Tizanidine 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

Tizanidine Tablets contain Tizanidine Hydrochloride equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of tizanidine (C₉H₈CIN₅S).

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.

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

3 ASSAY

PROCEDURE

Solution A: Water and phosphoric acid (44:6)

Buffer: 3.5 g/L of sodium 1-pentanesulfonate. Adjust with Solution A or 1 N sodium hydroxide to a pH of 3.0.

Mobile phase: Acetonitrile and Buffer (20:80)

Tizanidine related compound A solution: 0.1 mg/mL of USP Tizanidine Related Compound A RS in methanol

Tizanidine related compound B solution: 0.1 mg/mL of USP Tizanidine Related Compound B RS in methanol

Tizanidine related compound C solution: 0.1 mg/mL of USP Tizanidine Related Compound C. RS in methanol

System suitability solution: Transfer 23 mg of USP Tizanidine Hydrochloride RS to a 100-mL volumetric flask, and add 20 mL of Mobile phase and 10 mL each of Tizanidine related compound A solution, Tizanidine related compound B solution, and Tizanidine related compound C solution. Sonicate to dissolve the USP Tizanidine Hydrochloride RS, and dilute with Mobile phase to volume.

Standard solution: 0.046 mg/mL of USP Tizanidine Hydrochloride RS in Mobile phase

Sample solution: Transfer a weighed portion of finely powdered Tablets (NLT 20), equivalent to 20 mg of tizanidine, to a 500-mL volumetric flask. Add 250 mL of Buffer solution, sonicate for 15 min with occasional shaking, and shake by mechanical means for 15 min. Add 100 ml of acetonitrile, and mix. Allow to cool, and dilute with Buffer solution to volume. Centrifuge a portion of this solution at 2000 rpm or higher for 10 min. Pass a portion of this solution through a filter with a 0.45-µm or finer pore size, and use the filtrate.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 230 nm. For Identification B, use a diode array detector in the range of 210-400 nm.

Column: 4.6-mm x 25-cm; 5-µm packing L1

Column temperature: 50°

Flow rate: 1 mL/min

Injection volume: 10 µL

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times are listed in Table 1.]

Suitability requirements

Resolution: NLT 4.0 between tizanidine and tizanidine related compound C; NLT 4.0 between tizanidine and tizanidine 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 tizanidine (C₉H₈CIN₅S) in the portion of Tablets taken:

                          Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) ×100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

M_r1 = molecular weight of tizanidine, 253.71

M_r2 = molecular weight of tizanidine hydrochloride, 290.17 

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

4.1 DISSOLUTION (711)

4.1.1 Test 1

Medium: 0.1 N hydrochloric acid, 500 mL

Apparatus 1: 100 rpm

Time: 15 min

Solution A, Buffer, and Mobile phase: Prepare as directed in the Assay.

Standard solution: (L/500) mg/mL of USP Tizanidine Hydrochloride RS in Medium, where L is the label claim, in mg

Sample solution: Sample per Dissolution (711). Dilute with Medium to a concentration that is similar to the Standard solution.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 230 nm

Column: 4.6-mm x 25-cm; 5-µm packing L1

Column temperature: 50°

Flow rate: 1 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 percentage of the labeled amount of tizanidine (C₉H₈CIN₅S) dissolved:

                          Result = (r_U/r_S) × C_S × V × (1/L) × (M_r1/M_r2) ×100

r_U = peak response of tizanidine from the Sample solution

r_S = peak response of tizanidine from the Standard solution

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

V = volume of dissolution Medium, 500 mL

L = label claim, in mg

M_r1 = molecular weight of tizanidine, 253.71

M_r2 = molecular weight of tizanidine hydrochloride, 290.17 

Tolerances: NLT 80% (Q) of the labeled amount of tizanidine (C₉H₈CIN₅S) is dissolved.

4.1.2 Test 2

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

Medium: 0.1 N hydrochloric acid: 500 mL, deaerated

Apparatus 1: 100 грm

Time: 30 min

Standard solution: (L/500) mg/mL of USP Tizanidine Hydrochloride RS in Medium, where L is the label claim, in mg

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-um pore size.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: UV

Analytical wavelength: 228 nm

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of tizanidine (C₉H₈CIN₅S) dissolved:

                          Result = (A_U/A_S) x C_S x V x (1/L) x (M_r1/M_r2) x 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

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

V = volume of dissolution Medium, 500 mL

L = label claim, in mg

M_r1 = molecular weight of tizanidine, 253.71

M_r2 = molecular weight of tizanidine hydrochloride, 290.17

Tolerances: NLT 80% (Q) of the labeled amount of tizanidine (C₉H₈CIN₅S) is dissolved.

5 IMPURITIES

ORGANIC IMPURITIES

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

Sample solution: Transfer a weighed portion of finely powdered Tablets (NLT 20), equivalent to 20 mg of tizanidine, to a 100-mL volumetric flask. Add about 50 mL of Buffer solution, sonicate for about 15 min with occasional shaking, and shake by mechanical means for 15 min. Add 20 mL of acetonitrile, and mix. Allow to cool, dilute with Buffer solution to volume, and mix. Centrifuge a portion of this solution at 2000 rpm or higher for 10 min. Pass a portion of this solution through a filter with a 0.45-µm or finer pore size, and use the filtrate.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Tablets taken: 

                          Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) ×(1/F) × 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of tizanidine from the Standard solution

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

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

M_r1 = molecular weight of tizanidine, 253.71

M_r2 = molecular weight of tizanidine hydrochloride, 290.17

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1.

Table 1

^a Process impurity included for peak identification purposes only. Controlled in the drug substance.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers, and store at controlled room temperature.

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

USP REFERENCE STANDARDS (11)

USP Tizanidine Hydrochloride RS

USP Tizanidine Related Compound A RS

4-Amino-5-chloro-2,1,3-benzothiadiazole.

C₆H₄CIN₃S           185.63

USP Tizanidine Related Compound B RS

N-Acetyltizanidine.

C₁₁H₁₂CIN₅OS               295.75

USP Tizanidine Related Compound C RS

1-Acetylimidazolidine-2-thione.

C₅H₈N₂OS                 144.19