Cyclobenzaprine 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

Cyclobenzaprine Hydrochloride Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of cyclobenzaprine hydrochloride (C₂₀H₂₁N . HCl)

2 IDENTIFICATION

2.1 A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197M

Sample: Transfer an amount equivalent to 50 mg of cyclobenzaprine hydrochloride from a quantity of finely powdered Tablets to a small flask. Add 10 mL of methylene chloride, swirl to dissolve, and filter. Evaporate the clear filtrate to about 5 mL, transfer to a centrifuge tube, and add 1-2 mL of ether. Evaporate with the aid of a current of air to about 1 mL, and agitate until crystallization occurs. Wash the crystals with several portions of ether, and air-dry.

Acceptance criteria: Meet the requirements

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: 11.4 g/L of ammonium acetate in water. Adjust with ammonium hydroxide to a pH of 7.2.

Mobile phase: Methanol and Buffer (65:35)

Standard solution: 0.2 mg/mL of USP Cyclobenzaprine Hydrochloride RS in Mobile phase. Sonication may be used to aid in dissolution.

Sample solution: Nominally 0.2 mg/mL of cyclobenzaprine hydrochloride from NLT 20 finely powdered Tablets in Mobile phase prepared as follows. Transfer a suitable amount of the powder to a suitable volumetric flask. Add 60% of the flask volume of Mobile phase, and sonicate for 30 min. Allow the solution to cool to room temperature, and then dilute with Mobile phase to volume. Centrifuge the solution, and use the supernatant.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 226 nm

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 0.85%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of cyclobenzaprine hydrochloride (C₂₀H₂₁N . HCl) 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 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 1: 50 rpm

Time: 30 min

Sample solution: Pass a portion of the solution under test through a suitable filter, and dilute with Medium if necessary.

Standard solution: USP Cyclobenzaprine Hydrochloride RS in Medium with a concentration similar to the one expected in the Sample solution

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: UV

Analytical wavelength: 290 nm

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of the labeled amount of cyclobenzaprine hydrochloride (C₂H₂,NHCI) dissolved:

Result = (A_u/A_s) x C_s x V x (1/L) x 100

A_u = absorbance of the Sample solution

A_s = absorbance of the Standard solution

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

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

Tolerances: NLT 75% (Q) of the labeled amount of cyclobenzaprine hydrochloride (C20H2, NHCI) is dissolved.

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

5 IMPURITIES

Change to read:

5.1 ORGANIC IMPURITIES

Buffer and Mobile phase: Proceed as directed in the Assay.

Standard solution: 0.6 µg/mL each of USP Cyclobenzaprine Hydrochloride RS, USP Cyclobenzaprine Related Compound A RS, and USP Cyclobenzaprine Related Compound B RS in Mobile phase

Sample solution: Nominally 400 µg/mL of cyclobenzaprine hydrochloride from NLT 20 finely powdered Tablets in Mobile phase prepared as follows. Transfer a suitable amount of the powder to a suitable volumetric flask. Add 75% of the flask volume of Mobile phase, and sonicate for 30 min. Allow the solution to cool to room temperature, and then dilute with Mobile phase to volume. Centrifuge the solution, and use the supernatant.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 226 nm

Column: 4.6-mm x 25-cm; 5-µm packing LZ

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 10 µL

Run time: NLT 3 times the retention time of cyclobenzaprine

System suitability

Sample: Standard solution

[NOTE-See Table 1 for relative retention times.]

Suitability requirements

Resolution: NLT 2.0 between the cyclobenzaprine related compound A and cyclobenzaprine related compound B peaks

Relative standard deviation: NMT 2.0% for the cyclobenzaprine peak

Analysis

Sample: Standard solution and Sample solution

Calculate the percentage of any individual degradation product in the portion of Tablets taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of any individual 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 (µg/mL)

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

Acceptance criteria: See Table 1.

Table 1

a Process impurity included for identification only and not included in the calculation of total degradation products.

b 3-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-N,N-dimethyl-1-propanamine N-oxide.

c 10,11-Dihydro-N,N-dimethyl-5H-dibenzo[a,d]cycloheptene-A5Y, -propylamine.

d Dibenzo[a,d]cyclohepten-5-one.

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE:

Preserve in well-closed containers. Store at controlled room temperature.

6.2 USP REFERENCE STANDARDS (11)

USP Cyclobenzaprine Hydrochloride RS

USP Cyclobenzaprine Related Compound A RS

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

C₂₀H₂₃NO    293.40

USP Cyclobenzaprine Related Compound B RS

3-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-N-methyl-1-propanamine hydrochloride.

C₁₉H₁₉ON . HCI    297.82