Cyclobenzaprine Hydrochloride Extended-Release Capsules

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

Cyclobenzaprine Hydrochloride Extended-Release Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of cyclobenzaprine hydrochloride (C₂₀H₂₁N . HCI)

2 IDENTIFICATION

Change to read:

2.1 A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197A (CN 1-MAY-2020)

Standard: Transfer 90 mg of USP Cyclobenzaprine Hydrochloride RS to a 25-mL volumetric flask. Add 10 mL of water and sonicate for 30 s. Transfer the solution to a 40-mL vial. Add 10 mL of methylene chloride. Cap the vial and shake. Centrifuge, if necessary, and transfer the lower methylene chloride layer to a watch glass. Evaporate the solvent, and use the residue. [NOTE-The use of a glass vial and a centrifuge speed of NMT 2000 rpm may be suitable. An infrared heat lamp may be used to evaporate the solvent.]

Sample: Transfer a portion of the contents of NLT 10 Capsules containing nominally 90 mg of cyclobenzaprine hydrochloride to a 25-mL volumetric flask. Add 10 mL of water and sonicate for 30 s. Transfer the solution to a 40-mL vial. Add 10 mL of methylene chloride. Cap the vial and shake. Centrifuge, and transfer the lower methylene chloride layer to a watch glass. Evaporate the solvent, and use the residue. [NOTE-The use of a glass vial and a centrifuge speed of NMT 2000 rpm may be suitable. An infrared heat lamp may be used to evaporate the solvent.]

Analysis

Samples: Standard and Sample

Acceptance criteria: The maxima of the IR spectrum from the Sample correspond to those from the Standard.

2.2 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

Buffer: Add 3.7 mL of methanesulfonic acid per 1 L of water and adjust with diethylamine to a pH of 3.6.

Mobile phase: Acetonitrile, methanol, and Buffer (25.5:21.0:53.5)

Diluent: Acetonitrile and water (50:50)

Standard solution: 0.12 mg/mL of USP Cyclobenzaprine Hydrochloride RS in Diluent

Sample solution: Nominally 0.12 mg/mL of cyclobenzaprine hydrochloride from Capsules prepared as follows. Remove the contents of NLT 20 Capsules, and transfer a suitable portion of the contents to a volumetric flask. Add 80% of the final flask volume of Diluent. Stir and sonicate, if necessary. Dilute with Diluent to volume, and centrifuge. Use the supernatant.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 290 nm

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

Flow rate: 1.5 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 1.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of cyclobenzaprine hydrochloride (C₂₀H₂₁N . HCI) in the portion of Capsules taken:

Result = (r_u/r_s) x (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 Cyclobenzaprine Hydrochloride RS in the Standard solution (mg/mL)

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

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

4.1 DISSOLUTION (711)

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm, wire helix sinkers

Times: 2, 4, 8, and 16 h

Solution A: Transfer 10 empty Capsule shells to a 1-L volumetric flask. Add 80% of the final flask volume of Medium, which has been warmed to 37°, and stir until the Capsule shells have dissolved. Allow to cool, and dilute with Medium to volume.

Standard solution: (L/900) mg/mL of USP Cyclobenzaprine Hydrochloride RS in Medium, where L is the label claim of cyclobenzaprine hydrochloride in mg/Capsule

Sample solution: Centrifuge a portion of the solution under test. Use the supernatant.

Instrumental conditions

Mode: UV

Analytical wavelength: 290 nm

Cell: 1 cm

Blank: A mixture of Solution A and Medium prepared as follows. Transfer 10% of the final flask volume of Solution A to a suitable volumetric flask. Dilute with Medium to volume, centrifuge, and use the supernatant.

Analysis

Samples: Standard solution, Sample solution, and Blank

Correct the instrument by using the Blank.

