Naltrexone Hydrochloride Compounded Cream

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

Naltrexone Hydrochloride Compounded Cream contains NLT 90.0% and NMT 110.0% of the labeled amount of naltrexone hydrochloride (C₂₀H₂₃NO₄ · HCl).

Prepare Naltrexone Hydrochloride Compounded Cream 10 mg/g as follows (see Pharmaceutical Compounding-Nonsterile Preparations 〈795〉).

ᵃ PCCA, Houston, TX.

In an appropriately sized electronic mortar and pestle container, add Naltrexone hydrochloride, Hydrolyzed Hyaluronic Acid, and Glycerin. Add XemaTop Base. Mix the mixture with an electronic mortar and pestle for 2 min on a speed of about 1400–1450 rpm. Process through an ointment mill once at the middle setting and once at the finest setting to reduce the particle size of the active ingredient and reduce air content of the preparation. Return the mixture to the electronic mortar and pestle and mix again for 1 min on the low setting.

2 ASSAY

2.1 Procedure

Solution A: 0.1% trifluoroacetic acid in water

Solution B: 0.1% trifluoroacetic acid in acetonitrile

Mobile phase: See Table 1.

Table 1

Standard solution: Transfer 100 mg of USP Naltrexone RS to a 100-mL volumetric flask and dilute with water to volume. Sonicate for 15 s. Transfer 25 mL of the resultant solution to a 1000-mL volumetric flask and dilute with methanol to volume.

Sample solution: Transfer 0.5 g of Cream into a 50-mL centrifuge tube, add 2 mL of water, and vortex for 30 s. Sonicate for 1 min and vortex for 30 s. Add 17.5 mL of methanol to the mixture and vortex for 30 s. Sonicate the mixture for 2 min and vortex for 30 s. Sonicate the mixture again for 2 min and vortex for 30 s. Centrifuge the mixture for 20 min at 6000 rpm. Transfer 1 mL of the supernatant to a 10-mL volumetric flask and dilute with methanol to volume. Centrifuge for 10 min at 14 × 10³ rpm.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detection: UV 225 nm
• Column: 2.1-mm × 5-cm; 1.7-µm packing L1
• Temperatures
• Autosampler: 8°
• Column: 65°
• Flow rate: 1 mL/min
• Injection volume: 1 µL

System suitability

• Sample: Standard solution
• [Note-The retention time for naltrexone hydrochloride is about 0.82 min.]
• Suitability requirements
• Tailing factor: NMT 2.0
• Relative standard deviation: NMT 2.0% for replicate injections

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of naltrexone hydrochloride (C₂₀H₂₃NO₄ · HCl) in the portion of Cream taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × (M_r₁/M_r₂) × 100

rᵤ = peak response of naltrexone from the Sample solution

rₛ = peak response of naltrexone from the Standard solution

Cₛ = concentration of USP Naltrexone RS in the Standard solution (mg/g)

Cᵤ = concentration of naltrexone hydrochloride in the Sample solution (mg/g)

M_r₁ = molecular weight of naltrexone hydrochloride, 377.86

M_r₂ = molecular weight of naltrexone, 341.41

Acceptance criteria: 90.0%–110.0%

3 SPECIFIC TESTS

pH 〈791〉: 4.4–5.4

Viscosity-Rotational Methods 〈912〉: 350–3500 mPa·s

4 ADDITIONAL REQUIREMENTS

Packaging and Storage: Package in tight, light-resistant containers. Store at controlled room temperature or in a refrigerator.

Beyond-Use Date: NMT 180 days after the date on which it was compounded when stored at controlled room temperature or in a refrigerator.

Labeling: Label it to indicate that it is for external use only and to state the Beyond-Use Date.

USP Reference Standards 〈11〉

USP Naltrexone RS