Mirtazapine 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

Mirtazapine Orally Disintegrating Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of mirtazapine (C₁₇H₁₉N₃)

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K _{(CN 1-MAY-2020)}

Standard solution: Dissolve 30 mg of USP Mirtazapine RS in a separatory funnel containing 30 mL of water, and add 30 mL of n-hexane. Shake vigorously for 5 min. Allow the solution to separate into two layers. Filter the n-hexane layer through glass wool, and evaporate to dryness.

Sample solution: Transfer a quantity of finely powdered Tablets, equivalent to 30 mg of mirtazapine, to a separatory funnel. Add 30 mL of water and 30 mL of n-hexane. Shake vigorously for 5 min. Allow the solution to separate into two layers. Filter the n-hexane layer through glass wool, and evaporate to dryness.

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

Diluent: Acetonitrile and water (50:50)

Diluted phosphoric acid: Water and phosphoric acid (1000:3)

Buffer: Dissolve 1 g of monobasic potassium phosphate and 1.7 g of pentanesulfonic acid sodium salt in 1 L of water. Adjust with Diluted phosphoric acid to a pH of 4.7 ± 0.1, and filter.

Mobile phase: Acetonitrile and Buffer (25:75)

Standard stock solution: 0.3 mg/mL of USP Mirtazapine RS in Diluent

Standard solution: 0.036 mg/mL of USP Mirtazapine RS in Mobile phase from the Standard stock solution

Sample stock solution: 0.3 mg/mL of mirtazapine in Diluent (from NLT 20 Tablets, finely powdered). Sonicate for 15 min with occasional swirling, and shake for 30 min. (NOTE-Alternatively, dissolve 10 Tablets in a volume of a mixture of acetonitrile and water (90:10) to obtain a 0.3 mg/mL solution of mirtazapine. Shake or stir until the mixture is free from lumps.]

Sample solution: Nominally, 0.036 mg/mL of mirtazapine in Mobile phase obtained as follows: transfer 40 mL of the Sample stock solution into a centrifuge tube, and centrifuge at 3000 rpm for 10 min. Transfer 6.0 ml. of the supernatant into a 50-mL volumetric flask, and dilute with Mobile phase to volume. Pass the portion through a polypropylene membrane filter of 0.45-µm pore size. Discard at least the first 5 mL of filtrate.

Chromatographic system.

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 290 nm

Column: 4.6-mm x 15-cm; 5-µm packing L1

Flow rate: 1 mL/min

Injection size: 20 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 mirtazapine (C₁₇H₁₉N₃) in the portion of Tablets taken:

Result = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak response from the Sample solution

r_s = peak response from the Standard solution

C_s = concentration of USP Mirtazapine RS (mg/mL)

C_u = nominal concentration of mirtazapine in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

DISINTEGRATION (701): NMT 60 s

DISSOLUTION (711)

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

Time: 15 min

Sample solution: Sample per Dissolution (711). Pass through a filter of 0.45-µm pore size, and discard the first 5 mL of the filtrate.

Standard solution: 33 µg/mL of USP Mirtazapine RS in Medium

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857).)

Mode: UV

Analytical wavelength: 316 nm

Blank: Medium

Cell: 0.5 cm

Analysis: Determine the percentage of mirtazapine (C₁₇H₁₉N₃) dissolved:

Result = (A_u /A_s ) × C_s × V × (1/L) × 100

A_u = absorbance of the Sample solution

A_s = absorbance of the Standard solution

C_s = concentration of USP Mirtazapine RS in the Standard solution (mg/mL)

V = volume, 900 mL

L = label claim of mirtazapine (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of mirtazapine (C H N ) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

IMPURITIES

 Organic Impurities

Solution A: Dissolve 7.2 g of tetramethylammonium hydroxide pentahydrate in 4 L of water. Add 1 mL of triethylamine. Adjust with

phosphoric acid to a pH of 7.4.

Solution B: Acetonitrile, methanol, and tetrahydrofuran (170:145:85)

Diluent: Acetonitrile and water (50:50)

Mobile phase: See Table 1.

Table 1

System suitability solution: 0.3 mg/mL of USP Mirtazapine RS in Diluent

Standard solution: 0.015 mg/mL each of USP Mirtazapine RS, USP Mirtazapine Related Compound A RS, USP Mirtazapine Related

Compound B RS, USP Mirtazapine Related Compound C RS, and USP Mirtazapine Related Compound D RS in Diluent

Sample solution: Nominally, 1.5 mg/mL of mirtazapine in Diluent from NLT 5 Tablets

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 240 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Column temperature: 40°

Flow rate: 1.2 mL/min

Injection size: 10 µL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Tailing factor: NMT 2.0, System suitability solution

Relative standard deviation: NMT 2.0%, System suitability solution

Resolution: NLT 4.0 between the mirtazapine and mirtazapine related compound D peaks, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each individual specied impurity in the portion of Tablets taken:

Result = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak response of each individual specied impurity from the Sample solution

r_s = peak response of the corresponding related compound from the Standard solution

C_s = concentration of each individual impurity in the Standard solution (mg/mL)

C_u = nominal concentration of mirtazapine in the Sample solution (mg/mL)

Calculate the percentage of each individual unspecied impurity in the portion of Tablets taken:

Result = (r_u /r_s ) × (C_s /C_u ) × 100

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

r_s = peak response of mirtazapine from the Standard solution

C_s = concentration of mirtazapine in the Standard solution (mg/mL)

C_u = nominal concentration of mirtazapine in the Sample solution (mg/mL)

Acceptance criteria: See Table 2. [Note—Disregard any peak less than 0.05%.]

Table 2

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Store at controlled room temperature. Protect from light and moisture.

USP Reference Standards 〈11〉

USP Mirtazapine RS

USP Mirtazapine Related Compound A RS

1,2,3,4,10,14b-Hexahydropyrazino[2,1-a]pyrido[2,3-c][2]benzazepine.

C₁₆H₁₇N₃                       251.33

USP Mirtazapine Related Compound B RS

1,2,3,4,10,14b-Hexahydro-2-methylpyrazino[2,1-a]pyrido[2,3-c][2]benzazepine 2-oxide monohydrate.

C₁₇H₁₉N₃O · H₂O          299.36

USP Mirtazapine Related Compound C RS

2-Methyl-3,4,10,14b-tetrahydrobenzo[c]pyrazino[1,2-a]pyrido[3,2-f]azepin-1(2H)-one.

C₁₇H₁₇N₃                       279.34

USP Mirtazapine Related Compound D RS

2-Methyl-1,2,3,4-tetrahydrobenzo[c]pyrazino[1,2-a]pyrido[3,2-f]azepin-10(14bH)-one.

C₁₆H₁₇N₃                       279.34