Spironolactone Compounded Oral 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

Change to read:

Spironolactone Compounded Oral Suspension contains NLT 90.0% and NMT 110.0% of the labeled amount of spironolactone (C₂₄H₃₂O₄S).

Prepare Spironolactone Compounded Oral Suspension 5 mg/mL in Ora-Blend as follows (see Pharmaceutical Compounding—Nonsterile Preparations 〈795〉).

^a Spironolactone 25-mg tablet, Qualitest Pharmaceuticals, Huntsville, AL.

^b Perrigo Pharmaceuticals, Allegan, MI.

Crush the Spironolactone tablet(s) to a fine powder, and pass through a 40-mesh sieve. Wet the powder with a small amount of Ora-Blend, and triturate to make a smooth paste. Add the Ora-Blend to make the mortar contents pourable. Transfer the contents stepwise and quantitatively to a calibrated container using the remainder of the Ora-Blend. Add sufficient Ora-Blend to bring to final volume and (USP 1-May-2021) mix well.

Prepare Spironolactone Compounded Oral Suspension 5 mg/mL in SuspendIt as follows (see Pharmaceutical Compounding—Nonsterile Preparations 〈795〉).

^a PCCA, Houston, TX.

Place the Spironolactone powder in a suitable container and triturate to a fine powder. Add a small amount of SuspendIt, and mix well to form a smooth paste. Add a sufficient amount of SuspendIt to make a liquid that is pourable. Transfer contents stepwise and quantitatively to a calibrated container using additional amounts of the SuspendIt. Add a sufficient amount of SuspendIt to bring to final volume, and mix well.

(USP 1-May-2021)

2 ASSAY

Change to read:

PROCEDURE 1: ORAL SUSPENSION IN ORA-BLEND (USP 1-MAY-2021)

Mobile phase: Mix 435 mL of water with 2.7 mL of phosphoric acid and 50 mL of methanol. Combine the solution with 515 mL of acetonitrile and mix well. Filter and degas.

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

Sample solution: Shake each bottle of Oral Suspension thoroughly. Transfer 1.0 mL of Oral Suspension into a 25-mL volumetric flask, dilute with Mobile phase to volume, and mix well to dissolve.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 238 nm

Column: 4.6-mm × 25-cm; 5-µm packing L11

Flow rate: 1.0 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

[NOTE—The retention time for spironolactone is about 10.7 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 spironolactone (C₂₄H₃₂O₄S) in the portion of Oral Suspension taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of spironolactone from the Sample solution

r_S = peak response of spironolactone from the Standard solution

C_S = concentration of USP Spironolactone RS (USP 1-May-2021) in the Standard solution (mg/mL)

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

Acceptance criteria: 90.0%–110.0% Add the following:

PROCEDURE 2: ORAL SUSPENSION IN SUSPENDIT

Solution A: 30 mM sodium phosphate monobasic adjusted with phosphoric acid to a pH of 2.9 Mobile phase: Acetonitrile and Solution A (45:55)

Standard solution: 0.0075 mg/mL of spironolactone prepared from USP Spironolactone RS in Mobile phase

Sample solution: Shake each bottle of Oral Suspension thoroughly. Transfer 0.015 mL of Oral Suspension into a 10-mL volumetric flask, dilute with Mobile phase to volume, and mix well to dissolve. Sonicate for 5 min.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 240 nm

Column: 2.1-mm × 10-cm; 5-µm packing L1

Flow rate: 0.8 mL/min

Injection volume: 20 µL System suitability

Sample: Standard solution

[NOTE—The retention time for spironolactone is about 5.2 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 spironolactone (C₂₄H₃₂O₄S) in the portion of Oral Suspension taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of spironolactone from the Sample solution

r_S = peak response of spironolactone from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0% (USP 1-May-2021)

3 SPECIFIC TESTS

Change to read:

PH 〈791〉

Oral Suspension in Ora-Blend: 3.6–4.6

Oral Suspension in SuspendIt: 4.8–5.8 (USP 1-May-2021)

4 ADDITIONAL REQUIREMENTS

Change to read:

PACKAGING AND STORAGE: Package in tight, light-resistant containers. Store in a refrigerator (USP 1-May-2021) or at controlled room temperature.

LABELING: Label it to indicate that it is to be well shaken before use, and to state the Beyond-Use Date.

Change to read:

BEYOND-USE DATE: NMT 90 days after the date on which it was compounded when stored in a refrigerator (USP 1-May-2021) or at controlled room temperature.

USP REFERENCE STANDARDS 〈11〉

USP Spironolactone RS