Olanzapine Orally Disintegrating Tablets
DEFINITION
Olanzapine Orally Disintegrating Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of olanzapine (C17H20N4S).
IDENTIFICATION
• A. Infrared Absorption 
197K
197K
Standard:
Add 25 mg of USP Olanzapine RS to a suitable container containing 10 mL of water. Centrifuge for 5 min, and discard the supernatant. Dry the olanzapine under vacuum for 1 h at 60
.
.
Sample:
Place 1 Tablet in 10 mL of water in a centrifuge tube. Centrifuge for 5 min. Wash the precipitate with 5 mL of water, and centrifuge for 5 min. Discard the water, and repeat the process a third time. Dry the olanzapine under vacuum for 1 h at 60.
.
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.
ASSAY
• Procedure
Solution A:
Acetonitrile and water (20:80). Add 2 mL of perchloric acid to each L of the mixture.
Solution B:
Acetonitrile and water (60:40). Add 2 mL of perchloric acid to each L of the mixture.
Diluent:
Acetonitrile and water (35:65)
Mobile phase:
See Table 1.
Table 1
| Time (min) |
Solution A (%) |
Solution B (%) |
|---|---|---|
| 0 | 87 | 13 |
| 10 | 87 | 13 |
| 20 | 0 | 100 |
| 26 | 0 | 100 |
| 26.1 | 87 | 13 |
| 36 | 87 | 13 |
System suitability solution:
0.1 mg/mL of USP Olanzapine RS and 10 µg/mL of USP Olanzapine Related Compound C RS in Diluent
Standard solution:
0.1 mg/mL of USP Olanzapine RS in Diluent
Sample stock solution:
0.5–0.6 mg/mL of olanzapine from NLT 10 Tablets, prepared as follows. Transfer the Tablets to a suitable volumetric flask. Add Diluent to fill about 80% of the flask volume. Shake mechanically for 10 min, and dilute with Diluent to volume.
Sample solution:
Nominally, 0.1–0.12 mg/mL of olanzapine from the Sample stock solution in Diluent
Chromatographic system
Mode:
LC
Detector:
UV 260 nm
Column:
4.6-mm × 25-cm; 5-µm packing L7
Flow rate:
1 mL/min
Injection volume:
10 µL
System suitability
Samples:
System suitability solution and Standard solution
Suitability requirements
Resolution:
NLT 2.0 between the olanzapine and olanzapine related compound C peaks, System suitability solution
Tailing factor:
NMT 2.0 for the olanzapine peak, 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 olanzapine (C17H20N4S) in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of olanzapine from the Sample solution |
| rS | = | = peak response of olanzapine from the Standard solution |
| CS | = | = concentration of USP Olanzapine RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of olanzapine in the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Disintegration 701
701
Test 1:
NMT 10 s for each of 6 units
Test 2:
If the product complies with this test, the labeling indicates that the product meets USP Disintegration Test 2
Acceptance criteria:
NMT 30 s
• Dissolution 711
711
Medium:
0.1 N hydrochloric acid; 900 mL
Apparatus 2:
50 rpm
Time:
10 min
Standard solution:
(L/900) mg/mL of USP Olanzapine RS in Medium
Sample solution:
A portion of the solution under test may be either centrifuged or filtered through a suitable membrane filter of 0.45-µm pore size, discarding the first few mL. The filtrate or centrifugate may be suitably diluted.
Determine the amount of olanzapine (C17H20N4S) dissolved by using either the Spectrometric procedure or Chromatographic procedure described below:
Spectrometric procedure
Instrumental conditions
Mode:
UV-Vis
Analytical wavelength:
344 nm
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the labeled amount of olanzapine (C17H20N4S) dissolved:
Result = (AU/AS) × CS × V × (1/L) × 100
| AU | = | = absorbance of the Sample solution |
| AS | = | = absorbance of the Standard solution |
| CS | = | = concentration of USP Olanzapine RS in the Standard solution (mg/mL) |
| V | = | = volume of Medium, 900 mL |
| L | = | = label claim (mg/Tablet) |
Chromatographic procedure
Buffer:
6.8 g/L of sodium acetate trihydrate in water. Adjust with glacial acetic acid to a pH of 5.0.
