Megestrol Acetate 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

Megestrol Acetate Oral Suspension contains NLT 90.0% and NMT 110.0% of the labeled amount of megestrol acetate (C₂₄H₃₂O₄).

2 IDENTIFICATION

Thin-Layer Chromatographic Identification Test 〈201〉

Standard solution: 4.0 mg/mL of USP Megestrol Acetate RS in chloroform

Sample solution: Transfer Oral Suspension, equivalent to 160 mg of megestrol acetate, to a separatory funnel, add 50 mL of water and 40 mL of chloroform, and shake. Allow the phases to separate, and discard the aqueous layer.

Developing solvent system: Chloroform and ethyl acetate (4:1)

3 ASSAY

Procedure

Mobile phase: Acetonitrile and water (11:9)

Standard solution: 80 μg/mL of USP Megestrol Acetate RS in Mobile phase

Sample solution: A volume of Oral Suspension diluted with Mobile phase to obtain nominally 80 μg/mL of megestrol acetate

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 280 nm

Column: 3.9-mm × 30-cm; packing L1

Flow rate: 1.5 mL/min

Injection size: 25 μL

System suitability

Sample: Standard solution

Suitability requirements

Column efficiency: NLT 2500 theoretical plates

Tailing factor: NMT 1.4

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of C₂₄H₃₂O₄ in the portion of Oral 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 the Standard solution

C_S = concentration of USP Megestrol Acetate RS in the Standard solution (μg/mL)

C_U = nominal concentration of the Sample solution (μg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Test 1

Medium: 0.5% sodium lauryl sulfate in water; 900 mL

Apparatus 2: 25 rpm

Time: 30 min

Detector: UV 292 nm

Standard solution: 45 mg of USP Megestrol Acetate RS in a 250-mL volumetric flask. Add 12 mL of methanol, and place the flask in a warm water bath until the solid is dissolved. Dilute with Medium to volume. The final concentration is 180 μg/mL of megestrol acetate. Dilute with Medium, if necessary.

Sample solution: Transfer to the surface of the Medium in the dissolution vessel an accurately measured volume of Oral Suspension, freshly mixed and free from air bubbles, equivalent to 160 mg of megestrol acetate. At the sampling time, withdraw a volume of the solution under test and pass through a suitable filter with 0.45-μm pore size. Dilute with Medium, if necessary.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of C₂₄H₃₂O₄ released:

Result = (A_U /A_S ) × (C_S /V) × V_D × (100/L)

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of the Standard solution (mg/mL)

V = volume of Oral Suspension taken

V_D = volume of Medium, 900 mL

L = label claim (mg/mL)

Tolerances: NLT 80% (Q) of the labeled amount of C₂₄H₃₂O₄ is dissolved.

Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.

Medium: 0.5% sodium lauryl sulfate in water; 900 mL

Apparatus 2: 25 rpm

Time: 30 min

Detector: UV 292 nm, using 0.5-cm pathlength cuvettes

Standard solution: 45 mg of USP Megestrol Acetate RS in a 250-mL volumetric flask. Add 5 mL of methanol. Dilute with Medium to volume.

Transfer 10 mL of this solution to a 100-mL volumetric flask, and dilute with Medium to volume. The final concentration is 18 μg/mL.

Sample solution: [Note—Use a separate syringe for each vessel.] Withdraw more than 10 mL of the Oral Suspension, using a 10-mL syringe with a long cannula. Remove air bubbles from the syringe. Adjust the volume to the 10-mL mark on the syringe, and remove the needle.

Wipe the tip of the syringe, and weigh (gross weight). Operate the apparatus, and rapidly dispense the Oral Suspension to the side of the vessel at about halfway from the bottom. Similarly dispense the Oral Suspension into other vessels. Weigh each syringe after dispensing the sample (tare weight). Record sample weights. After completion of the dissolution, pass an aliquot through a suitable nylon filter with 0.45-μm pore size, and dilute 2.0 mL of the filtrate with Medium to 50.0 mL to obtain a solution having a theoretical concentration of about 18 μg/mL.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of C₂₄H₃₂O₄ released:

Result = (A_U /A_S ) × (C_S/W) × V_D × d × (100/L)

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of the Standard solution (mg/mL)

W = weight of the Oral Suspension taken (mg)

V_D = volume of the Medium in the dissolution vessel, 900 mL

d = density of the Oral Suspension (mg/mL), obtained by dividing the weight of Oral Suspension taken by 10 mL

L = label claim (mg/mL)

Tolerances: NLT 80% (Q) of the labeled amount of C₂₄H₃₂O₄ is dissolved.

Test 3: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.

Medium: 0.5% sodium lauryl sulfate in degassed water; 900 mL. [Note—Use ultrapure sodium lauryl sulfate with an Assay content of NLT 99.0%.]

Apparatus 2: 50 rpm

Time: 30 min

Determine the amount of C₂₄H₃₂O₄ dissolved by using the following method.

Mobile phase: Proceed as directed in the Assay.

Standard solution: 0.46 mg/mL of USP Megestrol Acetate RS in Mobile phase

Sample solution: Proceed as directed for Test 2, introducing the sample into the vessel over a 10- to 15-s period (about 1 mL/s).

Chromatographic system: Proceed as directed in the Assay.

Injection size: 10 μL

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of C₂₄H₃₂O₄ released:

Result = (r_U /r_S ) × (C_S/W) × V_D × d × (100/L)

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of the Standard solution (mg/mL)

W = weight of the Oral Suspension taken (mg)

V_D = volume of the Medium in the dissolution vessel, 900 mL

d = density of the Oral Suspension (mg/mL), obtained by dividing the weight of Oral Suspension taken by 10 mL

L = label claim (mg/mL)

Tolerances: NLT 80% (Q) of the labeled amount of C₂₄H₃₂O₄ is dissolved.

Deliverable Volume 〈698〉: Meets the requirements

5 SPECIFIC TESTS

pH 〈791〉: 3.0–4.7

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed, light-resistant containers.

Labeling: When more than one test for Dissolution is given, the labeling states the test used only if Test 1 is not used.

USP Reference Standards 〈11〉

USP Megestrol Acetate RS