Risperidone Orally Disintegrating 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 

Risperidone Orally Disintegrating Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of risperidone (C₂₃H₂₇FN₄O₂)

2 IDENTIFICATION 

Change to read: 

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. 

Add the following: 

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 

Change to read: Procedure 

Mobile phase: Acetonitrile, triuoroacetic acid, and water (200:1.5:800). Adjust with ammonium hydroxide to a pH of 3.0. Diluent: Methanol and 0.1 N hydrochloric acid (40:60) 

System suitability solution: 0.1 mg/mL of USP Risperidone Related Compounds Mixture RS prepared as follows. Transfer a suitable quantity of USP Risperidone Related Compounds Mixture RS to a suitable volumetric flask and dissolve  in 20% of the flask volume of methanol. Dilute with Diluent to volume. 

Standard solution: 0.1 mg/mL of USP Risperidone RS in Diluent 

Sample solution: Nominally  0.1 mg/mL of risperidone in Diluent from NLT 13 Tablets. [Note—Sonicate for 30 min.] Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 275 nm. For Identification B, use a diode array detector in the range of 200–400 nm.  Column: 3.0-mm × 15-cm; 3.5-µm packing L1 

Flow rate: 0.8 mL/min 

Injection volume: 10 µL 

Run time: NLT 2.2  times the retention time of risperidone 

System suitability 

Samples: System suitability solution and Standard solution 

[Note—For relative retention times, see Table 1.  ] 

Suitability requirements 

Resolution: NLT 1.8 between Z-oxime and bicyclorisperidone, System suitability solution 

Relative standard deviation: NMT 2.0%, Standard solution 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of risperidone  (C₂₃H₂₇FN₄O₂) in the portion of Tablets taken:  

Result = (r_U/r_S) × (C_S/C_U) × 100 

r_U = peak response of risedronate  from the Sample solution 

r_S = peak response of risedronate  from the Standard solution 

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

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

Acceptance criteria: 90.0%–110.0% 

4 PERFORMANCE TESTS 

Disintegration 〈701〉 

Test 1: NMT 30 s 

Test 2: NMT 60 s. [Note—If the product complies with this test, the labeling indicates that the product meets USP Disintegration Test 2.] Change to read: 

Dissolution 〈711〉 

Medium: 0.1 N hydrochloric acid; 500 mL 

Apparatus 2: 50 rpm 

Time: 10 min 

Buffer: 8.7 g/L of dibasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 7.8. 

Mobile phase: Acetonitrile and Buffer (45:55) 

Standard solution: (L/500) mg/mL of USP Risperidone RS in Medium, where L is the label claim in mg/Tablet Sample solution: Pass 10 mL of the solution under test through a suitable filter of 0.45-µm pore size. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 280 nm 

Column: 4.6-mm × 10-cm; 5-µm packing L1 

Column temperature: 28 ± 3° 

Flow rate: 2 mL/min 

Injection volume: 20 µL. [Note—Use 40 µL for Tablets labeled to contain 0.5 mg of risperidone.] 

Run time: NLT  2 times the retention time of risperidone 

System suitability 

Sample: Standard solution 

Suitability requirements 

Relative standard deviation: NMT 2.0% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of risperidone  (C₂₃H₂₇FN₄O₂) dissolved:  

Result = (r_U/r_S) × (C /L) × V × 100 

r_U = peak response from the Sample solution 

r_S = peak response from the Standard solution  

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

L = label claim (mg/Tablet) 

V = volume of Medium, 500 mL 

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

Change to read: 

Uniformity of Dosage Units 〈905〉: Meet the requirements 

5 IMPURITIES 

Change to read: 

Organic Impurities 

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

Analysis 

Sample: Sample solution 

Calculate the percentage of any individual impurity in the portion of Tablets taken: 

Result = (r_U/r_U2) × (1/F) × 100 

r_U1 = peak response of any individual impurity from the Sample solution 

r_U2 = peak response of risperidone from the Sample solution 

F = relative response factor (see   Table 1) 

Acceptance criteria: See Table 1.  

 Table 1 

a Process impurity; it is used to establish system suitability only. 

b (Z)-3-[2-[4-(2,4-Diuorophenyl)(hydroxyimino)methyl]-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one.

c 3-(4-Fluoro-2-hydroxyphenyl)-1-[2-(6,7,8,9-tetrahydro-2-methyl-4-oxo-4H-pyrido-[1,2-a]pyrimidin-3-yl)ethyl]-2-aza-1-azoniabicyclo[2.2.2]oct 2-ene. 

d cis-3-[2-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one,N-oxide. 

6 ADDITIONAL REQUIREMENTS 

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

Labeling: When more than one Disintegration test is given, the labeling states the Disintegration test used only if Test 1 is not used. USP Reference Standards 〈11〉 

USP Risperidone RS 

4H-Pyrido[1,2-a]pyrimidin-4-one, 3-[2-[4-(6-uoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-. 3-[2-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)piperidino]ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one. C₂₃H₂₇FN₄O₂ 410.48 

USP Risperidone Related Compounds Mixture RS 

Contains a mixture of the following four compounds: 

Risperidone. 

Risperidone cis-N-oxide: cis-3-[2-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4- one, N-oxide. 

Bicyclorisperidone: 3-(4-Fluoro-2-hydroxyphenyl)-1-[2-(6,7,8,9-tetrahydro-2-methyl-4-oxo-4H-pyrido-[1,2-a]pyrimidin-3-yl)ethyl]-2-aza-1- azoniabicyclo[2.2.2]oct-2-ene iodide. 

Z-Oxime: (Z)-3-[2-[4-(2,4-Diuorophenyl)(hydroxyimino)methyl]-1-piperidinyl]ethyl-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one.