Mobile phase:
Acetonitrile and Buffer (25:75)
Chromatographic system
Mode:
LC
Detector:
UV 250 nm
Column:
4.6-mm × 5-cm; 5-µm packing L1
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 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the labeled amount of olanzapine (C17H20N4S) dissolved:
Result = (rU/rS) × CS × V × (1/L) × 100
| rU | = | = peak response of olanzapine from the Sample solution |
| rS | = | = peak response of olanzapine from the Standard solution |
| CS | = | = concentration of USP Olanzapine RS (mg/mL) |
| V | = | = volume of Medium, 900 mL |
| L | = | = label claim (mg/Tablet) |
Tolerances:
NLT 80% (Q) of the labeled amount of olanzapine (C17H20N4S) is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
• Organic Impurities
Solution A:
Acetonitrile and water (20:80). Add 2 mL of perchloric acid to each L of the mixture.
Solution B:
Acetonitrile and water (60:40). Add 2 mL of perchloric acid to each L of the mixture.
Diluent:
Acetonitrile and water (35:65)
Mobile phase:
See Table 2.
Table 2
| Time (min) |
Solution A (%) |
Solution B (%) |
|---|---|---|
| 0 | 93 | 7 |
| 13 | 93 | 7 |
| 28 | 0 | 100 |
| 33 | 0 | 100 |
| 33.1 | 93 | 7 |
| 44 | 93 | 7 |
System suitability solution:
0.1 mg/mL of USP Olanzapine RS and 7 µg/mL of USP Olanzapine Related Compound C RS in Diluent
Standard solution:
1.5 µg/mL of USP Olanzapine RS in Solution A
Sensitivity solution:
0.15 µg/mL of USP Olanzapine RS from the Standard solution in Diluent
Sample solution:
Nominally, 0.3 mg/mL of olanzapine from NLT 10 Tablets, prepared as follows. Transfer the Tablets to a suitable volumetric flask. Add Diluent to fill about 80% of the flask volume. Shake mechanically for 25 min, and dilute with Diluent to volume. Dilute a portion of this solution with water to volume. Store the solution at 4. Use within 7 h.
. Use within 7 h.
Chromatographic system
Mode:
LC
Detector:
UV 230 nm
Column:
4.6-mm × 25-cm; 5-µm packing L7
Sample temperature:
4
Flow rate:
1 mL/min
Injection volume:
20 µL
System suitability
Samples:
System suitability solution, Standard solution, and Sensitivity solution
Suitability requirements
Resolution:
NLT 2.0 between the olanzapine and olanzapine related compound C peaks, System suitability solution
Tailing factor:
NMT 2.0 for the olanzapine peak, System suitability solution
Relative standard deviation:
NMT 5.0%, Standard solution
Signal-to-noise ratio:
NLT 10, Sensitivity solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each individual specified impurity and any individual unspecified degradation product in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
| rU | = | = peak response of each individual specified impurity from the Sample solution |
| rS | = | = peak response of olanzapine from the Standard solution |
| CS | = | = concentration of olanzapine in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of olanzapine in the Sample solution (mg/mL) |
| F | = | = relative response factor (see Table 3) |
Acceptance criteria:
See Table 3. [Note—Disregard any peak less than 0.05%. ]
Table 3
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Olanzapine lactama | 0.48 | 1.9 | 0.50 |
| Olanzapine thiolactamb | 0.75 | 1.0 | 0.50 |
| Olanzapine | 1.0 | — | — |
| Olanzapine related compound C | 1.2 | 0.79 | 0.50 |
| Olanzapine related compound Bc | 2.1 | 1.9 | 0.50 |
| Any individual unspecified degradation product | — | 1.0 | 0.20 |
| Total impurities | — | — | 1.5 |
|
a
(Z)-4-(4-Methylpiperazin-1-yl)-3-(2-oxopropylidene)-1H-benzo[b][1,4]diazepin-2(3H)-one.
b
(Z)-1-{4-(4-Methylpiperazin-1-yl)-2-thioxo-1H-benzo[b][1,4]diazepin-3(2H)-ylidene}propan-2-one.
c
2-Methyl-5,10-dihydro-4H-benzo[b]thieno[2,3-e][1,4]diazepin-4-one.
|
|||
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed 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. 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
11
USP Olanzapine RS 
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USP Olanzapine Related Compound C RS
2-Methyl-4-(4-methylpiperazin-1-yl)-10H-benzo[b]thieno[2,3-e][1,4]diazepine 4'-N-oxide.
C17H20N4OS 328.43
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2-Methyl-4-(4-methylpiperazin-1-yl)-10H-benzo[b]thieno[2,3-e][1,4]diazepine 4'-N-oxide.
C17H20N4OS 328.43
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Ravi Ravichandran, Ph.D.
Principal Scientific Liaison (301) 816-8330 |
(SM42010) Monographs - Small Molecules 4 |
| 701 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison (301) 816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison (301) 816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP38–NF33 Page 4619
Pharmacopeial Forum: Volume No. 39(3)