Olanzapine 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 

Olanzapine Orally Disintegrating Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of olanzapine (C₁₇H₂₀N₄S).

2 IDENTIFICATION 

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 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. 

3 ASSAY

Procedure 

Solution A: Acetonitrile and water (20:80). Add 2 mL of perchloric acid to each liter of the mixture. 

Solution B: Acetonitrile and water (60:40). Add 2 mL of perchloric acid to each liter of the mixture. 

Diluent: Acetonitrile and water (35:65) 

Mobile phase: See Table 1. 

Table 1 

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 Tablets (NLT 10), prepared as follows. Transfer the Tablets to a suitable volumetric flask. Add Diluent to ll 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 

(See Chromatography 〈621〉, System Suitability.) 

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 = (r_U/r_S) × (C_S/C_U) × 100 

r_U = peak response of olanzapine  from the Sample solution 

r_S = peak response of olanzapine  from the Standard solution 

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

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

Acceptance criteria: 90.0%–110.0% 

4 PERFORMANCE TESTS

Disintegration 〈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 

Change to read: 

Dissolution 〈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. Discard the first few milliliters. The filtrate or centrifugate may be suitably diluted. 

Determine the amount of olanzapine (C₁₇H₂₀N₄S) dissolved by using either the Spectrometric procedure or Chromatographic procedure.  

Spectrometric procedure 

Instrumental conditions 

(See Ultraviolet-Visible Spectroscopy 〈857〉.) 

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 = (A_U/A_S) × C_S × D  × V × (1/L) × 100 

A_U = absorbance of the Sample solution 

A_S = absorbance of the Standard solution 

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

D= dilution factor of the Sample solution  

V = volume of Medium, 900 mL 

L = label claim (mg/Tablet) 

Chromatographic procedure 

Buffer: 6.8 g/L of sodium acetate in water. Adjust with glacial acetic acid to a pH of 5.0. Mobile phase: Acetonitrile and Buffer (25:75) 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

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 = (r_U/r_S) × C_S × V × (1/L) × 100 

r_U = peak response of olanzapine from the Sample solution 

r_S = peak response of olanzapine from the Standard solution 

C_S = concentration of USP Olanzapine RS in the Standard solution (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 

5 IMPURITIES 

Change to read: 

Organic Impurities 

[Note—A few drops of acetonitrile, not to exceed 5% of the nal volume, may be added to the Standard solution and Sample solution before nal dilution to reduce foaming.] 

Buffer 1: Dissolve 3.3 mL of phosphoric acid in 1 L of water. Adjust with 50% of sodium hydroxide to a pH of 2.55 ± 0.05. Buffer 2: Dissolve 8.7 g of sodium dodecyl sulfate in 1 L of Buffer 1. Mix for NLT 30 min before use. 

Buffer 3: Dissolve 18.6 mg of edetate disodium (EDTA) in 1 L of Buffer 2. Mix for NLT 30 min before use. 

Solution A: Acetonitrile and Buffer 2 (48:52) 

Solution B: Acetonitrile and Buffer 2 (70:30) 

Diluent: Acetonitrile and Buffer 3 (40:60) 

System suitability solution: 20 µg/mL of USP Olanzapine RS and 2 µg/mL each of USP Olanzapine Related Compound B RS and USP Olanzapine Related Compound C RS in Diluent 

Standard solution: 2 μg/mL of USP Olanzapine RS in Diluent 

Sensitivity solution: 0.4 µg/mL of USP Olanzapine RS in Diluent from the Standard solution 

Sample solution: Nominally 400 μg/mL of olanzapine from Tablets prepared as follows. Transfer a known quantity of finely crushed powder from Tablets (NLT 20) to a suitable volumetric flask. Add about 60% of the flask volume of Diluent. Mechanically shake for 5 min, and sonicate for about 1 min. Dilute with Diluent to volume. Pass through a suitable filter of 0.45 μm-pore size. Discard the first 3 mL of the filtrate. [Note—Use freshly crushed powder for the sample preparation. The Sample solution should be injected immediately after preparation. Protect the solution from light at all times.] 

Mobile phase: See Table 2. 

Table 2 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 220 nm 

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

Temperatures 

Autosampler: 5° 

Column: 35° 

Flow rate: 1.5 mL/min 

Injection volume: 20 µL 

System suitability 

Samples: System suitability solution, Standard solution, and Sensitivity solution 

Suitability requirements 

Resolution: NLT 3.0 between olanzapine and olanzapine related compound C, System suitability solution 

Tailing factor: NMT 1.5 for the olanzapine peak, System suitability solution 

Relative standard deviation: NMT 2.0%, Standard solution 

Signal-to-noise ratio: NLT 10, Sensitivity solution 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of each degradation product in the portion of Tablets taken: 

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

r_U = peak response of each degradation product from the Sample solution 

r_S = peak response of olanzapine from the Standard solution 

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

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

F = relative response factor (see Table 3) 

Acceptance criteria: See Table 3. The reporting threshold is 0.1%. 

Table 3 

^a(Z)-3-(Hydroxymethylene)-4-(4-methylpiperazin-1-yl)-1,3-dihydro-2H-benzo[b][1,4]diazepine-2-thione.

^b(Z)-4-(4-Methylpiperazin-1-yl)-3-(2-oxopropylidene)-1H-benzo[b][1,4]diazepin-2(3H)-one. 

^c(Z)-1-{4-(4-Methylpiperazin-1-yl)-2-thioxo-1H-benzo[b][1,4]diazepin-3(2H)-ylidene}propan-2-one. 

^d(Z)-(4-(4-Methylpiperazin-1-yl)-2-thioxo-1,2-dihydro-3H-benzo[b][1,4]diazepin-3-ylidene)methyl acetate. 

6 ADDITIONAL REQUIREMENTS 

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

Change to read: 

Labeling: When more than one Disintegration test is given, the labeling states the Disintegration test used only if Test 1 is not used.  (USP 1- Aug-2022) 

Change to read: 

USP Reference Standards 〈11〉 

USP Olanzapine RS 

 USP Olanzapine Related Compound B RS 

2-Methyl-10H-thieno-[2,3-b][1,5]benzodiazepin-4[5H]-one; 

Also known as 2-Methyl-5,10-dihydro-4H-benzo[b]thieno[2,3-e][1,4]diazepin-4-one. 

C₁₂H₁₀N₂OS 230.29  

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