Orphenadrine Citrate Extended-Release 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

Orphenadrine Citrate Extended-Release Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of orphenadrine citrate (C₁₈H₂₃NO · C₆H₈O₇).

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 Assay.

3 ASSAY

Procedure

Buffer: 5.8 g/L of monobasic ammonium phosphate. Adjust with phosphoric acid to a pH of 3.2.

Mobile phase: Acetonitrile and Buffer (40:60)

System suitability solution: 0.1 mg/mL of USP Orphenadrine Citrate RS and 0.01 mg/mL each of USP Orphenadrine Related Compound B RS and USP Orphenadrine Related Compound C RS, in Mobile phase

Standard solution: 0.1 mg/mL of USP Orphenadrine Citrate RS

Sample stock solution: Nominally 0.5 mg/mL of orphenadrine citrate prepared as follows. Transfer a quantity of powder equivalent to NLT 100 mg of orphenadrine citrate, from finely powdered Tablets (NLT 20), to a suitable volumetric flask. Add 50% of the flask volume of Mobile phase. Sonicate for 5 min and shake for 15 min. Dilute with Mobile phase to volume. Pass through a suitable filter.

Sample solution: Nominally 0.1 mg/mL of orphenadrine citrate in Mobile phase from the Sample stock solution

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 225 nm

Column: 3.9-mm × 30-cm; 10-μm L1 packing

Flow rate: 2 mL/min

Injection volume: 20 μL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 1.2 between orphenadrine and orphenadrine related compound C; NLT 2.0 between orphenadrine citrate and orphenadrine related compound B, System suitability solution

Tailing factor: NMT 2.0, 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 orphenadrine citrate (C₁₈H₂₃NO · C₆H₈O₇) in the portion of Tablets 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 Orphenadrine Citrate RS in the Standard solution (mg/mL)

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

4.1 Test 1

Medium: Water; 900 mL, deaerated

Apparatus 2: 50 rpm

Times: 1, 2, 6, and 12 h

Buffer: 5.8 g/L of monobasic ammonium phosphate in water

Mobile phase: Acetonitrile and Buffer (40:60). Adjust with phosphoric acid to a pH of 3.2 ± 0.1.

Standard stock solution: 1 mg/mL of USP Orphenadrine Citrate RS in Mobile phase. Sonication may be used to promote dissolution.

Standard solution 0.1 mg/mL of USP Orphenadrine Citrate RS in Medium from a suitable volume of Standard stock solution and Medium

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size and discard the first few mL of the filtrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 225 nm

Column: 3.9-mm × 30-cm; 10-μm packing L1

Flow rate: 2 mL/min

Injection volume: 20 μL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis:

Samples: Standard solution and Sample solution

Calculate the concentration (C_i) of orphenadrine citrate (C₁₈H₂₃NO · C₆H₈O₇) dissolved in the portion of the sample withdrawn at each

time point (i) (mg/mL):

C_i = (r_U/r_S) × C_S

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)

Calculate the percentage of the labeled amount of orphenadrine citrate (C₁₈H₂₃NO · C₆H₈O₇) dissolved at each time point (i):

Result₁ = C₁ × V × (1/L) × 100

Result₂ = {[C₂ × (V − V_S)] + (C₁ × V_S)} × (1/L) × 100

Result₃ = {C₃ × [V − (2 × V_S)] + [(C₂ + C₁) × V_S]} × (1/L) × 100

Result₄ = {C₄ × [V − (3 × V_S)] + [(C₃ + C₂ + C₁) × V_S]} × (1/L) × 100

C_i = concentration of orphenadrine citrate in the portion of the sample withdrawn at time point (i) (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

V_S = volume of the Sample solution withdrawn at each time point (mL)

Tolerances: See Table 1.

Table 1

The percentages of the labeled amount of orphenadrine citrate (C₁₈H₂₃NO · C₆H₈O₇) dissolved at the times specified conform to

Dissolution 〈711〉, Acceptance Table 2.

4.2 Test 2

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

Medium: Water; 900 mL

Apparatus 2: 50 rpm

Times: 1, 4, and 12 h

Standard solution: 0.02 mg/mL of USP Orphenadrine Citrate RS in Medium

Sample solution: Withdraw 10 mL of the solution under test from each vessel at each specified time point. Replace 10 mL of Medium in each vessel. Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size. Transfer 1.0 mL of the filtrate to a 50-mL volumetric flask, and dilute with Medium to volume.

