Miconazole Compounded Ophthalmic Solution

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

Miconazole Compounded Ophthalmic Solution contains NLT 90.0% and NMT 110.0% of the labeled amount of miconazole (C₁₈H₁₄CI₄N₂O).

Prepare Miconazole Compounded Ophthalmic Solution 1% (10 mg/mL) as follows (see Pharmaceutical Compounding-Sterile Preparations (797)).

Add the Miconazole to a sterile container and gradually add the Polyoxyl 40 Hydrogenated Castor Oil. Mix into a smooth viscous mixture. Add the Lactic Acid Solution (88%) and mix thoroughly. Add 80 mL of the Sterile Water for Injection and stir vigorously until the Miconazole is completely dissolved. Transfer the contents stepwise and quantitatively to a sterile calibrated container and bring to final volume with Sterile Water for Injection. Pass through a sterile filter of 0.22-µm pore size into an empty sterile dropper bottle. [NOTE-Room temperature Sterile Water for Injection should be used to assist in solubilization.]

2 ASSAY

PROCEDURE

Mobile phase: Dissolve 5.7 g of ammonium acetate in 380 mL of water, and add 320 mL of methanol and 300 mL of acetonitrile. Mix well.

Standard solution: 0.05 mg/mL of miconazole prepared from USP Miconazole RS in methanol

Sample solution: Transfer 0.5 mL of Ophthalmic Solution to a 100-mL volumetric flask, dilute with methanol to volume, and vortex to mix.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 230 nm

Column: 2.0-mm × 10-cm; 2.5-µm packing L1

Column temperature: 55°

Flow rate: 0.35 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

[NOTE-The retention time for miconazole is about 18.0 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 miconazole (C₁₈H₁₄CI₄N₂O) in the portion of Ophthalmic Solution taken: 

                         Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of miconazole from the Sample solution

r_S = peak response of miconazole from the Standard solution 

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

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

Acceptance criteria: 90.0%-110.0%

3 SPECIFIC TESTS

PH (791): 2.9-3.9

STERILITY TESTS (71), Test for Sterility of the Product to Be Examined, Membrane Filtration: Meets the requirements

Change to read:

SUBVISIBLE PARTICULATE MATTER IN INTRAOCULAR SOLUTIONS (789) _{▲(CN 1-MAY-2024)}: Meets the requirements

4 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Package in sterile plastic ophthalmic dropper bottles for single-use in one patient only. Store in a refrigerator (2°-8°) or at controlled room temperature.

BEYOND-USE DATE: In the absence of performing and completing a sterility test, the storage conditions in Pharmaceutical Compounding - Sterile Preparations (797), 14.3 Establishing a BUD for a CSP apply. After successful completion of sterility testing, NMT 30 days after the date on which it was compounded when stored in a refrigerator (2°-8°); NMT 21 days after the date on which it was compounded when stored at controlled room temperature.

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

USP REFERENCE STANDARDS (11)

USP Miconazole RS