Phentermine Hydrochloride Tablets

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

Phentermine Hydrochloride Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of phentermine hydrochloride (C₁₀H₁₅N·HCI).

2 IDENTIFICATION

A.

Sample solution: Stir a portion of finely powdered Tablet contents in acetone to prepare a solution containing a nominal concentration at about 1 mg/mL of phentermine hydrochloride.

Analysis: Filter the Sample solution using an acetone resistant filter. Transfer 1 mL of the clear filtrate to a mortar containing about 200 mg of potassium bromide, triturate with a pestle, and air-dry to allow the acetone to evaporate. Place in an oven at 125° for 30 min to dry the mixture.

Acceptance criteria: The IR absorption spectrum of a potassium bromide dispersion prepared from the residue exhibits maxima only at the same wavelengths as that of a similar preparation of USP Phentermine Hydrochloride RS.

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

3 ASSAY

3.1 PROCEDURE

Mobile phase: Prepare a suitably degassed solution containing 0.03% diethylamine in methanol.

Internal standard solution: About 0.02 mg/mL of caffeine in Mobile phase

Standard solution: USP Phentermine Hydrochloride RS in the Internal standard solution, equivalent to 0.75 mg/mL of phentermine hydrochloride

Sample solution: Transfer an equivalent to 7.5 mg, from NLT 20 finely powdered Tablets, to a suitable flask. Pipet 10.0 mL of the Internal standard solution into the flask. Insert the stopper, mix, and sonicate for about 10 min. Pass through a filter of 0.5-µm pore size.

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm x 25-cm; packing L1

Flow rate: 1.5 mL/min

Injection volume: 10 µL

3.3 System suitability

Sample: Standard solution

[NOTE-The relative retention times for caffeine and phentermine are about 0.5 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 4 between caffeine and phentermine

Column efficiency: NLT 2000 theoretical plates

Relative standard deviation: NMT 2.0%

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of phentermine hydrochloride (C₁₀H₁₅N·HCI) in the portion of Tablets taken: 15

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

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

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

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

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

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

4.1 DISSOLUTION, Procedure for a Pooled Sample (711)

Medium: Water; 900 mL. Use 500 mL for Tablets containing 15 mg or less of phentermine hydrochloride.

Apparatus 2: 50 rpm

Time: 45 min

Solution A: Dissolve 1.1 g of sodium 1-heptanesulfonate in 1 L of water. Add 3.5 mL of glacial acetic acid, and mix.

Mobile phase: Methanol and Solution A (525:475). Filter, degas, and adjust with phosphoric acid to a pH of 2.5.

Sample solution: Filtered portion of the pooled sample under test

Standard solution: Dissolve USP Phentermine Hydrochloride RS in water, and dilute with water, if necessary, to obtain a known concentration approximately equivalent to the Sample solution.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 208 nm

Column: 4.6-mm x 25-cm; packing L1

Flow rate: 1 mL/min

Injection volume: 25 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of the labeled amount of phentermine hydrochloride (C₁₀H₁₅N·HCI) dissolved:

Result = (r_U/r_S) x C_S x V x (1/L)

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

V = volume of Medium, 900 mL or 500 mL

L = label claim (mg/Tablet)

Tolerances: NLT 75% (Q) of the labeled amount of phentermine hydrochloride (C₁₀H₁₅N·HCI) is dissolved.

Change to read:

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements (CN 1-Aug-2023)

Procedure for content uniformity

Sample solution: Proceed as directed in the Assay, except prepare the Sample solution as follows. Transfer 1 Tablet to each of 10 suitable containers, and add 1 mL of water and 10 mL of the Internal standard solution to each. Mix, sonicate for about 10 min after each Tablet has disintegrated, and filter.

(CN 1-Aug-2023)

5 ADDITIONAL REQUIREMENTS

5.1 PACKAGING AND STORAGE

Preserve in tight containers.

5.2 USP REFERENCE STANDARDS (11)

USP Phentermine Hydrochloride RS