Blank: Medium

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 210 nm

Analysis

Samples: Standard solution and Sample solution

Calculate the concentration (C_i) of orphenadrine citrate (C₁₈H₂₃NO · C₆H₈O₇) in the sample withdrawn from the vessel at each time point(i):

C = (A_U/A_S) × C_S

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

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

Calculate the percentage of the labeled amounts (Q_i) of orphenadrine citrate (C₁₈H₂₃NO · C₆H₈O₇) dissolved at each time point (i):

Result₁ = C₁ × V × (1/L) × 100

Result₂ = [(C₂ × V) + (C₁ × V )] × (1/L) × 100

Result₃ = {(C₃ × V) + [(C_{​​​​​​​2} + C₁ ) × V ]} × (1/L) × 100

C_i = concentration of orphenadrine citrate in the portion of the sample withdrawn at time point (i) (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

V_S = volume of the Sample solution withdrawn at each time point (mL)

Tolerances: See Table 2.

Table 2

The percentages of the labeled amount of orphenadrine citrate (C₁₈H₂₃NO · C₆H₈O₇) dissolved at the times specified conform to

Dissolution 〈711〉, Acceptance Table 2.

4.3 Test 3

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

Solution A: 0.45 M monobasic potassium phosphate prepared as follows. Mix 6.12 g of monobasic potassium phosphate and 12 mL of 10

N sodium hydroxide. Dilute with water to 100 mL.

Acid stage medium: 0.1 N hydrochloric acid; 800 mL

Buffer stage medium: pH 7.5 phosphate buffer (add 100 mL of Solution A to the Acid stage medium after 1 h); 900 mL

Apparatus 2: 50 rpm

Times: 1 h in Acid stage medium; 4 and 10 h in Buffer stage medium. The time in the Buffer stage medium includes the time in the Acid stage medium.

Standard solution: 0.11 mg/mL of USP Orphenadrine Citrate RS in Acid stage medium

Sample solution: Pass a portion of the solution under test through a suitable filter.

Blank: Acid stage medium

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 232 nm

Cell: 1 cm

Analysis

Samples: Standard solution and Sample solution

Calculate the concentration (C_i) of orphenadrine citrate (C₁₈H₂₃NO · C₆H₈O₇) in the sample withdrawn from the vessel at each time point (i):

C_i = (A_U/A_S) × C_S

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

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

Calculate the percentage of the labeled amounts (Q_i) of orphenadrine citrate (C₁₈H₂₃NO · C₆H₈O₇ dissolved at each time point (i):

Result₁ = C₁ × V_A × (1/L) × 100

Result₂ = {[C₂ × (V_B − V_S)] + (C₁ × V_S)} × (1/L) × 100

Result₃ = ({C₃ × [V_B − (2 × V_S)]} + [(C₂ + C₁) × V_S]) × (1/L) × 100

C_i = concentration of orphenadrine citrate in the portion of the sample withdrawn at time point (i) (mg/mL)

V_A = volume of Acid stage medium, 800 mL

L = label claim (mg/Tablet)

V_B = volume of Buffer stage medium, 900 mL

V_S = volume of the Sample solution withdrawn at each time point (mL)

Tolerances: See Table 3.

Table 3

The percentages of the labeled amount of orphenadrine citrate (C₁₈H₂₃NO · C₆H₈O₇) dissolved at the times specified conform to

Dissolution 〈711〉, Acceptance Table 2.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Organic Impurities

Buffer, Mobile phase, System suitability solution, Sample solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Analysis

Sample: Sample solution

Calculate the percentage of each degradation product in the portion of Tablets taken:

Result = (r_U/r_S) × (1/F) × 100

r_U = peak response of each degradation product from the Sample solution

r_S = peak response of orphenadrine from the Sample solution

F = relative response factor for each degradation product (see Table 4)

Acceptance criteria: See Table 4.

Table 4

^a The peak is due to counter ion and is not to be reported or included in total degradation products.

^b Also known as Phenyl(o-tolyl)methanol.

^c Also known as Phenyl(o-tolyl)methanone.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed, tight, light-resistant containers, and store at controlled room temperature.

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

Change to read:

USP Reference Standards 〈11〉

USP Orphenadrine Citrate RS

USP Orphenadrine Related Compound B RS

N-Ethyl-N,N-dimethyl [2-(2- (ERR 1-Feb-2022) methylbenzhydryloxy)ethyl]ammonium chloride; also known as N-Ethyl-N,N-dimethyl-2-[phenyl(2 (ERR 1-Feb-2022)-tolyl)methoxy]ethanaminium chloride.

C₂₀H₂₈ClNO 333.90

USP Orphenadrine Related Compound C RS

N-Methyl [2-(2-methylbenzhydryloxy)ethyl]amine hydrochloride;

Also known as N-Methyl-2-[phenyl(o-tolyl)methoxy]ethanamine hydrochloride.

C₁₇H₂₂ClNO 291.82