Add the following:
Risperidone Orally Disintegrating Tablets
DEFINITION
Risperidone Orally Disintegrating Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of risperidone (C23H27FN4O2).
IDENTIFICATION
• The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
Mobile phase:
Acetonitrile, trifluoroacetic acid, and water (200: 1.5: 800). Adjust with ammonium hydroxide to a pH of 3.0.
Diluent:
Methanol and 0.1 N HCl (40:60)
System suitability solution:
0.1 mg/mL of USP Risperidone Related Compounds Mixture RS prepared as follows: Dissolve first 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:
0.1 mg/mL of risperidone in Diluent from NLT 13 Tablets. [Note—Sonicate for 30 min. ]
Chromatographic system
Mode:
LC
Detector:
UV 275 nm
Column:
3.0-mm × 15-cm; 3.5-µm packing L1
Flow rate:
0.8 mL/min
Injection size:
10 µL
Run time:
2.2 times the retention time of risperidone
System suitability
Samples:
System suitability solution and Standard solution
[Note—For relative retention times, see Impurity Table 1 under Organic Impurities. ]
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 C23H27FN4O2 in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of risperidone from the Sample solution |
| rS | = | = peak response of risperidone from the Standard solution |
| CS | = | = concentration of USP Risperidone RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of risperidone in the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Disintegration 
701
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. ]
• Dissolution 711
711
Medium:
0.1 N HCl; 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 nylon filter of 0.45-µm pore size.
Chromatographic system
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 size:
20 µL. [Note—Use 40 µL for Tablets labeled to contain 0.5 mg of risperidone. ]
Run time:
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 C23H27FN4O2 dissolved:
Result = (rU/rS) × (CS/L) × V × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = 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.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
Procedure for content uniformity
Mobile phase:
Proceed as directed in the Dissolution test.
Standard solution:
(L/100) mg/mL of USP Risperidone RS in 0.1 N HCl, where L is the Tablet label claim in mg
Sample solution:
Transfer 1 Tablet to a 100-mL volumetric flask, and dilute with 0.1 N HCl to volume to obtain a nominal concentration of (L/100) mg/mL of risperidone, where L is the label claim in mg/Tablet. Sonicate for 30 min at 40.
.
Chromatographic system:
Proceed as directed in the Dissolution test.
Injection size:
20 µL
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C23H27FN4O2 in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of risperidone from the Sample solution |
| rS | = | = peak response of risperidone from the Standard solution |
| CS | = | = concentration of USP Risperidone RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of risperidone in the Sample solution (mg/mL) |
IMPURITIES
Organic Impurities
• Procedure
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 = (rU1/rU2) × (1/F) × 100
| rU1 | = | = peak response of any individual impurity from the Sample solution |
| rU2 | = | = peak response of risperidone from the Sample solution |
| F | = | = relative response factor (see Impurity Table 1) |
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Total impurities:
NMT 1.0%
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Z-oxime*,a | 0.59 | 1.0 | — |
| Bicyclorisperidoneb | 0.66 | 0.86 | 0.3 |
| Risperidone | 1.0 | 1.0 | — |
| Risperidone cis-N-oxidec | 1.7 | 0.97 | 0.5 |
| Any unspecified degradation product | — | 1.0 | 0.2 |
|
*
Process impurity; it is used to establish system suitability only.
a
(Z)-3-[2-[4-(2,4-Difluorophenyl)(hydroxyimino)methyl]-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one.
b
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.
c
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.
|
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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
11
USP Risperidone RS 
4H-Pyrido[1,2-a]pyrimidin-4-one, 3-[2-[4-(6-fluoro-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
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4H-Pyrido[1,2-a]pyrimidin-4-one, 3-[2-[4-(6-fluoro-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
Risperidone (98.9%)
Risperidone cis-N-oxide (0.5%): 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 monohydrate.
C23H29FN4O4 444.50
Bicyclorisperidone (0.3%): 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.
C23H28FIN4O4 538.40
Z-oxime (0.3%): (Z)-3-[2-[4-(2,4-Difluorophenyl)(hydroxyimino)methyl]-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one.
C23H28F2N4O2 430.29
Contains a 98.9/0.5/0.3/0.3 (area %) mixture of the following four compounds:
Risperidone (98.9%)
Risperidone cis-N-oxide (0.5%): 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 monohydrate.
C23H29FN4O4 444.50
Bicyclorisperidone (0.3%): 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.
C23H28FIN4O4 538.40
Z-oxime (0.3%): (Z)-3-[2-[4-(2,4-Difluorophenyl)(hydroxyimino)methyl]-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one.
C23H28F2N4O2 430.29
USP35
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Hariram Ramanathan, M.S.
Associate Scientific Liaison 1-301-816-8313 |
(SM42010) Monographs - Small Molecules 4 |
| 701 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 4575
Pharmacopeial Forum: Volume No. 36(6) Page 1565