Rivastigmine Tartrate 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 

Rivastigmine Tartrate Capsules contain an amount of Rivastigmine Tartrate equivalent to NLT 94.0% and NMT 105.0% of the labeled amount of rivastigmine (C₁₄H₂₂N₂O₂). 

2 IDENTIFICATION 

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: 8.6 mg/mL of monobasic ammonium phosphate in water. Adjust with ammonia solution to a pH of 7.0. 

Mobile phase: Methanol, acetonitrile, and Buffer (15:15:70) 

Standard solution: 0.064 mg/mL of USP Rivastigmine Tartrate RS in Mobile phase. [Note—Use a small amount of methanol (about 2% of the nal volume) to facilitate dissolution before diluting with Mobile phase to volume, and use sonication if necessary.] 

System suitability solution: 0.01 mg/mL each of USP Rivastigmine Related Compound A RS and USP Rivastigmine Related Compound B RS in Mobile phase 

Sample solution: Remove as completely as possible the contents of NLT 20 Capsules, and mix. Transfer a weighed portion of the combined contents, equivalent to about 48 mg of rivastigmine, to a 250-mL volumetric flask. Add 25 mL of methanol and 60 mL of Mobile phase, and sonicate for 15 min to disperse the contents. Dilute with Mobile phase to volume, mix well, and centrifuge. Dilute a portion of the supernatant with Mobile phase to obtain a solution having a concentration of 0.038 mg/mL of rivastigmine, based on the label claim. Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 215 nm 

Column: 4.6-mm × 25-cm; 5-µm packing L7 

Flow rate: 1.5 mL/min 

Injection size: 20 µL 

System suitability 

Samples: Standard solution and System suitability solution 

[Note—The relative retention times for rivastigmine related compound A, rivastigmine related compound B, and rivastigmine are 0.46, 0.57, and 1.0, respectively.] 

Suitability requirements 

Resolution: NLT 1.5 between rivastigmine related compound A and rivastigmine related compound B, System suitability solution Column efficiency: NLT 5000 theoretical plates, Standard solution 

Tailing factor: NMT 2.3, Standard solution 

Relative standard deviation: NMT 2.0%, Standard solution 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of C₁₄H₂₂N₂O₂ in the portion of Capsules taken: 

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

r_U = peak response of rivastigmine from from the Sample solution 

r_S = peak response of rivastigmine from the Standard solution 

C_S = concentration of USP Rivastigmine Tartrate RS in the Standard solution (mg/mL) 

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

M_r1 = molecular weight of rivastigmine, 250.34 

M_r2 = molecular weight of rivastigmine tartrate, 400.42 

Acceptance criteria: 94.0%–105.0% 

4 PERFORMANCE TESTS 

Dissolution 〈711〉 

Test 1 

Medium: Water; 500 mL, deaerated 

Apparatus 2: 50 rpm, with sinkers, if necessary 

Time: 30 min 

Buffer, Mobile phase, and System suitability solution: Prepare as directed in the Assay. 

Standard solution: 0.192 mg/mL of USP Rivastigmine Tartrate RS in Mobile phase. Further dilute with Medium to obtain a solution having a concentration similar to that expected in the Sample solution. 

Sample solutions: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size, discarding the first few mL. Chromatographic system and System suitability: Proceed as directed in the Assay. 

[Note—Use an injection size of 100 µL.] 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of C₁₄H₂₂N₂O₂ dissolved: 

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

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) 

M_r1 = molecular weight of rivastigmine, 250.34 

M_r2 = molecular weight of rivastigmine tartrate, 400.42 

V = volume of Medium (mL), 500 

L = Capsule label claim (mg) 

Tolerances: NLT 75% (Q) of the labeled amount of C₁₄H₂₂N₂O₂ is dissolved. 

Test 2: If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 2. Medium: Deaerated water; 500 mL 

Apparatus 2: 75 rpm 

Time: 15 min 

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

Standard solution: 0.192 mg/mL of USP Rivastigmine Tartrate RS in Mobile phase. Further dilute with Medium to obtain a solution having a concentration similar to that expected in the Sample solution. 

Sample solution: Pass a portion of the solution under test through a suitable lter of 0.45-µm pore size, discarding the rst few milliliters. Chromatographic system: Proceed as directed in the Assay. [Note—Use an injection volume of 100 µL.] 

System suitability 

Sample: Standard solution 

Suitability requirements 

Relative standard deviation: NMT 2.0% 

Tailing factor: NMT 2.3 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of rivastigmine (C₁₄H₂₂N₂O₂) dissolved: 

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

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) 

M_r1 = molecular weight of rivastigmine, 250.34 

M_r2 = molecular weight of rivastigmine tartrate, 400.42 

V = volume of Medium (mL), 500 

L = label claim (mg/Capsule) 

Tolerances: NLT 80% (Q) of the labeled amount of rivastigmine (C₁₄H₂₂N₂O₂) is dissolved. 

5 IMPURITIES 

Organic Impurities 

Procedure 

Buffer, Mobile phase, and System suitability solution: Prepare as directed in the Assay. 

Standard solution: 1.6 µg/mL of USP Rivastigmine Tartrate RS in Mobile phase 

Sample solution: Remove as completely as possible the contents of NLT 20 Capsules, and mix. Transfer a weighed portion of the combined

contents, equivalent to 25 mg of rivastigmine, to a 25-mL volumetric flask. Disperse in 10 mL of Mobile phase, and sonicate for 15 min. Dilute with Mobile phase to volume, mix well, and centrifuge. Use the supernatant. 

Chromatographic system: Proceed as directed in the Assay. 

System suitability 

Samples: System suitability solution and Standard solution 

Suitability requirements 

Resolution: NLT 1.5 between rivastigmine related compound A and rivastigmine related compound B, System suitability solution Relative standard deviation: NMT 10.0%, Standard solution 

Analysis 

Samples: Standard solution and Sample solution 

[Note—Identify the peaks using the relative retention times provided in Impurity Table 1.] 

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

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

r_U = peak response of each individual impurity from the Sample solution 

r_S = peak response of rivastigmine from the Standard solution 

C_S = concentration of USP Rivastigmine Tartrate RS in the Standard solution (mg/mL) 

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

M_r1 = molecular weight of rivastigmine, 250.34 

M_r2 = molecular weight of rivastigmine tartrate, 400.42 

F = relative response factor (see Impurity Table 1) 

Acceptance criteria 

Individual impurities: See Impurity Table 1. 

Total impurities: NMT 1.0% 

Impurity Table 1 

a (S)-3-[1-(Dimethylamino)ethyl]phenol.

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 Dissolution test used only if Test 1 is not used. USP Reference Standards 〈11〉 

USP Rivastigmine Tartrate RS 

USP Rivastigmine Related Compound A RS 

(+)-Di-(p-toluoyl)-d-tartaric acid. 

C20H18O8 386.35 

USP Rivastigmine Related Compound B RS 

(RS)-3-[1-(Dimethylamino)ethyl]phenyl dimethylcarbamate. C₁₃H₂₀N₂O₂ 236.32