Calculate the concentration (C) of cyclobenzaprine hydrochloride (C₂₀H₂₁N . HCI) dissolved at each time point (i): 

Result = (A_u/A_s) x C_s

A_u = absorbance from the Sample solution at time point i

A_s = absorbance from the Standard solution

C_s = concentration of USP Cyclobenzaprine Hydrochloride RS in the Standard solution (mg/mL)

Calculate the percentage of the labeled amount of cyclobenzaprine hydrochloride (C₂₀H₂₁N . HCI) dissolved at each time point (i):

Result₁ = C₁ x V x (1/L) x 100

Result₂ = {[C₂ x (V - V_s)] + (C₁ x V_s) x (1/L) x 100

Result₃ = ((C₃ x [V - (2 x V_s)] + [(C₂ + C1) × V_s) × (1/L) x 100

Result₄ = ((C₄ x [V - (3 x V_s)] + [(C₃ + C₂ + C₁) × V_s) × (1/L) × 100

C₁ = concentration of cyclobenzaprine hydrochloride in the portion of sample withdrawn at the specified time point (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/Capsule)

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

Table 1

The percentage of the labeled amount of cyclobenzaprine hydrochloride (C₂₀H₂₁N . HCI)) dissolved at the times specified conform to

Acceptance Table 2 in (711),

4.2 UNIFORMITY OF DOSAGE UNITS (905): Meet the requirements

5 IMPURITIES

5.1 ORGANIC IMPURITIES

Buffer: Dissolve 10 mL of n-butylamine in 900 mL of water, and adjust with acetic acid to a pH of 6.0. Dilute to 1 L.

Mobile phase: Acetonitrile, methanol, and Buffer (15:29:56)

Sensitivity solution: 0.001 mg/mL of USP Cyclobenzaprine Hydrochloride RS in Mobile phase

Standard solution: 0.02 mg/mL of USP Cyclobenzaprine Hydrochloride RS and 0.01 mg/mL of USP Amitriptyline Hydrochloride RS in Mobile phase

Sample solution: Nominally 2 mg/mL of cyclobenzaprine hydrochloride from Capsules prepared as follows. Remove the contents of NLT 20 Capsules, and transfer a suitable portion of the contents to a volumetric flask. Add 70% of the final flask volume of Mobile phase. Stir and sonicate, if necessary. Dilute with Mobile phase to volume, and centrifuge. Use the supernatant.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 239 nm

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

Flow rate: 1.2 mL/min

Injection volume: 20 µL

Run time: NLT 3.5 times the retention time of cyclobenzaprine

System suitability

Samples: Standard solution and Sensitivity solution

[NOTE-The relative retention times for cyclobenzaprine and amitriptyline are 1.0 and 1.3, respectively. For other relative retention times, see

Table 2.]

Suitability requirements

Resolution: NLT 2.5 between cyclobenzaprine and amitriptyline, Standard solution

Relative standard deviation: NMT 2.0% for cyclobenzaprine, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each unspecified degradation product in the portion of Capsules taken:

Result = (r_u/r_s) x (C_s/C_u) × 100

r_u = peak response of each unspecified degradation product from the Sample solution

r_s = peak response of cyclobenzaprine from the Standard solution

C_s = concentration of USP Cyclobenzaprine Hydrochloride RS in the Standard solution (mg/mL)

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

Acceptance criteria: See Table 2. Disregard peaks less than 0.05%.

Table 2

a 5-[3-(Dimethylamino)propyl]-5H-dibenzo[a,d]-cyclohepten-5-ol.

b This is a process impurity that is included in the table for identification purposes only. It is controlled in the drug substance and is not to be reported or included in the total impurities for the drug product.

c Dibenzo[a,d cycloheptene-5-one (also known as dibenzocycloheptenone).

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE:

Preserve in tight, light-resistant containers. Store at controlled room temperature.

6.2 USP REFERENCE STANDARDS (11)

USP Amitriptyline Hydrochloride RS

USP Cyclobenzaprine Hydrochloride RS