• Run time: NLT 3 times the retention time of phenylephrine

System suitability

• Sample: Standard solution
• Suitability requirements
• Tailing factor: 0.5–3.0 for both phenylephrine and diphenhydramine
• Relative standard deviation: NMT 2.0% for both phenylephrine and diphenhydramine

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amounts of phenylephrine hydrochloride (C₉H₁₃NO₂·HCl) and diphenhydramine hydrochloride (C₁₇H₂₁NO·HCl) dissolved:

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

rᵤ = peak response of diphenhydramine or phenylephrine from the Sample solution

rₛ = peak response of diphenhydramine or phenylephrine from the Standard solution

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

V = volume of Medium, 900 mL

L = label claim of diphenhydramine hydrochloride (L₁) or phenylephrine hydrochloride (L₂) (mg/Tablet)

Tolerances: NLT 75% (Q) of the labeled amounts of diphenhydramine hydrochloride (C₁₇H₂₁NO·HCl) and phenylephrine hydrochloride (C₉H₁₃NO₂·HCl) is dissolved.

4.2 Uniformity of Dosage Units 〈905〉: Meet the requirements

Delete the following:

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, and store at 20°–25°.

Change to read:

USP Reference Standards 〈11〉

• USP Diphenhydramine Hydrochloride RS
• USP Phenylephrine Hydrochloride RS