Sulfacetamide Sodium and Prednisolone Acetate Ophthalmic Ointment

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

Sulfacetamide Sodium and Prednisolone Acetate Ophthalmic Ointment is a sterile ointment containing NLT 90.0% and NMT 110.0% of the labeled amounts of sulfacetamide sodium (C₈H₉N₂NaO₃S · H₂O) and prednisolone acetate (C₂₃H₃₀O₆).

2 IDENTIFICATION

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the tests for

Sulfacetamide Sodium and Prednisolone Acetate in the Assay.

B. The UV absorption spectra of the major peak of the Sample solution and that of the Standard solution exhibit maxima and minima at the

same wavelengths, as obtained in the tests for Sulfacetamide Sodium and Prednisolone Acetate in the Assay.

3 ASSAY

Sulfacetamide Sodium

Diluent: Dilute methanol (1 in 5)

Mobile phase: Methanol, glacial acetic acid, and water (100:10:890), filtered and degassed

Standard solution: Transfer about 50 mg of USP Sulfacetamide Sodium RS to a 40-mL centrifuge tube. Add 10.0 mL of Diluent, insert the stopper in the tube, and mix using a vortex mixer for about 3 min to dissolve. Add 7.5 mL of heptane, insert the stopper in the tube, and mix using a vortex mixer for another 3 min. Centrifuge to effect separation of the phases. Withdraw and discard the upper heptane layer.

Transfer 3.0 mL of the bottom layer to a 500-mL volumetric flask, add Diluent to volume, and mix.

System suitability solution: Dissolve 3 mg of sulfanilamide in 100 mL of the Standard solution, and mix.

Sample solution: Transfer a quantity of Ophthalmic Ointment nominally equivalent to about 100 mg of sulfacetamide sodium to a 40-mL centrifuge tube. Add 15.0 mL of heptane, insert the stopper in the tube, and mix using a vortex mixer for about 3 min to dissolve the

Ophthalmic Ointment. Add 20.0 mL of Diluent, insert the stopper in the tube, and mix using a vortex mixer for 3 min. Centrifuge to effect separation of the phases. Withdraw and discard the upper heptane layer. Transfer 3.0 mL of the bottom layer to a 500-mL volumetric flask, dilute with Diluent to volume, and mix.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: 254-nm diode array

Column: 4.6-mm × 25-cm; packing L1

Flow rate: 1.5 mL/min

Injection volume: 90 μL

System suitability

Samples: Standard solution and System suitability solution

Suitability requirements

Resolution: NLT 3 between the sulfacetamide and sulfanilamide peaks, System suitability solution

Column efficiency: NLT 1500 theoretical plates, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of sulfacetamide sodium (C₈H₉N₂NaO₃S · H₂O) in the portion of Ophthalmic Ointment taken:

Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) × 100

r_U = peak response of sulfacetamide sodium from the Sample solution

r_S = peak response of sulfacetamide sodium from the Standard solution

C_S = concentration of USP Sulfacetamide Sodium RS, calculated on the anhydrous basis, in the Standard solution (mg/mL)

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

M_r1 = molecular weight of sulfacetamide sodium monohydrate, 254.24

M_r2 = molecular weight of anhydrous sulfacetamide sodium, 236.23

Acceptance criteria: 90.0%–110.0%

Prednisolone Acetate

Diluent: Dilute methanol (9 in 10)

Mobile phase: Acetonitrile and water (400:600), filtered and degassed Internal standard solution: 0.7 mg/mL of norethindrone in Diluent

Standard stock solution: 0.8 mg/mL of USP Prednisolone Acetate RS in Diluent

Standard solution: 0.04 mg/mL of USP Prednisolone Acetate RS prepared as follows. Transfer 5.0 mL of Standard stock solution to a 100-mL volumetric flask, add 5.0 mL of Internal standard solution, dilute with Diluent to volume, and mix.

Sample solution: Transfer a quantity of Ophthalmic Ointment nominally equivalent to about 4 mg of prednisolone acetate to a 50-mL centrifuge tube. Add 10.0 mL of heptane, and mix using a vortex mixer for about 2 min to dissolve the Ophthalmic Ointment. Add 5.0 mL of Internal standard solution and 20.0 mL of Diluent, and mix using a vortex mixer for 2 min. Centrifuge to effect separation of the phases.

Withdraw and discard the upper heptane layer. Transfer the lower layer to a 100-mL volumetric flask. Add Diluent to volume, and mix.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: 254-nm diode array

Column: 3.9-mm × 30-cm; packing L1

Flow rate: 1.5 mL/min

Injection volume: 40 μL

System suitability

Sample: Standard solution

[Note—The relative retention times for prednisolone acetate and norethindrone are about 1.0 and 1.5, respectively.]

Suitability requirements

Resolution: NLT 4.5 between the prednisolone and norethindrone peaks

Column eficiency: NLT 3000 theoretical plates for the prednisolone peak

Tailing factor: NMT 2.5 for the prednisolone peak

Relative standard deviation: NMT 1.5% for the peak response ratio of prednisolone acetate to norethindrone

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of prednisolone acetate (C₂₃H₃₀O₆) in the portion of Ophthalmic Ointment taken:

Result = (R_U/R_S ) × (C_S /C_U ) × 100

R_U = peak response ratio of prednisolone acetate to the internal standard peak from the Sample solution

R_S = peak response ratio of prednisolone acetate to the internal standard peak from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 SPECIFIC TESTS

Sterility Tests 〈71〉: Meets the requirements

Other Requirements: It meets the requirements for Particulate and Foreign Matter and Container Contents in Ophthalmic Products—Quality Tests

〈771〉, Drug Product Quality, Universal Tests, Particulate and Foreign Matter and Container Contents.

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in collapsible ophthalmic ointment tubes that are tamper-proof so that sterility is assured at time of first use.

USP Reference Standards 〈11〉

USP Prednisolone Acetate RS

USP Sulfacetamide Sodium RS