Brinzolamide Ophthalmic Suspension

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

Brinzolamide Ophthalmic Suspension is a sterile, aqueous suspension of Brinzolamide containing a suitable antimicrobial preservative. It contains NLT 90.0% and NMT 110.0% of the labeled amount of brinzolamide (C₁₂H₂₁N₃O₅S₃)

2 IDENTIFICATION

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

ASSAY

3 PROCEDURE

Buffer: 11.75 g/L of ammonium acetate in water. Adjust with acetic acid to a pH of 5.2.

Mobile phase: Methanol and Buffer (35:65)

Standard solution A: 0.2 mg/mL of USP Brinzolamide RS in Mobile phase

System suitability solution: 0.06 mg/mL of USP Brinzolamide Related Compound B.RS in Standard solution A

Sample solution: Nominally 0.2 mg/mL of brinzolamide in Mobile phase prepared as follows. Transfer a volume of Ophthalmic Suspension, equivalent to 10 mg of brinzolamide, into a 50-mL volumetric flask, and dilute with Mobile phase to volume.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm x 15-cm; 5-µm packing L1

Flow rate: 1.0 mL/min

Injection volume: 20 µL

System suitability

Samples: Standard solution A and System suitability solution

[ NOTE-The relative retention times for brinzolamide related compound B are between 0.48 and 0.61, and the relative retention time for brinzolamide is 1.0.]

Suitability requirements

Resolution: NLT 4.5 between the brinzolamide and brinzolamide related compound B peaks, System suitability solution

Tailing factor: NMT 2.0, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution A

Analysis

Samples: Standard solution A and Sample solution

Calculate the percentage of the labeled amount of brinzolamide (C₁₂H₂₁N₃O₅S₃) in the portion of Ophthalmic Suspension taken:

Result = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak response from the Sample solution

r_s = peak response from Standard solution A

C_s = concentration of USP Brinzolamide RS in Standard solution A (mg/mL)

C_u = nominal concentration of brinzolamide in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 IMPURITIES

4.1 LIMIT OF BRINZOLAMIDE RELATED COMPOUND A

Mobile phase: Dehydrated alcohol, chromatographic hexane, methanol, and diethylamine (55:40:5:0.2)

System suitability solution: 0.4 mg/mL of USP Brinzolamide RS and 0.02 mg/mL of USP Brinzolamide Related Compound A RS in dehydrated alcohol

Sample solution: Transfer a volume of Ophthalmic Suspension, equivalent to 10 mg of brinzolamide, to a 25-mL volumetric flask. Dilute with alcohol to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 25-cm; packing L51

Flow rate: 0.75 mL/min

Injection volume: 5 µL

System suitability

Sample: System suitability solution

[Note—The relative retention times for brinzolamide and brinzolamide related compound A are 1.0 and 1.2, respectively.]

Suitability requirements

Resolution: NLT 1.8 between the brinzolamide and brinzolamide related compound A peaks

Column eciency: NLT 2000 theoretical plates for the brinzolamide peak

Tailing factor: NMT 1.8 for the brinzolamide peak

Analysis

Sample: Sample solution

Calculate the percentage of brinzolamide related compound A in the portion of Ophthalmic Suspension taken:

Result = (r_u /r_T ) × 100

r_u = peak response for brinzolamide related compound A

r_T = sum of the peak responses for brinzolamide and brinzolamide related compound A

Acceptance criteria: NMT 1.5%

4.2 ORGANIC IMPURITIES

Buffer, Mobile phase, Standard solution A, System suitability solution, Sample solution, Chromatographic system, and System

suitability: Proceed as directed in the Assay.

Standard solution B: 2.5 µg/mL of USP Brinzolarnide Related Compound B RS in Mobile phase

Analysis

Samples: Sample solution and Standard solution B

Calculate the percentage of each impurity in the portion of Ophthalmic Suspension taken:

Result = (r_u /r_s ) × (C_s /C_u ) × (M_r1 /M_r2 ) × 100

r_u = peak response for each impurity from the Sample solution

r_s = peak response for brinzolamide related compound B from Standard solution B

C_s = concentration of USP Brinzolamide Related Compound B RS in Standard solution B (mg/mL)

C_u = nominal concentration of brinzolamide in the Sample solution (mg/mL)

M_r1 = molecular weight of des-ethyl brinzolamide, 356.46

M_r2 = molecular weight of des-ethyl brinzolamide oxalate, 445.49

Acceptance criteria

Any individual impurity: NMT 0.5%

Total impurities: NMT 2.0%

5 SPECIFIC TESTS

Sterility Tests 〈71〉: It meets the requirements when tested as directed for Test for Sterility of the Product to Be Examined, Membrane Filtration.

pH 〈791〉: 6.5–8.5

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store at a temperature between 4° and 30°.

Change to read:

USP Reference Standards 〈11〉

USP Brinzolamide RS

USP Brinzolamide Related Compound A RS

(S)-4-(Ethylamino)-2-(3-methoxypropyl)-3,4-dihydro-2H-thieno[3,2-e][1,2]thiazine-6-sulfonamide 1,1-dioxide. _{(CN 1-Dec-2023)}

C₁₂H₂₁N₃O₅S₃                                 383.50 _{(CN 1-Dec-2023)}

USP Brinzolamide Related Compound B RS

(R)-4-Amino-2-(3-methoxypropyl)-3,4-dihydro-2H-thieno[3,2-e][1,2]thiazine-6-sulfonamide 1,1-dioxide oxalate.

C₁₀H17N₃O₅S₃ · C₂H₂O₄                445.48 _{(CN 1-Dec-2023)}